Browsing by Author "Giesbrecht, David"

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    Potential Opportunities and Challenges of Deploying Next Generation Sequencing and CRISPR-Cas Systems to Support Diagnostics and Surveillance Towards Malaria Control and Elimination in Africa
    (Frontiers, 2022-07-13) Lyimo, Beatus; Popkin-Hall, Zachary; Giesbrecht, David; Mandara, Celine; Madebe, Rashid; Bakari, Catherine; Pereus, Dativa; Seth, Misago; Ngamba, Ramadhan; Mbwambo, Ruth; MacInnis, Bronwyn; Mbwambo, Daniel; Garimo, Issa; Chacky, Frank; Aaron, Sijenunu; Lusasi, Abdallah; Molteni, Fabrizio; Njau, Ritha; Cunningham, Jane; Lazaro, Samwel; Mohamed, Ally; Juliano, Jonathan; Bailey, Jeffrey; Ishengoma, Deus
    Recent developments in molecular biology and genomics have revolutionized biology and medicine mainly in the developed world. The application of next generation sequencing (NGS) and CRISPR-Cas tools is now poised to support endemic countries in the detection, monitoring and control of endemic diseases and future epidemics, as well as with emerging and re-emerging pathogens. Most low and middle income countries (LMICs) with the highest burden of infectious diseases still largely lack the capacity to generate and perform bioinformatic analysis of genomic data. These countries have also not deployed tools based on CRISPR-Cas technologies. For LMICs including Tanzania, it is critical to focus not only on the process of generation and analysis of data generated using such tools, but also on the utilization of the findings for policy and decision making. Here we discuss the promise and challenges of NGS and CRISPR-Cas in the context of malaria as Africa moves towards malaria elimination. These innovative tools are urgently needed to strengthen the current diagnostic and surveillance systems. We discuss ongoing efforts to deploy these tools for malaria detection and molecular surveillance highlighting potential opportunities presented by these innovative technologies as well as challenges in adopting them. Their deployment will also offer an opportunity to broadly build in-country capacity in pathogen genomics and bioinformatics, and to effectively engage with multiple stakeholders as well as policy makers, overcoming current workforce and infrastructure challenges. Overall, these ongoing initiatives will build the malaria molecular surveillance capacity of African researchers and their institutions, and allow them to generate genomics data and perform bioinformatics analysis in-country in order to provide critical information that will be used for real-time policy and decision-making to support malaria elimination on the continent.
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    Prevalence of subpatent Plasmodium falciparum infections in regions with varying transmission intensities and implications for malaria elimination in Mainland Tanzania
    (PMC PubMed Central, 2025-03-26) Seth, Misago; Popkin-Hall, Zachary; Madebe, Rashid; Budodo, Rule; Bakari, Catherine; Lyimo, Beatus; Giesbrecht, David; Moshi, Ramadhani; Mbwambo, Ruth; Francis, Filbert; Pereus, Dativa; Mbata, Doris; Challe, Daniel; Mandai, Salehe; Chacha, Gervas A; Kisambale, Angelina; Mbwambo, Daniel; Aaron, Sijenunu; Lusasi, Abdallah; Lazaro, Samwel; Mandara, Celine; Bailey, Jeffrey; Juliano, Jonathan; Gutman, Julie; Ishengoma, Deus
    Background Subpatent Plasmodium falciparum infections, defined as infections with parasite density below the detection limit of routine malaria diagnostic tests, contribute to infectious reservoirs, sustain transmission, and cause the failure of elimination strategies in target areas. This study assessed the prevalence of subpatent P. falci parum infections and associated risk factors in 14 regions of Mainland Tanzania. Methods The study used samples randomly selected from RDT‑negative dried blood spots (DBS) (n = 2685/10,101) collected in 2021 at 100 health facilities across 10 regions of Mainland Tanzania, and four communities in four addi tional regions. The regions were selected from four transmission strata; high (five regions), moderate (three regions), low (three regions), and very low (three regions). DNA was extracted by Tween‑Chelex method, and the Pf18S rRNA gene was amplified by quantitative polymerase chain reaction (qPCR). Logistic regression analysis was used to assess the associations between age groups, sex, fever status, and transmission strata with subpatent infection status, while linear regression analysis was used to assess the association between these factors and subpatent parasite density. Results Of the selected samples, 525/2685 (19.6%) were positive by qPCR for P. falciparum, and the positivity rates varied across different regions. Under‑fives (aOR: 1.4, 95% CI 1.04–1.88; p < 0.05) from health facilities had higher odds of subpatent infections compared to other groups, while those from community surveys (aOR: 0.33, 95% CI 0.15–0.72; p = 0.005) had lower odds. Participants from very low transmission stratum had significantly lower odds of subpatent infection compared to those from high transmission stratum (aOR = 0.53, 95% CI = 0.37–0.78; p < 0.01). The log‑trans formed median parasite density (interquartile range) was 6.9 (5.8–8.5) parasites/µL, with significantly higher parasitae mia in the low transmission stratum compared to a very low one (11.4 vs 7.0 parasites/µL, p < 0.001). Conclusion Even in very low transmission settings, the prevalence of subpatent infections was 13%, and in low trans mission settings it was even higher at 29.4%, suggesting a substantial reservoir that is likely to perpetuate transmis sion but can be missed by routine malaria case management strategies. Thus, control and elimination programmes may benefit from adoption of more sensitive detection methods to ensure that a higher proportion of subpatent infections are detected.