Targeted Next Generation Sequencing for malaria research in Africa: current status and outlook

Abstract

Targeted Next Generation Sequencing (TNGS) is an efficient and economical Next Generation Sequencing (NGS) platform and the preferred choice when specific genomic regions are of interest. So far, only institutions located in middle and high-income countries have developed and implemented the technology, however, the efficiency and cost savings, as opposed to more traditional sequencing methodologies (e.g. Sanger sequencing) make the approach potentially well suited for resource-constrained regions as well. In April 2018, scientists from the Plasmodium Diversity Network Africa (PDNA) and collaborators met during the 7th Pan African Multilateral Initiative of Malaria (MIM) conference held in Dakar, Senegal to explore the feasibility of applying TNGS to genetic studies and malaria surveillance in Africa. The group of scientists reviewed the current experience with TNGS platforms in sub-Saharan Africa (SSA) and identified potential roles the technology might play to accelerate malaria research, scientific discoveries and improved public health in SSA. Research funding, infrastructure and human resources were highlighted as challenges that will have to be mitigated to enable African scientists to drive the implementation of TNGS in SSA. Current roles of important stakeholders and strategies to strengthen existing networks to effectively harness this powerful technology for malaria research of public health importance were discussed.

Prostate Cancer Genomics Research Disparities in Africa: Advancing Knowledge in Resource Constrained Settings

“…However, in Africa there is a large deficit in infrastructure and funding required to carry out necessary genomics research, with only South Africa having dedicated government-sponsored grants for genomic research. 41 Rotimi and colleagues highlighted this deficit by demonstrating that all African cancer genomics research publications only represented 0.061% of total publications on cancer globally. 42 Additionally, for their CaP specific analyses, 14 of 375 (3.7%) relevant publications were found, this is fairly close to the percentage observed in this study (2.9% vs 3.7%).…”

“…Africa has the expertise but is severely underserved in terms of genomics research capacity and infrastructure. 41 Besides the self-driven studies from South Africa, 30 , 67 - 69 , 73 Cameroon, 74 Egypt 47 and Tunisia, 49 for all the other studies the laboratory-based genomics analyses were performed at a collaborating non-African centre ( Table 1 ). For 2 additional studies, dual analyses were performed on genomics platforms in Africa and the USA.…”

Strengthening Surveillance Systems for Malaria Elimination by Integrating Molecular and Genomic Data

“…One of the recommendations of the malERA expert panel is to improve the characterization of the parasite reservoir and develop new tools to assess transmission [4]. Those tools are available and are being progressively deployed in malaria endemic countries [67]. Currently HRM genotyping using SNPs offers a relatively low-cost, robust, and easy to implement method to study parasite population structure and molecular markers associated with antimalarial drug resistance [68,69].…”

“…Globally, a consensus has been established that good quality data are required to improve disease surveillance, especially in low-and middle-income countries (LMICs) [80]. The establishment of well-equipped reference laboratories with well-trained staff in most malaria endemic settings will require concerted efforts from different stakeholders, and several challenges ranging from funding to staff retention and procurement of required reagents are only a part of them [67,81,82]. However, the use of NGS could be centralized to very few sub-regional reference laboratories located in malaria endemic countries [36,83,84].…”

Immediate pools of malaria infections at diagnosis combined with targeted deep sequencing accurately quantifies frequency of drug resistance mutations

“…While traditional drug treatment efficacy studies are important for the detection of resistance to new antimalarials, once genomic resistance markers have been discovered and validated, molecular surveillance is a viable alternative allowing for broader and more cost-effective monitoring of drug resistance ( Apinjoh et al, 2019 ). Advances in experimental and computational methods of high-throughput sequencing (HTS) have made it both possible and affordable to interrogate numerous genomic loci from thousands of samples ( Ghansah et al, 2019 ). Moreover, the high depth data generated by HTS allows accurate quantification of mixed infections providing detection of single drug resistance mutations at a frequency at or below 1% ( Hathaway et al, 2018 ).…”