Symptom- and chest-radiography screening for active pulmonary tuberculosis in HIV-negative adults and adults with unknown HIV status.

BACKGROUND: Systematic screening in high-burden settings is recommended as a strategy for early detection of pulmonary tuberculosis disease, reducing mortality, morbidity and transmission, and improving equity in access to care. Questioning for symptoms and chest radiography (CXR) have historically been the most widely available tools to screen for tuberculosis disease. Their accuracy is important for the design of tuberculosis screening programmes and determines, in combination with the accuracy of confirmatory diagnostic tests, the yield of a screening programme and the burden on individuals and the health service. OBJECTIVES: To assess the sensitivity and specificity of questioning for the presence of one or more tuberculosis symptoms or symptom combinations, CXR, and combinations of these as screening tools for detecting bacteriologically confirmed pulmonary tuberculosis disease in HIV-negative adults and adults with unknown HIV status who are considered eligible for systematic screening for tuberculosis disease. Second, to investigate sources of heterogeneity, especially in relation to regional, epidemiological, and demographic characteristics of the study populations. SEARCH METHODS: We searched the MEDLINE, Embase, LILACS, and HTA (Health Technology Assessment) databases using pre-specified search terms and consulted experts for unpublished reports, for the period 1992 to 2018. The search date was 10 December 2018. This search was repeated on 2 July 2021. SELECTION CRITERIA: Studies were eligible if participants were screened for tuberculosis disease using symptom questions, or abnormalities on CXR, or both, and were offered confirmatory testing with a reference standard. We included studies if diagnostic two-by-two tables could be generated for one or more index tests, even if not all participants were subjected to a microbacteriological reference standard. We excluded studies evaluating self-reporting of symptoms. DATA COLLECTION AND ANALYSIS: We categorized symptom and CXR index tests according to commonly used definitions. We assessed the methodological quality of included studies using the QUADAS-2 instrument. We examined the forest plots and receiver operating characteristic plots visually for heterogeneity. We estimated summary sensitivities and specificities (and 95% confidence intervals (CI)) for each index test using bivariate random-effects methods. We analyzed potential sources of heterogeneity in a hierarchical mixed-model. MAIN RESULTS: The electronic database search identified 9473 titles and abstracts. Through expert consultation, we identified 31 reports on national tuberculosis prevalence surveys as eligible (of which eight were already captured in the search of the electronic databases), and we identified 957 potentially relevant articles through reference checking. After removal of duplicates, we assessed 10,415 titles and abstracts, of which we identified 430 (4%) for full text review, whereafter we excluded 364 articles. In total, 66 articles provided data on 59 studies. We assessed the 2 July 2021 search results; seven studies were potentially eligible but would make no material difference to the review findings or grading of the evidence, and were not added in this edition of the review. We judged most studies at high risk of bias in one or more domains, most commonly because of incorporation bias and verification bias. We judged applicability concerns low in more than 80% of studies in all three domains. The three most common symptom index tests, cough for two or more weeks (41 studies), any cough (21 studies), and any tuberculosis symptom (29 studies), showed a summary sensitivity of 42.1% (95% CI 36.6% to 47.7%), 51.3% (95% CI 42.8% to 59.7%), and 70.6% (95% CI 61.7% to 78.2%, all very low-certainty evidence), and a specificity of 94.4% (95% CI 92.6% to 95.8%, high-certainty evidence), 87.6% (95% CI 81.6% to 91.8%, low-certainty evidence), and 65.1% (95% CI 53.3% to 75.4%, low-certainty evidence), respectively. The data on symptom index tests were more heterogenous than those for CXR. The studies on any tuberculosis symptom were the most heterogeneous, but had the lowest number of variables explaining this variation. Symptom index tests also showed regional variation. The summary sensitivity of any CXR abnormality (23 studies) was 94.7% (95% CI 92.2% to 96.4%, very low-certainty evidence) and 84.8% (95% CI 76.7% to 90.4%, low-certainty evidence) for CXR abnormalities suggestive of tuberculosis (19 studies), and specificity was 89.1% (95% CI 85.6% to 91.8%, low-certainty evidence) and 95.6% (95% CI 92.6% to 97.4%, high-certainty evidence), respectively. Sensitivity was more heterogenous than specificity, and could be explained by regional variation. The addition of cough for two or more weeks, whether to any (pulmonary) CXR abnormality or to CXR abnormalities suggestive of tuberculosis, resulted in a summary sensitivity and specificity of 99.2% (95% CI 96.8% to 99.8%) and 84.9% (95% CI 81.2% to 88.1%) (15 studies; certainty of evidence not assessed). AUTHORS' CONCLUSIONS: The summary estimates of the symptom and CXR index tests may inform the choice of screening and diagnostic algorithms in any given setting or country where screening for tuberculosis is being implemented. The high sensitivity of CXR index tests, with or without symptom questions in parallel, suggests a high yield of persons with tuberculosis disease. However, additional considerations will determine the design of screening and diagnostic algorithms, such as the availability and accessibility of CXR facilities or the resources to fund them, and the need for more or fewer diagnostic tests to confirm the diagnosis (depending on screening test specificity), which also has resource implications. These review findings should be interpreted with caution due to methodological limitations in the included studies and regional variation in sensitivity and specificity. The sensitivity and specificity of an index test in a specific setting cannot be predicted with great precision due to heterogeneity. This should be borne in mind when planning for and implementing tuberculosis screening programmes.

Economic evaluation of patient costs associated with tuberculosis diagnosis and care in Solomon Islands.

BACKGROUND: Tuberculosis (TB) care can be costly for patients and their families. The End TB Strategy includes a target that zero TB affected households should experience catastrophic costs associated with TB care. Costs are catastrophic when a patient spends 20% or more of their annual household income on their TB diagnosis and care. In Solomon Islands the costs of TB care are unknown. The aim of this study was to determine the costs of TB diagnosis and care, the types of costs and the proportion of patients with catastrophic costs. METHODS: This was a nationally representative cross-sectional survey of TB patients carried out between 2017 and 2019. Patients were recruited from health care facilities, from all ten provinces in Solomon Islands. During an interview they were asked about the costs of TB diagnosis and care. These data were analysed using descriptive statistics to describe the costs overall and the proportions of different types of costs. The proportion of patients with catastrophic costs was calculated and a multivariate logistic regression was undertaken to determine factors associated with catastrophic costs. RESULTS: One hundred and eighty-three TB patients participated in the survey. They spent a mean of 716 USD (inter quartile range: 348-1217 USD) on their TB diagnosis and care. Overall, 62.1% of costs were attributable to non-medical costs, while income loss and medical costs comprised 28.5 and 9.4%, respectively. Overall, 19.7% (n = 36) of patients used savings, borrowed money, or sold assets as a financial coping mechanism. Three patients (1.6%) had health insurance. A total of 92.3% (95% CI: 88.5-96.2) experienced catastrophic costs, using the output approach. Being in the first, second or third poorest wealth quintile was significantly associated with catastrophic costs (adjusted odds ratio: 67.3, 95% CI: 15.86-489.74%, p <  0.001). CONCLUSION: The costs of TB care are catastrophic for almost all patients in Solomon Islands. The provision of TB specific social and financial protection measures from the National TB and Leprosy Programme may be needed in the short term to ameliorate these costs. In the longer term, advancement of universal health coverage and other social and financial protection measures should be pursued.

'A double-edged sword': Perceived benefits and harms of active case-finding for people with presumptive tuberculosis and communities-A qualitative study based on expert interviews.

BACKGROUND: Active case-finding (ACF), also referred to as community-based tuberculosis screening, is a component of the World Health Organization's End TB Strategy. ACF has potential benefits but also harms, which need to be carefully assessed when developing and implementing ACF policies. While empirical evidence on the benefits of ACF is still weak, evidence on the harms is even weaker. This study aimed to explore experts' views on the benefits and harms of ACF for people with presumptive TB and communities. METHODS: This was an exploratory study. Semi-structured interviews were conducted with a purposive sample of 39 experts from international, non-governmental/non-profit organizations, funders, government institutions, international societies, think tanks, universities and research institutions worldwide. Framework analysis was applied. RESULTS: Findings elaborated perceived benefits of ACF, including reaching vulnerable populations, reducing patient costs, helping raise awareness for tuberculosis among individuals and engaging communities, and reducing tuberculosis transmission. Perceived harms included increasing stigma and discrimination, causing false-positive diagnoses, as well as triggering other unintended consequences related to screening for tuberculosis patients, such as deportation of migrants once confirmed to have tuberculosis. Most of the perceived benefits of ACF could be linked to its objective of finding and treating persons with tuberculosis early (theme 1), while ACF was also perceived as a "double-edged sword" and could cause harms, if inappropriately designed and implemented (theme 2). The analysis underlined the importance of considering the benefits and harms of ACF throughout the screening pathway. The study provides new insights into the perceived benefits and harms of ACF from the perspectives of experts in the field. CONCLUSION: This study highlights gaps in the evidence base surrounding ACF and can stimulate further research, debate and analysis regarding the benefits and harms of ACF to inform contextual optimization of design and implementation of ACF strategies.

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.

First national tuberculosis patient cost survey in Lao People's Democratic Republic: Assessment of the financial burden faced by TB-affected households and the comparisons by drug-resistance and HIV status.

BACKGROUND: Tuberculosis (TB) patients incur large costs for care seeking, diagnosis, and treatment. To understand the magnitude of this financial burden and its main cost drivers, the Lao People's Democratic Republic (PDR) National TB Programme carried out the first national TB patient cost survey in 2018-2019. METHOD: A facility-based cross-sectional survey was conducted based on a nationally representative sample of TB patients from public health facilities across 12 provinces. A total of 848 TB patients including 30 drug resistant (DR)-TB and 123 TB-HIV coinfected patients were interviewed using a standardised questionnaire developed by the World Health Organization. Information on direct medical, direct non-medical and indirect costs, as well as coping mechanisms was collected. We estimated the percentage of TB-affected households facing catastrophic costs, which was defined as total TB-related costs accounting for more than 20% of annual household income. RESULT: The median total cost of TB care was US$ 755 (Interquartile range 351-1,454). The costs were driven by direct non-medical costs (46.6%) and income loss (37.6%). Nutritional supplements accounted for 74.7% of direct non-medical costs. Half of the patients used savings, borrowed money or sold household assets to cope with TB. The proportion of unemployment more than doubled from 16.8% to 35.4% during the TB episode, especially among those working in the informal sector. Of all participants, 62.6% of TB-affected households faced catastrophic costs. This proportion was higher among households with DR-TB (86.7%) and TB-HIV coinfected patients (81.1%). CONCLUSION: In Lao PDR, TB patients and their households faced a substantial financial burden due to TB, despite the availability of free TB services in public health facilities. As direct non-medical and indirect costs were major cost drivers, providing free TB services is not enough to ease this financial burden. Expansion of existing social protection schemes to accommodate the needs of TB patients is necessary.

Active case-finding policy development, implementation and scale-up in high-burden countries: A mixed-methods survey with National Tuberculosis Programme managers and document review.

BACKGROUND: The World Health Organization (WHO) stresses the importance of active case-finding (ACF) for early detection of tuberculosis (TB), especially in the 30 high-burden countries that account for almost 90% of cases globally. OBJECTIVE: To describe the attitudes of National TB Programme (NTP) managers related to ACF policy development, implementation and scale-up in the 30 high-burden countries, and to review national TB strategic plans. METHODS: This was a mixed-methods study with an embedded design: A cross-sectional survey with NTP managers yielded quantitative and qualitative data. A review of national TB strategic plans complemented the results. All data were analyzed in parallel and merged in the interpretation of the findings. RESULTS: 23 of the 30 NTP managers (77%) participated in the survey and 22 (73%) national TB strategic plans were reviewed. NTP managers considered managers in districts and regions key stakeholders for both ACF policy development and implementation. Different types of evidence were used to inform ACF policy, while there was a particular demand for local evidence. The NSPs reflected the NTP managers' unanimous agreement on the need for ACF scale-up, but not all included explicit aims and targets related to ACF. The NTP managers recognized that ACF may decrease health systems costs in the long-term, while acknowledging the risk for increased health system costs in the short-term. About 90% of the NTP managers declared that financial and human resources were currently lacking, while they also elaborated on strategies to overcome resource constraints. CONCLUSION: NTP managers stated that ACF should be scaled up but reported resource constraints. Strategies to increase resources exist but may not yet have been fully implemented, e.g. generating local evidence including from operational research for advocacy. Managers in districts and regions were identified as key stakeholders whose involvement could help improve ACF policy development, implementation and scale-up.

Income security during periods of ill health: a scoping review of policies, practice and coverage in low-income and middle-income countries.

The COVID-19 pandemic is a reminder that insufficient income security in periods of ill health leads to economic hardship for individuals and hampers disease control efforts as people struggle to stay home when sick or advised to observe quarantine. Evidence on income security during periods of ill health is growing but has not previously been reviewed as a full body of work concerning low-income and middle-income countries (LMICs). We performed a scoping review to map the range, features, coverage, protective effects and equity of policies that aim to provide income security for adults whose ill health prevents them from participating in gainful work. A total of 134 studies were included, providing data from 95% of LMICs. However, data across the majority of these countries were severely limited. Collectively the included studies demonstrate that coverage of contributory income-security schemes is low, especially for informal and low-income workers. Meanwhile, non-contributory schemes targeting low-income groups are often not explicitly designed to provide income support in periods of ill health, they can be difficult to access and rarely provide sufficient income support to cover the needs of eligible recipients. While identifying an urgent need for more research on illness-related income security in LMICs, this review concludes that scaling up and diversifying the range of income security interventions is crucial for improving coverage and equity. To achieve these outcomes, illness-related income protection must receive greater recognition in health policy and health financing circles, expanding our understanding of financial hardship beyond direct medical costs.

Epidemiology of tuberculosis in the Western Pacific Region: Progress towards the 2020 milestones of the End TB Strategy.

Since 2015, the End TB Strategy and the Regional Framework for Action on Implementation of the End TB Strategy in the Western Pacific 2016-2020 have guided national tuberculosis (TB) responses in countries and areas of the Region. This paper provides an overview of the TB epidemiological situation in the Western Pacific Region and of progress towards the 2020 milestones of the Strategy. A descriptive analysis was conducted of TB surveillance and programme data reported to WHO and estimates of the TB burden generated by WHO for the period 2000-2018. An estimated 1.8 million people developed TB and 90 000 people died from it in the Region in 2018. Since 2015, the estimated TB incidence rate and the estimated number of TB deaths in the Region decreased by 3% and 10%, with annual reduction rates of 1.0% and 3.4%, respectively. With current efforts, the Region is unlikely to achieve the 2020 milestones and other targets of the Strategy. Major challenges include: (1) wide variation in the geographical distribution and rate of TB incidence among countries; (2) a substantial proportion (23%) of TB cases that remain unreached, undiagnosed or unreported; (3) insufficient coverage of drug susceptibility testing (51%) for bacteriologically confirmed cases and limited use of WHO-recommended rapid diagnostics (11 countries reported < 60% coverage); (4) suboptimal treatment outcomes of TB (60% of countries reported < 85% success), of TB/HIV co-infection (79%) and of multidrug- or rifampicin-resistant TB (59%); (5) limited coverage of TB preventive treatment among people living with HIV (39%) and child contacts (12%); and (6) substantial proportions (35-70%) of TB-affected families facing catastrophic costs. For the Region to stay on track to achieve the End TB Strategy targets, an accelerated multisectoral response to TB is required in every country.

Factors influencing active tuberculosis case-finding policy development and implementation: a scoping review.

OBJECTIVE: To explore antecedents, components and influencing factors on active case-finding (ACF) policy development and implementation. DESIGN: Scoping review, searching MEDLINE, Web of Science, the Cochrane Database of Systematic Reviews and the World Health Organization (WHO) Library from January 1968 to January 2018. We excluded studies focusing on latent tuberculosis (TB) infection, passive case-finding, childhood TB and studies about effectiveness, yield, accuracy and impact without descriptions of how this evidence has/could influence ACF policy or implementation. We included any type of study written in English, and conducted frequency and thematic analyses. RESULTS: Seventy-three articles fulfilled our eligibility criteria. Most (67%) were published after 2010. The studies were conducted in all WHO regions, but primarily in Africa (22%), Europe (23%) and the Western-Pacific region (12%). Forty-one percent of the studies were classified as quantitative, followed by reviews (22%) and qualitative studies (12%). Most articles focused on ACF for tuberculosis contacts (25%) or migrants (32%). Fourteen percent of the articles described community-based screening of high-risk populations. Fifty-nine percent of studies reported influencing factors for ACF implementation; mostly linked to the health system (eg, resources) and the community/individual (eg, social determinants of health). Only two articles highlighted factors influencing ACF policy development (eg, politics). Six articles described WHO's ACF-related recommendations as important antecedent for ACF. Key components of successful ACF implementation include health system capacity, mechanisms for integration, education and collaboration for ACF. CONCLUSION: We identified some main themes regarding the antecedents, components and influencing factors for ACF policy development and implementation. While we know much about facilitators and barriers for ACF policy implementation, we know less about how to strengthen those facilitators and how to overcome those barriers. A major knowledge gap remains when it comes to understanding which contextual factors influence ACF policy development. Research is required to understand, inform and improve ACF policy development and implementation.

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.

The Financial Burden of Tuberculosis for Patients in the Western-Pacific Region.

The End Tuberculosis (TB) Strategy has the ambitious goal of ending the global TB epidemic by the year 2030, which is aligned to the Sustainable Development Goals. One of three high level indicators of the Strategy is the "catastrophic costs" indicator, which aims to determine the proportion of TB-affected households that incur TB-care related costs equivalent to 20% or more of their annual household income. The target is that zero percentage of TB-affected households will incur catastrophic costs related to TB care by the year 2020. In the Western Pacific Region of the World Health Organization, it is a priority to determine the financial burden of TB and then act to mitigate it. To date, eight countries in the Region have conducted nationally representative TB patient cost surveys to determine the costs of TB care. The results from four countries that have completed these surveys (i.e., Fiji, Mongolia, the Philippines, and Vietnam) indicate that between 35% and 70% of TB patients face catastrophic costs related to their TB care. With these results in mind, significant additional efforts are needed to ensure financial risk protection for TB patients, expand Universal Health Coverage, and improve access to social protection interventions. A multi-sectoral approach is necessary to achieve this ambitious goal by the year 2020.

Mapping tuberculosis treatment outcomes in Ethiopia.

BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious disease in Ethiopia, killing more than 30 thousand people every year. This study aimed to determine whether the rates of poor TB treatment outcome varied geographically across Ethiopia at district and zone levels and whether such variability was associated with socioeconomic, behavioural, health care access, or climatic conditions. METHODS: A geospatial analysis was conducted using national TB data reported to the health management information system (HMIS), for the period 2015-2017. The prevalence of poor TB treatment outcomes was calculated by dividing the sum of treatment failure, death and loss to follow-up by the total number of TB patients. Binomial logistic regression models were computed and a spatial analysis was performed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo (MCMC) simulation. Geographic clustering was assessed using the Getis-Ord Gi* statistic, and global and local Moran's I statistics. RESULTS: A total of 223,244 TB patients were reported from 722 districts in Ethiopia during the study period. Of these, 63,556 (28.5%) were cured, 139,633 (62.4%) completed treatment, 6716 (3.0%) died, 1459 (0.7%) had treatment failure, and 12,200 (5.5%) were lost to follow-up. The overall prevalence of a poor TB treatment outcome was 9.0% (range, 1-58%). Hot-spots and clustering of poor TB treatment outcomes were detected in districts near the international borders in Afar, Gambelia, and Somali regions and cold spots were detected in Oromia and Amhara regions. Spatial clustering of poor TB treatment outcomes was positively associated with the proportion of the population with low wealth index (OR: 1.01; 95%CI: 1.0, 1.01), the proportion of the population with poor knowledge about TB (OR: 1.02; 95%CI: 1.01, 1.03), and higher annual mean temperature per degree Celsius (OR: 1.15; 95% CI: 1.08, 1.21). CONCLUSIONS: This study showed significant spatial variation in poor TB treatment outcomes in Ethiopia that was related to underlying socioeconomic status, knowledge about TB, and climatic conditions. Clinical and public health interventions should be targeted in hot spot areas to reduce poor TB treatment outcomes and to achieve the national End-TB Strategy targets.

Cost-effectiveness of 3 months of weekly rifapentine and isoniazid compared with other standard treatment regimens for latent tuberculosis infection: a decision analysis study.

Background: Latent tuberculosis infection (LTBI) is a critical driver of the global burden of active TB, and therefore LTBI treatment is key for TB elimination. Treatment regimens for LTBI include self-administered daily isoniazid for 6 (6H) or 9 (9H) months, self-administered daily rifampicin plus isoniazid for 3 months (3RH), self-administered daily rifampicin for 4 months (4R) and weekly rifapentine plus isoniazid for 3 months self-administered (3HP-SAT) or administered by a healthcare worker as directly observed therapy (3HP-DOT). Data on the relative cost-effectiveness of these regimens are needed to assist policymakers and clinicians in selecting an LTBI regimen. Objectives: To evaluate the cost-effectiveness of all regimens for treating LTBI. Methods: We developed a Markov model to investigate the cost-effectiveness of 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H for LTBI treatment in a cohort of 10000 adults with LTBI. Cost-effectiveness was evaluated from a health system perspective over a 20 year time horizon. Results: Compared with no preventive treatment, 3HP-DOT, 3HP-SAT, 4R, 3RH, 9H and 6H prevented 496, 470, 442, 418, 370 and 276 additional cases of active TB per 10000 patients, respectively. All regimens reduced costs and increased QALYs compared with no preventive treatment. 3HP was more cost-effective under DOT than under SAT at a cost of US$27948 per QALY gained. Conclusions: Three months of weekly rifapentine plus isoniazid is more cost-effective than other regimens. Greater recognition of the benefits of short-course regimens can contribute to the scale-up of prevention and achieving the 'End TB' targets.

Spatiotemporal transmission and socio-climatic factors related to paediatric tuberculosis in north-western Ethiopia.

The burden of tuberculosis (TB) in children reflects continuing and recent transmission within a population. This study aimed to identify spatiotemporal and socio-climatic factors associated with paediatric TB in north-western Ethiopia. Multivariate Poisson regression models were computed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo simulation. A total of 2,240 children aged under 15 years diagnosed with TB during the years 2013- 2016 were included in the analysis. The annual TB incidence rates were 44 and 28 per 100,000 children, for children aged under 15 and 5 years, respectively. Spatial clustering of TB was observed in the border area of north-western Ethiopia. The spatio-temporal transmission of childhood TB was found to be associated with district level socio-climatic factors such as urbanisation [relative risk (RR): 1.8; 95% credible interval (CrI): 1.2, 2.6], lower educational status (RR: 1.5; 95% CrI: 1.0, 2.1), a high percentage of internal migration (RR: 1.3; 95% CrI: 1.0, 1.6), high temperature (RR: 1.3; 95% CrI: 1.0, 1.7) and high rainfall (RR: 1.5; 95% CrI: 1.1, 2.0). We conclude that interventions targeting hotspot districts with a high proportion of childhood TB are important to reduce TB transmission in northwest Ethiopia.

Spatial patterns of multidrug resistant tuberculosis and relationships to socio-economic, demographic and household factors in northwest Ethiopia.

BACKGROUND: Understanding the geographical distribution of multidrug-resistant tuberculosis (MDR-TB) in high TB burden countries such as Ethiopia is crucial for effective control of TB epidemics in these countries, and thus globally. We present the first spatial analysis of multidrug resistant tuberculosis, and its relationship to socio-economic, demographic and household factors in northwest Ethiopia. METHODS: An ecological study was conducted using data on patients diagnosed with MDR-TB at the University of Gondar Hospital MDR-TB treatment centre, for the period 2010 to 2015. District level population data were extracted from the Ethiopia National and Regional Census Report. Spatial autocorrelation was explored using Moran's I statistic, Local Indicators of Spatial Association (LISA), and the Getis-Ord statistics. A multivariate Poisson regression model was developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using a Bayesian Markov chain Monte Carlo (MCMC) simulation approach with Gibbs sampling, in WinBUGS. RESULTS: A total of 264 MDR-TB patients were included in the analysis. The overall crude incidence rate of MDR-TB for the six-year period was 3.0 cases per 100,000 population. The highest incidence rate was observed in Metema (21 cases per 100,000 population) and Humera (18 cases per 100,000 population) districts; whereas nine districts had zero cases. Spatial clustering of MDR-TB was observed in districts located in the Ethiopia-Sudan and Ethiopia-Eritrea border regions, where large numbers of seasonal migrants live. Spatial clustering of MDR-TB was positively associated with urbanization (RR: 1.02; 95%CI: 1.01, 1.04) and the percentage of men (RR: 1.58; 95% CI: 1.26, 1.99) in the districts; after accounting for these factors there was no residual spatial clustering. CONCLUSION: Spatial clustering of MDR-TB, fully explained by demographic factors (urbanization and percent male), was detected in the border regions of northwest Ethiopia, in locations where seasonal migrants live and work. Cross-border initiatives including options for mobile TB treatment and follow up are important for the effective control of MDR-TB in the region.

The Australian Master of Applied Epidemiology Program: Looking back, moving forward.

The Master of Applied Epidemiology Program is Australia's Field Epidemiology Training Program. It was established in 1991 and was run out of the National Centre for Population Health (NCEPH) at the Australian National University. The Program has a strong track record in using field-based training to produce competent applied epidemiologists who have contributed to public health in Australia and globally. A new funding model for the program was implemented in 2012, backed by funds from field placement partners and NCEPH. In this paper we review the program's origins and achievements, discuss the ongoing needs of the program and outline a vision for the future. Commun Dis Intell 2016;40(3):E326-E333.

Findings and implications of the Global Burden of Disease 2010 Study for the Pacific Islands.

The Global Burden of Disease 2010 Study is the largest study of its kind. It provides a large volume of information about the global burden of disease and associated risk factors. It estimates that lower respiratory infections, diabetes, diarrhea, and tuberculosis cause the greatest burden in the Pacific, and noncommunicable diseases caused a substantially greater burden in 2010 compared with 1990. Although the Pacific is considered to be a region rich in data, very little of these data has been analyzed, synthesized, and made publically available. Consequently, burden estimates for the Pacific are derived from models built with very limited data, and it is difficult to know how accurate they are. Health information in the Pacific needs strengthening, particularly in relation to data collection, analysis, use, and sharing. This will improve the reliability and comparability of burden of disease estimates.