"Arming half-baked people with weapons!" Information enclaving among professionals and the need for a care-centred model for antibiotic use information in Uganda, Tanzania and Malawi.

BACKGROUND: The overuse of antimicrobial medicines is a global health concern, including as a major driver of antimicrobial resistance. In many low- and middle-income countries, a substantial proportion of antibiotics are purchased over-the-counter without a prescription. But while antibiotics are widely available, information on when and how to use them is not. OBJECTIVE: We aimed to understand the acceptability among experts and professionals of sharing information on antibiotic use with end users - patients, carers and farmers - in Uganda, Tanzania and Malawi. METHODS: Building on extended periods of fieldwork amongst end-users and antibiotic providers in the three countries, we conducted two workshops in each, with a total of 44 medical and veterinary professionals, policy makers and drug regulators, in December 2021. We carried out extensive documentary and literature reviews to characterise antibiotic information systems in each setting. RESULTS: Participants reported that the general public had been provided information on medicine use in all three countries by national drug authorities, health care providers and in package inserts. Participants expressed concern over the danger of sharing detailed information on antibiotic use, particularly that end-users are not equipped to determine appropriate use of medicines. Sharing of general instructions to encourage professionally-prescribed practices was preferred. CONCLUSIONS: Without good access to prescribers, the tension between enclaving and sharing of knowledge presents an equity issue. Transitioning to a client care-centred model that begins with the needs of the patient, carer or farmer will require sharing unbiased antibiotic information at the point of care.

Perceived impacts of COVID-19 responses on routine health service delivery in Liberia and UK: cross-country lessons for resilient health systems for equitable service delivery during pandemics.

BACKGROUND: COVID-19 has caused significant public health problems globally, with catastrophic impacts on health systems. This study explored the adaptations to health services in Liberia and Merseyside UK at the beginning of the COVID-19 pandemic (January-May 2020) and their perceived impact on routine service delivery. During this period, transmission routes and treatment pathways were as yet unknown, public fear and health care worker fear was high and death rates among vulnerable hospitalised patients were high. We aimed to identify cross-context lessons for building more resilient health systems during a pandemic response. METHODS: The study employed a cross-sectional qualitative design with a collective case study approach involving simultaneous comparison of COVID-19 response experiences in Liberia and Merseyside. Between June and September 2020, we conducted semi-structured interviews with 66 health system actors purposively selected across different levels of the health system. Participants included national and county decision-makers in Liberia, frontline health workers and regional and hospital decision-makers in Merseyside UK. Data were analysed thematically in NVivo 12 software. RESULTS: There were mixed impacts on routine services in both settings. Major adverse impacts included diminished availability and utilisation of critical health services for socially vulnerable populations, linked with reallocation of health service resources for COVID-19 care, and use of virtual medical consultation in Merseyside. Routine service delivery during the pandemic was hampered by a lack of clear communication, centralised planning, and limited local autonomy. Across both settings, cross-sectoral collaboration, community-based service delivery, virtual consultations, community engagement, culturally sensitive messaging, and local autonomy in response planning facilitated delivery of essential services. CONCLUSION: Our findings can inform response planning to assure optimal delivery of essential routine health services during the early phases of public health emergencies. Pandemic responses should prioritise early preparedness, with investment in the health systems building blocks including staff training and PPE stocks, address both pre-existing and pandemic-related structural barriers to care, inclusive and participatory decision-making, strong community engagement, and effective and sensitive communication. Multisectoral collaboration and inclusive leadership are essential.

Qualitative study exploring lessons from Liberia and the UK for building a people-centred resilient health systems response to COVID-19.

INTRODUCTION: COVID-19 has tested the resilience of health systems globally and exposed existing strengths and weaknesses. We sought to understand health systems COVID-19 adaptations and decision making in Liberia and Merseyside, UK. METHODS: We used a people-centred approach to carry out qualitative interviews with 24 health decision-makers at national and county level in Liberia and 42 actors at county and hospital level in the UK (Merseyside). We explored health systems' decision-making processes and capacity to adapt and continue essential service delivery in response to COVID-19 in both contexts. RESULTS: Study respondents in Liberia and Merseyside had similar experiences in responding to COVID-19, despite significant differences in health systems context, and there is an opportunity for multidirectional learning between the global south and north. The need for early preparedness; strong community engagement; clear communication within the health system and health service delivery adaptations for essential health services emerged strongly in both settings. We found the Foreign, Commonwealth and Development Office (FCDO) principles to have value as a framework for reviewing health systems changes, across settings, in response to a shock such as a pandemic. In addition to the eight original principles, we expanded to include two additional principles: (1) the need for functional structures and mechanisms for preparation and (2) adaptable governance and leadership structures to facilitate timely decision making and response coordination. We find the use of a people-centred approach also has value to prompt policy-makers to consider the acceptance of service adaptations by patients and health workers, and to continue the provision of 'routine services' for individuals during health systems shocks. CONCLUSION: Our study highlights the importance of a people-centred approach, placing the person at the centre of the health system, and value in applying and adapting the FCDO principles across diverse settings.

Usability and acceptability of oral-based HCV self-testing among key populations: a mixed-methods evaluation in Tbilisi, Georgia.

BACKGROUND: Hepatitis C virus self-testing (HCVST) is an additional approach that may expand access to HCV testing. We conducted a mixed-methods cross-sectional observational study to assess the usability and acceptability of HCVST among people who inject drugs (PWID), men who have sex with men (MSM) and transgender (TG) people in Tbilisi, Georgia. METHODS: The study was conducted from December 2019 to June 2020 among PWID at one harm reduction site and among MSM/TG at one community-based organization. We used a convergent parallel mixed-methods design. Usability was assessed by observing errors made and difficulties faced by participants. Acceptability was assessed using an interviewer-administered semi-structured questionnaire. A subset of participants participated in cognitive and in-depth interviews. RESULTS: A total of 90 PWID, 84 MSM and 6 TG were observed performing HCVST. PWID were older (median age 35 vs 24) and had a lower level of education compared to MSM/TG (27% vs 59%). The proportion of participants who completed all steps successfully without assistance was 60% among PWID and 80% among MSM/TG. The most common error was in sample collection and this was observed more often among PWID than MSM/TG (21% vs 6%; p = 0.002). More PWID requested assistance during HCVST compared to MSM/TG (22% vs 8%; p = 0.011). Acceptability was high in both groups (98% vs 96%; p = 0.407). Inter-reader agreement was 97% among PWID and 99% among MSM/TG. Qualitative data from cognitive (n = 20) and in-depth interviews (n = 20) was consistent with the quantitative data confirming a high usability and acceptability. CONCLUSIONS: HCVST was highly acceptable among key populations in Georgia of relatively high educational level, and most participants performed HCVST correctly. A significant difference in usability was observed among PWID compared to MSM/TG, indicating that PWID may benefit from improved messaging and education as well as options to receive direct assistance when self-testing for HCV.

Sensitivity and specificity of OraQuick® HIV self-test compared to a 4th generation laboratory reference standard algorithm in urban and rural Zambia.

BACKGROUND: HIV self-testing (HIVST) has the potential to increase coverage of HIV testing, but concerns exist about intended users' ability to correctly perform and interpret tests, especially in poor communities with low literacy rates. We assessed the clinical performance of the 2016 prototype OraQuick® HIV Self-Test in rural and urban communities in Zambia to assess the sensitivity and specificity of the test compared to the national HIV rapid diagnostic test (RDT) algorithm and a laboratory reference standard using 4th generation enzyme immunoassays and HIV RNA detection. METHODS: Participants were recruited from randomly selected rural and urban households and one urban health facility between May 2016 and June 2017. Participants received a brief demonstration of the self-test, and then self-tested without further assistance. The research team re-read the self-test, repeated the self-test, drew blood for the laboratory reference, and conducted RDTs following the national HIV testing algorithm (Determine™ HIV1/2 (Alere) confirmed using Unigold™ HIV1/2 (Trinity Biotech)). Selected participants (N = 85) were videotaped whilst conducting the testing to observe common errors. RESULTS: Initial piloting showed that written instructions alone were inadequate, and a demonstration of self-test use was required. Of 2,566 self-test users, 2,557 (99.6%) were able to interpret their result. Of participants who were videoed 75/84 (89.3%) completed all steps of the procedure correctly. Agreement between the user-read result and the researcher-read result was 99.1%. Compared to the RDT algorithm, user-conducted HIVST was 94.1% sensitive (95%CI: 90.2-96.7) and 99.7% specific (95%CI: 99.3-99.9). Compared to the laboratory reference, both user-conducted HIVST (sensitivity 87.5%, 95%CI: 82.70-91.3; specificity 99.7%, 95%CI: 99.4-99.9) and the national RDT algorithm (sensitivity 93.4%, 95%CI: 89.7-96.1%; specificity 100% (95%CI: 99.8-100%) had considerably lower sensitivity. CONCLUSIONS: Self-testers in Zambia who used OraQuick® HIV Self-Test achieved reasonable clinical performance compared to the national RDT algorithm. However, sensitivity of the self-test was reduced compared to a laboratory reference standard, as was the national RDT algorithm. In-person demonstration, along with the written manufacturer instructions, was needed to obtain accurate results. Programmes introducing self-care diagnostics should pilot and optimise support materials to ensure they are appropriately adapted to context.

Developing laboratory capacity for Good Laboratory Practice certification: lessons from a Tanzanian insecticide testing facility.

Background: With increasing insecticide resistance in malaria-endemic countries there is an urgent need for safe and effective novel vector control products. To improve the capacity of facilities that test insecticides in sub-Saharan Africa, a programme is supporting seven facilities towards Good Laboratory Practice (GLP) certification, the globally recognized standard for quality management system (QMS) for the conduct of non-clinical and environmental studies. The World Health Organization (WHO) GLP Handbook provides guidance on a stepwise approach to implement a GLP compliant QMS. This study assesses auditor GLP checklists and timings outlined in the WHO GLP Handbook in the real-life context of a Tanzanian insecticide-testing facility, evaluating their implementation in this context. Methods and Principle Findings: We conducted document review and semi-structured interviews with staff at all levels of the test facility to explore factors that influenced progress towards GLP certification. We found that while auditor GLP checklists underemphasised computer systems, they were otherwise broadly applicable. Factors that delayed time to completion of GLP certification included the need for extensive infrastructure improvements, the availability of regional expertise related to GLP, the capacity of national and regional external systems and services to meet GLP compliance requirements, and training development required for Standard Operating Procedure implementation. Conclusion: The standards required for full GLP compliance are rigorous, with an expected completion timeline to implementation of 24 months. This study shows that in low and middle-income countries this timeline may be unrealistic due to challenges related to infrastructure development and lack of regional capacity and expertise. We recommend a comprehensive gap analysis when starting a project, including these areas which are beyond those recommended by the WHO GLP Handbook. These challenges can be successfully overcome and the experience in Tanzania provides key lessons for other facilities seeking GLP certification or the development of similar QMS.

Development of a Mobile Game to Influence Behavior Determinants of HIV Service Uptake Among Key Populations in the Philippines: User-Centered Design Process.

BACKGROUND: Opportunities in digital distribution place mobile games as a promising platform for games for health. However, designing a game that can compete in the saturated mobile games market and deliver persuasive health messages can feel like an insurmountable challenge. Although user-centered design is widely advocated, factors such as the user's subject domain expertise, budget constraints, and poor data collection methods can restrict the benefits of user involvement. OBJECTIVE: This study aimed to develop a playable and acceptable game for health, targeted at young key populations in the Philippines. METHODS: Authors identified a range of user-centered design methods to be used in tandem from published literature. The resulting design process involved a phased approach, with 40 primary and secondary users engaged during the initial ideation and prototype testing stages. Selected methods included participatory design workshops, playtests, playability heuristics, and focus group discussions. Subject domain experts were allocated roles in the development team. Data were analyzed using a framework approach. Conceptual frameworks in health intervention acceptability and game design guided the analysis. In-game events were captured through the Unity Analytics service to monitor uptake and game use over a 12-month period. RESULTS: Early user involvement revealed a strong desire for online multiplayer gameplay, yet most reported that access to this type of game was restricted because of technical and economic constraints. A role-playing game (RPG) with combat elements was identified as a very appealing gameplay style. Findings guided us to a game that could be played offline and that blended RPG elements, such as narrative and turn-based combat, with match-3 puzzles. Although the game received a positive response during playtests, gameplay was at times perceived as repetitive and predicted to only appeal to casual gamers. Knowledge transfer was predominantly achieved through interpretation of the game's narrative, highlighting this as an important design element. Uptake of the game was positive; between December 1, 2017, and December 1, 2018, 3325 unique device installs were reported globally. Game metrics provided evidence of adoption by young key populations in the Philippines. Game uptake and use were substantially higher in regions where direct engagement with target users took place. CONCLUSIONS: User-centered design activities supported the identification of important contextual requirements. Multiple data collection methods enabled triangulation of findings to mediate the inherent biases of the different techniques. Game acceptance is dependent on the ability of the development team to implement design solutions that address the needs and desires of target users. If target users are expected to develop design solutions, they must have adequate expertise and a significant role within the development team. Facilitating meaningful partnerships between health professionals, the games industry, and end users will support the games for health industry as it matures.

Ability to understand and correctly follow HIV self-test kit instructions for use: applying the cognitive interview technique in Malawi and Zambia.

INTRODUCTION: The ability to achieve an accurate test result and interpret it correctly is critical to the impact and effectiveness of HIV self-testing (HIVST). Simple and easy-to-use devices, instructions for use (IFU) and other support tools have been shown to be key to good performance in sub-Saharan Africa and may be highly contextual. The objective of this study was to explore the utility of cognitive interviewing in optimizing the local understanding of manufacturers' IFUs to achieve an accurate HIVST result. METHODS: Functionally literate and antiretroviral therapy-naive participants were purposefully selected between May 2016 and June 2017 to represent intended users of HIV self-tests from urban and rural areas in Malawi and Zambia. Participants were asked to follow IFUs for HIVST. We then conducted cognitive interviews and observed participants while they attempted to complete the HIVST steps using a structured guide, which mirrored the steps in the IFU. Qualitative data were analysed using a thematic approach. RESULTS: Of a total of 61 participants, many successfully performed most steps in the IFU. Some had difficulties in understanding these and made errors, which could have led to incorrect test results, such as incorrect use of buffer and reading the results prematurely. Participants with lower levels of literacy and inexperience with standard pictorial images were more likely to struggle with IFUs. Difficulties tended to be more pronounced among those in rural settings. Ambiguous terms and translations in the IFU, unfamiliar images and symbols, and unclear order of the steps to be followed were most commonly linked to errors and lower comprehension among participants. Feedback was provided to the manufacturer on the findings, which resulted in further optimization of IFUs. CONCLUSIONS: Cognitive interviewing identifies local difficulties in conducting HIVST from manufacturer-translated IFUs. It is a useful and practical methodology to optimize IFUs and make them more understandable.

Regulation of HIV self-testing in Malawi, Zambia and Zimbabwe: a qualitative study with key stakeholders.

INTRODUCTION: HIV self-testing (HIVST) is being introduced as a new way for more undiagnosed people to know their HIV status. As countries start to implement HIVST, assuring the quality and regulating in vitro diagnostics, including HIVST, are essential. We aimed to document the emerging regulatory landscape and perceptions of key stakeholders involved in HIVST policy and regulation prior to implementation in three low- and middle-income countries. METHODS: Between April and August 2016, we conducted semi-structured interviews in Malawi, Zambia and Zimbabwe to understand the relationships between different stakeholders on their perceptions of current and future HIVST regulation and the potential impact on implementation. We purposively sampled and interviewed 66 national-level key stakeholders from the Ministry of Health and the regulatory, laboratory, logistical, donor and non-governmental sectors. We used a thematic approach to analysis with an inductively developed common coding framework to allow inter-country comparison of emerging themes. RESULTS: In all countries, the national reference laboratory was monitoring the quality of HIVST kits entering the public sector. In Malawi, there was no legal mandate to regulate medical devices, in Zambia one regulatory body with a clear mandate had started developing regulations and in Zimbabwe the mandate to regulate was overlapping between two bodies. Stakeholders indicated that they had a poor understanding of the process and requirements for HIVST regulation, as well as lack of clarity and coordination between organizational roles. The need for good collaboration between sectors, a strong post-market surveillance model for HIVST and technical assistance to develop regulators capacity was noted as priorities. Key informants identified technical working groups as a potential way collaboration could be improved upon to accelerate the regulation of HIVST. CONCLUSION: Regulation of in vitro diagnostic devices, including HIVST, is now being recognized as important by regulators after a regional focus on pharmaceuticals. HIVST is providing an opportunity for each country to develop similar regulations to others in the region leading to a more coherent regulatory environment for the introduction of new devices.

Re-reading of OraQuick HIV-1/2 rapid antibody test results: quality assurance implications for HIV self-testing programmes.

INTRODUCTION: Scale-up of HIV self-testing (HIVST) will play a key role in meeting the United Nation's 90-90-90 targets. Delayed re-reading of used HIVST devices has been used by early implementation studies to validate the performance of self-test kits and to estimate HIV positivity among self-testers. We investigated the stability of results on used devices under controlled conditions to assess its potential as a quality assurance approach for HIVST scale-up. METHODS: 444 OraQuick® HIV-1/2 rapid antibody tests were conducted using commercial plasma from two HIV-positive donors and HIV-negative plasma (high-reactive n = 148, weak-reactive n = 148 and non-reactive n = 148) and incubated them for six months under four conditions (combinations of high and low temperatures and humidity). Devices were re-read daily for one week, weekly for one subsequent month and then once a month by independent readers unaware of the previous results. We used multistage transition models to investigate rates of change in device results, and between storage conditions. RESULTS AND DISCUSSION: There was a high incidence of device instability. Forty-three (29%) of 148 initially non-reactive results became false weak-reactive results. These changes were observed across all incubation conditions, the earliest on Day 4 (n = 9 kits). No initially HIV-reactive results changed to a non-reactive result. There were no significant associations between storage conditions and hazard of results transition. We observed substantial statistical agreement between independent re-readers over time (agreement range: 0.74 to 0.96). CONCLUSIONS: Delayed re-reading of used OraQuick® HIV-1/2 rapid antibody tests is not currently a valid methodological approach to quality assurance and monitoring as we observed a high incidence (29%) of true non-reactive tests changing to false weak-reactive and therefore its use may overestimate true HIV positivity.

Genetic characterization of Mycobacterium tuberculosis complex isolates circulating in Abuja, Nigeria.

OBJECTIVE: Nigeria ranks fourth among the high tuberculosis (TB) burden countries. This study describes the prevalence of drug resistance and the genetic diversity of Mycobacterium tuberculosis in Abuja's Federal Capital Territory. MATERIALS AND METHODS: Two hundred and seventy-eight consecutive sputum samples were collected from adults with presumptive TB during 2013-2014. DNA was extracted from Löwenstein-Jensen cultures and analyzed for the identification of nontuberculous mycobacteria species, detection of drug resistance with line probe assays, and high-throughput spacer oligonucleotide typing (spoligotyping) using microbead-based hybridization. RESULTS: Two hundred and two cultures were positive for M. tuberculosis complex, 24 negative, 38 contaminated, and 15 positive for nontuberculous mycobacteria. Five (2.5%) M. tuberculosis complex isolates were resistant to rifampicin (RIF) and isoniazid (multidrug resistant), nine (4.5%) to RIF alone, and 15 (7.4%) to isoniazid alone; two RIF-resistant isolates were also resistant to fluoroquinolones and ethambutol, and one multidrug resistant isolate was also resistant to ethambutol. Among the 180 isolates with spoligotyping results, 164 (91.1%) were classified as lineage 4 (Euro-American), 13 (7.2%) as lineage 5 (West African 1), two (1.1%) as lineage 2 (East Asia), and one (0.6%) as lineage 6 (West African 2). One hundred and fifty-six (86.7%) isolates were grouped in 17 clusters (2-108 isolates/cluster), of which 108 (60.0%) were grouped as L4.6.2/Cameroon (spoligotype international type 61). CONCLUSION: The description of drug resistance prevalence and genetic diversity of M. tuberculosis in this study may be useful for improving TB control in Nigeria.

Microbead-based spoligotyping of Mycobacterium tuberculosis from Ziehl-Neelsen-stained microscopy preparations in Ethiopia.

The worldwide dissemination of Mycobacterium tuberculosis strains has led to the study of their genetic diversity. One of the most used genotyping methods is spoligotyping, based on the detection of spacers in the clustered regularly interspaced short palindromic repeats (CRISPR) locus. This study assessed the performance of a microbead-based spoligotyping assay using samples extracted from Ziehl-Neelsen-stained smear-microscopy preparations and described the genetic diversity of Mycobacterium tuberculosis among new TB patients in Southern Nations, Nationalities and Peoples' Region (SNNPR) in Ethiopia. Among the 91 samples analysed, 59 (64.8%) generated spoligotyping patterns. Fifty (84.7%) samples were classified into 12 clusters (mostly Lineage 4 or 3) comprising 2-11 samples and nine had unique spoligotyping patterns. Among the 59 spoligotyping patterns, 25 belonged to the T1 sublineage, 11 to the T3-ETH, 5 to the URAL, 4 to the H3 and 14 to other L4 sublineages. There was a remarkable variation in genetic distribution in SNNPR compared to other regions of the country. Microbead-based spoligotyping is an easy-to-perform, high-throughput assay that can generate genotyping information using material obtained from smear microscopy preparations. The method provides an opportunity to obtain data of the M. tuberculosis genetic epidemiology in settings with limited laboratory resources.

Mycobacterium tuberculosis complex genotypes circulating in Nigeria based on spoligotyping obtained from Ziehl-Neelsen stained slides extracted DNA.

METHODS: All State TB control programmes in Nigeria were requested to submit 25-50 smear-positive Ziehl-Neelsen (ZN) stained slides for screening during 2013-2014. DNA was extracted from 929 slides for spoligotyping and drug-resistance analysis using microbead-based flow-cytometry suspension arrays. RESULTS: Spoligotyping results were obtained for 549 (59.1%) of 929 samples. Lineage 4 Cameroon sublineage (L4.6.2) represented half of the patterns, Mycobacterium africanum (L5 and L6) represented one fifth of the patterns, and all other lineages, including other L4 sublineages, represented one third of the patterns. Sublineage L4.6.2 was mostly identified in the north of the country whereas L5 was mostly observed in the south and L6 was scattered. The spatial distribution of genotypes had genetic geographic gradients. We did not obtain results enabling the detection of drug-resistance mutations. CONCLUSION/SIGNIFICANCE: We present the first national snapshot of the M. tuberculosis spoligotypes circulating in Nigeria based on ZN slides. Spoligotyping data can be obtained in a rapid and high-throughput manner with DNA extracted from ZN-stained slides, which may potentially improve our understanding of the genetic epidemiology of TB.

Establishing an international laboratory network for neglected tropical diseases: Understanding existing capacity in five WHO regions.

Background. Limited laboratory capacity is a significant bottleneck in meeting global targets for the control and elimination of neglected tropical diseases (NTD). Laboratories are essential for providing clinical data and monitoring data about the status and changes in NTD prevalence, and for detecting early drug resistance. Currently NTD laboratory networks are informal and specialist laboratory expertise is not well publicised, making it difficult to share global expertise and provide training, supervision, and quality assurance for NTD diagnosis and research. This study aimed to identify laboratories within five World Health Organisation regions (South-East Asia, Eastern Mediterranean, Americas, Western Pacific and Europe) that provide NTD services and could be regarded as national or regional reference laboratories, and to conduct a survey to document their networks and capacity to support NTD programmes. Methods. Potential NTD reference laboratories were identified through systematic searches, snowball sampling and key informants. Results. Thirty-two laboratories responded to the survey. The laboratories covered 17 different NTDs and their main regional and national roles were to provide technical support and training, research, test validation and standard setting. Two thirds of the laboratories were based in academic institutions and almost half had less than 11 staff. Although greater than 90 per cent of the laboratories had adequate technical skills to function as an NTD reference laboratory, almost all laboratories lacked systems for external verification that their results met international standards. Conclusions. This study highlights that although  many laboratories believed they could act as a reference laboratory, only a few had all the characteristics required to fulfil this role as they fell short in the standard and quality assurance of laboratory processes. Networks of high quality laboratories are essential for the control and elimination of disease and this study presents a critical first step in the development of such networks for NTDs.

Interventions to increase tuberculosis case detection at primary healthcare or community-level services.

BACKGROUND: Pulmonary tuberculosis is usually diagnosed when symptomatic individuals seek care at healthcare facilities, and healthcare workers have a minimal role in promoting the health-seeking behaviour. However, some policy specialists believe the healthcare system could be more active in tuberculosis diagnosis to increase tuberculosis case detection. OBJECTIVES: To evaluate the effectiveness of different strategies to increase tuberculosis case detection through improving access (geographical, financial, educational) to tuberculosis diagnosis at primary healthcare or community-level services. SEARCH METHODS: We searched the following databases for relevant studies up to 19 December 2016: the Cochrane Infectious Disease Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library, Issue 12, 2016; MEDLINE; Embase; Science Citation Index Expanded, Social Sciences Citation Index; BIOSIS Previews; and Scopus. We also searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), ClinicalTrials.gov, and the metaRegister of Controlled Trials (mRCT) for ongoing trials. SELECTION CRITERIA: Randomized and non-randomized controlled studies comparing any intervention that aims to improve access to a tuberculosis diagnosis, with no intervention or an alternative intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trials for eligibility and risk of bias, and extracted data. We compared interventions using risk ratios (RR) and 95% confidence intervals (CI). We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included nine cluster-randomized trials, one individual randomized trial, and seven non-randomized controlled studies. Nine studies were conducted in sub-Saharan Africa (Ethiopia, Nigeria, South Africa, Zambia, and Zimbabwe), six in Asia (Bangladesh, Cambodia, India, Nepal, and Pakistan), and two in South America (Brazil and Colombia); which are all high tuberculosis prevalence areas.Tuberculosis outreach screening, using house-to-house visits, sometimes combined with printed information about going to clinic, may increase tuberculosis case detection (RR 1.24, 95% CI 0.86 to 1.79; 4 trials, 6,458,591 participants in 297 clusters, low-certainty evidence); and probably increases case detection in areas with tuberculosis prevalence of 5% or more (RR 1.52, 95% CI 1.10 to 2.09; 3 trials, 155,918 participants, moderate-certainty evidence; prespecified stratified analysis). These interventions may lower the early default (prior to starting treatment) or default during treatment (RR 0.67, 95% CI 0.47 to 0.96; 3 trials, 849 participants, low-certainty evidence). However, this intervention may have may have little or no effect on treatment success (RR 1.07, 95% CI 1.00 to 1.15; 3 trials, 849 participants, low-certainty evidence), and we do not know if there is an effect on treatment failure or mortality. One study investigated long-term prevalence in the community, but with no clear effect due to imprecision and differences in care between the two groups (RR 1.14, 95% CI 0.65 to 2.00; 1 trial, 556,836 participants, very low-certainty evidence).Four studies examined health promotion activities to encourage people to attend for screening, including mass media strategies and more locally organized activities. There was some increase, but this could have been related to temporal trends, with no corresponding increase in case notifications, and no evidence of an effect on long-term tuberculosis prevalence. Two studies examined the effects of two to six nurse practitioner educational sessions in tuberculosis diagnosis, with no clear effect on tuberculosis cases detected. One trial compared mobile clinics every five days with house-to-house screening every six months, and showed an increase in tuberculosis cases.There was also insufficient evidence to determine if sustained improvements in case detection impact on long-term tuberculosis prevalence; this was evaluated in one study, which indicated little or no effect after four years of either contact tracing, extensive health promotion activities, or both (RR 1.31, 95% CI 0.75 to 2.30; 1 study, 405,788 participants in 12 clusters, very low-certainty evidence). AUTHORS' CONCLUSIONS: The available evidence demonstrates that when used in appropriate settings, active case-finding approaches may result in increase in tuberculosis case detection in the short term. The effect of active case finding on treatment outcome needs to be further evaluated in sufficiently powered studies.

FluoroType MTB system for the detection of pulmonary tuberculosis.

FluoroType MTB is a sensitive test for TB but specificity is low compared with fully integrated molecular systems http://ow.ly/WhEO30b1luY.

The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia.

BACKGROUND: In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. STUDY AIM: The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. METHODS: A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. RESULTS: Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm compared to culture-based algorithm (p = 0.003). Treatment success rates at 20 months of treatment were higher in patients diagnosed with the LPA-based algorithm (65.2%) as compared to those diagnosed with the culture-based algorithm (44.8%). Mortality was also lower in the LPA-based algorithm group (7.6%) compared to the culture-based algorithm group (15.9%). There was no statistically significant difference in smear and culture conversion rates between the two algorithms. CONCLUSION: The results of the study suggest that the introduction of LPA leads to faster time to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.

Developments in Impact Assessment of New Diagnostic Algorithms for Tuberculosis Control.

A modified presentation of the impact assessment framework is proposed that improves accessibility while continuing to provide a checklist of the evidence needed to support policy decisions on the implementation of new tools for the diagnosis of tuberculosis.

Tuberculosis case detection in Nigeria, the unfinished agenda.

OBJECTIVE: Underdetection of TB is a major problem in sub-Saharan Africa. WHO recommends countries should have at least 1 laboratory per 100,000 population. However, this recommendation is not evidence based. METHODS: We analysed surveillance data of the Nigerian National TB Control Programme (2008-2012) to describe TB case detection rates, their geographical distribution and their association with the density of diagnostic laboratories and HIV prevalence. RESULTS: The median CDR was 17.7 (range 4.7-75.8%) in 2008, increasing to 28.6% (range 10.6-72.4%) in 2012 (P < 0.01). The CDR2012 was associated with the 2008 baseline; however, states with CDR2008 < 30% had larger increases than states with CDR2008 > 30. There were 990 laboratories in 2008 and 1453 in 2012 (46.7% increase, range by state -3% to +118). The state CDR2012 could be predicted by the laboratory density (P < 0.001), but was not associated with HIV prevalence or the proportion of smear-positive cases. CDR2012 and laboratory density were correlated among states having < and > than 1 laboratory per 100,000 population. CONCLUSION: There are large variations in laboratory density and CDR across the Nigerian states. The CDR is associated with the laboratory density. A much larger number of diagnostic centres are needed. It is likely that a laboratory density above the recommended WHO guideline would result in even higher case detection, and this ratio should be considered a minimum threshold.