The project outlined here seeks to identify robust biomarkers of functional immunity to malaria, In endemic areas where differing transmission intensities have been noted. We anticipate that sustained, intensified control of malaria using long-lasting Insecticide Impregnated bed nets (LLINs) and Improved access to parasitological diagnosis and treatment with artemisinin combination therapy (ACT) will result In significantly lower levels of immune biomarkers, thus corresponding to a loss of parasitological and clinical Immunity. A major controlling force that determines the incidence and prevalence of malaria Infection and disease in endemic areas is the parasitological and clinical Immunity collectively refen'ed to as naturally acquired Immunity (NAI). Generally, NAI determines not only the age-speciflc Incidence and prevalence of P. falciparum (Pf) and P. vivax (Pv) infection, but also the expression of pathological processes that underlie the clinical manifestations of Infection. Improved understanding ofthe development and maintenance of NAI and the ability to cope with the severe manifestations of malaria are now particulariy Important, since effective public health interventions that reduce transmission are being deployed. With effective control measures NAI may be lost, resulting in an increased proportion of Individuals becoming susceptible should malaria be re-introduced to the population. This is especially Important in countries that border those where effective control has not been successfully maintained. Although absolute in vitro correlates of protection to malaria are unknown, consensus has emerged that there are specific biomarkers of immunity. These include elevated levels of serum antibodies directed at merozoite antigens (particulariy Invasion ligands) and/or variant surface antigen (VSA) on Infected erythrocytes, as well as robust lymphocyte proliferation and IFNy responses to blood-stage antigens. This study alms to address significant gaps in our knowledge of NAI mechanisms In malaria, with a focus to better understand what immune biomarkers signify NAI, and how measures of cellular and humoral Immunity evolve differentially according to age in populations. This study also alms to examine of the role of malaria transmission on NAI, and how reduction of malaria transmission by universal deployment of LLINs and ACT will affect NAI and Its duration.
With a global effort to control or eliminate malaria in many endemic areas of the worid, knowledge of the underiying mechanisms and biomarkers of naturally acquired Immunity will be invaluable In the design and evaluation of additional tools that prevent and treat malaria-related Illness, most especially In constructing vaccines that ultimately eliminate the disease.
|Kurtovic, Liriye; Behet, Marije C; Feng, Gaoqian et al. (2018) Human antibodies activate complement against Plasmodium falciparum sporozoites, and are associated with protection against malaria in children. BMC Med 16:61|
|Koepfli, Cristian; Waltmann, Andreea; Ome-Kaius, Maria et al. (2018) Multiplicity of Infection Is a Poor Predictor of Village-Level Plasmodium vivax and P. falciparum Population Prevalence in the Southwest Pacific. Open Forum Infect Dis 5:ofy240|
|Liu, Eugene W; Skinner, Jeff; Tran, Tuan M et al. (2018) Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens. Am J Trop Med Hyg 98:57-66|
|Nakajima, Rie; Supnet, Medalyn; Jasinskas, Algis et al. (2018) Protein Microarray Analysis of the Specificity and Cross-Reactivity of Influenza Virus Hemagglutinin-Specific Antibodies. mSphere 3:|
|Waltmann, Andreea; Koepfli, Cristian; Tessier, Natacha et al. (2018) Increasingly inbred and fragmented populations of Plasmodium vivax associated with the eastward decline in malaria transmission across the Southwest Pacific. PLoS Negl Trop Dis 12:e0006146|
|Koimbu, Gussy; Czeher, Cyrille; Katusele, Michelle et al. (2018) Status of Insecticide Resistance in Papua New Guinea: An Update from Nation-Wide Monitoring of Anopheles Mosquitoes. Am J Trop Med Hyg 98:162-165|
|White, Michael T; Karl, Stephan; Koepfli, Cristian et al. (2018) Plasmodium vivax and Plasmodium falciparum infection dynamics: re-infections, recrudescences and relapses. Malar J 17:170|
|Hofmann, Natalie E; Karl, Stephan; Wampfler, Rahel et al. (2017) The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea. Elife 6:|
|França, Camila Tenorio; White, Michael T; He, Wen-Qiang et al. (2017) Identification of highly-protective combinations of Plasmodium vivax recombinant proteins for vaccine development. Elife 6:|
|França, Camila T; Li Wai Suen, Connie S N; Carmagnac, Amandine et al. (2017) IgG antibodies to synthetic GPI are biomarkers of immune-status to both Plasmodium falciparum and Plasmodium vivax malaria in young children. Malar J 16:386|
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