Tuberculosis (TB) remains a major public health challenge, with financial and health impacts extending beyond treatment. Both the perspective adopted in cost-effectiveness analyses-which critically determines choices such as the inclusion of patient-incurred costs-and the extent to which long-term post-treatment considerations are incorporated have important policy implications. This study examines how the choice of timeframe and cost perspectives influence the estimated cost-effectiveness of TB interventions, particularly preventative measures. Using data from 19 WHO TB patient cost surveys and global epidemiological databases, we modelled a hypothetical preventative TB intervention, generating four incremental cost-effectiveness ratios (ICERs) per country under different analytical approaches. These included a conventional timeframe up to treatment completion, an extended timeframe incorporating post-TB effects, and two perspectives that either included or excluded patient-incurred costs. The approach yielding the lowest ICER (societal perspective; extended timeframe) was anchored in the primary analysis to a 1×GDP per capita threshold. Using this benchmark simplified cross-country comparisons and removed the need for health system cost estimates. Sensitivity and scenario analyses explored how threshold values influenced the relative impact of timeframe and costing perspective. ICERs were higher when patient costs were omitted or the post-TB period was excluded, peaking when both were absent. However, across all countries, post-TB considerations had a far greater impact on cost-effectiveness. On average, removing the post-TB period increased ICERs by over 50% (ranging from +19.3% in Ghana to +108% in Mongolia, societal perspective). Including patient-incurred costs increased the likelihood that prevention was cost-effective, particularly in low-GDP settings with lower willingness-to-pay thresholds. However, their impact was minimal above 2×GDP. Our study highlights how narrowly defining the financial and health burden of tuberculosis in cost-effectiveness analyses risks underestimating the benefits of interventions-particularly in lower-GDP countries where the socioeconomic burden of tuberculosis is greatest-which could lead to misguided policy decisions that overlook the full impact of tuberculosis.

BACKGROUND:The global burden of multimorbidity-the coexistence of two or more long-term conditions-is increasing. Limited access to primary care in sub-Saharan Africa means acute hospital admission is often the sentinel multimorbidity presentation. This prospective multicentre cohort study aimed to describe the burden, constituent diseases, and outcomes of multimorbidity among patients acutely admitted to hospital in Malawi and Tanzania. METHODS:Adults (ie, those aged ≥18 years) admitted to four hospitals (two tertiary and two district hospitals) with acute medical conditions were consecutively recruited within 24 h of presentation and followed up for 90 days. We estimated the prevalence of HIV infection, diabetes, hypertension, and chronic kidney disease using commercially available point-of-care tests, and captured self-reported and clinical diagnoses (n/N [%]). Health economic data were summarised by median and IQR and modelled using generalised linear models. All-cause 90-day mortality was summarised with Kalplan-Meier plots and analysed using Cox regression models. FINDINGS:1407 adults (657 [46·7%] were female and 750 [53·3%] were male; mean age was 52·3 years [SD 18·4]) were recruited. We examined multimorbidity prevalence in 1007 participants admitted to three hospitals that accept admissions directly from the community. Multimorbidity was found in 473 (47·0%) of 1007 participants and 292 (29·0%) had a single long-term condition. Outcomes at 90 days were determined for 1317 (93·6%) of 1407 participants. Adjusted 90-day mortality was higher in participants with multimorbidity (335 [41·7%] of 804; hazard ratio 1·5 [95% CI 1·1-2·1]) and those with one long-term condition (80 [28·3%] of 283; 1·5 [1·0-2·1]); compared with those with no long-term conditions (31 [13·5%] of 230). Health-related quality of life was lower in participants with multimorbidity compared with those with one long-term condition (median 0·402 [IQR -0·037 to 0·644] vs 0·557 [0·140 to 0·730]; p=0·005) at baseline, and at final observation (0·858 [0·667 to 1·00] vs 1·00 [0·589 to 1·00] respectively; p=0·01). In Tanzania, medical costs incurred by patients were higher in participants with multimorbidity compared with those with one long-term condition (relative effect 5·77 [95% CI 2·99-11·15]; p<0·0001). INTERPRETATION:Multimorbidity is common in patients admitted to hospital in Malawi and Tanzania and associated with worse survival and increased cost. Multimorbidity is an urgent public health threat that requires fundamental health-care delivery reform to address population needs. FUNDING:National Institute for Health and Care Research and Wellcome Trust. TRANSLATIONS:For the Chichewa and Kiswahili translations of the abstract see Supplementary Materials section.

Sepsis is a life-threatening condition with high mortality, especially in sub-Saharan Africa (SSA). Sepsis survivors may face long term consequences and experience poor health-related quality of life (HRQoL). By comparing HRQoL trajectories between sepsis cases and matched controls we sought to identify the longitudinal impact of sepsis on HRQoL in the SSA context. This study was nested within a longitudinal adult sepsis cohort admitted to hospital in Blantyre, Malawi. Two reference control groups matched to cases by age, sex, and geographical location were recruited: (1) hospital inpatients without sepsis and (2) community controls with no current illness. All participants were followed up to 180 days post-enrolment. HRQoL was assessed using EQ-5D-3L questionnaire and a visual analogue scale (VAS). Regression analysis was conducted to examine factors associated with HRQoL among sepsis survivors. A total of 425 participants: 225 sepsis cases, 100 hospital controls, and 100 community controls were recruited. HIV prevalence was higher among sepsis cases 143/225 (63.6%) compared to hospital controls 12/100 (12.0%) and community controls 18/100 (18.0%) p= <0.001. At baseline, sepsis cases had lower health utility scores (median 0.596, IQR: 0.365– 0.734 compared to hospital controls (0.666, IQR: 0.611 - 0.722) and community controls (0.900, IQR: 0.833 - 0.900). Over time, sepsis cases displayed fluctuating HRQoL, with a marked decline in utility scores at day 180 (0 IQR: 0 - 0) compared to relatively stable scores in both control groups. Regression analysis identified age, sex, duration of illness before admission and baseline utility score as significant predictors of HRQoL in the sepsis group. The findings reveal a severe and persistent reduction in HRQoL among patients admitted with sepsis in Malawi, suggesting a substantial post-discharge burden among survivors. These results point to a need for evidence-based prevention, early recognition of sepsis and post-sepsis support programs in SSA.

The disability-adjusted life year (DALY), a key metric for health resource allocation, encompasses morbidity through disability weights. Widely used in tuberculosis cost-effectiveness analysis (CEAs), DALYs play a significant role in informing intervention adopt/reject decisions. This study reviews the values and consistency of disability weights applied in tuberculosis-related CEAs. We conducted a systematic review using the Tufts CEA database, updated to July 2023 with searches in Embase, Scopus and PubMed. Eligible studies needed to have included a cost-per-DALY ratio, and additionally either evaluated a tuberculosis (TB) intervention or included tuberculosis-related weights. We considered all tuberculosis health states: with/without human immunodeficiency virus (HIV) coinfection, TB treatments and treatment side effects. Data were screened and extracted independently by combinations of two authors. A total of 105 studies spanning 2002–2023 across 50 countries (mainly low- and middle-income countries) were extracted. Disability weights were sourced primarily from the Global Burden of Disease (GBD; 100/165; 61

Background The prevalence of multimorbidity (the presence of two or more chronic health conditions) is rapidly increasing in sub–Saharan Africa. Hospital care pathways that focus on single presenting complaints do not address this pressing problem. This has the potential to precipitate frequent hospital readmissions, increase health system and out-of-pocket expenses, and may lead to premature disability and death. We aim to present a description of inpatient multimorbidity in a multicentre prospective cohort study in Malawi and Tanzania. Primary objectives Determine prevalence of multimorbid disease among adult medical admissions and measure patient outcomes. Health Economic: Measure economic costs incurred and changes in health-related quality of life (HRQoL) at 90 days post-admission. Situation analysis: Qualitatively describe pathways of patients with multimorbidity through the health system. Secondary objectives Determine hospital readmission free survival and markers of disease control 90 days after admission. Health Economic: Present economic costs from patient and health system perspective, sub-analyse costs and HRQoL according to presence of different diseases. Situation analysis: Understand health literacy related to their own diseases and experience of care for patients with multimorbidity and their caregivers. Methods This is a prospective longitudinal cohort study of adult (≥18 years) acute medical hospital admissions with nested health economic and situation analysis in four hospitals: 1) Queen Elizabeth Central Hospital, Blantyre, Malawi; 2) Chiradzulu District Hospital, Malawi; 3) Hai District Hospital, Boma Ng’ombe, Tanzania; 4) Muhimbili National Hospital, Dar-es-Salaam, Tanzania. Follow-up duration will be 90 days from hospital admission. We will use consecutive recruitment within 24 hours of emergency presentation and stratified recruitment across four sites. We will use point-of-care tests to refine estimates of disease pathology. We will conduct qualitative interviews with patients, caregivers, healthcare providers and policymakers; focus group discussions with patients and caregivers, and observations of hospital care pathways.

Larval Source Management (LSM) is an important tool for malaria vector control and is recommended by WHO as a supplementary vector control measure. LSM has contributed in many successful attempts to eliminate the disease across the Globe. However, this approach is typically labour-intensive, largely due to the difficulties in locating and mapping potential malarial mosquito breeding sites. Previous studies have demonstrated the potential for drone imaging technology to map malaria vector breeding sites. However, key questions remain unanswered related to the use and cost of this technology within operational vector control. Using Zanzibar (United Republic of Tanzania) as a demonstration site, a protocol was collaboratively designed that employs drones and smartphones for supporting operational LSM, termed the Spatial Intelligence System (SIS). SIS was evaluated over a four-month LSM programme by comparing key mapping accuracy indicators and relative costs (both mapping costs and intervention costs) against conventional ground-based methods. Additionally, malaria case incidence was compared between the SIS and conventional study areas, including an estimation of the incremental cost-effectiveness of switching from conventional to SIS larviciding. The results demonstrate that the SIS approach is significantly more accurate than a conventional approach for mapping potential breeding sites: mean

Background In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO’s 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. Methods A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. Results Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients’ direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. Conclusions While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

Background The STREAM stage 2 trial assessed two bedaquiline-containing regimens for rifampicin-resistant tuberculosis: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug for the first 2 months. We did a within-trial economic evaluation of these regimens. Methods STREAM stage 2 was an international, phase 3, non-inferiority randomised trial in which participants with rifampicin-resistant tuberculosis were randomly assigned (1:2:2:2) to the 2011 WHO regimen (terminated early), a 9-month injectable-containing regimen (control regimen), a 9-month all-oral regimen with bedaquiline (oral regimen), or a 6-month regimen with bedaquiline and an injectable for the first 2 months (6-month regimen). We prospectively collected direct and indirect costs and health-related quality of life data from trial participants until week 76 of follow-up. Cost-effectiveness of the oral and 6-month regimens versus control was estimated in four countries (oral regimen) and two countries (6-month regimen), using health-related quality of life for cost-utility analysis and trial efficacy for cost-effectiveness analysis. This trial is registered with ISRCTN, ISRCTN18148631. Findings 300 participants were included in the economic analyses (Ethiopia, 61; India, 142; Moldova, 51; Uganda, 46). In the cost-utility analysis, the oral regimen was not cost-effective in Ethiopia, India, Moldova, and Uganda from either a provider or societal perspective. In Moldova, the oral regimen was dominant from a societal perspective. In the cost-effectiveness analysis, the oral regimen was likely to be cost-effective from a provider perspective at willingness-to-pay thresholds per additional favourable outcome of more than US$4500 in Ethiopia, $1900 in India, $3950 in Moldova, and $7900 in Uganda, and from a societal perspective at thresholds of more than $15 900 in Ethiopia, $3150 in India, and $4350 in Uganda, while in Moldova the oral regimen was dominant. In Ethiopia and India, the 6-month regimen would cost tuberculosis programmes and participants less than the control regimen and was highly likely to be cost-effective in both cost-utility analysis and cost-effectiveness analysis. Reducing the bedaquiline price from $1 center dot 81 to $1 center dot 00 per tablet made the oral regimen cost-effective in the provider-perspective cost-utility analysis in India and Moldova and dominate over the control regimen in the provider-perspective cost-effectiveness analysis in India. Interpretation At current costs, the oral bedaquiline-containing regimen for rifampicin-resistant tuberculosis is unlikely to be cost-effective in many low-income and middle-income countries. The 6-month regimen represents a cost-effective alternative if injectable use for 2 months is acceptable. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.

BACKGROUND:Patient and health system costs for treating multidrug-resistant tuberculosis (MDR-TB) remain high even after treatment duration was shortened. Many patients do not finish treatment, contributing to increased transmission and antimicrobial resistance. A restructure of health services, that is more patient-centred has the potential to reduce costs and increase trust and patient satisfaction. The aim of the study is to investigate how costs would change in the delivery of MDR-TB care in Ethiopia under patient-centred and hybrid approaches compared to the current standard-of-care.METHODS:We used published data, collected from 2017 to 2020 as part of the Standard Treatment Regimen of Anti-Tuberculosis Drugs for Patients with MDR-TB (STREAM) trial, to populate a discrete event simulation (DES) model. The model was developed to represent the key characteristics of patients' clinical pathways following each of the three treatment delivery strategies. To the pathways of 1000 patients generated by the DES model we applied relevant patient cost data derived from the STREAM trial. Costs are calculated for treating patients using a 9-month MDR-TB treatment and are presented in 2021 United States dollars (USD).RESULTS:The patient-centred and hybrid strategies are less costly than the standard-of-care, from both a health system (by USD 219 for patient-centred and USD 276 for the hybrid strategy) and patient perspective when patients do not have a guardian (by USD 389 for patient-centred and USD 152 for the hybrid strategy). Changes in indirect costs, staff costs, transport costs, inpatient stay costs or changes in directly-observed-treatment frequency or hospitalisation duration for standard-of-care did not change our results.CONCLUSION:Our findings show that patient-centred and hybrid strategies for delivering MDR-TB treatment cost less than standard-of-care and provide critical evidence that there is scope for such strategies to be implemented in routine care. These results should be used inform country-level decisions on how MDR-TB is delivered and also the design of future implementation trials.

Objectives The co-occurrence of tuberculosis (TB) and multiple chronic communicable and non-communicable diseases is a growing concern in low- and middle-income countries (LMICs). Understanding this ‘complex TB multimorbidity’ (cTBMM) can contribute to improved patient care. We aimed to synthesise the prevalence of clusters of cTBMM and their impact on patient outcomes. Design Systematic review and meta-analysis. Setting LMICs. Papers We searched major databases from inception to 01/10/2020 to identify observational studies reporting primary (prevalence or risk) or secondary (related to disease burden) outcome data for people in LMICs with cTBMM. Titles, abstracts and full text screening, data extraction, and quality assessment were done in duplicate by independent reviewers, and random-effects meta-analyses were performed. Primary and secondary outcome measures Prevalence or risk of cTBMM (primary); any measure of burden of disease (secondary). Results From 21,884 search results, 82 studies representing 773,828 TB patients were included, reporting data on 78 different clusters of cTBMM. In TB patients, the most prevalent co-occurring conditions where depression and anxiety (15.3%, 95% confidence interval [CI] 10.7%-20.5%, 3 studies, 1,473 participants, I2=64%), HIV and anxiety (15.2%, 95%CI 11.3%-19.7%, 4 studies, 1,413 participants, I2=77%), and HIV and post-traumatic stress disorder (14.8%, 95%CI 13.9%-15.8%, 2 studies, 5,400 participants). Sparse evidence indicated lower treatment success and higher risks of death in people with cTBMM. Conclusions Although limited by high heterogeneity, this first systematic review and meta-analysis on cTBMM highlights that multiple conditions co-occurring in TB patients are common and that mental disorders often cluster together or with HIV. Further research assessing the burden of cTBMM and identifying effective health systems responses is required. Registration Prospero CRD42020214021. Strengths and limitations of this study ### Competing Interest Statement EMT declared that he attended the Tuberculosis Modelling and Analytics Consortium meetings (one in-person meeting in the previous 3 years. Istanbul 30/09/2019 - 03/10/2019), for which his travel and expenses were covered (total expenses claimed <150 GBP, reimbursed to him directly). All other authors declare no competing interests. ### Clinical Protocols ### Funding Statement This work was supported by Medical Research Council UK, grant number MC\_PC\_MR/T037806/1. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All the collected data is in the public domain.

BACKGROUND:The growing urban population imposes additional challenges for health systems in low- and middle-income countries (LMICs). We explored the economic burden and inequities in healthcare utilisation across slum, non-slum and levels of wealth among urban residents in LMICs. METHODS:This scoping review presents a narrative synthesis and descriptive analysis of studies conducted in urban areas of LMICs. We categorised studies as conducted only in slums, city-wide studies with measures of wealth and conducted in both slums and non-slums settlements. We estimated the mean costs of accessing healthcare, the incidence of catastrophic health expenditures (CHE) and the progressiveness and equity of health expenditures. The definitions of slums used in the studies were mapped against the 2018 UN-Habitat definition. We developed an evidence map to identify research gaps on the economics of healthcare access in LMICs. RESULTS:We identified 64 studies for inclusion, the majority of which were from South-East Asia (59%) and classified as city-wide (58%). We found severe economic burden across health conditions, wealth quintiles and study types. Compared with city-wide studies, slum studies reported higher direct costs of accessing health care for acute conditions and lower costs for chronic and unspecified health conditions. Healthcare expenditures for chronic conditions were highest amongst the richest wealth quintiles for slum studies and more equally distributed across all wealth quintiles for city-wide studies. The incidence of CHE was similar across all wealth quintiles in slum studies and concentrated among the poorest residents in city-wide studies. None of the definitions of slums used covered all characteristics proposed by UN-Habitat. The evidence map showed that city-wide studies, studies conducted in India and studies on unspecified health conditions dominated the current evidence on the economics of healthcare access. Most of the evidence was classified as poor quality. CONCLUSIONS:Our findings indicated that city-wide and slums residents have different expenditure patterns when accessing healthcare. Financial protection schemes must consider the complexity of healthcare provision in the urban context. Further research is needed to understand the causes of inequities in healthcare expenditure in rapidly expanding and evolving cities in LMICs.

Background There is growing awareness of the burden of post-TB morbidity, and its impact on the lives and livelihoods of TB affected households. However little work has been done to determine how post-TB care might be delivered in a feasible and sustainable way, within existing National TB Programmes (NTPs) and health systems, in low-resource, high TB-burden settings. In this programme of stakeholder engagement around post-TB care, we identified actors with influence and interest in TB care in Kenya and Malawi, including TB-survivors, healthcare providers, policy-makers, researchers and funders, and explored their perspectives on post-TB morbidity and care. Methods Stakeholder mapping was completed to identify actors with interest and influence in TB care services in each country, informed by the study team’s local, regional and international networks. Key international TB organisations were included to provide a global perspective. In person or online one-to-one interviews were completed with purposively selected stakeholders. Snowballing was used to expand the network. Data were recorded, transcribed and translated, and a coding frame was derived. Data were coded using NVivo 12 software and were analysed using thematic content analysis. Online workshops were held with stakeholders from Kenya and Malawi to explore areas of uncertainty and validate findings. Results The importance of holistic care for TB patients, which addresses both TB comorbidities and sequelae, was widely recognised by stakeholders. Key challenges to implementation include uncertainty around the burden of post-TB morbidity, leadership of post-TB services, funding constraints, staff and equipment limitations, and the need for improved integration between national TB and non-communicable disease (NCD) programmes for care provision and oversight. There is a need for local data on the burden and distribution of morbidity, evidence-informed clinical guidelines, and pilot data on models of care. Opportunities to learn from existing HIV-NCD services were emphasised. Discussion This work addresses important questions about the practical implementation of post-TB services in two African countries, exploring if, how, where, and for whom these services should be provided, according to a broad range of stakeholders. We have identified strong interest in the provision of holistic care for TB patients in Kenya and Malawi, and key evidence gaps which must be addressed to inform decision making by policy makers, TB programmes, and funders around investment in post-TB services. There is a need for pilot studies of models of integrated TB care, and for cross-learning between countries and from HIV-NCD services.

Background: The STREAM Stage 1 trial demonstrated that the Short-regimen reduced health system costs by 20-25%, and was associated with an earlier return to work and a reduction in the purchase of supplementary food. The health economic data collected permit a num- ber of secondary analyses, including differences patient costs by gender, and probabilistic estimates of the likeli- hood that the Short-regimen is cost-effective. Design/Methods: Patient data were collected at 12- week intervals from the start of treatment up to week 132. Mean spending and mean working hours at each week were estimated by gender. Probabilistic sensitiv- ity analyses were conducted via boostrapping trial data for both Ethiopia and South Africa. The probability of cost-effectiveness was estimated for each country, at a range of willingness-to-pay thresholds for the trial pri- mary outcome. Results: Men spent $221 (Short-regimen) or $249 (Long- regimen) more than women on supplements. Although men reported working longer hours than women, the difference was not substantial. From a health system perspective, the probability that the Short-regimen is cost-effective is above 95% if the willingness to pay threshold for each additional favourable outcome is less than US$19,000 in Ethiopia and US$14,500 in South Africa. Conclusions: Our results suggest that expenditure on supplementary food is a more important driver of gen- der differences in MDR-TB patient costs than hours worked, irrespective of regimen. They also suggest that the Short-regimen is highly likely to be cost-effective, al- though the trial primary outcome was a composite for which a willingness-to-pay threshold was challenging to determine precisely. Further research is required to de- termine why more was spent by men than women on supplementary food, and to establish relevant willing- ness-to-pay thresholds for MDR-TB favourable treat- ment outcomes.

Introduction A December 2019 WHO rapid communication recommended the use of 9-month all-oral regimens for treating multidrug-resistant tuberculosis (MDR-TB). Besides the clinical benefits, they are thought to be less costly than the injectable-containing regimens, for both the patient and the health system. STREAM is the first randomised controlled trial with an economical evaluation to compare all-oral and injectable-containing 9–11-month MDR-TB treatment regimens.Methods and analysis Health system costs of delivering a 9-month injectable-containing regimen and a 9-month all-oral bedaquiline-containing regimen will be collected in Ethiopia, India, Moldova and Uganda, using ‘bottom-up’ and ‘top-down’ costing approaches. Patient costs will be collected using questionnaires that have been developed based on the STOP-TB questionnaire. The primary objective of the study is to estimate the cost utility of the two regimens, from a health system perspective. Secondary objectives include estimating the cost utility from a societal perspective as well as evaluating the cost-effectiveness of the regimens, using both health system and societal perspectives. The effect measure for the cost–utility analysis will be the quality-adjusted life years (QALY), while the effect measure for the cost-effectiveness analysis will be the efficacy outcome from the clinical trial.Ethics and dissemination The study has been evaluated and approved by the Ethics Advisory Group of the International Union Against Tuberculosis and Lung Disease and also approved by ethics committees in all participating countries. All participants have provided written informed consent. The results of the economic evaluation will be published in a peer-reviewed journal.Trial registration number ISRCTN18148631.

Background: Although TB can be treated effectively, its early diagnosis in People Living with HIV (PLHIV) is still a challenge. We assessed the cost-effectiveness of a symptom-based screening for TB diagnosis in PLHIV compared with the hospital routine in Brazil.Methods: The economic evaluation was conducted alongside a randomized pragmatic clinical trial. We compared costs, Disability Adjusted Life Years (DALYs) and extra number of years lived between participants who were screened for TB at every appointment versus the hospital routine where TB screening is not mandatory. The cost-effectiveness was measured as the incremental cost-effectiveness ratio (ICER) per DALYs averted or life years saved. Sub-group analysis of the intervention group was conducted based on individuals who screened positive and negative at the first appointment. Lifelong costs and extra number of years lived were estimated through an individual-based simulation model. Findings: Between March 2014 and April 2017, 724 participants were included in the trial. The intervention did not avert DALYs (-0·1 [95% CI: -1·4, 1·3]), although it was cost saving by US$ 929 (95% CI: 342, 1 572) per patient. The intervention group with a negative screening at the first appointment had the highest cost-savings (US$ 1 324 [95% CI: 711, 1 977]) and more DALYs averted (1·1 [95% CI: -0·3, 2·6]) when compared with the control group. In the long term, screening for TB in HIV patients who reaced the health services at the earlier stages of the disease resulted in 3.8 life years gained (95% CI: 0·3, 7·4) and cost saving by $3 936 (95% CI: 2 317, $5 505) per patient. Interpretation: TB screening at every appointment was cost saving and more beneficial in HIV patients with less severe HIV disease both in the short term and for their full lifetime. Trial Registration: The clinical trial was registered at the Brazilian Registries for Clinical Trials (ReBec-22t943, http://www.ensaiosclinicos.gov.br/rg/RBR-22t943/). Funding Statement: CNPq, 470554/2013-4 and FACEPE, APQ-0184-4.06/13. We also thank the Institute for Health Technology Assessment (IATS) for the support with travel expenses and scholarships for the field work team. Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: The study was approved by the Fundacao Oswaldo Cruz (No 279.324) and the London School of Hygiene and Tropical Medicine (Ref: 7371) ethics committees. All patients signed a consent form.

Abstract Objective To investigate cost changes for health systems and participants, resulting from switching to short treatment regimens for multidrug-resistant (MDR) tuberculosis. Methods We compared the costs to health systems and participants of long (20 to 22 months) and short (9 to 11 months) MDR tuberculosis regimens in Ethiopia and South Africa. Cost data were collected from participants in the STREAM phase-III randomized controlled trial and we estimated health-system costs using bottom-up and top-down approaches. A cost–effectiveness analysis was performed by calculating the incremental cost per unfavourable outcome avoided. Findings Health-care costs per participant in South Africa were 8340.7 United States dollars (US$) with the long and US$ 6618.0 with the short regimen; in Ethiopia, they were US$ 6096.6 and US$ 4552.3, respectively. The largest component of the saving was medication costs in South Africa (67%; US$ 1157.0 of total US$ 1722.8) and social support costs in Ethiopia (35%, US$ 545.2 of total US$ 1544.3). In Ethiopia, trial participants on the short regimen reported lower expenditure for supplementary food (mean reduction per participant: US$ 225.5) and increased working hours (i.e. 667 additional hours over 132 weeks). The probability that the short regimen was cost–effective was greater than 95% when the value placed on avoiding an unfavourable outcome was less than US$ 19 000 in Ethiopia and less than US$ 14 500 in South Africa. Conclusion The short MDR tuberculosis treatment regimen was associated with a substantial reduction in health-system costs and a lower financial burden for participants.

TDR in close collaboration with the Global TB Programme at WHO and technical partners the WHO Global TB Programme is leading the development of ShORRT (Short, all-Oral Regimens For Rifampicin-resistant Tuberculosis), an operational research package to assess the effectiveness, safety, feasibility, acceptability, cost and impact (including on health-related quality of life) of the use of all-oral shorter drug regimens for adults and children with MDR/RR-TB.