This study aims to conduct pilot surveillance for Nipah virus (NiV), Japanese encephalitis virus (JEV), and Crimean-Congo hemorrhagic fever virus (CCHFV) in East Malaysia, Mexico, Mongolia, and Northern Vietnam. NiV is a highly lethal paramyxovirus that is transmitted from bats and pigs, causing severe encephalitis with a 58% fatality rate. JEV is a flavivirus transmitted by mosquitoes that causes encephalitis in rural and peri-urban Asia, with a 30% fatality rate for symptomatic cases. CCHFV is a bunyavirus transmitted by ticks or infected blood, causing severe hemorrhagic fever with 40% fatality in hospitalized cases. This study will partner with the National Bio and Agro-Defense Facility (NBAF) in attempting to identify and characterize viruses or serological evidence of such viral infections in wildlife and livestock in the four countries.  identify and characterize these viruses in Data from this study may inform future public health interventions and targeted surveillance efforts. 

Often serious viral illnesses are identified via carefully designed molecular laboratory tests.  However, sometimes these carefully designed tests for known pathogens will miss newly identified or rare pathogens.  Through this research project we are working closely with international collaborators and the US Department of Agriculture in seeking to identify such new or rare viruses. Specifically, this study seeks to identify Nipah viruses, Japanese encephalitis viruses, Crimean-Congo Hemorrhagic Fever viruses and other related viruses that might be causing hospitalizations in Malaysia, Mexico, Mongolia, and Vietnam. As we identify such viruses, we will characterize them with a goal of better understanding their epidemiology and developing countermeasures to reduce their future morbidity and mortality.

Summary

Mongolia has some of the highest ambient particulate matter (PM) concentrations in the world and frequently suffer epidemics of viral respiratory disease. There is some evidence to suggest that PM exposure may weaken the immune defense against respiratory viral infection thereby enhancing incidence and severity of infection but this has not been well studied. In collaboration with the Mongolian National University of Medical Sciences (MNUMS) and Duke University, we will test the hypothesis that PM exposure weakens the immune defense against respiratory viral infection through a main study and two pilot studies. Specifically we first aim to characterize the relationship between PM exposure and respiratory viral infection through a time-series analysis of weekly influenza-like illness rates in association with PM levels in two major Mongolian cities, Ulaanbaatar (UB) and Darkhan City (DC).

Secondly, we aim to examine immunological and viral responses to personal PM exposure by following 100 nonsmoking adults in both UB and DC every 6 months for three years and collect questionnaire data and biological specimens for lung function, inflammatory responses, and blood pressure. Air samplers will also be employed to measure both PM exposure and to detect airborne viruses.

The third aim of this project is to define the direct effects of PM exposure on epithelial integrity and immune signaling and the subsequent impact on anti-viral responses. This will be done through cell culture studies directly linked to aim 2 subjects (as cell donors).

Lastly, in the two pilot studies, we will explore the effects of PM and heavy metals in PM on pulmonary tuberculosis and bone mineral loss, respectively, in family members of the subjects enrolled for Aim 2. UTMB staff will provide guidance, training, and oversight for the measurement of viruses in bioaerosol samples collected in houses for Aim 2. UTMB Positive bioaerosol samples may also be transferred to UTMB for further characterization studies by UTMB staff.

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