||Dengue fever is an infection caused
by a virus which is transmitted by mosquitoes. In this
infection, there is a short duration fever (<7 days)
and severe muscle pain, pain behind the eyes, headache
and severe backache. Mortality is negligible.
Occasionally dengue fever may get complicated and may
cause what is called dengue Haemorrhagic Fever
(DHF)/Dengue Shock Syndrome (DSS). In this syndrome,
after an episode of fever resembling Dengue fever, the
defervescence of fever may be accompanied by a severe
volume depletion in the body causing shock and bleeding
manifestations, either of which may result in death. This
can also occur in epidemic proportions like dengue fever.
Dengue fever and its complications are essentially a
disease of this century (Halstead, 1992). The spread of
the dengue virus is closely linked to the development of
human settlements in this century and specially to the
urban development in developing countries. During the
18th and 19th centuries, epidemics occurred in newly
settled lands, largely due to domestic water storage,
necessary for drinking/livestock.
+For spread, it requires (i) favourable temperature of
>20°C which leads to more infectious mosquitoes a
situation common in tropical countries (ii) stagnant
clean water which occurs commonly in cities with ongoing
construction/demolition - typical of rapid urbanization
and (iii) rapid and close transmission - a situation
tailor-made by overcrowding seen in city slums and
multi-storeyed living quarters (Horton, 1996). Indeed,
outbreaks of dengue fever in urban areas can be explosive
with attack rates up to 70 per cent.
There are three important axioms about dengue. First,
once dengue fever comes to an area, epidemics of dengue
fever are likely to occur in subsequent years unless the
vector is eradicated entirely. Secondly, if dengue fever
has occurred in an area for a few seasons, dengue
hemorrhagic fever is inevitable. Third, most dengue fever
epidemics are noticed first in the cities of a particular
country. In successive years, the disease moves out
centrifugally to involve rural areas; example Thailand
which has seen the entire march of this virus starting
Dengue Fever to the Fatal DHF
Dengue viruses are of 4 strains - all of which
can cause dengue fever. However, if there is infection
with a second strain in a patient who has had dengue
fever caused by another strain previously, this person is
likely to develop Dengue Haemorrhagic Fever. The exact
pathologies is not clear, but it is believed that
antibodies produced after the first infection enhances
the subsequent infection related complement activation.
This complement activation causes generalized
permeability of the vasculature; altered blood
coagulability resulting from increased platelet
destruction. In an area which has the mosquito (Aedes
aegypti - the tiger mosquito) and the dengue virus (most
tropical countries), dengue fever is likely to occur in
the rainy seasons every year. If more than one strain
cause these illnesses, DHF will occur too.
Not all people who develop sequential infections get DHF.
The reason is not clear. One hypothesis (Halstead, 1992)
suggests that if antibodies are of neutralizing type,
they do not enhance the growth of subsequent dengue viral
infection. However, if there are no neutralizing
antibodies, the other antibodies enhance the viral
replication. The question still remains, why do some
people develop neutralizing antibodies and others do not.
In the Cuban epidemic of 1981, Blacks were affected 5
times less often than Whites. Perhaps, this example of
enhancement of a second infection by the first one is
unique among the entire spectrum of microbial infections
in human beings.
Dengue in children
If the present trend continues, it is likely
that epidemics may occur frequently. In countries where
dengue is endemic, DHF is among the ten leading causes of
death in children aged 1 to 14.
Experiences suggest that for every case of DHF stage
III/IV, there are 150-200 cases of dengue infections in
the community. The usual mortality is about 5 per cent if
treatment is adequately given.
DHF remained a disease of children and young adults for
almost two decades. However, the age group being affected
is changing. In Singapore, the median age for DHF in 1973
was 14 years with most fatalities occurring in children
below 10 years. However, in 1994 the median age increased
to 20 years (Goh, 1995). In the 1996 epidemic in Delhi,
more than half of the hospitalized patients were adults.
However, among the children with DHF, more than half were
in the 6-12 years age group. DHF may be fatal in 40 - 50%
of untreated patients (Benenson, 1990); however, with
appropriate treatment the mortality can be brought down
to 1 - 5% (Halstead, 1993).
The clinical diagnosis of dengue fever is made
only with a high index of suspicion or in an epidemic
situation. Many other infections causing short duration
febrile illness would be its differential diagnosis.
Dengue Hemorrhagic Fever (DHF) is diagnosed if a similar
illness is accompanied by thrombocytopenia (<1,00,000
platelets per cu mm) and presence of haemo-concentration
i.e., rise in Packed Cell Volume (PCV) by more than 20%
of baseline/recovery value (WHO criteria, 1996). If there
is pleural effusion or ascities, DHF may be diagnosed
even in the absence of haemo-concentration. In an
epidemic situation, over diagnosis is common. However,
health workers must be cautious in not missing other
mosquito-borne or water-borne illnesses which may occur
in the same milieu which is suitable for dengue e.g.,
malaria and typhoid fever. Occasionally, dengue fever may
be accompanied by minor or major bleeding manifestations
without haemo-concentration / hypotension. This needs to
be separately diagnosed because therapy is only
symptomatic here and for bleeding there is no need for
Patients with dengue fever are treated
symptomatically for fever and body-aches. In the scenario
where DHF is a possibility, one should avoid all
non-steroidal anti-inflammatory agents life ibuprofen,
aspirin, nimesulide etc. For fever, only paracetamol
should be used. Otherwise the bleeding tendency may be
enhanced because of possible platelet function
abnormalities due to use of above mentioned drugs. If
unusual bleeding manifestations occur with DF, they
should be treated with blood transfusion if hemorrhage is
significant enough to cause hypotension or severe
If DHF occurs, there are two major principles of
management. First, monitoring; perfusion should be
monitored by recording pulse rates, blood pressure and
pulse pressure by using appropriate cuff size and mercury
Sphygmomanometer, capillary refill time, temperature of
the peripheries, central venous pressures in selected
cases and packed cell volumes. Second, fluid rehydration
is instituted. Children with DF are given IV fluids if
they are vomiting. For DHF stages I and II, oral fluids
(75ml/kg over 6 hours) similar to that of moderate
dehydration in diarrhoea are given. If the child is
vomiting, the same volume is given parenterally with
frequent monitoring of perfusion and packed cell volumes.
For stages III and IV, 20 ml/kg lactated Ringers
solution is infused intravenously as fast as possible. If
hypotension persists, 10 ml/kg colloids (plasma/hemacel)
are infused. If improvement is seen, lactated
Ringers or normal saline is infused @ 5-10
ml/kg/hour for the next 48 hours or till the PCV drops
below 40. Frequent PCV monitoring is continued till the
child is euvolemic for 24 hours. Intravenous fluid are
discontinued when PCV drops below 40 or after 48 hours,
whichever is earlier.
The disease can be prevented by adopting the
- The elimination of
breeding places for the mosquito. Simply emptying
all water collection objects every week will
reduce growth of larvae. Water sources which
cannot be emptied can be treated with larvicidal
- The adult mosquito
may be additionally destroyed by adulticidal
space sprays given frequently.
- Personal protection
using protective clothing, mosquito repellent
cream, bed-nets etc. All these are difficult but
achievable tasks. In epidemic situations, fogging
with adulticidal drug sprays is recommended in
the area around a diagnosed case.
Presently, no vaccine
is available against dengue infection, and it is unlikely
to be available soon.
It has been suggested that in an area/country with poorly
developed health care set up, chemical vector control is
the most cost effective strategy; whereas better case
management is more cost effective where health system is
better developed (Shephard and Halstead, 1993). Of
course, environmental control, with elimination of
breeding places, is the most lasting measure.
The 1996 Delhi
Delhi witnessed an epidemic of Dengue/Dengue
Hemorrhagic Fever from August to November 1996. The first
case of DHF was admitted in AIIMS on the 18th of August.
However, the diagnosis of DHF was made through
post-mortem and presented on our weekly mortality audit.
Thereafter, due vigilance was exercised in the diagnosis
and treatment of cases. Most of the clinicians working
with us began to be convinced that the number of cases
with clinical diagnosis of DHF/DF were more than usual.
By definition, this was sufficient to predict an
epidemic. Case fatality rate was low. In the pediatrics
department of AIIMS, of the 240 cases admitted in various
stages, there were 18 deaths.
No systematic attempt was made to investigate the
epidemic. There was a crucial delay of 4 to 6 weeks in
making control measures.
This delay would not have occurred had there been a
central surveillance and monitoring unit. We feel that a
central body to monitor diseases of public health
importance must be constituted. This body should make
available, on a regular basis, the number of cases of
such diseases and in case of an outbreak or an epidemic,
it should take on the responsibility of providing
reliable information and monitoring of the outbreak.
Clinicians must be asked to notify any abnormal increase
in the number of cases they may notice to this central
body for necessary action.
During this epidemic, we interacted with many general
practitioners, pediatricians and other specialists. It
was quite evident that their knowledge and experience
regarding the nature and management of DHF was
Ignorance of doctors led to under as well as over
diagnosis of the disease and inappropriate treatment.
This underlines the need for continuing medical education
for both doctors and paramedical workers.
According to the WHO manual, children with fever,
thrombocytopenia, and bleeding without
haemo-concentration are classified as dengue fever with
abnormal bleeds. Our experience in this epidemic suggests
that such patients form a seizable proportion in an
epidemic and their management protocol needs to be
discussed in detail. These patients need less intravenous
fluids and more blood and blood products infusion.
In few children, intravenous fluid infusion improved
central venous pressure, decreased packed cell volume but
the blood pressure continued to remain low. This
indicated that the hypotension was probably due to
failure of pumping action of the heart rather than loss
of fluid from the vascular compartment. We investigated
these patients and demonstrated myocardial dysfunction by
Echocardiography. There is need to study whether
myocardial pump failure has any therapeutic implications
by studying a larger number of children. This would be in
order to decide the role of vasopressors in selected
Few atypical clinical features observed by us need to be
mentioned. These included hepatic encephalopathy
and dengue encephalopathy. These patients were initially
thought to be suffering from hepatitis or encephalopathy
but when tested for dengue were found to be positive.
Thus in an epidemic situation, certain atypical features
may cause problem in diagnosis. Similarly, conditions
such as malaria could also be confused with DHF. Children
who presented with anaemia, fever, bleeding, splenomegaly
and thrombocytopenia were found to be positive for
malarial parasite (falsiparum) and treated successfully.
It is suggested that since splenomegaly is rare in DHF,
presence of splenomegaly should raise the possibility of
other diagnosis. However, in areas with endemic malaria,
where spleen rates may be 1-10%, whether this holds true
needs to be studied. Few cases of typhoid were also
confused with DHF due to leucopenia,
thrombocytopenia, hypotension and bleeding. These
patients did not show marked improvement after
intravenous fluids suggesting an alternative diagnosis.
During the early part of the epidemic we were doing
Hess capillary tests on all the children. Later on
we realized that this test is difficult to carry out in
small children. On analysis of our data, we found that it
was positive in only 56% of patients. Low positivity
could be a reflection of improper techniques. We feel
that in children the tourniquet test is of limited value.
During the course of this epidemic, several questions
came up repeatedly which need to be resolved. These were
- What should be
the screening tests for OPD patients?
- How to reconcile
the differing sensitivity of platelet counts
done by smear, counter or other methods?
- Can the course of
the illness be predicted using clinical and
- Is there any role
for bolus steroids and gammaglobulins in the
- The research
question related to microbiology included the
need for the development of a rapid
diagnostic test and study of the pathogen of