Current Organisation

Institut Pasteur de Dakar

Current Job Title

Researcher and Principal Investigator

Biography

Project Title

Mobile nucleic acid testing of asymptomatic Plasmodium infections for malaria elimination

EDCTP Project Call

Senior Fellowship (SF)

Host Organisation

Project Objectives

To apply a field deployable and innovative sample-in-answer-out nucleic acid testing (AnyMDx) combined with multidisciplinary approaches to accompany a strategic active community-based intervention towards malaria elimination in two rural areas in Senegal. 1.2. Specific Our proposal will aim To assess the performances (sensitivity, specificity, reproducibility, and limits of detection) of AnyMDx diagnostic in laboratory conditions compared to qPCR reference test. To deploy AnyMDx in field settings for screening of asymptomatic Plasmodium infections in support of a Mass Screening And Test (MSAT) intervention strategy To track Plasmodium infections and measure exposure to mosquitoes following MSAT intervention To investigate the genetic make-up of remaining parasite populations by using in-depth genomic analysis of asymptomatic and clinical Plasmodium parasites To reinforce the fellow’s capacity toward independent leadership and build new capacities towards a critical mass of scientific leaders in Sub-Saharan Africa. Overview of workplan (1500 words) The current proposal aims to apply an innovative handheld and mobile malaria molecular diagnostic system (AnyMDx) for a community-based screening of low-density asymptomatic Plasmodium-infections in support of a malaria elimination intervention in low transmission settings in Senegal. The proposed project will combine laboratory and field -based investigations, multidisciplinary approaches, and interinstitutional collaborations to assess the operational performances of AnyMDx to guide a malaria elimination intervention in highly relevant low-malaria transmission areas (Dielmo and Ndiop, Sénégal).

Study Design

2.2.1. Study design and approaches Study sites and relevance. The field study will take place in Dielmo and Ndiop villages, two extensively described malaria endemic areas situated in the region of Fatick (Senegal) where longitudinal studies on determinants of malaria infections have been conducted since 1990 and 1993, respectively (40-42), thanks to the long-term collaboration between Institute Pasteur of Dakar (IPD), Institute for Research and Development (IRD) and the Ministry of Health of Senegal. The type of 24h/7days follow-up with a collection of demographic, clinical, parasitological, immunogenetic and entomological data helped to identify parameters associated with malaria infections (42). To identify all episodes of morbidity, all the villagers are put under daily medical surveillance. Globally, the control measures implemented have led to a dramatic decrease of malaria cases that evolved from 771 malaria attacks in 2000 to 17 malaria attacks in 2012 in Dielmo (42). This multidisciplinary approach rendered Dielmo and Ndiop villages true malaria observatories that allow real time assessment of implemented strategy and makes them suitable settings for novel technology assessment. However, highly sensitive diagnostics and innovative approaches are needed to detect the remaining residual cases that signed the existence of residual transmission. Thanks to the continuous support of IPD and IRD, at least one nurse and two medical field workers are permanently present in the village 24 hours a day, seven days a week. This would substantially facilitate the field deployment and contribute to the success of the project. Study population. The study population will include all villagers including febrile individuals participating in the Dielmo and Ndiop cohort studies and who are present in the villages during the study periods. The current project will integrate ongoing activities in Dielmo and Ndiop, thus no additional sampling will be necessary for the purpose

Project Summary

Increased international malaria control efforts have resulted in dramatic reduction in the global malaria incidence over the past decade. In some places, the efficiency of control measures has led to the thought that elimination could be obtained; in line with the ambitious goal of achieving worldwide malaria elimination endorsed by the World Health Organization. As the global public health objectives for malaria has evolved from control towards elimination, there is an increasing interest in the significance of asymptomatic infections and the optimal diagnostic test to identify and treat them. Current field diagnostics rely almost exclusively on microscopy and rapid diagnostic tests. While they perform sufficiently well for diagnosing patients with acute symptomatic malaria, both methods could miss significant proportions of asymptomatic parasite carriers due to their detection limit of ~50 parasites/μl. In response to the strong desire and urgent needs to develop field-deployable sensitive malaria diagnosis, a promising, highly sensitive, user-friendly and cost-effective "sample-in-answer-out" portable malaria molecular diagnostic system known as AnyMDx was recently developed. The proposed technology significantly simplifies the complex nucleic acid testing and offers low-cost and accurate diagnosis in a quick and automatic fashion, thus putting the power of a full diagnostic laboratory into the palms of healthcare workers’s hands. In a previous study conducted in Dielmo and Ndiop villages in Senegal, we revealed substantial submicroscopic Plasmodium carriage among asymptomatic individuals using laboratory-based qPCR approach with average prevalence of 7.6% and 9.52% in Dielmo and Ndiop, respectively. The spatio-temporal mapping of asymptomatic and clinical malaria infections in both villages revealed that 98% of clinical malaria attacks occured in households where an asymptomatic case existed. Moreover, we found no statistically significant association between asymptomatic carriage and the risk of developing subsequent clinical malaria episode at individual level althought a significantly risk of having an episode of clinical malaria was associated with asymptomatic Plasmodium infection at household level. Together, these strong scientific-based evidences are in favor of the likely success of a Mass Screening and Testing intervention for malaria elimination. In this context, the current proposal aims to apply multidisciplinary field and laboratory-based approaches along with a field-deployable innovative mobile nucleic acid testing to accompany a strategic community-based intervention towards malaria elimination in Dielmo and Ndiop villages. The proposal will also extensively contribute to professional development leadership for the fellow and to build new capacities in research through the training and mentorship of graduate students and postdoctoral fellows.