Dengue fever, DHF, DSS

Virus classification
Group: Group IV ((+)ssRNA)
Family: Flaviviridae
Genus: Flavivirus
Species: Dengue virus

 found in the tropics and Africa

 caused by four closely related virus serotypes of the genus Flavivirus
 also known as breakbone fever
 transmitted to humans by the Aedes aegypti or more rarely the Aedes
albopictus mosquito, which feed during the day

WHO
 2.5 billion people, two fifths of the world's population, are now at rIsk.
 Estimates 50 million cases of dengue infections worldwide every year.
 Disease is now endemic in more than 100 countries.[4]
 Signs and symptoms

 Sudden onset of severe headache, Muscle and joint pains (myalgias and
arthralgias—gives it the name break-bone fever or bonecrusher disease)

 Fever, and bright red petechiae rash- usually appears first on the lower limbs
and the chest may spread to most of the body.

 Sometimes gastritis associated abdominal pain, nausea, vomiting, or diarrhea

 Some cases -much milder symptoms- can be misdiagnosed as influenza or

other viral infection when no rash is present

 Classic DF lasts -six to seven days, with a smaller peak of fever at the trailing
end of the disease (the so-called biphasic pattern).

 Clinically, the platelet count will drop until the patient's temperature is normal

 Cases of DHF also show higher fever, variable haemorrhagic phenomena,

thrombocytopenia, and haemoconcentration.

 A small proportion of cases lead to dengue shock syndrome (DSS) which has a
high mortality rate.
 Diagnosis
 Usually made clinically- high fever, a petechial rash with thrombocytopenia and relative
leukopenia - low platelet and white blood cell count.

 The WHO definition of DHF ; all four criteria must be fulfilled

Fever, bladder problem, constant headaches, severe dizziness and loss of appetite.
Hemorrhagic tendency -- positive tourniquet test, (A blood pressure cuff is applied and inflated
to a point between the systolic and diastolic blood pressures for five minutes. The test is
positive if there are more than 20 petechiae per square inch (a petechia is a small red or
purple spot on the body, caused by a minor hemorrhage) spontaneous bruising, bleeding
from mucosa, gingiva, injection sites, etc.; vomiting blood, or bloody diarrhea

 Thrombocytopenia (<100,000 platelets per mm³ or estimated as less than 3 platelets per
high power field)
Evidence of plasma leakage (hematocrit more than 20% higher than expected, or drop in
haematocrit of 20% or more from baseline following IV fluid, pleural effusion, ascites,
hypoproteinemia)
 Encephalitic occurrences.

DSS is defined as dengue hemorrhagic fever plus:

 Weak rapid pulse,
 Narrow pulse pressure (less than 20 mm Hg)
 Cold, clammy skin and restlessness.
Serology and polymerase chain reaction (PCR) studies are available to confirm the diagnosis
of dengue if clinically indicated.
 Treatment

 Timely supportive therapy to tackle shock due to haemoconcentration and bleeding

 Increased oral fluid intake to prevent dehydration.

 Supplementation with intravenous fluids may be necessary to prevent dehydration and

significant concentration of the blood if the patient is unable to maintain oral intake.

 A platelet transfusion is indicated in rare cases if the platelet level drops significantly
(below 20,000)

 The presence of melena may indicate internal gastrointestinal bleeding requiring platelet
and/or red blood cell transfusion.

 Aspirin and non-steroidal anti-inflammatory drugs should be avoided as these drugs may
worsen the bleeding tendency associated with some of these infections. Patients may
receive paracetamol preparations to deal with these symptoms if dengue is suspected
 Epidemiology-2006
Red: Epidemic dengue. Blue: Aedes aegypti

 The first recognized Dengue epidemics occurred almost simultaneously in Asia, Africa,
and North America in the 1780s.

 A pandemic began in Southeast Asia in the 1950s, and by 1975 DHF had become a
leading cause of death among children in the region.

 By the late 1990s- dengue - most important mosquito-borne disease after malaria, with
around 40 million cases of DF and several hundred thousand cases of DHF each year.

 Significant outbreaks - every five or six months. The cyclical rise and fall in numbers of
dengue cases is thought to be the result of seasonal cycles
 DHF is more likely to occur in patients who have secondary infections by another one of
dengue fever's four serotypes.

 One model to explain this process is known as antibody-dependent enhancement (ADE), ---
increased uptake and virion replication during a secondary infection with a different strain
Virus uses Fc receptor present on the phagoccytic cells to enter the cell. Non-neutralizing Abs
to previously infecting strains act to increase the viral uptake and hence replication.
This process is also known as superinfection

 Reported cases of dengue are an under-representation of all cases (subclinical cases)

 With proper medical treatment the mortality rate - less than 1 in 1000

Country Specific Epidemics

1. Rio de Janeiro in February 2002 affecting around one million people and killing sixteen.

2. On March 20, 2008 - state of Rio de Janeiro, reported 23,555 cases of dengue, including 30
deaths, in less than three months. April 3, 2008, the number of cases reported rose to
55,000

3 Singapore, there are 4,000–5,000 reported cases of DF and DHF every year.
year 2003: six deaths from dengue shock syndrome
 Prevention

Vaccine development

 Not yet available

Many ongoing vaccine development programs eg Pediatric Dengue Vaccine Initiative set up
in 2003 – aim: accelerating the development and introduction of affordable and accessible
dengue vaccine(s)
Thai researchers are testing a dengue fever vaccine on 3,000–5,000 human volunteers
A number of other vaccine candidates are entering phase I or II testing
A vaccine to prevent dengue (Dengvaxia®) is licensed and available in some countries for
people ages 9-45 years old. The World Health Organization recommends that the vaccine
only be given to persons with confirmed prior dengue virus infection.

Mosquito control
 Two primary methods: larval control and adult mosquito control.

 IAedes mosquitos breed on water collections in plastic cups, used tires, broken bottles,
flower pots, etc. Periodic draining or removal of artificial containers

 Larvicide treatment is another effective way to control the vector larvae but the larvicide -
safe and long-lasting (e.g. pyriproxyfen).

 Fogging with insecticide is somewhat effective.

 Insect repellent, mosquito traps or mosquito nets

 In 1998, scientists from the Queensland Institute of Research in Australia and Vietnam's
Ministry of Health introduced a scheme that encouraged children to place a water bug, the
crustacean Mesocyclops, in water tanks and discarded containers where the Aedes aegypti
mosquito was known to thrive- This method is more cost-effective and more
environmentally friendly than pesticides, though not as effective, and requires the ongoing
participation of the community

 In 2009, scientists from the School of Integrative Biology at The University of Queensland

-by infecting Aedes mosquitos with the bacterium Wolbachia, the adult lifespan was reduced
by half. In the study, super-fine needles were used to inject 10,000 mosquito embryos with the
bacterium. Once an insect was infected, the bacterium would spread via its eggs to the next
generation. A pilot release of infected mosquitoes could begin in Vietnam within three years. If
no problems are discovered, a full-scale biological attack against the insects could be
launched within five years

Use as a biological weapon

Dengue fever was one of more than a dozen agents that the United States researched as
potential biological weapons before the nation suspended its biological weapons program