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.

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.

• 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 informed consent form
2. Stated willingness to comply with all study procedures and availability for the duration of the study
3. Male or female, aged 2-9 years
4. Live within approximately 5.5 km of study site
5. In good general health as evidenced by medical history
6. Willing to allow biological samples to be stored for future research.

EXCLUSION CRITERIA:

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

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.@@@