Investigating Vector-borne Determinants of Aedes-transmitted Arboviral Infections in Cambodia: An Observational Longitudinal Cohort Study in Children
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 775
- 试验地点
- 1
- 主要终点
- 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
研究概览
简要总结
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.
详细描述
Mosquito-borne viruses continue to cause significant global morbidity and mortality, particularly in Southeast Asia. When mosquitoes deliver the virus into the skin of humans while probing for a blood meal, they deposit also saliva, which contains a myriad of pharmacologically active compounds that modulate the host immune system. Most vaccines against vector-borne diseases under development ignore the importance of the complex infectious inoculum delivered by the mosquito vector and the subsequent host immune response to mosquito salivary proteins. Many studies of vector-borne disease do not evaluate what role vector-derived factors play in the host immune response of these infections. A cumulative body of evidence from animal models and limited retrospective human data demonstrates that a variety of vector-derived components, including salivary components, are codelivered with the pathogen and may play an important role in the establishment and dissemination of arboviral infection. Knowledge of the effect of these vector-derived factors on the development of arboviruses in the human is limited. Here, we will establish and follow a longitudinal pediatric cohort study to describe the burden of dengue virus and to carefully examine the immune response to exposure of the salivary proteins of Aedes aegypti, the mosquito vector of dengue, Zika and chikungunya viruses. This study will serve as a foundation so that future studies may contribute to further understanding how saliva immunity impacts arboviral disease development i Cambodia, a country endemic to these viruses.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 2 Years 至 9 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA:
- •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.
排除标准
- •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
研究组 & 干预措施
1
Healthy children aged 2 - 9 years
结局指标
主要结局
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
时间窗: Semi-Annual visits and sick/convalescent visits throughout study enrollment
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.
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
时间窗: Semi-annual visits and sick/convalescent visits throughout study enrollment
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.
次要结局
- 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)
- 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)
- 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)