Malaria transmission structure in the Peruvian Amazon through antibody signatures to Plasmodium vivax

Abstract

Background The landscape of malaria transmission in the Peruvian Amazon is temporally and spatially heterogeneous, presenting different micro-geographies with particular epidemiologies. Most cases are asymptomatic and escape routine malaria surveillance based on light microscopy (LM). Following the implementation of control programs in this region, new approaches to stratify transmission and direct efforts at an individual and community level are needed. Antibody responses to serological exposure markers (SEM) to Plasmodium vivax have proven diagnostic performance to identify people exposed in the previous 9 months. Methodology We measured antibody responses against 8 SEM to identify recently exposed people and determine the transmission dynamics of P. vivax in peri-urban (Iquitos) and riverine (Mazán) communities of Loreto, communities that have seen significant recent reductions in malaria transmission. Socio-demographic, geo-reference, LM and qPCR diagnosis data were collected from two cross-sectional surveys. Spatial and multilevel analyses were implemented to describe the distribution of seropositive cases and the risk factors associated with exposure to P. vivax. Principal findings Low local transmission was detected by qPCR in both Iquitos (5.3%) and Mazán (2.7%); however, seroprevalence indicated a higher level of (past) exposure to P. vivax in Mazán (56.5%) than Iquitos (38.2%). Age and being male were factors associated with high odds of being seropositive in both sites. Higher antibody levels were found in individuals >15 years old. The persistence of long-lived antibodies in these individuals could overestimate the detection of recent exposure. Antibody levels in younger populations (<15 years old) could be a better indicator of recent exposure to P. vivax. Conclusions The large number of current and past infections detected by SEMs allows for detailed local epidemiological analyses, in contrast to data from qPCR prevalence surveys which did not produce statistically significant associations. Serological surveillance will be increasingly important in the Peruvian Amazon as malaria transmission is reduced by continued control and elimination efforts.

Effect of out-of-village working activities on recent malaria exposure in the Peruvian Amazon using parametric g-formula

“…First, as a cross-sectional, this study is not designed to infer malaria transmission intensity. In this case, the seroprevalence reflects recent exposure to malaria infection (up to 9 months in the past) 31,33 , however no active infection data was used. Despite other studies demonstrating that malaria seroprevalence is a good proxy for malaria transmission intensity 11,60,61 , further longitudinal studies, to deal with potential regressions to the mean issues, are suggested to determine the causal effect on malaria transmission intensity.…”

“…Seropositivity to each marker was defined by using a Random Forests based classification algorithm previously validated in low P. vivax transmission contexts 33 . Further description of the serological makers and the measured structure of the transmission in the area could be found elsewhere 31 .…”

“…We conducted etiological and simulation studies to quantify the role of out-of-village working activities on recent malaria exposure in two population-based cross-sectional studies carried out in the Loreto Department, Peru. The designs of both studies were described elsewhere 31 . Briefly, both studies were conducted by the same research team in different months in 2018.…”

“…A structured questionnaire, georeferencing of households, and blood samples were collected in 10 villages in two districts of Loreto: Iquitos-mostly urbanin April 2018, and Mazán-mostly rural-in July 2018. Here, the-previously reported 31 -seropositivity status of the participants (based on a random forest classifier) was used in combination with a parametric g-formula (see details below) to compute the average causal effect of out-of-village mobility on malaria exposure. In addition, we simulated multiple scenarios of mobility restrictions (by proportion of travelers, gender, and age) to estimate the impact of such restriction policies in reducing malaria exposure in the Peruvian Amazon.…”

Human mobility and malaria risk in peri-urban and rural communities in the Peruvian Amazon

“…Although SNA and connectivity metrics yield no significant differences, geographic-specific characteristics must be considered when assessing their effect on malaria transmission(21,23). We found high heterogeneity in malaria transmission in the Loreto region at the micro-geographical level, with nearby communities having different transmission scenarios (20,21,23,37). Malaria transmission in the Mazan district is more intense than in the Iquitos district [Mean API 2019-2020: 37.93 and 2.95, respectively] (22).…”