Impact of TMP-SMX Prophylaxis on Malaria Infection and Immunity in Children in Uganda

Background: \- Malaria is a disease that affects many children and adults in Uganda and Africa. If it is not treated, it can make some people severely ill. TMP-SMX (Trade names Bactrim, Septrin) is a drug that is given to children born to HIV-positive mothers to help prevent infection. Studies have shown that TMP-SMX also may kill malaria infection in the very early stages of infection in the body, which may positively impact the way the body can fight malaria infection. Researchers want to know if giving TMP-SMX for 6 months longer than usual helps children fight malaria better in this way. Objective: \- To find out if taking TMP-SMX for longer than usual helps fight off malaria in infants. Eligibility: \- Infants 0-6 weeks of age who are HIV negative. Design: * Infants will be screened with a medical history and physical exam. A small amount of blood will be taken. The mothers medical records will be reviewed. Mothers will be asked about when they breastfeed. * Participants will take TMP-SMX according to their doctor s orders. In Uganda, mothers will get a mosquito net with insecticide on it as per standard of care. * Participants will come to the clinic once a month, every month, until the study ends in 2 3 years. Each visit will repeat the screening visit. * Participants will also visit the clinic every month for a medical history, physical exam, and different blood tests. * Six weeks after breastfeeding is stopped, children taking TMP-SMX will come into the clinic and will either be taken off the drug or will continue taking the drug for 6 more months. * If a child becomes sick, it is important that the mother bring him or her to the RHSP clinic in Rakai.