Although urbanization has long been associated with human development and progress,recent research has revealed that urban environments can also result in significant inequalitiesin many areas... Show moreAlthough urbanization has long been associated with human development and progress,recent research has revealed that urban environments can also result in significant inequalitiesin many areas including health. In particular, urban areas in low and middle incomecountries (LMIC), often see a widening gap in economic growth which contributes to healthdisparities between wealthy and underprivileged children. Several studies have establishedthe association between socioeconomic status (SES) and child health, showing that childrenof low-income parents had poorer health status. The rise of non-communicable diseases,the persistence of communicable disease, and the challenge of re-emerging diseases arecurrently a burden in developing countries. Given the rapid increases of urbanization andurban poverty in several developing countries including Indonesia, it is important to elaborateto what extent SES affects child health. We have done so, in relation to outcome of BCGvaccination, atopic sensitization, and intestinal barrier function. We have also investigatedthe interaction between intestinal parasitic infections and bacterial gut microbiota in orderto be able to delineate the contribution of this interaction on the function of intestinal barrier. Show less
Rapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate... Show moreRapid socio-economic growth accelerates urbanization in Indonesia, which changes many aspect of human lives, and potentially affect disease prevalence and outcome. This thesis aims to investigate the impacts of urbanization on human health, especially metabolic health and allergic disease, by incorporating many aspects of scientific investigation. Our cluster-randomized-controlled trial showed that, helminth infection, a characteristic feature of rural areas, and anthelmintic treatment, could significantly affect metabolic profiles and hormones. Thus, the ongoing deworming program in Indonesia require in parallel, monitoring of the metabolic health. Additionally, based on our prospective cohort study and analysis on a large scale nationally representative data, although Indonesian rural populations have relatively better metabolic profiles compared to urban, lifelong residence in rural areas does not protect their community members from adverse metabolic changes due to urbanization. Next, we observed that majority of individuals with diabetes in Indonesia were undiagnosed and untreated, especially in rural populations, which warrants extensive action plan from all related stakeholders. Lastly, high-dimensional data analyses on the systemic and nasal mucosal immune profiles revealed a stronger inflammatory immune responses in the nasal mucosal of Indonesian urban young adults with allergic rhinitis compared to their rural counterparts. Show less
In this thesis, the systemic host metabolic response to experimental Opistorchis felineus infection using Nuclear Magnetic Resonance spectroscopy has been investigated. Overall, the studies... Show moreIn this thesis, the systemic host metabolic response to experimental Opistorchis felineus infection using Nuclear Magnetic Resonance spectroscopy has been investigated. Overall, the studies examined the experimental model of opisthorchiasis, which included male and female animals, mild and severe infections, acute and chronic as well as biofluids and organs. Multi-block data analysis was applied to the model of chronic opisthorchiasis to delineate how infection affects the metabolic profile of infected versus uninfected animals at a detailed level, enhancing our understanding of this neglected disease affecting 56 million worldwide. Show less
In many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity,... Show moreIn many settings, adults with active or latent tuberculosis will also be coinfected with helminths. Our study aimed to investigate how anthelmintic treatment modulates antimycobacterial immunity, in a setting where helminth reinfection should not occur. We investigated the potential impact of helminth infection on immune responses to Mycobacterium tuberculosis (Mtb) in patients with latent Mtb infection with or without helminth infection (Strongyloides or Schistosoma), and tested T-cell responses before and after anthelmintic treatment. The study was performed in migrants resident in the United Kingdom, where reexposure and reinfection following anthelmintic treatment would not occur. The frequency of CD4(+)IFN-gamma(+) T cells was measured following stimulation with Mtb Purified Protein Derivative or ESAT-6/CFP-10 antigen, and concentrations of IFN-gamma in culture supernatants measured by ELISA and multiplex bead array. Helminth infection was associated with a lower frequency of CD4(+)IFN-gamma(+) T cells, which increased following treatment. Patients with helminth infection showed a significant increase in CD4(+)FoxP3(+) T cells (Treg) compared to those without helminth infection. There was a decrease in the frequency of Treg cells, and an associated increase in CD4(+)IFN-gamma(+) T cells after the anthelmintic treatment. Here, we show a potential role of Treg cells in reducing the frequency and function of antimycobacterial CD4(+)IFN-gamma(+) T cells, and that these effects are reversed after anthelmintic treatment. Show less
