Integrated epidemiological study of Dengue virus transmission in Java, Indonesia

Dengue virus (DENV) is one of the most important arbovirus infections which continues to be spread to many parts of the world. The widespread distribution of the vector Aedes sp, DENV genetic evolution, emergence of a new serotype, global warming, environmental changes, population growth and human mobility are some of the factors affecting DENV transmission. From the many studies conducted on DENV, there is still a lack of integrated research that includes several aspects that affect DENV transmission at a local scale. The aims for this study was to conduct an integrated study of DENV tranmission, covering entomology, DENV, and socio-economic and environmental factors using Banyumas Regency, Java Indonesia, as a model area. The uniqueness of demography, socioeconomy and environment of each area emphasizes the importance of this research. For the entomology factors, this study found that traditional larvae indices such as House Index (HI), Breteau Index (BI) and Container Index (CI), which have been applied for many decades in entomology surveys, are not relevant measurements for determing mosquito populations. These findings supported previous findings that larvae indices cannot predict the transmission risk level and is not correlated with DENV incidence. In this study, adult mosquito collections were found to be a better measurement of risk of DENV transmission. A high vertical transmission rate was also confirmed in an endemic area, which is possibly one explanation for DENV persistence in that area. From a knowledge, awareness and practice (KAP) survey, there is no correlation between knowledge, awareness and practice of DENV prevention and control, and there is also no association between KAP of people with the mosquito infestations in the area of study. This finding leads to the need for better strategies such as education campaigns about DENV prevention to ensure not only an increase in knowledge but also this knowledge translates into practices. During collection of serum samples from DENV infected patients a higher number of adult age groups reported DENV cases, indicating an age group shift from children to adults. Most of the samples (89% ) from positive result of IgG/IgM test had a secondary infection by serological test, which likely increases the possibility of developing severe clinical manisfestations. Many publications believe that secondary infection by different serotypes could cause severe DENV infection. Unfortunately, the serotyping and genotyping of the patient samples could not be completed due to time constraints, so the information of circulating serotypes and genotypes could not be obtained. It would be interesting to further analyse the serotypes and then correlate them with the less or more severe clinical manifestations and also capture the spread of disease from pylogenetic trees from the genotyping results. Based on spatio and spatio-temporal models, it can be concluded that socioeconomic factors, particularly the level of education and the employment structure were the most important risk factors of DENV infection. It was also revealed that enviromental factors had only a little influence on DENV infection, in contrast with many previous beliefs that global warming and environmental changes are the main factors of DENV infection. Human mobility was proposed to be the main explanation of this phenomenon since more educated people and people with good job type tend to have higher exposure to DENV infection due to their movement from home to work places or public areas. This also complements the fact that more adults reported DENV infection during the patient sample collection, suggesting that adult age groups possibly have a higher risk of DENV infection due to higher mobility, which means higher exposure to DENV infection. The possibility of having a secondary infection is also higher in adults since there has been more time to have the first infection and then the second infection. In order to complete this integrated study, the influence of temperature on mosquito immunity, in particular the RNA interference (RNAi) response was tested. Based on RNAi activity in 24°C, 28°C and 32°C, RNAi activity was slightly more efficient following the increase of temperature. In addition, the infection of Aag2 cells with SFV showed that the increasing temperature will result in lower virus replication. We can assume that the lower or higher temperature only contributes a minor effect on RNAi machinery in vitro. In conclusion, this integrated epidemiological study finds that current entomology surveys are not relevant, because they are not associated with the risk of transmission. In addition, socioeconomic factors rather than environmental factors are proposed to be the most significant factor for DENV infection. Findings such as age shift, secondary infection, human mobility and a high vertical transmission rate are important information which could help the public health sector in their planning and action on DENV prevention and control strategies