Age of Exposure and Immunity to Malaria in Infants
Overview
- Phase
- Not Applicable
- Intervention
- Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
- Conditions
- Malaria
- Sponsor
- Hospital Clinic of Barcelona
- Enrollment
- 349
- Locations
- 1
- Primary Endpoint
- (Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection
- Status
- Completed
- Last Updated
- 14 years ago
Overview
Brief Summary
The overall objective is to evaluate the effect of exposure to Plasmodium (P.) falciparum erythrocytic stage antigens during different periods of infancy on the development of naturally acquired immunity (NAI).
Hypothesis: Exposure to P. falciparum prior to 5 months of age does not result in the development of NAI, while exposure to P. falciparum after 5 months of age leads to the development of NAI. The risks of clinical malaria and anaemia during the second year of life will be compared between cohorts, as well as their correlations with the type and quality of immune responses (antibodies to several P. falciparum antigens, cytokines), oxidative stress markers and host genetic factors. These results should shed light on the determinants of the development of anti-P. falciparum responses early in life and the potential constraints to early life immunisation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Inclusion criteria for pregnant women:
- •Healthy HIV-negative pregnant females less than 50 years of age who attend the voluntary counseling and testing (VCT) center at the Maragra or Manhiça antenatal clinic,
- •Permanent residents of the Manhiça area and expecting to be living in the area with their infant for at least 2 years.
- •Inclusion criteria for newborn infants:
- •Healthy infants, weighing \>= 2 kg and having an alive mother.
Exclusion Criteria
- •Exclusion criteria for pregnant women:
- •Plan to leave the area in less than 2 years from the start of the study;
- •Women not willing to get tested for HIV infection at the VCT center;
- •Test positive for HIV;
- •Not willing to provide informed consent;
- •Cannot understand either Portuguese or Changana (consent forms are written in these languages).
- •Exclusion criteria for newborn infants:
- •Any obvious congenital malformation;
- •Any signs of cerebral asphyxia;
- •Any obvious neonatal infection;
Arms & Interventions
Late exposure group
Participants received monthly Sulfadoxine-Pyrimethamine (SP) plus Artesunate (AS) from 2.5-4.5 months of age and monthly placebo from 5.5-9.5 months of age.
Intervention: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
Early exposure group
Participants received monthly placebo from 2.5-4.5 months of age and monthly SP+AS from 5.5-9.5 months of age.
Intervention: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
Control group
Participants received monthly placebo from 2.5 to 9.5 months of age.
Intervention: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
Outcomes
Primary Outcomes
(Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection
Time Frame: from 12 to 24 months of age
Global comparison between the 3 groups of the time to first or only episode of clinical malaria (according to the primary case definition) in the second year of follow up detected by passive case detection in the According-To-Protocol cohort. In addition, pairwise comparisons of the 3 groups are also presented.
Secondary Outcomes
- (Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints.(12 to 24 months of age)
- Oxidative stress markers(multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age))
- Humoral and cellular immune responses(multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age))
- Host genetics(2.5 months of age)