Asthma symptoms, spirometry and air pollution exposure in schoolchildren in an informal settlement and an affluent area of Nairobi, Kenya.

BACKGROUND: Although 1 billion people live in informal (slum) settlements, the consequences for respiratory health of living in these settlements remain largely unknown. This study investigated whether children living in an informal settlement in Nairobi, Kenya are at increased risk of asthma symptoms. METHODS: Children attending schools in Mukuru (an informal settlement in Nairobi) and a more affluent area (Buruburu) were compared. Questionnaires quantified respiratory symptoms and environmental exposures; spirometry was performed; personal exposure to particulate matter (PM2.5) was estimated. RESULTS: 2373 children participated, 1277 in Mukuru (median age, IQR 11, 9-13 years, 53% girls), and 1096 in Buruburu (10, 8-12 years, 52% girls). Mukuru schoolchildren were from less affluent homes, had greater exposure to pollution sources and PM2.5. When compared with Buruburu schoolchildren, Mukuru schoolchildren had a greater prevalence of symptoms, 'current wheeze' (9.5% vs 6.4%, p=0.007) and 'trouble breathing' (16.3% vs 12.6%, p=0.01), and these symptoms were more severe and problematic. Diagnosed asthma was more common in Buruburu (2.8% vs 1.2%, p=0.004). Spirometry did not differ between Mukuru and Buruburu. Regardless of community, significant adverse associations were observed with self-reported exposure to 'vapours, dusts, gases, fumes', mosquito coil burning, adult smoker(s) in the home, refuse burning near homes and residential proximity to roads. CONCLUSION: Children living in informal settlements are more likely to develop wheezing symptoms consistent with asthma that are more severe but less likely to be diagnosed as asthma. Self-reported but not objectively measured air pollution exposure was associated with increased risk of asthma symptoms.

Worldwide Effects of Coronavirus Disease Pandemic on Tuberculosis Services, January-April 2020.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic.

Case Definition of Chronic Pulmonary Aspergillosis in Resource-Constrained Settings.

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings.

Gendered gaps to tuberculosis prevention and care in Kenya: a political economy analysis study.

BACKGROUND: Tuberculosis (TB) remains a public health concern in Kenya despite the massive global efforts towards ending TB. The impediments to TB prevention and care efforts include poor health systems, resource limitations and other sociopolitical contexts that inform policy and implementation. Notably, TB cases are much higher in men than women. Therefore, the political economy analysis (PEA) study provides in-depth contexts and understanding of the gender gaps to access and successful treatment for TB infection. DESIGN: PEA adopts a qualitative, in-depth approach through key informant interviews (KII) and documentary analysis. SETTING AND PARTICIPANTS: The KIIs were distributed among government entities, academia, non-state actors and community TB groups from Kenya. RESULTS: The themes identified were mapped onto the applied PEA analysis framework domains. The contextual and institutional issues included gender concerns related to the disconnect between TB policies and gender inclusion aspects, such as low prioritisation for TB programmes, limited use of evidence to inform decisions and poor health system structures. The broad barriers influencing the social contexts for TB programmes were social stigma and cultural norms such as traditional interventions that negatively impact health-seeking behaviours. The themes around the economic situation were poverty and unemployment, food insecurity and malnutrition. The political context centred around the systemic and governance gaps in the health system from the national and devolved health functions. CONCLUSION: Broad contextual factors identified from the PEA widen the disparity in targeted gender efforts toward men. Following the development of effective TB policies and strategies, it is essential to have well-planned gendered responsive interventions with a clear implementation plan and monitoring system to enhance access to TB prevention and care.

The burden of severe asthma in sub-Saharan Africa: Findings from the African Severe Asthma Project.

Background: Severe asthma is associated with high morbidity, mortality, and health care utilization, but its burden in Africa is unknown. Objective: We sought to determine the burden (prevalence, mortality, and activity and work impairment) of severe asthma in 3 countries in East Africa: Uganda, Kenya, and Ethiopia. Methods: Using the American Thoracic Society/European Respiratory Society case definition of severe asthma, we analyzed for the prevalence of severe asthma (requiring Global Initiative for Asthma [GINA] steps 4-5 asthma medications for the previous year to achieve control) and severe refractory asthma (remains uncontrolled despite treatment with GINA steps 4-5 asthma medications) in a cohort of 1086 asthma patients who had been in care for 12 months and had received all GINA-recommended medications. Asthma control was assessed by the asthma control questionnaire (ACQ). Results: Overall, the prevalence of severe asthma and severe refractory asthma was 25.6% (95% confidence interval [CI], 23.1-28.3) and 4.6% (95% CI, 3.5-6.0), respectively. Patients with severe asthma were (nonsevere vs severe vs severe refractory) older (39, 42, 45 years, P = .011), had high skin prick test reactivity (67.1%, 76.0%, 76.0%, P = .004), had lower forced expiratory volume in 1 second percentage (81%, 61%, 55.5%, P < .001), had lower quality of life score (129, 127 vs 121, P < .001), and had higher activity impairment (10%, 30%, 50%, P < .001). Factors independently associated with severe asthma were hypertension comorbidity; adjusted odds ratio 2.21 (1.10-4.47), P = .027, high bronchial hyperresponsiveness questionnaire score; adjusted odds ratio 2.16 (1.01-4.61), P = .047 and higher ACQ score at baseline 2.80 (1.55-5.08), P = .001. Conclusion: The prevalence of severe asthma in Africa is high and is associated with high morbidity and poor quality of life.

Scaling up interventions to achieve global tuberculosis control: progress and new developments.

Tuberculosis is still one of the most important causes of death worldwide. The 2010 Lancet tuberculosis series provided a comprehensive overview of global control efforts and challenges. In this update we review recent progress. With improved control efforts, the world and most regions are on track to achieve the Millennium Development Goal of decreasing tuberculosis incidence by 2015, and the Stop TB Partnership target of halving 1990 mortality rates by 2015; the exception is Africa. Despite these advances, full scale-up of tuberculosis and HIV collaborative activities remains challenging and emerging drug-resistant tuberculosis is a major threat. Recognition of the effect that non-communicable diseases--such as smoking-related lung disease, diet-related diabetes mellitus, and alcohol and drug misuse--have on individual vulnerability, as well as the contribution of poor living conditions to community vulnerability, shows the need for multidisciplinary approaches. Several new diagnostic tests are being introduced in endemic countries and for the first time in 40 years a coordinated portfolio of promising new tuberculosis drugs exists. However, none of these advances offer easy solutions. Achievement of international tuberculosis control targets and maintenance of these gains needs optimum national health policies and services, with ongoing investment into new approaches and strategies. Despite growing funding in recent years, a serious shortfall persists. International and national financial uncertainty places gains at serious risk. Perseverance and renewed commitment are needed to achieve global control of tuberculosis, and ultimately, its elimination.

Drug-resistant tuberculosis--current dilemmas, unanswered questions, challenges, and priority needs.

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.

Tuberculosis diagnostics and biomarkers: needs, challenges, recent advances, and opportunities.

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics.

Over-prescription of short-acting ß2-agonists remains a serious health concern in Kenya: results from the SABINA III study.

BACKGROUND: Despite a high asthma burden in Kenya, insights into asthma management practices, including prescription of short-acting ß2-agonists (SABAs), are lacking. Therefore, this study describes patient demographics, disease characteristics, and asthma treatment patterns in the Kenyan cohort of the SABA use IN Asthma (SABINA) III study. METHODS: Patients with asthma (aged ≥ 12 years) with medical records containing data for ≥ 12 months prior to the study visit from 19 sites across Kenya were included in this cross-sectional study and classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma [GINA] recommendations) and practice type (primary/specialist care). Data on severe exacerbation history, prescribed asthma treatments, and over-the-counter (OTC) SABA purchases in the 12 months before the study visit and asthma symptom control at the time of the study visit were collated using electronic case report forms. All analyses were descriptive in nature. RESULTS: Overall, 405 patients were analyzed (mean age, 44.4 years; female, 68.9%), of whom 54.8% and 45.2% were enrolled by primary care clinicians and specialists, respectively. Most patients were classified with mild asthma (76.0%, GINA treatment steps 1-2) and were overweight or obese (57.0%). Only 19.5% of patients reported full healthcare reimbursement, with 59% receiving no healthcare reimbursement. The mean asthma duration of patients was 13.5 years. Asthma was partly controlled/uncontrolled in 78.0% of patients, with 61.5% experiencing ≥ 1 severe exacerbation in the preceding 12 months. Crucially, 71.9% of patients were prescribed ≥ 3 SABA canisters, defined as over-prescription; 34.8% were prescribed ≥ 10 SABA canisters. Additionally, 38.8% of patients purchased SABA OTC, of whom 66.2% purchased ≥ 3 SABA canisters. Among patients with both SABA purchases and prescriptions, 95.5% and 57.1% had prescriptions for ≥ 3 and ≥ 10 SABA canisters, respectively. Inhaled corticosteroids (ICS), ICS with a long-acting ß2-agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 58.8%, 24.7%, and 22.7% of patients, respectively. CONCLUSIONS: SABA over-prescription occurred in almost three-quarters of patients, with over one-third of patients purchasing SABA OTC. Therefore, SABA over-prescription is a major public health concern in Kenya, underscoring an urgent need to align clinical practices with latest evidence-based recommendations.

Preterm birth, birth weight, infant weight gain and their associations with childhood asthma and spirometry: a cross-sectional observational study in Nairobi, Kenya.

BACKGROUND: In sub-Saharan Africa, the origins of asthma and high prevalence of abnormal lung function remain unclear. In high-income countries (HICs), associations between birth measurements and childhood asthma and lung function highlight the importance of antenatal and early life factors in the aetiology of asthma and abnormal lung function in children. We present here the first study in sub-Saharan Africa to relate birth characteristics to both childhood respiratory symptoms and lung function. METHODS: Children attending schools in two socioeconomically contrasting but geographically close areas of Nairobi, Kenya, were recruited to a cross-sectional study of childhood asthma and lung function. Questionnaires quantified respiratory symptoms and preterm birth; lung function was measured by spirometry; and parents were invited to bring the child's immunisation booklet containing records of birth weight and serial weights in the first year. RESULTS: 2373 children participated, 52% girls, median age (IQR), 10 years (8-13). Spirometry data were available for 1622. Child immunisation booklets were available for 500 and birth weight and infant weight gain data were available for 323 and 494 children, respectively. In multivariable analyses, preterm birth was associated with the childhood symptoms 'wheeze in the last 12 months'; OR 1.64, (95% CI 1.03 to 2.62), p=0.038; and 'trouble breathing' 3.18 (95% CI 2.27 to 4.45), p<0.001. Birth weight (kg) was associated with forced expiratory volume in 1 s z-score, regression coefficient (ß) 0.30 (0.08, 0.52), p=0.008, FVC z-score 0.29 (95% CI 0.08 to 0.51); p=0.008 and restricted spirometry, OR 0.11 (95% CI 0.02 to 0.78), p=0.027. CONCLUSION: These associations are in keeping with those in HICs and highlight antenatal factors in the aetiology of asthma and lung function abnormalities in sub-Saharan Africa.

Global, regional, and national estimates of tuberculosis incidence and case detection among incarcerated individuals from 2000 to 2019: a systematic analysis.

BACKGROUND: People who are incarcerated are at high risk of developing tuberculosis. We aimed to estimate the annual global, regional, and national incidence of tuberculosis among incarcerated populations from 2000 to 2019. METHODS: We collected and aggregated data for tuberculosis incidence and prevalence estimates among incarcerated individuals in published and unpublished literature, annual tuberculosis notifications among incarcerated individuals at the country level, and the annual number of incarcerated individuals at the country level. We developed a joint hierarchical Bayesian meta-regression framework to simultaneously model tuberculosis incidence, notifications, and prevalence from 2000 to 2019. Using this model, we estimated trends in absolute tuberculosis incidence and notifications, the incidence and notification rates, and the case detection ratio by year, country, region, and globally. FINDINGS: In 2019, we estimated a total of 125 105 (95% credible interval [CrI] 93 736-165 318) incident tuberculosis cases among incarcerated individuals globally. The estimated incidence rate per 100 000 person-years overall was 1148 (95% CrI 860-1517) but varied greatly by WHO region, from 793 (95% CrI 430-1342) in the Eastern Mediterranean region to 2242 (1515-3216) in the African region. Global incidence per 100 000 person-years between 2000 and 2012 among incarcerated individuals decreased from 1884 (95% CrI 1394-2616) to 1205 (910-1615); however, from 2013 onwards, tuberculosis incidence per 100 000 person-years was stable, from 1183 (95% CrI 876-1596) in 2013 to 1148 (860-1517) in 2019. In 2019, the global case detection ratio was estimated to be 53% (95% CrI 42-64), the lowest over the study period. INTERPRETATION: Our estimates suggest a high tuberculosis incidence rate among incarcerated individuals globally with large gaps in tuberculosis case detection. Tuberculosis in incarcerated populations must be addressed with interventions specifically tailored to improve diagnoses and prevent transmission as a part of the broader global tuberculosis control effort. FUNDING: National Institutes of Health.

A case for implementation of adult pneumococcal vaccine program in Africa: review and expert opinion.

Vaccines are considered as a therapeutic area for children; the scientific community focuses mainly on managing chronic disease when it comes to adults. There currently is an increase in the burden of vaccine preventable illnesses in adults. Adult vaccination has been shown to dramatically increase the health and quality of life of older populations. Therefore, adult vaccinations need to be approached as a public health issue, similar to smoking cessation programs, for example. According to the Kenya Non-Communicable Diseases and injuries poverty commission report, 2018. Kenya has a high percentage of disability adjusted life years (DALYs) from communicable diseases at 63%, while non-communicable diseases (NCDs) contribute 30% of the DALYs. Specific to pneumococcal pneumonia (PP) in adults, the Global burden of disease (GBD) study in 2016 found that 2,377,697 people of all ages died from lower respiratory tract infections (LRTI) in 2016. Of these, more people died from Streptococcus pneumonia(SP) than from all other studied respiratory pathogens combined. While the incidence of LRTIs in children under five years old was reducing, partly as a result of well-established vaccination programs in children, the incidence, morbidity and mortality of PP was increasing in older populations. The expert recommendations included the following; i) all individuals 65 years of age and above, and individuals with a predisposing comorbidity regardless of age, should receive the pneumococcal vaccine; ii) several systemic modules can be emulated from the successful childhood vaccines programs onto an adult vaccine program; iii) formulation of an effective vaccine program will require collaboration from the public, the government, healthcare providers, and the media, to create awareness; iv) stakeholders who need to be involved in vaccine policy development and implementation include medical professional associations, nurses, pharmacists, clinical officers, payers (private and public insurances), government, medical learning institutions and faith-based medical organizations.

Challenges and recommendations for the management of asthma in the Middle East and Africa.

Clinical presentation of asthma is variable, and its diagnosis can be a major challenge in routine health-care practice, especially in low-and-middle-income countries. The aim of asthma management is to achieve optimal asthma control and to reduce the risk of asthma exacerbations and mortality. In the Middle East and in Africa (MEA), several patient- and physician-related factors lead to misdiagnosis and suboptimal management of asthma. A panel of experts comprising of specialists as well as general health-care professionals met to identify challenges and provide recommendations for the management of asthma in MEA. The major challenges identified for diagnosis of asthma were lack of adequate knowledge about the disease, lack of specialized diagnostic facilities, limited access to spirometry, and social stigma associated with asthma. The prime challenges for management of asthma in MEA were identified as overreliance on short-acting ß-agonists (SABAs), underprescription of inhaled corticosteroids (ICS), nonadherence to prescribed medications, and inadequate insurance coverage for its treatment. The experts endorsed adapting the Global Initiative for Asthma guidelines at country and regional levels for effective management of asthma and to alleviate the overuse of SABAs as reliever medications. Stringent control over SABA use, discouraging over-the-counter availability of SABA, and using as-needed low-dose ICS and formoterol as rescue medications in mild cases were suggested to reduce the overreliance on SABAs. Encouraging SABA alone-free clinical practice in both outpatient and emergency department settings is also imperative. We present the recommendations for the management of asthma along with proposed regional adaptations of international guidelines for MEA.

TB morbidity estimates overlook the contribution of post-TB disability: evidence from urban Malawi.

INTRODUCTION: Despite growing evidence of the long-term impact of tuberculosis (TB) on quality of life, Global Burden of Disease (GBD) estimates of TB-related disability-adjusted life years (DALYs) do not include post-TB morbidity, and evaluations of TB interventions typically assume treated patients return to pre-TB health. Using primary data, we estimate years of life lost due to disability (YLDs), years of life lost due to premature mortality (YLL) and DALYs associated with post-TB cardiorespiratory morbidity in a low-income country. METHODS: Adults aged ≥15 years who had successfully completed treatment for drug-sensitive pulmonary TB in Blantyre, Malawi (February 2016-April 2017) were followed-up for 3 years with 6-monthly and 12-monthly study visits. In this secondary analysis, St George's Respiratory Questionnaire data were used to match patients to GBD cardiorespiratory health states and corresponding disability weights (DWs) at each visit. YLDs were calculated for the study period and estimated for remaining lifespan using Malawian life table life expectancies. YLL were estimated using study mortality data and aspirational life expectancies, and post-TB DALYs derived. Data were disaggregated by HIV status and gender. RESULTS: At treatment completion, 222/403 (55.1%) participants met criteria for a cardiorespiratory DW, decreasing to 15.6% after 3 years, at which point two-thirds of the disability burden was experienced by women. Over 90% of projected lifetime-YLD were concentrated within the most severely affected 20% of survivors. Mean DWs in the 3 years post-treatment were 0.041 (HIV-) and 0.025 (HIV+), and beyond 3 years estimated as 0.025 (HIV-) and 0.010 (HIV+), compared with GBD DWs of 0.408 (HIV+) and 0.333 (HIV-) during active disease. Our results imply that the majority of TB-related morbidity occurs post-treatment. CONCLUSION: TB-related DALYs are greatly underestimated by overlooking post-TB disability. The total disability burden of TB is likely undervalued by both GBD estimates and economic evaluations of interventions, particularly those aimed at early diagnosis and prevention.

The Structured Operational Research and Training Initiative for Strengthening Health Systems to Tackle Antimicrobial Resistance and Improve Public Health in Low-and-Middle Income Countries.

If research is to have an impact and change health outcomes for the better, the findings of the research should be translated into recommendations and actions that can influence policy and/or practice [...].

The WHO Global Tuberculosis 2021 Report - not so good news and turning the tide back to End TB.

OBJECTIVE: To review the data presented in the 2021 WHO global TB report and discuss the current constraints in the global response. INTRODUCTION AND METHODS: The WHO global TB reports, consolidate TB data from countries and provide up to date assessment of the global TB epidemic. We reviewed the data presented in the 2021 report. RESULTS: We noted that the 2021 WHO global TB report presents a rather grim picture on the trajectory of the global epidemic of TB including a stagnation in the annual decline in TB incidence, a decline in TB notifications and an increase in estimated TB deaths. All the targets set at the 2018 United Nations High Level Meeting on TB were off track. INTERPRETATION AND CONCLUSION: The sub-optimal global performance on achieving TB control targets in 2020 is attributed to the on-going COVID-19 pandemic, however, TB programs were already off track well before the onset of the pandemic, suggesting that the pandemic amplified an already fragile global TB response. We emphasize that ending the global TB epidemic will require bold leadership, optimization of existing interventions, widespread coverage, addressing social determinants of TB and importantly mobilization of adequate funding required for TB care and prevention.

Tuberculosis, HIV/AIDS and Malaria Health Services in sub-Saharan Africa - A Situation Analysis of the Disruptions and Impact of the COVID-19 Pandemic.

BACKGROUND: The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries' health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. METHODS: In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. RESULTS: The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. CONCLUSIONS: Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa's economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services.

Delamanid-containing regimens and multidrug-resistant tuberculosis: A systematic review and meta-analysis.

INTRODUCTION: Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. METHODS: We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. RESULTS: After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). CONCLUSIONS: In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events.

Rapid Diagnosis of XDR and Pre-XDR TB: A Systematic Review of Available Tools.

INTRODUCTION: No previous systematic reviews have comprehensively investigated the features of Xpert MTB/XDR and other rapid tests to diagnose pre-XDR/XDR-TB. The aim of this systematic review is to assess existing rapid diagnostics for pre-XDR/XDR-TB from a point-of-care perspective and describe their technical characteristics (i.e., sensitivity, specificity, positive and negative predictive values). METHODS: Embase, PubMed, Scopus, and Web of Science were searched to detect the articles focused on the accuracy of commercially available rapid molecular diagnostic tests for XDR-TB according to PRISMA guidelines. The analysis compared the diagnostic techniques and approaches in terms of sensitivity, specificity, laboratory complexity, time to confirmed diagnosis. RESULTS: Of 1298 records identified, after valuating article titles and abstracts, 97 (7.5%) records underwent full-text evaluation and 38 records met the inclusion criteria. Two rapid World Health Organization (WHO)-endorsed tests are available: Xpert MTB/XDR and GenoType MTBDRsl (VER1.0 and VER 2.0). Both tests had similar performance, slightly favouring Xpert, although only 2 studies were available (sensitivity 91.4-94; specificity 98.5-99; accuracy 97.2-97.7; PPV 88.9-99.1; NPV 95.8-98.9). CONCLUSIONS: Xpert MTB/XDR could be suggested at near-point-of-care settings to be used primarily as a follow-on test for laboratory-confirmed TB, complementing existing rapid tests detecting at least rifampicin-resistance. Both Xpert MTB/XDR and GenoType MTBDRsl are presently diagnosing what WHO defined, in 2021, as pre-XDR-TB.