Policy uptake and implementation of the RTS,S/AS01 malaria vaccine in sub-Saharan African countries: status 2 years following the WHO recommendation.

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.

Health Economics in a World of Uneconomic Growth.

Multiple, accelerating and interacting ecological crises are increasingly understood as constituting a major threat to human health and well-being. Unconstrained economic growth is strongly implicated in these growing crises, and it has been argued that this growth has now become "uneconomic growth", which is a situation where the size of the economy is still expanding, but this expansion is causing more harm than benefit. This article summarises the multiple pathways by which uneconomic growth can be expected to harm human health. It describes how health care systems-especially through overuse, low value and poor quality care-can themselves drive uneconomic growth. Health economists need to understand not only the consequences of environmental impacts on health care, but also the significance of uneconomic growth, and pay closer attention to the growing body of work by heterodox economists, especially in the fields of ecological and feminist economics. This will involve paying closer heed to the existence and consequences of diminishing marginal returns to health care consumption at high levels; the central importance of inequalities and injustice in health; and the need to remedy health economists' currently limited ability to deal effectively with low value care, overdiagnosis and overtreatment.

A synthesis of qualitative evidence of barriers and facilitators in implementing guidelines for TB testing in healthcare settings.

INTRODUCTION: The suboptimal case notification rates for tuberculosis (TB) globally could partly be due to the poor implementation of TB testing guidelines or policies. We identified, appraised and synthesized qualitative evidence exploring the barriers and facilitators to implementing TB testing guidelines. METHODS: We searched electronic databases and grey literature and included studies based on predefined inclusion criteria (PROSPERO registered protocol CRD42016039790) until 9th February 2023. We used the Critical Appraisal Skills Programme tool to assess the methodological quality of the included studies. Two authors reviewed the search output, extracted data and assessed methodological quality independently, resolving disagreements by consensus. We used the Supporting the Use of Research Evidence framework to identify themes and analyse and synthesize our data. We applied the Confidence in the Evidence from Reviews of Qualitative Research approach to assess the confidence of the review findings. RESULTS: Our search output was 6976 articles, from which we included 25 qualitative studies, mostly from low- and middle-income countries (n=19) and about national guidelines (n=22). All studies were from healthcare settings. Most barriers revolved around health system constraints involving the guidelines (low trust and adherence, ambiguous and poorly developed or adapted guidelines) and poorly resourced and organized health facilities to enable the implementation of the guidelines. Individual-level barriers included low trust and low awareness among recipients and providers of care. Donor dependence was the main socio-political constraint. These barriers were similar across all income settings except poorly resourced health facilities and social and political constraints which were only reported in low- and middle-income settings. The reported facilitators were improved trust and knowledge of guidelines, national leadership support and availability of training tools and opportunities for guidelines across all income settings. We had high confidence in most of the review findings. CONCLUSION: Limited guideline knowledge, trust and adherence related to poorly developed and disseminated guidelines in all income settings and poorly resourced facilities in low- and middle-income countries hinder the implementation of TB testing guidelines. This could be improved by better guideline training and adaptation and resourcing of health facilities. TRIAL REGISTRATION: The protocol of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42016039790, and published in a peer-reviewed journal.

Diagnostic Accuracy of Computer-Aided Detection During Active Case Finding for Pulmonary Tuberculosis in Africa: A Systematic Review and Meta-analysis.

Background: Computer-aided detection (CAD) may be a useful screening tool for tuberculosis (TB). However, there are limited data about its utility in active case finding (ACF) in a community-based setting, and particularly in an HIV-endemic setting where performance may be compromised. Methods: We performed a systematic review and evaluated articles published between January 2012 and February 2023 that included CAD as a screening tool to detect pulmonary TB against a microbiological reference standard (sputum culture and/or nucleic acid amplification test [NAAT]). We collected and summarized data on study characteristics and diagnostic accuracy measures. Two reviewers independently extracted data and assessed methodological quality against Quality Assessment of Diagnostic Accuracy Studies-2 criteria. Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Diagnostic Test Accuracy Studies (PRISMA-DTA) guidelines were followed. Results: Of 1748 articles reviewed, 5 met with the eligibility criteria and were included in this review. A meta-analysis revealed pooled sensitivity of 0.87 (95% CI, 0.78-0.96) and specificity of 0.74 (95% CI, 0.55-0.93), just below the World Health Organization (WHO)-recommended target product profile (TPP) for a screening test (sensitivity ≥0.90 and specificity ≥0.70). We found a high risk of bias and applicability concerns across all studies. Subgroup analyses, including the impact of HIV and previous TB, were not possible due to the nature of the reporting within the included studies. Conclusions: This review provides evidence, specifically in the context of ACF, for CAD as a potentially useful and cost-effective screening tool for TB in a resource-poor HIV-endemic African setting. However, given methodological concerns, caution is required with regards to applicability and generalizability.

Low-Value Surgical Procedures in Low- and Middle-Income Countries: A Systematic Scoping Review.

Importance: Overuse of surgical procedures is increasing around the world and harms both individuals and health care systems by using resources that could otherwise be allocated to addressing the underuse of effective health care interventions. In low- and middle-income countries (LMICs), there is some limited country-specific evidence showing that overuse of surgical procedures is increasing, at least for certain procedures. Objectives: To assess factors associated with, extent and consequences of, and potential solutions for low-value surgical procedures in LMICs. Evidence Review: We searched 4 electronic databases (PubMed, Embase, PsycINFO, and Global Index Medicus) for studies published from database inception until April 27, 2022, with no restrictions on date or language. A combination of MeSH terms and free-text words about the overuse of surgical procedures was used. Studies examining the problem of overuse of surgical procedures in LMICs were included and categorized by major focus: the extent of overuse, associated factors, consequences, and solutions. Findings: Of 4276 unique records identified, 133 studies across 63 countries were included, reporting on more than 9.1 million surgical procedures (median per study, 894 [IQR, 97-4259]) and with more than 11.4 million participants (median per study, 989 [IQR, 257-6857]). Fourteen studies (10.5%) were multinational. Of the 119 studies (89.5%) originating from single countries, 69 (58.0%) were from upper-middle-income countries and 30 (25.2%) were from East Asia and the Pacific. Of the 42 studies (31.6%) reporting extent of overuse of surgical procedures, most (36 [85.7%]) reported on unnecessary cesarean delivery, with estimated rates in LMICs ranging from 12% to 81%. Evidence on other surgical procedures was limited and included abdominal and percutaneous cardiovascular surgical procedures. Consequences of low-value surgical procedures included harms and costs, such as an estimated US $3.29 billion annual cost of unnecessary cesarean deliveries in China. Associated factors included private financing, and solutions included social media campaigns and multifaceted interventions such as audits, feedback, and reminders. Conclusions and Relevance: This systematic review found growing evidence of overuse of surgical procedures in LMICs, which may generate significant harm and waste of limited resources; the majority of studies reporting overuse were about unnecessary cesarean delivery. Therefore, a better understanding of the problems in other surgical procedures and a robust evaluation of solutions are needed.

Diagnostic test accuracy of artificial intelligence in screening for referable diabetic retinopathy in real-world settings: A systematic review and meta-analysis.

Retrospective studies on artificial intelligence (AI) in screening for diabetic retinopathy (DR) have shown promising results in addressing the mismatch between the capacity to implement DR screening and increasing DR incidence. This review sought to evaluate the diagnostic test accuracy (DTA) of AI in screening for referable diabetic retinopathy (RDR) in real-world settings. We searched CENTRAL, PubMed, CINAHL, Scopus, and Web of Science on 9 February 2023. We included prospective DTA studies assessing AI against trained human graders (HGs) in screening for RDR in patients with diabetes. Two reviewers independently extracted data and assessed methodological quality against QUADAS-2 criteria. We used the hierarchical summary receiver operating characteristics (HSROC) model to pool estimates of sensitivity and specificity and, forest plots and SROC plots to visually examine heterogeneity in accuracy estimates. From our initial search results of 3899 studies, we included 15 studies comprising 17 datasets. Meta-analyses revealed a sensitivity of 95.33% (95%CI: 90.60-100%) and specificity of 92.01% (95%CI: 87.61-96.42%) for patient-level analysis (10 datasets, N = 45,785) while, for the eye-level analysis, sensitivity was 91.24% (95%CI: 79.15-100%) and specificity, 93.90% (95%CI: 90.63-97.16%) (7 datasets, N = 15,390). Subgroup analyses did not provide variations in the diagnostic accuracy of country classification and DR classification criteria. However, a moderate increase was observed in diagnostic accuracy in the primary-level healthcare settings: sensitivity of 99.35% (95%CI: 96.85-100%), specificity of 93.72% (95%CI: 88.83-98.61%) and, a minimal decrease in the tertiary-level healthcare settings: sensitivity of 94.71% (95%CI: 89.00-100%), specificity of 90.88% (95%CI: 83.22-98.53%). Sensitivity analyses did not show any variations in studies that included diabetic macular edema in the RDR definition, nor studies with ≥3 HGs. This review provides evidence, for the first time from prospective studies, for the effectiveness of AI in screening for RDR in real-world settings. The results may serve to strengthen existing guidelines to improve current practices.

Perceptions and drivers of healthcare provider and drug dispenser practices for the treatment of malaria in pregnancy in the context of multiple first-line therapies in western Kenya: a qualitative study.

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.

Healthcare provider and drug dispenser knowledge and adherence to guidelines for the case management of malaria in pregnancy in the context of multiple first-line artemisinin-based combination therapy in western Kenya.

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 < 0.001). Most providers insisted on parasitological diagnosis, with 59% HF using microscopy and 85% DO using rapid diagnostic tests. More HF than DO providers could correctly name the drugs for treating uncomplicated malaria in the first trimester (oral quinine, or AL if quinine is unavailable) (90% vs. 58%, p < 0.001), second and third trimesters (artemisinin-based combination therapy) (84% vs. 70%, p = 0.07), and for severe malaria (parenteral artesunate/artemether) (94% vs. 60%, p < 0.001). Among HF providers, those in the MFT pilot had more knowledge of malaria treatment guidelines (67% vs. 49%, p = 0.08) and had received training on treatment of malaria in pregnancy (56% vs. 32%, p = 0.03). Few providers (10% HF and 12% DO) had adequate knowledge of malaria treatment in pregnancy, defined as the correct drug and dose for uncomplicated and severe malaria in all trimesters. CONCLUSIONS: Knowledge of national malaria in pregnancy treatment guidelines among providers in Western Kenya is suboptimal. Robust training on appropriate anti-malarial and dosage is needed, particularly given the recent change in recommendation for artemether-lumefantrine use in the first trimester. Supervision of DO and HF practices is essential for correct treatment of malaria in pregnancy in the context of MFT programmes.

Quality assessment of clinical practice guidelines in Kenya using the AGREE II tool: a methodological review.

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.

Sputum Color as a Marker for Bacteria in Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-analysis.

Rationale: Diagnosing bacterial infection as the etiology in acute exacerbations of chronic obstructive pulmonary disease (AECOPDs) remains challenging. Sputum discoloration is easily measured and often used as a marker of bacterial infection in AECOPD, although high-quality evidence for this practice is lacking. Objectives: To determine the diagnostic accuracy of sputum color as a marker for bacteria in AECOPD. Methods: Articles were searched for in electronic databases, and the gray literature were reviewed. Quality assessment of included articles was performed using the revised Quality Assessment of Diagnostic Accuracy Studies tool. A meta-analysis was conducted using a bivariate logistic regression model with random effects. Analysis was conducted on individual sputum samples rather than on individual participants so that each sample represented a unique index test. Results: Of the 1,600 candidate studies, 13 eligible studies satisfied the inclusion criteria. These included prospective cohort studies (n = 3), cross-sectional studies (n = 3), and secondary analyses of randomized controlled trials (n = 7). The included studies were all from Europe and North America. Most studies scored high risk of bias in at least one domain. In total, this systematic review and meta-analysis included 5,770 sputum samples. The estimated pooled sensitivity and specificity were 81% (95% confidence interval [CI], 70-88%) and 50% (95% CI, 35-65%), respectively, and these results were not significantly altered in a series of sensitivity analyses. Conclusions: Sputum color has limited value as a stand-alone test in diagnosing bacterial infection as the etiology in AECOPD because of its moderate sensitivity and poor specificity.

Overuse of medications in low- and middle-income countries: a scoping review.

Objective: To identify and summarize the evidence about the extent of overuse of medications in low- and middle-income countries, its drivers, consequences and potential solutions. Methods: We conducted a scoping review by searching the databases PubMed®, Embase®, APA PsycINFO® and Global Index Medicus using a combination of MeSH terms and free text words around overuse of medications and overtreatment. We included studies in any language published before 25 October 2021 that reported on the extent of overuse, its drivers, consequences and solutions. Findings: We screened 3489 unique records and included 367 studies reporting on over 5.1 million prescriptions across 80 low- and middle-income countries - with studies from 58.6% (17/29) of all low-, 62.0% (31/50) of all lower-middle- and 60.0% (33/55) of all upper-middle-income countries. Of the included studies, 307 (83.7%) reported on the extent of overuse of medications, with estimates ranging from 7.3% to 98.2% (interquartile range: 30.2-64.5). Commonly overused classes included antimicrobials, psychotropic drugs, proton pump inhibitors and antihypertensive drugs. Drivers included limited knowledge of harms of overuse, polypharmacy, poor regulation and financial influences. Consequences were patient harm and cost. Only 11.4% (42/367) of studies evaluated solutions, which included regulatory reforms, educational, deprescribing and audit-feedback initiatives. Conclusion: Growing evidence suggests overuse of medications is widespread within low- and middle-income countries, across multiple drug classes, with few data of solutions from randomized trials. Opportunities exist to build collaborations to rigorously develop and evaluate potential solutions to reduce overuse of medications.

Factors contributing to pre-treatment loss to follow-up in adults with pulmonary tuberculosis: a qualitative evidence synthesis of patient and healthcare worker perspectives.

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.

Rapid molecular tests for tuberculosis and tuberculosis drug resistance: a qualitative evidence synthesis of recipient and provider views.

BACKGROUND: Programmes that introduce rapid molecular tests for tuberculosis and tuberculosis drug resistance aim to bring tests closer to the community, and thereby cut delay in diagnosis, ensure early treatment, and improve health outcomes, as well as overcome problems with poor laboratory infrastructure and inadequately trained personnel. Yet, diagnostic technologies only have an impact if they are put to use in a correct and timely manner. Views of the intended beneficiaries are important in uptake of diagnostics, and their effective use also depends on those implementing testing programmes, including providers, laboratory professionals, and staff in health ministries. Otherwise, there is a risk these technologies will not fit their intended use and setting, cannot be made to work and scale up, and are not used by, or not accessible to, those in need. OBJECTIVES: To synthesize end-user and professional user perspectives and experiences with low-complexity nucleic acid amplification tests (NAATs) for detection of tuberculosis and tuberculosis drug resistance; and to identify implications for effective implementation and health equity. SEARCH METHODS: We searched MEDLINE, Embase, CINAHL, PsycInfo and Science Citation Index Expanded databases for eligible studies from 1 January 2007 up to 20 October 2021. We limited all searches to 2007 onward because the development of Xpert MTB/RIF, the first rapid molecular test in this review, was completed in 2009. SELECTION CRITERIA: We included studies that used qualitative methods for data collection and analysis, and were focused on perspectives and experiences of users and potential users of low-complexity NAATs to diagnose tuberculosis and drug-resistant tuberculosis. NAATs included Xpert MTB/RIF, Xpert MTB/RIF Ultra, Xpert MTB/XDR, and the Truenat assays. Users were people with presumptive or confirmed tuberculosis and drug-resistant tuberculosis (including multidrug-resistant (MDR-TB)) and their caregivers, healthcare providers, laboratory technicians and managers, and programme officers and staff; and were from any type of health facility and setting globally. MDR-TB is tuberculosis caused by resistance to at least rifampicin and isoniazid, the two most effective first-line drugs used to treat tuberculosis. DATA COLLECTION AND ANALYSIS: We used a thematic analysis approach for data extraction and synthesis, and assessed confidence in the findings using GRADE CERQual approach. We developed a conceptual framework to illustrate how the findings relate. MAIN RESULTS: We found 32 studies. All studies were conducted in low- and middle-income countries. Twenty-seven studies were conducted in high-tuberculosis burden countries and 21 studies in high-MDR-TB burden countries. Only one study was from an Eastern European country. While the studies covered a diverse use of low-complexity NAATs, in only a minority of studies was it used as the initial diagnostic test for all people with presumptive tuberculosis. We identified 18 review findings and grouped them into three overarching categories. Critical aspects users value People with tuberculosis valued reaching diagnostic closure with an accurate diagnosis, avoiding diagnostic delays, and keeping diagnostic-associated cost low. Similarly, healthcare providers valued aspects of accuracy and the resulting confidence in low-complexity NAAT results, rapid turnaround times, and keeping cost to people seeking a diagnosis low. In addition, providers valued diversity of sample types (for example, gastric aspirate specimens and stool in children) and drug resistance information. Laboratory professionals appreciated the improved ease of use, ergonomics, and biosafety of low-complexity NAATs compared to sputum microscopy, and increased staff satisfaction. Challenges reported to realizing those values People with tuberculosis and healthcare workers were reluctant to test for tuberculosis (including MDR-TB) due to fears, stigma, or cost concerns. Thus, low-complexity NAAT testing is not implemented with sufficient support or discretion to overcome barriers that are common to other approaches to testing for tuberculosis. Delays were reported at many steps of the diagnostic pathway owing to poor sample quality; difficulties with transporting specimens; lack of sufficient resources; maintenance of low-complexity NAATs; increased workload; inefficient work and patient flows; over-reliance on low-complexity NAAT results in lieu of clinical judgement; and lack of data-driven and inclusive implementation processes. These challenges were reported to lead to underutilization.  Concerns for access and equity The reported concerns included sustainable funding and maintenance and equitable use of resources to access low-complexity NAATs, as well as conflicts of interest between donors and people implementing the tests. Also, lengthy diagnostic delays, underutilization of low-complexity NAATs, lack of tuberculosis diagnostic facilities in the community, and too many eligibility restrictions hampered access to prompt and accurate testing and treatment. This was particularly the case for vulnerable groups, such as children, people with MDR-TB, or people with limited ability to pay. We had high confidence in most of our findings. AUTHORS' CONCLUSIONS: Low-complexity diagnostics have been presented as a solution to overcome deficiencies in laboratory infrastructure and lack of skilled professionals. This review indicates this is misleading. The lack of infrastructure and human resources undermine the added value new diagnostics of low complexity have for recipients and providers. We had high confidence in the evidence contributing to these review findings. Implementation of new diagnostic technologies, like those considered in this review, will need to tackle the challenges identified in this review including weak infrastructure and systems, and insufficient data on ground level realities prior and during implementation, as well as problems of conflicts of interest in order to ensure equitable use of resources.

Point-of-care viral load tests to detect high HIV viral load in people living with HIV/AIDS attending health facilities.

BACKGROUND: Viral load (VL) testing in people living with HIV (PLHIV) helps to monitor antiretroviral therapy (ART). VL is still largely tested using central laboratory-based platforms, which have long test turnaround times and involve sophisticated equipment. VL tests with point-of-care (POC) platforms capable of being used near the patient are potentially easy to use, give quick results, are cost-effective, and could replace central or reference VL testing platforms. OBJECTIVES: To estimate the diagnostic accuracy of POC tests to detect high viral load levels in PLHIV attending healthcare facilities. SEARCH METHODS: We searched eight electronic databases using standard, extensive Cochrane search methods, and did not use any language, document type, or publication status limitations. We also searched the reference lists of included studies and relevant systematic reviews, and consulted an expert in the field from the World Health Organization (WHO) HIV Department for potentially relevant studies. The latest search was 23 November 2020. SELECTION CRITERIA: We included any primary study that compared the results of a VL test with a POC platform to that of a central laboratory-based reference test to detect high viral load in PLHIV on HIV/AIDS care or follow-up. We included all forms of POC tests for VL as defined by study authors, regardless of the healthcare facility in which the test was conducted. We excluded diagnostic case-control studies with healthy controls and studies that did not provide sufficient data to create the 2 × 2 tables to calculate sensitivity and specificity. We did not limit our study inclusion to age, gender, or geographical setting. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the titles, abstracts, and full texts of the search results to identify eligible articles. They also independently extracted data using a standardized data extraction form and conducted risk of bias assessment using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Using participants as the unit of analysis, we fitted simplified univariable models for sensitivity and specificity separately, employing a random-effects model to estimate the summary sensitivity and specificity at the current and commonly reported World Health Organization (WHO) threshold (≥ 1000 copies/mL). The bivariate models did not converge to give a model estimate. MAIN RESULTS: We identified 18 studies (24 evaluations, 10,034 participants) defining high viral loads at main thresholds ≥ 1000 copies/mL (n = 20), ≥ 5000 copies/mL (n = 1), and ≥ 40 copies/mL (n = 3). All evaluations were done on samples from PLHIV retrieved from routine HIV/AIDS care centres or health facilities. For clinical applicability, we included 14 studies (20 evaluations, 8659 participants) assessing high viral load at the clinical threshold of ≥ 1000 copies/mL in the meta-analyses. Of these, sub-Saharan Africa, Europe, and Asia contributed 16, three, and one evaluation respectively. All included participants were on ART in only nine evaluations; in the other 11 evaluations the proportion of participants on ART was either partial or not clearly stated. Thirteen evaluations included adults only (n = 13), five mixed populations of adults and children, whilst in the remaining two the age of included populations was not clearly stated. The majority of evaluations included commercially available tests (n = 18). Ten evaluations were POC VL tests conducted near the patient in a peripheral or onsite laboratory, whilst the other 10 were evaluations of POC VL tests in a central or reference laboratory setting. The test types evaluated as POC VL tests included Xpert HIV-1 Viral Load test (n = 8), SAMBA HIV-1 Semi-Q Test (n = 9), Alere Q NAT prototype assay for HIV-1 (n = 2) and m-PIMA HIV-1/2 Viral Load test (n = 1). The majority of evaluations (n = 17) used plasma samples, whilst the rest (n = 3) utilized whole blood samples. Pooled sensitivity (95% confidence interval (CI)) of POC VL at a threshold of ≥ 1000 copies/mL was 96.6% (94.8 to 97.8) (20 evaluations, 2522 participants), and pooled specificity (95% CI) was 95.7% (90.8 to 98.0) (20 evaluations, 6137 participants). Median prevalence for high viral load (≥ 1000 copies/mL) (n = 20) was 33.4% (range 6.9% to 88.5%). Limitations The risk of bias was mostly assessed as unclear across the four domains due to incomplete reporting. AUTHORS' CONCLUSIONS: We found POC VL to have high sensitivity and high specificity for the diagnosis of high HIV viral load in PLHIV attending healthcare facilities at a clinical threshold of ≥ 1000 copies/mL.

Implementing essential diagnostics-learning from essential medicines: A scoping review.

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.

Point-of-care tests detecting HIV nucleic acids for diagnosis of HIV-1 or HIV-2 infection in infants and children aged 18 months or less.

BACKGROUND: The standard method of diagnosing HIV in infants and children less than 18 months is with a nucleic acid amplification test reverse transcriptase polymerase chain reaction test (NAT RT-PCR) detecting viral ribonucleic acid (RNA). Laboratory testing using the RT-PCR platform for HIV infection is limited by poor access, logistical support, and delays in relaying test results and initiating therapy in low-resource settings. The use of rapid diagnostic tests at or near the point-of-care (POC) can increase access to early diagnosis of HIV infection in infants and children less than 18 months of age and timely initiation of antiretroviral therapy (ART). OBJECTIVES: To summarize the diagnostic accuracy of point-of-care nucleic acid-based testing (POC NAT) to detect HIV-1/HIV-2 infection in infants and children aged 18 months or less exposed to HIV infection. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (until 2 February 2021), MEDLINE and Embase (until 1 February 2021), and LILACS and Web of Science (until 2 February 2021) with no language or publication status restriction. We also searched conference websites and clinical trial registries, tracked reference lists of included studies and relevant systematic reviews, and consulted experts for potentially eligible studies. SELECTION CRITERIA: We defined POC tests as rapid diagnostic tests conducted at or near the patient site. We included any primary study that compared the results of a POC NAT to a reference standard of laboratory NAT RT-PCR or total nucleic acid testing to detect the presence or absence of HIV infection denoted by HIV viral nucleic acids in infants and children aged 18 months or less who were exposed to HIV-1/HIV-2 infection. We included cross-sectional, prospective, and retrospective study designs and those that provided sufficient data to create the 2 × 2 table to calculate sensitivity and specificity. We excluded diagnostic case control studies with healthy controls. DATA COLLECTION AND ANALYSIS: We extracted information on study characteristics using a pretested standardized data extraction form. We used the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool to assess the risk of bias and applicability concerns of the included studies. Two review authors independently selected and assessed the included studies, resolving any disagreements by consensus. The unit of analysis was the participant. We first conducted preliminary exploratory analyses by plotting estimates of sensitivity and specificity from each study on forest plots and in receiver operating characteristic (ROC) space. For the overall meta-analyses, we pooled estimates of sensitivity and specificity using the bivariate meta-analysis model at a common threshold (presence or absence of infection). MAIN RESULTS: We identified a total of 12 studies (15 evaluations, 15,120 participants). All studies were conducted in sub-Saharan Africa. The ages of included infants and children in the evaluations were as follows: at birth (n = 6), ≤ 12 months (n = 3), ≤ 18 months (n = 5), and ≤ 24 months (n = 1). Ten evaluations were field evaluations of the POC NAT test at the point of care, and five were laboratory evaluations of the POC NAT tests.The POC NAT tests evaluated included Alere q HIV-1/2 Detect qualitative test (recently renamed m-PIMA q HIV-1/2 Detect qualitative test) (n = 6), Xpert HIV-1 qualitative test (n = 6), and SAMBA HIV-1 qualitative test (n = 3). POC NAT pooled sensitivity and specificity (95% confidence interval (CI)) against laboratory reference standard tests were 98.6% (96.1 to 99.5) (15 evaluations, 1728 participants) and 99.9% (99.7 to 99.9) (15 evaluations, 13,392 participants) in infants and children ≤ 18 months. Risk of bias in the included studies was mostly low or unclear due to poor reporting. Five evaluations had some concerns for applicability for the index test, as they were POC tests evaluated in a laboratory setting, but there was no difference detected between settings in sensitivity (-1.3% (95% CI -4.1 to 1.5)); and specificity results were similar. AUTHORS' CONCLUSIONS: For the diagnosis of HIV-1/HIV-2 infection, we found the sensitivity and specificity of POC NAT tests to be high in infants and children aged 18 months or less who were exposed to HIV infection.

Sputum colour as a marker for bacteria in acute exacerbations of COPD: protocol for a systematic review and meta-analysis.

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.