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Background Tuberculosis (TB) is a leading cause of death worldwide with over 90% of reported cases occurring in low- and middle-income countries (LMICs). Pre-treatment loss to follow-up (PTLFU) is a key contributor to TB mortality and infection transmission. Objectives We performed a scoping review to map available evidence on interventions to reduce PTLFU in adults with pulmonary TB, identify gaps in existing knowledge, and develop a conceptual framework to guide intervention implementation. Methods We searched eight electronic databases up to February 6 2024, medRxiv for pre-prints, and reference lists of included studies. Two review authors independently selected studies and extracted data using a predesigned form. We analysed data descriptively, presented findings in a narrative summary and developed a conceptual framework based on the Practical, Robust Implementation, and Sustainability Model to map the factors for effective intervention implementation. Results We reviewed 1262 records and included 17 studies. Most studies were randomized controlled trials (8/17, 47%). Intervention barriers included stigma and inadequate resources; enablers included mobile phones and TB testing and results on the same day. We identified eight interventions that reduced PTLFU: treatment support groups; mobile notifications; community health workers; integrated HIV/TB services; Xpert MTB/RIF as the initial diagnostic test; computer-aided detection with chest radiography screening; active linkage to care; and multi-component strategies. Conclusion Given the variation of healthcare settings, TB programs should consider contextual factors such as user acceptability, political commitment, resources, and infrastructure before adopting an intervention. Future research should utilize qualitative study designs, be people-centred, and include social and economic factors affecting PTLFU.

IntroductionHPV self-sampling is a relatively new, cost-effective and widely accepted method, however, uptake in LMICs remains limited. We aimed to map out the evidence and identify gaps in accuracy, acceptability, cost, equity and uptake of self-sampling vs. provider-sampling in LMICs.MethodsWe searched: MEDLINE, EMBASE, CINAHL, SCOPUS, Web of Science, and Global Index Medicus, from 1946 to July 2023. Inclusion criteria entailed studies focusing on self-sampling alone or compared to provider-sampling for HPV testing and reporting on at least one outcome of interest (accuracy, acceptability, cost, equity, or uptake). Two authors independently screened titles, abstracts, and full texts, resolving disagreements through discussion. Data was extracted by one reviewer independently, with quality checks by senior authors, and results were synthesised narratively.ResultsOur search yielded 3,739 records, with 124 studies conducted on 164,165 women aged 15–88 years between 2000 and 2023 included. Most studies were from the African region (n = 61, 49.2%). Designs included cross-sectional (n = 90, 81.1%), randomised (n = 5, 4.5%), modelling (n = 4, 3.6%), micro-costing (n = 2, 1.8%), and non-randomised crossover (n = 1, 0.9%) studies. Outcomes included; acceptability (n = 79, 63.7%), accuracy (n = 51, 41.1%), cost (n = 7, 5.6%), and uptake (n = 7, 5.6%). Most studies reported that participants preferred self-sampling, with only a few studies (n = 7, 8.9%) studies favouring provider-sampling. The sensitivity and specificity of self-sampling ranged from 37.5–96.8% and 41.6–100.0%, respectively. One study directly compared the sensitivity and specificity of dry self-collected vs. wet provider-collected sample transportation. Laboratory costs were similar, but overall costs were lower for self-sampling. Uptake was higher for self-sampling in five of the seven studies. Most studies (n = 106) mentioned equity factors like age (n = 69, 65.1%), education (n = 68, 64.2%) and place of residence (n = 59, 55.6%) but no analysis of their impact was provided.ConclusionHPV self-sampling is acceptable and cost-effective but, evidence of its accuracy shows varying sensitivity and specificity. Evidence on the accuracy of dry self-collected vs. wet provider-collected sample transportation is limited. Research evaluating HPV self-sampling’s accuracy, including comparisons of transportation modes, uptake, the impact of equity factors in LMICs and comparisons with high-income countries is essential to inform cervical cancer screening uptake.Systematic review registrationhttps://doi.org/10.17605/OSF.IO/34TUY.

Objective To perform critical methodological assessments on designs, outcomes, quality and implementation limitations of studies evaluating the impact of malaria rapid diagnostic tests (mRDTs) on patient-important outcomes in sub-Saharan Africa.Design A systematic review of study methods.Data sources MEDLINE, EMBASE, Cochrane Library, African Index Medicus and clinical trial registries were searched up to May 2022.Eligibility criteria Primary quantitative studies that compared mRDTs to alternative diagnostic tests for malaria on patient-important outcomes within sub-Sahara Africa.Data extraction and synthesis Studies were sought by an information specialist and two independent reviewers screened for eligible records and extracted data using a predesigned form using Covidence. Methodological quality was assessed using the National Institutes of Health tools. Descriptive statistics and thematic analysis guided by the Supporting the Use of Research Evidence framework were used for analysis. Findings were presented narratively, graphically and by quality ratings.Results Our search yielded 4717 studies, of which we included 24 quantitative studies; (15, 62.5%) experimental, (5, 20.8%) quasi-experimental and (4, 16.7%) observational studies. Most studies (17, 70.8%) were conducted within government-owned facilities. Of the 24 included studies, (21, 87.5%) measured the therapeutic impact of mRDTs. Prescription patterns were the most reported outcome (20, 83.3%). Only (13, 54.2%) of all studies reported statistically significant findings, in which (11, 45.8%) demonstrated mRDTs’ potential to reduce over-prescription of antimalarials. Most studies (17, 70.8%) were of good methodological quality; however, reporting sample size justification needs improvement. Implementation limitations reported were mostly about health system constraints, the unacceptability of the test by the patients and low trust among health providers.Conclusion Impact evaluations of mRDTs in sub-Saharan Africa are mostly randomised trials measuring mRDTs’ effect on therapeutic outcomes in real-life settings. Though their methodological quality remains good, process evaluations can be incorporated to assess how contextual concerns influence their interpretation and implementation.PROSPERO registration number CRD42018083816.

Abstract Background Concerns about emerging resistance to artemether-lumefantrine (AL) in Africa prompted the pilot introduction of multiple first-line therapies (MFT) in Western Kenya, potentially exposing women-of-childbearing-age (WOCBA) to anti-malarials with unknown safety profiles in the first trimester. The study assessed healthcare provider knowledge and adherence to national guidelines for managing malaria in pregnancy in the context of the MFT pilot. Methods From March to April 2022, a cross-sectional study was conducted in 50 health facilities (HF) and 40 drug outlets (DO) using structured questionnaires to assess pregnancy detection, malaria diagnosis, and treatment choices by trimester. Differences between HF and DO providers and between MFT and non-MFT HFs were assessed using Chi-square tests. Results Of 174 providers (77% HF, 23% DO), 56% were from MFT pilot facilities. Most providers had tertiary education; 5% HF and 20% DO had only primary or secondary education. More HF than DO providers had knowledge of malaria treatment guidelines (62% vs. 40%, p = 0.023), received training in malaria in pregnancy (49% vs. 20%, p = 0.002), and reported assessing for pregnancy in WOCBA (98% vs. 78%, p

Abstract Background Emergence of Plasmodium falciparum resistance to artemether-lumefantrine in Africa prompted the pilot introduction of multiple first-line therapies (MFT) against malaria in Kenya, potentially exposing women-of-childbearing-age (WOCBAs) to anti-malarials with unknown safety profiles in the first trimester. This qualitative study explored knowledge and perceptions among healthcare providers providing malaria treatment to WOCBAs and pregnant women. Methods In-depth interviews were conducted with purposively selected public and private health facility (HF) and drug outlet (DO) providers within and outside the pilot-MFT area. County health managers were interviewed about their knowledge of the national treatment guidelines. Transcripts were coded by content analysis using the World Health Organization health system building blocks (leadership/governance, financing, health workforce, health information systems, access to medicines, and service delivery). Results Thirty providers (HF:21, DO:9) and three health managers were interviewed. Eighteen providers were from HFs in the pilot-MFT area; the remaining three and all nine DOs were outside the pilot-MFT area. The analysis revealed that providers had not been trained in malaria case management in the previous twelve months. DO providers were unfamiliar with national treatment guidelines in pregnancy and reported having no pregnancy tests. Health managers were unable to supervise DOs due to resource limitations. Providers from HFs and DOs noted poor sensitivity of malaria rapid diagnostic tests (RDTs) and hesitancy among patients who associated malaria-RDTs with HIV testing. Almost all providers reported anti-malarial stock-outs, with quinine most affected. Patient preference was a major factor in prescribing anti-malarials. Providers in HFs and DOs reported preferentially using artemether-lumefantrine in the first trimester due to the side effects and unavailability of quinine. Conclusion Knowledge of malaria case management in drug outlets and health facilities remains poor. Improved regulation of DO providers is warranted. Optimizing treatment of malaria in pregnancy requires training, availability of malaria commodities, and pregnancy tests.

In October 2021, the WHO recommended the world’s first malaria vaccine—RTS,S/AS01—to prevent malaria in children living in areas with moderate-to-high transmission in sub-Saharan Africa (SSA). A second malaria vaccine, R21/Matrix-M, was recommended for use in October 2023 and added to the WHO list of prequalified vaccines in December 2023. This study analysis assessed the country status of implementation and delivery strategies for RTS,S/AS01 by searching websites for national malaria policies, guidelines and related documents. Direct contact with individuals working in malaria programmes was made to obtain documents not publicly available. 10 countries had documents with information relating to malaria vaccine implementation, 7 referencing RTS,S/AS01 and 3 (Burkina Faso, Kenya and Nigeria) referencing RTS,S/AS01 and R21/Matrix-M. Five other countries reported plans for malaria vaccine roll-out without specifying which vaccine. Ghana, Kenya and Malawi, which piloted RTS,S/AS01, have now integrated the vaccine into routine immunisation services. Cameroon and Burkina Faso are the first countries outside the pilot countries to incorporate the vaccine into national immunisation services. Uganda plans a phased RTS,S/AS01 introduction, while Guinea plans to first pilot RTS,S/AS01 in five districts. The RTS,S/AS01 schedule varied by country, with the first dose administered at 5 or 6 months in all countries but the fourth dose at either 18, 22 or 24 months. SSA countries have shown widespread interest in rolling out the malaria vaccine, the Global Alliance for Vaccines and Immunization having approved financial support for 20 of 30 countries which applied as of March 2024. Limited availability of RTS,S/AS01 means that some approved countries will not receive the required doses. Vaccine availability and equity must be addressed even as R21/Matrix-M becomes available.

Background Since 2018, over 14 million people have been treated for tuberculosis (TB) globally. However, pre-treatment loss to follow-up (PTLFU) has been shown to contribute substantially to patient losses in the TB care cascade with subsequent high community transmission and mortality rates. Objective To identify, appraise, and synthesise evidence on the perspectives of patients and healthcare workers on factors contributing to PTLFU in adults with pulmonary TB. Methods We registered the title with PROSPERO (CRD42021253212). We searched nine relevant databases up to 24 May 2021 for qualitative studies. Two review authors independently reviewed records for eligibility and extracted data. We assessed methodological quality with the Evidence for Policy and Practice Information Centre tool and synthesised data using the Supporting the Use of Research Evidence framework. We assessed confidence in our findings using Confidence in the Evidence from Reviews of Qualitative Research (GRADE-CERQual). Results We reviewed a total of 1239 records and included five studies, all from low- and middle-income countries. Key themes reported by patients and healthcare workers were communication challenges among healthcare workers and between healthcare workers and patients; knowledge, attitudes, and behaviours about TB and its management; accessibility and availability of facilities for TB care; and human resource and financial constraints, weakness in management and leadership in TB programmes. Patients’ change of residence, long waiting times, and poor referral systems were additional factors that contributed to patients disengaging from care. We had moderate confidence in most of our findings. Conclusion Findings from our qualitative evidence synthesis highlight multiple factors that contribute to PTLFU. Central to addressing these factors will be the need to strengthen health systems and offer people-centred care.

Objective To assess the quality of available and accessible national Clinical Practice Guidelines (CPGs) in Kenya using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool.Methods We searched the websites of the Kenyan Ministry of Health, professional associations and contacted experts in relevant organisations. Our scope was guidelines on maternal, neonatal, nutritional disorders, injuries, communicable and non-communicable diseases in Kenya published in the last 5 years until 30 June 2022. Study selection and data extraction were done by three independent reviewers with disagreements resolved via discussion or with a senior reviewer. We conducted a quality assessment using the online English version of AGREE II tool across six domains. Descriptive statistics were analysed using Stata software V.17. The primary outcome was the methodological quality of the included CPGs assessed by the AGREE II tool score.Results We retrieved 95 CPGs and included 24 in the analysis after screening for eligibility. The CPGs scored best in clarity of presentation and least in the rigour of development. In descending order, the appraisal scores (mean and CI) per domain were as follows: Clarity of presentation 82.96% (95% CI 78.35% to 87.57%) with all guidelines scoring above 50%. Scope and purpose 61.75% (95% CI 54.19% to 69.31%) with seven guidelines scoring less than 50%. Stakeholder involvement 45.25% (95% CI 40.01% to 50.49%) with 16 CPGs scoring less than 50%. Applicability domain 19.88% (95% CI 13.32% to 26.43%) with only one CPG scoring above 50%. Editorial independence 6.92% (95% CI 3.47% to 10.37%) with no CPG scoring above 50% and rigour of development 3% (95% CI 0.61% to 5.39%) with no CPG scoring at least 50%.Conclusion Our findings suggest that the quality of CPGs in Kenya is limited mainly by the rigour of development, editorial independence, applicability and stakeholder involvement. Training initiatives on evidence-based methodology among guideline developers are needed to improve the overall quality of CPGs for better patient care.

Abstract Background Chronic obstructive pulmonary disease (COPD) is a major cause of years of life lost globally. Acute exacerbations of COPD (AECOPD) drive disease progression, reduce quality of life and are a source of mortality in COPD. Approximately 50% of AECOPD are due to bacterial infections. Diagnosing bacterial infection as the aetiology of AECOPD however remains challenging as investigations are limited by practicality, accuracy and expense. Clinicians have traditionally used sputum colour as a marker of bacterial infection in AECOPD, despite the lack of high-quality evidence for this practice. The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy of sputum colour in the diagnosis of bacterial causes of AECOPD. Methods Articles will be searched for in electronic databases (MEDLINE, Google Scholar Scopus, Web of Science, Africa-Wide, CINAHL and Health Source Nursing Academy) and we will conduct a review of citation indexes and the grey literature. Two reviewers will independently conduct study selection, against pre-defined eligibility criteria, data extraction and quality assessment of included articles using the QUADAS-2 tool. We will perform a meta‐analysis using a bivariate logistic regression model with random effects. We will explore heterogeneity through the visual examination of the forest plots of sensitivities and specificities and through the inclusion of possible sources of heterogeneity as covariates in a meta-regression model if sufficient studies are included in the analysis. We also perform a sensitivity analysis to explore the effect of study quality on our findings. The results of this review will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement and will be submitted for peer-review and publication. Discussion The findings of this review will assist clinicians in diagnosing the aetiology of AECOPD and may have important implications for decision making in resource-limited settings, as well as for antimicrobial stewardship. Systematic review registration PROSPERO CRD42019141498

The World Health Organization (WHO) model list of Essential In vitro Diagnostic (EDL) introduced in 2018 complements the established Essential Medicines List (EML) and improves its impact on advancing universal health coverage and better health outcomes. We conducted a scoping review of the literature on implementing the WHO essential lists in Africa to inform the implementation of the recently introduced EDL. We searched eight electronic databases for studies reporting on implementing the WHO EDL and EML in Africa. Two authors independently conducted study selection and data extraction, with disagreements resolved through discussion. We used the Supporting the Use of Research Evidence (SURE) framework to extract themes and synthesised findings using thematic content analysis. We used the Mixed Method Appraisal Tool (MMAT) version 2018 to assess the quality of included studies. We included 172 studies reporting on EDL and EML after screening 3,813 articles titles and abstracts and 1,545 full-text papers. Most (75%, n = 129) studies were purely quantitative in design, comprising descriptive cross-sectional designs (60%, n = 104), 15% (n = 26) were purely qualitative, and 10% (n = 17) had mixed-methods approaches. There were no qualitative or randomised experimental studies about EDL. The main barrier facing the EML and EDL was poorly equipped health facilities-including unavailability or stock-outs of essential in vitro diagnostics and medicines. Financial and non-financial incentives to health facilities and workers were key enablers in implementing the EML; however, their impact differed from one context to another. Only fifty-six (33%) of the included studies were of high quality. Poorly equipped and stocked health facilities remain an implementation barrier to essential diagnostics and medicines. Health system interventions such as financial and non-financial incentives to improve their availability can be applied in different contexts. More implementation study designs, such as experimental and qualitative studies, are required to evaluate the effectiveness of essential lists.

INTRODUCTION: Use of good quality, evidence-informed and up-to-date clinical practice guidelines (CPGs) has the potential to impact health outcomes. This paper describes the development, implementation and evaluation of a dedicated CPG training course to address the training needs of CPG stakeholders in South Africa. METHODS: we first reviewed the content and teaching strategies of existing CPG courses. This review consisted of a systematic review of teaching and learning strategies for guideline teams and a document review of existing courses offered by international guideline groups, universities and professional groups. We then strengthened an existing CPG course and evaluated it.

Abstract Background Tuberculosis (TB) contact tracing is a key strategy for containing TB and provides addition to the passive case finding approach. However, this practice has not been implemented in Tanzania, where there is unacceptably high treatment gap of 62.1% between cases estimated and cases detected. Therefore calls for more aggressive case finding for TB to close this gap. We aimed to determine the magnitude and predictors of bacteriologically-confirmed pulmonary TB among household contacts of bacteriologically-confirmed pulmonary TB index cases in the city of Mwanza, Tanzania. Methods This study was carried out from August to December 2016 in Mwanza city at the TB outpatient clinics of Tertiary Hospital of the Bugando Medical Centre, Sekou-Toure Regional Hospital, and Nyamagana District Hospital. Bacteriologically-confirmed TB index cases diagnosed between May and July 2016 were identified from the laboratory registers book. Contacts were traced by home visits by study TB nurses, and data were collected using a standardized TB screening questionnaire. To detect the bacterioriologically-confirmed pulmonary TB, two sputum samples per household contact were collected under supervision for all household contacts following standard operating procedures. Samples were transported to the Bugando Medical Centre TB laboratory for investigation for TB using fluorescent smear microscopy, GeneXpert MTB/RIF and Löwenstein–Jensen (LJ) culture. Logistic regression was used to determine predictors of bacteriologically-confirmed pulmonary TB among household contacts. Results During the study period, 456 household contacts from 93 TB index cases were identified. Among these 456 household contacts, 13 (2.9%) were GeneXpert MTB/RIF positive, 18 (3.9%) were MTB-culture positive and four (0.9%) were AFB-smear positive. Overall, 29 (6.4%) of contacts had bacteriologically-confirmed pulmonary TB. Predictors of bacteriologically-confirmed pulmonary TB among household contacts were7being married (Odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4–8.0; p = 0.012) and consuming less than three meals a day (OR, 3.7; 95% CI, 1.6–8.7; p = 0.009). Conclusions Our data suggest that in Mwanza, Tanzania, seven in 100 contacts living in the same house with a TB patient develop bacteriologically-confirmed pulmonary TB. These results therefore underscore the need to implement routine TB contact tracing to control tuberculosis in high TB burden countries such as Tanzania.

Background Tuberculosis (TB) is a leading cause of death worldwide with over 90% of reported cases occurring in low- and middle-income countries (LMICs). Pre-treatment loss to follow-up (PTLFU) is a key contributor to TB mortality and infection transmission. Objectives We performed a scoping review to map available evidence on interventions to reduce PTLFU in adults with pulmonary TB, identify gaps in existing knowledge, and develop a conceptual framework to guide intervention implementation. Methods We searched eight electronic databases up to February 6 2024, medRxiv for pre-prints, and reference lists of included studies. Two review authors independently selected studies and extracted data using a predesigned form. We analysed data descriptively, presented findings in a narrative summary and developed a conceptual framework based on the Practical, Robust Implementation, and Sustainability Model to map the factors for effective intervention implementation. Results We reviewed 1262 records and included 17 studies. Most studies were randomized controlled trials (8/17, 47%). Intervention barriers included stigma and inadequate resources; enablers included mobile phones and TB testing and results on the same day. We identified eight interventions that reduced PTLFU: treatment support groups; mobile notifications; community health workers; integrated HIV/TB services; Xpert MTB/RIF as the initial diagnostic test; computer-aided detection with chest radiography screening; active linkage to care; and multi-component strategies. Conclusion Given the variation of healthcare settings, TB programs should consider contextual factors such as user acceptability, political commitment, resources, and infrastructure before adopting an intervention. Future research should utilize qualitative study designs, be people-centred, and include social and economic factors affecting PTLFU.

BACKGROUND: Several interventions for tuberculosis (TB) control have been recommended by the World Health Organization (WHO) over the past decade. These include isoniazid preventive therapy (IPT) for HIV-infected individuals and household contacts of infectious TB patients, diagnostic algorithms for rule-in or rule-out of smear-negative pulmonary TB, and programmatic treatment for multidrug-resistant TB. There is no systematically collected data on the type of evidence that is publicly available to guide the scale-up of these interventions in low- and middle-income countries. We investigated the availability of published evidence on their effectiveness, delivery, and cost-effectiveness that policy makers need for scaling-up these interventions at country level. METHODS AND FINDINGS: PubMed, Web of Science, EMBASE, and several regional databases were searched for studies published from 1 January 1990 through 31 March 2012 that assessed health outcomes, delivery aspects, or cost-effectiveness for any of these interventions in low- or middle-income countries. Selected studies were evaluated for their objective(s), design, geographical and institutional setting, and generalizability. Studies reporting health outcomes were categorized as primarily addressing efficacy or effectiveness of the intervention. These criteria were used to draw landscapes of published research. We identified 59 studies on IPT in HIV infection, 14 on IPT in household contacts, 44 on rule-in diagnosis, 19 on rule-out diagnosis, and 72 on second-line treatment. Comparative effectiveness studies were relatively few (n = 9) and limited to South America and sub-Saharan Africa for IPT in HIV-infection, absent for IPT in household contacts, and rare for second-line treatment (n = 3). Evaluations of diagnostic and screening algorithms were more frequent (n = 19) but geographically clustered and mainly of non-comparative design. Fifty-four studies evaluated ways of delivering these interventions, and nine addressed their cost-effectiveness. CONCLUSIONS: There are substantial gaps in published evidence for scale-up for five WHO-recommended TB interventions settings at country level, which for many countries possibly precludes program-wide implementation of these interventions. There is a strong need for rigorous operational research studies to be carried out in programmatic settings to inform on best use of existing and new interventions in TB control.