interventions ; malaria; reservoir of infection; genotyping ; gametocytes; molecular epidemiology; molecular monitoring; malaria elimination; infection dynamics
Lerch Anita, Koepfli Cristian, Hofmann Natalie E., Kattenberg Johanna H., Rosanas-Urgell Anna, Betuela Inoni, Mueller Ivo, Felger Ingrid (2019), Longitudinal tracking and quantification of individual Plasmodium falciparum clones in complex infections, in Scientific Reports
, 9(1), 3333-3333.
Gruenberg Maria, Moniz Clara Antunes, Hofmann Natalie Ellen, Wampfler Rahel, Koepfli Cristian, Mueller Ivo, Monteiro Wuelton Marcelo, Lacerda Marcus, de Melo Gisely Cardoso, Kuehn Andrea, Siqueira Andre M., Felger Ingrid (2018), Plasmodium vivax molecular diagnostics in community surveys: pitfalls and solutions, in Malaria Journal
, 17(1), 55-55.
Hofmann Natalie E, Gruenberg Maria, Nate Elma, Ura Alice, Rodriguez-Rodriguez Daniela, Salib Mary, Mueller Ivo, Smith Thomas A, Laman Moses, Robinson Leanne J, Felger Ingrid (2018), Assessment of ultra-sensitive malaria diagnosis versus standard molecular diagnostics for malaria elimination: an in-depth molecular community cross-sectional study, in The Lancet Infectious Diseases
, 18(10), 1108-1116.
Lerch Anita, Koepfli Cristian, Hofmann Natalie E., Messerli Camilla, Wilcox Stephen, Kattenberg Johanna H., Betuela Inoni, O’Connor Liam, Mueller Ivo, Felger Ingrid (2017), Development of amplicon deep sequencing markers and data analysis pipeline for genotyping multi-clonal malaria infections, in BMC Genomics
, 18(1), 864-864.
Hofmann Natalie E, Karl Stephan, Wampfler Rahel, Kiniboro Benson, Teliki Albina, Iga Jonah, Waltmann Andreea, Betuela Inoni, Felger Ingrid, Robinson Leanne J, Mueller Ivo (2017), The complex relationship of exposure to new Plasmodium infections and incidence of clinical malaria in Papua New Guinea, in eLife
, 6, e23708.
Plasmodium parasites from symptomatic individuals are relatively easy to diagnose owing to high densities and they usually get cleared by treatment. But most malaria infections even in low endemic areas are asymptomatic and often undetectable by microscopy due to low parasite densities. They remain uncured but may contribute substantially to transmission. Since the recent paradigm shift from malaria control to elimination, major efforts are undertaken worldwide to intensify control and interrupt local transmission of malaria. As in most areas it is not feasible to eliminate the mosquito vector, the road to elimination thus entails identifying and treating all infected individuals irrespective of symptoms. Yet, a major hurdle for successful control is detection of very low density infections. The currently used molecular methods are more sensitive, but still imperfect in detecting ultra-low parasitaemias. The extent of ultra-low density infections represents a major research gap, which we will address in this proposal. Aims: We propose to develop ultra-sensitive methods for detection of Plasmodium falciparum and P. vivax to investigate the magnitude of infections that are not detected by both, microscopy and standard PCR. These new assays will be validated for ultra-sensitive parasite detection in malaria surveillance and monitoring of interventions. A secondary objective is to investigate the contribution of the ultra-low density infections to transmission. The specific objectives are: ¦ To measure the proportion of parasites missed by microscopy and standard PCR in field surveys. ¦ To examine how host age and levels of malaria endemicity influence this proportion. ¦ To determine whether ultra-low density infections carry gametocytes and estimate their contribution to the human reservoir of infection to mosquitoes. ¦ To find ways to increase the sensitivity of parasite detection in large scale field surveys. Approach: Ultra-sensitive nucleic acid based detection methods for P. falciparum and P. vivax will be developed by targeting highly repetitive DNA markers and highly expressed stage-specific transcripts. Ultra-low density infections will be studied in different endemic settings and age groups, For P. vivax we compare PNG (high transmission), Thailand (low transmission) and Brazil (close to elimination), for P. falciparum 4 regions in Tanzania differing in endemicity. Gametocyte detection and genotyping in both species will be used for estimating the transmission potential and trans-mission dynamics. The transcriptome of P. vivax gametocytes will be mined to develop new assays for determination of sex ratios and new highly sensitive assays for genotyping P. vivax gametocytes. Expected outcomes: ¦ Basic epidemiological knowledge on so-far undetectable malaria infections gained from endemic areas world-wide. In the context of malaria elimination this information is a key priority. ¦ Improved sensitivity of malaria diagnosis on population level suitable for surveillance and assessing the impact of interventions and more accurate data for modeling infection dynamics.¦ Demonstrating that ultra-low density infections either do or do not contribute to the infectious reservoir will inform surveillance strategies and treatment policies. Results should assist policy makers in deciding on approaches to malaria control and elimination, i.e. mass treatment campaigns to clear all potential infections versus targeted treatment following diagnostic screening.