The 2006 Dengue Outbreak in Delhi, India

J. Commun. Dis. 40 (4) 2008 : 24-248 The 2006 Dengue Outbreak in Delhi, India Sinha N*, Gupta N*, Jhamb R*, Gulati S*, Kulkarni Ajit V* Abstract Dengue is a worldwide condition spread throughout the tropical and subtropical zones between 0 degrees north and 40 degrees south. It is endemic in South East Asia, the pacific, East and West Africa, the Caribbean and the Americas. Dengue outbreaks are occurring almost every three yearly in Delhi for the last 12 years. The latest outbreak was in the year 2006, which started late in August, peaked in the month of October and lasted till late November. We describe here the clinical, hematological and biochemical data of 70 patients of dengue fever diagnosed as per WHO criteria in Lok Nayak Hospital, New Delhi during this outbreak. Hematological parameters were estimated by automated counter and dengue serology was done by capture ELISA technique. The results displayed widespread effect of dengue fever on hematological and biochemical profile. Some of our patients also had atypical dengue manifestations. These results suggest that dengue fever is a major public health problem which can lead to significant morbidity and can even be fatal at times. All efforts should be made to prevent it. Key words : Dengue fever, Dengue, Dengue outbreak 2006, atypical manifestations in Delhi. INTRODUCTION Dengue fever, the most common arboviral disease transmitted globally, is caused by four antigenically distinct virus serotypes (DEN 1, DEN 2, DEN and DEN 4). The dengue virus, a member of flavivirus group in the family flaviviridae, is a single stranded enveloped RNA virus, 0 nm in diameter, which can grow in a variety of mosquitoes and tissue cultures. The four serotypes possess antigens that crossreact with yellow fever, Japanese Encephalitis and West Nile Viruses. The infection is transmitted by infected female Aedes mosquitoes. Dengue is a worldwide condition spread throughout the tropical and subtropical zones between 0 degrees north and 40 degrees south. It is endemic in South * Department of Medicine, Maulana Azad Medical College New Delhi-110002. Paper presented at 7th Joint Conference of ISMOCD and IAE, held from 27-10-2007 to 29-10- 2007 at Jodhpur. Abstract No VD-8 Correspondence to : Dr Naresh Gupta, Professor of Medicine, Room No. 121, B L Taneja Block, Maulana Azad Medical College, New Delhi-H0002. Ph: 09810154171. E-mail: doctornaresh@bol.net.in

244 Sinha N et al East Asia, the pacific, East and West Africa, the Caribbean and the Americas. Dengue hemorrhagic fever epidemics occur annually with major outbreaks occurring every three years. Factors responsible for dengue's spread include explosive population growth, unplanned urban over population with inadequate public health systems, poor vector contral and increased international recreational, business and military travel to endemic areas. Indeed dengue fever is fast emerging as a major global health problem. Dengue infections may be asymptomatic, may lead to classical dengue fever, dengue hemorrhagic fever and dengue shock syndrome. Certain atypical manifestations like encephalopathy, encephalitis, pneumonitis, myocarditis, disseminated intravascular coagulation, acalculous cholecystitis have also been reported. Mild dengue fever is characterized by biphasic fever, skin rash, headache, retroorbital pain, photophobia, cough, vomiting, myalgia, arthralgia, leucopenia, thrombocytopenia and lymphadenopathy, while dengue hemorrhagic fever apart from above manifestations also have overt hemorrhages l i k e e p i s t a x i s, g u m b l e e d, u p p e r gastrointestinal bleed. We present here the clinical and laboratory data of the 70 patients admitted in Lok Nayak Hospital during the 2006 dengue outbreak in Delhi. MATERIALS AND METHODS Lok Nayak hospital in Delhi is large government funded hospital, which caters to a large number of patients from all over Delhi and neighboring states. The dengue outbreak of the year 2006, which started late in August, peaked in the month of October and lasted till late November brought a number of dengue patients this hospital for evaluation. We describe here the clinical and laboratory parameters of 70 dengue patients admitted in hospital. The diagnostic criteria for dengue fever were as defined by WHO. Recommended case definition Dengue fever Clinical description : An acute febrile illness of 2-7 days duration with 2 or more of the following: headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, leucopenia. Laboratory criteria for diagnosis: One or more of the following: Isolation of the dengue virus from serum, plasma, leukocytes, or autopsy samples, Demonstration of a fourfold or greater change in reciprocal IgG or IgM antibody titers to one or more dengue virus antigens in paired serum samples, Demonstration of dengue virus antigen in autopsy tissue by immunohistochemistry or immunofluorescence or in serum samples by EIA, Detection of viral genomic sequences in autopsy tissue, serum or CSF samples by polymerase chain reaction (PCR). Case classification Suspected : A case compatible with the clinical description. Probable : A case compatible with the clinical description with one or more of the following : supportive serology (reciprocal hemagglutination-inhibition antibody titre greater than 1280, comparable IgG EIA titre or positive IgM antibody test in late acute or convalescent-phase serum specimen), Occurrence at same location and time as other confirmed cases of dengue fever. Confirmed : A case compatible with the clinical description, laboratory-confirmed. Criteria for Dengue Hemorrhagic Fever/ Dengue Shock Syndrome : Dengue Hemorrhagic Fever : A probable or confirmed case of Dengue and Hemorrhagic tendencies evidenced by one or more of the following:

The 2006 Dengue Outbreak in Delhi, India 245 Positive tourniquet test, Petechiae, ecchymoses or purpura, Bleeding mucosa and gastrointestinal tract, injection sites or other, Haematemesis or melaena and thrombocytopenia (100 000 cells or less per mm ) and evidence of plasma leakage due to increased vascular permeability, manifested by one or more of the following : more than 20% rise in average hematocrit for age and sex, more than 20% drop in hematocrit following volume replacement treatment compared to baseline signs of plasma leakage (pleural effusion, ascites, hypoproteinemia). Dengue shock syndrome : All the above criteria, plus evidence of circulatory failure manifested by rapid and weak pulse, and narrow pulse pressure (less than 20 mm Hg) or hypotension for age, cold, clammy skin and altered mental status. As per protocol, history and detailed clinical examination were recorded at admission. Biochemical and hematological parameters were noted. Dengue serology was carried by capture ELISA for IgG and IgM antibodies against dengue virus. Virus isolation and serotyping could not be done because of financial constraints. Eventually the clinical profile and the laboratory data of the patients were analyzed. RESULTS The mean age of the patients was 28 years, minimum age was 1 years and maximum age was 77 years (standard deviation 12.4 years). 81.1% of them were males and 18.9% were females. Fever was present in all the cases with average duration of fever being 5.4 days (standard deviation 2.26 days). The other presenting complaints were myalgias (62.25%), arthralgias ( 60 %), b l e e d i n g m a n i f e s t a t i o n s ( 6. 2 % ), headache(26.08%), vomiting (17.9%), and retrobulbar pain (12%). Hemorrhagic manifestations were observed in the form of rashes (5.79%), gum bleed (8.69%), upper gastrointestinal bleed (15.94%), and epistaxis (14.49%). 14.49% of patients had hypotension on presentation. Hepatomegaly and splenomegaly were observed in 4.4% and 5.79% patients respectively. Ascites and pleural effusion were seen in 4.4% and 5.79% patients respectively. Among the atypical manifestations, one patient had encephalitis, two had encephalopathy, myocarditis was present in one patient, DIC in one patient and one had demyelinating polyneuropathy. Acalculous cholecystitis was present in 2.9% of patients. The mean platelet counts on admission were 57,254/mm (standard deviation 40,49.16) and on discharge was 85,619/mm (SD 4,598.6). lowest platelet count on admission was 20,000/mm. Mean total leukocyte count on admission was 5771.64/mm (SD 2811.92) and on discharge was 586.11/mm (SD 1624.1) lowest leukocyte count on admission was 1000/mm hematocrit was available in 6 patients on admission and in 21 patients on discharge. Mean hematocrit on admission was.6% a n d o n d i s c h a r g e w e r e 4. 5 5. Hyperbilirubinemia was present in 5.6% patients. Transaminases were raised in more than twice the normal values in 4.64% patients, and minor rise (less than twice the normal) was seen in 20% patients. Among those who had elevated transaminases SGOT was more than SGPT in 65.71% patients, less than SGPT in 28.57% patients and equal to SGPT in 5.71% patients. Serum alkaline phosphatase was raised in 2.08% of patients. Dengue serology for IgM at admission was positive for 50% of patients, equivocal for.12% of patients and negative for 46.87% of patients. Dengue serology for IgG at admission was positive in 78.12%, equivocal in 1.56% and negative in 20.1%. Average duration of stay in hospital was.5 days.

246 Sinha N et al fever 100% myalgias arthralgias bleeding manifestations headache vomitting retroorbital pain 6.2% 26% 17.9% 12% 65.25% 60.00% 0% 20% 40% 60% 80% 100% 120% % value Figure 1 : Frequency of occurrence of various symptoms in dengue fever % value 20 16 12 8 4 5.79% 8.69% 15.94% 14.49% 5.79% 4.4% 5.79% 4.4% 14.49% 0 rashes gum bleed upper gi bleed epistaxix hypotension splenomegaly pleural effusion hepatomegaly ascites Figure 2 : Frequency of various hematological manifestations in dengue fever Figure : Frequency of occurrence of various physical signs in dengue fever 20.1% 46.87% 50% 1.56%.12% positive equivocal negative Figure 4 : Status of dengue serology for IgM on admission 78.12% positive equivocal negative Figure 5 : Status of dengue serology for IgG on admission

The 2006 Dengue Outbreak in Delhi, India 247 DISCUSSION Of all the arthropod-borne viral disease, dengue fever is the most common. It is endemic in more than 100 countries and 40% the world's population is at risk of this 2 disease. All 4 types of dengue viruses have been isolated from the affected Indian population. Cyclical epidemics of dengue are becoming more frequent. In New Delhi and adjoining areas, outbreaks of DF and DHF 4 have been reported in 1967, 1970, 1982, 1988, 5 1 5 1996 and in 200 The outbreak in 1996 was the largest one to occur in Delhi following which vigorous steps were taken to prevent and control it. Most of the patients in the present outbreak were young adults (mean age 28 years). A similar trend was also noted in the previous outbreak of dengue fever in Delhi in 5 1 1996 and in 200 outbreak in Delhi and also 6,7 from studies from Singapore. This may be due to the fact that adults are not immune to all strains of dengue fever. The average duration of prodromal fever was 5.4 days. Erythematous morbilliform macular or maculopapular rash was found in 5.79% of the cases. This finding is on the lower side of the figure reported 20% for Dengue outbreak in Delhi in 2001 and 6.7 % for 5 Dengue outbreak in Delhi in 1996 and in 9 patients of Vishakhapatnam. Bleeding manifestations were present in 6.2% of patients. This was lower when 1 8 compared to 72% in 200 and 71% in 1996. Bleeding manifestations were in the form of rash (5.79%), gum bleed (8.69%), upper gastrointestinal bleed (15.94%) and epistaxis (14.49%). The figures reported in dengue 1 outbreak of 200 were Gum bleeding and epistaxis (40%) and hematemesis in 22%. Hepatomegaly and splenomegaly were found in 4.4% and 5.79% cases respectively. While the figures for the same manifestation 1 are 10% and 5% in 200 outbreak, 20.4% & 8 8.2% in 1996 outbreak and 22.2% & 9.% in a 10 report from Calcutta. SGOT and SGPT were raised in a total of 6.64% of cases which is significantly higher than previous reported 16% in 200 1 outbreak. Impaired consciousness was found in (1 encephalopathy and 2 encephalitis) cases (4.28%) of cases compared 1 8 with 1.6% in 200 and 5.9% in 1996. The causes of encephalopathy can be various like intracranial hemorrhage, cerebral edema, hyponatremia, cerebral anoxia, fulminant hepatic failure with portosystemic encephalopathy, microcapillary hemorrhage, 11,12 release of toxic products and renal failure. Dengue encephalitis results from direct 1 invasion of ens by virus and is a rare entity. In a study from Thailand altered sensoruim had been reported but no evidence of encephalitis was found on autopsy of the 11 14 patient. A report in 1996 has effectively supported the hypothesis of the occurrence of a true encephalitis caused by dengue viruses, 15 and in another 1998 antigen was detected by immunohistochemistry and DEN-4 RNA in neurons, astrocytes, microglia and endothelial cells. Dengue specific IgM antibody was positive in 50% of cases compared to 70.2% in 1 8 200 and 85.2% in 1996. The sensitivity of this test depends on the duration of the prodromal illness. All the positive samples had a duration of fever of five or more day. A 16 study in 1992 using Mu capture ELISA in patients with confirmed DF showed that 96% th of 76 blood samples drawn between 7 and th 20 day after the onset of fever were positive. 17 In a study in Thailand in 1989 the sensitivity of this test was shown to be 97% in convalescent samples. Dengue specific IgG was positive in 78.12% of cases in our study. Inspite of increasing awareness among the people about the disease, preventive and control measures through mass media; we

248 Sinha N et al have not been able to control the DF. The result is again an outbreak of dengue in 2006. Reasons behind it may be overcrowding, abundant mosquito breeding sites like water coolers, metal receptacles, rubber tyres, and water storage tanks and changing lifestyle. An ideal climatic condition (rainy and cool dry reason during the months of September to October), a large susceptible population, and abundant mosquito breeding sites provided the backdrop for this outbreak. All the three factors of Epidemiological triad i.e. Agent (Dengue virus), host (susceptible population as no vaccine is available) and environment (abundant mosquito breeding areas) operate in combination with each other to initiate the disease process in man which ultimately leads to the emergence of an outbreak. It is high time we should open our eyes and help strengthening the vector control measures, dispose off artificial water collections, improve sanitation and involve the media in spreading anti-dengue measures on a large scale to curtail the occurrence of a repeat outbreak in near future. REFERENCES 1. Singh NP, Jhamb R, Agarwal SK, Gaiha M, Dewan R, Daga MK et al. The 200 outbreak of Dengue fever in Delhi, India. Southeast Asian J Trop Med Public health. 2995 Sep; 6(5): 1174-1178. 2. K Park, the Dengue Syndrome. Park's textbook of preventive and social medicine 2000; 16: 186-188.. World Health Organisation. Monograph on dengue and dengue heamorrhagic fever. Geneva; 199. 4. Srivastava VK, Suri S, Bhasin A, Srivastava L, Bharadwaj M. An epidemic of dengue hemorrhagic fever and dengue shock syndrome in Delhi: a clinical study. Ann Trap Paediatr. 1990; 10: 29-4. 5. Anuradha S, Singh NP, Rizvi SNA, Agarwal SK, Gur R, Mathur MD. The 1996 outbreak of dengue hemorrhagic fever in Delhi, India. Southeast Asian J Trop Med Public Health. 1998; 29(): 50-506. 6. Goh KT. Changing epidemiology of dengue in Singapore (letter). Lancet. 1995; 46:1098. 7. Chan KL, Ng SK, Chew LM. The 197 dengue hemorrhagic fever outbreak in Singapore and its control. Singapore Med J. 1977; 18: 81-9. 8. Sharma S, Sharma SK, Mohan A et al. Clinical profile of dengue hemorrhagic fever in adults during 1996 - Outbreak in Delhi, India. Dengue Bulletin. 1998; 22: 20-27. 9. Krishnamurthy K, Kasturi TE, Chittipantulu G. Clinical and pathological studies of a outbreak of dengue-like illness in Vishakapatnam. Indian J Med Res. 1965; 5: 800-812. 10. Aikat BK, Konar NR, Banerjee G. Hemorrhagic fever in Calcutta area. Indian J Med Res. 1964; 52: 660-75. 11. Nimmannitya S, Thisyakorn U, Hemsrichart Y. Dengue hemorrhagic fever with unusual manifestations. Southeast Asian J Trop Med Public Health. 1987; 19: 98-406. 12. Hemorrhagic encephalopathy in dengue shock syndrmone: a case report. Braz J Infect Dis. 2005; Jun: vol 9 No Salvador. 1. Dengue Encephalitis in French Guiana. Res Virol. 1998 Jul-Aug; 149(4): 25-28. 14. Lum LC, Lam SK, Choy YS, George R, Harun F. Dengue encephalitis: a true entity? Am J Trap Med Hyg. 54: 256-259, 1996. 15. Ramos C, Sanchez G, Pando RH, et al. Dengue virus in the brain of a fatal case of hemorrhagic dengue fever. Journal of Neurovirology. 4: 465-468, 1998. 16. Hayes EB, Gubler OJ. Dengue and dengue haemorrhagic fever. Pediatr Inf Dis J.1992; 11:11-17. 17. Innis BL, Nisalak A, Nimmanitya S, et al. An enzymelinked immunosorbent assay to characterize dengue infections, where dengue and Japanese encephalitis cocirculate. Am J Trap Med Hyg. 1989; 40: 418-427.