Study protocol: improving response to malaria in the Amazon through identification of inter-community networks and human mobility in border regions of Ecuador, Peru and Brazil.

INTRODUCTION: Understanding human mobility's role in malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. METHODS: We measure community connectivity across the study area using a respondent driven sampling design among key informants who are at least 18 years of age. 45 initial communities will be selected: 10 in Brazil, 10 in Ecuador and 25 in Peru. Participants will be recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses will be ranked and the 2-3 most connected communities will then be selected and surveyed. This process will be repeated for a third round of data collection. Community network matrices will be linked with each country's malaria surveillance system to test the effects of mobility on disease risk. ETHICS AND DISSEMINATION: This study protocol has been approved by the institutional review boards of Duke University (USA), Universidad San Francisco de Quito (Ecuador), Universidad Peruana Cayetano Heredia (Peru) and Universidade Federal Minas Gerais (Brazil). Results will be disseminated in communities by the end of the study.

Network Profile: Improving Response to Malaria in the Amazon through Identification of Inter-Community Networks and Human Mobility in Border Regions of Ecuador, Peru, and Brazil.

Objectives: Understanding human mobility's role on malaria transmission is critical to successful control and elimination. However, common approaches to measuring mobility are ill-equipped for remote regions such as the Amazon. This study develops a network survey to quantify the effect of community connectivity and mobility on malaria transmission. Design: A community-level network survey. Setting: We collect data on community connectivity along three river systems in the Amazon basin: the Pastaza river corridor spanning the Ecuador-Peru border; and the Amazon and Javari river corridors spanning the Brazil-Peru border. Participants: We interviewed key informants in Brazil, Ecuador, and Peru, including from indigenous communities: Shuar, Achuar, Shiwiar, Kichwa, Ticuna, and Yagua. Key informants are at least 18 years of age and are considered community leaders. Primary outcome: Weekly, community-level malaria incidence during the study period. Methods: We measure community connectivity across the study area using a respondent driven sampling design. Forty-five communities were initially selected: 10 in Brazil, 10 in Ecuador, and 25 in Peru. Participants were recruited in each initial node and administered a survey to obtain data on each community's mobility patterns. Survey responses were ranked and the 2-3 most connected communities were then selected and surveyed. This process was repeated for a third round of data collection. Community network matrices will be linked with eadch country's malaria surveillance system to test the effects of mobility on disease risk. Findings: To date, 586 key informants were surveyed from 126 communities along the Pastaza river corridor. Data collection along the Amazon and Javari river corridors is ongoing. Initial results indicate that network sampling is a superior method to delineate migration flows between communities. Conclusions: Our study provides measures of mobility and connectivity in rural settings where traditional approaches are insufficient, and will allow us to understand mobility's effect on malaria transmission.

The impact of sustained malaria control in the Loreto region of Peru: a retrospective, observational, spatially-varying interrupted time series analysis of the PAMAFRO program.

Background: Although malaria control investments worldwide have resulted in dramatic declines in transmission since 2000, progress has stalled. In the Amazon, malaria resurgence has followed withdrawal of Global Fund support of the Project for Malaria Control in Andean Border Areas (PAMAFRO). We estimate intervention-specific and spatially-explicit effects of the PAMAFRO program on malaria incidence across the Loreto region of Peru, and consider the influence of the environmental risk factors in the presence of interventions. Methods: We conducted a retrospective, observational, spatial interrupted time series analysis of malaria incidence rates among people reporting to health posts across Loreto, Peru between the first epidemiological week of January 2001 and the last epidemiological week of December 2016. Model inference is at the smallest administrative unit (district), where the weekly number of diagnosed cases of Plasmodium vivax and Plasmodium falciparum were determined by microscopy. Census data provided population at risk. We include as covariates weekly estimates of minimum temperature and cumulative precipitation in each district, as well as spatially- and temporally-lagged malaria incidence rates. Environmental data were derived from a hydrometeorological model designed for the Amazon. We used Bayesian spatiotemporal modeling techniques to estimate the impact of the PAMAFRO program, variability in environmental effects, and the role of climate anomalies on transmission after PAMAFRO withdrawal. Findings: During the PAMAFRO program, incidence of P. vivax declined from 42.8 to 10.1 cases/1000 people/year. Incidence for P. falciparum declined from 14.3 to 2.5 cases/1000 people/year over this same period. The effects of PAMAFRO-supported interventions varied both by geography and species of malaria. Interventions were only effective in districts where interventions were also deployed in surrounding districts. Further, interventions diminished the effects of other prevailing demographic and environmental risk factors. Withdrawal of the program led to a resurgence in transmission. Increasing minimum temperatures and variability and intensity of rainfall events from 2011 onward and accompanying population displacements contributed to this resurgence. Interpretation: Malaria control programs must consider the climate and environmental scope of interventions to maximize effectiveness. They must also ensure financial sustainability to maintain local progress and commitment to malaria prevention and elimination efforts, as well as to offset the effects of environmental change that increase transmission risk. Funding: National Aeronautics and Space Administration, National Institutes of Health, Bill and Melinda Gates Foundation.

Plasmodium vivax Landscape in Brazil: Scenario and Challenges.

Brazil is the largest country of Latin America, with a considerable portion of its territoritory within the malaria-endemic Amazon region in the North. Furthermore, a considerable portion of its territory is located within the Amazon region in the north. As a result, Brazil has reported half of the total malaria cases in the Americas in the last four decades. Recent progress in malaria control has been accompanied by an increasing proportion of Plasmodium vivax, underscoring a need for a better understanding of management and control of this species and associated challenges. Among these challenges, the contribution of vivax malaria relapses, earlier production of gametocytes (compared with Plasmodium falciparum), inexistent methods to diagnose hypnozoite carriers, and decreasing efficacy of available antimalarials need to be addressed. Innovative tools, strategies, and technologies are needed to achieve further progress toward sustainable malaria elimination. Further difficulties also arise from dealing with the inherent socioeconomic and environmental particularities of the Amazon region and its dynamic changes.