Chemopreventive Therapy for Malaria in Ugandan Children
Condition: Malaria
MeSH terms: Malaria
Intervention: trimethoprim-sulfamethoxazole (TS; TMP/SMX); sulfadoxine-pyrimethamine (SP); dihydroartemisinin-piperaquine (DP)
Intervention description: daily dosing, 20mgTMP/100mgSMX tabs, 80mgTMP/400mgSMX tabs; monthly dosing given as a single dose, 500mg/25mg tabs; monthly dosing given once a day for 3 consecutive days, 40mg/320mg tabs
Intervention MeSH terms: Pyrimethamine; Piperaquine; Sulfadoxine; Trimethoprim; Fanasil, pyrimethamine drug combination; Artenimol; Trimethoprim, Sulfamethoxazole Drug Combination; Sulfamethoxazole
Phase: Phase 3
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 600.0
Sex: All
Minimum age: 4 Months
Maximum age: 5 Months
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Chemoprevention; Uganda; Malaria; Trimethoprim-sulfamethoxazole; Sulfadoxine-pyrimethamine; Dihydroartemisinin-piperaquine

Summary:

      Young African children living in high transmission areas suffer the greatest burden of
      malaria. In most African countries, such as Uganda, the only current preventive measure
      against malaria in high transmission settings is the use of insecticide treated bednets
      (ITNs). Preliminary data show that even in the setting of ITN use, young children living in a
      high transmission setting suffer almost 4 episodes of clinical malaria per year, highlighting
      the need for new preventive strategies. Chemopreventive strategies offer a potential means of
      reducing the burden of malaria among young children living in a high transmission setting.
      This study will compare the efficacy and safety of 3 promising chemopreventive strategies
      (monthly dihydroartemisinin-piperaquine, monthly sulfadoxine-pyrimethamine, daily
      trimethoprim-sulfamethoxazole) with the current standard of no chemoprevention and will be
      conducted in two distinct patient populations: 1) HIV-unexposed children (HIV-uninfected
      children born to HIV-uninfected mothers) and 2) HIV-exposed children (HIV-uninfected children
      born to HIV-infected mothers). The intervention will begin in HIV-unexposed children when
      they reach 6 months of age, the time at which the incidence of malaria begins to increase,
      and will be continued until the children reach 24 months of age, which prior data suggest is
      when the incidence of malaria begins to decline due to the development of semi-immunity. In
      addition, study participants will be followed for one additional year following
      chemopreventive therapy to examine for "rebound" in the incidence of malaria following our
      intervention. HIV-exposed children will begin the intervention when they have completed
      breastfeeding and have been confirmed to remain HIV-uninfected. The intervention will
      continue until study participants reach 24 months of age and then the study participants will
      be followed for an additional year to examine for rebound in the incidence of malaria. It is
      anticipated that the results of this study will provide valuable comparative data on the
      effect of different chemopreventive strategies on malaria incidence in two distinct patient
      populations at high risk for malaria. In addition it is anticipated the results of this study
      will provide insight into the development of naturally acquired antimalarial immunity in the
      setting of chemopreventive therapy that will differ in terms of the drug regimens, the age at
      which the intervention is started, and the HIV status of the mothers.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age 4 -5 months

          2. Confirmed HIV status of biological mother

          3. Negative HIV DNA PCR test at time of enrollment for infants born to HIV-infected
             mothers

          4. Infants born to HIV-infected mothers must be breastfeeding

          5. Residency within 30km of the study clinic

          6. Agreement to come to the study clinic for any febrile episode or other illness and
             avoid medications given outside the study protocol

          7. Provision of informed consent by parent/guardian

        Exclusion Criteria:

          1. History of allergy or sensitivity to TS, SP, or DP

          2. Active medical problem requiring in-patient evaluation at the time of screening

          3. Intention of moving more that 30km from the study clinic during the follow-up period

          4. Chronic medical condition (i.e. malignancy) requiring frequent medical attention

          5. Living in the same household as a previously enrolled study participant

          6. QTc interval > 450 msec

          7. Other clinically significant ECG abnormalities such as arrhythmia, ischemia, or
             evidence of heart failure

          8. Family history of Long QT syndrome

          9. Current use of drugs that prolong the QT interval