Benign 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).

Diagnosis Of DF/DHF
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 fluid replacement.

Management Of DF/DHF
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 anaemia.
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 Ringer’s solution is infused intravenously as fast as possible. If hypotension persists, 10 ml/kg colloids (plasma/hemacel) are infused. If improvement is seen, lactated Ringer’s 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.

Prevention Of Dengue
The disease can be prevented by adopting the following measures:

• 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 like Abate.
• 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 Epidemic
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 inadequate.
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, thrombocy–topenia, 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 patients.
Few atypical clinical features observed by us need to be mentioned. These included hepatic encephalo–pathy 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 thrombocy–topenia 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, thrombocy–topenia, 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 laboratory indicators?
• Is there any role for bolus steroids and gammaglobulins in the management?
• The research question related to microbiology included the need for the development of a rapid diagnostic test and study of the pathogen of the disease.

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