Low-level Plasmodium vivax exposure, maternal antibodies, and anemia in early childhood: Population-based birth cohort study in Amazonian Brazil

Author(s)

Pincelli, Anaclara ^[1] ; Cardoso, Marly A. ^[2] ; Malta, Maira B. ^{[2, 3]} ; Johansen, Igor C. ^[1] ; Corder, Rodrigo M. ^[1] ; Nicolete, Vanessa C. ^[1] ; Soares, Irene S. ^[4] ; Castro, Marcia C. ^[5] ; Ferreira, Marcelo U. ^[1] ; Grp, MINA-Brazil Study Working

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Parasitol, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Publ Hlth, Dept Nutr, Sao Paulo - Brazil

^[3] Univ Catolica Santos, Grad Program Collect Hlth, Santos, SP - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[5] Harvard TH Chan Sch Publ Hlth, Dept Global Hlth & Populat, Boston, MA - USA

• Document type: Journal article
• Source: PLoS Neglected Tropical Diseases; v. 15, n. 7 JUL 2021.
• Web of Science Citations: 0

Abstract

Background Malaria causes significant morbidity and mortality in children under 5 years of age in sub-Saharan Africa and the Asia-Pacific region. Neonates and young infants remain relatively protected from clinical disease and the transplacental transfer of maternal antibodies is hypothesized as one of the protective factors. The adverse health effects of Plasmodium vivax malaria in early childhood-traditionally viewed as a benign infection-remain largely neglected in relatively low-endemicity settings across the Amazon. Methodology/Principal findings Overall, 1,539 children participating in a birth cohort study in the main transmission hotspot of Amazonian Brazil had a questionnaire administered, and blood sampled at the two-year follow-up visit. Only 7.1% of them experienced malaria confirmed by microscopy during their first 2 years of life- 89.1% of the infections were caused by P. vivax. Young infants appear to be little exposed to, or largely protected from infection, but children >12 months of age become as vulnerable to vivax malaria as their mothers. Few (1.4%) children experienced >= 4 infections during the 2-year follow-up, accounting for 43.4% of the overall malaria burden among study participants. Antenatal malaria diagnosed by microscopy during pregnancy or by PCR at delivery emerged as a significant correlate of subsequent risk of P. vivax infection in the offspring (incidence rate ratio, 2.58; P = 0.002), after adjusting for local transmission intensity. Anti-P. vivax antibodies measured at delivery do not protect mothers from subsequent malaria; whether maternal antibodies transferred to the fetus reduce early malaria risk in children remains undetermined. Finally, recent and repeated vivax malaria episodes in early childhood are associated with increased risk of anemia at the age of 2 years in this relatively low-endemicity setting. Conclusions/Significance Antenatal infection increases the risk of vivax malaria in the offspring and repeated childhood P. vivax infections are associated with anemia at the age of 2 years. Author summary Plasmodium vivax malaria causes frequent hospital admissions of infants and toddlers in areas of intense transmission in the Asia-Pacific region, often due to severe anemia, but its epidemiology and burden have been understudied in children from other endemic settings. Here we characterize the cumulative impact of P. vivax infections in infants and toddlers exposed to relatively low levels of malaria transmission in the Brazilian Amazon. We have previously shown that vivax malaria in pregnancy is associated with increased risk of maternal anemia and impaired fetal growth in this population. Now we show that the adverse effects of malaria extend to early childhood. Children born to mothers who had one or more infections during pregnancy are at an elevated risk of P. vivax malaria in their early life, although the transfer of maternal antibodies to the fetus may provide some short-term protection. Children who are repeatedly infected with P. vivax since birth are more likely to be anemic at the age of 2 years. These findings further challenge the traditional view of vivax malaria as a relatively benign infection in pregnancy and early childhood in the Amazon. (AU)

• FAPESP's process: 16/00270-6 - MINA study - Maternal and child health in Acre: birth cohort in the Western Brazilian Amazon
• Grantee: Marly Augusto Cardoso
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 17/05019-2 - Longitudinal analysis of childhood growth determinants in early childhood in Cruzeiro do Sul, state of Acre
• Grantee: Maíra Barreto Malta
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/18557-5 - Maternal IgG antibodies and protection against clinical Vivax Malaria in the first year of life
• Grantee: Anaclara Pincelli Cintra
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/07020-0 - Tracking the community-wide spread of SARS-CoV-2: outbreak size, transmission dynamics, clinical outcomes of infection, and duration of naturally acquired antibody responses in an Amazonian town
• Grantee: Vanessa Cristina Nicolete
• Support Opportunities: Scholarships in Brazil - Post-Doctoral