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Background: Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT)

Background: HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Cons

Objectives To improve care for patients with heart failure (HF): establishing local prevalence of HF by finding cases, validating diagnostic registers and reducing poly-pharmacy in patients where the HF diagnosis could be confirmed or excluded. Setting Urban general practices. Design Population-based, quality improvement intervention centrally led by the primary care trust. Participants Patients on HF registers, those who had had an echocardiogram, and patients receiving repeat prescriptions for beta-blockers, diuretics and angiotensin converting enzyme inhibitors. Excluding uncomplicated hypertensive and confirmed HF patients. Results Data were received from 77.4% of local practices. Thirty-three percent of HF patients were found to be misdiagnosed and thus removed from registers, whereas only 7% of newly diagnosed cases were added. The local prevalence of confirmed HF was 1.57% (95% CI 1.51-1.63). After medication review, 7% and 4.5% of patients had their doses altered for ACE inhibitors and beta-blockers, respectively. Medication was stopped for 2.7% of the patients. Conclusion The local prevalence of confirmed HF was lower than the national average. A clinically important proportion of HF patients had their medication reviewed or stopped, enhancing quality of care and patient safety. Clinical diagnosis was demonstrated to be frequently inaccurate with national implications for prevalence calculations within the Quality and Outcomes Framework. Indeed, national data for prevalence may be a poor marker for local performance. [ABSTRACT FROM AUTHOR]

Background: HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations.Methods and Findings: We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained.Conclusions: A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary. [ABSTRACT FROM AUTHOR]

We read with great interest the recent paper by Lo et al., who argue that there is an urgent need to ensure the quality of modelling evidence used to support international and national guideline development. Here we outline efforts by the Tuberculosis Modelling and Analysis Consortium, together with the World Health Organization Global Task Force on Tuberculosis Impact Measurement, to develop material to improve the quality and transparency of country-level tuberculosis modelling to inform decision-making., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Product development is a high-risk undertaking, especially so when investments are prioritized for low- and middle-income countries (LMICs) where markets may be smaller, fragile, and resource-constrained. New HIV prevention technologies, such as the dapivirine vaginal ring (DVR) and long-acting injectable cabotegravir (CAB-LA), are being introduced to these markets with one indication, meeting different needs of groups such as adolescent girls and young women (AGYW) and female sex workers (FSWs) in settings with high HIV burden. However, limited supply and demand have made their uptake a challenge. Economic evaluations conducted before Phase III trials can help optimize the potential public health value proposition of products in early-stage research and development (R&D), targeting investments in the development pathway that result in products likely to be available and taken up. Public investors in the HIV prevention pipeline, in particular those focused on innovative presentations such as multipurpose prevention technologies (MPTs), can leverage early economic evaluations to understand the intrinsic uncertainty in market characterization. In this perspective piece, we reflect on the role of economic evaluations in early product development and on methodological considerations that are central to these analyses. We also discuss methods, in quantitative and qualitative research that can be deployed in early economic evaluations to address uncertainty, with examples applied to the development of future technologies for HIV prevention and MPTs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chapman, Torres-Rueda, Metzler, Young Holt, Kahn-Woods, Thornton and Gomez.)

Background: The World Health Organization (WHO) plays a crucial role in producing global guidelines. In response to previous criticism, WHO has made efforts to enhance the process of guideline development, aiming for greater systematicity and transparency. However, it remains unclear whether these changes have effectively addressed these earlier critiques. This paper examines the policy process employed by WHO to inform guideline recommendations, using the update of the WHO Consolidated HIV Testing Services (HTS) Guidelines as a case study., Methods: We observed guideline development meetings and conducted semi-structured interviews with key participants involved in the WHO guideline-making process. The interviews were recorded, transcribed, and analysed thematically. The data were deductively coded and analysed in line with the main themes from a published conceptual framework for context-based evidence-based decision making: introduction, interpretation, and application of evidence., Results: The HTS guideline update was characterized by an inclusive and transparent process, involving a wide range of stakeholders. However, it was noted that not all stakeholders could participate equally due to gaps in training and preparation, particularly regarding the complexity of the Grading Recommendations Assessment Development Evaluation (GRADE) framework. We also found that WHO does not set priorities for which or how many guidelines should be produced each year and does not systematically evaluate the implementation of their recommendations. Our interviews revealed disconnects in the evidence synthesis process, starting from the development of systematic review protocols. While GRADE prioritizes evidence from RCTs, the Guideline Development Group (GDG) heavily emphasized "other" GRADE domains for which little or no evidence was available from the systematic reviews. As a result, expert judgements and opinions played a role in making recommendations. Finally, the role of donors and their presence as observers during GDG meetings was not clearly defined., Conclusion: We found a need for a different approach to evidence synthesis due to the diverse range of global guidelines produced by WHO. Ideally, the evidence synthesis should be broad enough to capture evidence from different types of studies for all domains in the GRADE framework. Greater structure is required in formulating GDGs and clarifying the role of donors through the process., Competing Interests: HI is employed by Unitaid, a hosted partnership of the World Health Organization. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ingold, Gomez, Stuckler, Vassall and Gafos.)

Appropriate costing and economic modeling are major factors for the successful scale-up of health interventions. Various cost functions are currently being used to estimate costs of health interventions at scale in low- and middle-income countries (LMICs) potentially resulting in disparate cost projections. The aim of this study is to gain understanding of current methods used and provide guidance to inform the use of cost functions that is fit for purpose. We reviewed seven databases covering the economic and global health literature to identify studies reporting a quantitative analysis of costs informing the projected scale-up of a health intervention in LMICs between 2003 and 2019. Of the 8725 articles identified, 40 met the inclusion criteria. We classified studies according to the type of cost functions applied-accounting or econometric-and described the intended use of cost projections. Based on these findings, we developed new mathematical notations and cost function frameworks for the analysis of healthcare costs at scale in LMICs setting. These notations estimate variable returns to scale in cost projection methods, which is currently ignored in most studies. The frameworks help to balance simplicity versus accuracy and increase the overall transparency in reporting of methods., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Eswatini has a high HIV prevalence but has made progress towards improving HIV-status awareness, ART uptake and viral suppression. However, there is still a delay in ART initiation, which could partly be attributed to positive HIV-retesting. This study examines reasons for, and factors associated with, positive HIV-retesting among Max ART participants in Eswatini. Data from 601 participants is included in this cross-sectional study. Descriptive statistics and logistic regressions were used. Of the participants, 32.8% has ever retested after a previous positive result. Most participants who retested did this because they could not accept their results (61.9% of all retesters). Other main reasons are related to external influences, gender or the progression of their HIV infection (respectively 18.3%, 10.2%, and 6.1% of all retesters). Participants without a current partner and participants with less time since their first positive test have lower odds of retesting. To decrease retesting and reduce the delay in ART initiation resulting from it, efforts could be made on increasing the acceptance of positive HIV results. Providing more information on the process of testing and importance of early ART initiation, could be part of the solution.

Introduction: In 2016, South Africa (SA) initiated a national programme to scale-up pre-exposure prophylaxis (PrEP) among female sex workers (FSWs), with ∼20,000 PrEP initiations among FSWs (∼14% of FSW) by 2020. We evaluated the impact and cost-effectiveness of this programme, including future scale-up scenarios and the potential detrimental impact of the COVID-19 pandemic., Methods: A compartmental HIV transmission model for SA was adapted to include PrEP. Using estimates on self-reported PrEP adherence from a national study of FSW (67.7%) and the Treatment and Prevention for FSWs (TAPS) PrEP demonstration study in SA (80.8%), we down-adjusted TAPS estimates for the proportion of FSWs with detectable drug levels (adjusted range: 38.0-70.4%). The model stratified FSW by low (undetectable drug; 0% efficacy) and high adherence (detectable drug; 79.9%; 95% CI: 67.2-87.6% efficacy). FSWs can transition between adherence levels, with lower loss-to-follow-up among highly adherent FSWs (aHR: 0.58; 95% CI: 0.40-0.85; TAPS data). The model was calibrated to monthly data on the national scale-up of PrEP among FSWs over 2016-2020, including reductions in PrEP initiations during 2020. The model projected the impact of the current programme (2016-2020) and the future impact (2021-2040) at current coverage or if initiation and/or retention are doubled. Using published cost data, we assessed the cost-effectiveness (healthcare provider perspective; 3% discount rate; time horizon 2016-2040) of the current PrEP provision., Results: Calibrated to national data, model projections suggest that 2.1% of HIV-negative FSWs were currently on PrEP in 2020, with PrEP preventing 0.45% (95% credibility interval, 0.35-0.57%) of HIV infections among FSWs over 2016-2020 or 605 (444-840) infections overall. Reductions in PrEP initiations in 2020 possibly reduced infections averted by 18.57% (13.99-23.29). PrEP is cost-saving, with $1.42 (1.03-1.99) of ART costs saved per dollar spent on PrEP. Going forward, existing coverage of PrEP will avert 5,635 (3,572-9,036) infections by 2040. However, if PrEP initiation and retention doubles, then PrEP coverage increases to 9.9% (8.7-11.6%) and impact increases 4.3 times with 24,114 (15,308-38,107) infections averted by 2040., Conclusions: Our findings advocate for the expansion of PrEP to FSWs throughout SA to maximize its impact. This should include strategies to optimize retention and should target women in contact with FSW services., (© 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

BACKGROUND: There are currently large gaps in unit cost data for TB, and substantial variation in the quality and methods of unit cost estimates. Uncertainties remain about sample size, range and comprehensiveness of cost data collection for different purposes. We present the methods and results of a project implemented in Kenya, Ethiopia, India, The Philippines and Georgia to estimate unit costs of TB services, focusing on findings most relevant to these remaining methodological challenges. METHODS: We estimated financial and economic unit costs, in close collaboration with national TB programmes. Gold standard methods included both top-down and bottom-up approaches to resource use measurement. Costs are presented in 2018 USD and local currency unit. RESULTS: Cost drivers of outputs varied by service and across countries, as did levels of capacity inefficiency. There was substantial variation in unit cost estimates for some interventions and high overhead costs were observed. Estimates were subject to sampling uncertainty, and some data gaps remain. CONCLUSION: This paper describes detailed methods for the largest TB costing effort to date, to inform prioritisation and planning for TB services. This study provides a strong baseline and some cost estimates may be extrapolated from this data; however, regular further studies of similar quality are needed to add estimates for remaining gaps, or to add new or changing services and interventions. Further research is needed on the best approach to extrapolation of cost data. Costing studies are best implemented as partnerships with policy makers to generate a community of mutual learning and capacity development.

The target populations and financing mechanisms for a new health technology may affect health inequalities in access and impact. We projected the distributional consequences of introducing nirsevimab for prevention of respiratory syncytial virus in a US birth cohort of infants through alternative reimbursement pathway scenarios. Using the RSV immunization impact model, we estimated that a vaccine-like reimbursement pathway would cover 32% more infants than a pharmaceutical pathway. The vaccine pathway would avert 30% more hospitalizations and 39% more emergency room visits overall, and 44% and 44%, respectively, in publicly insured infants. The vaccine pathway would benefit infants from poorer households., Competing Interests: Potential conflicts of interest. G. B. G., C. R., C. B. N., and S. S. C. are employees of Sanofi, a company which makes Nirsevimab, a monoclonal antibody for RSV prevention, and may own Sanofi shares. Sanofi employees were involved in all aspects of data collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. D. S. S. received grant funding from Sanofi. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

We investigated the effects of updating age-specific social contact matrices to match evolving demography on vaccine impact estimates. We used a dynamic transmission model of tuberculosis in India as a case study. We modelled four incremental methods to update contact matrices over time, where each method incorporated its predecessor: fixed contact matrix (M0), preserved contact reciprocity (M1), preserved contact assortativity (M2), and preserved average contacts per individual (M3). We updated the contact matrices of a deterministic compartmental model of tuberculosis transmission, calibrated to epidemiologic data between 2000 and 2019 derived from India. We additionally calibrated the M0, M2, and M3 models to the 2050 TB incidence rate projected by the calibrated M1 model. We stratified age into three groups, children (<15y), adults (≥15y, <65y), and the elderly (≥65y), using World Population Prospects demographic data, between which we applied POLYMOD-derived social contact matrices. We simulated an M72-AS01E-like tuberculosis vaccine delivered from 2027 and estimated the per cent TB incidence rate reduction (IRR) in 2050 under each update method. We found that vaccine impact estimates in all age groups remained relatively stable between the M0-M3 models, irrespective of vaccine-targeting by age group. The maximum difference in impact, observed following adult-targeted vaccination, was 7% in the elderly, in whom we observed IRRs of 19% (uncertainty range 13-32), 20% (UR 13-31), 22% (UR 14-37), and 26% (UR 18-38) following M0, M1, M2 and M3 updates, respectively. We found that model-based TB vaccine impact estimates were relatively insensitive to demography-matched contact matrix updates in an India-like demographic and epidemiologic scenario. Current model-based TB vaccine impact estimates may be reasonably robust to the lack of contact matrix updates, but further research is needed to confirm and generalise this finding., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: G.B.G. and R.C.H. report currently being employed at Sanofi Pasteur, unrelated to this work or TB.

Background: Differentiated service delivery (DSD) offers benefits to people living with HIV (improved access, peer support), and the health system (clinic decongestion, efficient service delivery). ART clubs, 15-30 clients who usually meet within the community, are one of the most common DSD options. However, evidence about the quality of care (QoC) delivered in ART clubs is still limited., Materials and Methods: We conducted a concurrent triangulation mixed-methods study as part of the Test & Treat project in northwest Tanzania. We surveyed QoC among stable clients and health care workers (HCW) comparing between clinics and clubs. Using a Donabedian framework we structured the analysis into three levels of assessment: structure (staff, equipment, supplies, venue), processes (time-spent, screenings, information, HCW-attitude), and outcomes (viral load, CD4 count, retention, self-worth)., Results: We surveyed 629 clients (40% in club) and conducted eight focus group discussions, while 24 HCW (25% in club) were surveyed and 22 individual interviews were conducted. Quantitative results revealed that in terms of structure, clubs fared better than clinics except for perceived adequacy of service delivery venue (94.4% vs 50.0%, p = 0.013). For processes, time spent receiving care was significantly more in clinics than clubs (119.9 vs 49.9 minutes). Regarding outcomes, retention was higher in the clubs (97.6% vs 100%), while the proportion of clients with recent viral load <50 copies/ml was higher in clinics (100% vs 94.4%). Qualitative results indicated that quality care was perceived similarly among clients in clinics and clubs but for different reasons. Clinics were generally perceived as places with expertise and clubs as efficient places with peer support and empathy. In describing QoC, HCW emphasized structure-related attributes while clients focused on processes. Outcomes-related themes such as improved client health status, self-worth, and confidentiality were similarly perceived across clients and HCW., Conclusion: We found better structure and process of care in clubs than clinics with comparable outcomes. While QoC was perceived similarly in clinics and clubs, its meaning was understood differently between clients. DSD catered to the individual needs of clients, either technical care in the clinic or proximate and social care in the club. Our findings highlight that both clinic and DSD care are required as many elements of QoC were individually perceived., Competing Interests: The Shinyanga and Simiyu Test & Treat program in Tanzania is funded by Gilead Sciences (USA). This does not alter our adherence to PLOS ONE policies on sharing data and materials. [GBG is currently employed by Sanofi Pasteur. Sanofi Pasteur was not involved in any way and did not provide funding for this study]. All other authors declare that they have no competing interests.

Health system constraints are increasingly recognized as an important addition to model-based analyses of disease control interventions, as they affect achievable impact and scale. Enabling activities implemented alongside interventions to relax constraints and reach the intended coverage may incur additional costs, which should be considered in priority setting decisions. We explore the use of group model building, a participatory system dynamics modelling technique, for eliciting information from key stakeholders on the constraints that apply to tuberculosis infection prevention and control processes within primary healthcare clinics in South Africa. This information was used to design feasible interventions, including the necessary enablers to relax existing constraints. Intervention and enabler costs were then calculated at two clinics in KwaZulu-Natal using input prices and quantities from the published literature and local suppliers. Among the proposed interventions, the most inexpensive was retrofitting buildings to improve ventilation (US$1644 per year), followed by maximizing the use of community sites for medication collection among stable patients on antiretroviral therapy (ART; US$3753) and introducing appointments systems to reduce crowding (US$9302). Enablers identified included enhanced staff training, supervision and patient engagement activities to support behaviour change and local ownership. Several of the enablers identified by the stakeholders, such as obtaining building permissions or improving information flow between levels of the health systems, were not amenable to costing. Despite this limitation, an approach to costing rooted in system dynamics modelling can be successfully applied in economic evaluations to more accurately estimate the 'real world' opportunity cost of intervention options. Further empirical research applying this approach to different intervention types (e.g. new preventive technologies or diagnostics) may identify interventions that are not cost-effective in specific contexts based on the size of the required investment in enablers., (© The Author(s) 2021. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

The M72/AS01 E tuberculosis vaccine showed 50% (95%CI: 2-74%) efficacy in a phase 2B trial in preventing active pulmonary tuberculosis disease, but potential cost-effectiveness of adolescent immunisation is unknown. We estimated the impact and cost-effectiveness of six scenarios of routine adolescent M72/AS01 E -like vaccination in South Africa and India. All scenarios suggested an M72/AS01 E -like vaccine would be highly (94-100%) cost-effective in South Africa compared to a cost-effectiveness threshold of $2480/disability-adjusted life-year (DALY) averted. For India, a prevention of disease vaccine, effective irrespective of recipient's M. tuberculosis infection status at time of administration, was also highly likely (92-100%) cost-effective at a threshold of $264/DALY averted; however, a prevention of disease vaccine, effective only if the recipient was already infected, had 0-6% probability of cost-effectiveness. In both settings, vaccinating 50% of 18 year-olds was similarly cost-effective to vaccinating 80% of 15 year-olds, and more cost-effective than vaccinating 80% of 10 year-olds. Vaccine trials should include adolescents to ensure vaccines can be delivered to this efficient-to-target population., (© 2022. The Author(s).)

Background: With antiretroviral therapy, more people living with HIV (PLHIV) in resource-limited settings are virally suppressed and living longer. WHO recommends differentiated service delivery (DSD) as an alternative, less resource-demanding way of expanding HIV services access. Monitoring client's health-related quality of life (HRQoL) is necessary to understand patients' perceptions of treatment and services but is understudied in sub-Saharan Africa. We assessed HRQoL among ART clients in Tanzania accessing two service models., Methods: Cross-sectional survey from May-August 2019 among stable ART clients randomly sampled from clinics and clubs in the Shinyanga region providing DSD and clinic-based care. HRQoL data were collected using a validated HIV-specific instrument-Functional Assessment of HIV infection (FAHI), in addition to socio-demographic, HIV care, and service accessibility data. Descriptive analysis of HRQoL, logistic regression and a stepwise multiple linear regression were performed to examine HRQoL determinants., Results: 629 participants were enrolled, of which 40% accessed DSD. Similar HRQoL scores [mean (SD), p-value]; FAHI total [152.2 (22.2) vs 153.8 (20.6), p 0.687] were observed among DSD and clinic-based care participants. Accessibility factors contributed more to emotional wellbeing among DSD participants compared to the clinic-based care participants (53.4% vs 18.5%, p =  < 0.001). Satisfactory (> 80% of maximum score) HRQoL scoring was associated with (OR [95% CI], p-value) being male (2.59 [1.36-4.92], p 0.004) among clinic participants and with urban residence (4.72 [1.70-13.1], p 0.001) among DSD participants., Conclusions: Similar HRQoL was observed in DSD and clinic-based care. Our research highlights focus areas to identify supporting interventions, ultimately optimizing HRQoL among PLHIV., (© 2021. The Author(s).)

Objectives: Patients with highly resistant tuberculosis have few treatment options. Bedaquiline, pretomanid and linezolid regimen (BPaL) is a new regimen shown to have favourable outcomes after six months. We present an economic evaluation of introducing BPaL against the extensively drug-resistant tuberculosis (XDR-TB) standard of care in three epidemiological settings., Design: Cost-effectiveness analysis using Markov cohort model., Setting: South Africa, Georgia and the Philippines., Participants: XDR-TB and multidrug-resistant tuberculosis (MDR-TB) failure and treatment intolerant patients., Interventions: BPaL regimen. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) Incremental cost per disability-adjusted life years averted by using BPaL against standard of care at the Global Drug Facility list price. (2) The potential maximum price at which the BPaL regimen could become cost neutral., Results: BPaL for XDR-TB is likely to be cost saving in all study settings when pretomanid is priced at the Global Drug Facility list price. The magnitude of these savings depends on the prevalence of XDR-TB in the country and can amount, over 5 years, to approximately US$ 3 million in South Africa, US$ 200 000 and US$ 60 000 in Georgia and the Philippines, respectively. In South Africa, related future costs of antiretroviral treatment (ART) due to survival of more patients following treatment with BPaL reduced the magnitude of expected savings to approximately US$ 1 million. Overall, when BPaL is introduced to a wider population, including MDR-TB treatment failure and treatment intolerant, we observe increased savings and clinical benefits. The potential threshold price at which the probability of the introduction of BPaL becoming cost neutral begins to increase is higher in Georgia and the Philippines (US$ 3650 and US$ 3800, respectively) compared with South Africa (US$ 500) including ART costs., Conclusions: Our results estimate that BPaL can be a cost-saving addition to the local TB programmes in varied programmatic settings., Competing Interests: Competing interests: GG is currently employed by Sanofi Pasteur as decision science expert. Sanofi Pasteur has not provided funding for this work. SM was employed by the TB Alliance at the start of this project. SC-S, SJ, DE and MS are employees of the TB Alliance., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The 2016-2017 Tanzania HIV Impact Survey (THIS) reported the accomplishments towards the 90-90-90 global HIV targets at 61-94-87, affirming the need to focus on the first 90 (i.e., getting 90% of people living with HIV (PLHIV) tested). We conducted a patient-pathway analysis to understand the gap observed, by assessing the alignment between where PLHIV seek healthcare and where HIV services are available in the Shinyanga region, Tanzania. We used existing and publicly available data from the National AIDS Control program, national surveys, registries, and relevant national reports. Region-wide, the majority ( n = 458/722, 64%) of THIS respondents accessed their last HIV test at public sector facilities. There were 65.9%, 45.1%, and 74.1% who could also access antiretroviral therapy (ART), CD4 testing, and HIV viral load testing at the location of their last HIV test, respectively. In 2019, the viral suppression rate estimated among PLHIV on ART in the Shinyanga region was 91.5%. PLHIV access HIV testing mostly in public health facilities; our research shows that synergies can be achieved to improve access to services further down the cascade in this sector. Furthermore, effective engagement with the private sector (not-for-profit and for-profit) will help to achieve the last mile toward ending the HIV epidemic.

Introduction: The World Health Organization recommends differentiated service delivery (DSD) to support resource-limited health systems in providing patient-centered HIV care. DSD offers alternative care models to clinic-based care for people living with HIV who are stable on antiretroviral therapy (ART). Despite good patient-related outcomes, there is limited evidence of their sustainability. Our review evaluated the reporting of sustainability indicators of DSD interventions conducted in sub-Saharan Africa (SSA)., Methods: We searched PubMed and EMBASE for studies conducted between 2000 and 2019 assessing DSD interventions targeting HIV-positive individuals who are established in ART in sub-Saharan Africa. We evaluated them through a comprehensive sustainability framework of constructs categorized into 6 domains (intervention design, process, external environment, resources, organizational setting, and people involvement). We scored each construct 1, 2, or 3 for no, partial, or sufficient level of evidence, respectively. Interventions with a calculated sustainability score (overall and domain-specific) of >90% or domain-specific median score >2.7 were considered likely to be sustainable., Results: Overall scores ranged from 69% to 98%. Top scoring intervention types included adherence clubs (98%) and community ART groups (95%) which comprised more than half of interventions. The highest scoring domains were design (2.9) and organizational setting (2.8). The domains of resources (2.4) and people involvement (2.3) scored lowest revealing potential areas for improvement to support DSD sustainability., Conclusions: With the right investment in stakeholder involvement and domestic funding, DSD models generally show potential for sustainability. Our results could guide informed decisions on which DSD intervention is likely to be sustainable per setting and highlight areas that could motivate further research., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Following success demonstrated with the HIV Self-Testing AfRica Initiative, HIV self-testing (HIVST) is being added to national HIV testing strategies in Southern Africa. An analysis of the costs of scaling up HIVST is needed to inform national plans, but there is a dearth of evidence on methods for forecasting costs at scale from pilot projects. Econometric cost functions (ECFs) apply statistical inference to predict costs; however, we often do not have the luxury of collecting large amounts of location-specific data. We fit an ECF to identify key drivers of costs, then use a simpler model to guide cost projections at scale., Methods: We estimated the full economic costs of community-based HIVST distribution in 92 locales across Malawi, Zambia, Zimbabwe, South Africa and Lesotho between June 2016 and June 2019. We fitted a cost function with determinants related to scale, locales organisational and environmental characteristics, target populations, and per capita Growth Domestic Product (GDP). We used models differing in data intensity to predict costs at scale. We compared predicted estimates with scale-up costs in Lesotho observed over a 2-year period., Results: The scale of distribution, type of community-based intervention, percentage of kits distributed to men, distance from implementer's warehouse and per capita GDP predicted average costs per HIVST kit distributed. Our model simplification approach showed that a parsimonious model could predict costs without losing accuracy. Overall, ECF showed a good predictive capacity, that is, forecast costs were close to observed costs. However, at larger scale, variations of programme efficiency over time (number of kits distributed per agent monthly) could potentially influence cost predictions., Discussion: Our empirical cost function can inform community-based HIVST scale-up in Southern African countries. Our findings suggest that a parsimonious ECF can be used to forecast costs at scale in the context of financial planning and budgeting., Competing Interests: Competing interests: GBG is currently employed by Sanofi Pasteur, France., (©World Health Organization 2021. Licensee BMJ.)

Introduction: Placing all clients with a positive diagnosis for HIV on antiretroviral therapy (ART) has cost implications both for patients and health systems, which could, in turn, affect feasibility, sustainability and uptake of new services. Patient-incurred costs are recognized barriers to healthcare access. Differentiated service delivery (DSD) models in general and community-based care in particular, could reduce these costs. We aimed to assess patient-incurred costs of a community-based DSD intervention (clubs) compared to clinic-based care in the Shinyanga region, Tanzania., Methods: Cross-sectional survey among stable ART patients (n = 390, clinic-based; n = 251, club-based). For each group, we collected socio-demographic, income and expenditure data between May and August 2019. We estimated direct and indirect patient-incurred costs. Direct costs included out-of-pocket expenditures. Indirect costs included income loss due to time spent during transport, accessing services and off work during illness. Cost drivers were assessed in multivariate regression models., Results: Overall, costs were significantly higher among clinic participants. Costs (USD) per year for clinic versus club were as follows: 11.7 versus 4.17 (p < 0.001) for direct costs, 20.9 versus 8.23 (p < 0.001) for indirect costs and 32.2 versus 12.4 (p < 0.001) for total costs. Time spent accessing care and time spent in illness (hours/year) were 38.3 versus 13.8 (p < 0.001) and 16.0 versus 6.69 (p < 0.001) respectively. The main cost drivers included transportation (clinic vs. club: 67.7% vs. 44.1%) for direct costs and income loss due to time spent accessing care (clinic vs. club: 60.4% vs. 56.7%) for indirect costs. Factors associated with higher total costs among patients attending clinic services were higher education level (coefficient [95% confidence interval]) 20.9 [5.47 to 36.3]) and formal employment (44.2 [20.0 to 68.5). Differences in mean total costs remained significantly higher with formal employment, rural residence, in addition to more frequent visits among clinic participants. The percentage of households classified as having had catastrophic expenditures in the last year was low but significantly higher among clinic participants (10.8% vs. 5.18%, p = 0.014)., Conclusions: Costs incurred by patients accessing DSD in the community are significantly lower compared to those accessing standard clinic-based care. DSD models could improve access, especially in resource-limited settings., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

Priority setting for infectious disease control is increasingly concerned with physical input constraints and other real-world restrictions on implementation and on the decision process. These health system constraints determine the 'feasibility' of interventions and hence impact. However, considering them within mathematical models places additional demands on model structure and relies on data availability. This review aims to provide an overview of published methods for considering constraints in mathematical models of infectious disease. We systematically searched the literature to identify studies employing dynamic transmission models to assess interventions in any infectious disease and geographical area that included non-financial constraints to implementation. Information was extracted on the types of constraints considered and how these were identified and characterised, as well as on the model structures and techniques for incorporating the constraints. A total of 36 studies were retained for analysis. While most dynamic transmission models identified were deterministic compartmental models, stochastic models and agent-based simulations were also successfully used for assessing the effects of non-financial constraints on priority setting. Studies aimed to assess reductions in intervention coverage (and programme costs) as a result of constraints preventing successful roll-out and scale-up, and/or to calculate costs and resources needed to relax these constraints and achieve desired coverage levels. We identified three approaches for incorporating constraints within the analyses: (i) estimation within the disease transmission model; (ii) linking disease transmission and health system models; (iii) optimising under constraints (other than the budget). The review highlighted the viability of expanding model-based priority setting to consider health system constraints. We show strengths and limitations in current approaches to identify and quantify locally-relevant constraints, ranging from simple assumptions to structured elicitation and operational models. Overall, there is a clear need for transparency in the way feasibility is defined as a decision criteria for its systematic operationalisation within models., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The accelerated vaccine development in response to the COVID-19 pandemic should lead to a vaccine being available early 2021, albeit in limited supply and possibly without full vaccine acceptance. We assessed the short-term impact of a COVID-19 immunization program with varying constraints on population health and non-pharmaceutical interventions (NPIs) needs., Methods: A SARS-CoV-2 transmission model was calibrated to French epidemiological data. We defined several vaccine implementation scenarios starting in January 2021 based on timing of discontinuation of NPIs, supply and uptake constraints, and their relaxation. We assessed the number of COVID-19 hospitalizations averted, the need for and number of days with NPIs in place over the 2021-2022 period., Results: An immunisation program under constraints could reduce the burden of COVID-19 hospitalizations by 9-40% if the vaccine prevents against infections. Relaxation of constraints not only reduces further COVID-19 hospitalizations (30-39% incremental reduction), it also allows for NPIs to be discontinued post-2021 (0 days with NPIs in 2022 versus 11 to 125 days for vaccination programs under constraints and 327 in the absence of vaccination)., Conclusion: For 2021, COVID-19 control is expected to rely on a combination of NPIs and the outcome of early immunisation programs. The ability to overcome supply and uptake constraints will help prevent the need for further NPIs post-2021. As the programs expand, efficiency assessments will be needed to ensure optimisation of control policies post-emergency use., Competing Interests: All authors are Sanofi employees and may hold shares and/or stock options in the company. This does not alter the adherence of the authors to PLOS ONE policies on sharing data and materials.

Background: One critical element to optimize funding decisions involves the cost and efficiency implications of implementing alternative program components and configurations. Program planners, policy makers and funders alike are in need of relevant, strategic data and analyses to help them plan and implement effective and efficient programs. Contrary to widely accepted conceptions in both policy and academic arenas, average costs per service (so-called "unit costs") vary considerably across implementation settings and facilities. The objective of this work is twofold: 1) to estimate the variation of VMMC unit costs across service delivery platforms (SDP) in Sub-Saharan countries, and 2) to develop and validate a strategy to extrapolate unit costs to settings for which no data exists., Methods: We identified high-quality VMMC cost studies through a literature review. Authors were contacted to request the facility-level datasets (primary data) underlying their results. We standardized the disparate datasets into an aggregated database which included 228 facilities in eight countries. We estimated multivariate models to assess the correlation between VMMC unit costs and scale, while simultaneously accounting for the influence of the SDP (which we defined as all possible combinations of type of facility, ownership, urbanicity, and country), on the unit cost variation. We defined SDP as any combination of such four characteristics. Finally, we extrapolated VMMC unit costs for all SDPs in 13 countries, including those not contained in our dataset., Results: The average unit cost was 73 USD (IQR: 28.3, 100.7). South Africa showed the highest within-country cost variation, as well as the highest mean unit cost (135 USD). Uganda and Namibia had minimal within-country cost variation, and Uganda had the lowest mean VMMC unit cost (22 USD). Our results showed evidence consistent with economies of scale. Private ownership and Hospitals were significant determinants of higher unit costs. By identifying key cost drivers, including country- and facility-level characteristics, as well as the effects of scale we developed econometric models to estimate unit cost curves for VMMC services in a variety of clinical and geographical settings., Conclusion: While our study did not produce new empirical data, our results did increase by a tenfold the availability of unit costs estimates for 128 SDPs in 14 priority countries for VMMC. It is to our knowledge, the most comprehensive analysis of VMMC unit costs to date. Furthermore, we provide a proof of concept of the ability to generate predictive cost estimates for settings where empirical data does not exist., Competing Interests: All authors declare no conflict of interest. Coauthors Forsythe S, Tchuenche M, and Bollinger LA are employed by Avenir Health and Chiwevu C is an independent consultant. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

New tuberculosis vaccines have made substantial progress in the development pipeline. Previous modelling suggests that adolescent/adult mass vaccination may cost-effectively contribute towards achieving global tuberculosis control goals. These analyses have not considered the budgetary feasibility of vaccine programmes. We estimate the maximum total cost that the public health sectors in India and China should expect to pay to introduce a M72/AS01 E -like vaccine deemed cost-effective at country-specific willingness to pay thresholds for cost-effectiveness. To estimate the total disability adjusted life years (DALYs) averted by the vaccination programme, we simulated a 50% efficacy vaccine providing 10-years of protection in post-infection populations between 2027 and 2050 in India and China using a dynamic transmission model of M. tuberculosis . We investigated two mass vaccination strategies, both delivered every 10-years achieving 70% coverage: Vaccinating adults and adolescents (age ≥10y), or only the most efficient 10-year age subgroup (defined as greatest DALYs averted per vaccine given). We used country-specific thresholds for cost-effectiveness to estimate the maximum total cost (C max ) a government should be willing to pay for each vaccination strategy. Adult/adolescent vaccination resulted in a C max of $21 billion (uncertainty interval [UI]: 16-27) in India, and $15B (UI:12-29) in China at willingness to pay thresholds of $264/DALY averted and $3650/DALY averted, respectively. Vaccinating the highest efficiency age group (India: 50-59y; China: 60-69y) resulted in a C max of $5B (UI:4-6) in India and $6B (UI:4-7) in China. Mass vaccination against tuberculosis of all adults and adolescents, deemed cost-effective, will likely impose a substantial budgetary burden. Targeted tuberculosis vaccination, deemed cost-effective, may represent a more affordable approach.

Background: Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India., Methods: We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027-2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses., Results: By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69-72) and 72% (UI: 70-74), and the PSI vaccine by 31% (UI: 30-32) and 44% (UI: 42-47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8-1.1) and 1.1 million (UI: 0.9-1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively., Conclusions: Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

Objective: Cost functions linked to transmission dynamic models are commonly used to estimate the resources required for infectious disease policies. We present a conceptual and empirical approach for estimating these functions, allowing for nonconstant marginal costs. We aim to expand on the current approach which commonly assumes linearity of cost over scale., Methods: We propose a theoretical framework adapted from the field of transport economics. We specify joint functions of production of services within a disease-specific program. We expand these functions to include qualitative insights of program expansion patterns. We present the difference in incremental total costs between an approach assuming constant unit costs and alternative approaches that assume economies of scale, scope and homogeneous or heterogeneous facility recruitment into the programme during scale-up. We illustrate the framework's application in tuberculosis, using secondary data from the literature and routine reporting systems in South Africa., Results: Economies of capacity and scope substantially change cost estimates over time. Cost data requirements for the proposed approach included standardized and disaggregated unit costs (for a limited number of outputs) and information on the facilities network available to the program., Conclusions: The defined functional form will determine the magnitude and shape of costs when outputs and coverage are increasing. This in turn will impact resource allocation decisions. Infectious diseases modelers and economists should use transparent and empirically based cost models for analyses that inform resource allocation decisions. This framework describes a general approach for developing these models., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objectives: New HIV infections remain higher in women than men in sub-Saharan Africa. Preexposure prophylaxis (PrEP) is an effective HIV prevention measure, currently prioritized for those at highest risk, such as female sex workers (FSWs), for whom it is most cost-effective. However, the greatest number of HIV infections in sub-Saharan Africa occurs in women in the general population. As countries consider wider PrEP scale-up, there is a need to weigh the population-level impact, cost, and relative cost-effectiveness to inform priority setting., Methods: We developed mathematical models of HIV risk to women and derived tools to highlight key considerations for PrEP programming. The models were fitted to South Africa, Zimbabwe, and Kenya, spanning a range of HIV burden in sub-Saharan Africa. The impact, cost, and cost-effectiveness of PrEP scale-up for adolescent girls and young women (AGYW), women 25 to 34 years old, and women 35 to 49 years old were assessed, accounting for differences in population sizes and the low program retention levels reported in demonstration projects., Results: Preexposure prophylaxis could avert substantially more infections a year among women in general population than among FSW. The greatest number of infections could be averted annually among AGYW in South Africa (24-fold that for FSW). In Zimbabwe, the greatest number of infections could be averted among women 25 to 34 years old (8-fold that for FSW); and in Kenya, similarly between AGYW and women 25 to 34 years old (3-fold that for FSW). However, the unit costs of PrEP delivery for AGYW, women 25 to 34 years old, and women 35 to 49 years old would have to reduce considerably (by 70.8%-91.0% across scenarios) for scale-up to these populations to be as cost-effective as for FSW., Conclusions: Preexposure prophylaxis has the potential to substantially reduce new HIV infections in HIV-endemic countries in sub-Saharan Africa. This will necessitate PrEP being made widely available beyond those at highest individual risk and continued integration into a range of national services and at community level to significantly bring down the costs and improve cost-effectiveness.

Objectives: Health systems face nonfinancial constraints that can influence the opportunity cost of interventions. Empirical methods to explore their impact, however, are underdeveloped. We develop a conceptual framework for defining health system constraints and empirical estimation methods that rely on routine data. We then present an empirical approach for incorporating nonfinancial constraints in cost-effectiveness models of health benefit packages for the health sector., Methods: We illustrate the application of this approach through a case study of defining a package of services for tuberculosis case-finding in South Africa. An economic model combining transmission model outputs with unit costs was developed to examine the cost-effectiveness of alternative screening and diagnostic algorithms. Constraints were operationalized as restrictions on achievable coverage based on: (1) financial resources; (2) human resources; and (3) policy constraints around diagnostics purchasing. Cost-effectiveness of the interventions was assessed under one "unconstrained" and several "constrained" scenarios. For the unconstrained scenario, incremental cost-effectiveness ratios were estimated with and without the costs of "relaxing" constraints., Results: We find substantial differences in incremental cost-effectiveness ratios across scenarios, leading to variations in the decision rules for prioritizing interventions. In constrained scenarios, the limiting factor for most interventions was not financial, but rather the availability of human resources., Conclusions: We find that optimal prioritization among different tuberculosis control strategies in South Africa is influenced by whether and how constraints are taken into consideration. We thus demonstrate both the importance and feasibility of considering nonfinancial constraints in health sector resource allocation models., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to appropriately plan for rollout and monitor impact of oral preexposure prophylaxis (PrEP). It is important to understand PrEP continuation and come to a consensus on how best to measure PrEP continuation. This study reviews data on PrEP continuation to document how it is reported, and to compare continuation over time and across populations., Design: A systematic review and meta-analysis., Methods: We searched MEDLINE, Embase and Global Health and reviewed abstracts from HIV conferences from 2017 to 2018 for studies reporting primary data on PrEP continuation. Findings were summarized along a PrEP cascade and continuation was presented by population at months 1, 6 and 12, with random-effects meta-analysis., Results: Of 2578 articles and 596 abstracts identified, 41 studies were eligible covering 22 034 individuals. Continuation data were measured and reported inconsistently. Results showed high discontinuation at month 1 and persistent discontinuation at later time points in many studies. Pooled continuation estimates were 66% at month 1 [n = 5348; 95% confidence interval (95% CI): 48-82], 63% at month 6 (n = 13 629; 95% CI: 48-77) and 71% at month 12 (n = 14 933; 95% CI: 60-81; higher estimate than previous timepoints due to inclusion of different studies). Adequate data were not available to reliably compare estimates across populations., Conclusion: This review found that discontinuation at one month was high, suggesting PrEP initiations may be a poor measure of effectiveness. Continuation declined further over time in many studies, indicating existing cross-sectional indicators may not be adequate to understand PrEP use patterns. Studies do not measure continuation consistently, and consensus is needed.

BACKGROUND: Despite a scarcity of tuberculosis (TB) cost data, a substantial body of evidence has been accumulating for drug-susceptible TB (DS-TB) treatment. In this study, we review unit costs for DS-TB treatment from a provider´s perspective. We also examine factors driving cost variations and extrapolate unit costs across low- and middle-income countries (LMICs). METHODS: We searched published and grey literature for any empirically collected TB cost estimates. We selected a subgroup of estimates looking at DS-TB treatment. We extracted information on activities and inputs included. We standardised costs into an average per person-month, fitted a multi-level regression model and cross-validated country-level predictions. We then extrapolated estimates for facility-based, directly observed DS-TB treatment across countries. RESULTS: We included 95 cost estimates from 28 studies across 17 countries. Costs predictions were sensitive to characteristics such as delivery mode, whether hospitalisation was included, and inputs accounted for, as well as gross domestic product per capita. Extrapolation results are presented with uncertainty intervals (UIs) for LMICs. Predicted median costs per 6 months of treatment were US$315.30 (95% CI US$222.60-US$417.20) for low-income, US$527.10 (95% CI US$395.70-US$743.70) for lower middle-income and US$896.40 (95% CI US$654.00-US$1214.40) for upper middle-income countries. CONCLUSIONS: Our study provides country-level DS-TB treatment cost estimates suitable for priority setting. These estimates, while not standing as a substitute for local high-quality primary data, can inform global, regional and national exercises.

Background: There is a need for easily accessible tuberculosis unit cost data, as well as an understanding of the variability of methods used and reporting standards of that data., Objective: The aim of this systematic review was to descriptively review papers reporting tuberculosis unit costs from a healthcare provider perspective looking at methodological variation; to assess quality using a study quality rating system and machine learning to investigate the indicators of reporting quality; and to identify the data gaps to inform standardised tuberculosis unit cost collection and consistent principles for reporting going forward., Methods: We searched grey and published literature in five sources and eight databases, respectively, using search terms linked to cost, tuberculosis and tuberculosis health services including tuberculosis treatment and prevention. For inclusion, the papers needed to contain empirical unit cost estimates for tuberculosis interventions from low- and middle-income countries, with reference years between 1990 and 2018. A total of 21,691 papers were found and screened in a phased manner. Data were extracted from the eligible papers into a detailed Microsoft Excel tool, extensively cleaned and analysed with R software (R Project, Vienna, Austria) using the user interface of RStudio. A study quality rating was applied to the reviewed papers based on the inclusion or omission of a selection of variables and their relative importance. Following this, machine learning using a recursive partitioning method was utilised to construct a classification tree to assess the reporting quality., Results: This systematic review included 103 provider perspective papers with 627 unit costs (costs not presented here) for tuberculosis interventions among a total of 140 variables. The interventions covered were active, passive and intensified case finding; tuberculosis treatment; above-service costs; and tuberculosis prevention. Passive case finding is the detection of tuberculosis cases where individuals self-identify at health facilities; active case finding is detection of cases of those not in health facilities, such as through outreach; and intensified case finding is detection of cases in high-risk populations. There was heterogeneity in some of the reported methods used such cost allocation, amortisation and the use of top-down, bottom-up or mixed approaches to the costing. Uncertainty checking through sensitivity analysis was only reported on by half of the papers (54%), while purposive and convenience sampling was reported by 72% of papers. Machine learning indicated that reporting on 'Intervention' (in particular), 'Urbanicity' and 'Site Sampling', were the most likely indicators of quality of reporting. The largest data gap identified was for tuberculosis vaccination cost data, the Bacillus Calmette-Guérin (BCG) vaccine in particular. There is a gap in available unit costs for 12 of 30 high tuberculosis burden countries, as well as for the interventions of above-service costs, tuberculosis prevention, and active and intensified case finding., Conclusion: Variability in the methods and reporting used makes comparison difficult and makes it hard for decision makers to know which unit costs they can trust. The study quality rating system used in this review as well as the classification tree enable focus on specific reporting aspects that should improve variability and increase confidence in unit costs. Researchers should endeavour to be explicit and transparent in how they cost interventions following the principles as laid out in the Global Health Cost Consortium's Reference Case for Estimating the Costs of Global Health Services and Interventions, which in turn will lead to repeatability, comparability and enhanced learning from others.

In the original version of this article, Fig. 3 was published in an incorrect format. The correct figure is published with this correction.