Core outcome sets for trials of interventions to prevent and to treat multimorbidity in adults in low and middle-income countries: the COSMOS study.

INTRODUCTION: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs. METHODS: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS. REGISTRATION: https://www.comet-initiative.org/Studies/Details/1580. RESULTS: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life. CONCLUSION: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs. PROSPERO REGISTRATION NUMBER: CRD42020197293.

Health inequalities at the intersection of multiple social determinants among under five children residing Nairobi urban slums: An application of multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA).

In this analysis we examine through an intersectionality lens how key social determinants of health (SDOH) are associated with health conditions among under-five children (<5y) residing in Nairobi slums, Kenya. We used cross-sectional data collected from Nairobi slums between June and November 2012 to explore how multiple interactions of SDoH shape health inequalities in slums. We applied multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) approach. We constructed intersectional strata for each health condition from combinations of significant SDoH obtained using univariate analyses. We then estimated the intersectional effects of health condition in a series of MAIHDA logistic regression models distinguishing between additive and interaction effects. We quantified discriminatory accuracy (DA) of the intersectional strata by means of the variance partitioning coefficient (VPC) and the area under the receiver operating characteristic curve (AUC-ROC). The total participants were 2,199 <5y, with 120 records (5.5%) dropped because health conditions were recorded as "not applicable". The main outcome variables were three health conditions: 1) whether a child had diarrhea or not, 2) whether a child had fever or not, and 3) whether a child had cough or not in the previous two weeks. We found non-significant intersectional effects for each health condition. The head of household ethnic group was significantly associated with each health condition. We found good DA for diarrhea (VPC = 9.0%, AUC-ROC = 76.6%) an indication of large intersectional effects. However, fever (VPC = 1.9%, AUC-ROC = 66.3%) and cough (VPC = 0.5%, AUC-ROC = 61.8%) had weak DA indicating existence of small intersectional effects. Our study shows pathways for SDoH that affect diarrhea, cough, and fever for <5y living in slums are multiplicative and shared. The findings show that <5y from Luo and Luhya ethnic groups, recent migrants (less than 2 years), and households experiencing CHE are more likely to face worse health outcomes. We recommend relevant stakeholders to develop strategies aimed at identifying these groups for targeted proportionate universalism based on the level of their need.

Comparing cross-sectional and longitudinal approaches to tuberculosis patient cost surveys using Nepalese data.

The World Health Organization has supported the development of national tuberculosis (TB) patient cost surveys to quantify the socio-economic impact of TB in high-burden countries. However, methodological differences in the study design (e.g. cross-sectional vs longitudinal) can generate different estimates making the design and impact evaluation of socio-economic protection strategies difficult. The objective of the study was to compare the socio-economic impacts of TB estimated by applying cross-sectional or longitudinal data collections in Nepal. We analysed the data from a longitudinal costing survey (patients interviewed at three time points) conducted between April 2018 and October 2019. We calculated both mean and median costs from patients interviewed during the intensive (cross-sectional 1) and continuation (cross-sectional 2) phases of treatment. We then compared costs, the prevalence of catastrophic costs and the socio-economic impact of TB generated by each approach. There were significant differences in the costs and social impacts calculated by each approach. The median total cost (intensive plus continuation phases) was significantly higher for the longitudinal compared with cross-sectional 2 (US$119.42 vs 91.63, P < 0.001). The prevalence of food insecurity, social exclusion and patients feeling poorer or much poorer were all significantly higher by applying a longitudinal approach. In conclusion, the longitudinal design captured important aspects of costs and socio-economic impacts, which were missed by applying a cross-sectional approach. If a cross-sectional approach is applied due to resource constraints, our data suggest that the start of the continuation phase is the optimal timing for a single interview. Further research to optimize methodologies to report patient-incurred expenditure during TB diagnosis and treatment is needed.

The economics of healthcare access: a scoping review on the economic impact of healthcare access for vulnerable urban populations in low- and middle-income countries.

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.

Patterns of multimorbidity and some psychiatric disorders: A systematic review of the literature.

Objective: The presence of two or more chronic diseases results in worse clinical outcomes than expected by a simple combination of diseases. This synergistic effect is expected to be higher when combined with some conditions, depending on the number and severity of diseases. Multimorbidity is a relatively new term, with the first fundamental definitions appearing in 2015. Studies usually define it as the presence of at least two chronic medical illnesses. However, little is known regarding the relationship between mental disorders and other non-psychiatric chronic diseases. This review aims at investigating the association between some mental disorders and non-psychiatric diseases, and their pattern of association. Methods: We performed a systematic approach to selecting papers that studied relationships between chronic conditions that included one mental disorder from 2015 to 2021. These were processed using Covidence, including quality assessment. Results: This resulted in the inclusion of 26 papers in this study. It was found that there are strong associations between depression, psychosis, and multimorbidity, but recent studies that evaluated patterns of association of diseases (usually using clustering methods) had heterogeneous results. Quality assessment of the papers generally revealed low quality among the included studies. Conclusions: There is evidence of an association between depressive disorders, anxiety disorders, and psychosis with multimorbidity. Studies that tried to examine the patterns of association between diseases did not find stable results. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021216101, identifier: CRD42021216101.

Effects of social determinants on children's health in informal settlements in Bangladesh and Kenya through an intersectionality lens: a study protocol.

INTRODUCTION: Several studies have shown that residents of urban informal settlements/slums are usually excluded and marginalised from formal social systems and structures of power leading to disproportionally worse health outcomes compared to other urban dwellers. To promote health equity for slum dwellers, requires an understanding of how their lived realities shape inequities especially for young children 0-4 years old (ie, under-fives) who tend to have a higher mortality compared with non-slum children. In these proposed studies, we aim to examine how key Social Determinants of Health (SDoH) factors at child and household levels combine to affect under-five health conditions, who live in slums in Bangladesh and Kenya through an intersectionality lens. METHODS AND ANALYSIS: The protocol describes how we will analyse data from the Nairobi Cross-sectional Slum Survey (NCSS 2012) for Kenya and the Urban Health Survey (UHS 2013) for Bangladesh to explore how SDoH influence under-five health outcomes in slums within an intersectionality framework. The NCSS 2012 and UHS 2013 samples will consist of 2199 and 3173 under-fives, respectively. We will apply Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy approach. Some of SDoH characteristics to be considered will include those of children, head of household, mothers and social structure characteristics of household. The primary outcomes will be whether a child had diarrhoea, cough, fever and acute respiratory infection (ARI) 2 weeks preceding surveys. ETHICS AND DISSEMINATION: The results will be disseminated in international peer-reviewed journals and presented in events organised by the Accountability and Responsiveness in Informal Settlements for Equity consortium and international conferences. Ethical approval was not required for these studies. Access to the NCSS 2012 has been given by Africa Population and Health Center and UHS 2013 is freely available.

Risk of SARS-CoV-2 infection among front-line healthcare workers in Northeast Brazil: a respondent-driven sampling approach.

OBJECTIVES: We assessed the prevalence of SARS-CoV-2 infection, personal protective equipment (PPE) shortages and occurrence of biological accidents among front-line healthcare workers (HCW). DESIGN, SETTING AND PARTICIPANTS: Using respondent-driven sampling, the study recruited distinct categories of HCW attending suspected or confirmed patients with COVID-19 from May 2020 to February 2021, in the Recife metropolitan area, Northeast Brazil. OUTCOME MEASURES: The criterion to assess SARS-CoV-2 infection among HCW was a positive self-reported PCR test. RESULTS: We analysed 1525 HCW: 527 physicians, 471 registered nurses, 263 nursing assistants and 264 physical therapists. Women predominated in all categories (81.1%; 95% CI: 77.8% to 84.1%). Nurses were older with more comorbidities (hypertension and overweight/obesity) than the other staff. The overall prevalence of SARS-CoV-2 infection was 61.8% (95% CI: 55.7% to 67.5%) after adjustment for the cluster random effect, weighted by network, and the reference population size. Risk factors for a positive RT-PCR test were being a nursing assistant (OR adjusted: 2.56; 95% CI: 1.42 to 4.61), not always using all recommended PPE while assisting patients with COVID-19 (OR adj: 2.15; 95% CI: 1.02 to 4.53) and reporting a splash of biological fluid/respiratory secretion in the eyes (OR adj: 3.37; 95% CI: 1.10 to 10.34). CONCLUSIONS: This study shows the high frequency of SARS-CoV2 infection among HCW presumably due to workplace exposures. In our setting, nursing assistant comprised the most vulnerable category. Our findings highlight the need for improving healthcare facility environments, specific training and supervision to cope with public health emergencies.

Protocol for the Addressing the Social Determinants and Consequences of Tuberculosis in Nepal (ASCOT) pilot trial.

BACKGROUND: The World Health Organization's End TB (tuberculosis) Strategy advocates social and economic support for TB-affected households but evidence from low-income settings is scarce. We will evaluate the feasibility and acceptability of a locally-appropriate socioeconomic support intervention for TB-affected households in Nepal. METHODS: We will conduct a pilot randomised-controlled trial with mixed-methods process evaluation in four TB-endemic, impoverished districts of Nepal: Pyuthan, Chitwan, Mahottari, and Morang. We will recruit 128 people with TB notified to the Nepal National TB Program (NTP) and 40 multisectoral stakeholders including NTP staff, civil-society members, policy-makers, and ASCOT (Addressing the Social Determinants and Consequences of Tuberculosis) team members. People with TB will be randomised 1:1:1:1 to four study arms (n=32 each): control; social support; economic support; and combined social and economic (socioeconomic) support. Social support will be TB education and peer-led mutual-support TB Clubs providing TB education and stigma-reduction counselling. Economic support will be monthly unconditional cash transfers during TB treatment with expectations (not conditions) of meeting NTP goals. At 0, 2, and 6 months following TB treatment initiation, participants will be asked to complete a survey detailing the social determinants and consequences of TB and their feedback on ASCOT. Complementary process evaluation will use focus group discussions (FGD), key informant interviews (KII), and a workshop with multi-sectoral stakeholders to consider the challenges to ASCOT's implementation and scale-up. A sample of ~100 people with TB is recommended to estimate TB-related costs. Information power is estimated to be reached with approximately 25 FGD and 15 KII participants. CONCLUSIONS: The ASCOT pilot trial will both generate robust evidence on a locally-appropriate, socioeconomic support intervention for TB-affected households in Nepal and inform a large-scale future ASCOT trial, which will evaluate the intervention's impact on catastrophic costs mitigation and TB outcomes. The trial is registered with the ISRCTN ( ISRCTN17025974).

Barriers and facilitators to accessing tuberculosis care in Nepal: a qualitative study to inform the design of a socioeconomic support intervention.

OBJECTIVE: Psychosocial and economic (socioeconomic) barriers, including poverty, stigma and catastrophic costs, impede access to tuberculosis (TB) services in low-income countries. We aimed to characterise the socioeconomic barriers and facilitators of accessing TB services in Nepal to inform the design of a locally appropriate socioeconomic support intervention for TB-affected households. DESIGN: From August 2018 to July 2019, we conducted an exploratory qualitative study consisting of semistructured focus group discussions (FGDs) with purposively selected multisectoral stakeholders. The data were managed in NVivo V.12, coded by consensus and analysed thematically. SETTING: The study was conducted in four districts, Makwanpur, Chitwan, Dhanusha and Mahottari, which have a high prevalence of poverty and TB. PARTICIPANTS: Seven FGDs were conducted with 54 in-country stakeholders, grouped by stakeholders, including people with TB (n=21), community stakeholders (n=13) and multidisciplinary TB healthcare professionals (n=20) from the National TB Programme. RESULTS: The perceived socioeconomic barriers to accessing TB services were: inadequate TB knowledge and advocacy; high food and transportation costs; income loss and stigma. The perceived facilitators to accessing TB care and services were: enhanced championing and awareness-raising about TB and TB services; social protection including health insurance; cash, vouchers and/or nutritional allowance to cover food and travel costs; and psychosocial support and counselling integrated with existing adherence counselling from the National TB Programme. CONCLUSION: These results suggest that support interventions that integrate TB education, psychosocial counselling and expand on existing cash transfer schemes would be locally appropriate and could address the socioeconomic barriers to accessing and engaging with TB services faced by TB-affected households in Nepal. The findings have been used to inform the design of a socioeconomic support intervention for TB-affected households. The acceptability, feasibility and impact of this intervention on TB-related costs, stigma and TB treatment outcomes, is now being evaluated in a pilot implementation study in Nepal.

Socio-protective effects of active case finding on catastrophic costs from tuberculosis in Ho Chi Minh City, Viet Nam: a longitudinal patient cost survey.

BACKGROUND: Many tuberculosis (TB) patients incur catastrophic costs. Active case finding (ACF) may have socio-protective properties that could contribute to the WHO End TB Strategy target of zero TB-affected families suffering catastrophic costs, but available evidence remains limited. This study measured catastrophic cost incurrence and socioeconomic impact of an episode of TB and compared those socioeconomic burdens in patients detected by ACF versus passive case finding (PCF). METHODS: This cross-sectional study fielded a longitudinal adaptation of the WHO TB patient cost survey alongside an ACF intervention from March 2018 to March 2019. The study was conducted in six intervention (ACF) districts and six comparison (PCF) districts of Ho Chi Minh City, Viet Nam. Fifty-two TB patients detected through ACF and 46 TB patients in the PCF cohort were surveyed within two weeks of treatment initiation, at the end of the intensive phase of treatment, and after treatment concluded. The survey measured income, direct and indirect costs, and socioeconomic impact based on which we calculated catastrophic cost as the primary outcome. Local currency was converted into US$ using the average exchange rates reported by OANDA for the study period (VND1 = US$0.0000436, 2018-2019). We fitted logistic regressions for comparisons between the ACF and PCF cohorts as the primary exposures and used generalized estimating equations to adjust for autocorrelation. RESULTS: ACF patients were poorer than PCF patients (multidimensional poverty ratio: 16 % vs. 7 %; p = 0.033), but incurred lower median pre-treatment costs (US$18 vs. US$80; p < 0.001) and lower median total costs (US$279 vs. US$894; p < 0.001). Fewer ACF patients incurred catastrophic costs (15 % vs. 30 %) and had lower odds of catastrophic cost (aOR = 0.17; 95 % CI: [0.05, 0.67]; p = 0.011), especially during the intensive phase (OR = 0.32; 95 % CI: [0.12, 0.90]; p = 0.030). ACF patient experienced less social exclusion (OR = 0.41; 95 % CI: [0.18, 0.91]; p = 0.030), but more often resorted to financial coping mechanisms (OR = 5.12; 95 % CI: [1.73, 15.14]; p = 0.003). CONCLUSIONS: ACF can be effective in reaching vulnerable populations and mitigating the socioeconomic burden of TB, and can contribute to achieving the WHO End TB Strategy goals. Nevertheless, as TB remains a catastrophic life event, social protection efforts must extend beyond ACF.

Economics of healthcare access in low-income and middle-income countries: a protocol for a scoping review of the economic impacts of seeking healthcare on slum-dwellers compared with other city residents.

INTRODUCTION: People living in slums face several challenges to access healthcare. Scarce and low-quality public health facilities are common problems in these communities. Costs and prevalence of catastrophic health expenditures (CHE) have also been reported as high in studies conducted in slums in developing countries and those suffering from chronic conditions and the poorest households seem to be more vulnerable to financial hardship. The COVID-19 pandemic may be aggravating the economic impact on the extremely vulnerable population living in slums due to the long-term consequences of the disease. The objective of this review is to report the economic impact of seeking healthcare on slum-dwellers in terms of costs and CHE. We will compare the economic impact on slum-dwellers with other city residents. METHODS AND ANALYSIS: This scoping review adopts the framework suggested by Arksey and O'Malley. The review is part of the accountability and responsiveness of slum-dwellers (ARISE) research consortium, which aims to enhance accountability to improve the health and well-being of marginalised populations living in slums in India, Bangladesh, Sierra Leone and Kenya. Costs of accessing healthcare will be updated to 2020 prices using the inflation rates reported by the International Monetary Fund. Costs will be presented in International Dollars by using purchase power parity. The prevalence of CHE will also be reported. ETHICS AND DISSEMINATION: Ethical approval is not required for scoping reviews. We will disseminate our results alongside the events organised by the ARISE consortium and international conferences. The final manuscript will be submitted to an open-access international journal. Registration number at the Research Registry: reviewregistry947.

How to reduce household costs for people with tuberculosis: a longitudinal costing survey in Nepal.

The aim of this study was to compare costs and socio-economic impact of tuberculosis (TB) for patients diagnosed through active (ACF) and passive case finding (PCF) in Nepal. A longitudinal costing survey was conducted in four districts of Nepal from April 2018 to October 2019. Costs were collected using the WHO TB Patient Costs Survey at three time points: intensive phase of treatment, continuation phase of treatment and at treatment completion. Direct and indirect costs and socio-economic impact (poverty headcount, employment status and coping strategies) were evaluated throughout the treatment. Prevalence of catastrophic costs was estimated using the WHO threshold. Logistic regression and generalized estimating equation were used to evaluate risk of incurring high costs, catastrophic costs and socio-economic impact of TB over time. A total of 111 ACF and 110 PCF patients were included. ACF patients were more likely to have no education (75% vs 57%, P = 0.006) and informal employment (42% vs 24%, P = 0.005) Compared with the PCF group, ACF patients incurred lower costs during the pretreatment period (mean total cost: US$55 vs US$87, P < 0.001) and during the pretreatment plus treatment periods (mean total direct costs: US$72 vs US$101, P < 0.001). Socio-economic impact was severe for both groups throughout the whole treatment, with 32% of households incurring catastrophic costs. Catastrophic costs were associated with 'no education' status [odds ratio = 2.53(95% confidence interval = 1.16-5.50)]. There is a severe and sustained socio-economic impact of TB on affected households in Nepal. The community-based ACF approach mitigated costs and reached the most vulnerable patients. Alongside ACF, social protection policies must be extended to achieve the zero catastrophic costs milestone of the End TB strategy.

Effectiveness of screening for tuberculosis in HIV: a pragmatic clinical trial

ABSTRACT OBJECTIVE: To verify the effectiveness of screening for tuberculosis (TB) on all-cause mortality and tuberculosis cases in newly diagnosed HIV-infected patients through a clinical algorithm based on recommendations of the World Health Organization. METHODS: From March 2014 to April 2016, a pragmatic randomized clinical trial was conducted with newly diagnosed and TB-free HIV-infected adults undergoing antiretroviral therapy for up to one month at a major tertiary hospital for HIV in the state of Pernambuco, Brazil. Participants were randomized into intervention and control groups using an automatically-generated random list, and followed-up for at least 6 months. The intervention group was screened for TB at hospital admission and at every follow-up visit through a series of questions addressing TB-related symptoms (cough, fever, night sweating, and weight loss). Patients presenting with any of these symptoms were referred to a pulmonologist and underwent sputum smear microscopy, sputum culture, and rapid molecular testing (GeneXpert). When at least one test result came back positive, TB treatment was initiated. In turn, if patients tested negative but presented with severe clinal symptoms, TB preventive treatment was initiated. Screening for TB was not performed systematically in the control group. The primary outcome assessed in this study was death from all causes, and secondary outcomes included sensitivity and specificity of this screening test, as well as its detection time. RESULTS: This study evaluated 581 patients, 377 in the intervention group (64.9%) and 204 in the control group (35.1%). In total, 36 patients died during the follow-up period. Of these, 26 (6.9%) were from the intervention group, reaching a cumulative mortality coefficient of 69 per 1,000 inhabitants, and 10 (4.9%) from the control group (p = 0.341), with a cumulative mortality coefficient of 49 per 1,000 inhabitants (p = 0.341).

Research protocol for a mixed-methods study to characterise and address the socioeconomic impact of accessing TB diagnosis and care in Nepal.

Background: WHO's 2015 End TB Strategy advocates social and economic (socioeconomic) support for TB-affected households to improve TB control. However, evidence concerning socioeconomic support for TB-affected households remains limited, especially in low-income countries. Protocol: This mixed-methods study in Nepal will: evaluate the socioeconomic impact of accessing TB diagnosis and care (Project 1); and create a shortlist of feasible, locally-appropriate interventions to mitigate this impact (Project 2). The study will be conducted in the Chitwan, Mahottari, Makawanpur, and Dhanusha districts of Nepal, which have frequent TB and poverty. The study population will include: approximately 200 people with TB (Cases) starting TB treatment with Nepal's National TB Program and 100 randomly-selected people without TB (Controls) in the same sites (Project 1); and approximately 40 key in-country stakeholders from Nepal including people with TB, community leaders, and TB healthcare professionals (Project 2). During Project 1, visits will be made to people with TB's households during months 3 and 6 of TB treatment, and a single visit made to Control households. During visits, participants will be asked about: TB-related costs (if receiving treatment), food insecurity, stigma; TB-related knowledge; household poverty level; social capital; and quality of life. During Project 2, stakeholders will be invited to participate in: a survey and focus group discussion (FGD) to characterise socioeconomic impact, barriers and facilitators to accessing and engaging with TB care in Nepal; and a one-day workshop to review FGD findings and suggest interventions to mitigate the barriers identified. Ethics and dissemination: The study has received ethical approval. Results will be disseminated through scientific meetings, open access publications, and a national workshop in Nepal.  Conclusions: This research will strengthen understanding of the socioeconomic impact of TB in Nepal and generate a shortlist of feasible and locally-appropriate socioeconomic interventions for TB-affected households for trial evaluation.

Developing Feasible, Locally Appropriate Socioeconomic Support for TB-Affected Households in Nepal.

Tuberculosis (TB), the leading single infectious diseases killer globally, is driven by poverty. Conversely, having TB worsens impoverishment. During TB illness, lost income and out-of-pocket costs can become "catastrophic", leading patients to abandon treatment, develop drug-resistance, and die. WHO's 2015 End TB Strategy recommends eliminating catastrophic costs and providing socioeconomic support for TB-affected people. However, there is negligible evidence to guide the design and implementation of such socioeconomic support, especially in low-income, TB-endemic countries. A national, multi-sectoral workshop was held in Kathmandu, Nepal, on the 11th and 12th September 2019, to develop a shortlist of feasible, locally appropriate socioeconomic support interventions for TB-affected households in Nepal, a low-income country with significant TB burden. The workshop brought together key stakeholders in Nepal including from the Ministry of Health and Population, Department of Health Services, Provincial Health Directorate, Health Offices, National TB Program (NTP); and TB/Leprosy Officers, healthcare workers, community health volunteers, TB-affected people, and external development partners (EDP). During the workshop, participants reviewed current Nepal NTP data and strategy, discussed the preliminary results of a mixed-methods study of the socioeconomic determinants and consequences of TB in Nepal, described existing and potential socioeconomic interventions for TB-affected households in Nepal, and selected the most promising interventions for future randomized controlled trial evaluations in Nepal. This report describes the activities, outcomes, and recommendations from the workshop.

The role of active case finding in reducing patient incurred catastrophic costs for tuberculosis in Nepal.

BACKGROUND: The World Health Organization (WHO) End TB Strategy has established a milestone to reduce the number of tuberculosis (TB)- affected households facing catastrophic costs to zero by 2020. The role of active case finding (ACF) in reducing patient costs has not been determined globally. This study therefore aimed to compare costs incurred by TB patients diagnosed through ACF and passive case finding (PCF), and to determine the prevalence and intensity of patient-incurred catastrophic costs in Nepal. METHODS: The study was conducted in two districts of Nepal: Bardiya and Pyuthan (Province No. 5) between June and August 2018. One hundred patients were included in this study in a 1:1 ratio (PCF: ACF, 25 consecutive ACF and 25 consecutive PCF patients in each district). The WHO TB patient costing tool was applied to collect information from patients or a member of their family regarding indirect and direct medical and non-medical costs. Catastrophic costs were calculated based on the proportion of patients with total costs exceeding 20% of their annual household income. The intensity of catastrophic costs was calculated using the positive overshoot method. The chi-square and Wilcoxon-Mann-Whitney tests were used to compare proportions and costs. Meanwhile, the Mantel Haenszel test was performed to assess the association between catastrophic costs and type of diagnosis. RESULTS: Ninety-nine patients were interviewed (50 ACF and 49 PCF). Patients diagnosed through ACF incurred lower costs during the pre-treatment period (direct medical: USD 14 vs USD 32, P = 0.001; direct non-medical: USD 3 vs USD 10, P = 0.004; indirect, time loss: USD 4 vs USD 13, P <  0.001). The cost of the pre-treatment and intensive phases combined was also lower for direct medical (USD 15 vs USD 34, P = 0.002) and non-medical (USD 30 vs USD 54, P = 0.022) costs among ACF patients. The prevalence of catastrophic direct costs was lower for ACF patients for all thresholds. A lower intensity of catastrophic costs was also documented for ACF patients, although the difference was not statistically significant. CONCLUSIONS: ACF can reduce patient-incurred costs substantially, contributing to the End TB Strategy target. Other synergistic policies, such as social protection, will also need to be implemented to reduce catastrophic costs to zero among TB-affected households.

Scoping review on vector-borne diseases in urban areas: transmission dynamics, vectorial capacity and co-infection.

BACKGROUND: Transmission dynamics, vectorial capacity, and co-infections have substantial impacts on vector-borne diseases (VBDs) affecting urban and suburban populations. Reviewing key factors can provide insight into priority research areas and offer suggestions for potential interventions. MAIN BODY: Through a scoping review, we identify knowledge gaps on transmission dynamics, vectorial capacity, and co-infections regarding VBDs in urban areas. Peer-reviewed and grey literature published between 2000 and 2016 was searched. We screened abstracts and full texts to select studies. Using an extraction grid, we retrieved general data, results, lessons learned and recommendations, future research avenues, and practice implications. We classified studies by VBD and country/continent and identified relevant knowledge gaps. Of 773 articles selected for full-text screening, 50 were included in the review: 23 based on research in the Americas, 15 in Asia, 10 in Africa, and one each in Europe and Australia. The largest body of evidence concerning VBD epidemiology in urban areas concerned dengue and malaria. Other arboviruses covered included chikungunya and West Nile virus, other parasitic diseases such as leishmaniasis and trypanosomiasis, and bacterial rickettsiosis and plague. Most articles retrieved in our review combined transmission dynamics and vectorial capacity; only two combined transmission dynamics and co-infection. The review identified significant knowledge gaps on the role of asymptomatic individuals, the effects of co-infection and other host factors, and the impacts of climatic, environmental, and socioeconomic factors on VBD transmission in urban areas. Limitations included the trade-off from narrowing the search strategy (missing out on classical modelling studies), a lack of studies on co-infections, most studies being only descriptive, and few offering concrete public health recommendations. More research is needed on transmission risk in homes and workplaces, given increasingly dynamic and mobile populations. The lack of studies on co-infection hampers monitoring of infections transmitted by the same vector. CONCLUSIONS: Strengthening VBD surveillance and control, particularly in asymptomatic cases and mobile populations, as well as using early warning tools to predict increasing transmission, were key strategies identified for public health policy and practice.

Cost of Tuberculosis Diagnosis and Treatment in Patients with HIV: A Systematic Literature Review.

OBJECTIVES: To summarize the costs of tuberculosis (TB) diagnosis and treatment in human immunodeficiency virus (HIV)-infected patients and to assess the methodological quality of these studies. METHODS: We included cost, cost-effectiveness, and cost-utility studies that reported primary costing data, conducted worldwide and published between 1990 and August 2016. We retrieved articles in PubMed, Embase, EconLit, CINAHL plus, and LILACS databases. The quality assessment was performed using two guidelines-the Consolidated Health Economic Evaluation Reporting Standards and the Tool to Estimate Patient's Costs. TB diagnosis was reported as cost per positive result or per suspect case. TB treatment was reported as cost of TB drugs, TB/HIV hospitalization, and treatment. We analyzed the data per level of TB/HIV endemicity and perspective of analysis. RESULTS: We included 34 articles, with 24 addressing TB/HIV treatment and 10 addressing TB diagnosis. Most of the studies were carried out in high TB/HIV burden countries (82%). The cost of TB diagnosis per suspect case varied from $0.5 for sputum smear microscopy to $175 for intensified case finding. The cost of TB/HIV hospitalization was higher in low/medium TB/HIV burden countries than in high TB/HIV burden countries ($75,406 vs. $2,474). TB/HIV co-infection presented higher costs than TB from the provider perspective ($814 vs. $604 vs. $454). Items such as "choice of discount rate," "patient interview procedures," and "methods used for valuing indirect costs" did not achieve a good score in the quality assessment. CONCLUSIONS: Our findings point to the need of generation of more standardized methods for cost data collection to generate more robust estimates and thus, support decision-making process.

Economic burden of HIV and TB/HIV coinfection in a middle-income country: a costing analysis alongside a pragmatic clinical trial in Brazil.

OBJECTIVE: The objective of this study was to measure the costs of people living with HIV (PLHIV) as well as active tuberculosis (TB/HIV), latent tuberculosis infection (LTBI/HIV) or without TB (HIV/AIDS). METHODS: We analysed the costs through the entire pathway of care during the prediagnosis and treatment periods from the Brazilian public health system perspective. We applied a combination of bottom-up and top-down approaches to capture and estimate direct medical and non-medical costs. We measured the mean cost per patient per type of care (inpatient, outpatient and emergency care) and disease category (HIV/AIDS, HIV/AIDS death, TB/HIV, TB/HIV death and LTBI/HIV). RESULTS: Between March 2014 and March 2016 we recruited 239 PLHIV. During the follow-up 26 patients were diagnosed and treated for TB and 5 received chemoprophylaxis for LTBI. During the prediagnosis and treatment period, the mean total costs for HIV or AIDS and AIDS death categories were US$1558 and US$2828, respectively. The mean total costs for TB/HIV and TB/HIV death categories were US$5289.0 and US$8281, respectively. The mean total cost for the LTBI/HIV category was US$882. CONCLUSIONS: Patients with TB/HIV impose a higher economic burden on the health system than HIV/AIDS and LTBI/HIV. Patients with LTBI/HIV were the lowest cost group among all disease categories, indicating that preventive TB treatment can avoid the further costs treating active TB. TRIAL REGISTRATION NUMBER: RBR-22t943, Results.

Systematic review of societal and health system cost of dengue in Latin America

Aim: to conduct a systematic literature review on dengue costs in Latin America, comparing study methodologies, disease costs and the economic impact of dengue in different countries. Methods: the literature search was carried out in the following electronic databases: MEDLINE/ PubMed, EMBASE and LILACS, for the period between 2004 and 2014. To make comparisons possible, the costs identified in the selected studies were converted to local currency values, adjusted to the consumer price index (2014) and converted to purchasing power parity (PPP). Results: 728 publications were identified in databases and 13 papers were selected for analysis. Nine of the thirteen studies were conducted from a societal perspective and three from a health system perspective. In most studies, indirect costs accounted for the largest percentage of total outpatient costs. In contrast, for hospitalized patients, direct medical costs showed the highest percentages. The economic impact of dengue was estimated at I$ 3.2 billion per year, ranging from I$ 1.4 to I$ 5.9 billion, when including the six sub-regions of the Americas. Conclusion: dengue represents a high cost for Latin American society and health system. Studies varied in terms of cost methodology (cost items included, such as direct medical and non-medical and indirect costs, and cost analysis) and the different epidemiological periods in which research was carried out (endemic and/or epidemic).