Utilization of Oxford Nanopore Technology for Human Infectious Diseases Detection and Surveillance in Africa: A Scoping Review
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Background: Nanopore‐based sequencing by Oxford Nanopore Technologies (ONT) offers rapid, cost‐effective, and portable sequencing. As an emerging technology, ONT must be evaluated for efficacy and practical application in both high‐ and low‐resource settings. This scoping review (SR) aimed to: 1) describe how nanopore technology is used in Africa for surveillance and diagnosis of human infectious diseases, 2) describe how nanopore technology aids in the real-time detection of infectious pathogens in Africa, and 3) identify challenges and opportunities for utilizing nanopore technology in Africa to study infectious diseases. Methods: This SR followed the Joanna Briggs Institute Reviewer’s Manual framework for SRs. English‐language studies published from January 1, 2008, to April 30, 2024 that used ONT on human specimens collected in Africa and targeted ≥1 microbial agent were included. Searches were performed in Embase, Medline, PubMed, CINAHL, and the Cochrane Library. The protocol was publicly available on the Open Science Framework (1) prior to data collection. Two independent reviewers screened studies using Covidence, and data was extracted using a custom REDCap instrument. Descriptive statistics and data visualization were performed in Microsoft Excel. Results: 1162 studies were identified and 93 (8%) underwent full-text review. The portable MinION Mk1B was the most common ONT device (65% of studies). Eighty-eight studies analyzed specimens from a single African country. Of these, 45% were sequenced in the same country, 7% in a different African Country, 11% in a non-African country, and 32% did not specify location. Specimen types included direct patient specimens (62%) and cultured isolates (35%), or a combination of both. Blood, serum, or plasma was most common (35%), followed by naso- or oropharyngeal specimens (27%). Forty-four studies used ONT during an active infectious diseases outbreak, 25 of which studied SARS-CoV-2. Seventy-two studies used ONT for genomic surveillance of infectious pathogens or antibiotic resistance genes, and one study used ONT for a direct clinical application. African-affiliated authors were included as first, middle, and last authors in 46% of studies, and 15% were published by entirely African-affiliated teams. Ten studies published information on workflow timeline and five studies published the per-specimen cost. Conclusions: ONT can enable timely and affordable sequencing in African countries as demonstrated through a small number of studies that accomplished these goals individually. Improved reporting of ONT-specific methodology is needed, including timelines, cost, barcoding, flow cell model, and the use of negative controls. Publications that provide these details will enhance reproducibility and support the development of new studies using ONT for the diagnosis and surveillance of infectious diseases in low resource settings.
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The manuscript is clearly presented, and the arguments are well developed. It has the potential to contribute meaningfully to the existing literature. The reviewers have raised minor concerns that should be addressed in a revised version.
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Comments to Author
Thank you for the opportunity to review this manuscript. The manuscript details an interesting scoping review, investigating the uptake and use of ONT sequencing in African countries. The manuscript aimed to describe the usage of ONT in Africa, elucidate its use specifically as a real-time detection solution for infectious disease in Africa, and to identify challenges and opportunities for this platform in Africa. In general, the article is comprehensively written and informative for readers who wish to know more about this topic, although some sections appear a little overlong. The number of figures and tables is minimal, and some of the data presented throughout the Results section may be better suited for presentation using such tables and figures. The Introduction provides an overview of NGS …
Comments to Author
Thank you for the opportunity to review this manuscript. The manuscript details an interesting scoping review, investigating the uptake and use of ONT sequencing in African countries. The manuscript aimed to describe the usage of ONT in Africa, elucidate its use specifically as a real-time detection solution for infectious disease in Africa, and to identify challenges and opportunities for this platform in Africa. In general, the article is comprehensively written and informative for readers who wish to know more about this topic, although some sections appear a little overlong. The number of figures and tables is minimal, and some of the data presented throughout the Results section may be better suited for presentation using such tables and figures. The Introduction provides an overview of NGS compared with Sanger sequencing, followed by a detailed history of ONT devices. This section in particular seems to lack conciseness at times and adds unnecessary length to the article. Although potentially useful to a novice perhaps first selecting which ONT platform to use, the section beginning on line 129 contains a lot of information that is not always explicitly relevant to the research question nor the results obtained - making the section more concise may be beneficial for more readers and would be welcomed. Instead, consider expanding the concept of 'equitable use' of the technology. This becomes more apparent in the Discussion section but would be welcomed in the Introduction to better contextualise some of the goals. However, the rest of the introduction adequately establishes the research need, and the three goals are clearly established. The Methods section is generally good, clearly setting out the search strategy, I/E criteria, and screening protocol. A good range of databases are used, and the study appears to be conducted according to established guidelines on scoping reviews. It commended and acknowledged that the study design was published prior to the study being carried out. It may be beneficial to provide a brief explanation of why only English-language studies were included, similar to why the date range of 2008-present was selected (Line 266). A minor suggestion would be to include Supplementary Table 1 in the Methods section, so readers are better oriented for the Discussion section. The Results section may be somewhat difficult to follow throughout, perhaps due to not knowing the study questions without prior reference to Supplementary Table 1. It may be better to present some of the described data in tables or figures, even if similar to figure 4b. It may also help orient the reader to explicitly refer to the study goals in the section headings, and to highlight any results as particularly noteworthy. The Discussion is well presented in general and directly refers to the study goals. As an alternative to providing justification for the exclusion of non-English language articles, perhaps it could be stated as a potential limitation of the study. Table 1 in the conclusion is concise and informative and may be better served earlier in the manuscript. Limited reference to existing literature is made throughout this section, limiting contextualisation. Perhaps some discussion about ONT uptake in other, non-African LMIC's may be beneficial for the reader and add strength to the work. The abstract was informative, although the conclusions reported could be linked to the three stated goals more explicitly. Minor comments: Figure 1: In figure 1, panel 1, the second bullet point is not specific to NGS workflow (particularly in the context of clinical infectious disease diagnosis). Consider removing or revising this to better reflect NGS workflows across clinical and research sectors. Figure 1: In figure 1, panel 4, it states "Convert RNA to cDNA". I suggest revising this to "If RNA was extracted, convert to cDNA" for the avoidance of doubt. Line 108-109: SMRT is introduced but no additional details are provided. It would be helpful to highlight any specific advantages or disadvantages more explicitly compared to ONT in the next sentence, to orient the reader in the focus of ONT. Line 226: This section should be more explicit in the link between evaluating uptake/use of ONT and local authorship. Line 266: Justification for the date range is provided, but not for the language search. Given the importance placed upon local authorship in the Introduction, please clarify why other languages were excluded. Alternatively consider mentioning this in the study limitations. Figure 3: This is called in the text as a result of the search strategy and may be better placed as the first figure in the results section. Results section: consider whether some results could be presented as tables or figures. Line 582: A limitation of the search strategy may be the exclusion of articles not published in English, particularly in searched for literature originating countries that may have a different national or official language. Table 1: Would be welcome to see this informative table earlier in the manuscript. Table 1: "add solution" should be removed from the Justification column and a potential solution added to the Solutions column.
Please rate the manuscript for methodological rigour
Very good
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
Overall, this manuscript is well written and could contribute much to the examination of human diseases in Africa. I do however have some minor comments that I believe must be fixed before the paper is accepted. Line 81 - Introduction. For me, this section too much background on the technology itself, rather than how it applies to disease detection in Africa specifically. I would suggest an introduction framed more about why this technology is suited to solving the issues you raise about disease surveillance in Africa. For example, I do not think it is important to mention adaptive sampling or enrichment mode, or a section on the types of flow cells, or the Library Preparation in detail. Line 106-111 - This is quite an important statement I think, and should be referenced. Why would SMRT or PacBio …
Comments to Author
Overall, this manuscript is well written and could contribute much to the examination of human diseases in Africa. I do however have some minor comments that I believe must be fixed before the paper is accepted. Line 81 - Introduction. For me, this section too much background on the technology itself, rather than how it applies to disease detection in Africa specifically. I would suggest an introduction framed more about why this technology is suited to solving the issues you raise about disease surveillance in Africa. For example, I do not think it is important to mention adaptive sampling or enrichment mode, or a section on the types of flow cells, or the Library Preparation in detail. Line 106-111 - This is quite an important statement I think, and should be referenced. Why would SMRT or PacBio technologies not be just as good as ONT for disease detection? Line 264 - Would limiting the search to just the English language limit results from Africa, that may be in more local languages? Line 404 - Id like to know more about this clinical application, because I am wondering why ONT was uniquely suited to identifying this strain of C. jejuni, and how that helped with the treatment of the patient? This could be a really important case study and backs up your manuscript if it can be shown to be uniquely helpful. Line 463 - I was wondering if there are any other similar studies to compare the use of ONT technology to? For example, I am sure South East Asian / South American countries could have similar issues in obtaining this technology for a reasonable price. And would tell you if African is being affected more than others. Line 519 - I am not completely sold on why ONT would be better than using other cheaper methods for diagnosing and testing infectious agents? I am sure that a PCR would be the quickest and easiest still, alongside other more specific strain testing (although I am aware they often require overnight growth). Could you maybe explain a little on why ONT would be better than those options?
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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