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The 2001 dengue epidemic in Chennai
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     1 Centre for Research in Medical Entomology, (Indian Council of Medical Research),Chennai, India

    2 Kanchi Kamakoti Childs Trust Hospital, Nungambakkam, Chennai, India

    Abstract

    Dengue is emerging as a serious public health problem in Tamil Nadu. The present surveillance system is unlikely to generate proper information on the epidemiology of the disease, which is essential for planning and development of relevant control/preventive measures against dengue. OBJECTIVE: Between November 2001 and January 2002, a descriptive study was undertaken on children with clinical dengue attending Kanchi Kamakoti Child Trust Hospital (KKCTH, a major private referral pediatric hospital in Tamil Nadu, India) to define the magnitude of dengue burden, the natural hostory of this disease in terms of clinical presentation, and outcome of the infections in hospitalized children (<15) with clinical dengue. METHODS: The sera collected from patients analyzed for dengue specific IgM and IgG antibodies by IgM, IgG antibody capture enzyme linked immunosorbent assay (ELISA) using alternatively two commercial kits. World Health Organization clinical case definition was adopted to categorize the dengue confirmed children. RESULTS: Dengue was diagnosed in 74.5% (143) of the 192 hospitalized children with clinical dengue. A considerable proportion (20%) of the total dengue infections were constituted by infants less than 1 yr of age. DF [dengue fever], DHF [dengue hemorrhagic fever] and DSS [dengue shock syndrome] were diagnosed in 65%, 11.2% and 23.8% of 143 dengue confirmed patients respectively. Though severe dengue (DSS + DHF) was present in 35% of the patients, the mortality rate was low during the study period due to timely diagnosis and clinical management of the patients. Conclusion: In developing countries like India, building of laboratory capacity for diagnosis and combat-mode ready preparedness for the management of dengue cases in emergency situation may reduce dengue-related mortality. This can be achieved in a wider scale through an integrated approach through the community, professionals and the public health departments.

    Keywords: Dengue hemorrhagic fever; Dengue shock syndrome; Clinical management

    Dengue, the most important mosquito-borne viral disease, is endemic in more than 100 countries.[1] Dengue constitutes a major cause of pediatric morbidity and mortality in South East Asian countries.[2] Dengue has become a major public health problem in tropical and subtropical regions.[3] In recent years, in spite of a poor/no dengue surveillance system in developing countries, the number of cases recorded and reported has increased markedly. Dengue outbreaks often are not recognized until hundreds of people are affected. In addition, dengue virus infections display a disease spectrum from undifferentiated dengue fever (DF) to severe forms resulting in under-reporting of mild dengue cases.

    In India, dengue virus activity has been reported in many parts of the country with sudden epidemics over the last few years. Seasonal and cyclic epidemic pattern of dengue is a recent phenomenon in Northern India. The DF, DHF and DSS have spread dramatically in many parts of the country.[4],[5], [6],[7],[8] Though all age groups were affected in these epidemics, the occurrence was high among children more than 6 yr; and few infants also presented symptoms of DHF.[9] The present surveillance system is unlikely to generate proper information on the epidemiology of the disease which is essential for planning and development of relevant control/preventive measures against dengue.

    The new dengue paradigm viz, the burst of sudden disease activity, persistence and diffusion of the disease in different areas has secured a foot-hold in Southern India and has emerged as a serious public health problem. In Tamil Nadu, annual reports of dengue cases and deaths due to dengue were ranging from 128 to 264 and 2 to 21 respectively up to the year 2000. Recently, between October 2001 and January 2002, an epidemic of dengue emerged in Chennai, Tamil Nadu, affecting adults and children; majority of the victims were children less than 15 yrs of age. Between November 2001 and January 2002, a descriptive study was undertaken on children with clinical dengue attending Kanchi Kamakoti Childs Trust Hospital (KKCTH, a major private referral pediatric hospital in Tamil Nadu, India) to define the magnitude of dengue burden, the natural history of this disease in terms of clinical presentation, and outcome of the infections in hospitalized children (<15 yr) with clinical dengue.

    Materials and methods

    Study Site

    Chennai, a coastal metropolitan city and capital of Tamil Nadu state has an area of 2162 km with 4.55 million population. The literacy rate is 80% as per 2001 census. The drinking water scarcity is a chronic problem in Chennai and has forced the inhabitants to collect and store water in containers and in overhead tanks in their houses.

    Subjects of the Study

    The study was conducted in collaboration with the pediatricians in KKTCH, Chennai. All the pediatricians who attend pediatric medical wards in the hospital were informed about the study and requested to record clinical data systematically in the hospital case sheets during the study period (between November 2001 and January 2002). Two hundred and fifty-five children (<15 yr of age) with clinical dengue (enrollment criteria consisting of acute febrile illness) and two or more of the signs/symptoms i.e., headache, myalgia, arthralgia, retro-orbital pain, rashes, haemorrhagic manifestations and cold clammy skin etc. attending the hospital during the study period were investigated. Detailed clinical examination findings and results of laboratory tests were available for 192 hospitalized children and thus forming the study group. Subjects included both the sexes. Diagnosis of dengue included clinical and serological criteria.

    Laboratory Diagnosis

    The sera collected from patients on the day of admission in the hospital were analyzed for dengue specific IgM and IgG antibodies by IgM, IgG antibody capture enzyme linked Immunosorbent assay (ELISA)[10] using alternatively two commercial kits (Pan bio, Australia and Omega, Scotland) depending upon their availability. Results were expressed as per the manufacturer's instructions. Paired sera could not be collected due to practical difficulties (patients were discharged soon after the recovery). Other laboratory investigations like hemoglobin, hematocrit, platelet count and leukocyte count were done. Serial hematocrit and platelet count were done twice in many patients. Skiagram of chest, liver function tests were done in some of the patients.

    Virus Isolation

    Virus isolation in Toxorhynchites splendens mosquitoes was attempted with seven serum samples. Laboratory-reared fourth instar larvae of Toxorhynchites splendens were inoculated intracerebrally with the serum and incubated for 14 days at 320 C. The head squeeze smears were stained with monoclonal antibodies specific for dengue virus serotypes [kind gift from Dr.D.J.Gubler, CDC, Fortcollins, USA] and anti-mouse immunoglobulins labelled with fluorescent isothiocyanate [Dakopats, Denmark] and visualized under ultraviolet microscope.

    Case Definition

    After thorough clinical evaluation, the pediatricians categorized the dengue-confirmed children using World Health Organization (WHO) clinical case definition.[11] Children with dengue, based on antibody response without the evidence of hemorrhagic manifestations and plasma leakage, were considered to have dengue fever; those with fever (2-7 days), hemorrhagic manifestations (bleeding gums, hematemesis/melaena), thrombocytopenia (100000 cells per mm3 or less) and evidence for plasma leakage documented by haemoconcentration, pleural or abdominal effusions by X-ray without shock were given a diagnosis of DHF. Dengue shock syndrome was defined in children with the above mentioned criteria for DHF plus evidence of circulatory failure manifested by rapid and weak pulse, narrow pulse pressure, hypotension for age, cold, clammy skin and restlessness.

    Statistical Analysis

    Clinical and laboratory findings were entered into the SPSS for windows data base program. Descriptive statistics was used for data analysis. The analysis of variance test was used for comparison of proportions; (P = < 0.05) was considered to be statistically significant.

    Results

    Demographic Information

    Between October 2001 and January 2002, there was an epidemic of dengue in Chennai, with a peak in October. The case occurrence was reported to be high among pediatric group. The number of cases confirmed during the study period was considered as the representative of the cases reported (about 700 cases) to the health surveillance system in Chennai. Of 192 children enrolled in the study, 143 (74.5%) were laboratory confirmed for dengue, consisting of approximately equal numbers of males (53%) and females (47%). The demographic information is given in table1 with 29 (20%) infants below one yr of age, 41 (28.7%) 1-5 yr old and 95 (51%) 6-15 yr old. Though children of 6-15 yr represented 50% of total KKCTH admissions of clinical dengue, two-third (66%) of them contributed to admissions with severe dengue.

    Clinical Features

    The major clinical features elicited from 143 dengue confirmed children included fever, vomiting, rashes, edema, retro-orbital puffiness, bleeding diathesis, hepatomegaly, thrombocytopenia etc. Invariably, fever was present in all the children. Complaints like myalgia, arthralgia, and headache could not be ascertained in young children. Vomiting was recorded in 40% of the cases. Purpric rashes were present in 60% of DF cases. Edema (lower extremities) and retro-orbital puffiness were seen in 15.3% and 22% of cases respectively. Hepatomegaly was seen in majority (95%) of the patients. Nearly 62% of the patients had platelet count less than 80,000/mm3; packed cell volume (PCV) was ranging from 30 to 40% in 56% of the subjects. Leucopoenia was present in 67% of cases.

    Clinical Categorization

    Categorization of dengue confirmed patients according to WHO clinical criteria is shown in Figure1. DF was diagnosed in 93 (65%), DHF in 16 (11.2%) and DSS in 34. (23.8%) of 143- dengue positive children Figure1. The mean age for DF and DHF+ DSS was 4.5 yr and 7.5 yr respectively. The distribution of disease spectrum in different age groups in relation to total DF, DHF and DSS has shown that occurrence of DF was in all the age groups: 25.8% (< 1 yr), 31.2% (1-5 yr), and 43% (6-15 yr) table2. In general, the distribution pattern of DF cases followed that of total dengue admissions. However, there was higher representation for DF cases from infant group (25.8% of DF cases against 18.2% of admissions) and a slight under representation from the 6-15 yr children (43% cases against 49.5% of admissions) table1table2. Fifty children including five infants suffered from severe dengue (DHF/DSS). The proportion of severe forms (DHF/DSS) was more in the older age group with a significant difference (P= < 0.01). These children (75% DHF and 62% DSS in 6-15 yrs) contributed significantly to hospital admissions which was greater than their representation in the total admissions (49.5%) table1table2.

    The proportion of DF, DHF and DSS out of the positives within a given age-group has shown that majority (82.8%) of the infants suffered from DF and a few (17.2%) presented severe (DHF/DSS) disease. Among the higher age group (6-15 yr), DF and DHF/DSS were distributed in 54.8% and 45.2% respectively. Majority of the infants irrespective of the severity of the disease would appear to have been hospitalized, whereas most of the older children were considered for hospitalization depending on the severity of dengue. A dengue virus was isolated from 5 of seven sera. Virus types identified were DEN-4, [n = 3] DEN-3 [n=2].

    Discussion

    There are variations in the characteristics of dengue epidemic from region to region within India pertaining to the host population and the virus serotype and the disease pattern. Generations of information on dengue outbreaks from various dengue prone areas are essential to identify target population, vectors, and environmental factors, which are favorable for the burst of dengue. This information will be useful to plan suitable anti-dengue measures and the author's institute is one of the WHO recognized centers for developing strategies to minimize risk of dengue infection through community based approaches in this region and received an institutional strengthening grant for this purpose.

    During 2001 dengue-epidemics in Chennai, an investigation was carried out on hospitalized children with clinical dengue to define few characteristics of this epidemic. In the present study, dengue confirmed cases were selected based only on the positive results from the IgM capture ELISA because majority of the patients included in the present study would have been referred from elsewhere, and is likely that many may be in the defervescence period during which time detection of dengue specific antibodies by ELISA is considered as a sensitive, specific and rapid method for confirmation of dengue infections.

    In earlier dengue-epidemics in Tamil Nadu, children were affected with the mortality rate of 26.3%.[4] During this epidemic, both adults and children were affected with a higher incidence among children with less mortality (during the study period). Both adults[5],[12],[13] and children[7],[9] were affected and the mortality rate among the adults was 6.6%.[12] Investigations on dengue infections among pediatric group have reported that 9 to 10% of the dengue infections were in infants[7],[9] and the overall mortality was 9.3%[7] and 6%.[9] The infants suffered from severe dengue also in these epidemics. In Thailand, dengue is almost a pediatric disease and dengue in infancy (£ 2 yrs) is a serious medical concern constituting 7.7% and 2.9% of dengue infections.[14], [15]

    Here, a considerable proportion (20%) of the confirmed dengue infections was constituted by infants below 1yr age and is greater than the proportion of cases in Thailand, where they have included children up to 2 years of age as infants.[14] However, the common futures shared between these studies were that during infancy, primary dengue infections were common and severe forms were less common with low mortality.[14] Dengue infections (mild and severe forms) are being reported in Sri Lanka also.[16] The reason behind the high incidence of dengue among infants reported here remains to be elucidated. It appears from the hospital admission records, in the case of infants, owing to their fragility and inability to communicate, parents seek for earlier medical attention from private pediatric referral hospitals with multi-facilities. Moreover, in a metropolitan city like Chennai, higher socioeconomic communities are aware of dengue infections and the complications. In this investigation, disease classification by expert clinicians based on accurate clinical evaluation and laboratory results has led to a better understanding of clinical features, age-wise distribution of dengue disease spectrum during the 2001 dengue epidemic in Chennai. The higher incidence of dengue seen in children in this epidemic may pose a serious pediatric problem of public health concern in future in Tamil Nadu.

    It appears that in some parts of the world, dengue is maintaining an endemic-epidemic situation with circulation of more than one dengue serotype viruses, with occurrence of new epidemics caused by dominant serotypes Presumably, dengue appears to maintain similar endemic-epidemic pattern in Chennai. However, dengue-endemicity levels in Chennai remain to be assessed, with regular serological and virological studies. It was reported that DEN-3 subtype III was responsible for DHF epidemics in Sri Lanka and the phylogenetic analysis has shown that the present subtype III has originated from Indian subcontinent.[17] It remains to be known whether DEN-3 serotype isolated in the present study belongs to subtype III. This study is the first of its kind with clinical, serological and virological parameters in an epidemic year. The authors do understand the importance of other laboratory tests (RT-PCR) for detection of dengue serotypes. For such tests, infrastructural facilities are being created. Though the proportion of DHF/DSS is very high in this group of patients, the mortality was low during the study period, due to early diagnosis and prompt treatment provided by the hospital. This underlines the importance of building of laboratory capacity for diagnosis and combat-mode ready preparedness for the management of dengue cases in emergency situation. This can be achieved in a wider scale through an integrated approach of the community, professionals and the public health departments.

    Acknowledgements

    The authors thank the Director, the staff and the patients of Kanchi Kamakoti Childs Trust Hospital (KKCTH), Chennai for their kind co-operation and also thank the Indian Council of Medical Research, Delhi and Dr. A.P. Dash, the Director in charge, CRME for their moral support. Acknowledgement is due to Dr. D.J. Augustin, Department of Public Health and Preventive Medicine, Govt. of Tamil Nadu, Chennai for his kind co-operation. The dengue case details were kindly given by Mr. G.S. Rajarathinam and Mr. B. Dhanraj, the Chennai Corporation, Chennai Health Department. Sincere thanks to, Shri.K.Venkatasubramani and Shri. T. Balaji for the technical help and all the laboratory and field supporting staff of the Centre for Research in Medical Entomology, Madurai, involved in this study.

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