Time to bring female genital schistosomiasis out of neglect.

BACKGROUND: Female genital schistosomiasis (FGS) is a chronic gynaecological disease affecting girls and women in sub-Saharan Africa (SSA), caused by the parasite Schistosoma (S.) haematobium. FGS is associated with sexual dysfunction, reproductive tract morbidity and increased prevalence of HIV and cervical precancer lesions. SOURCE OF DATA: Key peer-reviewed published literature. AREAS OF AGREEMENT: FGS screening and diagnosis require costly equipment and specialized training, seldom available in resource-limited settings. FGS surveillance is not included in wider schistosomiasis control strategies. The interplay of FGS with other SRH infections is not fully understood. Integration of FGS within sexual and reproductive health (SRH) control programmes needs to be explored. AREAS OF CONTROVERSY: There are no standardized methods for individual or population-based FGS screening and diagnosis, hindering accurate disease burden estimates and targeted resource allocation. Treatment recommendations rely on public health guidelines, without rigorous clinical evidence on efficacy. GROWING POINTS: Integrating FGS screening with SRH programmes offers an opportunity to reach at-risk women with limited access to healthcare services. Home-based self-sampling coupled with handheld colposcopes operated by primary healthcare workers show promise for FGS diagnosis and surveillance at scale. AREAS TIMELY FOR DEVELOPING RESEARCH: There is growing interest in decentralizing strategies for FGS screening and diagnosis. The accurate predictions on the 'cost-effectiveness' of these approaches will determine their affordability and feasibility within the overburdened health systems in SSA. Clinical trials are needed to optimize FGS treatment. Longitudinal studies can expand on the epidemiological knowledge on co-morbidities and integration within other SRH interventions.

A health decision analytical model to evaluate the cost-effectiveness of female genital schistosomiasis screening strategies: The female genital schistosomiasis SCREEN framework.

Female genital schistosomiasis is a chronic gynaecological disease caused by the waterborne parasite Schistosoma (S.) haematobium. It affects an estimated 30-56 million girls and women globally, mostly in sub-Saharan Africa where it is endemic, and negatively impacts their sexual and reproductive life. Recent studies found evidence of an association between female genital schistosomiasis and increased prevalence of HIV and cervical precancer lesions. Despite the large population at risk, the burden and impact of female genital schistosomiasis are scarcely documented, resulting in neglect and insufficient resource allocation. There is currently no standardised method for individual or population-based female genital schistosomiasis screening and diagnosis which hinders accurate assessment of disease burden in endemic countries. To optimise financial allocations for female genital schistosomiasis screening, it is necessary to explore the cost-effectiveness of different strategies by combining cost and impact estimates. Yet, no economic evaluation has explored the value for money of alternative screening methods. This paper describes a novel application of health decision analytical modelling to evaluate the cost-effectiveness of different female genital schistosomiasis screening strategies across endemic settings. The model combines a decision tree for female genital schistosomiasis screening strategies, and a Markov model for the natural history of cervical cancer to estimate the cost per disability-adjusted life-years averted for different screening strategies, stratified by HIV status. It is a starting point for discussion and for supporting priority setting in a data-sparse environment.

Correction: COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

[This corrects the article DOI: 10.1371/journal.pmed.1003815.].

COVID-19 vaccination in Sindh Province, Pakistan: A modelling study of health impact and cost-effectiveness.

BACKGROUND: Multiple Coronavirus Disease 2019 (COVID-19) vaccines appear to be safe and efficacious, but only high-income countries have the resources to procure sufficient vaccine doses for most of their eligible populations. The World Health Organization has published guidelines for vaccine prioritisation, but most vaccine impact projections have focused on high-income countries, and few incorporate economic considerations. To address this evidence gap, we projected the health and economic impact of different vaccination scenarios in Sindh Province, Pakistan (population: 48 million). METHODS AND FINDINGS: We fitted a compartmental transmission model to COVID-19 cases and deaths in Sindh from 30 April to 15 September 2020. We then projected cases, deaths, and hospitalisation outcomes over 10 years under different vaccine scenarios. Finally, we combined these projections with a detailed economic model to estimate incremental costs (from healthcare and partial societal perspectives), disability-adjusted life years (DALYs), and incremental cost-effectiveness ratio (ICER) for each scenario. We project that 1 year of vaccine distribution, at delivery rates consistent with COVAX projections, using an infection-blocking vaccine at $3/dose with 70% efficacy and 2.5-year duration of protection is likely to avert around 0.9 (95% credible interval (CrI): 0.9, 1.0) million cases, 10.1 (95% CrI: 10.1, 10.3) thousand deaths, and 70.1 (95% CrI: 69.9, 70.6) thousand DALYs, with an ICER of $27.9 per DALY averted from the health system perspective. Under a broad range of alternative scenarios, we find that initially prioritising the older (65+) population generally prevents more deaths. However, unprioritised distribution has almost the same cost-effectiveness when considering all outcomes, and both prioritised and unprioritised programmes can be cost-effective for low per-dose costs. High vaccine prices ($10/dose), however, may not be cost-effective, depending on the specifics of vaccine performance, distribution programme, and future pandemic trends. The principal drivers of the health outcomes are the fitted values for the overall transmission scaling parameter and disease natural history parameters from other studies, particularly age-specific probabilities of infection and symptomatic disease, as well as social contact rates. Other parameters are investigated in sensitivity analyses. This study is limited by model approximations, available data, and future uncertainty. Because the model is a single-population compartmental model, detailed impacts of nonpharmaceutical interventions (NPIs) such as household isolation cannot be practically represented or evaluated in combination with vaccine programmes. Similarly, the model cannot consider prioritising groups like healthcare or other essential workers. The model is only fitted to the reported case and death data, which are incomplete and not disaggregated by, e.g., age. Finally, because the future impact and implementation cost of NPIs are uncertain, how these would interact with vaccination remains an open question. CONCLUSIONS: COVID-19 vaccination can have a considerable health impact and is likely to be cost-effective if more optimistic vaccine scenarios apply. Preventing severe disease is an important contributor to this impact. However, the advantage of prioritising older, high-risk populations is smaller in generally younger populations. This reduction is especially true in populations with more past transmission, and if the vaccine is likely to further impede transmission rather than just disease. Those conditions are typical of many low- and middle-income countries.

The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China.

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.

Informing Balanced Investment in Services and Health Systems: A Case Study of Priority Setting for Tuberculosis Interventions in South Africa.

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.

Estimating Cost Functions for Resource Allocation Using Transmission Models: A Case Study of Tuberculosis Case Finding in South Africa.

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.

Estimating the Impact of Tuberculosis Case Detection in Constrained Health Systems: An Example of Case-Finding in South Africa.

Mathematical models are increasingly being used to compare strategies for tuberculosis (TB) control and inform policy decisions. Models often do not consider financial and other constraints on implementation and may overestimate the impact that can be achieved. We developed a pragmatic approach for incorporating resource constraints into mathematical models of TB. Using a TB transmission model calibrated for South Africa, we estimated the epidemiologic impact and resource requirements (financial, human resource (HR), and diagnostic) of 9 case-finding interventions. We compared the model-estimated resources with scenarios of future resource availability and estimated the impact of interventions under these constraints. Without constraints, symptom screening in public health clinics and among persons receiving care for human immunodeficiency virus infection was predicted to lead to larger reductions in TB incidence (9.5% (2.5th-97.5th percentile range (PR), 8.6-12.2) and 14.5% (2.5th-97.5th PR, 12.2-16.3), respectively) than improved adherence to diagnostic guidelines (2.7%; 2.5th-97.5th PR, 1.6-4.1). However, symptom screening required large increases in resources, exceeding future HR capacity. Even under our most optimistic HR scenario, the reduction in TB incidence from clinic symptom screening was 0.2%-0.9%-less than that of improved adherence to diagnostic guidelines. Ignoring resource constraints may result in incorrect conclusions about an intervention's impact and may lead to suboptimal policy decisions. Models used for decision-making should consider resource constraints.

Empirical estimation of resource constraints for use in model-based economic evaluation: an example of TB services in South Africa.

BACKGROUND: Evidence on the relative costs and effects of interventions that do not consider 'real-world' constraints on implementation may be misleading. However, in many low- and middle-income countries, time and data scarcity mean that incorporating health system constraints in priority setting can be challenging. METHODS: We developed a 'proof of concept' method to empirically estimate health system constraints for inclusion in model-based economic evaluations, using intensified case-finding strategies (ICF) for tuberculosis (TB) in South Africa as an example. As part of a strategic planning process, we quantified the resources (fiscal and human) needed to scale up different ICF strategies (cough triage and WHO symptom screening). We identified and characterised three constraints through discussions with local stakeholders: (1) financial constraint: potential maximum increase in public TB financing available for new TB interventions; (2) human resource constraint: maximum current and future capacity among public sector nurses that could be dedicated to TB services; and (3) diagnostic supplies constraint: maximum ratio of Xpert MTB/RIF tests to TB notifications. We assessed the impact of these constraints on the costs of different ICF strategies. RESULTS: It would not be possible to reach the target coverage of ICF (as defined by policy makers) without addressing financial, human resource and diagnostic supplies constraints. The costs of addressing human resource constraints is substantial, increasing total TB programme costs during the period 2016-2035 by between 7% and 37% compared to assuming the expansion of ICF is unconstrained, depending on the ICF strategy chosen. CONCLUSIONS: Failure to include the costs of relaxing constraints may provide misleading estimates of costs, and therefore cost-effectiveness. In turn, these could impact the local relevance and credibility of analyses, thereby increasing the risk of sub-optimal investments.

Cluster randomized evaluation of Adolescent Girls Empowerment Programme (AGEP): study protocol.

BACKGROUND: Adolescents in less developed countries such as Zambia often face multi-faceted challenges for achieving successful transitions through adolescence to early adulthood. The literature has noted the need to introduce interventions during this period, particularly for adolescent girls, with the perspective that such investments have significant economic, social and health returns to society. The Adolescent Girls Empowerment Programme (AGEP) was an intervention designed as a catalyst for change for adolescent girls through themselves, to their family and community. METHODS/DESIGN: AGEP was a multi-sectoral intervention targeting over 10,000 vulnerable adolescent girls ages 10-19 in rural and urban areas, in four of the ten provinces of Zambia. At the core of AGEP were mentor-led, weekly girls' group meetings of 20 to 30 adolescent girls participating over two years. Three curricula - sexual and reproductive health and lifeskills, financial literacy, and nutrition - guided the meetings. An engaging and participatory pedagogical approach was used. Two additional program components, a health voucher and a bank account, were offered to some girls to provide direct mechanisms to improve access to health and financial services. Embedded within AGEP was a rigorous multi-arm randomised cluster trial with randomization to different combinations of programme arms. The study was powered to assess the impact across a set of key longer-term outcomes, including early marriage and first birth, contraceptive use, educational attainment and acquisition of HIV and HSV-2. Baseline behavioural surveys and biological specimen collection were initiated in 2013. Impact was evaluated immediately after the program ended in 2015 and will be evaluated again after two additional years of follow-up in 2017. The primary analysis is intent-to-treat. Qualitative data are being collected in 2013, 2015 and 2017 to inform the programme implementation and the quantitative findings. An economic evaluation will evaluate the incremental cost-effectiveness of each component of the intervention. DISCUSSION: The AGEP program and embedded evaluation will provide detailed information regarding interventions for adolescent girls in developing country settings. It will provide a rich information and data source on adolescent girls and its related findings will inform policy-makers, health professionals, donors and other stakeholders. TRIAL REGISTRATION: ISRCTN29322231 . March 04 2016; retrospectively registered.

Randomized evaluation and cost-effectiveness of HIV and sexual and reproductive health service referral and linkage models in Zambia.

BACKGROUND: Provision of HIV prevention and sexual and reproductive health services in Zambia is largely characterized by discrete service provision with weak client referral and linkage. The literature reveals gaps in the continuity of care for HIV and sexual and reproductive health. This study assessed whether improved service delivery models increased the uptake and cost-effectiveness of HIV and sexual and reproductive health services. METHODS: Adult clients 18+ years of age accessing family planning (females), HIV testing and counseling (females and males), and male circumcision services (males) were recruited, enrolled and individually randomized to one of three study arms: 1) the standard model of service provision at the entry point (N = 1319); 2) an enhanced counseling and referral to add-on service with follow-up (N = 1323); and 3) the components of study arm two, with the additional offer of an escort (N = 1321). Interviews were conducted with the same clients at baseline, six weeks and six months. Uptake of services for HIV, family planning, male circumcision, and cervical cancer screening at six weeks and six months were the primary endpoints. Pairwise chi-square and multivariable logistic regression statistical tests assessed differences across study arms, which were also assessed for incremental cost-efficiency and cost-effectiveness. RESULTS: A total of 3963 clients, 1920 males and 2043 females, were enrolled; 82 % of participants at six weeks were tracked and 81 % at six months; follow-up rates did not vary significantly by study arm. The odds of clients accessing HIV testing and counseling, cervical cancer screening services among females, and circumcision services among males varied significantly by study arm at six weeks and six months; less consistent findings were observed for HIV care and treatment. Client uptake of family planning services did not vary significantly by study arm. Integrated services were found to be more efficiently provided than vertical service provision; the cost-effectiveness for HIV/AIDS and cervical cancer was high in the enhanced service models. CONCLUSIONS: Study results provide evidence for increasing the linkages and integration of a selection of HIV and sexual and reproductive health services. The study provided cost-effective service delivery models that enhanced the likelihood of clients accessing some additional needed health services. TRIAL REGISTRATION: ISRCTN84228514 Retrospectively registered. The study was retrospectively registered in the ISRCTN clinical trials registry on 06 October 2015. The first recruitment of participants occurred on 17 December 2013.

Measurement and valuation of health providers' time for the management of childhood pneumonia in rural Malawi: an empirical study.

BACKGROUND: Human resources are a major cost driver in childhood pneumonia case management. Introduction of 13-valent pneumococcal conjugate vaccine (PCV-13) in Malawi can lead to savings on staff time and salaries due to reductions in pneumonia cases requiring admission. Reliable estimates of human resource costs are vital for use in economic evaluations of PCV-13 introduction. METHODS: Twenty-eight severe and twenty-four very severe pneumonia inpatients under the age of five were tracked from admission to discharge by paediatric ward staff using self-administered timesheets at Mchinji District Hospital between June and August 2012. All activities performed and the time spent on each activity were recorded. A monetary value was assigned to the time by allocating a corresponding percentage of the health workers' salary. All costs are reported in 2012 US$. RESULTS: A total of 1,017 entries, grouped according to 22 different activity labels, were recorded during the observation period. On average, 99 min (standard deviation, SD = 46) were spent on each admission: 93 (SD = 38) for severe and 106 (SD = 55) for very severe cases. Approximately 40 % of activities involved monitoring and stabilization, including administering non-drug therapies such as oxygen. A further 35 % of the time was spent on injecting antibiotics. Nurses provided 60 % of the total time spent on pneumonia admissions, clinicians 25 % and support staff 15 %. Human resource costs were approximately US$ 2 per bed-day and, on average, US$ 29.5 per severe pneumonia admission and US$ 37.7 per very severe admission. CONCLUSIONS: Self-reporting was successfully used in this context to generate reliable estimates of human resource time and costs of childhood pneumonia treatment. Assuming vaccine efficacy of 41 % and 90 % coverage, PCV-13 introduction in Malawi can save over US$ 2 million per year in staff costs alone.

Cost-effectiveness of eye care services in Zambia.

OBJECTIVE: To estimate the cost-effectiveness of cataract surgery and refractive error/presbyopia correction in Zambia. METHODS: Primary data on costs and health related quality of life were collected in a prospective cohort study of 170 cataract and 113 refractive error/presbyopia patients recruited from three health facilities. Six months later, follow-up data were available from 77 and 41 patients who had received cataract surgery and spectacles, respectively. Costs were determined from patient interviews and micro-costing at the three health facilities. Utility values were gathered by administering the EQ-5D quality of life instrument immediately before and six months after cataract surgery or acquiring spectacles. A probabilistic state-transition model was used to generate cost-effectiveness estimates with uncertainty ranges. RESULTS: Utility values significantly improved across the patient sample after cataract surgery and acquiring spectacles. Incremental costs per Quality Adjusted Life Years gained were US$ 259 for cataract surgery and US$ 375 for refractive error correction. The probabilities of the incremental cost-effectiveness ratios being below the Zambian gross national income per capita were 95% for both cataract surgery and refractive error correction. CONCLUSION: In spite of proven cost-effectiveness, severe health system constraints are likely to hamper scaling up of the interventions.

Health systems analysis of eye care services in Zambia: evaluating progress towards VISION 2020 goals.

BACKGROUND: VISION 2020 is a global initiative launched in 1999 to eliminate avoidable blindness by 2020. The objective of this study was to undertake a situation analysis of the Zambian eye health system and assess VISION 2020 process indicators on human resources, equipment and infrastructure. METHODS: All eye health care providers were surveyed to determine location, financing sources, human resources and equipment. Key informants were interviewed regarding levels of service provision, management and leadership in the sector. Policy papers were reviewed. A health system dynamics framework was used to analyse findings. RESULTS: During 2011, 74 facilities provided eye care in Zambia; 39% were public, 37% private for-profit and 24% owned by Non-Governmental Organizations. Private facilities were solely located in major cities. A total of 191 people worked in eye care; 18 of these were ophthalmologists and eight cataract surgeons, equivalent to 0.34 and 0.15 per 250,000 population, respectively. VISION 2020 targets for inpatient beds and surgical theatres were met in six out of nine provinces, but human resources and spectacles manufacturing workshops were below target in every province. Inequalities in service provision between urban and rural areas were substantial. CONCLUSION: Shortage and maldistribution of human resources, lack of routine monitoring and inadequate financing mechanisms are the root causes of underperformance in the Zambian eye health system, which hinder the ability to achieve the VISION 2020 goals. We recommend that all VISION 2020 process indicators are evaluated simultaneously as these are not individually useful for monitoring progress.

Costs and Cost-Effectiveness of Biomedical, Non-Surgical HIV Prevention Interventions: A Systematic Literature Review.

BACKGROUND: Considerable evidence on the costs and cost-effectiveness of biomedical, non-surgical interventions to prevent human immunodeficiency virus (HIV) transmission has been generated over the last decade. This study aims to synthesize findings and identify remaining knowledge gaps to suggest future research priorities. METHODS: A systematic literature review was carried out in August 2020 using the MEDLINE, Embase, Global Health and EconLit databases to retrieve economic evaluations and costing studies of oral pre-exposure prophylaxis (PrEP), injectable long-acting PrEP, vaginal microbicide rings and gels, HIV vaccines and broadly neutralizing antibodies. Studies reporting costs from the provider or societal perspective were included in the analysis. Those reporting on behavioural methods of prevention, condoms and surgical approaches (voluntary medical male circumcision) were excluded. The quality of reporting of the included studies was assessed using published checklists. RESULTS: We identified 3007 citations, of which 87 studies were retained. Most were set in low- and middle-income countries (LMICs; n = 53) and focused on the costs and/or cost-effectiveness of oral PrEP regimens (n = 70). Model-based economic evaluations were the most frequent study design; only two trial-based cost-effectiveness analyses and nine costing studies were found. Less than half of the studies provided practical details on how the intervention would be delivered by the health system, and only three of these, all in LMICs, explicitly focused on service integration and its implication for delivery costs. 'Real-world' programme delivery mechanisms and costs of intervention delivery were rarely considered. PrEP technologies were generally found to be cost-effective only when targeting high-risk subpopulations. Single-dose HIV vaccines are expected to be cost-effective for all groups despite substantial uncertainty around pricing. CONCLUSIONS: A lack of primary, detailed and updated cost data, including above-service level costs, from a variety of settings makes it difficult to evaluate the cost-effectiveness of specific delivery modes at scale, or to evaluate strategies for services integration. Closing this evidence gap around real-world implementation is vital, not least because the strategies targeting high-risk groups that are recommended by PrEP models may incur substantially higher costs and be of limited practical feasibility in some settings.

Cost-effectiveness of tuberculosis infection prevention and control interventions in South African clinics: a model-based economic evaluation informed by complexity science methods.

INTRODUCTION: Nosocomial Mycobacterium tuberculosis (Mtb) transmission substantially impacts health workers, patients and communities. Guidelines for tuberculosis infection prevention and control (TB IPC) exist but implementation in many settings remains suboptimal. Evidence is needed on cost-effective investments to prevent Mtb transmission that are feasible in routine clinic environments. METHODS: A set of TB IPC interventions was codesigned with local stakeholders using system dynamics modelling techniques that addressed both core activities and enabling actions to support implementation. An economic evaluation of these interventions was conducted at two clinics in KwaZulu-Natal, employing agent-based models of Mtb transmission within the clinics and in their catchment populations. Intervention costs included the costs of the enablers (eg, strengthened supervision, community sensitisation) identified by stakeholders to ensure uptake and adherence. RESULTS: All intervention scenarios modelled, inclusive of the relevant enablers, cost less than US$200 per disability-adjusted life-year (DALY) averted and were very cost-effective in comparison to South Africa's opportunity cost-based threshold (US$3200 per DALY averted). Two interventions, building modifications to improve ventilation and maximising use of the existing Central Chronic Medicines Dispensing and Distribution system to reduce the number of clinic attendees, were found to be cost saving over the 10-year model time horizon. Incremental cost-effectiveness ratios were sensitive to assumptions on baseline clinic ventilation rates, the prevalence of infectious TB in clinic attendees and future HIV incidence but remained highly cost-effective under all uncertainty analysis scenarios. CONCLUSION: TB IPC interventions in clinics, including the enabling actions to ensure their feasibility, afford very good value for money and should be prioritised for implementation within the South African health system.

Infectious Disease Modelling of HIV Prevention Interventions: A Systematic Review and Narrative Synthesis of Compartmental Models.

BACKGROUND: The HIV epidemic remains a major public health problem. Critical to transmission control are HIV prevention strategies with new interventions continuing to be developed. Mathematical models are important for understanding the potential impact of these interventions and supporting policy decisions. This systematic review aims to answer the following question: when a new HIV prevention intervention is being considered or designed, what information regarding it is necessary to include in a compartmental model to provide useful insights to policy makers? The primary objective of this review is therefore to assess suitability of current compartmental HIV prevention models for informing policy development. METHODS: Articles published in EMBASE, Medline, Econlit, and Global Health were screened. Included studies were identified using permutations of (i) HIV, (ii) pre-exposure prophylaxis (PrEP), circumcision (both voluntary male circumcision [VMMC] and early-infant male circumcision [EIMC]), and vaccination, and (iii) modelling. Data extraction focused on study design, model structure, and intervention incorporation into models. Article quality was assessed using the TRACE (TRAnsparent and Comprehensive Ecological modelling documentation) criteria for mathematical models. RESULTS: Of 837 articles screened, 48 articles were included in the review, with 32 unique mathematical models identified. The substantial majority of studies included PrEP (83%), whilst fewer modelled circumcision (54%), and only a few focussed on vaccination (10%). Data evaluation, implementation verification, and model output corroboration were identified as areas of poorer model quality. Parameters commonly included in the mathematical models were intervention uptake and effectiveness, with additional intervention-specific common parameters identified. We identified key modelling gaps; critically, models insufficiently incorporate multiple interventions acting simultaneously. Additionally, population subgroups were generally poorly represented-with future models requiring improved incorporation of ethnicity and sexual risk group stratification-and many models contained inappropriate data in parameterisation which will affect output accuracy. CONCLUSIONS: This review identified gaps in compartmental models to date and suggests areas of improvement for models focusing on new prevention interventions. Resolution of such gaps within future models will ensure greater robustness and transparency, and enable more accurate assessment of the impact that new interventions may have, thereby providing more meaningful guidance to policy makers.

Health Economics Research on Non-surgical Biomedical HIV Prevention: Identifying Gaps and Proposing a Way Forward.

BACKGROUND AND OBJECTIVE: Although HIV prevention science has advanced over the last four decades, evidence suggests that prevention technologies do not always reach their full potential. Critical health economics evidence at appropriate decision-making junctures, particularly early in the development process, could help identify and address potential barriers to the eventual uptake of future HIV prevention products. This paper aims to identify key evidence gaps and propose health economics research priorities for the field of HIV non-surgical biomedical prevention. METHODS: We used a mixed-methods approach with three distinct components: (i) three systematic literature reviews (costs and cost effectiveness, HIV transmission modelling and quantitative preference elicitation) to understand health economics evidence and gaps in the peer-reviewed literature; (ii) an online survey with researchers working in this field to capture gaps in yet-to-be published research (recently completed, ongoing and future); and (iii) a stakeholder meeting with key global and national players in HIV prevention, including experts in product development, health economics research and policy uptake, to uncover further gaps, as well as to elicit views on priorities and recommendations based on (i) and (ii). RESULTS: Gaps in the scope of available health economics evidence were identified. Little research has been carried out on certain key populations (e.g. transgender people and people who inject drugs) and other vulnerable groups (e.g. pregnant people and people who breastfeed). Research is also lacking on preferences of community actors who often influence or enable access to health services among priority populations. Oral pre-exposure prophylaxis, which has been rolled out in many settings, has been studied in depth. However, research on newer promising technologies, such as long-acting pre-exposure prophylaxis formulations, broadly neutralising antibodies and multipurpose prevention technologies, is lacking. Interventions focussing on reducing intravenous and vertical transmission are also understudied. A disproportionate amount of evidence on low- and middle-income countries comes from two countries (South Africa and Kenya); evidence from other countries in sub-Saharan Africa as well as other low- and middle-income countries is needed. Further, data are needed on non-facility-based service delivery modalities, integrated service delivery and ancillary services. Key methodological gaps were also identified. An emphasis on equity and representation of heterogeneous populations was lacking. Research rarely acknowledged the complex and dynamic use of prevention technologies over time. Greater efforts are needed to collect primary data, quantify uncertainty, systematically compare the full range of prevention options available, and validate pilot and modelling data once interventions are scaled up. Clarity on appropriate cost-effectiveness outcome measures and thresholds is also lacking. Lastly, research often fails to reflect policy-relevant questions and approaches. CONCLUSIONS: Despite a large body of health economics evidence on non-surgical biomedical HIV prevention technologies, important gaps in the scope of evidence and methodology remain. To ensure that high-quality research influences key decision-making junctures and facilitates the delivery of prevention products in a way that maximises impact, we make five broad recommendations related to: improved study design, an increased focus on service delivery, greater community and stakeholder engagement, the fostering of an active network of partners across sectors and an enhanced application of research.

Time to change the way we think about tuberculosis infection prevention and control in health facilities: insights from recent research.

In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently.