Correction: Addressing TB multimorbidity in policy and practice: An exploratory survey of TB providers in 27 high-TB burden countries.

[This corrects the article DOI: 10.1371/journal.pgph.0001205.].

The Targeted Maximum Likelihood estimation to estimate the causal effects of the previous tuberculosis treatment in Multidrug-resistant tuberculosis in Sudan.

INTRODUCTION: This study used Targeted Maximum Likelihood Estimation (TMLE) as a double robust method to estimate the causal effect of previous tuberculosis treatment history on the occurrence of multidrug-resistant tuberculosis (MDR-TB). TMLE is a method to estimate the marginal statistical parameters in case-control study design. The aim of this study was to estimate the causal effect of the previous tuberculosis treatment on the occurrence of MDR-TB using TMLE in Sudan. METHOD: A case-control study design combined with TMLE was used to estimate parameters. Cases were MDR-TB patients and controls were and patients who cured from tuberculosis. The history of previous TB treatment was considered the main exposure, and MDR-TB as an outcome. A designed questionnaire was used to collect a set of covariates including age, time to reach a health facility, number of times stopping treatment, gender, education level, and contact with MDR-TB cases. TMLE method was used to estimate the causal association of parameters. Statistical analysis was carried out with ltmle package in R-software. Result presented in graph and tables. RESULTS: A total number of 430 cases and 860 controls were included in this study. The estimated risk difference of the previous tuberculosis treatment was (0.189, 95% CI; 0.161, 0.218) with SE 0.014, and p-value (<0.001). In addition, the estimated risk ratio was (16.1, 95% CI; 12.932, 20.001) with SE = 0.014 and p-value (<0.001). CONCLUSION: Our findings indicated that previous tuberculosis treatment history was determine as a risk factor for MDR-TB in Sudan. Also, TMLE method can be used to estimate the risk difference and the risk ratio in a case-control study design.

Small airways obstruction and its risk factors in the Burden of Obstructive Lung Disease (BOLD) study: a multinational cross-sectional study.

BACKGROUND: Small airways obstruction is a common feature of obstructive lung diseases. Research is scarce on small airways obstruction, its global prevalence, and risk factors. We aimed to estimate the prevalence of small airways obstruction, examine the associated risk factors, and compare the findings for two different spirometry parameters. METHODS: The Burden of Obstructive Lung Disease study is a multinational cross-sectional study of 41 municipalities in 34 countries across all WHO regions. Adults aged 40 years or older who were not living in an institution were eligible to participate. To ensure a representative sample, participants were selected from a random sample of the population according to a predefined site-specific sampling strategy. We included participants' data in this study if they completed the core study questionnaire and had acceptable spirometry according to predefined quality criteria. We excluded participants with a contraindication for lung function testing. We defined small airways obstruction as either mean forced expiratory flow rate between 25% and 75% of the forced vital capacity (FEF25-75) less than the lower limit of normal or forced expiratory volume in 3 s to forced vital capacity ratio (FEV3/FVC ratio) less than the lower limit of normal. We estimated the prevalence of pre-bronchodilator (ie, before administration of 200 µg salbutamol) and post-bronchodilator (ie, after administration of 200 µg salbutamol) small airways obstruction for each site. To identify risk factors for small airways obstruction, we performed multivariable regression analyses within each site and pooled estimates using random-effects meta-analysis. FINDINGS: 36 618 participants were recruited between Jan 2, 2003, and Dec 26, 2016. Data were collected from participants at recruitment. Of the recruited participants, 28 604 participants had acceptable spirometry and completed the core study questionnaire. Data were available for 26 443 participants for FEV3/FVC ratio and 25 961 participants for FEF25-75. Of the 26 443 participants included, 12 490 were men and 13 953 were women. Prevalence of pre-bronchodilator small airways obstruction ranged from 5% (34 of 624 participants) in Tartu, Estonia, to 34% (189 of 555 participants) in Mysore, India, for FEF25-75, and for FEV3/FVC ratio it ranged from 5% (31 of 684) in Riyadh, Saudi Arabia, to 31% (287 of 924) in Salzburg, Austria. Prevalence of post-bronchodilator small airways obstruction was universally lower. Risk factors significantly associated with FEV3/FVC ratio less than the lower limit of normal included increasing age, low BMI, active and passive smoking, low level of education, working in a dusty job for more than 10 years, previous tuberculosis, and family history of chronic obstructive pulmonary disease. Results were similar for FEF25-75, except for increasing age, which was associated with reduced odds of small airways obstruction. INTERPRETATION: Despite the wide geographical variation, small airways obstruction is common and more prevalent than chronic airflow obstruction worldwide. Small airways obstruction shows the same risk factors as chronic airflow obstruction. However, further research is required to investigate whether small airways obstruction is also associated with respiratory symptoms and lung function decline. FUNDING: National Heart and Lung Institute and Wellcome Trust. TRANSLATIONS: For the Dutch, Estonian, French, Icelandic, Malay, Marathi, Norwegian, Portuguese, Swedish and Urdu translations of the abstract see Supplementary Materials section.

Association of respiratory symptoms and lung function with occupation in the multinational Burden of Obstructive Lung Disease (BOLD) study.

BACKGROUND: Chronic obstructive pulmonary disease has been associated with exposures in the workplace. We aimed to assess the association of respiratory symptoms and lung function with occupation in the Burden of Obstructive Lung Disease study. METHODS: We analysed cross-sectional data from 28 823 adults (≥40 years) in 34 countries. We considered 11 occupations and grouped them by likelihood of exposure to organic dusts, inorganic dusts and fumes. The association of chronic cough, chronic phlegm, wheeze, dyspnoea, forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1)/FVC with occupation was assessed, per study site, using multivariable regression. These estimates were then meta-analysed. Sensitivity analyses explored differences between sexes and gross national income. RESULTS: Overall, working in settings with potentially high exposure to dusts or fumes was associated with respiratory symptoms but not lung function differences. The most common occupation was farming. Compared to people not working in any of the 11 considered occupations, those who were farmers for ≥20 years were more likely to have chronic cough (OR 1.52, 95% CI 1.19-1.94), wheeze (OR 1.37, 95% CI 1.16-1.63) and dyspnoea (OR 1.83, 95% CI 1.53-2.20), but not lower FVC (ß=0.02 L, 95% CI -0.02-0.06 L) or lower FEV1/FVC (ß=0.04%, 95% CI -0.49-0.58%). Some findings differed by sex and gross national income. CONCLUSION: At a population level, the occupational exposures considered in this study do not appear to be major determinants of differences in lung function, although they are associated with more respiratory symptoms. Because not all work settings were included in this study, respiratory surveillance should still be encouraged among high-risk dusty and fume job workers, especially in low- and middle-income countries.

Prevalence and risks of tuberculosis multimorbidity in low-income and middle-income countries: a meta-review.

OBJECTIVES: Co-occurrence of tuberculosis (TB) with other chronic conditions (TB multimorbidity) increases complexity of management and adversely affects health outcomes. We aimed to map the prevalence of the co-occurrence of one or more chronic conditions in people with TB and associated health risks by systematically reviewing previously published systematic reviews. DESIGN: Systematic review of systematic reviews (meta-review). SETTING: Low-income and middle-income countries (LMICs). PAPERS: We searched in Medline, Embase, PsycINFO, Social Sciences Citation Index, Science Citation Index, Emerging Sources Citation Index and Conference Proceedings Citation Index, and the WHO Global Index Medicus from inception to 23 October 2020, contacted authors and reviewed reference lists. Pairs of independent reviewers screened titles, abstracts and full texts, extracted data and assessed the included reviews' quality (AMSTAR2). We included systematic reviews reporting data for people in LMICs with TB multimorbidity and synthesised them narratively. We excluded reviews focused on children or specific subgroups (eg, incarcerated people). PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence or risk of TB multimorbidity (primary); any measure of burden of disease (secondary). RESULTS: From the 7557 search results, 54 were included, representing >6 296 000 people with TB. We found that the most prevalent conditions in people with TB were depression (45.19%, 95% CI: 38.04% to 52.55%, 25 studies, 4903 participants, I2=96.28%, high quality), HIV (31.81%, 95% CI: 27.83% to 36.07%, 68 studies, 62 696 participants, I2=98%, high quality) and diabetes mellitus (17.7%, 95% CI: 15.1% to 20.0.5%, 48 studies, 48,036 participants, I2=98.3%, critically low quality). CONCLUSIONS: We identified several chronic conditions that co-occur in a significant proportion of people with TB. Although limited by varying quality and gaps in the literature, this first meta-review of TB multimorbidity highlights the magnitude of additional ill health burden due to chronic conditions on people with TB. PROSPERO REGISTRATION NUMBER: CRD42020209012.

What are the barriers to the diagnosis and management of chronic respiratory disease in sub-Saharan Africa? A qualitative study with healthcare workers, national and regional policy stakeholders in five countries.

OBJECTIVES: Chronic respiratory diseases (CRD) are among the top four non-communicable diseases globally. They are associated with poor health and approximately 4 million deaths every year. The rising burden of CRD in low/middle-income countries will strain already weak health systems. This study aimed to explore the perspectives of healthcare workers and other health policy stakeholders on the barriers to effective diagnosis and management of CRD in Kenya, Malawi, Sudan, Tanzania and Uganda. STUDY DESIGN: Qualitative descriptive study. SETTINGS: Primary, secondary and tertiary health facilities, government agencies and civil society organisations in five sub-Saharan African countries. PARTICIPANTS: We purposively selected 60 national and district-level policy stakeholders, and 49 healthcare workers, based on their roles in policy decision-making or health provision, and conducted key informant interviews and in-depth interviews, respectively, between 2018 and 2019. Data were analysed through framework approach. RESULTS: We identified intersecting vicious cycles of neglect of CRD at strategic policy and healthcare facility levels. Lack of reliable data on burden of disease, due to weak information systems and diagnostic capacity, negatively affected inclusion in policy; this, in turn, was reflected by low budgetary allocations for diagnostic equipment, training and medicines. At the healthcare facility level, inadequate budgetary allocations constrained diagnostic capacity, quality of service delivery and collection of appropriate data, compounding the lack of routine data on burden of disease. CONCLUSION: Health systems in the five countries are ill-equipped to respond to CRD, an issue that has been brought into sharp focus as countries plan for post-COVID-19 lung diseases. CRD are underdiagnosed, under-reported and underfunded, leading to a vicious cycle of invisibility and neglect. Appropriate diagnosis and management require health systems strengthening, particularly at the primary healthcare level.

Addressing TB multimorbidity in policy and practice: An exploratory survey of TB providers in 27 high-TB burden countries.

In people with TB, co-existence of long-term conditions (e.g., depression, diabetes and HIV) and risk factors (e.g.,alcohol misuse, malnutrition, and smoking) are associated with increased mortality and poor treatment outcomes including delayed recovery, TB treatment failure and relapse. However, it is unclear as to what extent these comorbidities are addressed in TB policy and practice. Between August and October 2021, we conducted an online cross-sectional survey in high-TB burden countries. We recruited a purposive sample of TB health workers, managers, policy makers, advisors and advocates from these countries. The survey enquired about the extent to which various comorbid conditions are: (a) mentioned in TB policies, plans, and guidelines; (b) screened, diagnosed, treated or referred to specialist services by TB healthcare workers. We summarised using descriptive analysis. Of the 1100 potential respondents contacted in 33 countries, 543 responded but only 446 (41%) from 27 countries provided sufficient data for inclusion in the study. We found no notable differences between these providing insufficient data and those completing the survey. HIV, diabetes mellitus, depression and tobacco and alcohol use disorders were identified as the most common and concerning comorbid conditions in TB. HIV was screened for and managed by TB services in most countries. Screening for diabetes and/or tobacco and alcohol use disorders was offered by almost half of all TB services but only a few offered relevant treatments. Depression was rarely screened for, almost never treated, and only infrequently referred to specialist services. Most respondents felt confident in screening/diagnosing these comorbid conditions but not in treating these conditions. With the exception of HIV, chronic comorbid conditions are only partially screened for and rarely managed within TB services. Mental health conditions are for the most part neglected. Given their adverse impact on TB outcomes, integrating screening and management of these comorbidities within TB programmes offers a significant opportunity to meet TB targets, address non-communicable diseases and improve patient well-being.

Prevalence and Population-Attributable Risk for Chronic Airflow Obstruction in a Large Multinational Study.

Rationale: The Global Burden of Disease program identified smoking and ambient and household air pollution as the main drivers of death and disability from chronic obstructive pulmonary disease (COPD). Objectives: To estimate the attributable risk of chronic airflow obstruction (CAO), a quantifiable characteristic of COPD, due to several risk factors. Methods: The Burden of Obstructive Lung Disease study is a cross-sectional study of adults, aged ≥40, in a globally distributed sample of 41 urban and rural sites. Based on data from 28,459 participants, we estimated the prevalence of CAO, defined as a postbronchodilator FEV1-to-FVC ratio less than the lower limit of normal, and the relative risks associated with different risk factors. Local relative risks were estimated using a Bayesian hierarchical model borrowing information from across sites. From these relative risks and the prevalence of risk factors, we estimated local population attributable risks. Measurements and Main Results: The mean prevalence of CAO was 11.2% in men and 8.6% in women. The mean population attributable risk for smoking was 5.1% in men and 2.2% in women. The next most influential risk factors were poor education levels, working in a dusty job for ≥10 years, low body mass index, and a history of tuberculosis. The risk of CAO attributable to the different risk factors varied across sites. Conclusions: Although smoking remains the most important risk factor for CAO, in some areas, poor education, low body mass index, and passive smoking are of greater importance. Dusty occupations and tuberculosis are important risk factors at some sites.

Exploring the consequences of decentralization: has privatization of health services been the perceived effect of decentralization in Khartoum locality, Sudan?

BACKGROUND: The health system of Sudan has experienced several forms of decentralization, as well as, a radical reform. Authority and governance of secondary and tertiary health facilities have been shifted from federal to state levels. Moreover, the provision of health care services have been moved from large federal tertiary level hospitals such as Khartoum Teaching Hospital (KTH) and Jafaar Ibnoaf Hospital (JIH), located in the center of Khartoum, to smaller district secondary hospitals like Ibrahim Malik (IBMH), which is located in the southern part of Khartoum. Exploring stakeholders' perceptions on this decentralisation implementation and its relevant consequences is vital in building an empirical benchmark for the improvement of health systems. METHODS: This study utilised a qualitative design which is comprised of in-depth interviews and qualitative content analysis with an inductive approach. The study was conducted between July and December 2015, and aimed at understanding the personal experiences and perceptions of stakeholders towards decentralisation enforcement and the implications on public health services, with a particular focus on the Khartoum locality. It involved community members residing in the Khartoum Locality, specifically in catchments area where hospital decentralisation was implemented, as well as, affiliated health workers and policymakers. RESULTS: The major finding suggested that privatisation of health services occurred after decentralisation. The study participants also highlighted that scrutiny and reduction of budgets allocated to health services led to an instantaneous enforcement of cost recovery user fee. Devolving KTH Khartoum Teaching and Jafar Ibnoaf Hospitals into peripherals with less. Capacity, was considered to be a plan to weaken public health services and outsource services to private sector. Another theme that was highlighted in hospitals included the profit-making aspect of the governmental sector in the form of drug supplying and profit-making retail. CONCLUSIONS: A change in health services after the enforcement of decentralisation was illustrated. Moreover, the incapacitation of public health systems and empowerment of the privatisation concept was the prevailing perception among stakeholders. Having contextualised in-depth studies and policy analysis in line with the global liberalisation and adjustment programmes is crucial for any health sector reform in Sudan.

Assessment of the risk factors associated with multidrug-resistant tuberculosis in Sudan: a case-control study.

OBJECTIVES: The emergence of multidrug-resistant tuberculosis (MDR-TB) is a major challenge for the global control of tuberculosis (TB). The aim of this study was to determine the risk factors associated with MDR-TB in Sudan. METHODS: This case-control study was conducted from May 2017 to February 2019. Patients newly diagnosed with MDR-TB were selected as cases, and controls were selected from TB patients who responded to first-line anti-TB drugs. A questionnaire was designed and used to collect data from study participants. Logistic regression was used to evaluate associations between risk factors and MDR-TB infection. The best multivariate model was selected based on the likelihood ratio test. RESULTS: A total of 430 cases and 860 controls were selected for this study. A history of previous TB treatment (adjusted odds ratio [aOR], 54.85; 95% confidence interval [CI], 30.48 to 98.69) was strongly associated with MDR-TB infection. We identified interruption of TB treatment (aOR, 7.62; 95% CI, 3.16 to 18.34), contact with MDR-TB patients (aOR, 5.40; 95% CI, 2.69 to 10.74), lower body weight (aOR, 0.89; 95% CI, 0.87 to 0.91), and water pipe smoking (aOR, 3.23; 95% CI, 1.73 to 6.04) as factors associated with MDR-TB infection. CONCLUSIONS: Previous TB treatment and interruption of TB treatment were found to be the main predictors of MDR-TB. Additionally, this study found that contact with MDR-TB patients and water pipe smoking were associated with MDR-TB infection in Sudan. More efforts are required to decrease the rate of treatment interruption, to strengthen patients' adherence to treatment, and to reduce contact with MDR-TB patients.

Conflict and tuberculosis in Sudan: a 10-year review of the National Tuberculosis Programme, 2004-2014.

BACKGROUND: Sudan is a fragile developing country, with a low expenditure on health. It has been subjected to ongoing conflicts ever since 1956, with the Darfur crisis peaking in 2004. The conflict, in combination with the weak infrastructure, can lead to poor access to healthcare. Hence, this can cause an increased risk of infection, greater morbidity and mortality from tuberculosis (TB), especially amongst the poor, displaced and refugee populations. This study will be the first to describe TB case notifications, characteristics and outcomes over a ten-year period in Darfur in comparison with the non-conflict Eastern zones within Sudan. METHODS: A cross-sectional review of the National Tuberculosis Programme (NTP) data from 2004 to 2014 comparing the Darfur conflict zone with the non-conflict eastern zone. RESULTS: New case notifications were 52% lower in the conflict zone (21,131) compared to the non-conflict zone (43,826). Smear-positive pulmonary TB (PTB) in the conflict zone constituted 63% of all notified cases, compared to the non-conflict zone of 32% (p < 0.001). Extrapulmonary TB (EPTB) predominated the TB notified cases in the non-conflict zone, comprising 35% of the new cases versus 9% in the conflict zone (p < 0.001). The loss to follow up (LTFU) was high in both zones (7% conflict vs 10% non-conflict, p < 0.001) with a higher rate among re-treatment cases (12%) in the conflict zone. Average treatment success rates of smear-positive pulmonary TB (PTB), over ten years, were low (65-66%) in both zones. TB mortality among re-treatment cases was higher in the conflict zone (8%) compared to the non-conflict zone (6%) (p < 0.001). CONCLUSION: A low TB case notification was found in the conflict zone from 2004 to 2014. High loss to follow up and falling treatment success rates were found in both conflict and non-conflict zones, which represents a significant public health risk. Further analysis of the TB response and surveillance system in both zones is needed to confirm the factors associated with the poor outcomes. Using context-sensitive measures and simplified pathways with an emphasis on displaced persons may increase access and case notification in conflict zones, which can help avoid a loss to follow up in both zones.

A comparison of smartphone and paper data-collection tools in the Burden of Obstructive Lung Disease (BOLD) study in Gezira state, Sudan.

INTRODUCTION: Data collection using paper-based questionnaires can be time consuming and return errors affect data accuracy, completeness, and information quality in health surveys. We compared smartphone and paper-based data collection systems in the Burden of Obstructive Lung Disease (BOLD) study in rural Sudan. METHODS: This exploratory pilot study was designed to run in parallel with the cross-sectional household survey. The Open Data Kit was used to programme questionnaires in Arabic into smartphones. We included 100 study participants (83% women; median age = 41.5 ± 16.4 years) from the BOLD study from 3 rural villages in East-Gezira and Kamleen localities of Gezira state, Sudan. Questionnaire data were collected using smartphone and paper-based technologies simultaneously. We used Kappa statistics and inter-rater class coefficient to test agreement between the two methods. RESULTS: Symptoms reported included cough (24%), phlegm (15%), wheezing (17%), and shortness of breath (18%). One in five were or had been cigarette smokers. The two data collection methods varied between perfect to slight agreement across the 204 variables evaluated (Kappa varied between 1.00 and 0.02 and inter-rater coefficient between 1.00 and -0.12). Errors were most commonly seen with paper questionnaires (83% of errors seen) vs smartphones (17% of errors seen) administered questionnaires with questions with complex skip-patterns being a major source of errors in paper questionnaires. Automated checks and validations in smartphone-administered questionnaires avoided skip-pattern related errors. Incomplete and inconsistent records were more likely seen on paper questionnaires. CONCLUSION: Compared to paper-based data collection, smartphone technology worked well for data collection in the study, which was conducted in a challenging rural environment in Sudan. This approach provided timely, quality data with fewer errors and inconsistencies compared to paper-based data collection. We recommend this method for future BOLD studies and other population-based studies in similar settings.