Hospital Seroprevalence of Dengue Virus Infection among Adults of Urban Dhaka

Background: Global incidence of dengue has increased dramatically over the last few decades. In Bangladesh, there is a high transmission of Dengue in urban and peri-urban areas of Dhaka and other major cities. Seasonal variation, improper surveillance, underreporting of dengue infection have made difficult to estimate disease burden of dengue. Objective: This study was aimed to observe the rate of seropositivity by ELISA for Dengue IgG patients presenting to hospital. Methods: This is a cross-sectional study done in seven medical college hospital in urban Dhaka from January 2018 to March 2018. A small amount of blood was taken obtaining informed written consent in patients selected by purposive sampling during presenting to hospitals and a pre-tested questionnaire was fill to gather socio-demographic and relevant epidemiological data. Results: A total of 695 patients were included in this study with a mean age 34.9±16.49. Dengue IgG was positive in 349 (51.2%), positivity was found highest (70%) in Shahabuddin Medical College Hospital and lowest (25%) in Uttara Adhunik Medical College. Dengue IgG positive patients were more literate (82% vs 74.2%), more from urban setting (51.2% vs 41.8%), had more monthly income, had more garden (26.8% vs 23.3%) and stagnant water (25.5% vs 23%) in comparison to IgG negative patients. Conclusion: This study revealed that high seroprevalence posing risk to develop severe dengue and indicating high disease burden which warranted large scale well design population-based study.


Introduction
Dengue is an arboviral infection i.e. viral disease transmitted by arthropod Aedes mosquitoes. Dengue infection may cause febrile illness varying from undifferentiated viral-like illness to potentially life-threatening condition called severe dengue. Dengue is widespread throughout the tropic and subtropics in urban and semi-urban areas. Global incidence of dengue infection has increased dramatically that over a few decades half of the population at risk of dengue infection and today dengue virus poses a major threat to global public health. 1 The actual number of dengue infection is under-reported due to variable severity and diverse presentation and many cases are misclassified. It is estimated about 390 million dengue infection occurs per year worldwide of which 96 million people manifest with dengue fever and 3.9 billion people in 128 countries are at risk of dengue infection. [2][3] The first dengue case was reported from Dhaka in 1964 then sporadic cases also reported during 1997-78 and 1996-97 but true transmission and prevalence were not known. [4][5] The first identified epidemic of DF and dengue hemorrhagic fever (DHF) in Bangladesh, took place during the monsoon season of 2000 and resulted in 5,521 officially reported cases with admission having 93 fatalities. 6 With the predominance of DEN-3, all four dengue serotypes have been found in circulation in recent years. 7-10 From 2000-2009, ninety one percent of all reported dengue cases were from Dhaka making it the most endemic urban area of the country. 11 Though secondary infection with different serotype (mostly DEN-2, DEN-3) is associated with severe dengue, sometimes primary infection with DEN-3 causes severe dengue in this region. 12 As dengue case reporting relies on dengue seropositive cases presented to hospitals which mainly includes severe dengue, reported dengue cases over twodecade did not reflected the true image of magnitude of infection and current status is probably only the 'tip of iceberg'. It has been well documented that passive surveillance involving case notifications does not accurately reflect the burden of dengue in such a geographical location. 13 There is seasonal distribution and incidence correlates with rainfall. 14 During 2000 -2017 data showed that 49.73% cases occurred during the monsoon (May to August) and 49.22% of cases occurred during postmonsoon (September to December) and since 2014 pre-monsoon transmission has been observed which is more than seven times than before. 15 Climatic change such as average rainfall, humidity, temperature, rapid unplanned urbanisation, poor waste management are the strong predictor of change of ecology leading to rapid increase of dengue cases and first-time massive Chikungunya outbreak in 1917 in Dhaka. 15 Given the absence of adequate surveillance, variability of transmission and seasonal distribution of incidence make the estimation of disease burden difficult. The validity of the existing incidence data is unclear because notification and surveillance were not extensively done. A notionally representative study of seroprevalence from 70 communities indicated seroprevalence ranged from 3% in the northern part of Bangladesh to more than 80% in Dhaka city. 16 High population density and ecological conditions in the urban and semi-urban areas of Dhaka city have been favourable for dengue transmission for the last 15 years, suggesting a rather stable endemic transmission pattern. However, the real infection pressure and household and environmental risk factors are not known accurately. High seroprevalence is probably associated with high transmission in young age and peri-urban area and severe dengue. Hospital seroprevalence will help to estimate disease burden, to know the risk factor associated with transmission and to identify vulnerable groups having infection and severe disease; thus to help to intervene for prevention appropriately. In this descriptive study seroprevalence for dengue was estimated testing IgG antibody and risk factors for dengue transmission were documented in afebrile patients presented inpatient and outpatient department of seven medical college hospital in Dhaka city. Enam Medical College Hospital was selected as satellite urban and peri-urban area. Patients presenting outpatient for any cause were chosen for convenient sampling and after selecting the first responder, every 3rd patient was taken. After every male responder enrolled, one female responder was tried to be enroll to reduce gender gap. One hundred patient from each hospital was selected and total 700 patients was the department of Medicine of Dhaka Medical College. Seven medical college hospitals were selected from arbitrary four main quadrant of Dhaka city (figure I).   II). The proportion of highly educated patients was markedly higher in Dengue higher in seropositive patients than seronegative patients. In dengue IgG seropositive patients 51.0% presented from urban setting which was higher than that of seronegative patients. A good number of seropositive patients presented from semi-urban and rural setting. Thirtythree percent (n=30) of patient positive for IgG had monthly income BDT >25000, 44.0% and 23.0% of positive IgG patients had monthly income BDT 10,000-Taka 25,000 and BDT< 10,000 respectively. Mosquito net use rate was higher in seropositive patients than

Discussion
In this hospital-based study, seropositivity rate for dengue IgG among patients was high which was 51.2% (n=349). True seroprevalence of Dengue infection of Dhaka is not known. A population-based cross-sectional serosurvey of anti-dengue antibody in 12 of 90 wards of Dhaka city was done by Dhar et al in 2012 and showed very high seroprevalence which was 80% and 83.3% for pre-monsoon and postmonsoon respectively. 17 Rahman et al analysed retrospectively in 225 samples of blood from patients presenting the Diabetic Association of Bangladesh Hospital, which showed 69.33% was positive for Anti Dengue IgG and IgM and 38.22% positive for dengue IgG. 8 In our study seropositivity is lower than other studies mentioned above. As various patients of urban, semi-urban, slum and rural patients from different part of the country presents those medical college hospitals as highest level referral. In the present study, only 47.0% of patients were from urban setting, rest from semi-urban, rural setting. Among seropositive patients 84.2 presented from urban and semi-urban areas, only 15.6% of patients from rural setting. If total participants were from urban setting then seropositivity would have even been higher.
This high seroprevalence in Dhaka should also be regarded as an indicator of significant under-reporting of dengue virus-associated illness. In recent years predominant serotypes of dengue virus in metropolitan Dhaka were DEN3 but all for serotypes are present in this region. 11 High seroprevalence of dengue poses a major risk factor for secondary dengue infections and more severe diseases, such as dengue hemorrhagic fever, expanded dengue syndrome if a new dengue serotype to which there has been limited prior exposure is introduced in the existing other seropositive areas.
The positive relationship between the presence of antibodies and increasing age is indicative of cumulative dengue infection. Many other studies have reported that dengue antibody prevalence increases with age and on-going virus transmission, over many years, is often cited as the reason for this pattern. 20 Only 11.1% of seropositive patients under 20 years of age. Although dengue has been known to be a disease of children previously, the current trends in Bangladesh and also in surrounding countries experiencing increased incidence of elderly dengue.
Socioeconomic characteristics found in this study is important. Patients with dengue IgG positive tended to be more literate, more highly educated and more economically affluent in comparison to patients to patients with dengue IgG negative. Most of the seropositive patients were from urban area. It has been observed that there is variation in the spatial distribution of dengue transmission; the highest transmission occurs in densely populated and urban area and moderate transmission occurs in the periurban area. 18 In the present study high proportion of seropositivity in patients from 'Paka' (well-structured building) type house in urban area indicate presence environment helpful for mosquito breeding and dengue transmission and presence of garden and stagnant water were more marked in patients with dengue IgG positive than dengue IgG negative patients. In the case of Bangladesh, improving financial capability has resulted in changes in social values, taste such as keeping ornamental plants indoors has become a custom. This trend has become more prevalent among the middle and upper-middle socio-economic class, which was reflected in the high proportion of dengue cases among this demographic cohorts during the 2000 epidemic. 19 The presence of the garden was found in 26.8% of patients with seropositive for dengue. Unplanned urbanisation has lead densely populated Dhaka city with scarcity of parks and gardens in residential areas.
There is also tendency to do roof garden with the conception of green Dhaka which is unplanned and not regulated by any authority. The high seroprevalence may be also due to these inappropriate roof garden in Dhaka city. In the present, 25.5% of patients reported stagnant water in and around their house. Low socioeconomic residential area risk factor may be attributed to poor settlement and housing structures, high population density, presence of inter-domiciliary potential mosquito breeding sites such as plastic bucket, plastic drum, clay pot, tire dub, and coconut shell, cans, vehicle tires in such urban zones. 15 Further multi-scale research is necessary to investigate risk factors encompassing both socioeconomic status, indoor and outdoor environment.

Conclusion
This study revealed a high seroprevalence of Dengue infection which may provoke further larger-scale population-based study. High prevalence poses a risk for high incidence of severe Dengue disease which is a major public health concern for local and regional public health authority. Formulation of an active DENV surveillance system is urgently warranted, particularly to estimate the impact of Dengue disease burden in the city of Dhaka and other areas of the country.