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.

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.

Implementation and resource needs for long-acting PrEP in low- and middle-income countries: a scoping review.

INTRODUCTION: Several low- and middle-income countries (LMICs) are preparing to introduce long-acting pre-exposure prophylaxis (LAP). Amid multiple pre-exposure prophylaxis (PrEP) options and constrained funding, decision-makers could benefit from systematic implementation planning and aligned costs. We reviewed national costed implementation plans (CIPs) to describe relevant implementation inputs and activities (domains) for informing the costed rollout of LAP. We assessed how primary costing evidence aligned with those domains. METHODS: We conducted a rapid review of CIPs for oral PrEP and family planning (FP) to develop a consensus of implementation domains, and a scoping review across nine electronic databases for publications on PrEP costing in LMICs between January 2010 and June 2022. We extracted cost data and assessed alignment with the implementation domains and the Global Health Costing Consortium principles. RESULTS: We identified 15 implementation domains from four national PrEP plans and FP-CIP template; only six were in all sources. We included 66 full-text manuscripts, 10 reported LAP, 13 (20%) were primary cost studies-representing seven countries, and none of the 13 included LAP. The 13 primary cost studies included PrEP commodities (n = 12), human resources (n = 11), indirect costs (n = 11), other commodities (n = 10), demand creation (n = 9) and counselling (n = 9). Few studies costed integration into non-HIV services (n = 5), above site costs (n = 3), supply chains and logistics (n = 3) or policy and planning (n = 2), and none included the costs of target setting, health information system adaptations or implementation research. Cost units and outcomes were variable (e.g. average per person-year). DISCUSSION: LAP planning will require updating HIV prevention policies, technical assistance for logistical and clinical support, expanding beyond HIV platforms, setting PrEP achievement targets overall and disaggregated by method, extensive supply chain and logistics planning and support, as well as updating health information systems to monitor multiple PrEP methods with different visit schedules. The 15 implementation domains were variable in reviewed studies. PrEP primary cost and budget data are necessary for new product introduction and should match implementation plans with financing. CONCLUSIONS: As PrEP services expand to include LAP, decision-makers need a framework, tools and a process to support countries in planning the systematic rollout and costing for LAP.

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.

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.

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.

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.

Complexity and evidence in health sector decision-making: lessons from tuberculosis infection prevention in South Africa.

To better understand and plan health systems featuring multiple levels and complex causal elements, there have been increasing attempts to incorporate tools arising from complexity science to inform decisions. The utilization of new planning approaches can have important implications for the types of evidence that inform health policymaking and the mechanisms through which they do so. This paper presents an empirical analysis of the application of one such tool-system dynamics modelling (SDM)-within a tuberculosis control programme in South Africa in order to explore how SDM was utilized, and to reflect on the implications for evidence-informed health policymaking. We observed group model building workshops that served to develop the SDM process and undertook 19 qualitative interviews with policymakers and practitioners who partook in these workshops. We analysed the relationship between the SDM process and the use of evidence for policymaking through four conceptual perspectives: (1) a rationalist knowledge-translation view that considers how previously-generated research can be taken up into policy; (2) a programmatic approach that considers existing goals and tasks of decision-makers, and how evidence might address them; (3) a social constructivist lens exploring how the process of using an evidentiary planning tool like SDM can shape the understanding of problems and their solutions; and (4) a normative perspective that recognizes that stakeholders may have different priorities, and thus considers which groups are included and represented in the process. Each perspective can provide useful insights into the SDM process and the political nature of evidence use. In particular, SDM can provide technical information to solve problems, potentially leave out other concerns and influence how problems are conceptualized by formalizing the boundaries of the policy problem and delineating particular solution sets. Undertaking the process further involves choices on stakeholder inclusion affecting whose interests may be served as evidence to inform decisions.

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.].

Cost-effectiveness of routine adolescent vaccination with an M72/AS01E-like tuberculosis vaccine in South Africa and India.

The M72/AS01E 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/AS01E-like vaccination in South Africa and India. All scenarios suggested an M72/AS01E-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.

Using system dynamics modelling to estimate the costs of relaxing health system constraints: a case study of tuberculosis prevention and control interventions in South Africa.

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.

Stark choices: exploring health sector costs of policy responses to COVID-19 in low-income and middle-income countries.

OBJECTIVES: COVID-19 has altered health sector capacity in low-income and middle-income countries (LMICs). Cost data to inform evidence-based priority setting are urgently needed. Consequently, in this paper, we calculate the full economic health sector costs of COVID-19 clinical management in 79 LMICs under different epidemiological scenarios. METHODS: We used country-specific epidemiological projections from a dynamic transmission model to determine number of cases, hospitalisations and deaths over 1 year under four mitigation scenarios. We defined the health sector response for three base LMICs through guidelines and expert opinion. We calculated costs through local resource use and price data and extrapolated costs across 79 LMICs. Lastly, we compared cost estimates against gross domestic product (GDP) and total annual health expenditure in 76 LMICs. RESULTS: COVID-19 clinical management costs vary greatly by country, ranging between <0.1%-12% of GDP and 0.4%-223% of total annual health expenditure (excluding out-of-pocket payments). Without mitigation policies, COVID-19 clinical management costs per capita range from US$43.39 to US$75.57; in 22 of 76 LMICs, these costs would surpass total annual health expenditure. In a scenario of stringent social distancing, costs per capita fall to US$1.10-US$1.32. CONCLUSIONS: We present the first dataset of COVID-19 clinical management costs across LMICs. These costs can be used to inform decision-making on priority setting. Our results show that COVID-19 clinical management costs in LMICs are substantial, even in scenarios of moderate social distancing. Low-income countries are particularly vulnerable and some will struggle to cope with almost any epidemiological scenario. The choices facing LMICs are likely to remain stark and emergency financial support will be needed.

Modelling the effect of infection prevention and control measures on rate of Mycobacterium tuberculosis transmission to clinic attendees in primary health clinics in South Africa.

BACKGROUND: Elevated rates of tuberculosis in healthcare workers demonstrate the high rate of Mycobacterium tuberculosis (Mtb) transmission in health facilities in high-burden settings. In the context of a project taking a whole systems approach to tuberculosis infection prevention and control (IPC), we aimed to evaluate the potential impact of conventional and novel IPC measures on Mtb transmission to patients and other clinic attendees. METHODS: An individual-based model of patient movements through clinics, ventilation in waiting areas, and Mtb transmission was developed, and parameterised using empirical data from eight clinics in two provinces in South Africa. Seven interventions-codeveloped with health professionals and policy-makers-were simulated: (1) queue management systems with outdoor waiting areas, (2) ultraviolet germicidal irradiation (UVGI) systems, (3) appointment systems, (4) opening windows and doors, (5) surgical mask wearing by clinic attendees, (6) simple clinic retrofits and (7) increased coverage of long antiretroviral therapy prescriptions and community medicine collection points through the Central Chronic Medicine Dispensing and Distribution (CCMDD) service. RESULTS: In the model, (1) outdoor waiting areas reduced the transmission to clinic attendees by 83% (IQR 76%-88%), (2) UVGI by 77% (IQR 64%-85%), (3) appointment systems by 62% (IQR 45%-75%), (4) opening windows and doors by 55% (IQR 25%-72%), (5) masks by 47% (IQR 42%-50%), (6) clinic retrofits by 45% (IQR 16%-64%) and (7) increasing the coverage of CCMDD by 22% (IQR 12%-32%). CONCLUSIONS: The majority of the interventions achieved median reductions in the rate of transmission to clinic attendees of at least 45%, meaning that a range of highly effective intervention options are available, that can be tailored to the local context. Measures that are not traditionally considered to be IPC interventions, such as appointment systems, may be as effective as more traditional IPC measures, such as mask wearing.

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.

Cross-sectional assessment of tuberculosis and HIV prevalence in 13 correctional facilities in Zambia.

OBJECTIVE: To determine the prevalence of tuberculosis (TB) and HIV in 13 Zambian correctional facilities. METHODS: Cross-sectional study. SETTING: 13 correctional facilities in seven of the 10 provinces in Zambia. PARTICIPANTS: All incarcerated individuals were eligible for TB and HIV screening and testing. Of the total study population of 9695 individuals, which represent 46.2% of total correctional population at the beginning of the study, 8267 and 8160 were screened for TB and HIV, respectively. INTERVENTIONS: TB and HIV screening and testing was done between July 2018 and February 2019. PRIMARY OUTCOME MEASURES: All forms of TB, bacteriologically confirmed TB, drug-resistant TB, HIV. RESULTS: Prevalence of all forms of TB and bacteriologically confirmed TB was 1599 (1340-1894) per 100 000 population and 1056 (847-1301) per 100 000 population, respectively. Among those with bacteriologically confirmed TB, 4.6% (1.3%-11.4%) had drug-resistant TB.There was no statistically significant difference in the prevalence of all forms of TB, bacteriologically confirmed TB and drug resistant TB between adults and juveniles: (p=0.82), (p=0.23), (p=0.68) respectively. Of the bacteriologically confirmed TB cases, 28.7% were asymptomatic. The prevalence of HIV was 14.3% (13.6%-15.1%). The prevalence of HIV among females was 1.8 times the prevalence of HIV among males (p=0.01). CONCLUSION: Compared with the study in 2011 which screened inmates representing 30% of the country's inmate population, then the prevalence of all forms of TB and HIV in correctional facilities has reduced by about 75% and 37.6%, respectively. However, compared with the general population, the prevalence of all forms of TB and HIV was 3.5 and 1.3 times higher, respectively. TB/HIV programmes in correctional facilities need further strengthening to include aspects of juvenile-specific TB programming and gender responsive HIV programming.

Building resource constraints and feasibility considerations in mathematical models for infectious disease: A systematic literature review.

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.

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.

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.

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.