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Peace Corps

Technical Guideline 810

Acute Diarrhea

1. PURPOSE
This guideline addresses the diagnosis and management of acute diarrheal syndromes due to
infectious causes.
2. BACKGROUND
Acute diarrhea represents one of the most common complaints of Volunteers located in
developing countries. While diarrhea can be related to many factors, including change in
diet, it is often the result of an infection with one of a variety of organisms (viral, bacterial or
parasitic), contracted by ingesting food or water which has been contaminated with fecal
pathogens.
Most people will consider any increase in stool frequency or softening of the stool to be due
to diarrhea. Significant diarrhea is best defined as:
Diarrhea:

More than four liquid stools in one 24 hour period

Dysentery:

Diarrhea with mucus or blood

Acute:

Lasting less than 14 days

Chronic:

Lasting more than 14 days

Commonly, diarrhea is self limiting, resolving in a few days with no specific treatment
required other than adequate fluid replacement. Sometimes, however, diarrhea can be
serious or even life threatening (usually because of dehydration.) It is important to be able to
recognize patients in whom the diarrhea is potentially serious and to be able to correctly
investigate when necessary and provide treatment.
There are three main mechanisms by which pathogens can cause diarrhea. They may:
Invade/destroy the mucosal lining of the bowel (e.g., shigella, non-typhoid salmonellae,
E. histolytica)
Produce toxins which cause fluid to move into the bowel. Also known as secretory
diarrhea. (e.g., Vibrio cholerae, enterotoxigenic E. coli)
Cause a malabsorption like syndrome (e.g., giardia)
3. PREVENTION
Avoidance of contaminated water and food is the primary strategy in preventing diarrhea
among Volunteers.
Water must be assumed to be contaminated unless it is known to be safe; i.e., potential
pathogens are removed or inactivated. Boiling remains the simplest and most effective
method of water disinfection. Water that has been boiled for three minutes is safe for
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drinking, even under the most extreme field conditions. Other methods which may be used
but may be less effective in some situations are described in ATTACHMENT A. Of these, only
filtering through a 1-2 micron filter followed by iodine or chlorine treatment is as effective as
boiling. Iodine and chlorine are less effective against protozoal cysts (ameba and giardia)
and are not effective against cryptosporidium cysts. The true frequency of cryptosporidium
infections is not known and is probably underestimated. Diarrhea due to cryptosporidium
typically persists for 10-14 days and is self-limited in healthy persons. Whenever possible,
water should be completely disinfected using one of the first two methods.
Many types of water filters marketed for travelers and rural use are ineffective against one or
more common pathogens. Usually iodine or chlorine must be used in addition to a water
filter. At this time, the water filters which use both a 1-2 micron filter to remove parasites
and cysts and an iodine resin to inactivate bacteria and viruses appear to be effective.
Conclusive field testing of such filters is lacking.
The complete cooking of food inactivates pathogens. Food should be eaten immediately
after cooking as a delay can allow bacteria to multiply again, and cooked food should be
protected from flies and other sources of recontamination. Soaking vegetables in a chlorine
solution after scrubbing them to remove dirt and other particles appears to be effective but
cannot completely disinfect heavily contaminated foods. After washing, soak the items in a
solution of one tablespoon household bleach per gallon for 15 minutes and then rinse in
treated water.
4. PROPHYLAXIS
While antibiotics have been shown to reduce the risk and severity of travelers diarrhea for
short-term travelers, there is also a significant risk of an adverse reaction to the drugs
themselves. This is especially so for Volunteers who remain in an area for several years.
Volunteers should not be given prophylactic antibiotics. They should be instructed in food
and water precautions and self management of minor diarrhea, along with seeking medical
attention when necessary.
5. HISTORY, EXAMINATION, AND LABORATORY TESTS
Taking a full history and performing a comprehensive examination will guide the practitioner
to the likely cause of an episode of diarrhea and its severity. Laboratory tests may be used to
confirm this clinical suspicion.
See Table 5.1 Clues to the Etiology of Infectious Diarrhea, Table 5.2 Evaluation of Acute
Diarrhea and Table 5.3 Management of Acute Diarrhea on the following pages.

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5.1

Clues To The Etiology Of Infectious Diarrhea


POSSIBLE PATHOGENS

CLUE

ANATOMIC LOCATION

Infrequent, large volume


stools

Small bowel origin

Giardiasis, enterotoxigenic
E. coli, early shigellosis or
cholera

Frequent, relatively small


volume stools

Large bowel origin

Amebiasis, shigellosis,
salmonellosis,
campylobacter

Tenesmus, fecal
urgency, dysentery

Colitis

same as above

Prominent fever

Mucosal invasion

same as above; plus


rotavirus, Norwalk (virus)

Prominent vomiting

Gastroenteritis

Bacterial toxin (staph


aureus, b. cereus);
rotavirus, Norwalk (virus)

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5.2 EVALUATION OF ACUTE DIARRHEA


Subjective (History should include details on the following):

Frequency (number of stools/day)


Timing (day/night)
Consistency of stool
Color of stool
Presence of abdominal pain
Passage of blood or mucus with stool
Presence of fever
Presence of vomiting / fluid intake
Medication taken (before and after onset of symptoms)
Dietary information
Friends or family members with similar symptoms (common source of infection?)
Significant past history
When patient last voided

Objective
Physical findings

Vital signs:
Inspection:
Palpation:
Auscultation:

BP, pulse, temperature, postural hypotension (occurs in dehydration)


Look for dry mouth, sunken eyes, reduced skin turgor
Abdominal distention, tenderness, masses
Bowel sounds (present, absent, increased, reduced)

Laboratory Tests (when necessary- see Table 5.3)

Microscopic stool examination: stool is commonly examined for WBCs (indicating


inflammation/invasion of the bowel wall) and ova/parasites.
Stool culture: for bacterial pathogens
CBC
Electrolytes (potassium depletion, hyper- or hyponatremia, acid-base disorder)

Assessment
When assessing a patient with diarrhea, the following questions must be answered:
1.
2.
3.
4.
5.
6.

Is the patient dehydrated or likely to become dehydrated?


What is the most likely cause of the diarrhea?
What investigations (if any) are required?
What treatment (if any) is required?
What instructions should be given to the patient?
What follow-up is required?

Plan
See Table 5.3 MANAGEMENT OF ACUTE DIARRHEA

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5.3 MANAGEMENT OF ACUTE DIARRHEA

PATIENT WITH
ACUTE DIARRHEA
TREATMENT:
Fever, dysentery or
severe diarrhea

NO

- Oral fluids
- Observe
- Symptomatic treatment
(see text)
- Further workup if prolonged

YES
MORE SEVERE ILLNESS; EVALUATE
:
- Fecal RBC/WBC
- Stool O & P
- Stool culture
- Malaria smear (if appropriate)
- CBC

Inflammatory
diarrhea* or
fever

Give empiric
antibiotic therapy,
consider IV fluids

YES

NO

Treat for identified pathogens


* Inflammatory diarrhea
is
likely if the stool contains blood
or mucus or the patient has a
significant fever

Patient
improves

NO

CONSULT
APCMO/OMS

YES
DIARRHEA
RESOLVED

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6. SUPPORTIVE CARE
Avoidance of hypovolemia with adequate hydration is the most critical therapy for acute
diarrheal illnesses. The average adult with diarrhea should drink a minimum of 2-3 Liters
daily. Oral rehydration solutions can be easily mixed up by the PCV.
Two acceptable recipes are as follows:
Add to 1 Liter of clean water: tsp of salt, tsp of baking soda and 4 tbsps of
Sugar
Add to 1 Liter of clean water: tsp of salt and 8 tsps of Sugar
These solutions can be flavored with some fruit juice or other soft drink.
The benefits of dietary changes other than adequate oral hydration have not been established
in controlled studies. Diets similar to the BRAT (banana, rice, applesauce, and toast) diet
should not make the diarrhea worse and will provide some calories. With most diarrheal
illnesses, individuals develop some degree of lactose intolerance. Dairy products should be
avoided during the acute diarrhea episode and for several weeks after.
7. EMPERIC ANTIBIOTIC THERAPY AND USE OF ANTIDIARRHEAL
MEDICATION
When acute diarrhea is severe, contains blood or mucus, or is associated with a significant
fever, an invasive bacterial pathogen is likely. In these cases, consideration should be given
to the use of antibiotics even before the laboratory results are available.
Antibiotics for use in severe or invasive bacterial diarrhea
Ciprofloxacin 500mg two times daily for 3 days
or
Azithromycin, 1 gm in a single dose
* Azithromycin is preferred in southeast Asia due to development of quinolone-resistant
Campylobacter jejuni

Motility inhibiting agents [diphenoxylate (Lomotil) and loperamide (Imodium)] reduce


frequency of diarrhea and cramping, however exacerbation or prolongation of illness can
occur. To reduce the likelihood of complications, they should not be used when symptoms
of dysentery (fever, abdominal pain, or bloody stool) are present. Short-term use (less than
48 hours) in relatively mild cases, particularly when traveling, is widely practiced and is
generally safe. Fluid loss into the bowel can continue despite temporary relief from diarrhea,
so oral hydration should be emphasized.
Bulking agents (Kaolin and Pectin) can improve the consistency of diarrheal stool but have
not been shown to decrease the symptoms of infectious diarrhea.
Relatively high dose bismuth subsalicylate (Pepto-Bismol: 30 ml (1 oz.) liquid or 2 tabs
(525mg) every 30 min for 8 doses per day for 1-2 days) acts as an antisecretory agent and is

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effective in shortening the course of infectious diarrhea in about 50% of cases. Do not
exceed this dosage.
8. MANAGEMENT OF SPECIFIC PATHOGENS
8.1

Bacterial Diarrhea (Enterotoxigenic E. coli (ETEC), salmonella, shigella, and


campylobacter)

Bacterial diarrhea is usually associated with the sudden onset of frequent watery
stools, crampy abdominal pain, and sometimes fever, nausea or vomiting. WBCs,
blood and mucus may be present in the stool.

Bacterial diarrhea usually resolves spontaneously in 3-5 days. Fluid replacement


with electrolyte solution is the most important part of the treatment.

The use of antibiotics may shorten the duration of an episode of bacterial diarrhea.
Pathogenic bacteria quickly develop antibiotic resistance, therefore antibiotics are
reserved for use in only the more severe cases.

It is important to determine if there is inflammation of the bowel wall, (blood or


mucus in the stool or fever) as this indicates a more severe illness which should be
investigated with stool culture and microscopy. Consideration should also be given
to the empiric use of antibiotics (see section 6.) Amebic dysentery can also produce
this clinical picture.
Antibiotics for use in severe or invasive bacterial diarrhea
Ciprofloxacin 500mg two times daily for 3 days (other quinolones may be used)
or
Azithromycin, 1 gm in a single dose
* Azithromycin is preferred in southeast Asia due to development of quinolone-resistant
Campylobacter jejuni

8.2

Viral diarrhea

8.3

Cholera is rarely seen in travelers or expatriates. Its occurrence in epidemics and


voluminous quantity of liquid stool (rice water stool) passed distinguish it from
other bacterial causes of diarrhea.

While viral diarrhea is a major cause of morbidity and mortality in children, in


adults it usually presents as a mild illness similar to mild bacterial diarrhea. The
illness is self limiting and ensuring adequate fluid intake is all that is required.

Giardiasis (Giardia lamblia)

Infection occurs by the ingestion of contaminated water, including rivers and


streams contaminated by infected animals, fecal-oral transmission (person-toperson), and occasionally by contaminated food.

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Most people infected with giardia remain asymptomatic, especially those who have
been previously infected and have developed some immunity.

When symptoms do develop, patients may be ill for weeks or months with loose
foul-smelling stools, belching and flatus, abdominal cramps and weight loss.

The diagnosis is confirmed by finding giardia cysts on microscopic examination of


the stool. Recovery of cysts in the stool is often difficult, requiring repeated stool
examinations and/or presumptive therapy when the diagnosis is suspected.

A stool test to detect giardia antigen is available, however presumptive treatment


for suspected giardiasis remains a practical method of managing this condition.
Treatment of Giardia
Tinidazole 2gm orally once
or
Metronidazole 250 mg three times daily for 5 days

8.4

Volunteers diagnosed and treated for giardiasis should have their stool
examinations repeated to assess the efficacy of the treatment.

Infrequently, giardiasis may persist despite standard treatment. Quinacrine 100mg


three times daily for 5 days can be used for suspected treatment-resistant giardiasis.

Other intestinal flagellated protozoans (Trichomonas hominis, Chilomastix mesnili,


Enteromonas hominis) are non-pathogenic and do not require treatment.

Amebiasis (Entamoeba histolytica)

Infection occurs by the ingestion of viable cysts from fecally contaminated water,
food, or hands.

There are three main clinical presentations of amebiasis:


Asymptomatic Carriers

Most people infected with E. histolytica do not develop diarrhea but remain
asymptomatic and continue to pass cysts in their stool (which can infect others.)
These cysts may be found when the patient is being investigated for an episode
of acute diarrhea.

Asymptomatic carriers are treated with a luminal agent.


Treatment of Asymptomatic Carriers (luminal agents)
Paromomycin (Humatin) 500mg three times daily for 7 days
or
Iodoquinol (Yodoxin) 650mg three times daily for 20 days
or
Diloxanide furoate (Furamide) 500 mg three times daily for 10 days

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Amebic Colitis

When diarrhea does develop, it is often foul-smelling and associated with


flatulence. Bouts of diarrhea may alternate with periods of relatively normal
bowel function. This presentation may be difficult to distinguish from
giardiasis. Less common is acute amebic dysentery characterized by an acute
diarrheal episode associated with fever, severe cramping, and gross blood in the
stool.

Both cysts and trophozoites are found in the stool of persons with symptomatic
intestinal amebiasis. If only cysts are seen despite careful stool examination
another cause should be sought.

Other species of ameba (Entamoeba coli, Entamoeba hartmanni, Endolimax


nana, Iodamoeba buetschlii) are non-pathogenic and do not require treatment.
Treatment of Amebic Colitis
Metronidazole 750mg PO or IV three times daily for 10 days
or
Tinidazole 2gm PO daily for 3 days (higher doses may be necessary in severe
disease)
followed by
Luminal agent (as above)

Volunteers diagnosed and treated for amebiasis should have their stool
examinations repeated to assess the efficacy of the treatment.

Extraintestinal Amebiasis

Amebic disease outside the intestinal tract is rare, however an amebic liver
abscess is the most likely cause of a liver abscess in a Volunteer.

Symptoms usually involve the insidious onset of fever, sweats, fatigue, and
weight loss. A more acute presentation involves high fever, right upper
quadrant pain, nausea and vomiting.

Diagnosis is confirmed by demonstrating a multi-loculated cyst in the liver on


ultrasound. Amebic serology is positive in 90% of cases and LFTs may be
elevated. Stool microscopy is frequently negative for cysts or trophozoites.

Initial treatment is medical and laparotomy or aspiration can usually be avoided.


Always consult OMS.
Treatment of Extraintestinal Amebiasis
Metronidazole 750mg PO or IV three times daily for 10 days
or
Tinidazole 2gm PO daily for 5 days
Consult OMS

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8.5

Antibiotic Induced Diarrhea

It is not unusual for patients being treated with antibiotics to develop diarrhea. This
is due to an alteration in the normal bowel flora. Usually antibiotic-induced
diarrhea resolves quickly when the antibiotics are stopped.

If the diarrhea persists after the antibiotics have been stopped, there may be an
overgrowth of Clostridium difficile in the bowel (present in 3% of healthy adults)
producing pseudomembranous colitis. Some laboratories are able to identify C.
difficile toxin in stool specimens.
Treatment of Antibiotic Induced Diarrhea
Mild:

Stop antibiotics (when appropriate)


Metronidazole 250mg PO four times daily for 7 days if diarrhea persists
or worsens

Severe:

Vancomycin 125mg PO four times daily for 7 days

9. SIDE EFFECTS OF MEDICATIONS


Metronidazole/Tinidazole
Abdominal pain, metallic taste, severe vomiting if alcohol consumed within 48 hours
(antabuse-like reaction), stomatitis, glossitis. Contraindicated in first trimester of
pregnancy.
Paromomycin
GI disturbances.
Iodoquinol
Rash, acne, nausea, diarrhea, cramps, thyroid enlargement; or peripheral neuropathy
(rare, prolonged use at high doses.) Optic neuritis has not been reported with Iodoquinol.
Diloxanide
Flatulence (common), nausea, vomiting.
Quinacrine
Dizziness, headache, rash, yellow discoloration of the skin, toxic psychosis (rare) acute
hepatic necrosis (rare.)

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REFERENCES
Drugs for Parasitic Infections, The Medical Letter, August 2004
Centers for Disease Control and Prevention. Health Information for International Travel, 20032004, Atlanta, Georgia, 2003

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TG 810, Attachment A

SUMMARY OF WATER DISINFECTION METHODS


Recommended methods
Heat
Effective against all common intestinal pathogens
Boil for 1 minute
Boil 3 minutes altitudes > 2000m (6500 feet) due to the
decreased boiling point at increased altitude
Filtration alone
Gravity-drip filters with pore size of 1 micron effectively
remove parasitic cysts and most bacteria, but does not
adequately remove viruses and smaller bacteria
Filtration + chlorine
Adding chlorine to filtered water kills viruses and any residual
bacteria
Add two drops of household chlorine bleach (5%
concentration) per liter of filtered water and wait 15 minutes
Chlorine alone
The most commonly used disinfection method used
worldwide
Effective against bacteria and viruses. Requires prolonged
exposure to kill giardia
Not effective against cryptosporidium
Add four drops of household chlorine bleach (5%) per liter of
water and wait 60 minutes
Not as effective with cloudy water. Recommend straining with
a cloth before treating
Iodine tablets alone
Has similar effectiveness to chlorine
Not effective against cryptosporidium
Add two tablets per liter of water and wait 30 to 60 minutes
depending on the temperature (decreased effectiveness in
colder water)
Is physiologically active. Not recommended for pregnant
women or people with thyroid disease
Recommended for only several weeks of emergency use
Other methods
Aquatabs (sodium
Has similar effectiveness to chlorine
dichloroisocyanurate
Not effective against cryptosporidium
Available in tablet form
Chlorine Dioxide
Kills most waterborne pathogens, including cryptosporidium
Tablet and liquid forms are available
Ultraviolet
Effective against bacteria, viruses and cryptosporidium
Effect depends on UV dose and exposure time
Commercial devices are available
Solar irradiation and heating
Clear water in transparent plastic bottles on a reflective
surface exposed to sunlight for a minimum of 6 hours
substantially improves the quality of water in austere
emergency situations

Adapted from the CDC Yellow Book 2014, Chapter 2: Water Disinfection for Travelers
______________________________________________________________________________
Office of Volunteer Support

August 2015

Peace Corps
Technical Guideline 815

STOOL EXAMINATION FOR PARASITES

1. PURPOSE
To provide guidance in the techniques of stool examination and the interpretation of the
results.
2. BACKGROUND
Intestinal diseases are one of the most common types of illness among Volunteers. PCMOs
must have a good understanding of these diseases and be aware of the techniques used to
diagnose them. Bacterial cultures of the stool, when available, are appropriate for the
evaluation of acute, severe diarrhea. (See Technical Guideline 810 Acute Diarrhea, Table
5.2) Fecal white blood cells are also an important clue in acute cases. More often, stool
examination for ova and parasites is performed to evaluate chronic diarrhea or to screen for
the presence of pathogenic organisms.
3. EXAMINATION OF STOOL FOR OVA & PARASITES (O & P)
Microscopic stool examination requires formal training and periodic competency testing.
PCMOs are not expected to be able to perform microscopic stool examinations (other than
for fecal white blood cells) but must be familiar with the techniques and quality control (if
any) used by their referral labs. Many laboratories in the U.S. and abroad are not able to
consistently and correctly identify pathogens. It is generally recommended that stool
specimens be periodically submitted to a reference lab in the U.S. or elsewhere to help assess
the reliability of in-country testing. See Technical Guideline 360 Use of U.S.
Laboratories.
Ova or parasites are found in less than 50% of specimens from infected persons.
Examination of three specimens collected on different days typically increases the detection
rate to 80-90%. Good lab technique and a skilled microscopist are critical in the correct
identification of pathogenic organisms.
Two different O & P examinations can be performed:
(1)

Saline wet mount examination


Saline is added to fresh stool and examined. Used for the detection of moving
flagellates and trophozoites of amoeba.

(2)

Permanent stain examination


Used to detect ova, cysts, and parasites. Trichrome and iron-hematoxylin are the
two most commonly used stains. Fresh or preserved specimens can be used (see
below.)

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New methods of detecting parasites in fecal samples, such as fluorescence


microscopy using monoclonal antibody for Cryptosporidum, are available.
Stool concentration procedures should be used before either test to increase the sensitivity of
the examination. The simplest concentration method is sedimentation of feces in a tube. The
sediment than can be examined. Other concentration methods may be used in the referral
laboratories.
4. COLLECTION AND HANDLING OF STOOL SPECIMENS
Collection

Ask the Volunteer to pass stool into a large, clean container, then transfer several
tablespoons of stool into the smaller feces container.

Feces must not be contaminated with urine or water.

Usually three specimens, collected on sequential days, are required.

Time limits for testing


As specimens degenerate over time, the following time limits apply from passage of feces
until testing is performed:
For wet mount:

Diarrheal stool

Examination best within 30 minutes

Formed stool

Examination best within 3 hours

For permanent stain:

Diarrheal stool

Examination best within 30 minutes

Formed stool

Examine stool within 3 hours; otherwise refrigerate (for up to 12


hours). If it will be more than 12 hours before the examination,
preserve the specimen with MIF.

For culture:

Culture is best performed within 24 hours. Refrigerate stool if culture is not to be


performed immediately.

Preserving stool specimens using MIF or 10% Formalin solution


MIF (Merthiolate/Iodine/Formalin) can be added to stool specimens to preserve them for
future O & P examination. 10% formalin solution can also be used as a stool preservative.

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MIF kit or formalin can be used both by Volunteers on site (to forward specimens to
PCMOs) and Health Units (to forward specimens to laboratories).

Preserved (MIF or formalin treated) specimens cannot be used for bacterial culture.

False negative results


The following substances can cause false negative results on O & P if used within three
days of the examination:

Oil or oil-based laxatives

Barium preparations (used for contrast x-ray studies)

Magnesium or aluminum salts (present in most antacids).

5. INTERPRETATION OF O&P FINDINGS


See ATTACHMENT A - A GUIDE TO O&P RESULTS. Clinical information on the
management of intestinal parasites and helminthes is also included in Technical Guideline
810 Acute Diarrhea and Technical Guideline 820 Intestinal Worms.

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TG 815 ATTACHMENT A
GUIDE TO O&P RESULTS
1. POTENTIALLY PATHOGENIC INTESTINAL PARASITES
Treatment may be required.
Protozoa

Entamoeba histolytica (cysts and trophs)


Dientamoeba fragilis (trophs)
Giardia lamblia (cysts and trophs)
Balantidium coli (cysts and trophs)
Isospora species (oocysts)
Blastocystis hominis (symptomatic)

Helminths

Ascaris lumbricoides (roundworm)


Enterobius vermicularis (pinworm)
Trichuris trichiura (Whipworm)
Ankylostoma duodenale or Necator americanus eggs (hookworm)
Strongyloides stercoralis larvae
Taenia saginata (beef tapeworm) / Taenia solium (pork tapeworm) eggs are very similar
Diphyllobothrium latum (fish tapeworm)
Dipylidium caninum (dog/cat tapeworm)
Hymenolepis nana (dwarf tapeworm)
Hymenolepis diminuta (rodent tapeworm)
Schistosoma species (bilharzia)
Paragonimus westermani (lung fluke)
Fasciolopsis buski/hepatica - eggs are indistinguishable
Opisthorchis species (Clonorchis)
Heterophyes/Metagonimus - eggs are very similar

2. NON-PATHOGENIC ORGANISMS
No treatment required

Entamoeba coli (cysts and trophs)


Entamoeba hartmanni (cysts and trophs)
Endolimax nana (cysts and trophs)
Iodamoeba butschlii (cysts and trophs)
Chilomastix mesnili (cysts and trophs)
Trichomonas hominis (trophs)
Enteromonas hominis (cysts and trophs)
Retortamonas intestinalis (cysts and trophs)
Blastocystis hominis (asymptomatic)

3. OTHER FINDINGS
RBC (red blood cells)
Indicates gastrointestinal tract bleeding
WBC (white blood cells)
Indicates inflammation of the bowel. Investigation and treatment may be required (see TG 810
Acute Diarrhea.)
Charcot-Leyden crystals, starch granules, fat or oil, and budding yeasts
Relatively common and not in themselves significant in the absence of symptoms.

Peace Corps
Technical Guideline 840

PREVENTION OF MALARIA

1. PURPOSE
To provide Peace Corps Medical Officers (PCMOs) with guidance on malaria prevention for
Volunteers.

2. BACKGROUND
Malaria is a mosquito-borne parasitic disease endemic to many areas of the world served by
Peace Corps Volunteers. It is a serious and sometimes fatal disease. As such, the Office of
Medical Services (OMS) employs a comprehensive prevention program to prevent malaria in
Volunteers. Medical officers and Volunteers are required to rigorously adhere to the
components of the program. Components of the program include:

Primary prevention: the provision of personal protective equipment, i.e., mosquito nets,
insect repellent, and insect spray to all Volunteers serving in malaria endemic areas.
Screening on windows and doors of Volunteer living areas is strongly encouraged.

Secondary prevention: the provision of malaria chemoprophylaxis, including postdeparture prophylaxis and presumptive anti-relapse therapy (PART) when indicated, to
all Volunteers serving in malaria endemic areas.

Education: the provision of education to PCMOs and Volunteers on malaria prevention


measures, including mosquito avoidance strategies and the proper use of
chemoprophylactic medication.

Policy: OMS policy that requires all Volunteers serving in malaria endemic areas to
rigorously adhere to malaria prevention measures, i.e., use of personal protective
equipment and chemoprophylaxis, throughout their tour of duty.

The OHS Epidemiology and Surveillance Unit coordinates Peace Corps malaria case
surveillance.
Specific guidance on the diagnosis and treatment of malaria is addressed in Technical
Guideline 845 Treatment of Malaria.

3. GENERAL CONSIDERATIONS
Malaria is caused by one of five protozoan species of the genus Plasmodium: P. falciparum,
P. vivax, P. ovale, P. malariae, and P. knowlesi. All are transmitted by the bite of an
infected female Anopheles mosquito. P. falciparum is the most dangerous species among the
five. It poses the greatest risk of death to non-immune persons and is the species most likely
to develop resistance to antimalarial drugs. P. vivax and P. ovale have a dormant liver phase
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TG 840
Malaria Prevention

that may persist in the liver for up to four years and cause recurrences after routine
chemoprophylaxis is discontinued. PART is used to eradicate these species from the liver
and prevent late relapses of malaria. P. malariae is the least common species of malaria. It
has a dormant blood borne phase that can cause recurrences years after leaving an infected
area.
3.1

Geographic Distribution and Resistance Patterns


Malarial transmission occurs in large areas of Central and South America, Hispaniola,
Sub-Saharan Africa, the Indian subcontinent, Southeast Asia, the Middle East, and
Oceania. ATTACHMENT A provides a general illustration of the worldwide
distribution of malaria. P. falciparum and P. malariae are present in most malarial
areas. P. vivax and P. ovale are present in all malarial areas except Haiti and the
Dominican Republic.
A detailed list of malaria by country is available at:
http://www.cdc.gov/malaria/travelers/country_table/a.html
Drug resistance Antimalarial selection should include the considerations of regions
with malarial drug resistance.
The resistance of P. falciparum to chloroquine is widespread; regions with chloroquineresistant and chloroquine-sensitive malaria are summarized below:
Chloroquine-resistant P. falciparum is widespread in endemic areas of Africa, Asia and
Oceania.
Chloroquine-sensitive P. falciparum exists in Mexico, the Caribbean, Central America
west and north of the Panama Canal, and parts of North Africa, the Middle East, and
China.
P. falciparum strains resistant to chloroquine , mefloquine and sulfonamides are rare,
but are prevalent in the regions of Thailand bordering Burma (Myanmar) and
Cambodia (e.g., eastern provinces of Myanmar and western provinces of Cambodia),
and in parts of China, Laos, and Vietnam.
Chloroquine-resistant P. vivax is widespread in Indonesian Papua and Papua New
Guinea (See UpToDate for latest information).

3.2

Life Cycle of the Malarial Parasite


The Plasmodium genus of protozoan parasites has a life cycle that is split between a
vertebrate host and an insect vector. In general, the host is man and the insect vector is
the Anopheles mosquito. Asexual development occurs in the human host, and sexual
development occurs in the mosquito. The basic life cycle of the parasite is illustrated in
ATTACHMENT B.

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4. PERSONAL PROTECTION MEASURES


The Office of Medical Services requires all Volunteers serving in malaria endemic areas to
limit their exposure to infectious mosquitoes and to use personal protection measures to
prevent malaria. Anopheles mosquitoes bite at night, with peak biting between 10 p.m. and 4
a.m. Medical officers should advise Volunteers to limit their exposure to mosquitoes during
these hours.
Use of personal protection measures is an important primary prevention measure. Consistent
use of personal protection measures reduces the number of mosquito bites; this can
significantly reduce the risk of malaria and can also reduce the risk of other mosquito-borne
infections, e.g., dengue. Standard personal protection measures are listed below. Medical
officers should insure that Volunteers understand these measures and should encourage their
use.

Clothing: Wear light or bright clothing that covers most of the body, e.g., long sleeved
shirts, long pants, and socks. Mosquitoes are attracted to dark clothing after dusk.
Permethrin-sprayed clothing provides maximum protection.

Mosquito Nets: Sleep under mosquito netting. Netting should have small mesh and
should not be damaged. When used properly, nets over cots and beds provide excellent
protection against mosquitoes and crawling insects. Nets impregnated with permethrin
provide maximum protection. Permethrin- impregnated nets can be procured, at no
charge to post, through the Post Logistic Support in Administrative Services
(M/AS/PLS). See TG 240, 15.4 Mosquito Nets.

Insect Repellent: Apply insect repellent. Use preparations that contain 30-35% N, N
diethylmethylbenzamide (DEET). . Preparations containing Picaridin 20% have equal
efficacy with preparations containing DEET 35%. When applied properly, these
preparations are effective for several hours. In addition, Volunteers should: (1) avoid
applying repellants with high-concentrations of DEET (>35%) to their skin - high
concentration products have rarely been associated with toxic encephalopathy in children;
(2) avoid inhaling or ingesting repellents; (3) avoid getting repellents in their eyes, (4)
wash repellent-treated skin after coming indoors, and (5) if using both sunscreen and
insect repellent, apply sunscreen first, preferably about 20 minutes before the insect
repellent. Insect repellents can reduce the effectiveness of sunscreen by about one third.
PCVs are encouraged to reapply repellent after bathing or sweating, if they are still at risk

Insect Spray: When needed, use Pyrethroid-containing flying-insect spray in living and
sleeping areas during evening and nighttime hours. Sprays should be used for at least a
half-hour before retiring. Insect spray may be provided at the discretion of the post.
Pyrethroid-containing insect sprays can be procured locally or through PLS. Permethrin
may be sprayed on clothing for additional protection against mosquitoes.

Screens: Stay in well-screened areas during mosquito feeding times. In malaria endemic
areas, OMS strongly recommends window and door screening of Volunteer living areas.

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Local Area Mosquito Control Measures


Mosquitoes breed in stagnant or slow moving water found in places such as water barrels or
catchments, discarded tires or pottery, stumps of trees, large leaves, and flower beds.
Therefore, PCMOs should instruct Volunteers to cover all household water containers and,
when possible, make every effort to eliminate or properly drain standing water within 30
meters of their living areas. This may decrease the number of mosquitoes to which they are
exposed. In humid, forested areas, decreasing the mosquito population may not be a
practical consideration.

5. CHEMOPROPHYLAXIS
The Office of Medical Services requires PCMOs to provide all Volunteers serving in malaria
endemic areas with appropriate chemoprophylaxis during their service and following close of
service (COS). This includes the provision of sufficient medication for post-exposure and
PART and the provision of chemoprophylaxis during vacation, home leave, medical
evacuation, and other departures from country. Volunteers residing in non-malaria endemic
areas who travel to malaria endemic areas should also be provided with appropriate
chemoprophylaxis.
The Office of Medical Services also requires PCMOs to educate Volunteers about the
following: (1) the life cycle of the malaria parasite (see ATTACHMENT B); (2) the proper
use of chemoprophylactic medication; and (3) the importance of uninterrupted
chemoprophylaxis.
Chemoprophylaxis is the use of antimalarial medication to suppress clinically significant
disease. Antimalarial medications do not prevent infection with the malaria parasite; rather,
they suppress clinical disease by attacking the parasites at different stages of its life cycle.
There are no antimalarials that are 100% effective or without side effects.
Peace Corps primarily uses two types of chemoprophylactics: suppressive and PART.
Suppressive chemoprophylactics, e.g., chloroquine, doxycycline, mefloquine, and Malarone
kill blood (asexual) stages of plasmodia, thereby suppressing clinically significant illness.
PART, e.g., primaquine, attacks liver stages of the parasite, thereby preventing disease.
PART is directed against the relapsing malarias, P. vivax and P. ovale (see Section 11
below). Therefore, prophylaxis prior to arriving in country (pre-exposure prophylaxis) or
immediately upon arrival in country (loading dose), and prophylaxis following departure
from country (PART), is required.
5.1

Choice of Chemoprophylaxis
Optimal malarial prophylaxis takes into consideration the most effective antimalarial
agent, side effects and Volunteer adherence.
There is no first-line drug in Peace Corps. All antimalarial drugs are utilized, as
appropriate, in suppressing malaria. Drug options include chloroquine, mefloquine,
doxycycline and atovaquone-proguanil (Malarone). Medical officers should, therefore,

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individualize their choice of chemoprophylactic agent for each Volunteer based on the
following considerations:

KEYS TO OPTIMAL MALARIA PROPHYLAXIS


Consider:

Area-specific OMS recommendations (see Section 5.2 below).

Drug-resistance profile in country, i.e., the Volunteers risk of exposure to


chloroquine-resistant P. falciparum malaria.

Drug contraindications and precautions.

Other factors:

Tolerance; includes the likelihood of Volunteer adherence to a particular


chemoprophylactic regimen (see Sections 5.3 and 8 below).

Dosing schedules, i.e., weekly versus daily dosing. Regimens that


require daily dosing may increase the opportunity for non-compliance,
whether accidental, intentional, or associated with illness.

For additional information on malaria chemoprophylaxis, PCMOs should refer to the


most current issues of Health Information for International Travel (Yellow Book)
published by the CDC. This book is available on the World Wide Web at
www.cdc.gov/travel/reference.htm. Additional references and resources on malaria
risk and prophylaxis are included below.
Book
Centers for Disease Control and Prevention (CDC). Health Information for International
Travel 2014. Oxford University Press, New York 10016. Atlanta: Department of Health and
Human Services, Public Health Service, Centers for Disease Control and Prevention,
National Center for Emerging and Zoonotic Infectious Diseases, Division of Global
Migration and Quarantine; available online at
http://wwwnc.cdc.gov/travel/yellowbook/2014/table -of-contents
Internet
CDC malaria map: http://cdc-malaria.ncsa.u/uc.edu
CDC malaria website (includes health information for international travel):
http://www.cdc.gov/malaria
CDC travelers health website: http://wwwnc.cdc.gov/travel
WHO malaria website: http://www.who.int/topics/malaria/en/
Medications sheets published by CDC:
http://www.cdcc.gov/malaria/references_resources/fsp.html
CDC stories on people with malaria: http://www.cdc.gov/malaria/stories/index.html
CDC Malaria 101 for the Health Care Provider CME:
http://www.cdc.gov/parasites/cme/malaria/index.html

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Phone
CDC (800) CDC-INFO
CDC Malaria Hotline (treatment): (770) 488-7788 (M-F 9 a.m.- 5 p.m. EST); (after hours
request to speak with the Malaria Branch Clinician).
International Society of Travel Medicine: 1-(770)-736-7060

5.2

Recommended Chemoprophylactic Regimens


The Office of Medical Services bases its recommendations for malaria chemoprophylaxis
on the most recent guidance from the CDC. In general, CDC chemoprophylaxis
recommendations are based on the overall rate of malaria transmission, i.e., malaria
risk, and the presence of chloroquine-resistant P. falciparum, in a given area. Malaria
risk estimates, i.e., the estimated risk of a traveler acquiring malaria, are primarily
derived from World Health Organization (WHO) surveillance data and can vary
markedly from area to area and year to year. The Office of Medical Services does not
endorse guidance for malaria prophylaxis that is not consistent with CDC guidelines.

Areas with chloroquine-sensitive P. Falciparum .

Chloroquine should be strongly considered for chemoprophylaxis in areas where


chloroquine-sensitive P. falciparum exists. Chloroquine is usually well tolerated.
Volunteers who experience uncomfortable adverse reactions may tolerate the drug
better by taking it with meals. If adverse reactions persist, alternative
chemoprophylactic agents should be discussed and initiated.
When possible, chloroquine prophylaxis should begin one to two weeks prior to arrival
in country. If this is not possible, Volunteers should start chloroquine prophylaxis just
prior to departure or immediately upon their arrival in a malarial area. Chloroquine
should be continued once weekly during service and for four weeks following
exposure.
Apart from its bitter taste, chloroquine is usually well tolerated. Minor side effects
include gastrointestinal disturbances, dizziness, blurred vision, and headache;
gastrointestinal problems may be alleviated by taking the drug with food. It has been
associated with triggering flares of psoriasis and pruritus, although serious side effects
are rare. Pruritus occurs in up to 25 percent of darked skinned individuals of African
descent due to concentration of the drug in skin; this is not an allergic reaction. Retinal
injury, which can occur when high doses of chloroquine are used to treat rheumatoid
arthritis, does not occur with the weekly dosages used for malaria prevention.
Chloroquine is safe for use in pregnancy. (See UpToDate for the latest information)
If chloroquine cannot be taken due to co-existing medical conditions or chloroquine
intolerance, alternative agents should be used. These include doxycycline, mefloquine,
and Malarone.

Areas where chloroquine-resistant P. falciparum EXISTS.

There is no first-line drug in Peace Corps. All antimalarial drugs are utilized, as
appropriate, in suppressing malaria. Drug options include atovaquone-proguanil
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(Malarone), doxycycline and mefloquine. If a particular chemoprophylactic agent cannot


be taken due to co-existing medical conditions or drug intolerance, alternative agents
should be used.
Atovaquone-proguanil (Malarone) is administered daily beginning one to two days
prior to exposure, during exposure, and for one week following exposure. The drug is
well tolerated, with excellent profiles of safety and efficacy. Adverse effects may
include gastrointestinal upset, insomnia, headache, rash and mouth ulcers.
Atovaquone-proguanil is contraindicated in patients with creatinine clearance <30 mL
per minute and it is not recommended for use in pregnant women due to insufficient
safety data
Doxycycline is administered daily beginning one to two days prior to exposure, daily
during exposure, and daily for four weeks following exposure. Noncompliance with
this daily regimen is an important reason for doxycycline prophylaxis failure.
Doxycycline is usually well tolerated, but has been associated with gastrointestinal
upset; less commonly, ultraviolet photosensitivity, Candida vaginitis, and rare cases of
esophageal ulceration may also occur. The drug should be taken with fluids and food; it
should not be administered immediately before lying down. Sunscreen should be
applied liberally for the duration of prophylaxis. It is advisable to offer women
antifungal self treatment for management of Candida vaginitis (eg, fluconazole).
Doxycycline is contraindicated in pregnant women and in children <8 years of age.
Mefloquine is administered weekly beginning at least two weeks prior to exposure,
during exposure, and for four weeks following exposure. Some individuals experience
adverse effects from mefloquine; most are mild, self-limited, and do not require
discontinuation of the drug. The most frequent adverse effects are gastrointestinal
upset, lightheadedness, headache, difficulty concentrating, mood swings, and strange
dreams. About 5 percent of travelers experience disabling neuropsychiatric adverse
effects requiring discontinuation of the drug. These include anxiety, depression,
nightmares, paranoid ideation, and dizziness. About 1 in 10,000 travelers experience
severe neuropsychiatric reactions such as seizures and psychosis. Adverse effects
appear to be more common among women and less frequent among children. Most
adverse effects requiring mefloquine discontinuation occur within the first three doses.
Contraindications to mefloquine include known hypersensitivity to the drug, a history
of seizures or major psychiatric disorder, and a recent history of depression or anxiety.
Development of psychiatric symptoms (such as depression, anxiety, restlessness or
confusion) while taking mefloquine should be viewed as a possible prelude to other
events; in such circumstances it is advisable to stop the drug immediately and switch to
a different prophylaxis agent. Mefloquine has also been associated with sinus
bradycardia and QT interval prolongation; therefore, it should be used with caution in
patients with cardiac conduction disorders.
For pregnant patients who cannot avoid travel to areas with chloroquine-resistant P.
falciparum, mefloquine may be safely administered during all trimesters.

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Areas with localized chloroquine-resistant P. falciparum

In some countries, chloroquine-resistant P. falciparum may be localized to specific


areas of the country. Such areas are shrinking and mainly occur in South America
(outside of the Amazon basin) and in Southern Asia (India and Nepal). In these areas,
chloroquine prophylaxis is reasonable if the incidence of malaria has been closely
monitored and where drug resistance has not been observed. Medical officers should
consult OMS for guidance on the use of chloroquine in such areas.
5.3

Volunteer Adherence
All Volunteers serving in malaria endemic areas are at high risk for infection with the
malaria parasite. To suppress clinical infection, OMS requires all Volunteers serving in
malaria endemic areas to rigorously adhere to a chemoprophylactic regimen throughout
their tour of duty and following COS. This includes the use of chemoprophylaxis during
vacation, home leave, medical evacuation, and other departures from country. Volunteer
failure to comply with OMS-recommended malaria prevention measures can result in
symptomatic malaria infections. These infections cause significant illness, impair
Volunteer effectiveness, result in unnecessary financial costs, and, tragically, occasionally
result in Volunteer death.
To encourage Volunteer adherence, PCMOs should: (1) educate Volunteers on the
importance of primary and secondary malaria prevention strategies; (2) provide
Volunteers information on the various chemoprophylactic regimens (see
ATTACHMENT C Antimalarial Chemoprophylaxis, Advantages and
Disadvantages, and ATTACHMENT D Antimalarial Medication Information
Sheets); (3) instruct Volunteers to consult the PCMO if adverse reactions to
chemoprophylaxis occur; and (4) counsel Volunteers who state they are unwilling or
unable to follow OMS-required malaria prevention strategies and, when appropriate,
offer alternative prophylactic antimalarial medication (see Section 8 below).
During pre-service training, Trainees will participate in group and individual discussions
with a medical officer to decide whether a weekly medication schedule or a daily
medication schedule and which agent would be best for the individual Trainee to assure
100% compliance for the entirety of his/her PC service.
Volunteers should not stop any chemoprophylactic regimen without consulting the
PCMO. Improper self-discontinuation of prophylaxis places a Volunteer at risk for
malaria. Volunteers who are unable to comply with malaria prevention strategies due to
willful misconduct or disregard for the Peace Corps Volunteer Health Program should be
referred to the Country Director for administrative action (see MS 262 Section 3.2).

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The flow chart below is a guideline for dealing with PCVs who contract malaria. Every
case must be handled individually and discussions and medical recommendations must be
documented appropriately in the medical record. Do not forget to discuss mosquito bite
avoidance measures as well as chemoprophylactic use. For any given PCV, there is no
set number of documented cases of malaria that would necessarily lead to an action
to separate.

Mefloquine Medication Guide


Medical officers are required to distribute the Mefloquine Medication Guide
(ATTACHMENT E) to all Volunteers taking mefloquine, and to obtain a signed
Mefloquine Medication Guide Acknowledgement form (ATTACHMENT F). The
acknowledgement form should be obtained prior to starting the Volunteer on prophylaxis
and filed in the Volunteers health record.
This policy is consistent with the July 2003 FDA-approved patient labeling and legal
requirement that a Mefloquine Medication Guide is supplied to patients when mefloquine
is dispensed. The purpose of the medication guide is to help ensure patients understand the
risks of malaria and the rare but potentially serious neuropsychiatric adverse events
associated with use of mefloquine. It also provides information on how they can recognize
these neuropsychiatric risks and take early action to prevent serious harm.

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6. STARTING CHEMOPROPHYLAXIS
In general, the CDC recommends that travelers start chemoprophylaxis one to two weeks
prior to arrival in a malarial area. If this is not possible, the CDC advises travelers to start
antimalarials just prior to their departure or immediately upon their arrival in a malariaendemic area. Both strategies, when combined with mosquito avoidance and personal
protective measures, i.e., insect repellent, bed nets, and screens, are effective in preventing
acute malaria. Therefore, for Peace Corps Trainees, OMS recommends that malaria
prophylaxis be started either during staging or immediately upon arrival in country.
Loading Dose
In countries where Volunteers do not receive antimalarial medication prior to departure from
the U.S. and the PCMO suspects that Volunteers may be immediately and intensely exposed
to malaria upon their arrival in country, they should consult OMS for guidance. In such
cases, OMS will consider whether to recommend a loading dose of a chemoprophylactic
agent that can rapidly produce protective blood levels. In general, a loading dose is only
used for Volunteers taking mefloquine, but this is discouraged by OMS For those PCVs who
choose to use mefloquine, it is recommended that the PCV/T be placed on daily doxycycline
during the first two weeks of mefloquine treatment. A loading dose is not required for
Volunteers taking doxycycline and no data exists to support a loading dose in Volunteers
taking chloroquine or Malarone.
7. CHEMOPROPHYLACTIC AGENTS
This following table is a summary of dosing schedules, adverse reactions, and
contraindications of common chemoprophylactic agents used by Peace Corps. Additional
information is also available in the Antimalarial Medication Information Sheets (see
ATTACHMENT D.

CHEMOPROPHYLACTIC AGENTS

Drug
Atovaquoneproguanil
(Malarone)

Tablet
size

Dose and
Frequency

250 mg
atovaquon
e and 100
mg
proguanil

One tablet
daily

Discontinuation
duration (time
after last
exposure)
7 days

Adverse Reactions
Adverse reactions
include abdominal
pain (17%),
nausea (12%),
vomiting (12%),
headache (10%),
diarrhea (8%),
weakness (8%),
loss of appetite
(5%), and
dizziness.
Mouth ulcers,
cough, pruritus,
urticaria, blood
disorders, and
hair loss have
also been
reported

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Contraindications
Contraindicated in persons with:

severe renal
impairment (creatinine
clearance < 30
ml/min).
Should b e avoided in persons
who are taking:

tetracyclines.
Tetracyclines cause a
40% decrease in
atovaquone
concentrations.

Metopramide and
rifampin. Both drugs
reduce the plasma
concentration of
atovaquone

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Chloroquine
phosphate
(Aralen and
generic agents)

500 mg
salt (300
mg base)

One tablet
weekly

4 weeks

Reports of sleep
disturbance and
unusual dreams;
reactions tend to
be no more
frequent than for
mefloquine users.
May cause
depression,
blurred vision,
nausea, pruritus,
headache, or
paresthesias.

Persons with
porphyria.
May interfere with
antibody response to
human diploid cell
rabies intradermal
vaccines.

Reports of rare,
severe, adverse
reactions
including
neuropsychiatric,
e.g., extrapyramidal
symptoms,
neuropathies,
agitation, and
psychosis
(1/13,600 people)
May worsen
symptoms of
psoriasis.
[Retinopathy in
persons with a
history of longterm, high dose,
chloroquine use,
i.e., a total
cumulative
exposure > 60
gms (approx. 4
years of weekly
medication).
Routine eye
exams q6 months
are indicated in
these individuals.]
Doxycycline
hyclate
(Vibramycin,
Vibra-Tabs,
other brands,
and generic
agents);
doxycycline
monohydrate
(Monodox,
Adoxa, and
generic agents)

100 mg

One tablet
daily

4 weeks

Minor adverse
reactions include
photosensitivity,
increased
incidence of
monilial vaginitis,
and
gastrointestinal
disturbance. May
cause
esophagitis,
especially if taken
at night.

Mefloquine
hydrochloride
(Lariam and
generic agents)

250 mg
salt (228
mg base)

One tablet
weekly

4 weeks

Minor adverse
reactions include
GI disturbance
and dizziness;
reactions tend to
be transient and

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Pregnancy
Persons allergic to
tetracycline or other
macrolide antibiotics.

Contraindicated in persons with:

a known
hypersensitivity to
mefloquine or related
compounds, e.g.,
quinine.

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self-limited.
Infrequent reports
of chest pain,
edema and
dyspepsia.
Reports of sleep
disturbances and
unusual dreams;
reactions tend to
be no more
frequent than for
chloroquine users.
May cause
psychiatric
symptoms ranging
from anxiety,
paranoia, and
depression to
hallucinations and
psychotic
behavior. On
occasion, these
symptoms have
been reported to
continue long after
mefloquine has
been stopped
Reports of rare,
severe, adverse
reactions, the
most common
being
neuropsychiatric ,
e.g. tremor,
ataxia, mood
changes, and
panic attacks
(1/10,000-13,000
people).

active depression, a
recent history of
depression,
generalized anxiety
disorder, psychosis,
schizophrenia or other
major psychiatric
disorders.

History of convulsions
or seizures.
Not recommended in persons
with:

cardiac conduction
defects, e.g., A-V
block, bundle branch
block, or a prolonged
QT interval.

atrial or ventricular
arrhythmias.

are on beta-blockers
for the cardiac
conduction defects and
arrhythmias listed
above.
Use with caution in persons
with:
a previous history of
depression.

Rare cases of
suicidal ideation
and suicide,
though no
relationship to
drug
administration has
been confirmed

Mefloquine, Malarone and doxycycline may also be used in chloroquine -sensitive areas as necessary.

7.5

Agents Not Recommended for Chemoprophylaxis


The following chemoprophylactic agents are not listed as malaria prophylactic options
by the CDC and are not recommended by OMS.

Chloroquine/Proguanil (Paludrine)

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Pyrimethamine-sulfadoxine (Fansidar): Fatal allergic reactions have been reported


with prophylactic use of Fansidar (1/11,000-26,000 users) (Mendel, et al., 2000).
Life-threatening reactions have not been reported with single doses used for the
treatment of malaria.

Pyrimethamine (Daraprim)

Pyrimethamine-dapsone (Maloprim)

Amodiaquine

Halofantrine (Halfan)

8. ASSESSING ANTIMALARIAL TOLERANCE


Preventing acute malaria depends not only upon the effectiveness of specific antimalarial
agents, but also upon the Volunteers compliance with, and tolerance of, a recommended
chemoprophylactic regimen.
Medical officers are encouraged to consider antimalarial tolerance when determining optimal
chemoprophylactic therapy for Volunteers. Tolerance includes the Volunteers previous
experience with antimalarial medications the likelihood of Volunteer adherence to a
particular chemoprophylactic regimen.
When a Volunteer complains of side effects or intolerance which he or she attributes to a
particular antimalarial medication, and then requests that the PCMO switch him/her from the
recommended chemoprophylactic agent to another agent, the PCMO should do the
following:

If the request for an alternative agent is clinically appropriate, switch regimens.

If the request for an alternative agent is not climically appropriate, assess the Volunteers
reasons for requesting an alternative agent and consider switching to an alternative agent
to improve adherence.

Consult OMS or the RMO if a Volunteer is unwilling or unable to maintain adherence


with their chemoprophylaxis regimen.

8.1

Switching Antimalarials
When switching from one antimalarial to another, care is necessary to avoid a gap in
protective blood levels. This is especially important in Trainees as blood levels may be
low for several weeks after starting a weekly chemoprophylactic agent. It is also
important for Volunteers who have been in a malarial area for many weeks and are
likely to already be infected.
Daily Dose to a Daily Dose
When switching from a daily dose of doxycycline or Malarone to a daily dose of
doxycycline or Malarone, no overlap is necessary.

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Daily Dose to a Weekly Dose

When switching from a daily dose of doxycycline or Malarone to a weekly dose of


mefloquine, overlap both regimens for four weeks. An alternate, although less
preferred, approach may be to provide a three-day loading dose of mefloquine (Not
FDA approved: mefloquine 250mg daily for three consecutive days).

Weekly Dose to a Daily Dose

When switching from weekly mefloquine or chloroquine to daily doxycycline or


Malarone, no overlap is necessary.

Weekly Dose to a Weekly Dose

It is unusual to switch from weekly chloroquine to weekly mefloquine but in these rare
instances, a three-day loading dose of mefloquine should be provided. Medical officers
should contact OMS for guidance prior to starting mefloquine therapy in these cases.
9. MISSED DOSES

Missed Weekly Dose (Chloroquine or Mefloquine)

If a dose of a weekly chemoprophylactic agent is missed, the Volunteer should take that
missed dose as soon as they remember it, and continue on their regular schedule.

Missed Daily Dose (Doxycycline or Malarone)

If a dose of a daily chemoprophylactic agent is missed, the Volunteer should resume daily
dosing immediately. No loading dose is necessary when resuming chemoprophylaxis with
these agents. Volunteers should be advised against doubling up on their antimalarial when
resuming chemoprophylaxis after missing a dose of their medication.
Volunteers are more likely to forget drugs that are given daily and this may lead to
breakthrough cases of malaria. If this occurs, the PCMO should discuss the option of a
weekly drug (if clinically appropriate) with the Volunteer..

10. SHORT TERM TRAVEL TO MALARIA ENDEMIC AREAS


Occasionally, Volunteers serving in non-malaria endemic areas will require intermittent
malaria prophylaxis for short-term travel. In such cases, OMS recommends that PCMOs
follow the guidance outlined in this guideline. Special attention should be paid to Section 5.2
Recommended Chemophylactic Regimens, Section 5.3 Volunteer Adherence noting that
PCMOs are required to distribute the Mefloquine Medication Guide (ATTACHMENT E)
to all Volunteers taking mefloquine and to obtain a signed Mefloquine Medication Guide
Acknowledgement form (ATTACHMENT F). Section 11 Leaving the Malaria Endemic
Area should be reviewed with the Volunteer. Medical officers serving in non-malaria
endemic areas should contact OMS if they have questions about malaria preventio n.

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11. LEAVING THE MALARIA ENDEMIC AREA


11.1 Presumptive Anti-Relapse Therapy (PART)
The Office of Medical Services requires all Volunteers who have been in a malaria
endemic area for more than four weeks1 , where P. ovale and P. vivax exist, to take
PART (terminal prophylaxis). At present, these areas include all malaria endemic
countries except Haiti and the Dominican Republic where these forms of malaria have
not been reported.
Primaquine phosphate is the drug of choice for malaria terminal prophylaxis (see
Section 11.2 below). Primaquine is effective against the liver stages (hypnozoites) of P.
vivax and P. ovale and decreases the risk of late relapses of malaria. Such relapses
typically occur 6-12 months after stopping chemoprophylaxis and can occur as long as
four years after prophylaxis is discontinued. Primaquine is the only drug that is
effective against the dormant liver stage of the parasite.
Presumptive Ant-relapse Therapy
AREAS WHERE P.OVALE AND P.VIVAX MALARIA EXIST
Drug
Primaquine

Dose

Adverse Reactions

Post Exposure:
30 mg base (52.6)
mg salt) once
daily for 14 days.
Start 2 weeks
following final
departure from the
malaria endemic
area if the
Volunteer is taking
chloroquine,
mefloquine, or
doxycycline.
Start 1 week
following final
departure from the
malaria endemic
area if the
Volunteer is taking
Malarone.

Minor adverse
reactions include
headaches,
abdominal cramps,
nausea, vomiting
and pruritus.
Methemoglobinemia
is common but
rarely necessitates
discontinuation of
therapy.

Contraindications

May cause severe


hemolysis in G6PDdeficient individuals.
Before primaquine is used,
G6PD deficiency must be
excluded by appropriate
laboratory testing.

Leukopenia and
agranulocytosis
occur rarely.

As per CDC: No reasonable data exist to support the use of primaquine in individuals who are exposed to P.

vivax or P. ovale for less than 4 weeks.


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11.2 Primaquine Phosphate

Post Exposure Dose: Primaquine phosphate 30 mg base (52.6 mg salt) once daily
for 14 days. Primaquine should be started 2 weeks following final departure from
the malaria endemic area if the Volunteer is taking chloroquine, mefloquine, or
doxycycline; and 1 week following final departure if the Volunteer is taking
Malarone. Primaquine should be given concurrently with all antimalarials except
Malarone.

The enzyme G6PD is required for Primaquine metabolism. Because G6PD


deficiency is associated with severe hemolysis, all Volunteers must be tested
for G6PD deficiency prior to being given primaquine. Medical Officers
must clearly document G6PD test results in the Volunteer health record and
should not issue primaquine to Volunteers with any degree of G6PD
deficiency (see Section 12 below).

Regular Malaria Prophylaxis: Volunteers should continue to take their regular


malaria prophylaxis regimen (with the exception of Malarone) for four weeks after
leaving a malarial area. Volunteers taking Malarone should continue for one week
after leaving a malarial area.

Adverse Reactions: Minor side effects include headaches, abdominal cramps,


nausea, vomiting and pruritus. Methemoglobinemia is also common, but rarely
necessitates interruption of therapy. Leukopenia and agranulocytosis occur rarely.

Contraindications: Primaquine can cause hemolysis in persons with G6PD


deficiency. Hemolysis may be mild or severe. Medical Officers should not give
Volunteers with an abnormal or low G6PD test result primaquine (see section
11 below).

Pregnancy: Primaquine is contraindicated during pregnancy. Pregnant Volunteers


departing malaria endemic areas should be issued a PC-127C Authorization for
Payment of Medical/Dental Services for an OB/GYN prenatal consultation, to
include recommendations regarding terminal malaria prophylaxis (see TG 170
Pregnancy).

11.3 Close of Service Procedures in Malaria Endemic Areas


Medical Officers must provide all Volunteers leaving malaria endemic areas with the
following:

See also Malaria Prophylaxis in TG 330 under Section 4.4 Physical Exam.

Malaria prophylaxis according to the guidance outlined above. This should include:
(1) post-exposure prophylaxis as outlined above and in TG 330 Attachment G, and
(2) an additional 30 day supply of a malaria prophylaxis medication, e.g.,
mefloquine, doxycycline, or Malarone, if the Volunteer will be traveling in a
malaria endemic area prior to returning to the U.S If the Volunteer will be
traveling for more than 30 days, provide them with the website
(http://www.istm.org/AF_CstmClinicDirectory.asp)where they can find a travel
clinic in the country they will be visiting to obtain prophylaxis.

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December 2014

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TG 840
Malaria Prevention

Medications for one course of interim self-treatment of malaria for use should the
Volunteer develop symptoms of acute malaria (see TG 845.5.1 Interim SelfTreatment Regimens for medications and dosing schedules).

PART according to the guidance outlined in Section 11.1 Presumptive AntiRelapse Therapy above.

Handout titled Instructions for Volunteers: COS Guidelines for Preventing


Malaria (see TG 330, ATTACHMENT G), to include:

Education and instruction on post-departure malaria prophylaxis.

Education and instruction on PART.

Instructions to report their Peace Corps service and exposure to malaria to


their HOR physician. P. vivax and P. ovale may relapse despite compliance
with primaquine PART.

12. G6PD TESTING


The Office of Medical Services requires that all Volunteers be tested for G6PD deficiency
prior to the administration of primaquine. Glucose-6-Phosphate Dehydrogenase (G6PD) is
an enzyme in red blood cells that is involved with glucose metabolism. Persons with G6PD
deficiency are at risk for hemolytic anemia when taking primaquine. Hemolysis may be
severe in some people.
All Trainees going to malaria endemic areas of Africa are tested for G6PD deficiency prior to
Peace corps service. If a Trainees G6PD status is unknown, and the Trainee is serving in a
malaria endemic area, testing should be done in country if a reliable laboratory exists in
country. Preferably, the test should be done during pre-service training (PST) so that if a
Trainee terminates service early, his/her G6PD status will be known prior to departure.
If a reliable laboratory is not available in country, PCMOs should provide Volunteers with a
PC-127C Authorization of Payment of Medical/Dental Services for G6PD deficiency
testing in the U.S. This may be done during service or at COS.
Medical officers may use Quest Diagnostics for G6PD level determination if post can
reliably ship blood to the U.S. in less than 48 hours. Blood should be sent anticoagulated in
a lavender-top tube. Samples received more than 48 hours after collection may be falsely
reported as having low G6PD activity due to sample deterioration (see TG 360 Use of U.S.
Laboratories).
Volunteers who have not been tested for G6PD deficiency prior to COS should not be issued
primaquine. These Volunteers should be issued a 127C authorization for, primary care
consultation for G6PD testing and terminal malaria prophylaxis as indicated.
In addition, Volunteers: (1) whose test results have not been received, (2) whose test results
are not clearly documented in the health record, or (3) whose test results report any degree of
G6PD deficiency should not be issued primaquine. Medical officers may contact OMS for
assistance obtaining results.
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December 2014

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TG 840
Malaria Prevention

G6PD Test Results


Test results must be obtained and clearly documented on the cover of the Volunteer health
record prior to the administration of primaquine. The laboratory report should be filed in the
health record under In-Service Diagnostics.

Normal: Normal or G6PD present test results done in country or at a U.S. lab are
acceptable. When indicated, these Volunteers may be given primaquine.

Abnormal: Medical officers should issue the Volunteer a 127C authorization for
primary care consultation for evaluation of G6PD deficiency and terminal malaria
prophylaxis as indicated. A copy of the lab report should be attached to the 127C.
PCMOs should instruct Volunteers with abnormal results to remain on their malaria
prophylaxis until their G6PD status is confirmed. Medical officers should not give
primaquine to a Volunteer with an abnormal or abnormally low G6PD result.

No result available at COS: Volunteers who have not been tested for G6PD deficiency
prior to COS should not be given primaquine.

13. CHEMOPROPHYLAXIS IN PREGNANCY


In addition to the following guidance, PCMOs should refer to the current edition of Health
Information for International Travel published by the CDC for additional information on
antimalarial recommendations in pregnant women, nursing mothers, and children.

Pregnant Volunteers: Severe cases of malaria can occur during pregnancy. Pregnancy
alters the immune system and malaria may adversely affect the outcome of pregnancy.
Therefore, all pregnant Volunteers are required to take malaria chemoprophylaxis. The
CDC recommended drugs of choice in pregnancy are:

Chloroquine-sensitive areas: Chloroquine 300 mg (500 mg base) weekly.

Chloroquine-resistant areas: Mefloquine 250 mg weekly if the potential benefit


justifies the potential risk to the fetus.

Doxycycline and primaquine are contraindicated during pregnancy.

Malarone is not currently recommended by the CDC for use in pregnancy. Medical
officers should consult OMS in situations where a pregnant Volunteer is unable to
take mefloquine.

Pregnant Volunteers located in areas with chloroquine-resistant malaria should be placed


on mefloquine and evacuated or separated from the malarial area within one week of
pregnancy diagnosis (see TG 170.4.1 Pregnancy in Areas with Chloroquine-resistant
Malaria). Weekly mefloquine should be continued for 4 weeks after leaving the endemic
area.

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December 2014

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Malaria Prevention

14. STORAGE OF ANTIMALARIAL DRUGS


An overdose of antimalarial drugs can be fatal, especially in children. Medical officers
should dispense antimalarial drugs in childproof containers. Medical officers should also
instruct Volunteers to always store medication in childproof containers and out of the reach
of children.

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Malaria Prevention

REFERENCES
Arguin PM, Keystone, JS. Prevention of malaria infection in travelers. In: UpToDate, Basow,
DS (Ed), UpToDate, Waltham, MA, 2012.
Boudreau, Shuster, Sanchez et al. Tolerability of Prophylactic Lariam Regimens. Trop Med
Parasitol 1992, 44:257.
Cox-Singh J, Davis TM, Lee KS, et al. Plasmodium knowlesi malaria in humans is widely
distributed and potentially life threatening. Clin Infect Dis 2008; 46:165.
Freedman DO. Clinical practice. Malaria prevention in short-term travelers. N Engl J Med
2008; 359:603.
Goldsmith R. & Heynemann D. Tropical Medicine and Parasitology. Norwalk, CT:
Appleton & Lange, 1989.
Hill DR, Ericsson CD, Pearson RD, et al. The practice of travel medicine: guidelines by the
Infectious Diseases Society of America. Clin Infect Dis 2006; 43:1499.
http://www.cdc.gov/malaria/travelers/drugs.html (Accessed on November 23, 2012).
Kochar DK, Saxena V, Singh N, et al. Plasmodium vivax malaria. Emerg Infect Dis 2005;
11:132.
Krause G, Schneberg I, Altmann D, Stark K. Chemoprophylaxis and malaria death rates.
Emerg Infect Dis 2006; 12:447.
Leder K, Black J, O'Brien D, et al. Malaria in travelers: a review of the GeoSentinel
surveillance network. Clin Infect Dis 2004; 39:1104.
Lobel H. O. & Kozarsky P. E. Update on prevention of malaria for travelers. JAMA, 278,
1767-1771, 1997.
Lobel H. O., Miani, M., Eng T., et al. Long-term malaria prophylaxis with weekly
mefloquine. Lancet, 1993, 341: pp. 848-851.
Mali S, Steele S, Slutsker L, et al. Malaria surveillance - United States, 2008. MMWR
Surveill Summ 2010; 59:1.
Mali S, Kachur SP, Arguin PM, et al. Malaria surveillance--United States, 2010. MMWR
Surveill Summ 2012; 61:1.
Mandell, G. L., Douglas, R. G., and Bennett, J. E. Principals and Practice of Infectious
Diseases, 5th edition. Churchill Livingston, 2000.
Navy and Marine Corps Public Health Center. Pocket Guide to Malaria Prevention and
Control. Portsmouth, Virginia. 2011.

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December 2014

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TG 840
Malaria Prevention

Overbosch, D., et al., Atovaquone-proguanil versus mefloquine for malaria prophylaxis in


nonimmune travelers: results from a randomized, double-blind study. Clinical Infectious
Diseases, 2001. 33(7): pp. 1015-21.
Schlagenhauf, P., Mefloquine, in Travelers' Malaria, P. Schlagenhauf, Editor. 2001, BC
Decker Inc.: Hamilton, Ontario. pp. 188-209.
Steffen R., Fuchs E., Schildknecht J., et al. Mefloquine compared with other malaria
chemoprophylactic regimens in tourists visiting East Africa. Lancet, 1993, 341, pp. 12991303.
Steffen, R., et al., Malaria chemoprophylaxis among European tourists in tropical Africa: use,
adverse reactions, and efficacy. Bull World Health Organ, 1990. 68(3): pp. 313-22.
Wilson ME, Weld LH, Boggild A, et al. Fever in returned travelers: results from the
GeoSentinel Surveillance Network. Clin Infect Dis 2007; 44:1560.

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December 2014

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TG 840 Attachment A

Worldwide Distribution
of Malaria
From

CDC Health Information for


International Travel 2014
(The Yellow Book)

December 2014

TG 840 ATTACHMENT B

LIFE CYCLE OF THE MALARIAL PARASITE

The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles
mosquito inoculates sporozoites into the human host
. Sporozoites infect liver cells
and mature into
schizonts
, which rupture and release merozoites
. (Of note, in P. vivax and P. ovale a dormant stage
[hypnozoites] can persist in the liver and cause relapses by invading the bloodstream weeks, or even years
later.) After this initial replication in the liver (exo-erythrocytic schizogony
), the parasites undergo asexual
multiplication in the erythrocytes (erythrocytic schizogony
). Merozoites infect red blood cells
. The ring
stage trophozoites mature into schizonts, which rupture releasing merozoites
. Some parasites differentiate
into sexual erythrocytic stages (gametocytes)
. Blood stage parasites are responsible for the clinical
manifestations of the disease.
The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles
mosquito during a blood meal
. The parasites multiplication in the mosquito is known as the sporogonic
cycle
. While in the mosquito's stomach, the microgametes penetrate the macrogametes generating
zygotes
. The zygotes in turn become motile and elongated (ookinetes)
which invade the midgut wall of the
mosquito where they develop into oocysts
. The oocysts grow, rupture, and release sporozoites
, which
make their way to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host
perpetuates the malaria life cycle
.

TG 840 Attachment C
Antimalarial Chemoprophylaxis: Advantages and Disadvantages
Chloroquine is highly effective, but can be use only in those areas of the world where the malaria is sensitive to
the medication. The usual dosing one tablet weekly
Advantages
Disadvantages
Highly effective preventive medication
Possible stomach upset often made better if taken with
food
Once weekly dosing
Possible problems with vision
Stays in the system for a long time providing some
Possible problems with hearing or ringing in the ears
antimalarial activity if a dose is delayed
Should not be used during pregnancy
Mefloquine is highly effective. The usual dosing is one tablet weekly
Advantages
Disadvantages
Highly effective preventive medication
Should not be used by individuals with a history of most
mental health issues
Weekly dosing could be an advantage for those not
Should not be used by individuals with a history of
used to taking daily meds
seizures
Stays in the system for a long time providing some
Should not be used by individuals with a history of
antimalarial activity if a dose is delayed
disturbances of the electrical conduction of the heart
Only antimalarial medication approved for pregnancy
Possible worsening or development of sleep
disturbance including nightmares; severe anxiety;
paranoia; hallucinations; depression; restlessness;
unusual behavior; confusion; suicidal thoughts [subject
of FDA boxed warning]
Possible development of dizziness, room spinning, ear
ringing, loss of balance which may persist or become
permanent [subject of FDA boxed warning]
Possible stomach upset
Possible headache
Atovaquone/Proguanil (Malarone) is highly effective. The usual dosing is one tablet daily
Advantages
Disadvantages
Highly effective preventive medication
Since atovaquone/proguanil is also used as a secondline treatment for active malaria, it cannot be used for
treatment if used for daily suppression
Once daily dosing for those already taking daily meds
Possible stomach upset
Should not be used during pregnancy
Doxycycline is highly effective. The usual dosing is one tablet/capsule daily
Advantages
Disadvantages
Highly effective preventive medication
Must be taken with at least 8 oz. of water and
preferably food
Once daily dosing for those already taking daily meds
Does not stay in the system for a long time and must be
taken at roughly the same time every day
Only agent with no malaria resistance demonstrated
Possible increased sun sensitivity in approximately 20%
of users. Must be compulsive with use of sun screen
Also effective in preventing or suppressing several other Possible heartburn and stomach upset which is
tropical infectious diseases (rickettsial disease and
significantly less likely if taken with a full glass of water
leptospirosis)
or food
Possibly improve acne
Possible increased chance of developing yeast
infections (vaginal)
Cannot be used during pregnancy
** This is not intended to be an exhaustive list of side effects of these medications. Your PCMO can provide more detailed
information.

December, 2014

TG 840 ATTACHMENT D

Chloroquine Tablets
(Anti-Malarial Medication)
MEDICATION INFORMATION SHEET
What is chloroquine?
Chloroquine is one of several types of drugs used to prevent and treat malaria. The type of drug
prescribed for you will be based on the area of the world you are traveling to and your medical conditions.
How do I take the tablets?

Take with food to prevent stomach upset.


Take this medication exactly as prescribed.
It is important that you not miss any doses and that you take the drug on a
regularly scheduled basis.
Store at room temperature away from sunlight and moisture.
Do not share this medication with others.
Do not donate blood for 3 years after taking chloroquine.

Are there any side effects (adverse reactions)?

This medication may cause nausea, vomiting, stomach upset, cramps, loss of
appetite, diarrhea, tiredness, weakness, or headache. These effects should subside
as your body adjusts to the medication. If these symptoms persist or become
severe, inform your Peace Corps health provider.
Contact your Peace Corps health provider if any of the following side effects
occur: changes in your sight, blurred vision, trouble seeing at night, problems
focusing clearly, difficulty hearing, or ringing in the ears.
An allergic reaction to this drug is unlikely, but seek immediate medical attention
if any of these symptoms occur: rash, itching, swelling, dizziness, or trouble
breathing.
If you notice other effects not listed above, contact your Peace Corps health
provider.

Is there any reason I should not take chloroquine?

Tell your Peace Corps health provider if you have pre-existing liver disease,
blood disorders, or psoriasis.

Children are very sensitive to the effects of chloroquine. It is important to keep


this and all medication out of the reach of children.

Tell your Peace Corps health provider of all prescription and nonprescription
R
R
drugs you may use, especially cimetidine (Tagamet ), kaolin (Kaopectate ), or
R
magnesium trisilicate (Gaviscon ).

Do not start or stop any medicine without Peace Corps health care provider
approval.
Page 1

TG 840 ATTACHMENT D

What if Im pregnant or breast-feeding?

This medication should be used only when clearly needed during pregnancy. Discuss
the risks and benefits with your Peace Corps health provider.

Small amounts of this medication are found in breast milk. Consult with your Peace
Corps health provider before breast-feeding.
What should I do if I miss a dose?

If you miss a dose, take the missed dose as soon as you remember and then continue
the usual dosing schedule. DO NOT double-up the dose to catch up unless
instructed to by a Peace Corps health care provider.
What should I do if I overdose?

If overdose is suspected, contact your Peace Corps health provider immediately.

You can avoid getting malaria!


Avoid mosquitoes and reduce mosquito bites
Wear light or bright clothing that covers most of your body (long
sleeved shirts, long pants, socks). Permethrin treated clothing
provides maximum protection.
Use mosquito nets over cots, beds, and tents. Permethrin treated nets
provide maximum protection.
Use insect repellent on all exposed areas of skin or clothing. The
most effective compounds contain N,N- diethylmethylbenzamide
(DEET).
Use pyrethroid-containing flying-insect spray or coils in living and
sleeping areas during evening and nighttime hours.
Remain in areas with screened windows and doors.
Eliminate mosquito-breeding sites by emptying or draining standing
water collected in outdoor containers or debris (discarded tires,
pottery, tree stumps).
Be sure your medical record shows that you received this medication.

Page 2

TG 840 ATTACHMENT D

Doxycycline
(Anti-Malarial Medication)
Medication Information Sheet
What is doxycycline?

Doxycycline is one of several types of drugs used to prevent and treat malaria. The
type of drug prescribed for you will be based on the area of the world you are
traveling to and your medical conditions.

Doxycycline is an antibiotic used to treat a wide variety of bacterial infections


(including the prevention and treatment of anthrax).
How do I take the medication?

Take each dose with a full glass of water (4 oz or 120 ml) or more.

Do not lie down for 30 minutes after taking this drug.

Take with food or milk if stomach upset occurs unless your Peace Corps health
provider directs you otherwise.

Avoid taking antacids containing magnesium, aluminum, or calcium, sucralfate, iron


preparations or vitamin (zinc) products within 2-3 hours of taking this medication.
These products bind with the medicine preventing its absorption.

Antibiotics work best when the amount of medicine in your body is kept at a constant
level. Do this by taking the medicine at evenly spaced intervals, such as at the same
hour each day or night.

Take this medication as prescribed. It is important that you not miss any doses and
that you take the drug on a regularly scheduled basis.

Store at room temperature away from moisture and sunlight.

Do not share this medication with others.


Are there any side effects (adverse reactions)?

This medication may cause stomach upset, diarrhea, nausea, headache or vomiting. If
these symptoms persist or worsen, notify your Peace Corps health provider.

These symptoms are unlikely, but report to your Peace Corps health provider if they
occur: stomach pain, yellowing of the eyes or skin, vision changes, mental changes.

Doxycycline increases sensitivity to sunlight.

Use of this medication for prolonged or repeated periods may result in a secondary
infection (e.g., oral, bladder or vaginal yeast infection).

In the unlikely event that you have an allergic reaction to this drug, seek immediate
medical attention. Symptoms of an allergic reaction include: rash, itching, swelling,
dizziness, or trouble breathing.

If you notice other effects not listed above, contact your Peace Corps health provider.

Page 3

TG 840 ATTACHMENT D

Is there any reason I should not take doxycycline?

Tell your Peace Corps health provider your complete medical history, especially liver
problems, kidney problems, allergies, especially drug allergies, trouble swallowing,
esophagus problems (e.g., hiatal hernia, GERD [gastro-esophageal reflux disease]).

Doxycycline may make you more prone to sunburn. Wear protective clothing, use a
sunscreen if needed, and limit your sun exposure.

This drug should not be used by children up to 8 years of age because its use may
permanently discolor their teeth or cause other problems. Caution is advised in older
children also.

Tell your Peace Corps health provider of all prescription and nonprescription drugs
you may use, especially other antibiotics, live vaccines, sucralfate, antacids, vitamins,
warfarin, or iron.

This medicine may decrease the effectiveness of oral contraceptives. Consult your
Peace Corps health provider about other types of birth control.

Do not start or stop any medicine without Peace Corps health care provider approval.
What if Im pregnant or breast-feeding?

This medication is not recommended for use during pregnancy. Consult your Peace
Corps health provider before using this medication.

This drug passes into breast milk and has had undesirable effects on nursing infants.
Therefore, its use is not recommended while breast-feeding. Consult your Peace
Corps health provider before breast-feeding.
What should I do if I miss a dose?

If you should miss a dose, take the missed dose as soon as you remember and then
continue the usual dosing schedule. DO NOT double-up the dose to catch up.
What should I do if I overdose?

If overdose is suspected, contact your Peace Corps health provider immediately.


You can avoid getting malaria!

Avoid mosquitoes and reduce mosquito bites


Wear light or bright clothing that covers most of your body (long sleeved shirts, long
pants, socks). Permethrin treated clothing provides maximum protection.
Use mosquito nets over cots, beds, and tents. Permethrin treated nets provide
maximum protection.
Use insect repellent on all exposed areas of skin or clothing. The most effective
compounds contain N,N- diethylmethylbenzamide (DEET).
Use pyrethroid-containing flying-insect spray or coils in living and sleeping areas
during evening and nighttime hours.
Remain in areas with screened windows and doors.
Eliminate mosquito-breeding sites by emptying or draining standing water collected
in outdoor containers or debris (discarded tires, pottery, tree stumps).
Be sure your medical record shows that you received this medication.

Page 4

TG 840 ATTACHMENT D

Mefloquine Tablets
(Anti-Malarial Medication)
Medication Information Sheet
What is mefloquine?
Mefloquine is one of several types of drugs used to prevent and treat malaria. The type of
drug prescribed for you will be based on the area of the world you are traveling to and your
medical conditions.
How do I take the tablets?

Take with food or milk to prevent stomach upset.

Do not take this on an empty stomach.

Take this medication as prescribed.

It is important that you not miss any doses and that you take the drug on a regularly
scheduled basis.

Store at room temperature away from sunlight and moisture.

Do not share this medication with others.


Are there any side effects (adverse reactions)?

This medication may cause stomach upset, stomach pain, nausea, vomiting, diarrhea,
headache, insomnia, vivid dreams, or lightheadedness. These effects should subside
as your body adjusts to the medication. If these symptoms persist or become severe,
inform your Peace Corps health provider.

This medication may cause dizziness or restlessness. Use caution when driving or
engaging in activities requiring alertness.

Contact your Peace Corps health provider immediately if any of the following side
effects occur; an alternative antimalarial will be substituted: unexplained anxiety,
mood changes, depression, hallucinations, restlessness, or confusion.

An allergic reaction to this drug is unlikely, but seek immediate medical attention if
any of these symptoms occur: rash, itching, swelling, dizziness, or trouble breathing.

If you experience an irregular heartbeat or notice other effects not listed above,
contact your Peace Corps health provider.
Is there any reason I should not take mefloquine?

Tell your Peace Corps health provider your complete medical history, especially
psychiatric problems, heart problems, seizure disorders, and allergies, especially
drug allergies.

Page 5

TG 840 ATTACHMENT D

Use with caution in children.


Tell your Peace Corps health provider of all prescription and nonprescription drugs
you may use, especially beta-blockers (e.g., atenolol, propranolol), chloroquine,
quinine, quinidine, or valproic acid (e.g., depakene or depakote).
Do not start or stop any medicine without Peace Corps health care provider approval.

What if Im pregnant or breast-feeding?

This medication should be use only when clearly needed during pregnancy. Discuss
the risks and benefits with your Peace Corps health provider.

This drug is excreted into breast milk. Consult with your Peace Corps health
provider before breast-feeding.
What should I do if I miss a dose?

If you miss a dose, take the missed dose as soon as you remember and then continue
the usual dosing schedule. DO NOT double-up the dose to catch up unless
instructed to by a Peace Corps health care provider.
What should I do if I overdose?

If overdose is suspected, contact your Peace Corps health provider immediately.


Symptoms of overdose may include vomiting and diarrhea.

You can avoid getting malaria!

Avoid mosquitoes and reduce mosquito bites

Wear light or bright clothing that covers most of your body (long
sleeved shirts, long pants, socks). Permethrin treated clothing provides
maximum protection.

Use mosquito nets over cots, beds, and tents. Permethrin treated nets
provide maximum protection.

Use insect repellent on all exposed areas of skin or clothing. The


most effective compounds contain N,N- diethylmethylbenzamide (DEET).

Use pyrethroid-containing flying-insect spray or coils in living and


sleeping areas during evening and nighttime hours.

Remain in areas with screened windows and doors.

Eliminate mosquito-breeding sites by emptying or draining standing


water collected in outdoor containers or debris (discarded tires, pottery, tree
stumps).

Be sure your medical record shows that you received this medication.

Page 6

TG 840 ATTACHMENT D

Atovaquone/Proguanil
R
(Malarone )
(Anti-Malarial Medication)
Medication Information Sheet
What is atovaquone/proguanil (Malarone)?
Atovaquone/proguanil (Malarone) is a combination drug, one of several drugs used to
prevent and treat malaria. The type of drug prescribed for you will be based on the area of
the world you are traveling to and your medical conditions.
How do I take the mediation?

Take by mouth usually once daily with food or a milky drink.

Take as directed by your Peace Corps health provider.

Your dosage and how long you will take this medication will depend on the reason
for its use (prevention or active infection).

Dosage for children is based on the childs weight and the reasons for its use
(prevention or active infection).

If you vomit within 1 hour of taking this medication, repeat the dose.

It is important that you not miss any doses and that you take the drug on a regularly
scheduled basis.

Store at room temperature between 36 and 86 degrees F (2 and 30 degrees C) away


from light and moisture.

Do not share this medication with others.


Are there any side effects (adverse reactions)?

This medication may cause nausea, vomiting, stomach pain, headache, or diarrhea. If
these symptoms persist or worsen, contact your Peace Corps health provider
promptly.

Contact your Peace Corps health provider immediately if any of these serious side
effects occur: loss of appetite, weight loss, unusual fatigue, or dizziness.

Contact your Peace Corps health provider immediately if any of these unlikely but
serious side effects occur: severe vomiting or diarrhea, fever, muscle or back pain.

An allergic reaction to this drug is unlikely, but seek immediate medical attention if
any of these symptoms occur: rash, itching, swelling, dizziness, or trouble breathing.

If you notice other effects not listed above, contact your Peace Corps health provider.
Is there any reason I should not take Malarone?

Tell your Peace Corps health provider your complete medical history, especially
kidney problems, previous treatments with this medication, recent severe vomiting or

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TG 840 ATTACHMENT D

diarrhea , and any allergies, especially drug allergies.


Caution is advised when using this drug in the elderly because they may be more
sensitive to the effects of the drug.
Tell your Peace Corps health provider of all prescription and nonprescription drugs
you may use, especially tetracycline, metoclopramide, rifamycins (e.g., rifampin,
rifabutin), or other products containing proguanil.
This medication may interfere with certain laboratory tests (e.g., transaminases).
Make sure your Peace Corps health providers know you use this drug.
Do not start or stop any medicine without Peace Corps health care provider approval.

What if Im pregnant or breast-feeding?

This medication should be used only when clearly needed during pregnancy. Also
use protective clothing, insect repellents, and bed nets if you are pregnant and
traveling to an area at high risk for malaria. Discuss risks and benefits with your
Peace Corps health provider.

One of the drugs (proguanil) in this product passes into breast milk. Consult your
Peace Corps health provider before breast-feeding.
What should I do if I miss a dose?

If you miss a dose, take the missed dose as soon as you remember and then continue
the usual dosing schedule. DO NOT double the dose to catch up.
What should I do if I overdose?

If overdose is suspected, contact your Peace Corps health provider immediately.


Symptoms of overdose may include stomach pain, rash, hair loss, or scaly skin on the
palms of the hands and bottom of the feet.

You can avoid getting malaria!


Avoid mosquitoes and reduce mosquito bites
Wear light or bright clothing that covers most of your body (long sleeved
shirts, long pants, socks). Permethrin treated clothing provides maximum
protection.
Use mosquito nets over cots, beds, and tents. Permethrin treated nets
provide maximum protection.
Use insect repellent on all exposed areas of skin or clothing. The most
effective compounds contain N,N- diethylmethylbenzamide (DEET).
Use pyrethroid-containing flying-insect spray or coils in living and sleeping
areas during evening and nighttime hours.
Remain in areas with screened windows and doors.
Eliminate mosquito-breeding sites by emptying or draining standing water
collected in outdoor containers or debris (discarded tires, pottery, tree
stumps).

Be sure your medical record shows that you received this medication.

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TG 840 ATTACHMENT D

Primaquine Phosphate
(Anti-Malarial Medication)
Medication Information Sheet

What is primaquine phosphate?


It is one of several types of drugs used to prevent and treat malaria.
Primaquine phosphate is the specific drug used to eliminate P. ovale and
P. vivax parasites from your liver. These species may reside harmlessly in
your liver for months or years without causing any symptoms, but they can
cause malaria months or years later (called relapsing malaria). Special
treatment called terminal prohylaxis is required to eliminate these
parasites from your system. While the malaria infection these species
cause is not as serious as malaria caused by P. falciparum, it can be very
uncomfortable.
How do I take the tablets?

You have been given 28 tablets (15 mg) by your provider


Take two (2) tablets by mouth daily for 14 days
It may be taken with food if stomach upset occurs, but not with
antacids
For best results, take each dose at the same time every day. This
will ensure a constant level of medication in your blood
Take this medication for the full time prescribed. Stopping therapy
too soon may result in a reinfection
Store at room temperature away from sunlight and moisture
Do not share medications with others

TERMINAL PROPHYLAXIS
WHEN TO START PRIMAQUINE (30 MG)
POST-DEPARTURE PROPHYLAXIS
(Following Departure from a Malarial
Endemic Area)
Mefloquine
Start on Day 15 (2 weeks following
departure)
Chloroquine
Start on Day 15 (2 weeks following
departure)
Doxycycline
Start on Day 15 (2 weeks following
departure)
Malarone
Start on Day 8 (1 week following
departure)
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TG 840 ATTACHMENT D

Are there any side effects (adverse reactions)?

You may have an upset stomach, stomach cramps, nausea,


vomiting, loss of appetite, or muscle weakness, especially during the
first several days as you body adjusts to the medication. If any of
these symptoms persists or become severe, inform your Peace
Corps health provider.
Notify your Peace Corps health provider if you develop a rash, rapid
heart rate, changes in vision, hearing trouble, ringing in the ears, or
dark urine while taking this medication.

Is there any reason I should not take primaquine phosphate?

If your G6PD level is low or absent, you should NOT take primaquine
If your G6PD is low or absent, your PCMO will give you authorization
(PC-127C) for G6PD retest and consultation with your home of
record physician
Individuals with low or absent G6PD levels should only take
primaquine if recommended, and supervised, by a medical
professional
If you have arthritis, psoriasis, lupus, liver disease or allergies to
primaquine
If you are pregnant or breast-feeding. Discuss the risks and benefits
with your Peace Corps health provider.

What should I do if I miss a dose?

If you miss one or more doses for any reason, take ONE dose as
soon as possible and then continue on your usual dosing schedule.
DO NOT double-up the dose to catch up unless instructed to by a
Peace Corps health care provider.

What should I do if I overdose?

If overdose is suspected, contact your Peace Corps health provider


immediately. Taking more than one dose can cause serious
adverse effects.

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Mefloquine Patient Information Guide

Mefloquine guide

Page 1

Mefloquine Patient Information Guide

Mefloquine guide

Page 2

Mefloquine Patient Information Guide

Mefloquine guide

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TG 840 ATTACHMENT F

MEFLOQUINE MEDICATION GUIDE ACKNOWLEDGEMENT

Instructions: To be completed by all Volunteers prior to starting malaria prophylaxis with


mefloquine, and filed in the Volunteer health record under In-Service Notes.

Date

I,
___, have received and read the June 2013,
Mefloquine (mefloquine hydrochloride) Medication Guide.
If, at any time, I experience what I feel are possible side effects from Mefloquine, I
will promptly discuss the situation with my Medical Officer, and I may be placed on
alternative anti-malaria prophylactic medication.

Signature

10/5/2003

Peace Corps
Technical Guideline 845

DIAGNOSIS AND TREATMENT OF MALARIA


1. PURPOSE
Provide guidance on malaria case diagnosis, treatment, monitoring and reporting procedures.

2. BACKGROUND
Malaria is one of the 10 most prevalent and deadly diseases in the world. Between 300-500
million clinical cases occur every year with over 1.2-2.7 million deaths. Ninety percent of
these occur in sub-Saharan Africa. Malaria is a parasitic disease spread by the bite of the
Anopheles mosquito. For additional information on the malaria parasite and for specific
guidance on malaria prevention, see Technical Guideline 840 Prevention of Malaria.
The Office of Medical Services (OMS) bases its recommendations for the presumptive
treatment of malaria on the most recent guidance from the Centers for Disease Control and
Prevention (CDC). Recommendations for the treatment of confirmed cases of malaria are
based on a review of current literature, expert consensus opinion, and evidence-based
guidelines where they exist.
For additional information regarding the diagnosis and treatment of malaria, Peace Corps
Medical Officers (PCMOs) should refer to additional information from CDC at the following
internet site: http://www.cdc.gov/malaria/diagnosis_treatment/tx_clinicians.htm

3. GENERAL CONSIDERATIONS
The incubation period for malarial parasites varies from 7 to 28 days, depending on the
species. The incubation period is the time that elapses between exposure, i.e., the bite of an
infected mosquito, and infection, i.e., the development of clinical symptoms of malaria. The
average incubation period for P. falciparum is 9-14 days.
Infection with the species P. falciparum can be life threatening. The parasite alters red blood
cells causing the cells to stick to the sides of blood vessels. When the level of parasitemia is
high, the cells sludge and clump together, eventually blocking capillaries throughout the
body. This is called microvascular sequestration. In the absence of medical treatment,
parasitemia of more than 5% is often fatal. Severe infection can also lead to coma, severe
anemia, cerebral malaria, hypoglycemia, renal failure, acidosis, convulsions, and death.
Infections with the species P. vivax, P. ovale, and P. malaria are rarely life-threatening,
however, symptoms may be severe. With these species, the percent of parasitized red blood
cells is rarely more than 1%; sludging usually does not occur, and complications are less
common.

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TG 845
Malaria Diagnosis and Treatment

4. MALARIA EVALUATION & DIAGNOSIS


Since few Volunteers serving in malarial areas can escape mosquito bites during their
service, and no preventative drugs are completely effective, PCMOs should assume that all
Volunteers are infected with the malaria parasite and that any Volunteer may develop the
clinical signs and symptoms of malaria infection.
The definitive diagnosis of malaria relies on the identification of parasites in the peripheral
blood (see Section 4.3 below). However, if a peripheral blood smear is not available or is
negative, PCMOs should always consider the diagnosis of malaria in any febrile Volunteer
who has been in a malarial area for more than one week and is experiencing any of the
symptoms outlined in the table below.
4.1

Signs and Symptoms

KEY SYMPTOMS

KEY SIGNS

Periodic attacks of chills, fever, and


sweating
Headache
Myalgia, Fatigue
Vomiting, Cramps
Lethargy, Coma

Periodic fever
Jaundice
Liver tenderness
Splenomegaly
Pulmonary edema (severe)
Renal failure (severe)

Malaria classically presents with nonspecific and irregular fever, chills, headache, and
malaise. Symptoms generally develop 10 days to 4 weeks after an infective bite. Often
there is a prodromal phase of the disease that is similar to a non-specific viral illness.
Initial symptoms may progress over 1-2 days to include any of the following:

Malaise, myalgia, backache

Mild or severe headache, dizziness, fatigue

Anorexia, nausea, vomiting, diarrhea

Slight fever with chills

Dry cough, shortness of breath

In practice, presenting symptoms are variable. The disease may present with
nonspecific respiratory or gastrointestinal symptoms or, in more serious cases of P.
falciparum malaria, with shock, delirium, and coma. Vomiting occurs in
approximately 20% of patients, and mild diarrhea in less than 5%. Signs and symptoms
also depend on the malaria species, the Volunteers degree of immunity, and whether
the Volunteer has regularly taken chemoprophylaxis.

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Malaria Diagnosis and Treatment

Fever Periodicity
A cyclical or periodic fever pattern may or may not be present. If present, fevers may
show an every-other-day (tertian / 48 hour) periodicity in P. vivax, P. ovale and P.
falciparum malaria, or an every-third-day (quartan / 72 hour) periodicity in P. malariae
malaria. Periodicity corresponds to the release of merozoites from the red blood cells
in the asexual cycle.
4.2

Physical Exam
Most physical signs are nonspecific. The Volunteer may seem only slightly ill, or may
appear pale and sallow. There may be sweating, anxiety, and distress. Common
clinical findings on physical exam include the following (Mandell, et al., 2000):

Vital Signs:

Temperature: may range from normal to 105F (40.6C). Most Volunteers


will have a temperature of 102F or higher at some time in their illness.

Blood Pressure: orthostatic hypotension (90-100 mmHg systolic); caused


by a decrease in effective intravascular volume secondary to marked
peripheral vasodilation.

Respiratory Rate: tachypnea.

Pulse: tachycardia.

Skin:

May be cool and pale or warm and dry; mild jaundice may be present.

Palms and lips may appear pale or cyanotic.

Eyes:

Conjunctivae may be pale.

Sclerae may appear yellow due to hemolysis.

Chest:

Lungs: scattered rales; rarely, evidence of consolidation or pulmonary


edema.

Cardiac: normal except for tachycardia.

Abdomen:

Generalized tenderness to palpation.

Spleen: moderate splenomegaly. Usually appears when acute symptoms


have continued for 4 or more days or if there has been long-term infection
with malaria. Spleen may be extremely delicate due to the sudden
stretching of the capsule and is prone to rupture, especially in P. vivax
malaria. Vigorous palpation of the spleen is dangerous and should be
avoided.

Liver: tender hepatomegaly.

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Malaria Diagnosis and Treatment

Lymphadenopathy: Does not occur in malaria and its presence in a Volunteer with
malaria should prompt a search for additional etiology.

Musculoskeletal: Despite complaints of myalgia and arthralgia, neither muscle


tenderness nor joint effusions are present. Peripheral edema is usually absent.

Neurologic: Normal with the exception of delirium and other minor behavioral
changes that may result from high fever.

4.3 Laboratory Diagnosis and Findings

KEY LABORATORY TESTS


Thick and thin blood smears
Complete blood count with peripheral smear
Liver function tests (ALT, AST, direct/indirect billirubin, albumin)

Thick and Thin Blood Smears


The identification of parasites on thick and thin blood smears of peripheral blood is the
mainstay of malaria diagnosis. Symptoms may precede a detectable level of
parasitemia by a few days, so smears should be examined at least twice a day until
parasites are detected. Efforts should be made to quantify the level of parasitemia as it
is useful to determine a baseline parasitemia from which the response to therapy can be
monitored. Efforts to diagnosis the malaria species may also be made; however, most
laboratory technicians are not experienced in the morphologic differentiation of
Plasmodial species. Also, PCMOs should not base treatment on the type of species
reported on peripheral blood smear examination. Treatment should always be based on
the types of malaria species in country (see Section 6 below). Slides should be saved
and sent to the CDC for species confirmation (see Section 10 below).
Thick smears are more sensitive in detecting malaria parasites because the blood is
concentrated, allowing a greater volume of blood to be examined. Thick smears should
only be used for detecting the presence of parasites and quantifying parasitemia, not for
species diagnosis. Thick smears, however, are more difficult to read, and thin smears
may be preferred by some laboratories that have limited experience. Thin smears may
be used for detecting parasites and should be used for making species diagnosis.
On microscopic examination, Plasmodium parasites are always intracellular, and they
demonstrate, if stained correctly, blue cytoplasm with a red chromatin dot.
Preparation and Microscopic Examination of Peripheral Blood Smear
Peripheral blood smears are prepared in all cases of suspected malaria infection. In the
Peace Corps setting, these peripheral blood smears are prepared by both Volunteers and
PCMOs. Medical Officers should supply all Volunteers serving in malaria-endemic
areas with Peace Corps Malaria Kits. These Kits contain all the materials needed for
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TG 845
Malaria Diagnosis and Treatment

smear preparation, i.e., slides, lancets, alcohol wipes and band-aids. The Kits can be
procured through the Overseas Support Division in Administrative Services
(M/AS/OSD). For ordering information see TG 240.15.2 MIF Kits and Malaria Kits.
Medical Officers are responsible for teaching Volunteers when and how to prepare
proper malaria blood smears. Training should occur during Pre-Service Training (PST)
and In-Service Training (IST). Illustrated instructions for preparing blood smears are
included in ATTACHMENT A of this TG and in Appendix B of the Pre-Service
Health Training Module on Malaria.
If malaria is suspected, Volunteers and PCMOs should prepare thick and thin smears
according to the following guidelines:

Prepare smears whenever malaria is suspected according to the instructions in


ATTACHMENT A.

Prepare smears immediately regardless of fever spikes or time of day.

Prepare smears every 6 to 8 hours for several days. Numerous blood smears may
be required to identify parasites.
Because the level of parasitemia varies from hour to hour especially for P.
falciparum infections in which parasites may be difficult to find obtain and
examine blood at 6-8 hour intervals for a minimum of 3 days, during and between
fever spikes.

Send smears to a reliable local laboratory for staining and examination. Smears
may be stained and examined in the Peace Corps Health Unit if facilities and
trained personnel exist.

Send all smears to the CDC according the instructions outlined in Section 10 Case
Reporting.

Other Laboratory Tests

Complete Blood Count (CBC) to include peripheral smear; peripheral smear may
demonstrate hemolytic anemia, leukopenia, and thrombocytopenia.

Liver Function Tests (LFTs) to include ALT, AST, direct/indirect bilirubin, and
albumin; results may demonstrate elevated levels of ALT, AST due to hepatic
congestion, elevated indirect bilirubin levels from hemolysis and hypoalbuminemia
from impaired liver function.

Serum glucose level; may reveal hypoglycemia

Other Diagnostic Tests

Fluorescent stain (QBC method): This method, which requires special capillary
tubes, a centrifuge, and a fluorescent microscope, is reported to be as sensitive as a
thick smear examination for the detection of low levels of parasitemia. The test

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Malaria Diagnosis and Treatment

requires expert technical skills, and overdiagnosis of malaria by those using this
method is common. It does not replace thin and thick smear examination.

Antigen test for P. falciparum: This test, a rapid and simply accomplished dipstick
antigen capture assay, appears promising for field diagnosis; however, it is
currently not available for widespread clinical use. Also, sensitivity decreases with
low parasite density.

ELISA for P.falciparum: Serologic tests are not useful in the diagnosis of acute
malaria attacks. Antibodies to malaria may persist for 10 or more years and the test
does not differentiate past from present infection.

4.4 Differential Diagnosis


Malaria may mimic numerous diseases, from influenza to mental illness. It can be
especially difficult to distinguish between acute malaria, typhoid fever, and dengue
fever. Symptoms of malaria are not specific and are often confused with:

Amebiasis

Dengue Fever

Relapsing fever

Hypoperfusion/shock

Meningococcemia

Influenza

Viral encephalitis

Typhoid

Tuberculosis

Acute gastroenteritis

5. INTERIM SELF-TREATMENT OF PRESUMED MALARIA


The Office of Medical Services requires PCMOs to provide all Volunteers serving in
malarial areas with medication for the interim self-treatment of presumed malaria. Interim
self-treatment is recommended for non-immune individuals who are at risk of infection with
malaria and who may not have prompt access to medical care, e.g., Peace Corps Volunteers.
The intent of interim self-treatment is to reduce or control symptoms and to allow the
Volunteer time to obtain medical attention and follow-up. The appropriate medication (see
section 5.1 below) and ATTACHMENT B Instructions for Volunteer Emergency SelfTreatment should be included in the Volunteer Health Kit.
Medical Officers are required to educate Volunteers on the proper management and treatment
of presumed malaria. This includes instruction on the preparation of peripheral blood smears
(see ATTACHMENT A and Section 4.3 above), medication use, and the need to seek
immediate medical attention when malaria infection is suspected. Education should occur
during PST and IST.
5.1

Interim Self-Treatment Regimens


The Office of Medical Services recommends the following interim self-treatment
regimens for all Volunteers serving in malaria endemic areas.

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Malaria Diagnosis and Treatment

Coartem (one tablet contains 20 mg artemether and 120 mg lumefantrine) is the


drug of choice for interim self-treatment of malaria. All Volunteers should read the
Coartem Medication Guide and sign the acknowledgement form, available as
ATTACHMENT D, before being issued or using this medication.
COARTEM 4 tablets orally at the time of initial diagnosis, again after
8 hours, then twice daily for the following 2 days (4 tablets each time
for total course of 24 tablets)
Note: Coartem should be taken with high fat food and drinks such as milk as this
markedly improves absorption of drugs.

Malarone or Quinine sulfate and doxycycline are alternative regimen if Coartem is


contraindicated or poorly tolerated.
MALARONE 4 tablets orally as a single dose daily for 3 days
Or
QUININE SULFATE 650 mg orally 3 times daily for 3 days
AND
DOXYCYCLINE 100 mg twice a day for 7 days

Medical Officers should not use mefloquine, Fansidar, or halofantrine, for the
interim self-treatment of malaria (see Section 6.3 below).

Note: For specific information see also Health Information for International Travel,
(Yellow Book), available from the CDC, or on the world wide web at
www.cdc.gov/travel/reference.htm
5.2

Special Circumstances
Oceania (Papua New Guinea, Solomon Islands, and Vanuatu): Volunteers who are
days away from medical care and are exposed to both drug resistant P. falciparum and
P. vivax, should be provided with, and instructed in the use of, two of the interim selftreatment regimens in case of delays receiving medical attention.

6. TREATMENT OF UNCOMPLICATED MALARIA

KEY PRINCIPALS OF MALARIA MANAGEMENT


Recognize early infection due to P. falciparum.
Rapidly institute effective antimalarial chemotherapy by the appropriate route of
administration.
Recognize, and provide therapy for, complications.

Monitor the immediate and long-term clinical and parasitologic


response to treatment.
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TG 845
Malaria Diagnosis and Treatment

It is imperative that PCMOs maintain a high index of suspicion and a willingness to


presumptively treat Volunteers in malaria endemic areas who exhibit signs and symptoms of
malaria infection. Medical Officers should not delay treatment for an ill Volunteer with
presumed malaria. Delaying treatment worsens the prognosis and may result in significant
disease complications and treatment complications secondary to the use of potentially toxic
intravenous drugs. The mortality rate for P. falciparum malaria, if not adequately and
promptly treated, can be as high as 25%.
Treatment of confirmed or presumed malaria involves immediate drug treatment and
supportive therapy. A patient with P. falciparum malaria may deteriorate within hours.
Medical Officers should always base treatment on the assumption that P. falciparum malaria
is present in country. Treatment should not be based on the type of malaria species reported
on peripheral blood smear examination. Lab error or co-infection with P. falciparum could
be fatal if inadequate treatment is provided.
6.1

Treatment Regimens for Uncomplicated Malaria


The Office of Medical Services recommends the following treatment regimens for
uncomplicated malaria in Volunteers.

Areas where chloroquine-resistant P. falciparum has NOT been reported.


CHLOROQUINE PHOSPHATE (500 mg salt = 300 mg base)
Day 1
Day 2
Day 3

2 tablets orally followed by 1 tablet 6 hours later


1 tablet orally
1 tablet orally

Total dose = 2500 mg salt or 1500 mg base

Areas where chloroquine-resistant P. falciparum EXISTS.


COARTEM 4 tablets orally at the time of initial diagnosis, again after 8
hours, then twice daily for the following 2 days (4 tablets each time for total
course of 24 tablets)
OR
MALARONE 4 tablets as a single dose daily for 3 consecutive days**
Total daily dose = 1 gm atovaquone and 400 mg proguanil hydrochloride.
OR
QUININE SULFATE 650 mg orally 3 times daily for 3 days
AND
DOXYCYCLINE 100 mg orally twice daily for 7 days.
Note: Malarone should not be used for treatment in individuals who are taking
Malarone for malaria chemoprophylaxis

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TG 845
Malaria Diagnosis and Treatment

Areas with multi-drug resistant P. falciparum malaria


COARTEM 4 tablets orally at the time of initial diagnosis, again after 8 hours,
then twice daily for the following 2 days (4 tablets each time for total course of
24 tablets)
OR
QUININE SULFATE 650 mg orally 3 times daily for 7 days
AND
DOXYCYCLINE 100 mg twice a day for 7 days

6.2

Monitoring
To confirm response to treatment, PCMOs should monitor the Volunteers clinical
response to treatment and the level of parasitemia on peripheral blood smears. Blood
smears should be examined 2-3 times a day to determine whether the parasitemia is
decreasing. Failure to reduce parasitemia in the first 24-48 hours of treatment should
raise the possibility of drug failure. Also, no significant clinical response to treatment
in 24-48 hours, or the persistence of parasites after the fifth day, implies treatment
failure and PCMOs should start an alternative treatment regimen. Monitoring should
continue until the parasite level is zero.

6.3

Agents Not Recommended for Treatment of Malaria


Medical Officers should not use the following medications for the treatment of
presumed or confirmed uncomplicated malaria in Volunteers.

Mefloquine: Treatment doses of mefloquine have been associated with severe


cardiac and neruopsychiatric adverse reactions.

Halofantrine: Treatment doses of halofantrine have been associated with severe


cardiac adverse reactions including death. Its absorption is also erratic making
correct dosing unreliable.
Halofantrine affects cardiac conduction. Its use in combination with mefloquine
has been associated with sudden death. The combined use of halofantrine and
mefloquine is absolutely contraindicated.

Fansidar: Treatment with Fansidar has been associated with fatal reactions
including Stevens Johnson Syndrome and Toxic Epidermal Necrolysis.

7. TREATMENT OF COMPLICATED MALARIA


Complicated malaria is a medical emergency. Complicated malaria is malaria with any of
the associated complications listed below. If not treated promptly and aggressively, death
can result, sometimes within 24 hours. Medical Officers should consult OMS or an Area
Peace Corps Medical Officer (APCMO) immediately if complicated malaria is suspected.

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Malaria Diagnosis and Treatment

Volunteers with complicated malaria usually require hospitalization and medical evacuation
(medevac).
Complicated malaria is almost always due to P. falciparum and is associated with a mortality
of 15-20%. In severe P. falciparum infections, red blood cell parasitemia is often, though not
always, higher than 3-5%. The prognosis is poor when there are multiple complications or if
there are any mature parasites in the peripheral blood. Other species of malaria may produce
severe or complicated infection; however, the complications listed below are almost
exclusively due to the red blood cell sludging seen with P. falciparum.
Complications include:

Cerebral malaria - characterized by headache, mental disturbances, neurologic signs,


retinal hemorrhages, convulsions, delirium, and coma. Mortality is as high as 25%, even
with appropriate medical care.

Hyperpyrexia

Hemolytic anemia - may lead to severe anemia and hemoglobinuria which may cause
urine to turn black (blackwater fever).

Pulmonary edema - may be associated with cardiac failure.

Acute tubular necrosis and renal failure - secondary to renal microvascular damage or
hemoglobinuria; may lead to acute renal failure or severe anemia.

Lactic acidosis

Hypoglycemia

Cardiac dysrhythmias

Gastrointestinal syndromes - including secretory diarrhea and dysentery; results from


damage to the bowel.

7.1

Treatment Regimens for Complicated Malaria

KEY TREATMENT APPROACH FOR COMPLICATED MALARIA


Consult OMS or an APCMO.
Start treatment as soon as the diagnosis is suspected.
Calculate dosage according to patient weight.
Give medication intervenously.
Give loading dose of medication (not indicated if patient has received quinine,
quinidine, or mefloquine in the last 24 hours).
If patient is comatose, place on his or her side and consider giving a single
parenteral dose of Phenobarbital (5-20mg/kg) to prevent convulsions.
Measure parasite count and hematocrit every 6-8 hours.
Consider exchange transfusion in patients with high level of parasitemia
(>10%), or in severely ill patients with with parasitemia levels between 5-10% if

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Malaria Diagnosis and Treatment

it can be provided safely.


Switch to oral medication as soon as patient can tolerate tablets, and response
to treatment is confirmed.
Observe patients carefully for drug toxicity and complications.

Volunteers who present with, or develop, malaria complications should be treated


according to the treatment regimen outlined below. Parenteral treatment is indicated
for all Volunteers with complications irrespective of the malaria species present in a
particular geographic location.
QUININE DIHYDROCHLORIDE (IV) (20 mg salt = 16.7 mg base)
Loading dose*: 20 mg/kg (salt) in 250 ml IV fluid** over 4 hours. Never
administer by an IV push.
Eight hours after loading dose: begin 10 mg/kg (max. 600 mg) in 250 mg
IV fluid** over 4 hours.
Repeat every 8 hours until able to take oral medication.
Start oral quinine (650 mg 3 times a day) when able to take oral
medication. Complete a 3-5 day course of therapy with oral quinine; 7
days in multi-drug resistant areas.
AND
(when stable and able to tolerate oral medication)
DOXYCYCLINE 100 MG orally twice a day for 7 days
*

Published sources caution about the use of a loading dose when quinine, quinidine, or
treatment doses of mefloquine have been taken in the preceding 24 hours. Recognizing the
possibility of cardiac arrhythmias, adequate blood levels of quinine must be achieved as soon
as possible and may be life-saving.
As hypoglycemia and hypovolemia are both frequently observed, D5/NS or D5/.5NS are the
preferred IV fluids.

**

7.2

Alternate Regimen

If quinine dihydrochloride is not available.


QUINIDINE GLUCONATE (IV)
(continuous infusion pump not available)
Loading dose*: 24 mg/kg salt (15mg/kg base) in 250 ml IV fluid** over 4
hours.
Eight hours after loading dose: begin 12 mg/kg salt (7.5 mg/kg base) in
250 mg IV fluid** over 4 hours.
Repeat every 8 hours until able to take oral medication.
Start oral quinine (650 mg 3 times a day) when able to take oral
medication. Complete a 3-5 day course of therapy with oral quinine; 7
days in multi-drug resistant areas.

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QUINIDINE GLUCONATE (IV)


(continuous infusion pump is available)
Loading dose*: 10 mg/kg salt (6.25mg/kg base) in 250 ml IV fluid** over 2
hours.
Followed by a continuous infusion of 0.02 mg/kg/min salt (0.0125
mg/kg/min base) for up to 72 hours as described above
Repeat every 8 hours until able to take oral medication.
Start oral quinine (650 mg 3 times a day) when able to take oral
medication. Complete a 3-5 day course of therapy with oral quinine; 7
days in multi-drug resistant areas.
* see above; ** see above

7.3

Monitoring
Monitoring of complicated malaria should include the following:

7.4

Vital signs

Parasite concentration via peripheral smear examination.

Hematocrit/hemoglobin, and serum electrolytes.

Blood glucose: Administer IV or PO glucose as necessary to prevent


hypoglycemia.

Cardiac status (ECG required for quinidine treatment).

Fluid status: Use two IV lines if one is needed for fluid replacement.

Urinary output

Medication monitoring:

Regulate IV quinine carefully, as too rapid an infusion may cause seizures,


hypotension, cardiovascular collapse, heart block, ventricular fibrillation, or
death.

Do not use steroids or mannitol in the management of complicated or


cerebral malaria. They have been shown to worsen clinical outcome
(White, N., 1996).

Quinidine is more likely to produce cardiac conduction changes and should


always be monitored in an intensive care setting when possible. However, if
monitoring is not readily available, prompt administration of quinine or
quinidine is critical in the management of severe, life-threatening malaria

Exchange Transfusion
Exchange transfusion is recommended for cerebral malaria and should be strongly
considered for parasitemia >10% or for progressive pulmonary or renal failure. One or
two total body exchanges may be necessary. Patients requiring this therapy are

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transfused with whole blood or the equivalent blood components. Medical Officers
should consult with OMS immediately if an exchange transfusion is being considered.

8. DRUGS USED IN THE TREATMENT OF MALARIA


8.1

8.2

Chloroquine

Effectiveness: Highly effective against erythrocytic forms of P. vivax, P. ovale, P.


malariae, and sensitive strains of P. falciparum. It rapidly controls acute attacks of
malaria with most patients becoming afebrile within 1 to 2 days.

Adverse Reactions: Generally well tolerated. Mild gastrointestinal irritation is


common; pruritis and exacerbation of psoriasis are not uncommon; headache,
dizziness, and blurred vision occur infrequently. Dysphoria, and very rarely, a
transient neuropsychiatric syndrome or cerebellar dysfunction may be seen.

Contraindications: Should be used with caution in patients with hepatic disease


and in patients with severe gastrointestinal, neurologic, and blood disorders.
Chloroquine is not hepatotoxic but it is widely distributed, and converted to active
metabolites, in the liver. Should not be administered with gold salts due to
increased risks of dermatitis.

Precautions: May interfere with the antibody response to intradermal human


diploid cell rabies vaccine.

Malarone (Atovaquone and Proguanil)

Effectiveness: A good alternative in the treatment of chloroquine resistant P.


falciparum malaria. Generally, well or better tolerated than most drugs at doses
necessary for treatment of malaria.

Adverse Reactions: Treatment limiting adverse drug reactions occur in less than
1% of patients receiving treatment doses, and serious drug reactions attributable to
treatment doses are rare. The most commonly reported adverse reactions include
abdominal pain (17%), nausea (12%), vomiting (12%), headache (10%), diarrhea
(8%), weakness (8%), loss of appetite (5%), and dizziness.
Elevated ALTs and ASTs occur in patients treated with Malarone and at a greater
frequency than patients treated with mefloquine; however the differences were not
significant and values returned to normal by day 28 in most patients. Although the
clinical significance of these elevations is unknown, studies have not shown liver
enzyme elevations to be treatment limiting (Looareesuwan, S., et al., 1999).

Contraindications: Contraindicated in persons with severe renal impairment


(creatinine clearance < 30 ml/min); and in persons with known hypersentivity to
atovaquone or proguanil hydrchloride or any component of the formulation

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8.3

8.4

Precautions:

Malarone should not be used for treatment of acute malaria in individuals


who are taking Malarone for malaria chemoprophylaxis due to possible
Malarone-resistant disease

Concomitant use of tetracyclines, metoclopramide or rifampin reduces the


plasma concentration of atovaquone and, therefore, should be avoided.

Malarone may not be adequate treatment for P. vivax malaria. In cases of


suspected of P. vivax malaria, additional therapy, e.g., Primaquine, may be
necessary. Medical Officers should contact their APCMO or OMS for
guidance in these cases.

Coartem (artemether and lumefantrine)

Effectivenesss: Effective drug in the treatment of acute malaria. Demonstrates high


cure rates, over 95%, even in multi-drug resistant areas. It is not for use as a
prophylactic and there is no experience on the treatment of complicated malaria
with Coartem. Coartem should be taken with high fat food and drinks such as milk
as this markedly improves absorption of drugs. Patients who vomit within one hour
of taking the medication should repeat the dose.

Adverse Reactions: Treatment is generally well tolerated. Common side effects are
sleep disorder, headache, dizziness, palpitation, abdominal pain, anorexia, diarrhea,
vomiting, rash, pruritis, cough, arthralgia, myalgia, asthenia and fatigue. On ECG
monitoring, QT prolongation without clinical symptoms has been observed in
patients treated with Coartem.

Contraindications: Hypersensitivity to the active substances or to any of the


additives. The safe use of the Coartem during pregnancy has not been established.

Precautions: Patients receiving Coartem should be warned that dizziness or


fatigue/asthenia may occur in which case they should not drive or use machines.

Quinine Sulfate (oral form); Quinine Dihydrochloride (IV form)

Effectivenesss: Effective drug in the treatment of acute malaria and remains more
than 85% effective nearly everywhere (NEJM, 1996). Acts rapidly against the
asexual erthyrocyctic stages of all four Plasmodium species.

Adverse Reactions: Treatment is not well tolerated, and compliance with the 7 day
courses of treatment required for resistant P. falciparum infections is poor. Oral
compounds are extremely bitter. Adverse reactions often induce the complex of
cinchonism (nausea, vomiting, dysphoria, tinnitus, and high-tone deafness). These
reactions are dose related and reversible. Less common adverse reactions include
urticaria, angioedema of the face, itching, agranulocytosis, hepatitis, and
hypoglycemia in patients with high parasitemia. Serious toxic reactions are rare.

Contraindications: Hemolysis, with a potential for hemolytic anemia, may occur in


patients with G6PD deficiency.

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8.5

Precautions: Quinine should always be administered with caution and should


never be given IV push. Improper administration of IV quinine resulting from too
rapid an infusion may cause seizures, hypotension, cardiovascular collapse, heart
block, ventricular fibrillation, or death.

Quinidine Gluconate (IV form)

Effectivenesss: Effective drug for the treatment of severe malaria. There are no
reports of resistance to quinidine in any strains of Plasmodia.

Adverse Reactions: Quinidine is toxic to the heart if given too quickly or in too high
a dose. ECG changes including prolonged QT intervals are common, but lifethreatening arrhythmias are rare with proper doses. Most adverse reactions are
gastrointestinal including nausea, vomiting, abdominal pain, diarrhea, and
esophagitis. Symptoms of mild to moderate cinchonism may appear in sensitive
patients after one dose of the drug. Less frequent adverse reactions include
urticaria, skin flushing with intense itching, and hypersensitivity reactions of
angioedema, acute asthmatic episode, and liver toxicity

Contraindications: Quinidine is contraindicated in patients who are known to be


allergic to it, or who have developed thrombocytopenic purpura during prior
therapy with quinidine or quinine. In the absence of a functioning artificial
pacemaker, quinidine is also contraindicated in any patient whose cardiac rhythm is
dependent upon a junctional or idioventricular pacemaker, including patients in
complete atrioventricular block. Quinidine is also contraindicated in patients who,
like those with myasthenia gravis, might be adversely affected by an anticholinergic
agent.

Precautions: Quinidine should always be administered with caution. Infusion


should be stopped temporarily if the ECG shows prolongation of the QRS interval
by >50%, or if the QT interval is prolonged >50% of the preceding R-R interval.
Hypotension may occur if infusion is too rapid.

9. TREATMENT OF PREGNANT VOLUNTEERS


Medical Officers are required to consult OMS immediately if a pregnant Volunteer develops
malaria. Medical Officers should also review TG 170 Pregnancy. Prompt treatment of
pregnant Volunteers with malaria is essential and should be initiated as outlined below. P.
falciparum malaria is associated with low birth weight, fetal distress, premature labor,
miscarriage, stillbirth, and hypoglycemia.

In pregnant Volunteers, the OMS preferred drug of choice in areas with chloroquine
sensitive P. falciparum malaria is chloroquine (see Section 6.1 for dosing
schedules). In areas with chloroquine-resistant P. falciparum malaria, the
recommended treatment is Quinine in combination with clindamycin. Quinine
treatment should continue for 7 days for infections acquired in Southeast Asia and
for 3 days for infections acquired in Africa or South America; clindamycin
treatment should continue for 7 days regardless of where the infection was

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Malaria Diagnosis and Treatment

acquired. PCMOs should consult OMS in treatment planning for any pregnant
Volunteer in areas with chloroquine resistant P. falciparum malaria. Doxycycline
is contraindicated during pregnancy, and the CDC does not currently recommend
the use of Malarone in pregnant women unless the potential benefit outweighs the
potential risk to the fetus, e.g., a pregnant woman who has acquired P. falciparum
malaria in an area of multi-drug resistance and who could not tolerate other
treatment options. The safe use of the Coartem during pregnancy has not been
established.

10. LABORATORY SUPPORT


Confirmatory test for malaria can be done at the CDC.
Include the following items when sending the specimen to the CDC.

Malaria Case Record (see ATTACHMENT C )

Peripheral blood smears

Blood or serum for drug testing, i.e., Mefloquine or Malarone levels. Chloroquine and
doxycycline levels may be requested on a case by case basis.

Drug levels should be requested irrespective of Volunteer-reported adequate


chemoprophylaxis. Mefloquine metabolite levels are several times higher than parent drug
levels when mefloquine has been taken regularly.
For information on sending specimens to the CDC, see Technical Guideline 360 Use of U.S.
Laboratories.

REFERENCE
de Alencar, F.E., et al., Atovaquone and proguanil for the treatment of malaria in Brazil.
Journal of Infectious Disease, 1997. 175(6): pp. 1544-7.
Centers for Disease Control and Prevention (CDC). Health Information for International
Travel, 2003-2004, Atlanta, Georgia, 2003.
Centers for Disease Control and Prevention (CDC). Malarone for Malaria Treatment and
Prophylaxis, Atlanta, Georgia, 2000.
Goldsmith R. & Heynemann D. Tropical Medicine and Parasitology. Norwalk, CT:
Appleton & Lange, 1989.
Looareesuwan, S., et al., Efficacy and safety of atovaquone/proguanil compared with
mefloquine for treatment of acute Plasmodium falciparum malaria in Thailand. American
Journal of Tropical Medicine and Hygiene, 1999. 60(4): pp. 526-32.

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Mandell, G. L., Douglas, R. G., and Bennett, J. E. Principals and Practice of Infectious
Diseases, 5th edition. Churchill Livingston, 2000.
Navy Environmental Health Center. Navy Medical Department Guide to Malaria Prevention
and Control, Norfolk, Virginia, 1991.
White, N.J. The Treatment of Malaria. The New England Journal of Medicine, Vol. 335:
800-806, No. 11, September 12, 1996.

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TG 845 ATTACHMENT A

PREPARATION OF BLOOD SMEARS


FOR MICROSCOPIC EXAMINATION AND MALARIA DIAGNOSIS

To establish the diagnosis of malaria, thick and thin blood smears from fresh peripheral blood
are required. Medical Officer and Volunteers should prepare smears anytime malaria is
suspected, regardless of fever spikes or time of day. All of the materials needed for smear
preparation are contained in the Peace Corps Malaria Kit.
Peripheral blood is obtained by pricking the finger (see Figure A-1). Thick and thin smears
should be made on separate slides, however, smears may be made on the same slide (see
Figure A-2).

* In Figures A-1 and A-2 hands are shown ungloved to better illustrate their placement during the procedures.
However, PCMOs should always wear gloves while processing blood specimens to prevent transmission of
bloodborne pathogens (see Technical Guideline 260 Infection Control).

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TG 845 ATTACHMENT A

Fixing Slides (PCMOs only):

Thin film: Air dry. Fix with methyl alcohol. Stain. If no parasites are found, wait until the
thick film is dry and examine it for organisms that might not have been detected on the thin
preparation.

Thick film: Air dry. Stain unfixed.

Slides may be stained using a Wright-Giemsa stain; however, Wright stain alone will not reliably
show Plasmodium parasites. For best results, smears should be stained with a 3% Giemsa
solution (pH of 7.2) for 30-45 minutes. On microscopic examination, Plasmodium parasites are
always intracellular, and they demonstrate, if stained correctly, blue cytoplasm with a red
chromatin dot.
In P. falciparum infections, the parasite density should be estimated by counting the percentage
of red blood cells infected - not the number of parasites - under an oil immersion lens on a thin
film.

Reference: Adapted from Holtz, T., Kachur, S. P., et al. Malaria Surveillance United States, 1998. In: CDC
Surveillance Summaries. MMWR, December 7, 2001, 50; (No. SS05): 1-18.

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TG 845 ATTACHMENT B

INSTRUCTIONS FOR VOLUNTEERS


EMERGENCY SELF-TREATMENT OF PRESUMED MALARIA
Dear Volunteer,
In your Peace Corps Health Kit, you have been issued antimalarial medication for the emergency
self-treatment of presumed malaria. The specific medication, i.e., Malarone, or
Quinine/Doxycycline, has been selected for you based on the type of malaria in your country, the
prophylactic antimalarial drug you are taking, and your personal medical history. You should
only take the medication provided to you, and you should only take the medication if you feel
your symptoms are due to acute malaria and you are unable to access medical care
immediately.
Signs and symptoms of acute malaria include:

High fever (may be cyclic)


Shaking chills
Sweats
Muscle aches

Headache
Nausea (occasionally)
Vomiting (occasionally)
Diarrhea (rarely)

Understand that many of the signs and symptoms of malaria mimic other viral and bacterial
illnesses and, often, presumed malaria is not malaria. If you have regularly taken your
prophylactic anti-malarial medication, you should not develop acute malaria. However, if you
do experience some or all of the above symptoms, you should: (1) carefully consider the cause
of your symptoms, and (2) if you feel that these symptoms may be from malaria, follow the
directions for emergency self-treatment of malaria below.
DIRECTIONS FOR EMERGENCY SELF-TREATMENT
1. Take the anti-malarial drug in your Health Kit.

Coartem and Malarone are the drugs of choice for emergency self-treatment of
malaria
COARTEM 4 tablets orally at the time of initial diagnosis, again after 8 hours,
then twice daily for the following 2 days (4 tablets each time for total course
of 24 tablets)
Note: Coartem should be taken with high fat food and drinks such as milk as
this markedly improves absorption of drugs.
Or
MALARONE 4 tablets orally as a single dose daily for 3 days
Note: Do not take Malarone for emergency self-treatment
if you taking Malarone for antimalarial prophylaxis.

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TG 845 ATTACHMENT B

Quinine/Doxycycline is the drug of choice for a few select individuals. If these


medications are in your Health Kit, discuss the dosing procedure with your PCMO.
QUININE SULFATE 650 mg orally 3 times daily for 3 days
AND
DOXYCYCLINE 100 mg twice a day for 7 days

2. Make blood smears: Blood smears are required for your PCMO to make the diagnosis
of malaria. You were trained how to make these smears during Pre-Service Training
(PST). A Malaria Kit and a handout with instructions on slide preparation are in your
Health Kit. Using the supplies in the Malaria Kit, do the following:

Make at least two thick blood smears.

Make at least one thin blood smear. Thin smears may be more accurate for malaria
diagnosis.

Make the first slide when you start your self-treatment medication.

Make the second slide approximately 6 hours after starting self-treatment.

3. SEEK MEDICAL ATTENTION !!


Contact the PCMO immediately and arrange for travel to the Peace Corps Health Unit or
to a regional medical facility approved by the PCMO. This is necessary so that the
PCMO or an approved health care provider can confirm the diagnosis, provide adequate
treatment and manage any complications or associated conditions.
The purpose of emergency self-treatment is to control the signs and symptoms of malaria
and to allow you time to obtain medical attention and follow-up. Emergency selftreatment medication may, or may not, be effective treatment for malaria. You must
seek immediate medical attention!

4. Continue regular chemoprophylaxis: Unless instructed otherwise by the PCMO,


continue to take your regular prophylactic antimalarial medication.

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TG 845 ATTACHMENT C

Peace Corps: Malaria Case Record

Send this form, the blood slides, and blood for drug testing to: Centers for Disease Control and Prevention,
Malaria Epidemiology Branch, 4770 Buford Highway, MS F22, Atlanta, GA 30341 Fax: (770) 488-7761

TG 845 ATTACHMENT D

PEACE CORPS
COARTEM MEDICATION GUIDE
What is Coartem?
Coartem is a medication to treat malaria. Coartem tablets contain a combination of artemether (20mg) and
lumefantrine (120mg). These two medications work to clear the body of malaria parasites, and, when combined, are
especially effective against multi-drug-resistant strains of P. falciparum malaria.
Coartem is in the class of medications known as ACT, or "Artemether Combination Therapies." The World
Health Organization has determined that ACT are the preferred course of treatment for uncomplicated P. falciparum
malaria.
What are the risks of malaria?
Malaria is a parasitic disease that is transmitted by mosquito bites. The malaria parasite enters your blood cells
and destroys them.
Symptoms of malaria include shaking chills, headache, muscle aches, and tiredness, and sometimes even
nausea, vomiting, and diarrhea. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes)
because of the loss of red blood cells.
Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure,
seizures, mental confusion, coma, and death. Malaria is a leading cause of death around the world. More than 1
million people die of malaria each year.
Why do I need Coartem?
You can prevent malaria by taking personal protective measures such as mosquito nets over your bed when you
sleep, anti-mosquito insect repellant that contains DEET, wearing long pants and long-sleeve shirts with collars.
Anti-malarial medications such as Lariam (mefloquine), doxycycline, and Malarone (atovaquone/proguanil) also
protect against malaria if taken properly.
If you do contract malaria, you can treat it with proper medications like Coartem if symptoms are identified
quickly and treatment is begun appropriately. Failure to adequately prevent or treat malaria can result in illness,
permanent injury or disability, and even death.
Who should NOT take Coartem?
Pregnant women in their first trimester should NOT take Coartem if you feel that you might be pregnant,
notify your health care provider immediately, before you take Coartem. Those with hypersensitivity reactions to
either artemether or lumefantrine, the two components of Coartem, should not take Coartem if you have had
allergic reactions to either artemether or lumefantrine in the past, notify your health care provider.
How do I take Coartem?
Coartem is taken as FOUR tablets, two times a day, for three days. You should take each dose of four tablet
with a meal to increase the absorption of the medication from your stomach. Recommended foods include milk,
cheese, and meat.
What are the risks of Coartem?
Every medication has possible side effects. Side effects from Coartem may include dizziness, fatigue,
decreased or absent appetite, nausea, vomiting, abdominal pain, heart palpitations, muscle aches, sleep disorders,
joint pains, headache, and rash. Many of these symptoms may be caused by malaria itself and may not be due to
Coartem. In addition, many of these side effects have been reported as mild or moderate; studies have found no
serious or persistent neurological side effects from use of Coartem. If you feel you may be experiencing side effects
from Coartem, contact your medical officer immediately.
Is Coartem approved by the U.S. Food and Drug Administration (FDA)?
Coartem was approved for use since 1999. Although Coartem is eligible for approval by the FDA, its manufacturers
have not yet submitted the drug for FDA approval. However, Coartem has been identified as a drug of choice by the
World Health Organization (WHO) for treatment of malaria. The Peace Corps is permitted to use Coartem because
it is an effective treatment for malaria and complies with Peace Corps guidelines.

PEACE CORPS
COARTEM MEDICATION GUIDE
ACKNOWLEDGEMENT

I, _________________________________, have received, read and understand the Peace Corps'


Coartem Medication Guide.
I understand that malaria is a serious and potentially fatal disease and that proper use of antimosquito measures as well as anti-malarial medications can prevent malaria. I also understand
that proper use of Coartem as directed by my Medical Officer can effectively treat the disease. I
understand that failure to use proper preventive or treatment measures may result in substantial
illness, injury, disability and/or death.
If, at any time, I experience what I feel are possible side effects from Coartem, I will promptly
discuss the situation with my Medical Officer, and I may be placed on alternative anti-malaria
treatment.

________________________________
Signature

_____________
Date

Peace Corps
Technical Guideline 850

SCHISTOSOMIASIS

1. PURPOSE

To provide Peace Corps Medical Officers (PCMOs) with guidance on schistosomiasis


prevention, diagnosis and treatment

To provide PCMOs with guidance on COS treatment for Volunteers who serve in
schistosomiasis endemic areas

2. BACKGROUND
Schistosomiasis, also known as bilharzia, is a parasitic disease endemic to many areas of the
world served by Peace Corps Volunteers. Among human parasitic diseases, schistosomiasis
ranks second behind malaria in terms of socioeconomic and public health importance in
tropical and subtropical areas. The disease is endemic in 73 developing countries and infects
more than 200 million people. It is a serious disease that, if left undiagnosed and untreated,
can result in major morbidity or mortality.
As such, the Office of Health Services (OHS) attempts to: (1) prevent schistosomiasis
infections in Volunteers, (2) treat those Volunteers who become symptomatic during service
and (3) treat all PCVs living in endemic areas during service. Components of this prevention
and management strategy include:

Education: the provision of education to PCMOs and Volunteers on schistosomiasis


prevention measures, to include personal behaviors and strategies for avoiding exposure
and interventions to reduce the risk of infection when exposure occurs.

Policy: OHS policy that requires all Volunteers serving in schistosomiasis endemic areas
to adhere to schistosomiasis infection prevention measures, i.e., avoidance of known risk
areas and employment of risk reduction strategies throughout their Volunteer service.

Evaluation and Treatment: evaluation and treatment, if medically indicated, of Volunteers


with signs or symptoms consistent with schistosomiasis infection.

COS Treatment: all PCVs living in endemic areas are treated with Praziquantel at COS.

3. EPIDEMIOLOGY/LIFE CYCLE
Schistosomiasis occurs when human skin comes in contact with contaminated fresh water in
which specific species of snails that carry schistosomes are living. Disease transmission occurs
only in fresh water and only in areas where the specific snail host is present. Medical Officers
and Volunteers should, however, assume that all rivers, streams, lakes, and other bodies of
fresh water in schistosomiasis endemic areas are contaminated.
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Schistosomiasis

The pathophysiology of schistosomal disease reflects the geographic distribution and the unique
life cycle of the parasite. Schistosomal disease results directly from schistosome eggs being
deposited in host tissue and from the granulomatous host response to them. It is the eggs, not
the worms that are responsible for most of the pathology associated with the disease.

3.1 Geographic Distribution and Resistance Patterns


The three major species that infect humans are S. haematobium endemic in Africa and the
Middle East, S. mansoni endemic in Africa, parts of South America, the Caribbean and the
Middle East; and S. japonicum endemic in China, Southeast Asia, and the Philippines.
Other species include S. mekongi located in the Mekong River area of Southeast Asia, and
S. intercalatum located in Central and West Africa (see table below).

Site

Species

Urinary

S. haematobium

Geographic Distribution 1, 2
Africa southern Africa, sub-Saharan Africa, Lake Malawi, the Nile River
valley in Egypt.
Middle East Iran, Iraq, Saudi Arabia, Syria, Yemen

Intestinal

S. mansoni

Africa - southern Africa, sub-Saharan Africa, Lake Malawi, the Nile River
valley in Egypt.
Middle East - Iran, Iraq, Saudi Arabia, Syria, Yemen
South America including Brazil, Venezuela, Surinam
Caribbean Antigua, Dominican Republic, Guadeloupe, Martinique,
Montserrat, St. Lucia (low risk).

S. intercalatum

Africa Rain forest areas of central Africa

S. japonicum

Asia Southern China, Indonesia, Philippines

S. mak ongi

Southeast Asia Laos, Cambodia

1 Centers for Disease Control and Prevention. http://www.cdc.gov/parasites/schistosomiasis/epi.html


2 World Health Organization. Schistosomiasis Fact Sheet No. 115. March 2013

ATTACHMENT A also provides a general illustration of the worldwide distribution of


schistosomiasis.
3.2 Life Cycle of the Schistosome Parasite
The life cycle of the schistosome parasite requires the presence of human carriers, fresh
water, and a species-specific intermediate snail host. Transmission occurs when the
cercarial form of the parasite penetrates human skin. The basic life cycle is illustrated in
ATTACHMENT B.

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Schistosomiasis

4. PREVENTION OF SCHISTOSOMISASIS INFECTION


There is no vaccine against schistosomiasis; and there are no drugs approved as
chemoprophylactic agents. Avoidance of exposure to contaminated water remains the only
reliable prevention measure.
The Schistosoma parasites can penetrate the skin of persons who are wading, swimming,
bathing, washing, or otherwise in contact with contaminated water. Therefore, to reduce or
eliminate potential schistosomiasis exposure, OHS requires PCMOs educate Volunteers on
disease specific prevention measures. Education should include personal behaviors and
strategies for avoiding exposure, country specific information that may assist Volunteers in
avoiding exposure and disease specific interventions to reduce the risk of infection when
exposure occurs.
The Office of Health Services also requires all Volunteers serving in schistosomiasis endemic
areas to observe schistosomiasis prevention measures. These include, but are not limited to,
the following precautions.

Avoid contact with, including swimming in, all freshwater bodies of water; this includes
lakes, ponds, rivers, streams, irrigation systems, dams, canals and other bodies of
freshwater. All freshwater bodies of water in endemic areas are potentially contaminated.
Swimming in the ocean or well-maintained, chlorinated pools is safe.

Do not bathe in any of the freshwater sources mentioned above. Bathe in water that is
made safe by the following methods: (1) allowing the water to stand for greater than 48
hours during which time the cercariae die; (2) heating the water for 5 minutes at 150 F; or
(3) filtering with a water filter or fine mesh filter.

Never drink untreated water from any of the freshwater sources mentioned above.
Infection can occur through the skin of the lips and mouth. Drink safe water. Drinking
water should be made safe using the water disinfection methods described in TG 810
ATTACHMENT A Water Disinfection Methods.

Though several prevention measures associated water contact have been examined (application
of DEET to the skin prior to freshwater exposure and vigorous towel drying after freshwater
exposure), these measures are not proven to provide significant protection against schistosomal
infection. The only measure that reliably prevents schistosomiasis is avoidance of contact with
freshwater in endemic countries.

5. CLINICAL FEATURES
All Volunteers with signs or symptoms suggestive of possible schistosomiasis infection must
be evaluated. The definitive diagnosis of schistosomiasis is made by identification of eggs in
urine (S. haematobium) or stool (all species); or a history of fresh water exposure in an
endemic area and a positive antibody titer.

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Schistosomiasis

5.1 Signs and Symptoms


Most Volunteers who become infected with schistosomiasis are asymptomatic, do not
recall symptoms of acute infection, and appear to have a light infection with few adult
worms present. If symptoms are present, they vary according to the stage of infection
and the worm location of the specific schistosome species.
Key symptoms and signs of acute and early chronic infection include the following:

Fever
Cough
Malaise, Fatigue
Arthralgias, Myalgias
Abdominal pain
Diarrhea (may be bloody)

Urticaria
Right Upper Quadrant pain
Hepatosplenomegaly
Eosinophilia
Hematuria, dysuria (chronic)

The three clinical stages of schistosomal infection are:


Stage 1: Dermatitis

Secondary to skin invasion by cercariae.

Stage 2: Acute

Secondary to systemic hypersensitivity to egg and larval


antigens.

Stage 3: Chronic

Secondary to granulomatous reactions to eggs and egg


antigens; if left untreated, results in fibro-occlusive disease.

Schistosomal (Cercarial) Dermatitis


Schistosomal dermatitis is a pruritic, papular or urticarial rash that occurs at the site of
cercarial penetration. The reaction may develop a few hours after infection or may appear
up to one week later, and may last a few hours to several days. At this early stage of
infection, most people have no complaints and no clinical symptoms. Some may
complain of burning or irritation of the skin followed, in some cases, by urticaria.
The differential diagnosis of schistosomal dermatitis includes allergy, insect bites, and
contact dermatitis.
Acute Schistosomiasis (Katayama Fever)
The acute stage of infection, known as Katayama Fever is a hypersensitivity reaction to
the schistosome antigens. It occurs most often with S. mansoni or S. japonicum. The
syndrome is most often seen in persons with no previous exposure to the disease, such as
Volunteers.
Symptoms usually develop 2 8 weeks after exposure to contaminated water, but may
even develop months later. The onset of symptoms usually coincides with the onset of
egg deposition and often precedes the appearance of eggs in urine or feces. Eggs, if
found in urine or feces, typically appear 40-50 days after exposure but may take over 90
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days to appear. By this time, the acute stage may be over, with symptoms having
resolved over a period of several weeks.
Often the patient becomes suddenly ill with presentations varying from mildly ill with to
extremely ill. Symptoms include fever (99-105 F), chills, nonproductive cough,
headache, anorexia, weight loss, generalized myalgias, right-upper quadrant pain, and
diarrhea (may be bloody). Lymphadenopathy and hepatosplenomegaly may be present.
When the acute infection is massive in a patient with no previous exposure to
schistosomes, the resulting illness can be serious and life threatening.
Early Chronic Schistosomiasis
Symptoms of early chronic disease may be seen in Peace Corps Volunteers. These
symptoms usually appear 10-12 weeks after infection when some, of the many of
thousands, of eggs released each day by an adult worm, reach the lumen of the bowel or
bladder and cause inflammation of these organs. Symptoms of intestinal disease
typically include fatigue, abdominal pain, vague, nonspecific intestinal complaints and
diarrhea. The diarrhea may progress to dysenteric bloody diarrhea and subsequent iron
deficiency anemia. Symptoms of urinary tract disease include dysuria, frequency and
hematuria.
Early Neurologic Manifestations
Rarely, schistosomiasis involves the central nervous system (CNS). Egg deposition in
the brain or around the spinal cord may produce seizures and/or a transverse myelitis-like
syndrome. Cerebral mass lesions may result from egg deposition in or around brain
tissue. Most reported cases of cerebral schistosomiasis are caused by S. japonicum, and
most cases of schistosomal tranverse myelitis by S. mansoni or S. haematobium.
Symptoms of both syndromes may include severe headache and neck stiffness, central
nervous system (CNS) changes, both generalized and focal, and paralysis. In severe
cases infection may result in death.
PCMOs should consider the possibility of neuroschistosomiasis in all patients who have a
history of freshwater exposure in schistosomiasis endemic areas and CNS abnormalities,
even in the absence of classic signs and symptoms of acute disease.
Neuroschistosomiasis can occur several months after exposure to infested water and in
low-intensity infections in which eggs may be undetectable or difficult to identify in
urine or stool.
Late Chronic Schistosomiasis
Late chronic disease is responsible for most of the morbidity and mortality associated
with the disease. Chronic schistosomiasis occurs almost exclusively in lifetime residents
of endemic areas and is very rarely seen in expatriates or Peace Corps Volunteers.
During the late chronic stage of infection, schistosome eggs, and the antigens they
secrete, can accumulate in target organs, which eventually results in granuloma
formation, scarring and fibrosis. The intensity and duration of infection determine the

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amount of antigen released and the severity of fibro-obstructive disease. S. haematobium


affects the urinary tract, i.e., the bladder, ureters, and kidneys, and S. mansoni, S.
japonicum, S. mekongi, and S. intercalatum affect the intestine and liver.
Neuroschistosomiasis can also occur years after initial infection, though this is less
common than in the early chronic phase
5.2 Physical Exam
Physical exam is often unremarkable. Physical findings vary with the stage of the illness,
worm location, worm burden, and target-organ involvement.
Schistosomal Dermatitis

Skin: Nonspecific, erythematous, macular or maculopapular rash. Vesicles may be


present. No particular patterns are observed, except that the rash is found only on areas of
skin that came into contact with the infected water. No other symptoms are present
Acute and Early Chronic Schistosomiasis

Vital Signs: Temperature may range from normal to 105F (40.6C); blood pressure,
respiratory rate and pulse may be elevated secondary to fever

Skin: Nonspecific, erythematous, macular or maculopapular rash; petechial rash or


urticaria may be present

Chest: Lungs normal or cough; Cardiac normal

Abdomen: Generalized tenderness to palpation may be present

Spleen: Moderate splenomegaly

Liver: RUQ tenderness with hepatomegaly

Extremities: Peripheral edema is usually absent; paralysis, if neurologic involvement

Lymphadenopathy: May be generalized and present

Musculoskeletal: Despite complaints of myalgia and arthralgia, neither muscle


tenderness nor joint effusions are present

Neurologic: Seizures and/or altered mental status if CNS involvement; paralysis

5.3 Laboratory Diagnosis and Findings


The detection of schistosome eggs in urine or feces is diagnostic of schistosomiasis.
PCMOs should identify the best available in-country laboratory to perform these exams.
Because intensity of infection is associated with morbidity, quantitative assessment of
eggs is important for determining severity of infection, but not necessary for diagnosis or
treatment.
If there is no history of previous schistosomiasis infection, a positive serologic antibody
titer in a Volunteer is also considered diagnostic of the disease.

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Urinalysis and Urine Microscopy


A urinalysis with microscopy must be performed to detect eggs of S. haematobium
whenever schistosomiasis is suspected.
S. haematobium egg excretion peaks between 10 a.m. and 2 p.m., thus samples should
ideally be obtained around noon when excretion is maximal. Because eggs are not shed
at a steady rate during the day, egg identification may be improved with concentration
and examination of a 24-hour urine collection.
Stool Examination and Stool Microscopy
A stool specimen examination with microscopy must be performed whenever
schistosomiasis is suspected. Eggs can be present in the stool in infections with all
Schistosoma species, but are especially common in infections with S. mansoni and S.
japonicum.
A stool specimen of 2-10 mg of fecal material with or without suspension in saline is
required for examination. Since eggs may be passed intermittently or in small amounts
repeat examinations - as many as three specimens - may be required for diagnosis.
Concentration and examination of a 24-hour stool collection or other concentration
techniques that improve egg identification may be required.
Serology (Antibody Detection)
In individuals who are suspected to have schistosomiasis and in whom eggs cannot be
identified, serologic antibody testing may be a useful tool in the diagnosis of
schistosomiasis. However antibody testing cannot distinguish between past, current,
active or chronic disease so is not useful for individuals with a history of past disease and
treatment. It also may not become positive for at least 4 6 weeks after infection.
Keeping these limitations in mind, positive schistosome serology in individuals with a
history of freshwater exposure in an endemic area, no history of past schistosome
infections, and no prior treatment of disease, is considered presumptive evidence of
infection and treatment should be initiated.
OHS does not recommend screening, via antibody testing, of Volunteers who are
asymptomatic, even with a history of fresh water exposure. The Office of Health
Services does support in-service diagnostic antibody testing when clinically indicated.
Schistosoma antibody testing can be done by the local lab, if available, or sent to Quest
Diagnostics. Samples should no longer be sent to the CDC for schistosomal antibody
testing.
Blood Tests and Chemistries
When schistosomiasis is suspected, the following laboratory tests should be performed as
these tests may provide additional supportive evidence of infection:

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Complete Blood Count (CBC): Peripheral eosinophilia is a common finding in most forms
of schistosomiasis and may reach between 15-50%, particularly in acute infection.
Eosinophilia, however, has a broad differential diagnosis and, in isolation, is not considered
diagnostic of shistosomiasis, nor is it required for the diagnosis of schistosomiasis.

Liver function tests (ALT, AST, GGT, alkaline phosphate, direct/indirect billirubin,
albumin): Alkaline phosphate and GGT may be increased with hepatic granulomatosis.
Transaminiases are generally not affected. Elevations may be caused by any coexisting
hepatocellular disease, e.g., hepatitis.
Imaging Studies
Radiography is an important diagnostic tool in the evaluation of sequelae and
complications of chronic schistosomiasis, however, radiographic findings are extremely
rare in the usually, lightly infected, Volunteer population. Thus, the following exams
should not routinely be performed.

CXR, plain x-ray film of the abdomen, IVP, ultrasound, echocardiography, cystoscopy,
endoscopy, CT scan and MRI
Persistent or severe symptoms may require follow-up exams. CT scan and MRI may be
useful in the evaluation of CNS disease.

5.4 Differential Diagnosis


Differential diagnosis of acute schistosomiasis includes other causes of fever of unknown
origin including:

Malaria
Viral illness

Acute bacterial infection or sepsis


Allergic reaction

6. TREATMENT OF SCHISTOSOMIASIS
Praziquantel is the current drug of choice for treating acute and chronic schistosomiasis based
on its spectrum of activity, safety, and cost.
Cercarial Dermatitis

Treatment is symptomatic with oral antihistamines and topical hydrocortisone cream.


Rarely, short courses of systemic steroids or antihistamines may be used to treat severely
symptomatic individuals.

Counseling regarding schistosomiasis prevention (see Section 4 above).

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Acute Schistosomiasis
In general, immediate treatment is indicated and should be initiated when one or more of
the following findings are present:

CRITERIA FOR IMMEDIATE TREATMENT


1.

Eggs identified in the urine or stool.

2.

Positive antibody serology in a symptomatic patient (see Section 5.3).

3.

Positive history of exposure, AND signs and symptoms of acute disease (see
Section 5.2), AND a strong clinical suspicion of schistosomiasis infection.

When microscopic examination of stool and urine for eggs is negative or not
available, or when antibody titers are pending or indeterminate, PCMOs should
maintain a high index of suspicion of disease and consider treatment when the
following findings are present:

CRITERIA FOR TREATMENT CONSIDERATION


(High Index of Suspicion)
Positive history of exposure AND one or more of the following signs or symptoms of
disease:
1.

History of dermatitis and/or fever-like syndrome.

2.

Hematuria - isolated hematuria, i.e., in the absence of other signs or symptoms of


disease, is not considered diagnostic of schistosomiasis.

3.

Eosinophillia - isolated eosinophilia, i.e., in the absence of other signs or symptoms


of disease, is not considered diagnostic of schistosomiasis.

4.

Any evidence of chronic schistosomal disease (see Section 5.1).

When initiating treatment, PCMOs must consider the following:

Acute schistosomiais is a serious disease and treatment should be initiated


immediately, regardless of time since exposure or schistosomal species.

Adequate treatment, however, depends upon timing of treatment and schistosomal


species. Therefore, if treatment was started earlier than 4-6 weeks after infection with S.
japonicum, 6-8 weeks after infection with S. mansoni, and 10-12 weeks after infection
with S. haematobium, it should be repeated within two to three months. Treatment
which occurs too early, i.e., during the phase of infection before adult worms have
developed, which is also before egg production begins, may not be effective in curing
schistosomiasis

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In the acute stage eggs may not be present, still, the presumptive diagnosis of acute
schistosomiasis may be made on clinical suspicion reinforced by the presence of any of
the above mentioned signs or symptoms of disease.

When there is a high index of suspicion of disease and no laboratory confirmation of


infection, PCMOs should consider repeat testing and OHS consultation.

6.1

Immediate Management Measures


Once the diagnosis of acute schistosomiasis is made - presumptive or definitive - the
following management measures should be employed:

Ensure fever control.

Ensure adequate hydration. Consider IV therapy.

Consider antibiotics and/or anti-malarials as indicated.

Monitor for acute complications, i.e., volume depletion and gastrointestinal (GI)
bleeding, CNS.

Be aware that treatment will not immediately relieve the symptoms of acute
schistosomiasis as symptoms are due to an immunological reaction. Symptoms may
transiently worsen as the killed worms release antigen increasing the strength of the
immunological reaction.

6.2

Treatment Regimens for Schistosomiasis

Praziquantel is the drug of choice for treating schistosomiasis. For uncomplicated


schistosomiasis infections in Volunteers, OHS recommends the following treatment
regimens:
S. haematobium, S. mansoni, and S. intercalatum

PRAZIQUANTEL 40 mg/kg/d in two (20 mg/kg doses) x 1 day


4-6 hours apart, with food

S. japonicum, S. mekongi

PRAZIQUANTEL 60 mg/kg/d in three (20 mg/kg doses) x 1 day


4-6 hours apart, with food

ATTACHMENT C Schistosomiasis Treatment Dosing is a quick reference to


assist with determining weight based dosing.

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TG 330, ATTACHMENT J Praziquantel Medication Information Sheet


should be given to all PCVs who receive Praziquantel.
o Effectiveness: Praziquantel is active against all schistosomal species. It is also
active against all clinical forms and stages of the disease except the developing
worms, which are present during the first 4-6 weeks after infection with S.
japonicum, 6-8 weeks after infection with S. mansoni, and 10-12 weeks after
infection with S. haematobium.
It reliably cures 65-90% of patients and substantially decreases the worm burden
and egg production in those who are not cured. Cure rates are higher for those
with light infections, such as Volunteers, than for those with high egg counts.
Most patients with early disease and without severe end-organ complications
recover completely.
o Adverse Reactions: Praziqantel is generally well tolerated. Reactions that are
reported are usually mild and short-lived. Minor adverse reactions are observed
in up to 50% of individuals; these include abdominal discomfort, dizziness,
drowsiness, headache, sweating, dry mouth, dry eyes, and ringing or buzzing in
the ears. Hives, itching, nausea, vomiting, diarrhea, anorexia and fever are
occasionally reported.
o Contraindications: Documented hypersensitivity; ocular cysticercosis; in those
persons coinfected with neurocysticercosis (seizures could be induced);
hydantonins and systemic steroids may reduce serum praziquantel concentration
possibly leading to treatment failures.

Oxamniquine (Vansil) had previously been an alternative drug for treating S. mansoni, but
is no longer readily available.

Steroids
Steroids have been used in the management of acute schistosomiasis; however, there
are no clinical trials to assess optimal therapy. Nevertheless, steroids may be useful
prior to treatment in heavily infected persons to control the heightened immunologic
reaction to worm antigens after Praziquantel is given. Treatment may exacerbate
symptoms as a result of increased antigen release.
Corticosteroids should be used only for persons who are extremely toxic appearing
and whose symptoms fail to respond or worsen with treatment. Use with CNS
involvement to prevent inflammation and edema around the eggs. Prednisolone 40
mg/day for 5 days is the recommended dosing.
For persons with mild symptoms, non-steroidal anti-inflammatory agents should be
used.

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6.3 Treatment of Pregnant Volunteers


PCMOs are required to consult OHS if a pregnant Volunteer develops schistosomiasis.
Praziquantel is the OHS preferred drug of choice. Treatment may be deferred until after
the first trimester.
6.4 Volunteer Education and Counseling
At the time of diagnosis, PCMOs should strongly encourage the Volunteer to avoid
repeated exposure to contaminated water and should review the disease prevention
measures outlined in Section 4. In addition, PCMOs should insure the Volunteer
understands the following: (1) the presence of anti-schistosomal antibodies does not
reliably prevent re-infection; and (2) re-infection is possible and serious systemic
complications, while infrequent, do occur.
Volunteers who exhibit repeated high risk behavior through freshwater contact and do
not comply with schistosomiasis prevention strategies due to willful misconduct or
disregard for the Peace Corps Volunteer Health Program should be referred to the
Country Director for administrative action (see TG 155 Non-Compliance with Medical
Policies or Instructions).
6.5 Post-Treatment Follow-Up
The Office of Health Services requires PCMOs to monitor Volunteers post treatment for
symptom resolution and determination of cure. Medical Officers should:

Reevaluate the Volunteer for resolution of symptoms. Most symptoms will improve within
a few weeks of treatment with Praziquantel, although resolution of some may take several
months.
Persistent symptoms warrant follow-up exams as indicated, e.g., cystoscopy, ultrasound or
urologic evaluation for hematuria or other GU symptoms; endoscopy or GI referral for
blood in the stool or other GI symptoms, etc.

If eggs were identified in urine or stool prior to treatment, repeat urine or stool exams at 12 months and 3-4 months to confirm the disappearance of eggs and to assess efficacy of
treatment. Praziquantel is not 100% effective; therefore, PCMOs should monitor urine or
stool for the disappearance of eggs.

Retreat if indicated. Eggs may be shed for months after successful therapy or natural death
of worms. Eggs may or may not be viable, but because the tests required to distinguish live
from dead eggs are not readily available, PCMOs should repeat treatment every few
months until eggs are no longer detectable. Treatment should arrest egg laying, granuloma
formation, and future complications.

In those with negative exams for eggs, if praziquantel does not relieve the symptoms that
are attributed to schistosomiasis, consider another etiology.

Do not repeat antibody testing. Repeated antibody testing following treatment is not
clinically indicated. Antibody levels are likely to persist for many years; the duration of
positive antibody test following treatment is not known.

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6.6 COS Treatment

Starting in March 2012, all Volunteers living in Schistosomasis endemic regions are to be
treated empirically with Praziquantel at COS for possible exposure.
Volunteers are adults considered to be at risk which is the rational for empiric treatment of
Schistosomiasis. See the WHO strategy for treatment at:
http://www.who.int/schistosomiasis/strategy/en/index.html
Treatment should be given within 72 hours of COS a labeled container with detailed
instructions
See Section 6.2 for appropriate treatment regimens
Provide TG 330, ATTACHMENT J Praziquantel Medication Information Sheet to all
Volunteers receiving praziquantel

REFERENCES
UpToDate, Treatment and Prevention of Schistosomiasis, July 2013,
http://www.uptodate.com/contents/treatment-and-prevention-ofschistosomiasis?detectedLanguage=en&source=search_result&search=schistosomiasis&select
edTitle=3%7E65&provider=noProvider
UpToDate, Diagnosis of Schistosomiasis, July 2013,
http://www.uptodate.com/contents/diagnosis-ofschistosomiasis?detectedLanguage=en&source=search_result&search=schistosomiasis&select
edTitle=2%7E65&provider=noProvider
UpToDate, Treatment and Prevention of Schistosomiasis, July 2013,
http://www.uptodate.com/contents/treatment-and-prevention-ofschistosomiasis?detectedLanguage=en&source=search_result&search=schistosomiasis&select
edTitle=3%7E65&provider=noProvider
Center for Disease Control and Prevention, Division of Parasitic Disease,
www.dpd.cdc.gov/dpdx
Centers for Disease Control and Prevention. Yellow Book (Health Information for
International Travel, 2014).
Medscape, Schistosomiasis, March 1, 2013, http://emedicine.medscape.com/article/228392overview
Uniformed Services University of the Health Sciences, Schistosomiasis, Tropical Medicine
Central Resource, Chapter 2. http://tmcr.usuhs.edu/tmcr/chapter2/intro.htm
World Health Organization, Schistosomiasis. Fact Sheet No. 115, March 2013.
World Health Organization, Preventive Chemotherapy in Human Helminthiasis, 2006,
http://whqlibdoc.who.int/publications/2006/9241547103_eng.pdf
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TG 850 ATTACHMENT A

WORLDWIDE DISTRIBUTION OF SCHISTOSOMIASIS

The map shows schistosomiasis-endemic areas worldwide, categorized by areas where hepatic/intestinal
schistosomiasis occurs, where urinary schistosomiasis occurs, and where both types occur.
Hepatic/intestinal schistosomiasis is endemic in most of the eastern half of South America. Both types
are endemic in most African countries and the Middle East. Hepatic/intestinal schistosomiasis is endemic
in China; Thailand; Laos; Cambodia; and most other countries in Southeast Asia. Urinary schistosomiasis
is endemic in Turkey; Syria; Jordan; Iraq; Iran; India.
Note:
Urinary Schistosomiasis = S. haematobium;

Hepatic/Intestinal Schistosomiasis = S. mansoni in Africa, Middle East, South America, and the
Caribbean; S. intercalatum in Africa; S. japonicum, S. mekongi, and S. malaynensis in Asia.

The map represents a general illustration of the worldwide distribution of schistosomiais. PCMOs should
follow the guidance for schistosomiais prevention and treatment outlined in the text of Technical Guideline
850 Schistosomiais.
Map adapted from Health Information for International Travel, 2014 (Yellow Book). Published by the
Centers for Disease Control and Prevention., http://wwwnc.cdc.gov/travel/yellowbook/2014/chapter-3infectious-diseases-related-to-travel/schistosomiasis

November 2013

TG 850 ATTACHMENT B

LIFE CYCLE OF THE SCHISTOSOMIASIS PARASITE

Eggs are eliminated with feces or urine


. Under optimal conditions the eggs hatch and release miracidia
, which swim and penetrate specific snail intermediate hosts
. The stages in the snail include 2
generations of sporocysts and the production of cercariae
. Upon release from the snail, the infective
cercariae swim, penetrate the skin of the human host
, and shed their forked tail, becoming
schistosomulae
. The schistosomulae migrate through several tissues and stages to their residence in
the veins ( ,
). Adult worms in humans reside in the mesenteric venules in various locations, which at
times seem to be specific for each species
. For instance, S. japonicum is more frequently found in the
superior mesenteric veins draining the small intestine
, and S. mansoni occurs more often in the superior
mesenteric veins draining the large intestine
. However, both species can occupy either location, and
they are capable of moving between sites, so it is not possible to state unequivocally that one species only
occurs in one location. S. haematobium most often occurs in the venous plexus of bladder
, but it can
also be found in the rectal venules. The females (size 7 to 20 mm; males slightly smaller) deposit eggs in
the small venules of the portal and perivesical systems. The eggs are moved progressively toward the
lumen of the intestine (S. mansoni and S. japonicum) and of the bladder and ureters (S. haematobium),
and are eliminated with feces or urine, respectively
. Pathology of S. mansoni and S. japonicum
schistosomiasis includes: Katayama fever, hepatic perisinusoidal egg granulomas, Symmers pipe stem
periportal fibrosis, portal hypertension, and occasional embolic egg granulomas in brain or spi nal cord.
Pathology of S. haematobium schistosomiasis includes: hematuria, scarring, calcification, squamous cell
carcinoma, and occasional embolic egg granulomas in brain or spinal cord.

Diagram adapted from the CDC DPDx website (www.dpd.cdc.gov/dpdx).


Reviewed November 2013

TG 850 Attachment C

SCHISTOSOMIASIS TREATMENT DOSES


PRAZIQUANTEL 600 mg scored tablets
S. mansoni, S. haematobium, S. intercalatum
Dosage 40 mg/kg total divided into two oral doses in 1 day, 4-6 hours apart, with food
Pounds
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250

Kilograms
45.5
50.0
54.5
59.1
63.6
68.2
72.7
77.3
81.8
86.4
90.9
95.5
100.0
104.5
109.1
113.6

Total Dose
1820 mg
2000 mg
2180 mg
2364 mg
2544 mg
2728 mg
2908 mg
3092 mg
3272 mg
3456 mg
3636 mg
3820 mg
4000 mg
4180 mg
4364 mg
4544 mg

Divided Dose
910 mg
1000 mg
1090 mg
1182 mg
1272 mg
1364 mg
1454 mg
1546 mg
1636 mg
1728 mg
1818 mg
1910 mg
2000 mg
2090 mg
2182 mg
2272 mg

# of tablets for each of dose


1 1/2
1 3/4
2
2
2 1/4
2
2 1/2
2 3/4
2 3/4
3
3
3 1/4
3 1/2
3 1/2
3 3/4
3 3/4

S. japinicum, S. mekongi (Indonesia, China, Philippines, Cambodia, Laos)


Dosage 60 mg/kg total divided into two oral doses in 1 day, 4-6 hours apart, with food
Pounds
100
110
120
130
140
150
160
170
180
190
200
210
220
230
240
250

Kilograms
45.5
50.0
54.5
59.1
63.6
68.2
72.7
77.3
81.8
86.4
90.9
95.5
100.0
104.5
109.1
113.6

Total Dose
2730 mg
3000 mg
3270 mg
3546 mg
3816 mg
4092 mg
4362 mg
4638 mg
4908 mg
5184 mg
5454 mg
5730 mg
6000 mg
6270 mg
6546 mg
6816 mg

Divided Dose
1365 mg
1500 mg
1635 mg
1773 mg
1908 mg
2046 mg
2181 mg
2319 mg
2454 mg
2592 mg
2727 mg
2865 mg
3000 mg
3135 mg
3273 mg
3408 mg

# of tablets for each dose


2 1/4
2 1/2
2 3/4
3
3 1/4
3 1/2
3 3/4
4
4 1/4
4 1/2
4 3/4
5
5
5 1/4
5 1/2
5 3/4
November 2013

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