Age of Exposure and Immunity to Malaria in Infants

October 27, 2011 updated by: Hospital Clinic of Barcelona

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

349

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mozambique
    • Maputo
      • Manhiça, Maputo, Mozambique, 1929
        • Centro de Investigação em Saude da Manhiça

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 1 week (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
Monthly chemoprophylaxis with SP (Fansidar® 500/25 mg) plus Artesunate (AS, Arsumax® 50 mg) or placebo (provided by Roche and Sanofi-Aventis) was administered according to the following age-based dosing schedule: ½ tablet of SP or placebo and ½ tablet of AS or placebo on the first day and ½ tablet of AS or placebo on the second and third days.
Experimental: 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.
Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
Monthly chemoprophylaxis with SP (Fansidar® 500/25 mg) plus Artesunate (AS, Arsumax® 50 mg) or placebo (provided by Roche and Sanofi-Aventis) was administered according to the following age-based dosing schedule: ½ tablet of SP or placebo and ½ tablet of AS or placebo on the first day and ½ tablet of AS or placebo on the second and third days.
Placebo Comparator: Control group
Participants received monthly placebo from 2.5 to 9.5 months of age.
Drug: Sulfadoxine-pyrimethamine (SP) + Artesunate (AS)
Monthly chemoprophylaxis with SP (Fansidar® 500/25 mg) plus Artesunate (AS, Arsumax® 50 mg) or placebo (provided by Roche and Sanofi-Aventis) was administered according to the following age-based dosing schedule: ½ tablet of SP or placebo and ½ tablet of AS or placebo on the first day and ½ tablet of AS or placebo on the second and third days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
(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.
from 12 to 24 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
(Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints.
Time Frame: 12 to 24 months of age
Global comparison between the 3 study groups of the time to first or only episode of clinical malaria (according to the secondary case definitions) in the second year of follow up detected by passive case detection. Other endpoints include multiple episodes of malaria, time to first or only episode of anaemia, total hospital visits and prevalence of parasitaemia and anaemia at different time points. In addition, pairwise comparisons of the 3 groups are also presented.
12 to 24 months of age
Oxidative stress markers
Time Frame: multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)
Quantification of the antioxidant/pro-oxidant status over the first two years of life in relation to age of first exposure to infection.
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
Time Frame: multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)
Quantification of antibody and cytokine responses to P. falciparum protein antigens and toxins over the first two years of life in relation to age of first exposure to infection
multiple time points during the first two years of life (2.5, 5.5, 10.5, 15 and 24 months of age)
Host genetics
Time Frame: 2.5 months of age
Analysis of haematological genetic factors, polymorphisms in genes involved in inflammatory or immunological responses to malaria and polymorphisms in genes involved in the Th1/Th2 immunological pathway.
2.5 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospital Clinic of Barcelona

Collaborators

European Commission

Investigators

  • Principal Investigator: Pedro Alonso, MD, PhD, Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona
  • Principal Investigator: Carlota Dobaño, PhD, Barcelona Center for International Health Research, Hospital Clinic/University of Barcelona

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2005

Primary Completion (Actual)

March 1, 2009

Study Completion (Actual)

March 1, 2009

Study Registration Dates

First Submitted

September 30, 2005

First Submitted That Met QC Criteria

September 30, 2005

First Posted (Estimate)

October 4, 2005

Study Record Updates

Last Update Posted (Estimate)

October 28, 2011

Last Update Submitted That Met QC Criteria

October 27, 2011

Last Verified

October 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AgeMal

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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