Children repeatedly exposed to malaria from birth are more likely to be anemic by the age of two

The conclusion was published by Brazilian researchers in PLOS Neglected Tropical Diseases. They followed 1,539 children in a part of Amazonia that accounts for 18% of infections by Plasmodium vivax in Brazil.

By André Julião  |  Agência FAPESP – According to a study conducted in Cruzeiro do Sul in the state of Acre, North Brazil, babies are relatively protected against malaria in the first year of their lives, but after that infections are more frequent, making infants and toddlers susceptible to anemia, which can impair child development. Cruzeiro do Sul ranks fourth among Brazilian cities for cases of malaria in proportion to the local population.

“The first two years of life are critical for neurological development. Iron deficiency, the main cause of anemia in children, has an irreversible impact on child development. As a result, it also affects human capital and the health of future adolescents and adults in malaria-endemic areas,” said Marly Augusto Cardoso, a professor at the University of São Paulo’s School of Public Health (FSP-USP) in Brazil.

Cardoso was the principal investigator for the study, which was conducted as part of a broader survey supported by FAPESP on maternal and child health and nutrition in Acre (MINA). The findings are published in PLOS Neglected Tropical Diseases.

“This is the first population-based birth cohort study of the western Brazilian Amazon,” Cardoso said. Cohort studies are important to epidemiologists because they record whether participants are exposed to the disease of interest, and then track participants to see if they develop the disease. “The aim was to identify the determinants of maternal and child health in the first 1,000 days of the baby’s life. Besides the problems found in other parts of Brazil and other low- and medium-income countries, Cruzeiro do Sul has the additional health hazard of endemic malaria. We’re investigating the occurrence of other tropical infectious diseases, such as dengue and chikungunya, as well as malaria.”

Cruzeiro do Sul has 89,000 inhabitants and is located on the Peruvian border about 700 km from Rio Branco, the state capital. The number of laboratory-confirmed clinical malaria cases in the city was 231.9 per 1,000 inhabitants in 2016. The Juruá Valley region, to which it belongs, accounts for 18% of malaria cases in Brazil. 

The study followed 1,539 children from birth until they were two years old, covering the period 2015-18. Anemia was detected in 12.6% of 860 children tested for hemoglobin levels at the age of two or thereabouts. None was diagnosed with severe anemia, but the researchers believe the proportion of anemic children is higher in rural areas not covered by the study.

A previous study by the group showed a high prevalence of post-partum maternal anemia (40%) in the same area. The problem is widespread in Brazil and aggravated in women who contract malaria at the start of pregnancy, typically affecting their offspring for life. 

According to the researchers, lower prevalence of malaria in the first year of life may be associated with the transfer of maternal antibodies during pregnancy. However, the study measured only total antibodies in mothers and children, so it is not yet known whether they can actually inhibit infection by the parasite. Special care of newborns, including use of mosquito nets and avoiding transmission by staying at home, could be another explanation for this lower prevalence.

Recurrent episodes

A small number of participants were diagnosed with malaria during the course of the study (7.1%). However, over 40% of the recorded cases were in children who had four or more episodes in the period. Plasmodium vivax, the most prevalent malaria parasite in South America, may remain dormant in the human liver for months so that several episodes of the disease can occur as a result of a single mosquito bite.

“We found that most of the children had no symptoms during their first thousand days, but some infected children became severe cases and suffered from recurring episodes. Some had as many as nine episodes in the first two years of their lives, with a direct impact on anemia and other factors that impair child development,” said Anaclara Pincelli, first author of the article. Pincelli is a PhD candidate at the Biomedical Sciences Institute (ICB-USP). Her thesis advisor is Marcelo Urbano Ferreira, a professor at ICB-USP supported by FAPESP and a co-author of the article. Her master’s research focused on the prevalence of malaria and anemia in the mothers of children included in the study during pregnancy and childbirth.

The study analyzed only clinical cases, in which malaria is diagnosed and treated, Pincelli stressed. The effects of asymptomatic cases are poorly understood. They may have some impact on public health but were not analyzed in the study, which was also confined to patients in the urban area who could be contacted throughout the period. Inhabitants of rural areas, where the incidence of malaria is higher and health service coverage is deficient, are known to account for more cases than the urban population. “The impact of the disease is probably worse than we were able to show,” Pincelli said.

The authors conclude that there is an urgent need for improved malaria prevention strategies during the first 1,000 days of life in endemic areas, including weekly prophylaxis with antimalarials following treatment during pregnancy, and routine malaria screening during antenatal and infant care, as recommended by Brazil’s Ministry of Health.

In 2021, the project was expanded to verify the occurrence of COVID-19 in the cohort, now aged five. Preliminary results for the first 700 children tested have not yet been published, but show that at least 40% have total antibodies against the disease, indicating that they have had contact with SARS-CoV-2.

In this new phase of the study, the researchers will be able to produce even more data for use by policymakers in this and other endemic areas for tropical diseases, as well as obtaining an insight into the links between these diseases and COVID-19.

The article “Low-level Plasmodium vivax exposure, maternal antibodies, and anemia in early childhood: Population-based birth cohort study in Amazonian Brazil” is at: journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0009568.