COMMUNICABLE DISEASES

TYPHOID FEVER (ENTERIC FEVER)

- Epidemiology:
o An estimated 22M cases of typhoid fever
and 200,000 related deaths occur
worldwide each year.
o Approximately 400 cases of typhoid fever
among persons with onset of illness in the
US, most of who are recent travellers.
o Risk is greatest for people living & travellers
to South Asia and developing countries in
Asia, Africa, the Caribbean, Central and
South America.
o Rapid population growth increased
urbanization, inadequate human waste
treatment, limited water supply, overburden
health care system.

Salmonella
- Gram (-) rods, facultative aerobic, motile with
peritrichate flagella, non spore forming
- Enterobacteriacea
- 1-3 m to __ 5 m in size
- Salmonella currently comprise 2000 serotypes
- Two groups:
o Enteric fever group
o Food poisoning group
- Killed at 550C in one hour or at 600C in 15 minutes or
boiling or chlorination of water.

- Transmission: Typhoid Fever

o Ingestion of contaminated food or drink by
stool (rarely urine)
o Person to person transmission through oral-
fecal route (household contact)
o Health care worker after exposure to
infected patients or contaminated linen can
also be infected.
o Sewage – contaminated water or shellfish
o Man is the only known reservoir of infection
or carriers
- Increase susceptibility:
o Decrease stomach acid – age <1 year old,
antacid, achlorydia, gastrectomy.
Classical Typhoid Fever
o Decrease intestinal integrity – inflammatory
bowel disease. GI surgery, alteration of GI
flora by antibiotic.
- Pathogenesis:
o Bacilli penetrate the mucous membrane of
the distal ileum via the M cells/microfold
cells.
o Phagocytosed by macrophages in the Peyers
patches.
o The infected macrophages via the
lymphatics spread the infection to the
reticuloendothelial tissues like the liver,
spleen, lymph node, and bone marrow.
o Once the bacilli has achieve critical number
through replication, the macrophage will
secrete cytokines causing the s/s of fever,
abdominal pain.
o Recruitment of additional mononuclear cells
and lymphocytes is likely to cause hepatos-
plenomegaly, mesenteric lymph-
adenopathy and enlargement and necrosis
of the peyers patches.
- Incubation period = 10-14 days (3-21 days)
- High grade fever (>75%), stepladder (12%), prolonf if
untreated
- Abdominal pain (20-40%), diffuse with tenderness
- Prodrome:
o Chills, headache, anorexia, cough,
weakness, sorethroat, dizziness, muscle
pain, diarrhea, or constipation
- Typhoid should be considered in any patient with
prolonged unexplained fever in endemic areas abd in
those with a history of recent travel to endemic area.
- Prolonged fever, rose spots, relative bradycardia and
leucopenia make typhoid strongly suggestive.
- First week:
o Classically presents with step-ladder fashion
rise in temperature (40-410C) over 4-5 days,
accompanied by headache, vague
abdominal pain, and constipation.
- Second week:
o Between the 7th-10th day of illness, mild
hepatosplenomegaly occurs in majority of
patients. Relative bradycardia may occur.
o Rose spots may be seen
- Third week:
o The patient will appear in a typhoid state:
 A state of prolonged apathy,
toxemia, delirium, disorientation
and/or coma
 Diarrhea (pea soup) will then be
apparent
 If left untreated by this time, there
is a high risk (5-10%) of intestinal
hemorrhage and perforation.
- Early PE findings:
o Rose spots
 Faint blanching salmon colored,
maculopapular rash on the trunk
and chest appearing at the end of
the first week (30%)
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o Epistaxis o Lymphopenia
o Hepatosplenomegaly o Slightly elevated PTT and aPTT
o Bradycardia o Decrease fibrinogen
- Atypical manifestations: o Increase fibrin degradation product in
o Isolated severe headaches that may mimic subclinical DIC
meningitis o Increase liver transaminases
o Acute Lobar Pneumonia o Imaging studies
o Isolated Arthralgias
o Urinary Symptoms - Complications:
o Severe Jaundice o Intestinal perforation
o Fever alone o GI bleeding
o Neuropsychiatric symptoms – delirium
- Differential diagnosis: o Rarely:
o Malaria  Pancreatic, Hepatic, Splenic
o Hepatitis Abscess
o Bacterial enteritis  Endocarditis, Pericarditis,
o Dengue fever Myocarditis
o Leptospirosis  Orchitis
o Amebic liver abscess  Hepatitis
o Acute HIV infection  Meningitis
 Pneumonia
- Laboratory Diagnosis:  Nephritis, GN
o Gold standard-(+) culture:  Arthritis
 Blood culture yield is 90% in the 1 st  Osteomyelitis
week, decreases 50% by 3rd week.  Parotitis
 Other specimen for culture: stool,
urine, rose spot, bone marrow, o Carrier state (1-5%) – shedding in the stool
gastric or intestinal secretion or urine.
 Bone marrow C/S remain highly
sensitive (>90%) inspite of used of o Neurologic manifestations:
antibiotic for < 5 days.  Occur in 2-40%
o Serologic test – Typhi dot  Meningitis
o PCR – being develop  Guillain-Barré syndrome
o Widal test (?)  Neuritis
 Dectect agglutinating antibodies in  Neuropsychiatric symptoms
the blood against Salmonella (described as “muttering delirium”
antigens O-somatic and H-flagellar or “coma vigil”), with picking at
 In the absence of recent bedclothes or imaginary objects
immunization, AB to O >1:640 is “Typhoid psychosis” – long term or
suggestive but not specific. permanent.
 Usually begin to become (+) during
the second week. o Typhoid Relapse
 Has a low sensitivity, specificity and  Recurrence of fever
positive predictive value in  Up to 10% of patients
developing countries which  Usually within 2-3 weeks of fever
changes with the geographical resolution
areas  Milder s/s
 Sharing of O and H antigens by  Associated with the same strain
other Salmonella serotypes and type and antibiotic susceptibility
other members of profile.
Enterobacteriaceae makes the role
of Widal test even more
controversial
 Not recommended in the Phils.

o Typhi dot test

 ELISA kit
 Detects IgM and IgG antibodies
against the outer membrane
protein (OMP) of the Salmonella
typhi.
 Becomes (+) within 7-14 days (2-3
days) of infection.
 Separately identifies IgM and IgG
antibodies.

- Non specific lab findings:

o Moderate anemia
o Elevated ESR
o Thrombocytopenia

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strain of S.typhi by the Swiss

- Carriers Serum and Vaccine Institute.
o May be temporary or chronic  Intramuscular: Vi capsular
 Temporary (convalescent or polysachharide vaccine (ViCPS)
incubatory) carriers usually excrete (Typhim Vi, manufactured by
bacilli up to 6-8 weeks Sanofi Pasteur).
 Chronic carriers are persons who  Both vaccines protect 50-80% of
excrete the bacilli for more than a recipients
year after a clinical attack  No evidence on safety during
 2-5% patients may pregnancy.
become Gallbladder o Oral Ty21a vaccine:
carriers  One capsule every 48 hours x 4
 By the end of one year, 3- doses
4% of cases continue to  Should be kept refrigerated (not
excrete typhoid bacilli. frozen)
 Chronic carriage common in:  Should be taken with cool liquid no
 Women warmer than 370C (98.60F),
 Infants approximately 1 hour before meal.
 Persons with biliary  Regimen should be completed 1
abnormalities. week before potential exposure
 Concurrent bladder  Not recommended to infants or
infection with children younger than 6 years of
Schistosoma age.
haematobium.  Should not be given in
immunocompromise
- Treatment:  Booster every 5 years.
o Supportive o Vi capsular polysaccharide Vaccine (ViCPS)
o Antibiotics – Chloramphenical, TMP-SMX,  Single dose of one 0.5mL (25 g)
Ampicillin, Amoxicillin, Quinolones, dose that is administered
Ceftriaxone, Azithromycin* intramuscularly.
o Antimicrobial therapy should be guided by
 Should be given at least 2 weeks
data on antimicrobial sensitivity, particularly
for travellers to South Asia before expected exposure.
o Dexamethasone*  Not recommended for infants and
children younger than 2 years of
- MDR age
o Emerged in 1989 in China and South East
 Booster every 2 years
Asia
- Adverse Reaction:
o Contains plasmids encoding resistance to
Fever Headache Local R
Choramphenicol, Ampicillin, and
Ty21a 0-5% 0-5% N/A
Trimetophrim.
ViCPS 0-1% 16-20% Erythema/induration
o Increasing resistance to Ciprofloxacin
1cm
- Surgical care:
o Simple closure for intestinal perforation
o Small bowel resection for multiple
perforation TETANUS
o Cholecystectomy if antibiotic failed to Disease characterized by increase muscle tone and spasm
eradicate gallbladder carriage. cause by the action on the central nervous system of a potent
neurotoxin produce by Clostridium tetani.
- Prevention:
o Immunization: Clostridium tetani
 Natural infection and vaccination - Gram positive anaerobic bacteria
do not give lifetime protection - With an oval terminal spore resembling a tennis
 Proper hygiene racket
o Indications for vaccination: - Ubiquitous, can be found in soil, human and animal
 Travelers going to endemic areas intestine and feces.
who will be staying for prolonged - Vegetative form is sensitive to:
period of time. o Heat and Oxygen
 Persons with intimate exposure to - Spores are resistant to:
a documented S. typhi carrier o Heat (autoclave for 10-15 minutes) and
 Microbiology lab. technologist who usual antiseptic and can survive in dry soil
work frequently for years.
 Immigrants - “Drumstick” or “tennis racket” shape due to the
 Military personnel/those expose to terminal spore.
unhygienic environment. - Epidemiology:
o Vaccines: 2 types o Not a seasonal disease
 Oral live, attenuated vaccine o Affects: non-immunized persons, partially
(Vivotif Berna vaccine, immunized persons and fully immunized
manufactured from the Ty21a

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persons who fail to maintain adequate

immunity with booster doses of the vaccine.
o Any wound or closed infected area can
serve as a nidus for the disease, such as:
 Punctured wounds, lacerations,
abrasions
 Dental caries
 Middle ear infection
 Oral stomatitis
 Pellet implantation in the penis
o Complications of chronic conditions:
 Skin ulcers
 Abscesses
 Gangrene

Severe type of tetanus:

- Infection of umbilical stump among the newborns –
Tetanus neonatorum
- Septic abortion
- Burns
- Crush injuries
- Bone fractures especially compound fracture
- Blasting or missile injuries
- Gangrene
- Narcotic addicts
- Frost bite

Tetanospasmin
- Heavy chain
o Mediates binding to nerve cell receptors
and transport proteins for entry into the
cells
- Light chain
o Responsible for inhibiting the release of
neurotransmitter producing clinical tetanus.
- Motor endplate
- Spinal cord
- Brain
- Sympathetic nervous system

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neurons to increase to multiply unchecked

muscle tone and pro- resulting to classical duce
rigidity tetanic spasms

2. Prevention of the release Acetylcholine in autonomic

and peripheral somatic fibers*
3. The damage to the myoneural junctions and other
synapses appears to be permanent and requires
sprouting of new synapses for recovery*

Clinical Course of Tetanus in a Non-Immunized Persons

depends on:
1. Quantity of toxin produced
a. Quicker onset
b. Rapid progression
c. More severe
2. Length of the neural pathways that the toxin must
traverse to reach the neuroaxis

Incubation Period:
- 2 days to months (average of 2 weeks)
- Directly related to the distance of primary wound
infection from the CNS.
- Shortened incubation period tends to be associated
with more severe disease.

Onset Period:
Pathogenesis: - Time interval between initial symptoms and
occurrence of spasms.
Contamination of wounds on any damaged or devitalized - Shorter onset period especially less than 48 hours
tissues with the spores of Clostridium tetani. In a wound tend to be associated with more severe disease and
environment of low oxidation-reduction potential or worse prognosis.
anaerobic condition.
Tetanus Neonatorum:
- Infection of the umbilical stump
- Failure of aseptic technique
Spores germinate to vegetative bacilli - Inadequately immunized mother
- Generalized weakness and failure to feed
- Rigidity and muscle spasm
- Poor prognosis below 10 days old.

The vegetative organisms produce potent neurotoxin Generalized Tetanus:

(tetanospasmin).
Via lymphatic & vascular circulation, it binds to neural
ganglioside/other receptor at the end plates of all nerves
including myoneural junction.
- Most common form
- Progressive involving more muscle groups in
descending fashion
- Involvement of the masseter muscles and orbicularis
oris muscles (trismus or lockjaw)
- Sardonic smile (risus sardonicus)
- Muscles of the neck, shoulder, back (opisthotonus)
- Muscles of the abdomen (abdominal rigidity) and
proximal limbs.

Localized Tetanus:
- Usually occur in partially immune and non-immune
who receive protective dose of immunoglobulin
From the myoneural junction it is carried by retrograde axonal rather than therapeutic dose
transport system to the ventral horns of the spinal cord or - Spasm of muscles occur at the site of inoculation
motor nuclei of the cranial nerves. - May evolve to generalize form
- Favorable prognosis

Cephalic Tetanus:
- Primary due to infection of the head, particularly the
Interferes or prevents the release of the neurotransmitters ear
- Isolated or combined involvement of the cranial
nerves, particularly the 7th cranial nerves.
1. Glycine and Gamma- AminoButyric Acid from the - May remain localized or evolved into a severe
presynaptic inhibitory fibers generalized tetanus
- Instead of spasms, may be manifested as paralysis of
muscles closest to the site of injury resulting from
higher concentrations of toxin in the brain stem.
Allows lower motor Allow excitatory reflexes
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AUTONOMIC DYSFUNCTION:
- Sweating/Dehydration Antibiotics:
- Hyperthermia - Mild Tetanus:
- Cardiac arrhythmias o Penicillin G Sodium
- Hypertension  Adult: 1-2 million units q 4 hrs
- Hypotension  Children: 30 mg/kg/day
o Metronidazole
Interomediolateral cell column: T1-L2  Adult: 500 mg every 8 hrs
- The loss of inhibition by interomediolateral cell  Children: 30 mg/kg/day
column of the spinal cord produces a marked - Moderate Tetanus:
elevation of the catecholamine plasma levels and o Metronidazole
excretion.  Adult: 500 mg every 8 hrs
 Children: 30 mg/kg/day in 3
Clinical Stages: divided doses
- Stage I – MILD o Ampicillin
o Mild or localized muscle rigidity, trismus,  Adult: 200 mg/kg/day
risus  Children: 150 mg/kg/day
o No major spasms or dysphagia
o Incubation period: 11 days and above o Cephalosporins
o Onset period: 7 days and above  Adult: 150-200 mg/kg/day
o Course of illness: 7-10 days  Children: 50-100 mg/kg/day
- Stage II – MODERATE - Severe Tetanus
o Infrequent, mild, short spasms (less than 12 o Metronidazole
spasms/24 hrs)  Adult: 500mf every 8 hrs
o Trismus, risus  Children: 30 mg/kg/day in 3
o Dysphagia divided doses PLUS>>
o Muscle rigidity o Cephalosporins
o Incubation period: 8-10 days  Adult: 150-200 mg/kg/day
o Onset period: 4-6 days  Children: 50-100mg/kg/day
o Course of illness: 14 days-1 month PLUS>>
- Stage III – SEVERE o Aminoglycosides
o More frequent, prolonged and severe
spasms sufficient to interfere with Tetanus antitoxin/immunoglobulin:
swallowing and ventilation - Equine Tetanus Antitoxin (TAT)
o Severe trismus o Adult, Children, Infant: 40,000 IU (1/2 given
o Severe muscular rigidity IM, ½ given IV)
o Tachycardia and arrhythmias o Neonates: 20,000 IU (1/2 given IM, ½ given
o Profuse sweating and dehydration IV)
o Incubation period: 7 days and below - Tetanus Immunoglobulin (TIG)
o Onset period: 3 days and below o Adult, Children, Infant: 3,000 IU by IV drip or
o Course of illness: 1-2 months IM
o Neonates: 1,000 IU by IV drip or IM
Complication of non-neonatal tetanus:
- Respiratory failure Anti-spasm:
- Pneumonia - To prevent muscle spasms – DIAZEPAM
- Venous thrombosis or pulmonary embolism - Mild to Moderate Tetanus:
- Autonomic instability o Adult: 0.4-0.8 mg/kg/dose by IV bolus
- Cardiac arrest and myocarditis due to excessive o Neonates & Children: 0.2 mg/kg/dose by IV
catecholamine output bolus
- Fractures of the spine or long bones - Severe Tetanus: IV drip and IV bolus
- Infection related to the original wound (sepsis) o Adult: 60 mg in 500 cc D5W at 2-3
- Decubitus ulcers doses/day
- Acute peptic ulcers 10 mg IV every 2-8 hours according to the
severity of spasms
Diagnosis: o Children: 2.5-5 mg IV every 2-8 hours
- Base on clinical presentation only according to the severity of the spasms.
- Laboratory examinations cannot confirm or exclude
the condition General support:
- Antitetanus antibodies cannot be detected in most - Cardiopulmonary monitoring (ICU care for severe
tetanus patients. and complicated cases)
- Quiet room
Treatment goal: - Avoid or limit stimulation
- To eliminate the vegetative form of bacteria that - Protection of the airway
produce the toxin – ANTIBIOTICS - Wounds explored, cleansed, debrided
- To neutralize unbound toxin – ANTITOXIN
- Control spasm – SEDATIVE/MUSCLE RELAXANT Prognosis:
- To provide general and specific support.. - Related to the age of the patient, immune status,
cause of primary infection
- Poor in patients at extreme ages
- Poor in patients with shorter interval of spasm

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- Stiffness may persist for a long time but recovery is

the rule for uncomplicated cases.