Sylvatic Transmission and Reservoir Potential of Zika, Dengue, and Chikungunya Viruses of Co-located Humans and Long-tailed Macaques in Thailand and Cambodia

Overview

Background: Zika, dengue, and chikungunya are spread by mosquitos. These diseases have a major impact on public health. This is especially true in in Southeast Asia. Non-human primates (such as macaques) could play an essential role in spreading these diseases. Researchers want to further understand the relationship between humans and these primates. They want to see how this affects how mosquito-borne viruses are spread in Southeast Asia. Objective: To describe the prevalence of Zika virus, dengue virus, and chikungunya virus in the blood of people who live close to long-tailed macaques in Thailand and Cambodia. Eligibility: Healthy people aged 18-55 who have lived or worked within approximately 10 kilometers of the Wat Amphae Phnom monkey habitat in Kampong Speu, Cambodia, for a minimum of 2 years Design: Participation will last 1 day. Participants will be screened in person through an interview. Their medical history will be reviewed. Participants will give information about themselves. This will include sex, age, and behaviors related to the spread of mosquito-borne disease. For example, they will be asked about the number of water containers at their home. They will be asked about recent travel. They will be asked about the extent of their contact with the macaques. Participants will give a blood sample….

Full Title of Study: “Investigating the Sylvatic Transmission and Reservoir Potential of Zika, Dengue, and Chikungunya Viruses of Co-located Humans and Long-tailed Macaques of Thailand and Cambodia”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: February 28, 2022

Detailed Description

Arboviral epidemics continue to emerge suddenly and spread of disease is unpredictable. The 2015-16 Zika epidemic resulted in a high case number in Thailand, but not in neighboring Cambodia. It is known that nonhuman primates (NHPs) are important reservoirs of arboviruses, but the importance of their epidemiological role in the transmission of arboviruses is not clearly understood. While transmission dynamics are complex and require consideration of many variables, primate reservoirs are not routinely sampled, particularly in Southeast Asia, because of the level of operational complexity and skill required. Here, we propose a serological survey for evidence of Zika virus (ZIKV), dengue virus (DENV), and chikungunya virus (CHIKV) exposure in long-tailed macaques and human adults who live or work in close proximity to these monkeys in Thailand and Cambodia. We hypothesize that ZIKV seroprevalence in both humans and macaques will be higher in Thailand than Cambodia. With the current rise of arboviral diseases around the world, we hope the results of this study contribute to better understanding of the epidemiology and burden of arboviral diseases in this region.

Arms, Groups and Cohorts

  • 1
    • Adults ages 18-55 with ZIKV, DENV, and/or CHIKV seroprevalence.

Clinical Trial Outcome Measures

Primary Measures

  • Assessment of seroprevalence via screening ELISA and/or PRNTSO titers for ZIKV, DENV, and CHIKV in Cambodian adults.
    • Time Frame: Day 0
    • PRNT assays are the gold standard to detect virus-specific antibodies given multiple circulating flaviviruses in Southeast Asia. Understanding the prevalence of these Aedes transmitted viruses, and how they differ across the Mekong region, is critical to understanding the risk to Cambodians of future epidemics.
  • Assessment of seroprevalence via screening ELISA and/or PRNTSO titers for ZIKV, DENV, and CHIKV in Cambodian macaques as compared to humans.
    • Time Frame: Day 0
    • Because primates can be amplifying hosts of these viruses, it is critical to understand the prevalence of these Aedes-transmitted viruses in macaques as well.

Secondary Measures

  • Comparative assessment of seroprevalence via PRNTSO titers for ZIKV, DENV, and CHIKV in Cambodian adults and macaques to that of Thai adults and macaques.
    • Time Frame: Day 0
    • Understanding how the prevalence of these Aedes transmitted viruses differs across the Mekong region is critical for cross-border disease detection and management, particularly given the high level of human migration in the Greater Mekong Subregion.
  • Assessment of reactivity to salivary gland homogenate of Aedes aegypti as detected by ELISA or western blot in human and macaque sera.
    • Time Frame: Day 0
    • Characterizing vector salivary protein reactivity profiles (mosquitos, ticks, fleas) in Cambodians with vector- borne disease is the first step to better understanding transmission patterns, responsible vectors, and Cambodians’ risk of exposure to these vectors.

Participating in This Clinical Trial

Inclusion Criteria

In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Provision of signed and dated ICF 2. Able to provide informed consent 3. Stated willingness to comply with study procedures 4. Male or female, aged 18-55 years 5. Live/work within approximately 10 km of the Wat Amphae Phnom monkey habitat for minimum of 2 years 6. In good general health as evidenced by screening medical history 7. Willing to allow biological samples to be stored for future research EXCLUSION CRITERIA:

1. Any underlying, chronic, or current medical condition that, in the opinion of the investigator, would interfere with participation in the study (e.g., inability or great difficulty in drawing blood)

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 55 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • National Institute of Allergy and Infectious Diseases (NIAID)
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Jessica E Manning, M.D., Principal Investigator, National Institute of Allergy and Infectious Diseases (NIAID)
  • Overall Contact(s)
    • Jessica E Manning, M.D., (301) 761-7129, jessica.manning@nih.gov

References

Bhatt S, Gething PW, Brady OJ, Messina JP, Farlow AW, Moyes CL, Drake JM, Brownstein JS, Hoen AG, Sankoh O, Myers MF, George DB, Jaenisch T, Wint GR, Simmons CP, Scott TW, Farrar JJ, Hay SI. The global distribution and burden of dengue. Nature. 2013 Apr 25;496(7446):504-7. doi: 10.1038/nature12060. Epub 2013 Apr 7.

Ruchusatsawat K, Wongjaroen P, Posanacharoen A, Rodriguez-Barraquer I, Sangkitporn S, Cummings DAT, Salje H. Long-term circulation of Zika virus in Thailand: an observational study. Lancet Infect Dis. 2019 Apr;19(4):439-446. doi: 10.1016/S1473-3099(18)30718-7. Epub 2019 Feb 27. Erratum in: Lancet Infect Dis. 2019 Mar 8;:.

Weaver SC, Lecuit M. Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med. 2015 Mar 26;372(13):1231-9. doi: 10.1056/NEJMra1406035. Review.

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