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Cycle 1

Principal Investigator: Isra Wahid, Universitas Hasanuddin
NIH-Supported Collaborator: David Severson, University of Notre Dame
Title of NIH Award: Diapause in Culex mosquitoes
Project dates: October 2013 - April 2019

Project Overview

Arthropod-borne viruses are a concern in areas like Indonesia (an emerging pathogen ‘hotspot’) because of the ease with which vectors can transfer RNA viruses between wildlife, humans and livestock, and because of the large variety of pathogenic viruses already known to exist. However, there are no known records of these pathogenic viruses (such as West Nile, Sepik, Banna) in Indonesia though they are known to exist at similar latitudes. Dengue virus, present in Indonesia, is an emerging global health threat, and disease prevention depends completely on avoiding the mosquito host that transmits the virus from human to human. No other dengue disease prevention or treatment methods exist. Preliminary evidence suggests that there may be differences in allele frequencies related vector competence to transmit Dengue virus. This study seeks to understand the genetic composition of mosquito populations seasonally and among communities in order to predict levels of mosquito diversity and movement within and between communities, and to assess vector competence to transmit dengue viruses throughout a transmissions season. This study will make a survey of potentially pathogenic arboviruses from mosquitoes collected throughout Indonesia aimed at identifying viruses, their vectors, as well as temporal transmission characteristics towards discovery and informing intervention programs. The primary objective of this study is to survey for potentially pathogenic mosquito-borne arboviruses in their vectors to geographically map risk, estimate force of infection, and identify potential emerging pandemic threats. A secondary objective focusing on the dengue virus vector will investigate if there is a temporal change in the vector genotype with associated impacts on vector competence between the wet and dry seasons. This study will entail systematic collections of mosquitoes in all ecological zones prevalent on the island of Sulawesi. The study team will identify vectors to species to determine the diversity of mosquitoes and ID those known to harbor human pathogens. The researchers will also perform virus isolation in vertebrate cell cultures towards virus identification. Finally, the researchers will examine seasonal effects on Ae. aegypti population genetics and DENV susceptibility. It is expeced that the study team will collect circulating viruses that have never been recorded at these sites and the possibility exists of identifying novel viruses in the preliminary survey. Vector results will enable the characterization of geographic vector-virus transmission systems and will allow a better understanding of local dengue transmission and hence better intervention strategies.

PH 1-16 Indonesia photo 1PH 1-16 Indonesia photo 2
Mosquito capture nets placed between the village and the mosquito breeding site.Mosquito collection efforts by Dr. Wahid and his team (photo courtesy Dr. Wahid)

Summary of Overall Activities:

While the project began in 2013, the research activities did not truly begin until January 2014. During the study period, the team collected a vast amount (50,000+) of mosquito samples from all of main genera: Anopheles, Culex, Aedes and stored them in the laboratory freezer while waiting for the virus control clearances from the CDC collaborator to ensure there were no additional viruses in the mosquitoes. While waiting the virus control, the team analyzed part of the collected samples, with help and donations from local clinicians who commonly encounter patients with endemic dengue. None of the samples appeared to be positive. Unfortunately, it took almost two years for the CDC permit of virus control exportation from the CDC, and the controls arrived in our lab just few month before the end of study period.

To be able to start analyzing the samples the team received an extension. Unfortunately, after this long period of time, the team found that none of the preserved samples had positive results for arboviruses, despite more than 20.000 tested. Probably, most of the samples spent too long in freezer and degraded due to limited capacity of the lab freezer. As such, the team decided to re-collect samples and received a further extension to do so. They chose three sites from West and South Sulawesi provinces, each with multiple collection windows. The project team managed to collect 16.980 mosquitoes from nine genera and found a Bunyaviridae family positive in one pool of Culex trinaenorhyncus mosquitoes. The sequencing results was Bunyawera virus (BUNV) with 99% percent identity to the NCBI database of Bunyawera viruses. The Bunyawera virus is the prototype of Bunyaviridae family from genus Orthobunyavirus, which was first isolated in 1943 at West Uganda (Alatoom and Payne, 2009). This group was known been transmitted blood feeding arthropods. The team is now writing a manuscript on the new report of Bunyawera virus in Indonesia.

The team also developed more links with other national and international researchers with the help of their collaborators who had other projects in Indonesia. The team established many national links, both governmental and non-governmental, such as the national MoH and itsn subdirectorate of Vectors, Arboviruses, And Malaria, and the Tahija Foundation, which is developing wolbachia -infected Aedes for dengue control (in collaboration with an Australian university funded by the Bill and Melinda Gates Foundation). The team also connected with international researchers from foreign universities such as: CDC (US)-funded lab in Eijkman Institute (Indonesia), San Diego University (US), Roma Tre University (Italy), St. Andrew University and Surrey University both from UK, Kitasato University (Japan) and Chiang Mai University (Thailand), and also organizations including UNICEF and WHO, to support further mosquito-related research.

This networking resulted in additional national and international research grants from UNICEF (2014-2015, 2018), Militari Health Institute (2015-2016), JSPS Japan (2018-2022), Medical Research Council UK (2018, 2019-2021), and the Ministry of Higher Education, Research and Technology of Indonesia (2019-2020). On average, the team accepted about USD 100.000 each year during the Peer project period. Several publication were published from the developed network, while several others are waiting for submission and acceptance.

While conducting the activities, the team closely communicated with governmental organization such the Ministry of Health (MOH), Provincial Health Office (PHO) of South Sulawesi and West Sulawesi, District Heath Office (DHO). These agencies used their influence to help implement study results including helping DHO of Makassar City improve their vector controls for dengue and reduce dengue incidence by about 83% (a manuscript of this results had been submitted and reviewed in open source journal of PLOS NTD). The team also made an agreement with PHO of South Sulawesi to use Hasanuddin University labs as one of their referral laboratory in case of infectious diseases outbreak and/or investigation of unknown fever causes. The team was also invited to give training to health officers on mosquito-borne diseases diagnostics and vector surveillance of malaria, dengue, and filariasis. They gave training on vector surveillance and mapping to health officer from the eastern part of Indonesia and to military health staff from all Indonesian military regions (KODAM), to Port Health Officers (KKP) representative from all over Indonesia, and to the Primary Health Clinic staffs of four tsunami-affected districts of Central Sulawesi also on vector surveillance and mapping. The MOH then appointed the team as panel experts for vectors and malaria, while PHO of South Sulawesi and DHO Makssar City appointed the project team as their vector-borne diseases consultant.

Internally, the team’s research activities also influenced the medical faculty to give more support for medical researches. The new dean decided to involve undergraduate student in ongoing research of their academic staff, adding more budget for research grants for the academic staff, and built a new molecular lab for infectious tropical diseases and animal experiments.
Health Cycle 1 Recipients