Age of Exposure and Immunity to Malaria in Infants

Conditions

Malaria

Keywords

natural acquired immunity,, clinical malaria,, P. falciparum,, age,, exposure,, neonatal immunology,, infants

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.

Ariff A, Song Y, Aguilar R, Nhabomba A, Manaca MN, Khoo SK, Wiertsema S, Bassat Q, Barbosa A, Quintó L, Laing IA, Guinovart C, Alonso PL, Dobaño C, Le Souëf P, Zhang G.

2023-06-071 citations

10.1186/s12936-023-04549-8

A Balanced Proinflammatory and Regulatory Cytokine Signature in Young African Children Is Associated With Lower Risk of Clinical Malaria

Carlota Dobaño, Augusto Nhabomba, Maria Nélia Manaca, Tamara Berthoud, Ruth Aguilar et al. (16 authors)

Clinical Infectious Diseases2018-10-3013 citations

10.1093/cid/ciy934

Impact of age of first exposure to Plasmodium falciparum on antibody responses to malaria in children: a randomized, controlled trial in Mozambique

Augusto Nhabomba, Caterina Guinovart, Alfons Jiménez, Maria Nélia Manaca, Llorenç Quintó et al. (15 authors)

Malaria Journal2014-03-2723 citations

10.1186/1475-2875-13-121

The role of age and exposure to Plasmodium falciparum in the rate of acquisition of naturally acquired immunity: a randomized controlled trial.

Guinovart C, Dobaño C, Bassat Q, Nhabomba A, Quintó L, Manaca MN, Aguilar R, Rodríguez MH, Barbosa A, Aponte JJ, Mayor AG, Renom M, Moraleda C, Roberts DJ, Schwarzer E, Le Souëf PN, Schofield L, Chitnis CE, Doolan DL, Alonso PL.

2012-03-0733 citations

10.1371/journal.pone.0032362

Interventions

DRUGSulfadoxine-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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

No minimum to 1 Weeks

Healthy volunteers

Yes

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.

Design outcomes

Primary

Measure	Time frame	Description
(Clinical) Time to first or only episode of clinical malaria in the second year of life detected by passive case detection	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

Measure	Time frame	Description
(Clinical) Time to first or only episode of malaria (using other case definitions), anaemia and other clinical endpoints.	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.
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)	Quantification of the antioxidant/pro-oxidant status over the first two years of life in relation to age of first exposure to infection.
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)	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
Host genetics	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.

Countries

Mozambique

Outcome results

None listed