Investigating Vector-Borne Determinants of Aedes Transmitted Arboviral Infections in Cambodia: An Observational Longitudinal Cohort Study in Children

NCT03534245 | Completed

• 2 other identifiers: 99991810018-I-N100
• Study Type: observational
• Target: 775
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Some mosquitos carry viruses that can cause disease. Some examples are dengue and Zika. The mosquitos spread disease by biting people and infecting them with the virus. Children, elderly people, and people who are already sick are especially likely to get infected. Researchers want to learn more to help make new medicines to treat these viral infections. Objective: To learn more about how mosquitos infect people, and why young children are more likely to get sick than other people. Eligibility: Healthy children 2-9 years old who live near the study site. This is Kampong Speu District Referral Hospital in Chbar Mon, Cambodia. Design: At visit 1, participants will have a physical exam. A small amount of blood will be taken from their arm or finger. Parents will answer questions about the participant s general health and medical history. Participants will come back to the study site every wet season and every dry season for the next 3 years. The visits will be the same as visit 1 and take about 1 hour. If at any time during the study the participant gets a fever and has other symptoms that could be caused by these viral diseases, they should be brought to the study site. These symptoms might include headache, pain behind the eyes, muscle pain, or joint pain. They can also include a rash that lasts longer than 12 hours. Participation ends after the final study visit in late 2021. ...

Conditions

Dengue Fever

Keywords

Mosquito Salivary Protein; Dengue Fever; Zika; Chikungunya; Kampong Speu; Natural History

Outcome Measures

Primary Outcomes (2)

• Prevalence of symptomatic and inapparent dengue infection (serotypes 1-4) as detected semiannually via ELISA assay (binary outcome present/absent) over a three-year period in Kampong Speu in children aged 2-9 years old

  Detailed knowledge of dengue seroprevalence and transmission season variability will help establish an epidemiological foundation to prepare for larger future studies such as disease incidence studies or vector interventional trials.

  Semi-Annual visits and sick/convalescent visits throughout study enrollment

• Prevalence of Aedes aegypti salivary gland homogenate reactivity as detected by ELISA assay (binary outcome present/absent) during wet and dry seasons over a three-year period in Kampong Speu in children aged 2-9 years old

  Characterizing the Ae. aegypti salivary protein reactivity profile in Cambodians is the first step prior to assessing how Ae. aegypti saliva exposure modulates disease in humans.

  Semi-annual visits and sick/convalescent visits throughout study enrollment

Secondary Outcomes (5)

• Western blot analysis of sera from participants with strongest ELISA positivity to Ae. aegypti whole salivary gland homogenate compared to Anopheles and Culex to assess cross-reactive immunogenicity to mosquito saliva versus specific Aedes marke...

  Semi-annual visits and sick/convalescent visits throughout study enrollment

• Positive RT-PCR result for diagnosis of dengue, chikungunya, and Zika viruses (or IgM capture ELISAs for dengue as needed)

  Semi-annual visits and sick/convalescent visits throughout study enrollment

• Geographic information system with all data components (mosquito catch sites, houses, schools) referenced by latitude and longitude in addition to a series of map layers (point maps, smoothed maps) to evaluate relationships between IgG intensity...

  Semi-annual visits and sick/convalescent visits throughout study enrollment

• Seroconversion to Ae. aegypti salivary homogenate in relationship to season (wet versus dry) and collected time-dependent variables defined as mean and maximum rainfall, temperature and humidity inaddition to monthly fingerpricks to evaluate ...

  Semi-annual visits and sick/convalescent visits throughout study enrollment

• Capture a minimum of 25 female Aedes aegypti mosquitoes for transcriptional comparison to LMVR-reared Aedes aegypti mosquitoes

  Duration of study enrollment

Study Arms (1)

1

Healthy children aged 2 - 9 years

Eligibility Criteria

• Age: 2 Years - 9 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Community-based cohort of children from the town of Chbar Mon in Kampong Speu, Cambodia, who live within 5.5 km to the Kampong Speu District Referral Hospital.@@@

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 2-9 years
• Live within approximately 5.5 km of study site
• In good general health as evidenced by medical history
• Willing to allow biological samples to be stored for future research.

You may not qualify if:

• Current or prior use within last 6 months of any immunosuppression (e.g. intravenous immunoglobulin, steroids, interferon therapy)
• Treatment with another investigational drug, vaccine, or other intervention within six months of screening

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Kampong Speu Referral Hospital

Chbar Mon, Kampong Speu, Cambodia

Location

Related Publications (6)

• 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.

  PMID: 23563266 BACKGROUND

• Pingen M, Bryden SR, Pondeville E, Schnettler E, Kohl A, Merits A, Fazakerley JK, Graham GJ, McKimmie CS. Host Inflammatory Response to Mosquito Bites Enhances the Severity of Arbovirus Infection. Immunity. 2016 Jun 21;44(6):1455-69. doi: 10.1016/j.immuni.2016.06.002.

  PMID: 27332734 BACKGROUND

• Machain-Williams C, Mammen MP Jr, Zeidner NS, Beaty BJ, Prenni JE, Nisalak A, Blair CD. Association of human immune response to Aedes aegypti salivary proteins with dengue disease severity. Parasite Immunol. 2012 Jan;34(1):15-22. doi: 10.1111/j.1365-3024.2011.01339.x.

  PMID: 21995849 BACKGROUND

• Odio CD, Yek C, Hasund CM, Man S, Ly P, Nhek S, Chea S, Lon C, Voirin C, Huy R, Leang R, Huch C, Lamirande EW, Whitehead SS, Oliveira F, Manning JE, Katzelnick LC. Immunity to Non-Dengue Flaviviruses Impacts Dengue Virus Immunoglobulin G Enzyme-Linked Immunosorbent Assay Specificity in Cambodia. J Infect Dis. 2025 Feb 20;231(2):e337-e344. doi: 10.1093/infdis/jiae422.

  PMID: 39297691 DERIVED

• Manning JE, Chea S, Parker DM, Bohl JA, Lay S, Mateja A, Man S, Nhek S, Ponce A, Sreng S, Kong D, Kimsan S, Meneses C, Fay MP, Suon S, Huy R, Lon C, Leang R, Oliveira F. Development of Inapparent Dengue Associated With Increased Antibody Levels to Aedes aegypti Salivary Proteins: A Longitudinal Dengue Cohort in Cambodia. J Infect Dis. 2022 Oct 17;226(8):1327-1337. doi: 10.1093/infdis/jiab541.

  PMID: 34718636 DERIVED

• Manning JE, Oliveira F, Parker DM, Amaratunga C, Kong D, Man S, Sreng S, Lay S, Nang K, Kimsan S, Sokha L, Kamhawi S, Fay MP, Suon S, Ruhl P, Ackerman H, Huy R, Wellems TE, Valenzuela JG, Leang R. The PAGODAS protocol: pediatric assessment group of dengue and Aedes saliva protocol to investigate vector-borne determinants of Aedes-transmitted arboviral infections in Cambodia. Parasit Vectors. 2018 Dec 20;11(1):664. doi: 10.1186/s13071-018-3224-7.

  PMID: 30572920 DERIVED

MeSH Terms

Conditions

Dengue; Zika Virus Infection; Chikungunya Fever

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral; Alphavirus Infections; Togaviridae Infections

Study Officials

• Luiz F Oliveira, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2018
• First Posted: May 23, 2018
• Study Start: July 1, 2018
• Primary Completion: January 25, 2022
• Study Completion: January 25, 2022
• Last Updated: May 1, 2026

Record last verified: 2025-08-05

Locations

CA (1)