A Birth Cohort Study

Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.BACKGROUND: Relatively few Amazonian infants have clinical malaria diagnosed, treated and notified before their first birthday, either because they are little exposed to an infection or remain asymptomatic once infected. Here we measure the proportion of children who have experienced Plasmodium vivax infection and malaria by 2 years of age in the main transmission hotspot of Amazonian Brazil. METHODS: We measured IgG antibodies to 3 blood-stage P. vivax antigens at the 1- and 2-year follow-up assessment of 435 participants in a population-based birth cohort. Children's malaria case notifications were retrieved from the electronic database of the Ministry of Health. We used multiple Poisson regression models to identify predictors of serologically proven P. vivax infection and clinical vivax malaria during the first 2 years of life. RESULTS: Overall, 23 [5.3%; 95% confidence interval (CI): 3.5-7.8%) children had antibodies to ≥2 antigens detected during at least one follow-up assessment, consistent with past P. vivax infection(s). Fifteen (3.4%; 95% CI: 2.1-5.6%) children had clinical vivax episodes notified during the first 2 years of life; 7 of them were seronegative. We estimate that half of the infections remained unnotified. Children born to women who experienced P. vivax infection during pregnancy were more likely to be infected and develop clinical vivax malaria, while those breast-fed for ≥12 months had their risk of being P. vivax-seropositive (which we take as evidence of blood-stage P. vivax infection during the first 2 years of life) decreased by 79.8% (95% CI: 69.3-86.7%). CONCLUSION: P. vivax infections in early childhood are underreported in the Amazon, are associated with anemia at 2 years of age, and appear to be partially prevented by prolonged breastfeeding.publishersversionepub_ahead_of_prin

Epidemiology of Disappearing Plasmodium vivax Malaria: A Case Study in Rural Amazonia

Background: New frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings. Methods: Eight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease. Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance

SARS-CoV-2 seropositivity and COVID-19 among 5 years-old Amazonian children and their association with poverty and food insecurity

Background The epidemiology of childhood SARS-CoV-2 infection and COVID-19-related illness remains little studied in high-transmission tropical settings, partly due to the less severe clinical manifestations typically developed by children and the limited availability of diagnostic tests. To address this knowledge gap, we investigate the prevalence and predictors of SARS-CoV-2 infection (either symptomatic or not) and disease in 5 years-old Amazonian children. Methodology/Principal findings We retrospectively estimated SARS-CoV-2 attack rates and the proportion of infections leading to COVID-19-related illness among 660 participants in a population-based birth cohort study in the Juruá Valley, Amazonian Brazil. Children were physically examined, tested for SARS-CoV-2 IgG and IgM antibodies, and had a comprehensive health questionnaire administered during a follow-up visit at the age of 5 years carried out in January or June-July 2021. We found serological evidence of past SARS-CoV-2 infection in 297 (45.0%; 95% confidence interval [CI], 41.2–48.9%) of 660 cohort participants, but only 15 (5.1%; 95% CI, 2.9–8.2%) seropositive children had a prior medical diagnosis of COVID-19 reported by their mothers or guardians. The period prevalence of clinically apparent COVID-19, defined as the presence of specific antibodies plus one or more clinical symptoms suggestive of COVID-19 (cough, shortness of breath, and loss of taste or smell) reported by their mothers or guardians since the pandemic onset, was estimated at 7.3% (95% CI, 5.4–9.5%). Importantly, children from the poorest households and those with less educated mothers were significantly more likely to be seropositive, after controlling for potential confounders by mixed-effects multiple Poisson regression analysis. Likewise, the period prevalence of COVID-19 was 1.8-fold (95%, CI 1.2–2.6-fold) higher among cohort participants exposed to food insecurity and 3.0-fold (95% CI, 2.8–3.5-fold) higher among those born to non-White mothers. Finally, children exposed to household and family contacts who had COVID-19 were at an increased risk of being SARS-CoV-2 seropositive and–even more markedly–of having had clinically apparent COVID-19 by the age of 5 years. Conclusions/Significance Childhood SARS-CoV-2 infection and COVID-19-associated illness are substantially underdiagnosed and underreported in the Amazon. Children in the most socioeconomically vulnerable households are disproportionately affected by SARS-CoV-2 infection and disease. Author summary The epidemiology of childhood COVID-19 in the tropics remains a relatively neglected research topic, in part because SARS-CoV-2 typically causes fewer severe illnesses, hospitalizations, and deaths in children than in adults. Here we show that 45% of 660 participants in a birth cohort study in the Brazilian Amazon had SARS-CoV-2 antibodies at the age of 5 years, although only 5% of them reported previously diagnosed COVID-19 episodes–implying that as many as 8 in 9 SARS-CoV-2 infections had remained undiagnosed in these young children. Only 16% of the seropositive children had reportedly experienced cough, shortness of breath, and/or loss of taste or smell. The most socioeconomically vulnerable participants were more likely to have experienced SARS-CoV-2 infection and overt COVID-19 by the age of 5 years. Importantly, children exposed to household food insecurity, which affects 54% of our study participants, had their COVID-19 risk increased by 76%

Number of malarial infections diagnosed by conventional microscopy (CM) and quantitative real-time PCR (qPCR), according to the presence or absence of malaria-related symptoms, during 8 consecutive cross-sectional surveys in the population of Remansinho, Brazil (2010–13).

<p>Dates of cross-sectional surveys were: survey 1 1, March–May, 2010; survey 2, May–July, 2010; survey 3, October–November, 2010; survey 4, March–April, 2011; survey 5, October–November, 2011; survey 6, April–May, 2012; survey 7, October–November, 2012; survey 8, April–May, 2013. Polyethylene bed-nets treated with 2% permethrin (Olyset Net) were distributed to the entire study population in August, 2012.</p><p>Number of malarial infections diagnosed by conventional microscopy (CM) and quantitative real-time PCR (qPCR), according to the presence or absence of malaria-related symptoms, during 8 consecutive cross-sectional surveys in the population of Remansinho, Brazil (2010–13).</p

Proportion of <i>P.vivax</i> infections diagnosed during 8 consecutive cross-sectional surveys in Remansinho, Brazil, that were symptomatic (black bar segments) and asymptomatic (white bar segments) according to parasite density estimated by quantitative PCR.

<p>The bar widths are proportional to the number of cases within each parasite density class. A total of 129 <i>P. vivax</i> infections were classified according to the presence of symptoms and parasite density.</p

Correlation between length of residence in Amazonia (in years), a proxy of cumulative exposure to malaria, and the probability of having a <i>P. vivax</i> infection (continuous red line) and a clinical vivax malaria episode (continuous black line).

<p>Lines represent median individual probabilities derived from the final (fully adjusted) mixed-effects logistic regression models; the shaded area surrounding the lines represent interquartile ranges.</p

Kaplan-Meier estimates of the proportion of <i>P. vivax</i>-infected (continuous black line) and uninfected (continuous red line) asymptomatic subjects who remained free of slide-confirmed clinical vivax malaria over the follow-up period.

<p>Dashed lines represent the respective 95% confidence intervals. The small vertical tick-marks indicate the occurrence of a slide positive case of <i>P.vivax</i>, corresponding to the right censoring of the individual survival time. A Cox proportional hazards model revealed no significant difference, between the two groups, in overall risk of vivax malaria episodes, after controlling for potential confounders (hazard ratio = 1.07; 95% CI, 0.52–2.22, <i>P</i> = 0.840).</p

Venn diagram showing the proportion of <i>P. vivax</i> infections diagnosed by quantitative PCR during 8 consecutive cross-sectional surveys in Remansinho, Brazil, that were asymptomatic, subpatent (i.e., missed by conventional microscopy) and agametocytemic.

<p>The latter group comprises infections with no <i>pvs25</i> gene transcripts detected by quantitative reverse transcriptase PCR; note that all agametocytemic infections were both asymptomatic and subpatent.</p