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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI089686-03
Application #
8378154
Study Section
Special Emphasis Panel (ZAI1-AWA-M)
Project Start
Project End
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
3
Fiscal Year
2012
Total Cost
$224,056
Indirect Cost
$53,109
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Lerch, Anita; Koepfli, Cristian; Hofmann, Natalie E et al. (2017) Development of amplicon deep sequencing markers and data analysis pipeline for genotyping multi-clonal malaria infections. BMC Genomics 18:864
Messerli, Camilla; Hofmann, Natalie E; Beck, Hans-Peter et al. (2017) Critical Evaluation of Molecular Monitoring in Malaria Drug Efficacy Trials and Pitfalls of Length-Polymorphic Markers. Antimicrob Agents Chemother 61:
Fran├ža, 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
Schofield, Louis; Ioannidis, Lisa J; Karl, Stephan et al. (2017) Synergistic effect of IL-12 and IL-18 induces TIM3 regulation of ?? T cell function and decreases the risk of clinical malaria in children living in Papua New Guinea. BMC Med 15:114
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:
Jain, Aarti; Taghavian, Omid; Vallejo, Derek et al. (2016) Evaluation of quantum dot immunofluorescence and a digital CMOS imaging system as an alternative to conventional organic fluorescence dyes and laser scanning for quantifying protein microarrays. Proteomics 16:1271-9
Hupalo, Daniel N; Luo, Zunping; Melnikov, Alexandre et al. (2016) Population genomics studies identify signatures of global dispersal and drug resistance in Plasmodium vivax. Nat Genet 48:953-8
Koepfli, Cristian; Nguitragool, Wang; Hofmann, Natalie E et al. (2016) Sensitive and accurate quantification of human malaria parasites using droplet digital PCR (ddPCR). Sci Rep 6:39183
Guo, Suqin; He, Lishan; Tisch, Daniel J et al. (2016) Pilot testing of dipsticks as point-of-care assays for rapid diagnosis of poor-quality artemisinin drugs in endemic settings. Trop Med Health 44:15
de Assis, Rafael Ramiro; Ludolf, Fernanda; Nakajima, Rie et al. (2016) A next-generation proteome array for Schistosoma mansoni. Int J Parasitol 46:411-5

Showing the most recent 10 out of 69 publications