AAS Open Research最新文献

{"title":"Use of a mutation-specific genotyping method to assess for HIV-1 drug resistance in antiretroviral-naïve HIV-1 Subtype C-infected patients in Botswana.","authors":"Dorcas Maruapula, Iain J MacLeod, Sikhulile Moyo, Rosemary Musonda, Kaelo Seatla, Kesaobaka Molebatsi, Melvin Leteane, Max Essex, Simani Gaseitsiwe, Christopher F Rowley","doi":"10.12688/aasopenres.13107.1","DOIUrl":"10.12688/aasopenres.13107.1","url":null,"abstract":"<p><p><b>Background:</b> HIV-1 drug resistance poses a major threat to the success of antiretroviral therapy. The high costs of available HIV drug resistance assays prohibit their routine usage in resource-limited settings. Pan-degenerate amplification and adaptation (PANDAA), a focused genotyping approach based on quantitative PCR (qPCR), promises a fast and cost-effective way to detect HIV drug resistance mutations (HIVDRMs).  Given the high cost of current genotyping methods, we sought to use PANDAA for screening key HIVDRMs in antiretroviral-naïve individuals at codons 103, 106 and 184 of the HIV-1 reverse transcriptase gene. Mutations selected at these positions have been shown to be the most common driver mutations in treatment failure.  <b>Methods:</b> A total of 103 samples from antiretroviral-naïve individuals previously genotyped by Sanger population sequencing were used to assess and verify the performance of PANDAA. PANDAA samples were run on the ABI 7500 Sequence Detection System to genotype the K103N, V106M and M184V HIVDRMs. In addition, the cost per sample and reaction times were compared. <b>Results:</b> Sanger population sequencing and PANDAA detected K103N mutation in three (2.9%) out of 103 participants.  There was no evidence of baseline V106M and M184V mutations observed in our study. To genotype the six HIVDRMs it costs approximately 40 USD using PANDAA, while the reagents cost per test for Sanger population sequencing is approximately 100 USD per sample. PANDAA was performed quicker compared to Sanger sequencing, 2 hours for PANDAA versus 15 hours for Sanger sequencing. <b>Conclusion:</b> The performance of PANDAA and Sanger population sequencing demonstrated complete concordance. PANDAA could improve patient management by providing quick and relatively cheap access to drug-resistance information.</p>","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":"50"},"PeriodicalIF":0.0,"publicationDate":"2020-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112461/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39032660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient loyalty to HIV care in an HIV facility in Eldoret, Kenya: A mediated mediation","authors":"F. Cherop, M. Korir, Vincent Bagire, J. Wachira","doi":"10.12688/AASOPENRES.13121.1","DOIUrl":"https://doi.org/10.12688/AASOPENRES.13121.1","url":null,"abstract":"Patient loyalty is the continuous commitment and engagement in care where patients can improve and sustain quality of life through continuous use of medical care. Identifying strengths and weaknesses in providing excellent quality care is a key measure of success of healthcare professionals and hospital management. However, few studies have examined patient loyalty from a strategic leadership perspective within HIV health care systems. The purpose of this study is to determine how patient loyalty to HIV care is influenced by multiple factors in a healthcare system environment. The study employs a mixed-methods approach guided by the complexity theory and the theory of planned behavior. A total of 444 surveys with (50 healthcare providers and 394 adult HIV-infected patients) currently on antiretroviral drugs, as well as 22 in-depth interviews with healthcare providers will be conducted. The study will be done at AMPATH Eldoret Kenya. We will use stratified proportionate and census sampling methods to select study participants for the survey while purposive and convenient sampling techniques will be used for in-depth interviews. Structured questionnaires and interviewer guides will guide data collection. Quantitative data analysis will entail hierarchical regression to test direct effects while multiple regression will test the mediation effects using the Hayes PROCESS Model No.6 in SPSS. Qualitative data analysis will be conducted using a thematic analytical method.","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48154206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Institutionalizing research capacity strengthening in LMICs: A systematic review and meta-synthesis.","authors":"Marta Vicente-Crespo, O. Agunbiade, J. Eyers, M. Thorogood, S. Fonn","doi":"10.12688/aasopenres.13116.1","DOIUrl":"https://doi.org/10.12688/aasopenres.13116.1","url":null,"abstract":"Background: Evidence on effective strategies to ensure sustainability of research capacity strengthening interventions in low- and middle-income country (LMIC) institutions is lacking. This systematic review identified publications describing research capacity building programs and noted their effect, their contexts, and the mechanisms, processes and social actors employed in them. Methods: We searched online databases for the period 2011-2018. Inclusion criteria were that the publications 1) described the intervention; 2) were implemented in LMICs; 3) were based in, or relevant to, university staff or post docs; 4) aimed to improve research capacity; 5) aimed to effect change at the institutional level. Two reviewers screened titles, abstracts and full text in consecutive rounds, a third resolved disagreements. Two people extracted the data of each full text using a data extraction tool covering data relevant to our question. Results: In total 4052 citations were identified and 19 papers were included, which referred to 14 interventions. Only three interventions mentioned using a conceptual framework to develop their approach and none described using a theory of change to assess outcomes. The most frequent inputs described were some method of formal training, promotion of a research-conducive environment and establishment of research support systems. A range of outcomes were reported, most frequently an increased number of publications and proportion of staff with PhDs. When factors of success were discussed, this was attributed to a rigorous approach to implementation, adequate funding, and local buy-in. Those who mentioned sustainability linked it to availability of funds and local buy-in. The lack of a common lexicon and a framework against which to report outcomes made comparison between initiatives difficult. Conclusions: The reduced number of interventions that met the inclusion criteria suggests that programs should be well-described, evaluated systematically, and findings published so that the research capacity strengthening community can extract important lessons.","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":"43"},"PeriodicalIF":0.0,"publicationDate":"2020-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"48574559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recruiting students for the COVID-19 emergency response: lessons from eight African countries","authors":"V. Mkenda, M. Woolhouse, F. Mutapi, Geoffrey Banda","doi":"10.12688/aasopenres.13115.1","DOIUrl":"https://doi.org/10.12688/aasopenres.13115.1","url":null,"abstract":"Background: This paper examines how African countries can innovatively use pre-qualified undergraduate and postgraduate students, as well as retired clinical, laboratory and epidemiological technocrats in dealing with medical emergency situations, such as the COVID-19 pandemic. Methods: An online questionnaire was sent to key informants in six universities and two research institutions working with the Tackling Infections to Benefit Africa (TIBA) program eight African countries.  The return rate was 88.9% and data was analysed using the framework method. Results: Students and other personnel trained in the medical and health professions are a valuable resource that can be mobilised by African governments during medical emergency situations. These are found in research, academia, non-governmental organisations, and government.  However, without clear plans and mechanisms for recruiting, supervising and remunerating or reimbursing the costs of engaging someone not employed by the government, the legitimation and authority for such recruitment becomes a challenge. Currently, postgraduate students in the biomedical sciences are the most preferred because of their level of experience and exposure to medical techniques. They also have a degree certificate, which serves as a quality and competence assurance tool. Engagement of postgraduate medical students undergoing their residence programmes also seems a lot easier. While on the other hand, undergraduate students, who are the majority, are considered underexposed and with low technological capabilities. They also lack certificates needed to ensure competence, although we argue that not all tasks during pandemics require specialized skills. Conclusion: As a step towards strengthening national disaster preparedness capacities, African governments need to develop plans that clarify protocols for engaging, training, supervising and protecting students, especially undergraduates and those taking non-biomedical courses. Such plans may form part of the National Pandemic Response Plan, while considering both specialised and non-specialized roles of emergency response.","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46888324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Validation of self-reported physical activity by accelerometry among primary school children in Kilimanjaro, Tanzania: a pilot study.","authors":"Mary Vincent Mosha,&nbsp;Elizabeth Kasagama,&nbsp;Philip Ayieko,&nbsp;Jim Todd,&nbsp;Sia E Msuya,&nbsp;Heiner Grosskurth,&nbsp;Suzanne Filteau","doi":"10.12688/aasopenres.13118.1","DOIUrl":"https://doi.org/10.12688/aasopenres.13118.1","url":null,"abstract":"<p><p><b>Background:</b> Self-reports are commonly used to assess physical activity in children.  Existing self-reports for physical activity have not been validated for use among primary school children in Kilimanjaro, Tanzania. In order to understand if primary school children can accurately report their physical activity, we examined the validity of self-reported physical activity against accelerometer measured physical activity. <b>Methods:</b> A community based cross-sectional study was conducted from May to July, 2018 among four primary schools in Moshi municipal and Moshi rural districts, Kilimanjaro, Tanzania.  A total of 51 primary school children aged 9-11 years were enrolled using a simple random sampling technique. A self-reported questionnaire was used to collect physical activity related variables. In addition, children wore accelerometers for seven consecutive days to capture physical activity movements. Spearman's rank test and Bland Altman plots were used for assessing validity and agreement between self-reports and accelerometer moderate to vigorous physical activity (MVPA). <b>Results:</b> The mean age of the study participants was 10 (SD=0.8) years. Majority of the study participants were female 32 (63%). A moderate, positive correlation was found between self-reports and accelerometer MVPA (rho=0.36, p=0.009). Accelerometer had higher MVPA compared to self-reports. Children who reported walking to school had higher MVPA for both accelerometer and self- reports compared to children who use other means of transport to school, e.g. school buses (p < 0.001). <b>Conclusions:</b> This study found the moderate positive correlation between self-reports and accelerometers. Self-reports are prone to errors due to recall bias, and this interferes their validity.  More research is needed to develop better self-reported measures with specific activities which can easily be recalled by children. Also, researchers have to be aware of self-reports validity limitation.</p>","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":"40"},"PeriodicalIF":0.0,"publicationDate":"2020-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132476/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39035112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Career development for infection and immunity research in Uganda: a decade of experience from the Makerere University - Uganda Virus Research Institute research and training programme.","authors":"Damalie Nakanjako, Flavia Zalwango, Pamela Wairagala, Fiona Luboga, Irene Andia Biraro, Victoria Diana Bukirwa, Mary Gorrethy Mboowa, Steve Cose, Janet Seeley, Alison Elliott","doi":"10.12688/aasopenres.13066.2","DOIUrl":"10.12688/aasopenres.13066.2","url":null,"abstract":"<p><p><b>Background:</b> The Makerere University/Uganda Virus Research Institute (UVRI) Centre of Excellence for Infection & Immunity Research and Training (MUII) is a collaborative programme supporting excellence in Infection and Immunity (I&I) research in Uganda. Set up in 2008, MUII aims to produce internationally competitive Ugandan and East African I&I research leaders, and develop human and infrastructural resources to support research and training excellence. We undertook an internal evaluation of MUII's achievements, challenges and lessons learned between 08-2008 and 12-2019, to inform programmes seeking to build Africa's health research expertise. <b>Methods:</b> Quantitative data were abstracted from programme annual reports. Qualitative data were obtained in 03-04/2019: a cross-sectional evaluation was undertaken among a purposefully selected representative sample of 27 trainees and two programme staff. Qualitative data was analysed according to pre-determined themes of achievements, challenges, lessons learned and recommendations for improvement. <b>Results:</b> By 12-2019, MUII had supported 68 fellowships at master's-level and above (50% female: 23 Masters, 27 PhD, 15 post-doctoral, three group-leaders) and over 1,000 internships. Fellows reported career advancement, mentorship by experts, and improved research skills and outputs. Fellows have published over 300 papers, secured grants worth over £20m, established over 40 international collaborations, and taken on research and academic leadership positions in the country. Key lessons were: i) Efficient administration provides a conducive environment for high quality research; ii) Institutions need supportive policies for procurement, including provisions for purchases of specific biological research reagents from international manufacturers; iii) Strong international and multi-disciplinary collaboration provides a critical mass of expertise to mentor researchers in development; and iv) Mentorship catalyses young scientists to progress from graduate trainees to productive academic researchers, relevant to society's most pressing health challenges. <b>Conclusions:</b> Sustainable academic productivity can be achieved through efficient operational support, global collaboration and mentorship to provide solutions to Africa's health challenges.</p>","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":"26"},"PeriodicalIF":0.0,"publicationDate":"2020-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372530/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38400275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the MUII-plus mentorship programme: reflections of Fellows’ experiences and lessons for other programmes","authors":"Irene Andia Biraro, Emmanuella Driciru, Rehema Namaganda, Fiona Luboga, Charles Kato Drago, A. Wajja, B. Okech, Mary Gorrethy N. Mboowa, Raymond Muganyizi, Moses Kizza, S. Cose, V. Bukirwa, D. Nakanjako, A. Elliott","doi":"10.12688/aasopenres.13091.1","DOIUrl":"https://doi.org/10.12688/aasopenres.13091.1","url":null,"abstract":"Background: The MUII mentorship programme began 11 years ago with a successful group mentorship model. Over the years, the programme has evolved and is presently anchored on the “GROW” approach. This model allows individuals to: set Goals (What I want?); Reflect (Where am I now?); think of Options (What can I do?); What to implement (my actions?). It is intended to help fellows (current, honorary, alumni) herein referred to as mentees achieve their short, medium, and long-term research, career and professional goals. Methods: A mixed methods study combining a cross-sectional survey, one focus group discussion and 11 in-depth key informant interviews were carried out between November 2018 and January 2019 to 1) assess the status of the mentorship programme, 2) perform a strength weakness opportunity and threats (SWOT) analysis, and 3) identify factors relevant for sustainability. Results: An open invitation was made to 52 fellows to participate in the survey, and 23 responded. Among respondents, the largest proportions were male [70% (16/23)], and PhD fellows [35% (8/23)]. The respondents rated the fellowship experience as excellent [65% (15/23)], and most [78% (18/23)] revealed they had benefitted greatly from the programme. The SWOT analysis revealed outstanding strengths of having regular fellows’ meetings for peer support, and availability of international collaborations, linkages and exposure. Opportunities identified included large pool of mentees within MUII-plus and evidence of fellows taking up leadership positions. The biggest threat to the mentorship programme was the busy schedule of mentors. Conclusions: The MUII-plus mentorship programme has strong potential to offer research and career mentorship to its fellows. To promote sustainability of the programme, there is a need for innovative ways to engage mentors; such as digital platforms (e-mentorship) for greater mentor-mentee interactions.","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41847933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The wearing of face masks in African countries under the COVID-19 crisis: luxury or necessity?","authors":"Zohra Aloui-Zarrouk, Lahcen El Youssfi, K. Badu, Adeniyi Francis Fagbamigbe, D. Matoke-Muhia, C. Ngugi, N. Dukhi, G. Mwaura","doi":"10.12688/aasopenres.13079.1","DOIUrl":"https://doi.org/10.12688/aasopenres.13079.1","url":null,"abstract":"The unforeseeable global crisis of the spread of coronavirus disease 2019 (COVID-19) has caused almost all affected countries to adopt a range of protective measures as recommended by the World Health Organization. However, the speed, type and level of adoption of these protective measures have been remarkably different. Social distancing and quarantine were the main measures adopted in addition to observing basic hygiene. Based on the available evidences, WHO continues to recommend wearing of face masks for healthcare workers and for those people caring for COVID-19 patients. However, some countries and organisations have recommended, and some have even made it mandatory, for their citizens to wear face masks. Particularly in low- and middle-income countries, protecting by wearing face masks is viewed as an affordable yet proactive preventive measure to avoid and slow down viral spread based on the experience of other affected countries. However, the wearing of face masks is controversial due to shortages in their stocks and uncertainty around the quality of masks, as well as their efficiency as a protective mechanism. Masks should be used based on appropriate use and management guidelines. This paper discusses the wearing of face masks from the perspective of low- and middle-income countries, particularly in Africa; and then makes some recommendations that will greatly inform policy makers on epidemic mitigation strategies throughout the African continent.","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45596026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SNPs in IL4 and IFNG show no protective associations with human African trypanosomiasis in the Democratic Republic of the Congo: a case-control study.","authors":"Olivier Fataki Asina, Harry Noyes, Bruno Bucheton, Hamidou Ilboudo, Annette MacLeod, Dieudonné Mumba Ngoyi","doi":"10.12688/aasopenres.12999.1","DOIUrl":"10.12688/aasopenres.12999.1","url":null,"abstract":"<p><p><b>Background:</b> Human African trypanosomiasis (HAT) is a protozoal disease transmitted by tsetse flies. Infection with trypanosomes can lead directly to active HAT or latent infection with no detectable parasites, which may progress to active HAT or to spontaneous self-cure. Genetic variation could explain these differences in the outcome of infection. To test this hypothesis, polymorphisms in 17 candidate genes were tested ( <i>APOL1</i> [ <i>G1 and G2</i>], <i>CFH, HLA-A, HPR, HP, IL1B, IL12B, IL12RB1, IL10, IL4R, MIF, TNFA</i> <i>, IL6, IL4, IL8, IFNG</i>, and <i>HLA-G</i>). <b>Methods:</b> Samples were collected in Democratic Republic of the Congo. 233 samples were genotyped: 100 active HAT cases, 33 from subjects with latent infections and 100 negative controls. Commercial service providers genotyped polymorphisms at 96 single nucleotide polymorphisms (SNPs) on 17 genes. Data were analyzed using Plink V1.9 software and R. Loci, with suggestive associations (uncorrected p < 0.05) validated using an additional 594 individuals, including 164 cases and 430 controls. <b>Results:</b> After quality control, 87 SNPs remained in the analysis. Two SNPs in <i>IL4</i> and two in <i>IFNG</i> were suggestively associated (uncorrected p<0.05) with a differential risk of developing a <i>Trypanosoma brucei gambiense</i> infection in the Congolese population. The <i>IFNG</i> minor allele (rs2430561, rs2069718) SNPs were protective in comparison between latent infections and controls. Carriers of the rs2243258_T and rs2243279_A alleles of <i>IL4</i> and the rs2069728_T allele of <i>IFNG</i> had a reduced risk of developing illness or latent infection, respectively. None of these associations were significant after Bonferroni correction for multiple testing. A validation study using more samples was run to determine if the absence of significant association was due to lack of power. <b>Conclusions:</b> This study showed no evidence of an association of HAT with <i>IL4</i> and <i>IFNG</i> SNPs or with <i>APOL1 G1</i> and <i>G2</i> alleles, which have been found to be protective in other studies.</p>","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":"35"},"PeriodicalIF":0.0,"publicationDate":"2020-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38411570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of <i>Mycobacterium</i> <i>tuberculosis</i> DNA in CD34 ⁺ peripheral blood mononuclear cells of Ugandan adults with latent infection: a cross-sectional and nested prospective study.","authors":"Jonathan Mayito, Irene Andia Biraro, Stephen T Reece, Adrian R Martineau, David P Kateete","doi":"10.12688/aasopenres.13108.1","DOIUrl":"10.12688/aasopenres.13108.1","url":null,"abstract":"<p><p><b>Background</b>: Tuberculin skin test and interferon gamma release assay (IGRA) show limitations in diagnosing latent tuberculosis infection (LTBI) and poorly predict progression to active tuberculosis. This study will explore detection of <i>Mycobacterium tuberculosis</i> ( <i>M.tb</i>) DNA in CD34 ⁺ peripheral blood mononuclear cells (PBMCs) as a biomarker for LTBI and monitoring chemoprophylaxis response. <b>Methods:</b> In a cross-sectional study, 120 household contacts (60 HIV positive and 60 HIV negative) will be recruited. Also, 10 patients with sputum positive pulmonary tuberculosis and 10 visitors from low incidence countries with no history of TB treatment will be recruited as positive and negative controls, respectively. Participants will donate 100 ml (50 ml for TB patients) of blood to isolate PBMCs using density gradient centrifugation. Isolated PBMCs will be separated into CD34 ⁺ and CD34 ^- enriched cellular fractions. DNA from each fraction will be purified, quantified and subjected to droplet digital PCR targeting <i>IS6110</i> (a <i>M.tb</i> Complex multi-copy gene) and <i>rpoB</i>, a single copy gene. Also, 4 ml of blood will be drawn for IGRA. In a nested prospective study, 60 HIV positive participants will be given 300 mg of Isoniazid Preventive Therapy (IPT) daily for six months, after which they will donate a second 100 ml blood sample that will be processed as described above. Data from the cross-sectional study will be analysed to determine the proportion of individuals in whom <i>M.tb</i> DNA is detectable in CD34 ⁺ and CD34 ^- fractions and number of <i>M.tb</i> genomes present. Data from the prospective study will be analysed to compare the proportion of individuals with detectable <i>M.tb</i> DNA in CD34 ⁺ and CD34 ^- fractions, and median <i>M.tb</i> genome copy number, post vs pre-IPT. <b>Discussion:</b> This study will determine whether detection of <i>M.tb</i> DNA in CD34 ⁺ PBMCs holds promise as a biomarker for LTBI and monitoring chemoprophylaxis response.</p>","PeriodicalId":34179,"journal":{"name":"AAS Open Research","volume":" ","pages":"34"},"PeriodicalIF":0.0,"publicationDate":"2020-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7422845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38294554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}