Clinical trial NCT00231452: Age of Exposure and Immunity to Malaria in Infants
Official title: Age of Exposure and Immunity to Malaria in Infants
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Malaria
Keywords: natural acquired immunity,
clinical malaria,
P. falciparum,
age,
exposure,
neonatal immunology,
infants
Lead sponsor: Hospital Clinic of Barcelona
Sponsor class: OTHER
Collaborators: name: European Commission
First posted: 2005-10-04
Enrollment: 349
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL

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.


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;
* Same gender Twins;
* Low birth weight (\<2 kg).

Primary outcomes:
measure: (Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection
timeFrame: from 12 to 24 months of age
Secondary outcomes:
measure: (Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints.
timeFrame: 12 to 24 months of age
measure: Oxidative stress markers
timeFrame: multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)
measure: Humoral and cellular immune responses
timeFrame: multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)
measure: Host genetics
timeFrame: 2.5 months of age
Other outcomes:
Locations:
city: Manhiça
country: Mozambique
facility: Centro de Investigaçao em Saude da Manhiça
state: Maputo
Study officials:
affiliation: Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona
name: Pedro Alonso, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona
name: Carlota Dobaño, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dobano C, Nhabomba AJ, Manaca MN, Berthoud T, Aguilar R, Quinto L, Barbosa A, Rodriguez MH, Jimenez A, Groves PL, Santano R, Bassat Q, Aponte JJ, Guinovart C, Doolan DL, Alonso PL. A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria. Clin Infect Dis. 2019 Aug 16;69(5):820-828. doi: 10.1093/cid/ciy934.
citation: Nhabomba AJ, Guinovart C, Jimenez A, Manaca MN, Quinto L, Cistero P, Aguilar R, Barbosa A, Rodriguez MH, Bassat Q, Aponte JJ, Mayor A, Chitnis CE, Alonso PL, Dobano C. Impact of age of first exposure to Plasmodium falciparum on antibody responses to malaria in children: a randomized, controlled trial in Mozambique. Malar J. 2014 Mar 27;13:121. doi: 10.1186/1475-2875-13-121.
citation: Guinovart C, Dobano C, Bassat Q, Nhabomba A, Quinto L, Manaca MN, Aguilar R, Rodriguez MH, Barbosa A, Aponte JJ, Mayor AG, Renom M, Moraleda C, Roberts DJ, Schwarzer E, Le Souef PN, Schofield L, Chitnis CE, Doolan DL, Alonso PL. The role of age and exposure to Plasmodium falciparum in the rate of acquisition of naturally acquired immunity: a randomized controlled trial. PLoS One. 2012;7(3):e32362. doi: 10.1371/journal.pone.0032362. Epub 2012 Mar 7.