Associations between transmission factors with Status of Immunoglobulin M Anti-Denguevirus in Cirebon District, West Java Province, Indonesia

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1 Scholarly Journal of Scientific Research and Essay (SJSRE) Vol. 4(2), pp , February 2015 Available online at ISSN Scholarly-Journals Full Length Research Paper Associations between transmission factors with Status of Immunoglobulin M Anti-Denguevirus in Cirebon District, West Java Province, Indonesia Lukman Hakim Loka Litbang P2B2 Ciamis, National Institute of Health Research and Development (NIHRD) of Ministry of Health Republic of Indonesia. lukmahak61@gmail.com. Accepted 28 January, 2015 Morbidity of dengue hemorrhagic fever in Indonesia is still high due to factors of transmission which has not completely known yet, disease control is still conducted based on the cases. This study aimed to obtain information about factors related to the status of IgM anti-dengue virus. Studies have been conducted in village Klayan district Gunungjati regency Cirebon using cross sectional design. Variable study are 10 independent variables consist of 5 environment variables and 5 host variables, whereas dependent variable is status of IgM anti-dengue virus. The resulting data were analyzed using bivariate and multivariate analyses to determine relationship between independent with dependent variable. 200 respondents were surveyed, 56% are known to live in house with high density, 85% at house with limited lighting, 41.5% in house with positive water container (not covered), 96% at house with optimal air temperature, 62% in house with optimal air humidity, and 23.5% at house with a positive mosquito Aedes spp larvae. Respondents who have a habit to stay outside of the house is 51.5%, abnormal nutritional status is 34%, age group <5 years is 10.5%, ever get DHF are 16%, and positive IgM antidengue virus is 17.5 %. Bivariate analysis showed that three independent variables are significantly associated with dependent variable; whereas the multivariate analysis showed that two variables are significantly associated with the dependent variable. It was concluded, that the variables which significantly associated with status of IgM anti-dengue virus is respondent who have a habit to stay outside of the house, nutritional status and age groups. The estimated chances of IgM anti-dengue virus can be calculated based on the respondent who has a habit to stay outside of the house and nutritional status variable. Keywords: Transmission factor, IgM anti-dengue virus, outside of the house respondent, nutritional status, age groups. INTRODUCTION Transmission of dengue virus is caused by mosquitoes Ae.aegypti and Ae.albopictus as a primer vector (Weissenbock et al., 2010) with 8-10 days of extrinsic incubation and 4-6 days of intrinsic incubation periods that followed by immune response (Kristina et al., 2004) Several studies have shown that mosquitoes Aedes spp. associated with high or low transmission of dengue virus in the community, but the transmission does not always lead to dengue hemorrhagic fever (DHF) in humans because it still depends on other factors such as the vector capacity, virulence of the dengue virus, and host immune status (Lubis, 1990) which is influenced nutritional status and age (Aspinall, 2005). Other studies have shown that children who are undernourished have lower risk for contracting the dengue virus, but if get the transmission, they are at higher risk for getting dengue shock syndrome (DSS) and even death. In the others hand, obese children have a higher risk of contracting dengue fever compared the children with normal nutritional status (Kalayanarooj et al., 2003). When dengue virus enters the body for the first time, the first infection can occur which may give symptoms of dengue fever, pathogenesis is still not clearly (Soegijanto, 2006); clinical symptoms will be different when someone gets a transmission of the differ virus serotypes (Hadinegoro et al., 2001).

2 Hakim 21 Heterologous secondary reaction hypothesis explains that the first transmission of dengue virus (primary infection) will cause immune reactions, then when the transmission is repeated (secondary infection) with different dengue virus serotypes, within a few days will result in proliferation of lymphocytes to produce antibody immunoglobulin G (IgG) anti-dengue and causing DHF (Recker et al., 2009). Cirebon Regency was the region with DHF high morbidity and often get outbreak. The number of cases in 2007 are 1535 people with the incidence rate (IR) 0.732, in 2008 are 1523 people (IR = ), and in 2009 are 1411 people (IR = ) (Hakim and Superiyatna, 2009). Research in 2008 showed that 10.10% of the population Cirebon regency had contracted the dengue virus (IgG positive and IgM or IgG) (Res, 2009). These data suggest that DHF is still a problem in Cirebon regency so that necessary the appropriate controls to prevent further transmission The purpose of this study was to know the relationship of environment and host factors with status of IgM antidengue virus. Further purpose is to know about the most dominant variable and calculate the probability of happening from IgM anti-dengue virus antibodies based on a binary logistic analysis of environmental and host factors. METHODS This study is an explanatory research with cross sectional analysis design, it was conducted in the Klayan village, sub district Gunungjati, Cirebon regency of West Java, Indonesia in May The study has been carried out with data collection consist of the environmental variables are the household density, abiotic environmental of house (consist of quality of lighting, presence of not closed water containers, temperature and humidity), and the presence of mosquito larvae of Aedes spp; and host variables consisting of the activity of occupants in outside the home, nutritional status, age group and history of dengue morbidity. In addition, the examination the status of IgM anti-dengue virus using a rapid diagnostic tests (RDT). Data collected was processed be created two categories based on its relationship with the incidence of IgM anti-dengue virus, which does not risk factor (coded 0) and risk factor (coded 1), while the category of IgM anti-dengue virus are negative status (coded 0) and positive (coded 1), then, bivariate analysis between each of the independent variables (environmental factors and host) with the dependent variable (status of IgM antidengue virus) were done. Variables that significantly correlated with the dependent variable (p value <0.05) and the variables that generate p value <0.25, then performed a multivariate analysis (binary logistic) to calculate the probability of infection which are characterized by the presence of IgM anti-dengue virus. RESULTS The number of respondents who observed is 200 people in 69 families, consisted of 44 people from the RT 16, RT 17 of 46 people, 23 people from the RT 18, 40 people from the RT 19, 16 people from the RT 20, and 31 people from the RT 21. Based on the sex, consisted of 114 female (57%) and 86 male (43%); oldest respondents aged 67 years and the youngest 1 year old. Variables of study Data collection and processing of environment variables showed that respondents living in less dense category house are 88 people (44.00%), the remaining is live in dense category house. Whereas the respondents who lives at home with optimal lighting is 30 people (15.00%), the remaining is living in not optimal home category; respondents who stayed at home with negative result where the water containers is not covered are 117 people (58.50%), the remaining were respondent who positives; respondents which stay at home with not optimal air temperature were 8 people (4.00%), the remaining is stay at home with optimal category; respondents which stay at home with not optimal air humidity are 76 people (38.00%), the remaining stay at home with optimal category; and respondents which stay at home with negative result of Aedes mosquito larvae were 153 people (76.50%), the remaining are stay at home with positive category. Collection and processing five types of data of host variables showed respondents with outdoor activities at high categories was 97 people (48.59%), respondents with normal nutritional status are 132 people (66.00%), respondents in the age group> 5 years are 179 people (89.50%), respondents who had not been ever sick DHF are 168 people (84.00%), and respondents with negative IgM anti-dengue virus are 165 people (82.50%), the negative categories derived from 61 peoples negative, and positive IgG 4 people (Table 1). Associations between independent variables with dependent variable Bivariate analysis showed three significant independent variables associated with dependent variable which are outdoor activity (p value = 1.243, prevalence ratio / RP = 1.243, 95% CI: to 1.416), nutritional status (p value = 0.005, RP = 1.220, 95% CI: to 1.433), and age groups (p value = 0.004, RP = 1.496, 95% CI: to 2.177). In addition, also found two variables that produce p value <0.25 which were the density of the household variables (p value = 0.138) and a variable history of dengue illness (p value = 0.166) (Table 2). Three

3 Scholarly J. Sci. Res. and Essay 22 Table 1. The results of bivariate analysis between the independent with the dependent variable. Environmental variables Variables No risk factor category Risk factor category Category F % Category f % 1. Household density Less dense 88 44,0 Dense ,0 2. Abiotic environment a. Quality of lighting Optimal 30 15,0 Not optimal ,0 b. Presence of not closed water containers Negative ,5 Positive 83 41,5 c. Air temperature Not optimal 8 4,0 Optimal ,0 d. Air humidity Not optimal 76 38,0 Optimal ,0 3. Presence of Aedes mosquito larvae Negative ,5 Positive 47 23,5 Host variables 1. Activity of occupants in outside the home High 97 48,5 Low ,5 2. Nutritional status Normal ,0 Not normal 68 34,0 3. Age groups >5 year ,5 <5 year 21 10,5 4. History of dengue illness Never ,0 Ever 32 16,0 5. Status of IgM anti-dengue virus Negative ,5 Positive 35 17,5 Table 2. The results of bivariate analysis between the ten independent variables with the dependent variable No Variables P value RP 95% CI Lower Upper 1 Household density 0,138 1,087 0,959 1,232 2 Abiotic environment Quality of lighting 0,567 1,012 0, Presence of not closed water containers 0,354 1,038 0,909 1,184 Air temperature 0,577 1,063 0,812 1,393 Air humidity 0, ,909 1,176 3 Presence of Aedes mosquito larvae 0,384 0,960 0,834 1,106 4 Activity of occupants in outside the home 0,001 1,243 1,092 1,416 5 Nutritional status 0,005 1,220 1,038 1,433 6 Age groups 0,004 1,496 1,028 2,177 7 History of dengue illness 0,166 1,119 0,906 1,382 independents variable are significantly associated with dependent variable, and two variables that resulted p value <0.25, it was used as predictors in the multivariate analysis using binary logistic regression. Probability IgM anti-dengue virus Multivariate analysis with five predictor variables resulted two variables are significantly associated with status of IgM anti-dengue virus consist outdoor activities (p value = 0.004) and nutritional status (p value = 0.022), 3 other variables are not significantly related with status of IgM anti-dengue virus. Further analysis resulted two variables as a confounding are variable density of occupants and age group variable, but not resulted the inter-action among the variables. Variable which biggest association with the incidence of IgM anti dengue is activity of occupants outside the home ( = 1.294), further is nutritional status ( = 0.944). Whereas the form of a model to estimate the incidence of IgM anti-dengue virus based on value of two predictor variables is:

4 Hakim 23 Description: P = magnitude of opportunities for the happened of IgM anti-dengue virus (in%), e = constanta (2.218), X1 = value of the variable occupant activities outside the home that is 0 = high, and 1 = low; X2 = the value of nutritional status variable that is 0 = normal, and 1 = abnormal. Furthermore, based on the form of this prediction model, it can be calculated probability occurrence of IgM anti-dengue virus, i.e. if all the predictor variable value is 1 which means have a risk to get IgM anti-dengue virus, the probability to happen the IgM anti-dengue virus are 67.58%. Conversely, if the value of all predictor variables is 0 which means have no risk to get IgM anti-dengue virus, the probability is 9.88%. DISCUSSION Bivariate analysis resulted only 3 variables significantly associated with dependent variable (status of IgM antidengue virus), i.e. the occupant activities outside the home (p value = 0.001), nutritional status (p value = 0.005) and age groups (p value = 0.004). These three variables are risk factors associated with the presence of IgM anti-dengue virus due to its resulting RP> 1, i.e. the RP of low/high category of occupant activities outside the home = (CI 95% : ), RP of abnormal/normal category of nutritional status variables = (CI 95%: ), and RP of <5 year/>5 year category of age groups = (CI 95%: ) (Table 2). Activities outside the categories of residents are low to be a factor associated with the transmission of dengue virus that producing IgM antibodies due to the respondent was longer at home during the day will be more frequently exposed to dengue virus. Klayan village is an area with high dengue morbidity, so being at home have a higher risk of contracting dengue virus. Nutritional status associated with the status of immunity against infectious diseases, so people with not normal nutritional status will be easier to get dengue virus infection and transmission than those with normal nutritional status. Whereas the age group <5 years be a factor related to the status of IgM anti-dengue due to the activities and jobs. The results of this study are similar to the results of the research has been done before, for example the results of research conducted by Maron GM in El Salvador by observing the nutritional status of DHF patients compared with healthy people. This study shows, the percentage of DHF patients in people with normal nutritional status (0.6%), lower than those with less nutritional status (5.7%) or over nutrition (5.1%), although this difference as statistically was not significantly different (Maron et al., 2010). These results showed that people with not normal nutritional status (less on or more), more susceptible to dengue virus infection compared with those with normal nutritional status. Another study conducted by Kalayanarooj in Thailand showed that people with better nutritional status, had a 1.01 times chance to be infected by dengue viruses than people with normal nutritional status (Kalayanarooj and Nimmannitya, 2003). Whereas Egger JR has proved that age group were influencing on the transmission of dengue virus because the age group related with job and activities, apart from that age group also influencing clinical manifestations of DHF patients (Egger and Coleman, 2007). Age and nutritional status also influencing the immune system that helps the human DNA repair; prevent infections caused by fungi, bacteria, viruses, and other organisms, and also produce antibodies to fight foreign bacteria and viruses that enter the body (Aspinall, 2005), decreasing function of the body's immune system will increase susceptibility to disease (Fatmah, 2006). Thus, respondents who have good nutritional status (normal) and are in no vulnerable age group (> 5 years), have higher protection than that is on the contrary, so it is more protected from dengue virus infection. Dengue virus is transmitted by mosquitoes, especially Ae.aegypti is a domestic mosquito, or living in households with a human (Knowlton et al., 2009), therefore transmission of dengue virus are more prevalent in the home. In this study, variables related to the presence of the respondent within or outside the home are variable of occupant activities outside the home and the age group, and was shown to be significantly associated with status of IgM anti-dengue virus. Respondents with outside activities in low categories (more at home during the day), proved more get a risk for dengue virus infected (RP = 1.243). Respondents in the age group <5 years, also get a risk higher for contracting dengue virus (RP = 1.496) because generally only move in the house or the surrounding environment, unless brought away by adults. Research sites (villages Klayan) is the region with the highest dengue transmission in the district of Cirebon during the last 3 years (Hakim and Superiyatna, 2009), so it is possible density of the dengue virus in the village Klayan higher than elsewhere in Cirebon regency. This could lead to dengue virus transmission rates will be high so it was in the village Klayan have a higher risk of contracting dengue virus than be somewhere else. Household density variable is not significantly associated with status of IgM anti-dengue virus (p value 0.138), because it is an intermediary variable transmission of dengue virus. The household density affects the frequency of biting mosquitoes Aedes spp to humans, the biting frequency will higher in the dense house compare in homes that are less dense (Hakim and Kusnandar, 2010). Likewise, abiotic environmental variables consisting of lighting quality of home, the presence of water kontiner not covered, the air temperature and humidity inside the house, and the

5 Scholarly J. Sci. Res. and Essay 24 presences of mosquito larvae Aedes spp, each not significantly associated with status of IgM anti-dengue virus (p value> 0.05), because all these variables are also only associated with the population and bionomic of the mosquito Aedes spp (Knowlton et al., 2009). Although the transmission of dengue viruses prevalent in the home, but home abiotic environmental and the presence of mosquito larvae of Aedes spp, were not significantly associated with the dependent variable because it is not directly related to the transmission of dengue virus, but through the intermediary variables i.e. mosquito populations. Study in Jepara and Ujungpandang reported, for transmission of dengue virus in humans, beside the mosquito population is still dependent on other factors such as capacity vector, dengue virus virulence and host immune status (Lubis, 1990). Whereas, the vector capacity beside is influenced by the vector mosquito populations, also be influenced by frequency of mosquito bites per day (multiple bites), geotropic cycle length, age of the mosquito, the dengue virus extrinsic incubation and the proportion of infective mosquitoes (Canyon, 2000). Thus, abiotic environmental factors and the presence of mosquito larvae of Aedes spp are indirect cause of infection and the presence of IgM antidengue virus as it is still dependent on other variables. Variable of history of dengue illness is not related to status of IgM anti-dengue virus (p value 0.166) allegedly due to dengue virus antibodies which are formed due to dengue in pain, has been lost from the body of respondents. People who have infected by one serotype of dengue virus, usually immune to the same serotype due to it had been formed the anti-dengue antibodies for certain period (Kurane, 2007), usually days (Soegijanto, 2002). In this study were found 34 of respondents who have a history of dengue illness even all hospitalized, the last time illness was in 2010 (no respondents who are sick of DHF in 2011). The study was conducted in May 2011, so if the history of DHF illness resulting the dengue antibodies, it has lost because more than 90 days. Multivariate analysis that simultaneously analyzed three significantly independent variables associated with the dependent variable plus two variables that resulted p value <0.25 (household density and history of dengue illness), resulted two significantly variables associated with status of IgM anti-dengue virus (p value <0.05) and two variables as confounding. Thus, the probability of occurrence of IgM anti-dengue virus calculated based on two variables: activity of occupants in outside the home and nutritional status. Based on this prediction model, if the respondent has a low category of activities outside the home and not normal nutritional status, probability to get IgM anti-dengue virus is 67.58%. Conversely, respondents with high category of outside activities and normal nutritional status, the probability to get the IgM anti-dengue virus were 9.88%. Small value of the estimating of the IgM anti-dengue virus, caused only 2 variables as predictors, while the cause of dengue virus transmission is very complex, involving many factors and variables CONCLUSION This study has confirmed that activities outside the home occupants, nutritional status and age group, shown to be associated with the happening of IgM anti-dengue virus; whereas the density of the household, home abiotic environment, the presence of Aedes mosquito larvae, and a history of dengue illness is not shown to be associated with the presence of IgM anti-dengue virus. To estimate the presence of IgM anti-dengue virus can only be calculated based on the value of variable of the occupant activities outside the home and nutritional status. ACKNOWLEDGEMENT We would like to thank all who had been assisted in this research, from start to finish. Especially we thank to the supervisor from Diponegoro University, Semarang, chief of Loka Litbang P2B2 Ciamis, chief of medical officer of Cirebon, chief and staff of public health center of Gunungjati, and also head and the entire of community of Klayan village. REFERENCES Aspinall, R. (2005). Ageing and the Immune System in vivo: Commentary on the 16th session of British Society for Immunology Annual Congress Harrogate December Immunity and Ageing Vol 2: Canyon, D. (2000). Advances in Aedes aegypti Biodynamis and Vector Capacity, Tropical Infectious and Parasitic Diseases Unit, School of Public Health and Tropical Medicine, James Cook University. Egger, J.R. and Coleman, P.G. (2007). 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