Horn of Africa Malaria Molecular Survey (HAMMS project): (funded by Gates Foundation)
The Horn of Africa (HoA) presents a particular problem for malaria control and elimination as all of the major threats – Pfhrp2/3 gene deletions, antimalarial and insecticide resistance and a new malaria vector (Anopheles stephensi) – have converged in this region
The aims of this project are: (i) to build a robust malaria surveillance and response system in the HoA (ii) to conduct parasite genomic surveillance in the HoA (iii) to conduct Anopheles stephensi surveillance in the HoA
This investment fits with the Malaria PST strategy to build regional capacity for MMS in endemic countries under BOW 1.2.2. It builds on our existing investments to the same grantee to to set up a national network for MMS in Ethiopia (INV-035257, ended Sep 2023) and to conduct Pfhrp2/3 deletion surveillance (INV-023730, ends Jan 2024)
The group has been collaborating with national and international partners, with long and productive collaboration with Armeur Hansen Research institute (AHRI) in Ethiopia.
The group is currently participating in Horn of Africa Malaria Molecular Survey (HAMMS), led by AHRI, funded by Bill Gates foundation with our partner the Malaria Control Program at the Federal Ministry of Health, Sudan.
Our focus in this collaboration is to survey HRPS/2 deletions among Plasmodium falciparum parasite in 10 states in Sudan.
Primary results (outcomes and outputs) this project will achieve or significantly contribute to
The historic steady decline in malaria burden has been compromised since 20151. This has been attributed to emerging challenges (see WHO-published malaria threats maps2) including insecticide resistance, parasite histidine rich protein (hrp)2/3 gene deletions, drug resistance, and invasive vectors. Remarkably, these emerging threats have geographically converged in the Horn of Africa (HoA). The best example of the consequences of this convergence is a dry-season malaria outbreak in Dire Dawa, Ethiopia – linked to Anopheles stephensi spreading parasites with pfhrp2/3 gene deletions and drug resistance alleles (R622I) (Tadesse et al., in press, Nat. Med.). In 2023, case incidence increased nationwide in Ethiopia by 153% compared to its baseline in 2021 (week 1-20) (Fig. 1). Enhanced surveillance and rapid mitigation/control is urgently needed in the region. Malaria control and/or elimination strategies are guided by district level stratification, based on annual parasite incidence data3 that lack granularity and is unable to capture relevant spatial and temporal changes and are thus not able to guide tailored response4,5. In this study, by using surveillance as an intervention, we aim to generate regular temporal and spatial evidence on parasite and vector populations supported by improved metrics - malaria molecular surveillance (MMS) - to guide real-time sub-nationally tailored intervention, with parallel monitoring and evaluation.
Primary aim: This proposal intends to establish a university-malaria program network for surveillance of converging biological threats in the Horn of Africa and demonstrate a model for real-time and granular molecular surveillance to inform policy by identifying locally informative genetic targets and adopting and customizing a highly sensitive, targeted, and multiplexed Plasmodium and Anopheles genotyping toolkit.
The challenge: Malaria control and/or elimination strategies are guided by district level stratification, based on annual parasite incidence data. Despite its value, this incidence data-based district level stratification lacks granularity and is unable to capture relevant spatial and temporal changes. Sentinel sites set up for continuous and real-time collection of evidence to inform responses rely on health facility workers who are overburdened by routine health service activities. This present infrastructure only generates parasite data (HIS-based incidence). Challenges include timeliness of reporting, rates of testing of suspected cases and reporting completeness, lack of utilization of improved metrics such as malaria molecular surveillance (MMS). The present surveillance system fails to capture the spatial and temporal emergence and spread of biological threats, as well as drivers of these challenges (and consequently malaria). These multi-sectorial gaps in infrastructure and capacity demonstrate a suboptimal system insufficient to collate and analyze evidence required for baseline understanding and for timely and targeted decision making in a geography laden with emerging threats.
Aim 1: Develop and optimize university-based regional coordination, capacity building, and targeted evidence generation and response system. By using surveillance as an intervention, regular temporal and spatial evidence generation on parasite and vector populations supported by improved metrics - including MMS, will be crucial in guiding sub-nationally tailored strategies and implementing warning systems, with parallel monitoring and evaluation. This proposal intends to establish a university-based sentinel surveillance network for focal and directed operationally relevant evidence generation that will also function as a HoA hub – thereby instilling regional sustainability and resilience. This surveillance system with enhanced supervision and rapid reporting mechanisms will pilot the best available gold standard malaria surveillance data towards threat detection, improved data granularity, timeliness and quality, and appropriate responses to outbreaks/epidemics. This regional hub will enable sustainable capacity development - a long-term solution to the challenge of self-reliance.
Approach: The development of a standardized network of academic institution-based surveillance system that functions alongside the NMCPs to produce targeted evidence – including genomic data – in real time, will result in a first ever regional malaria evidence and response network. This will be based at the Armauer Hansen Research Institute (AHRI) that leads an ongoing university network in Ethiopia that contains eleven universities through the clinical research network (CRN) supported by the MoH. The utilization of the CRN to train the workforce for upscaled molecular detection of COVID-19 during the pandemic was a perfect example of the potential in the academic institutions. The established BMGF-funded Ethiopian Malaria Genomic Epidemiology Network (EMAGEN, Dr. Tadesse) and the CRN will be used to build standardized capacity within and between included countries, with locally-driven, regional coordination and leadership being key. In the first phase of this study, considering recent reports on the heterogeneous distribution of the converging biological threats in the region, we aim to focus the establishment of the network (and thus the sampling frame) to settings that are (i) shared between neighboring countries with predicted high population mobility (human, parasite and vector), (ii) host internally and cross-border displaced communities due to the continued crisis, and (iii) have reported presence of one or more of the biological threats. Taking this into account, we aim to target 3 major corridors in Ethiopia: (i) northwest of the country that borders Sudan and Eritrea that reported very high prevalence of parasites with pfhrp2/3 gene deletion and pfkelch13 R622I mutation, (ii) east and northeast of Ethiopia bordering Djibouti where An. stephensi was reported to be highly diverse and was first reported (potential point of entry) and known to have refugee camps for IDPs and from neighboring countries such as Eritrea, and (iii) south and southwest Ethiopia bordering Sudan and South Sudan with reports
Investigators:
1-Professor Maowia M. Mukhtar (mmukhtar@tropmedicine.org)
Professor of Immunology with ling history of research in malaria epidemiology, diagnosis and immunology
2-Professor Elwaleed M. Elamin (wmelamin@hotmail.com)
Professor of Molecular Biology. Expert in pathology and parasitology
3-Dr. Fadwa Mohamed Saad Mohamed (fadwamdsaad@gmail.com)
Dr. Fadwa Mohamed earned her clinical Medical Doctorate in community medicine and Master of Science in Community medicine, is the current director of the national malaria control program at the Federal Ministry of Health, Sudan
4-Dr. Khansa Ahmed (khansaalsoni1996sasa@gmail.com)
Assistant director, National Malaria Control Program, Federal Ministry of Health,
Sudan