Malaria Resilience in South America: Epidemiology, Vector Biology, and Immunology Insights from the Amazonian International Center of Excellence in Malaria Research Network in Peru and Brazil

Abstract

The 1990s saw the rapid reemergence of malaria in Amazonia, where it remains an important public health priority in South America. The Amazonian International Center of Excellence in Malaria Research (ICEMR) was designed to take a multidisciplinary approach toward identifying novel malaria control and elimination strategies. Based on geographically and epidemiologically distinct sites in the Northeastern Peruvian and Western Brazilian Amazon regions, synergistic projects integrate malaria epidemiology, vector biology, and immunology. The Amazonian ICEMR's overarching goal is to understand how human behavior and other sociodemographic features of human reservoirs of transmission-predominantly asymptomatically parasitemic people-interact with the major Amazonian malaria vector, Nyssorhynchus (formerly Anopheles) darlingi, and with human immune responses to maintain malaria resilience and continued endemicity in a hypoendemic setting. Here, we will review Amazonian ICEMR's achievements on the synergies among malaria epidemiology, Plasmodium-vector interactions, and immune response, and how those provide a roadmap for further research, and, most importantly, point toward how to achieve malaria control and elimination in the Americas.

Figure 1.

Amazonian International Center of Excellence in Malaria Research (ICEMR) Program Organization. The Amazonian ICEMR focuses on three approaches to understanding malaria transmission. The project seeks to comprehend malaria epidemiology and diagnostics in highly heterogeneous sites in the Amazon (Project 1), vector biology, ecology and genetics of local vectors (Project 2), and the transmission biology, clinical pathogenesis, and asymptomatic malaria immunology (Project 3). The integration from these projects grants the basis for mathematical modeling to understand the disease dynamics and design effective public health interventions for malaria control and elimination. The ICEMR receives support from Core A (Administration) and Core B (Data Management and Biostatistics). This figure appears in color at www.ajtmh.org.

Figure 2.

Drone imagery for the detection of Nyssorhynchus darlingi breeding sites. In recent years, unnamed aerial vehicles (UAVs) have become feasible tools for vector disease monitoring. (A) An UAV or drone employing multispectral cameras to collect aerial images from a rural riverine community in the Peruvian Amazon. (B) An image of a flooded area located in the Santa Rita village, within the district of Iquitos in the Amazonian region of Loreto, Peru. Later on, image analysis will be used to determine the presence and location of possible Ny. darlingi breeding sites. This figure is open access and permission to reuse it is through Creative Commons.

Figure 3.

Immune response against Plasmodium vivax infection. Monocytes, neutrophils, and CD8⁺ T cells mediate parasite killing through production of mitochondrial reactive oxygen species (mROS), SOD, and cytotoxic granules, respectively. Parasite killing by monocyte is antibody dependent. Cytokines produced by innate cells and act on cells from adaptive immune response, shaping effector functions of CD4⁺ T helper cells and Treg. Parasite burden and cytokines are associated with symptoms and trigger the expression of chemokines, chemokine receptors and activation and inhibitory molecules. The production of IFN-gamma is probably affected by this environment. The IL-21 is also induced by P. vivax infection, leading to T follicular helper (Tfh) expansion and it is associated with antibody production by plasma cells. The number of malaria episodes are associated with increased frequencies of Tfh cells and classical memory B cells, probably impacting protection.