Tropical Infection

Diseases
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

GSH - Tropmed - 2010 1

DENGUE FEVER/DENGUE
HEMORHAGIC FEVER

Gatot Sugiharto, MD, Internist

Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya
GSH - Tropmed - 2010 2
 Introduction(1)
Dengue fever is a clinical illness with
symptoms ranging from a nonspecific viral
syndrome such as fever, severe headache,
sore throat, rash, and muscle pain, and
joint pain, to severe and fatal hemorrhagic
Primarily a disease of the tropics, and the
viruses that cause it are maintained in a
cycle that involves humans and Aedes
aegypti, a domestic, day-biting mosquito
that prefers to feed on humans
 Introduction(2)
Dengue is one of the most important
mosquito-born viral diseases affecting
humans.
Viral life cycle involves humans and the
mosquito vector Aedes aegypti, some others
by Aedes albopictus
The disease is caused by 4 serotypes of the
Dengue virus, a member of the genus RNA-
Flavivirus: DEN-1, DEN-2, DEN-3, DEN-4.
Infection with the DEN virus can result in
Dengue Fever (DF), Dengue Hemorrhagic
Fever (DHF) and Dengue Shock Syndrome
 History
The first suspected epidemics of dengue
fever being reported during 1779 to 1780
in Asia, Africa, and North America.
The dengue virus was first isolated in
Japan in 1943, but this work was not
immediately published.
At the same time, Dr. Albert Sabin, working
with the U. S. Army Commission on dengue
and sandfly Fever, identified the dengue
virus.
Global Spread of Dengue

50-100 million infections/year

Countries with active dengue + Aedes aegypti

FOUR VIRUSES
Life time immunity follows infection to
one type.
Second, third and possibly four
infections are possible.
CHILDREN first infections are mild,
largely inapparent.
ADULTS - first infections may produce
DF, some viruses more overt than
others.
 Characteristics of the Aedes
Mosquito
One distinct physical
feature black and
white stripes on its
body and legs.

Bites during the day.

Lays its eggs in clean,

stagnant water. Close-up of an Aedes mosquito
 2.The virus localizes and
replicates in various
target organs, for
example, local lymph
nodes and the liver.
3.The virus is then
released from these
tissues and spreads
6.The virus replicates in through the blood to
the mosquito midgut, the infect white blood cells
ovaries, nerve tissue and and other lymphatic
fat body. It then escapes tissues.
into the body cavity, and 4.The virus is then
later infects the salivary released from these
glands. tissues and circulates in
7.The virus replicates in the blood.
the salivary glands and 5.The mosquito ingests
when the mosquito bites blood containing the
another human, the cycle virus
Pathogene
sis
Pathogenesis
 Symptoms
A sudden onset of fever 3 5 days after bitten by a dengue-
infected mosquito, usually continues for 2 to 7 days and can be
as high as 104 to 106
Severe headache, muscle pain, joint pain, conjunctivitis, severe
orbital pain, backache, anorexia, and nausea and vomiting
Other symptoms : rash, minute reddish/purplish spots, nose
bleeds, or bleeding gums.
Hemorrhagic manifestations usually occur about the time that
the body temperature falls back to or below normal
During the hemorrhagic, signs of circulatory failure may appear.
Evidence of a capillary leak syndrome : reduced blood volume
(hypovolemia), shock, and death can follow.
Prolonged fatigue and depression continue through the recovery
stage.
Physical & lab finding
Dengue Disease Course Summary in
Untreated Individuals

Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 Day 7

EXPOSUR High fever, headache, etc.

E lasting 2 to 7 days
Incubation 3-5
Days

Day 8 Day 9 Day 10 Day 11 Day 12 Day 13 Day 14

High fever, headache, etc.
Mortality rate for
lasting 2 to 7 days
untreated DHF can be
as high as 20%

18 June 2001 16
 Diagnosis
Clinical picture
Detection of anti-dengue immunoglobulin
(Ig) M or IgG antibody in a patient's blood
serum
Isolated from human blood after
mosquito inoculation, or from mosquito
cell cultures, by immunofluorescence
using serotype-specific monoclonal
antibodies (MAbs).
Detection of dengue virus by culture is
the definitive diagnostic test, but
18 June 2001 17
practical limitation its use
 Clinical spectrum
There are actually four dengue clinical
syndromes:
1.Undifferentiated fever;
2.Classic dengue fever;
3.Dengue hemorrhagic fever, or DHF;
and
4.Dengue shock syndrome, or DSS.
Dengue shock syndrome is actually a
severe form of DHF.
 Diagnostic criteria
Clinical Definition for Dengue Fever :
Acute febrile viral disease frequently
presenting with headaches, bone or joint
pain, muscular pains, rash, and leucopenia
Clinical Definition for Dengue Hemorrhagic
Fever :
Fever, or recent history of acute fever
Hemorrhagic manifestations
Low platelet count (100,000/mm3 or less)
Objective evidence of leaky capillaries
elevated hematocrit (20% or more over
baseline)
low albumin
pleural or other effusions
Diagnostic criteria
Clinical Definition for Dengue Shock
Syndrome :
4 criteria for DHF + evidence of
circulatory failure manifested indirectly
by all of the following:
Rapid and weak pulse
Narrow pulse pressure (< 20 mm
Hg) OR
hypotension for age
Cold, clammy skin and altered
mental status
Frank shock is direct evidence of
Grade 1 Grades of DHF
Fever and nonspecific constitutional symptoms
Positive tourniquet test is only hemorrhagic
manifestation
Grade 2
Grade 1 manifestations + spontaneous
bleeding
Grade 3
Signs of circulatory failure (rapid/weak pulse,
narrow pulse pressure, hypotension,
cold/clammy skin)
Grade 4
Profound shock (undetectable pulse and BP)
Grades of DHF
Hemorrhagic Manifestations of Dengue
Skin hemorrhages: petechiae,
purpura, ecchymoses
Gingival bleeding
Nasal bleeding
Gastrointestinal bleeding:
Hematemesis, melena, hematochezia
Hematuria
Increased menstrual flow
 Red flag in DHF
Danger Signs in Dengue Hemorrhagic
Fever ;
Abdominal pain - intense and sustained
Persistent vomiting
Abrupt change from fever to hypothermia,
with sweating and prostration
Restlessness or somnolence

Signs of impending shock and should

alert clinicians that the patient needs
close observation and fluids.
 Treatment
Supportive care
Keep patient hydrated to prevent shock
Hospitalization of patients with advanced
symptoms
Symptomatic treatment : antipyretic
For complete treatment protocol refer to the
following reference:
Dengue hemorrhagic fever: diagnosis,
treatment, prevention and control. World
Health Organization. 2006
18 June 2001 27
 Fluid
replaceme
nt
Shock
Manageme
nt in
Dengue
HIV / AIDS
Gatot Sugiharto, MD, Internist
Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma
University Surabaya

GSH - Tropmed - 2010 30

 INTRODUCTION(1)
Human Immunodeficiency Virus
H = Infects only Human beings
I = Immunodeficiency virus weakens the immune
system and increases the risk of infection
V = Virus that attacks the body
Acquired Immune Deficiency Syndrome
A = Acquired, not inherited
I = Weakens the Immune system
D = Creates a Deficiency of CD4+ cells in the
immune system
S = Syndrome, or a group of illnesses taking
place at the same time
DR. S.K CHATURVEDI
 INTRODUCTION(2)
The HIV : virus that causes AIDS.
HIV attacks the immune system by destroying
CD4 positive (CD4+) T cells, a type of white
blood cell that is vital to fighting off infection
vulnerable to other infections, diseases and
other complications.
AIDS is the final stage of HIV infection.
AIDS is diagnosed when someone has one or
more opportunistic infections, such as
pneumonia or tuberculosis, and has a
dangerously low number of CD4+ T cells (less
than 200 cells/cmm blood).
 HIV
Class of viruses : retroviruses, RNA virus
HIV uses an enzyme called reverse
transcriptase to convert its RNA into DNA
(deoxyribonucleic acid) and then proceeds to
replicate itself using the cell's machinery.
HIV belongs to a subgroup lentiviruses, or
"slow" viruses having a long time period
between initial infection and beginning of
serious symptoms unaware of HIV infection,
can spread the virus to others.
Similar versions of HIV : feline
immunodeficiency virus (FIV) in cats and simian
immunodeficiency virus (SIV) in monkeys and
PMTCT Policy for Barbados - Dr.
34
Anton Best, MOH
PMTCT Policy for Barbados - Dr.
35
Anton Best, MOH
HIV
structur
e
 HIV/AIDS transmission
1. Sexual transmission
Heterosexual
Homosexual
2. Blood and blood products
IV drug use
Transfusions
Haemophilia
Other (knives, needle)
3. Vertical transmission
During pregnancy
During birth
Breastfeeding
 HIV is not transmitted
Coughing, sneezing
by
Insect bites
Touching, hugging
Water, food
Kissing
Public baths
Handshakes
Work or school contact
Using telephones
Sharing cups, glasses, plates, or other utensils
DR. S.K CHATURVEDI
 Pathogenesis
HIV destroys CD4 positive (CD4+) T cells, which
are crucial for the human immune system.
less equipped to fight off infection and disease
resulting in the development of AIDS.
Most people who are infected can carry the
virus for years before developing any serious
symptoms until the number of CD4+ T cells
decline
Antiretroviral help reduce the amount of virus in
the body, preserve CD4+ T cells and
dramatically slow the destruction of the
immune system.
 Generally people in good health have roughly
800 to 1,200 CD4+ T cells per cmm of blood.
Some people who have been diagnosed with
AIDS have fewer than 50 CD4+ T cells in
their entire body.
HIV
Replicati
on Cycle
 Steps in the HIV Replication Cycle
1. Fusion of the HIV cell to the host cell surface.
2. HIV RNA, reverse transcriptase, integrase, and
other viral proteins enter the host cell.
3. Viral DNA is formed by reverse transcription.
4. Viral DNA is transported across the nucleus and
integrates into the host DNA.
5. New viral RNA is used as genomic RNA and to
make viral proteins.
6. New viral RNA and proteins move to cell surface
and a new, immature, HIV virus forms.
7. The virus matures by protease releasing
individual HIV proteins.
 Progression of HIV Infection

Progression of HIV disease is measured by:

CD4+ count
Degree of immune suppression
Lower CD4+ count means decreasing
immunity
Viral load
Amount of virus in the blood
Higher viral load means more immune
suppression

DR. S.K CHATURVEDI

 Clinical Progressionof HIV
Acute Primary Infection
Once HIV enters the body, the virus infects a large
number of CD4+ Tcells and replicates rapidly.
During this acute phase of infection, the blood has a
high number of HIV copies (viral load) that spread
throughout the body, seeding in various organs,
particularly the lymphoid organs such as the
thymus, spleen, and lymph nodes.
During this phase, the virus may integrate and hide
in the cells genetic material. Shielded from the
immune system, the virus lies dormant for an
extended period of time
In the acute phase of infection, up to 70 percent of
HIV-infected people suffer flu-like symptoms.
The Immune System Strikes Back
Two to four weeks after exposure to the virus,
the immune system fights back with killer T cells
(CD8+ T cells) and B-cell-produced antibodies.
HIV levels in the blood are dramatically reduced.
At the same time, CD4+ T cell counts rebound
and for some individuals, the number rises to its
original level.
Clinical Latency
During this phase, a person infected with HIV
may remain free of HIV-related symptoms for
several years despite the fact that HIV continues
to replicate in the lymphoid organs where it
Progression to AIDS
The immune system eventually
deteriorates to the point that the human
body is unable to fight off other infections.
The HIV viral load in the blood dramatically
increases while the number of CD4+ T cells
drops to dangerously low levels
HIV-infected person is diagnosed with AIDS
when he or she has one or more
opportunistic infections, such as pneumonia
or tuberculosis, and has fewer than 200
CD4+ T cells per cubic millimeter of blood.
Natural History of HIV
Infection
Natural History of HIV
Infection

DR. S.K CHATURVEDI

 Early symptoms
In the initial stages of HIV infection, most people
will have very few, if any, symptoms. Within a
month or two after infection, individuals may
experience a flu-like illness, including:
Fever, headache , tiredness
Enlarged lymph nodes in the neck and groin area
These symptoms usually disappear within a week
to a month and are often mistaken for another viral
infection, such as influenza (flu).
However, during this period people are highly
infectious because HIV is present in large quantities
in genital fluids and blood.
Some people infected with HIV may experience
more severe symptoms initially or a longer
 Later Symptoms
Rapid weight loss
Recurring fever or profuse night sweats
Extreme and unexplained fatigue
Prolonged swelling of the lymph glands in the
armpits, groin or neck
Diarrhea that lasts for more than a week
Sores of the mouth, anus or genitals
Pneumonia
Red, brown, pink or purplish blotches on or under
the skin or inside the mouth, nose or eyelids
Memory loss, depression and other neurological
disorders.
Each of these symptoms can be related to other
illnesses. The only way to determine if you are
HIV spectrum
Virus can be transmitted during each
stage
Seroconversion : Infection with HIV,
antibodies develop
Asymptomatic : No signs of HIV,
immune system controls virus
production
Symptomatic : Physical signs of HIV
infection, some immune suppression
AIDS : Opportunistic infections, end-
stage disease DR. S.K CHATURVEDI
ABC Approach
The ABC Approach to prevent sexual
transmission of HIV

Abstain
Be faithful
Use a Condom

Limits of the ABC-Approach

Lack of resources
Gender inequality
 Types of HIV Tests
Healthcare providers can test a sample of blood to
see if it contains human antibodies (disease-fighting
proteins) specific to HIV. The two key types of HIV
antibody tests are the enzyme-linked
immunosorbent assay (ELISA) and the Western blot.
However, these antibody tests may not detect HIV
antibodies in someone who has been recently
infected with HIV (within one to three months of
infection). In these situations, healthcare providers
can test the blood for the presence of HIV genetic
material. This test is extremely critical for
identifying recently infected individuals who are at
risk for unknowingly infecting others with HIV.
Voluntary Counselling and Testing
(VCT)
Why should I get tested?
How does the test work?
Where to get tested?
Voluntary testing vs. Mandatory testing
Confidential testing and Anonymous
testing
Home sampling and testing
 Treatment
Antiretroviral drugs (ARVs)
Are not a cure
Slow down the process of replication of HIV in the
human body

Prevent and treat Opportunistic Infections

Prevent mother-to-child-transmission
During pregnancy and delivery
Safer infant feeding

Access to services / availability of drugs

Availability, Coverage, Impact
 Treatment
Important role of institutions (hospitals, clinics,
VCT centres)

Conditions to support treatment

Medication adherence plan

Living positively
Adopt a healthy diet
Exercise regularly
Avoid alcohol and tobacco, or certainly minimize their
consumption
Reduce stress
Avoid all forms of infection (when possible) because
they may compromise your health and further weaken
ones immune system
 Treatment of HIV Infection

Today, there are 31 antiretroviral drugs (ARVs)

approved by the U.S. Food and Drug
Administration (FDA) to treat HIV infection.
These treatments do not cure people of HIV or
AIDS. Rather, they suppress the virus, even to
undetectable levels, but they do not completely
eliminate HIV from the body
By suppressing the amount of virus in the body,
people infected with HIV can nowlead longer
and healthier lives.
However, they can still transmit the virus and
must continuously take antiretroviral drugs in
order to maintain their health quality.
 Post Exposure Prophylaxis (PEP) for
Healthcare Workers
Intact skin, mouth or nose: immediately wash
with soap and water and rinse thoroughly to
remove all potentially infectious particles.
Cut or punctured skin: allow to bleed fully.
Eye: flush immediately with water, then irrigate
with normal saline for 30 minutes.
Consider post exposure prophylaxis (PEP) if high
risk of transmission:
4 week course of zidovudine (ZDV)
preferable to start within 1-2 hours

Source: CDC 1996.

22-58
 Post Exposure Treatment of Healthcare
Workers, continued
HIV testing immediately, 6 weeks, 6
months and 12 months
Treatment, if started, should continue for
4 weeks. Any or all drugs may be
declined by exposed worker.
For lesser exposures, prophylaxis is not
recommended.

22-59
 Prevention
Currently, there isno vaccine to prevent HIV
infection nor is there acure for HIV/AIDS. To
reduce risk of becoming infected with HIV or
transmitting the virus to others:
Consistent use of male latex condoms can help
protect against HIV infection.
Get tested regularly for HIV
Practice abstinence
Remain faithful to your spouse or partner
Consistently use male latex or female
polyurethane condoms
Do not share needles