AAS Open Research最新文献

Background: AmpC beta-lactamase-producing bacteria are associated with increased resistance to third-generation cephalosporins. Here, we describe plasmid-mediated AmpC beta-lactamase-producing enterobacteria isolated from urban and rural dwellers in Uganda. Methods: Stool and urine from 1,448 individuals attending outpatient clinics in Kampala and two rural districts in central Uganda were processed for isolation of Escherichia coli and Klebsiella. Following antibiotic susceptibility testing, cefoxitin resistant isolates, and amoxicillin/clavulanate resistant but cefoxitin susceptible isolates, were tested for AmpC beta-lactamase production using the cefoxitin-cloxacillin double-disc synergy test. Carriage of plasmid-mediated AmpC beta-lactamase-encoding genes (pAmpC) and extended spectrum beta-lactamase (ESBL) encoding genes was determined by PCR. Results: Nine hundred and thirty E. coli and 55 Klebsiella were recovered from the cultured samples, yielding 985 isolates investigated (one per participant). One hundred and twenty-nine isolates (13.1%, 129/985) were AmpC beta-lactamase producers, of which 111 were molecularly characterized for pAmpC and ESBL gene carriage. pAmpC genes were detected in 60% (67/111) of the AmpC beta-lactamase producers; pAmpC genes were also detected in 18 AmpC beta-lactamase non-producers and in 13 isolates with reduced susceptibility to third-generation cephalosporins, yielding a total of 98 isolates that carried pAmpC genes. Overall, the prevalence of pAmpC genes in cefoxitin resistant and/or amoxicillin/clavulanate resistant E. coli and Klebsiella was 59% (93/157) and 26.1% (5/23), respectively. The overall prevalence of pAmpC-positive enterobacteria was 10% (98/985); 16.4% (45/274) in Kampala, 6.2% (25/406) Kayunga, and 9.2% (28/305) Mpigi. Ciprofloxacin use was associated with carriage of pAmpC-positive bacteria while residing in a rural district was associated with protection from carriage of pAmpC-positive bacteria. Conclusion: pAmpC beta-lactamase producing enterobacteria are prevalent in urban and rural dwellers in Uganda; therefore, cefoxitn should be considered during routine susceptibility testing in this setting.

Background: Research site monitoring (RSM) is an effective way to ensure compliance with Good Clinical Practice (GCP). However, RSM is not offered to trainees (investigators) at African Institutions routinely. The Makerere University/Uganda Virus Research Institute Centre of Excellence in Infection and Immunity Research and Training (MUII-Plus) introduced internal monitoring to promote the quality of trainees' research projects. Here, we share our monitoring model, experiences and achievements, and challenges encountered. Methods: We analysed investigators' project reports from monitoring visits undertaken from April 2017 to December 2019. Monitors followed a standard checklist to review investigator site files and record forms, and toured site facilities. We planned four monitoring visits for each trainee: one at site initiation, two interim, and a closeout monitoring visit. A team of two monitors conducted the visits. Results: We monitored 25 out of the 26 research projects in progress between April 2017 and December 2019. Compliance with protocols, standard operating procedures, GCP, and GCLP improved with each monitoring visit. Median (IQR) compliance rate was 43% (31%, 44%) at site initiation visit for different monitoring items, 70% (54%, 90%) at the 1st interim monitoring visit, 100% (92%, 100%) at 2nd interim monitoring visit and all projects achieved 100% compliance at site closeout.  All investigators had good work ethics and practice, and appropriate facilities. Initially, some investigators' files lacked essential documents, and informed consent processes needed to be improved. We realized that non-compliant investigators had not received prior training in GCP/GCLP, so we offered them this training. Conclusions: Routine monitoring helps identify non-compliance early and improves the quality of research. We recommend continuous internal monitoring for all research studies. Investigators conducting research involving human subjects should receive GCP/GCLP training before commencing their projects. Institutional higher degrees and research ethics committees should enforce this as a requirement for project approvals.

Background: Emerging data from Africa indicates remarkably low numbers of reported COVID-19 deaths despite high levels of disease transmission. However, evolution of these trends as the pandemic progresses remains unknown. More certain are the devastating long-term impacts of the pandemic on health and development evident globally. Research tailored to the unique needs of African countries is crucial. UKCDR and GloPID-R have launched a tracker of funded COVID-19 projects mapped to the WHO research priorities and research priorities of Africa and less-resourced countries and published a baseline analysis of a living systematic review (LSR) of these projects.  Methods: In-depth analyses of the baseline LSR for COVID-19 funded research projects in Africa (as of 15th July 2020) to determine the funding landscape and alignment of the projects to research priorities of relevance to Africa.  Results: The limited COVID-19 related research across Africa appears to be supported mainly by international funding, especially from Europe, although with notably limited funding from United States-based funders. At the time of this analysis no research projects funded by an African-based funder were identified in the tracker although there are several active funding calls geared at research in Africa and there may be funding data that has not been made publicly available. Many projects mapped to the WHO research priorities and five particular gaps in research funding were identified, namely: investigating the role of children in COVID-19 transmission; effective modes of community engagement; health systems research; communication of uncertainties surrounding mother-to-child transmission of COVID-19; and identifying ways to promote international cooperation. Capacity strengthening was identified as a dominant theme in funded research project plans. Conclusions: We found significantly lower funding investments in COVID-19 research in Africa compared to high-income countries, seven months into the pandemic, indicating a paucity of research targeting the research priorities of relevance to Africa.

Background: International development partners and research councils are increasingly funding research management and support (RMS) capacity strengthening initiatives in sub-Saharan Africa (SSA) as part of a broader investment in strengthening national and regional research systems.  However, the evidence-base to inform RMS capacity strengthening initiatives is limited at present. This research note presents a synthesis of 28 RMS capacity assessments completed in 25 universities/research institutions from across 15 SSA countries between 2014 and 2018.  Methods: All 28 capacity assessments were completed following a standardised methodology consisting of semi-structured interviews conducted with research and research support staff at the respective institution as well as document reviews and observation of onsite facilities. Data were extracted from the 28 reports detailing the findings of each assessment according to a framework synthesis approach. Results: In total, 13 distinct capacity gap categories emerged from across the 28 RMS capacity assessment reports.  Almost all the institutions assessed faced multiple gaps in RMS capacity within and across each of these 13 categories. The 13 categories were not independent of each other and were often closely inter-connected. Commonalities were also evident across multiple categories, the two most obvious of which were severe fiscal constraints and the often-complex bureaucracy of the institutional operating environment. Conclusions: The synthesis findings reveal multiple, commonly shared RMS capacity gaps in universities and research institutions across SSA. No single intervention type, or focus, would be sufficient to strengthen capacity across all 13 areas; rather, what is needed to facilitate a significant shift in RMS capacity within such SSA universities and research institutions is a combination of interventions, consisting of differing levels of cost and complexity, variously led (or supported) by both internal and external actors.

Background: 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.  Methods: 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. Results: 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. Conclusion: 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.