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

Augusto J Nhabomba1*, Caterina Guinovart123, Alfons Jiménez23, Maria N Manaca1, Llorenç Quintó23, Pau Cisteró2, Ruth Aguilar123, Arnoldo Barbosa1, Mauricio H Rodríguez1, Quique Bassat123, John J Aponte123, Alfredo Mayor123, Chetan E Chitnis4, Pedro L Alonso123 and Carlota Dobaño123*

Author Affiliations

1 Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique

2 Barcelona Centre for International Health Research (CRESIB, Hospital Clínic - Universitat de Barcelona), Barcelona, Catalonia, Spain

3 CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain

4 International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India

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Malaria Journal 2014, 13:121  doi:10.1186/1475-2875-13-121

Published: 27 March 2014



The impact of the age of first Plasmodium falciparum infection on the rate of acquisition of immunity to malaria and on the immune correlates of protection has proven difficult to elucidate. A randomized, double-blind, placebo-controlled trial using monthly chemoprophylaxis with sulphadoxine-pyrimethamine plus artesunate was conducted to modify the age of first P. falciparum erythrocytic exposure in infancy and assess antibodies and malaria risk over two years.


Participants (n = 349) were enrolled at birth to one of three groups: late exposure, early exposure and control group, and were followed up for malaria morbidity and immunological analyses at birth, 2.5, 5.5, 10.5, 15 and 24 months of age. Total IgG, IgG subclasses and IgM responses to MSP-119, AMA-1, and EBA-175 were measured by ELISA, and IgG against variant antigens on the surface of infected erythrocytes by flow cytometry. Factors affecting antibody responses in relation to chemoprophylaxis and malaria incidence were evaluated.


Generally, antibody responses did not vary significantly between exposure groups except for levels of IgM to EBA-175, and seropositivity of IgG1 and IgG3 to MSP-119. Previous and current malaria infections were strongly associated with increased IgG against MSP-119, EBA-175 and AMA-1 (p < 0.0001). After adjusting for exposure, only higher levels of anti-EBA-175 IgG were significantly associated with reduced clinical malaria incidence (IRR 0.67, p = 0.0178).


Overall, the age of first P. falciparum infection did not influence the magnitude and breadth of IgG responses, but previous exposure was critical for antibody acquisition. IgG responses to EBA-175 were the strongest correlate of protection against clinical malaria.

Trial registration NCT00231452.

Malaria; Antibodies; Acquired immunity; Age; Exposure; Plasmodium falciparum