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There is inconclusive evidence on the association between ambient air pollution and pulmonary tuberculosis (PTB) incidence, tuberculosis-related hospital admission and mortality. This review aimed to assess the extent to which selected air pollutants are associated to PTB incidence, hospital admissions and mortality. This was a systematic review of studies published in English from January 1st, 1946, through May 31st, 2022, that quantitatively assessed the association between PM2.5, PM10, NO2, SO2, CO, O3 and the incidence of, hospital admission or death from PTB. Medline, Embase, Scopus and The Cochrane Library were searched. Extracted data from eligible studies were analysed using STATA software. Random-effect meta-analysis was used to derive pooled adjusted risk and odds ratios. A total of 24 studies (10 time-series, 5 ecologic, 5 cohort, 2 case–control, 1 case cross-over, 1 cross-sectional) mainly from Asian countries were eligible and involved a total of 437,255 tuberculosis cases. For every 10 μg/m3 increment in air pollutant concentration, there was a significant association between exposure to PM2.5 (pooled aRR = 1.12, 95% CI: 1.06–1.19, p

Background\ud The World Health Organization (WHO) End TB Strategy stresses universal access to drug susceptibility testing (DST). DST determines whether Mycobacterium tuberculosis bacteria are susceptible or resistant to drugs. Xpert MTB/XDR is a rapid nucleic acid amplification test for detection of tuberculosis and drug resistance in one test suitable for use in peripheral and intermediate level laboratories. In specimens where tuberculosis is detected by Xpert MTB/XDR, Xpert MTB/XDR can also detect resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin.\ud \ud Objectives\ud To assess the diagnostic accuracy of Xpert MTB/XDR for pulmonary tuberculosis in people with presumptive pulmonary tuberculosis (having signs and symptoms suggestive of tuberculosis, including cough, fever, weight loss, night sweats).\ud \ud To assess the diagnostic accuracy of Xpert MTB/XDR for resistance to isoniazid, fluoroquinolones, ethionamide, and amikacin in people with tuberculosis detected by Xpert MTB/XDR, irrespective of rifampicin resistance (whether or not rifampicin resistance status was known) and with known rifampicin resistance.\ud \ud Search methods\ud We searched multiple databases to 23 September 2021. We limited searches to 2015 onwards as Xpert MTB/XDR was launched in 2020.\ud \ud Selection criteria\ud Diagnostic accuracy studies using sputum in adults with presumptive or confirmed pulmonary tuberculosis. Reference standards were culture (pulmonary tuberculosis detection); phenotypic DST (pDST), genotypic DST (gDST),composite (pDST and gDST) (drug resistance detection).\ud \ud Data collection and analysis\ud Two review authors independently reviewed reports for eligibility and extracted data using a standardized form. For multicentre studies, we anticipated variability in the type and frequency of mutations associated with resistance to a given drug at the different centres and considered each centre as an independent study cohort for quality assessment and analysis. We assessed methodological quality with QUADAS‐2, judging risk of bias separately for each target condition and reference standard. For pulmonary tuberculosis detection, owing to heterogeneity in participant characteristics and observed specificity estimates, we reported a range of sensitivity and specificity estimates and did not perform a meta‐analysis. For drug resistance detection, we performed meta‐analyses by reference standard using bivariate random‐effects models. Using GRADE, we assessed certainty of evidence of Xpert MTB/XDR accuracy for detection of resistance to isoniazid and fluoroquinolones in people irrespective of rifampicin resistance and to ethionamide and amikacin in people with known rifampicin resistance, reflecting real‐world situations. We used pDST, except for ethionamide resistance where we considered gDST a better reference standard.\ud \ud Main results\ud We included two multicentre studies from high multidrug‐resistant/rifampicin‐resistant tuberculosis burden countries, reporting on six independent study cohorts, involving 1228 participants for pulmonary tuberculosis detection and 1141 participants for drug resistance detection. The proportion of participants with rifampicin resistance in the two studies was 47.9% and 80.9%. For tuberculosis detection, we judged high risk of bias for patient selection owing to selective recruitment. For ethionamide resistance detection, we judged high risk of bias for the reference standard, both pDST and gDST, though we considered gDST a better reference standard.\ud \ud Pulmonary tuberculosis detection\ud \ud ‐ Xpert MTB/XDR sensitivity range, 98.3% (96.1 to 99.5) to 98.9% (96.2 to 99.9) and specificity range, 22.5% (14.3 to 32.6) to 100.0% (86.3 to 100.0); median prevalence of pulmonary tuberculosis 91.3%, (interquartile range, 89.3% to 91.8%), (2 studies; 1 study reported on 2 cohorts, 1228 participants; very low‐certainty evidence, sensitivity and specificity).\ud \ud Drug resistance detection\ud \ud People irrespective of rifampicin resistance\ud \ud ‐ Isoniazid resistance: Xpert MTB/XDR summary sensitivity and specificity (95% confidence interval (CI)) were 94.2% (87.5 to 97.4) and 98.5% (92.6 to 99.7) against pDST, (6 cohorts, 1083 participants, moderate‐certainty evidence, sensitivity and specificity).\ud \ud ‐ Fluoroquinolone resistance: Xpert MTB/XDR summary sensitivity and specificity were 93.2% (88.1 to 96.2) and 98.0% (90.8 to 99.6) against pDST, (6 cohorts, 1021 participants; high‐certainty evidence, sensitivity; moderate‐certainty evidence, specificity).\ud \ud People with known rifampicin resistance\ud \ud ‐ Ethionamide resistance: Xpert MTB/XDR summary sensitivity and specificity were 98.0% (74.2 to 99.9) and 99.7% (83.5 to 100.0) against gDST, (4 cohorts, 434 participants; very low‐certainty evidence, sensitivity and specificity).\ud \ud ‐ Amikacin resistance: Xpert MTB/XDR summary sensitivity and specificity were 86.1% (75.0 to 92.7) and 98.9% (93.0 to 99.8) against pDST, (4 cohorts, 490 participants; low‐certainty evidence, sensitivity; high‐certainty evidence, specificity).\ud \ud Of 1000 people with pulmonary tuberculosis, detected as tuberculosis by Xpert MTB/XDR:\ud \ud ‐ where 50 have isoniazid resistance, 61 would have an Xpert MTB/XDR result indicating isoniazid resistance: of these, 14/61 (23%) would not have isoniazid resistance (FP); 939 (of 1000 people) would have a result indicating the absence of isoniazid resistance: of these, 3/939 (0%) would have isoniazid resistance (FN).\ud \ud ‐ where 50 have fluoroquinolone resistance, 66 would have an Xpert MTB/XDR result indicating fluoroquinolone resistance: of these, 19/66 (29%) would not have fluoroquinolone resistance (FP); 934 would have a result indicating the absence of fluoroquinolone resistance: of these, 3/934 (0%) would have fluoroquinolone resistance (FN).\ud \ud ‐ where 300 have ethionamide resistance, 296 would have an Xpert MTB/XDR result indicating ethionamide resistance: of these, 2/296 (1%) would not have ethionamide resistance (FP); 704 would have a result indicating the absence of ethionamide resistance: of these, 6/704 (1%) would have ethionamide resistance (FN).\ud \ud ‐ where 135 have amikacin resistance, 126 would have an Xpert MTB/XDR result indicating amikacin resistance: of these, 10/126 (8%) would not have amikacin resistance (FP); 874 would have a result indicating the absence of amikacin resistance: of these, 19/874 (2%) would have amikacin resistance (FN).\ud \ud Authors' conclusions\ud Review findings suggest that, in people determined by Xpert MTB/XDR to be tuberculosis‐positive, Xpert MTB/XDR provides accurate results for detection of isoniazid and fluoroquinolone resistance and can assist with selection of an optimised treatment regimen. Given that Xpert MTB/XDR targets a limited number of resistance variants in specific genes, the test may perform differently in different settings. Findings in this review should be interpreted with caution. Sensitivity for detection of ethionamide resistance was based only on Xpert MTB/XDR detection of mutations in the inhA promoter region, a known limitation. High risk of bias limits our confidence in Xpert MTB/XDR accuracy for pulmonary tuberculosis.\ud \ud Xpert MTB/XDR's impact will depend on its ability to detect tuberculosis (required for DST), prevalence of resistance to a given drug, health care infrastructure, and access to other tests.

Background Further work is required to understand the intrapulmonary pharmacokinetics of first-line anti-tuberculosis drugs. This study aimed to describe the plasma and intrapulmonary pharmacokinetics of rifampicin, isoniazid, pyrazinamide, and ethambutol, and explore relationships with clinical treatment outcomes in patients with pulmonary tuberculosis. Methods Malawian adults with a first presentation of microbiologically confirmed pulmonary tuberculosis received standard 6-month first-line therapy. Plasma and intrapulmonary samples were collected 8 and 16 weeks into treatment and drug concentrations measured in plasma, lung/airway epithelial lining fluid (ELF), and alveolar cells. Population pharmacokinetic modeling generated estimates of drug exposure (Cmax and AUC) from individual-level post hoc Bayesian estimates of plasma and intrapulmonary pharmacokinetics. Results One-hundred fifty-seven patients (58% HIV coinfected) participated. Despite standard weight-based dosing, peak plasma concentrations of first-line drugs were below therapeutic drug-monitoring targets. Rifampicin concentrations were low in all 3 compartments. Isoniazid, pyrazinamide, and ethambutol achieved higher concentrations in ELF and alveolar cells than plasma. Isoniazid and pyrazinamide concentrations were 14.6-fold (95% CI, 11.2–18.0-fold) and 49.8-fold (95% CI, 34.2–65.3-fold) higher in ELF than plasma, respectively. Ethambutol concentrations were highest in alveolar cells (alveolar cell–plasma ratio, 15.0; 95% CI, 11.4–18.6). Plasma or intrapulmonary pharmacokinetics did not predict clinical treatment response. Conclusions We report differential drug concentrations between plasma and the lung. While plasma concentrations were below therapeutic monitoring targets, accumulation of drugs at the site of disease may explain the success of the first-line regimen. The low rifampicin concentrations observed in all compartments lend strong support for ongoing clinical trials of high-dose rifampicin regimens., First-line anti-tuberculosis drugs achieve higher concentrations in the lung than in plasma in patients on treatment. Despite standard weight-based dosing, rifampicin concentrations are particularly low in plasma, epithelial lining fluid, and alveolar cells. Dose refinement may be required.

Treatment compliance is an important aspect for tuberculosis prevention and control. Poor compliance to treatment can lead to the development of drug-resistant tuberculosis. The aim of this study was to explore the factors affecting treatment compliance for tuberculosis patients. Facility based unmatched case control study was done among the forty non-compliance and eighty compliance pulmonary tuberculosis patients registered at selected directly observed treatment short-course centers of six districts. Data were collected using in-depth interview guideline with the tuberculosis focal person and Focus Group Discussion with tuberculosis patients. A total of 120 respondents, 40 cases and 80 controls were enrolled in the study. About 72.5% of the cases and 56.2% of the controls were male. Five significant independent risk factors for non-compliance to TB treatment were identified. The qualitative session confirmed geographical barriers, inaccessibility to health facility, economic barriers, difficulty in convincing people, knowledge about Directly observed treatment shortcourse program, longer medication period, migration and stigma as a major barrier for treatment compliance. Wider ranges of barriers are prevalent in context of tuberculosis treatment pathway and outcome. Knowledge of the tuberculosis patients and attitude of the family plays a vital role in treatment compliance. Directly observed treatment shortcourse playing tremendous role to ensure treatment adherence has been identified as major barrier to adherence as well. Enablers of adherence need to be emphasized to address the barriers.

Current methods for tuberculosis treatment monitoring are suboptimal. We evaluated plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide concentrations before and during tuberculosis treatment as biomarkers. Plasma MMP-1, MMP-8, and MMP-10 concentrations significantly decreased during treatment. Plasma MMP-8 was increased in sputum Mycobacterium tuberculosis culture–positive relative to culture-negative participants, before (median, 4993 pg/mL [interquartile range, 2542–9188] vs 698 [218–4060] pg/mL, respectively; P = .004) and after (3650 [1214–3888] vs 720 [551–1321] pg/mL; P = .008) 6 months of tuberculosis treatment. Consequently, plasma MMP-8 is a potential biomarker to enhance tuberculosis treatment monitoring and screen for possible culture positivity.

BackgroundMitigating the socioeconomic impact of tuberculosis (TB) is key to the WHO End TB Strategy. However, little known about socioeconomic well-being beyond TB-treatment completion. In this mixed-methods study, we describe socioeconomic outcomes after TB-disease in urban Blantyre, Malawi, and explore pathways and barriers to financial recovery.MethodsAdults ≥15 years successfully completing treatment for a first episode of pulmonary TB under the National TB Control Programme were prospectively followed up for 12 months. Socioeconomic, income, occupation, health seeking and cost data were collected. Determinants and impacts of ongoing financial hardship were explored through illness narrative interviews with purposively selected participants.Results405 participants were recruited from February 2016 to April 2017. Median age was 35 years (IQR: 28–41), 67.9% (275/405) were male, and 60.6% (244/405) were HIV-positive. Employment and incomes were lowest at TB-treatment completion, with limited recovery in the following year: fewer people were in paid work (63.0% (232/368) vs 72.4% (293/405), p=0.006), median incomes were lower (US$44.13 (IQR: US$0–US$106.15) vs US$72.20 (IQR: US$26.71–US$173.29), pConclusionsTB-affected households remain economically vulnerable even after TB-treatment completion, with limited recovery in income and employment, persistent financial strain requiring dissaving, and ongoing school interruptions. Measures of the economic impact of TB disease should include the post-TB period. Interventions to protect the long-term health and livelihoods of TB survivors must be explored.

Objectives\ud This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows:\ud \ud To determine the accuracy of Xpert MTB/RIF and Xpert Ultra for screening for tuberculosis in adults irrespective of signs or symptoms of pulmonary tuberculosis in the general population (i.e. low‐risk population).\ud \ud To determine the accuracy of Xpert MTB/RIF and Xpert Ultra for screening of pulmonary tuberculosis in adults in the following high‐risk groups.\ud \ud People living with HIV.\ud \ud Household contacts of people with tuberculosis.\ud \ud Patients residing in high‐tuberculosis‐burden settings attending primary health facilities.\ud \ud Homeless people.\ud \ud Miners.\ud \ud People with diabetes mellitus.\ud \ud People who abuse alcohol.\ud \ud Smokers.\ud \ud People residing in prisons.\ud \ud Healthcare workers.\ud \ud To determine the accuracy of Xpert MTB/RIF and Xpert Ultra for the detection of rifampicin resistance in the general population and in the high‐risk groups and settings described above.\ud \ud Secondary objectives\ud To compare the accuracy of Xpert MTB/RIF and Xpert Ultra in the above high‐risk groups and settings.\ud \ud To investigate potential sources of heterogeneity in accuracy estimates, including the percentage of participants with tuberculosis symptoms, tuberculosis burden, tuberculosis/HIV burden, and MDR‐TB burden.

Objective: To evaluate the utility of a volunteer health development army in conducting population screening for active tuberculosis (TB) in a rural community in southern Ethiopia. Methods: A population-based cross-sectional survey was conducted in six kebeles (the lowest administrative units). Volunteer women community workers led a symptom screening programme to identify adults ≥15 years of age with TB in the community. Individuals with a cough for ≥2 weeks had spot and morning sputum samples taken, which were examined using acid-fast bacillus (AFB) smear microscopy, culture, and Xpert MTB/RIF. Results: All 24 517 adults in the study area had a symptom screen performed; 544 (2.2%) had had a cough for ≥2 weeks. Among those with a positive symptom screen, 13 (2.4%) were positive on sputum AFB smear microscopy, 13 (2.4%) had a positive culture, and 32 (5.8%) had a positive Xpert MTB/RIF test. Overall, 34 TB cases (6%) were identified by culture and/or Xpert, corresponding to a prevalence of 139 per 100 000 persons. Conclusions: This study demonstrated the capability of community health workers (volunteer and paid) to rapidly conduct a large-scale population TB screening evaluation and highlight the high yield of such a programme in detecting previously undiagnosed cases when combined with Xpert MTB/RIF testing. This could be a model to implement in other similar settings. Keywords: Community TB, Prevalence, Health development army, Ethiopia

Mass gatherings pose a risk for tuberculosis (TB) transmission and reactivation of latent TB infection. The annual Hajj pilgrimage attracts 2 million pilgrims many from high TB-endemic countries. We evaluated the burden of undiagnosed active pulmonary TB in pilgrims attending the 2015 Hajj mass gathering. We conducted a prospective cross-sectional study in Mecca, Kingdom of Saudi Arabia, for nonhospitalized adult pilgrims from five high TB-endemic countries. Enrollment criteria were the presence of a cough and the ability to produce a sputum sample. Sputum samples were processed using the Xpert MTB-RIF assay. Data were analyzed for drug-resistant TB, risk factors, and comorbidities by the country of origin. Of 1,164 consenting pilgrims enrolled from five countries: Afghanistan (316), Bangladesh (222), Nigeria (176), Pakistan (302), and South Africa (148), laboratory results were available for 1,063 (91.3%). The mean age of pilgrims was 54.5 (range = 18-94 years) with a male to female ratio of 2.6:1; 27.7% had an underlying comorbidity, with hypertension and diabetes being the most common, 20% were smokers, and 2.8% gave a history of previous TB treatment. Fifteen pilgrims (1.4%) had active previously undiagnosed drug-sensitive pulmonary TB (Afghanistan [12; 80%], Pakistan [2; 13.3%], and Nigeria [1; 6.7%]). No multidrug-resistant TB cases were detected. Pilgrims from high TB-endemic Asian and African countries with undiagnosed active pulmonary TB pose a risk to other pilgrims from over 180 countries. Further studies are required to define the scale of the TB problem during the Hajj mass gathering and the development of proactive screening, treatment and prevention guidelines.

Background Xpert MTB/RIF (Xpert MTB/RIF) and Xpert MTB/RIF Ultra (Xpert Ultra), the newest version, are the only World Health Organization (WHO)‐recommended rapid tests that simultaneously detect tuberculosis and rifampicin resistance in persons with signs and symptoms of tuberculosis, at lower health system levels. A previous Cochrane Review found Xpert MTB/RIF sensitive and specific for tuberculosis (Steingart 2014). Since the previous review, new studies have been published. We performed a review update for an upcoming WHO policy review. Objectives To determine diagnostic accuracy of Xpert MTB/RIF and Xpert Ultra for tuberculosis in adults with presumptive pulmonary tuberculosis (PTB) and for rifampicin resistance in adults with presumptive rifampicin‐resistant tuberculosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register, MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, to 11 October 2018, without language restriction. Selection criteria Randomized trials, cross‐sectional, and cohort studies using respiratory specimens that evaluated Xpert MTB/RIF, Xpert Ultra, or both against the reference standard, culture for tuberculosis and culture‐based drug susceptibility testing or MTBDRplus for rifampicin resistance. Data collection and analysis Four review authors independently extracted data using a standardized form. When possible, we also extracted data by smear and HIV status. We assessed study quality using QUADAS‐2 and performed meta‐analyses to estimate pooled sensitivity and specificity separately for tuberculosis and rifampicin resistance. We investigated potential sources of heterogeneity. Most analyses used a bivariate random‐effects model. For tuberculosis detection, we first estimated accuracy using all included studies and then only the subset of studies where participants were unselected, i.e. not selected based on prior microscopy testing. Main results We identified in total 95 studies (77 new studies since the previous review): 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis and 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert MTB/RIF and Xpert Ultra on the same participant specimen. Tuberculosis detection Of the total 86 studies, 45 took place in high tuberculosis burden and 50 in high TB/HIV burden countries. Most studies had low risk of bias. Xpert MTB/RIF pooled sensitivity and specificity (95% credible Interval (CrI)) were 85% (82% to 88%) and 98% (97% to 98%), (70 studies, 37,237 unselected participants; high‐certainty evidence). We found similar accuracy when we included all studies. For a population of 1000 people where 100 have tuberculosis on culture, 103 would be Xpert MTB/RIF‐positive and 18 (17%) would not have tuberculosis (false‐positives); 897 would be Xpert MTB/RIF‐negative and 15 (2%) would have tuberculosis (false‐negatives). Xpert Ultra sensitivity (95% confidence interval (CI)) was 88% (85% to 91%) versus Xpert MTB/RIF 83% (79% to 86%); Xpert Ultra specificity was 96% (94% to 97%) versus Xpert MTB/RIF 98% (97% to 99%), (1 study, 1439 participants; moderate‐certainty evidence). Xpert MTB/RIF pooled sensitivity was 98% (97% to 98%) in smear‐positive and 67% (62% to 72%) in smear‐negative, culture‐positive participants, (45 studies). Xpert MTB/RIF pooled sensitivity was 88% (83% to 92%) in HIV‐negative and 81% (75% to 86%) in HIV‐positive participants; specificities were similar 98% (97% to 99%), (14 studies). Rifampicin resistance detection Xpert MTB/RIF pooled sensitivity and specificity (95% Crl) were 96% (94% to 97%) and 98% (98% to 99%), (48 studies, 8020 participants; high‐certainty evidence). For a population of 1000 people where 100 have rifampicin‐resistant tuberculosis, 114 would be positive for rifampicin‐resistant tuberculosis and 18 (16%) would not have rifampicin resistance (false‐positives); 886 would be would be negative for rifampicin‐resistant tuberculosis and four (0.4%) would have rifampicin resistance (false‐negatives). Xpert Ultra sensitivity (95% CI) was 95% (90% to 98%) versus Xpert MTB/RIF 95% (91% to 98%); Xpert Ultra specificity was 98% (97% to 99%) versus Xpert MTB/RIF 98% (96% to 99%), (1 study, 551 participants; moderate‐certainty evidence). Authors' conclusions We found Xpert MTB/RIF to be sensitive and specific for diagnosing PTB and rifampicin resistance, consistent with findings reported previously. Xpert MTB/RIF was more sensitive for tuberculosis in smear‐positive than smear‐negative participants and HIV‐negative than HIV‐positive participants. Compared with Xpert MTB/RIF, Xpert Ultra had higher sensitivity and lower specificity for tuberculosis and similar sensitivity and specificity for rifampicin resistance (1 study). Xpert MTB/RIF and Xpert Ultra provide accurate results and can allow rapid initiation of treatment for multidrug‐resistant tuberculosis., Xpert MTB/RIF and Xpert Ultra for diagnosing pulmonary tuberculosis and rifampicin resistance in adults Why is improving the diagnosis of pulmonary tuberculosis important? Tuberculosis causes more deaths globally than any other infectious disease. When detected early and effectively treated, tuberculosis is largely curable, but in 2017, around 1.6 million people died of tuberculosis. Xpert MTB/RIF and Xpert Ultra, the newest version, are World Health Organization‐recommended tests that simultaneously detect tuberculosis and rifampicin resistance in persons with tuberculosis symptoms. Rifampicin is an important anti‐tuberculosis drug. Not recognizing tuberculosis early may result in delayed diagnosis and treatment, severe illness, and death. An incorrect tuberculosis diagnosis may result in anxiety and unnecessary treatment. What is the aim of this review? To determine how accurate Xpert MTB/RIF and Xpert Ultra are for diagnosing pulmonary tuberculosis (PTB) and rifampicin resistance in adults. This is an update of the 2014 Cochrane Review. What was studied in this review? Xpert MTB/RIF and Xpert Ultra, with results measured against culture (benchmark). What are the main results in this review? 95 studies: 86 studies (42,091 participants) evaluated Xpert MTB/RIF for tuberculosis; 57 studies (8287 participants) for rifampicin resistance. One study compared Xpert Ultra and Xpert MTB/RIF. For PTB, Xpert MTB/RIF was sensitive (85%), registering positive in people who actually had tuberculosis, and specific (98%), i.e. it did not register positive in people who were actually negative. Xpert Ultra had higher sensitivity than Xpert MTB/RIF (88% versus 83%) in one study. For rifampicin resistance, Xpert MTB/RIF was highly sensitive (96%) and specific (98%). Xpert Ultra gave similar results. Xpert MTB/RIF was better for diagnosing tuberculosis in HIV‐negative than in HIV‐positive people. How confident are we in the results of this review? Confident. We included many studies and used the best reference standards. Who do the results of this review apply to? People with presumed PTB or rifampicin resistance. What are the implications of this review? In theory, among 1000 people where 100 have tuberculosis on culture, 103 would be Xpert MTB/RIF‐positive and 18 (17%) would not have tuberculosis (false‐positives); 897 would be Xpert MTB/RIF‐negative and 15 (2%) would have tuberculosis (false‐negatives). Among 1000 people where 100 have rifampicin resistance, 114 would be positive for rifampicin resistance and 18 (16%) would not have rifampicin resistance (false‐positives); 886 would be negative for rifampicin resistance and four (0.4%) would have rifampicin resistance (false‐negatives). How up‐to‐date is this review? To 11 October 2018.

We read with interest the review article entitled “Imaging features of extrapulmonary tuberculosis” (EPTB), which rightly concludes that imaging plays an important role in the diagnosis and follow-up of EPTB (Gambhir et al., 2017). However, rather than a systematic review of all available modalities, this review appears to have focused on promoting the potential role of positron emission tomography–computed tomography (PET–CT) imaging, as the authors concluded that it may play a role in the diagnosis and follow-up of patients, especially in developing countries.

This is a protocol for a Cochrane Review (Diagnostic test accuracy). The objectives are as follows:\ud \ud To determine the diagnostic accuracy of Xpert® MTB/RIF for the detection of extrapulmonary TB by site of disease in people suspected of having extrapulmonary TB. The role of Xpert® MTB/RIF would be a replacement for standard practice.\ud \ud To determine the diagnostic accuracy of Xpert® MTB/RIF for detection of rifampicin resistance in people suspected of having extrapulmonary TB. The role of Xpert® MTB/RIF would be an initial test for replacement for culture-based DST.\ud \ud We plan to investigate the impact of covariates on heterogeneity in estimates of test accuracy across the included studies.\ud Detection of extrapulmonary TB\ud \ud The covariates of interest are: HIV prevalence; condition of the specimen (fresh versus frozen); sample input volume (for liquid specimens); homogenization step (for tissue specimens); smear status of specimen; past history of TB; and prevalence of extrapulmonary TB. In addition, we plan to explore whether the WHO standard operating procedures for a given type of specimen were followed and can explain the observed heterogeneity in accuracy estimates. For TB meningitis we plan to investigate whether the use of a concentration step prior to the use of Xpert® MTB/RIF has an impact on accuracy estimates. In addition, for detection of lymph node TB, pleural TB, and TB meningitis, we plan to adjust accuracy estimates by applying a latent class meta-analysis model to account for the imperfect nature of culture as the reference standard.\ud Detection of rifampicin resistance detection\ud \ud The covariate of interest is the prevalence of rifampicin resistance.

Variable exposure to anti-tuberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampicin. We evaluated the contribution of Single Nucleotide Polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC, CES-1) to inter-individual pharmacokinetic variability in Malawi. 174 adults with pulmonary TB underwent sampling of plasma rifampicin concentrations at 2- and 6-hours post-dose. Data from a prior cohort of 47 intensively sampled, similar patients from the same setting were available to support population pharmacokinetic model development in NONMEM v7.2©, using a two-stage strategy to improve information during the absorption phase. Contrary to recent studies in South Africa and Uganda, SNPs in SLCO1B1 did not explain variability in AUC0-∞ of rifampicin. No pharmacokinetic associations were identified with AADAC or CES-1 SNPs, which were rare in the Malawian population. Pharmacogenetic determinants of rifampicin exposure may vary between African populations. SLCO1B1 and other novel candidate genes, as well as non-genetic sources of inter-individual variability, should be further explored in geographically diverse, adequately powered cohorts.

Noncommunicable diseases (NCDs) are a major and increasing global health issue. The World Health Organization (WHO) estimates that NCDs represent 63% of all global deaths of which 3.9 million are due to chronic respiratory diseases (CRDs) and Chronic Obstructive Pulmonary Disease (COPD) in particular. COPD is now the third most common cause of death globally; 90% of these deaths occur in Low and Middle Income Countries (LMICs). COPD affects 329 million people, almost 5% of the world's population. In addition, asthma affects 334 million people, again representing almost 5% of the world's population. There is limited literature published on the epidemiology of COPD and Asthma from Sub-Saharan Africa (SSA) and Middle East and North Africa (MENA). Both diseases are under-diagnosed and underestimated in both SSA and MENA regions. The burden of COPD in sub-Saharan Africa is disputed and reports offer variable prevalence estimates, ranging from 4.1% to almost 22.2%. SSA and MENA countries report similar mortality rates from COPD of 18 per 100,000 population (2001 data). Asthma is a less common cause of death than COPD but is a major cause of morbidity; WHO estimates that there are 250,000 deaths per year from asthma, mainly in LMICs and it remains in the top twenty causes of disability in children globally. Risk factors for CRD are genetic and environmental; the latter dominated by air pollution exposures including tobacco smoke, household air pollution, outdoor air pollution and occupational exposures.

FluoroType MTB is a sensitive test for TB but specificity is low compared with fully integrated molecular systems

Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB.\ud Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research.

Only 25% of multidrug-resistant tuberculosis (MDR-TB) cases are currently diagnosed. Line probe assays (LPAs) enable rapid drug-susceptibility testing for rifampicin (RIF) and isoniazid (INH) resistance and Mycobacterium tuberculosis detection. Genotype MTBDRplusV1 was WHO-endorsed in 2008 but newer LPAs have since been developed. This systematic review evaluated three LPAs: Hain Genotype MTBDRplusV1, MTBDRplusV2 and Nipro NTM+MDRTB. Study quality was assessed with QUADAS-2. Bivariate random-effects meta-analyses were performed for direct and indirect testing. Results for RIF and INH resistance were compared to phenotypic and composite (incorporating sequencing) reference standards. M. tuberculosis detection results were compared to culture. 74 unique studies were included. For RIF resistance (21 225 samples), pooled sensitivity and specificity (with 95% confidence intervals) were 96.7% (95.6–97.5%) and 98.8% (98.2–99.2%). For INH resistance (20 954 samples), pooled sensitivity and specificity were 90.2% (88.2–91.9%) and 99.2% (98.7–99.5%). Results were similar for direct and indirect testing and across LPAs. Using a composite reference standard, specificity increased marginally. For M. tuberculosis detection (3451 samples), pooled sensitivity was 94% (89.4–99.4%) for smear-positive specimens and 44% (20.2–71.7%) for smear-negative specimens. In patients with pulmonary TB, LPAs have high sensitivity and specificity for RIF resistance and high specificity and good sensitivity for INH resistance. This meta-analysis provides evidence for policy and practice., Line probe assays have high accuracy for detection of RIF resistance and INH resistance http://ow.ly/USX5305tqFV

The lack of healthcare access contributes to large numbers of tuberculosis (TB) cases being missed and has led to renewed interest in outreach approaches to increase detection. It is however unclear whether outreach activities increase case detection or merely identify patients before they attend health facilities. We compared adults with cough of >2 weeks' duration recruited in health facilities (1202 participants) or in urban slums (2828 participants) in Nigeria. Participants provided demographic and clinical information and were screened using smear microscopy. The characteristics of smear-positive and smear-negative individuals were compared stratified by place of enrolment. Two hundred nine health facility participants (17.4%) and 485 community-based participants (16.9%) were smear positive for pulmonary TB. Community-based smear-positive cases were older (mean age, 36.3 vs. 31.8 years), had longer cough duration (10.3 vs. 6.8 weeks) and longer duration of weight loss (4.6 vs. 3.6 weeks) than facility-based cases; and they complained more of fever (87.4% vs. 74.6%), chest pain (89.0% vs. 67.0%) and anorexia (79.5% vs. 55.5%). Community smear-negative participants were older (mean, 39.4 vs. 34.0 years), were more likely to have symptoms and were more likely to have symptoms of longer duration than smear-negative facility-based participants. Patients with pulmonary TB identified in the community had more symptoms and longer duration of illness than facility-based patients, which appeared to be due to factors differentially affecting access to healthcare. Community-based activities targeted at urban slum populations may identify a different TB case population than that accessing stationary services.

Tuberculosis (TB) remains one of the world's major health burdens with 9.6 million new infections globally. Though considerable progress has been made in reduction of TB incidence and mortality, there is a continuous need for lower cost, simpler and more robust means of diagnosis. One method that may fulfil these requirements is in the area of breath analysis. In this study we analysed the breath of 21 patients with pulmonary or extra-pulmonary TB, recruited from a UK teaching hospital (University Hospital Coventry and Warwickshire) before or within 1 week of commencing treatment for TB. TB diagnosis was confirmed by reference tests (mycobacterial culture), histology or radiology. 19 controls were recruited to calculate specificity; these patients were all interferon-gamma release assay negative (T.SPOT(®).TB, Oxford Immunotec Ltd.). Whole breath samples were collected with subsequent chemical analysis undertaken by Ion Mobility Spectrometry. Our results produced a sensitivity of 81% and a specificity of 79% for all cases of TB (pulmonary and extra-pulmonary). Though lower than other studies analysing pulmonary TB alone, we believe that this technique shows promise, and a higher sensitivity could be achieved by further improving our sample capture methodology.

Funding: Liverpool Integrated Clinical Academic Training Programme, experience at another institution (ADM); Wellcome Trust Clinical PhD Fellowship 105392/B/14/Z. Bronchoscopy is an established research tool in Malawi, enabling collection of pulmonary samples for immunological, pharmacological, and microbiological studies. It is, however, an invasive clinical procedure that offers no direct benefit to volunteering participants when used in a research capacity alone, and thus informed consent is essential. This study aimed to explore TB patients' understanding of research bronchoscopy, what would motivate them to participate in research bronchoscopy, and their concerns, in order to inform consenting processes for future clinical studies. We used a qualitative research design. Two focus group discussions were conducted with community members and TB patients to understand their perceptions of bronchoscopy. Transcripts were coded by multiple coauthors and thematic content analysis was used to analyse main findings. We found that Malawian patients with pulmonary TB were willing to participate in a study using research bronchoscopy for health assessment and access to improved healthcare. We identified information of value to potential participants when consenting to that may lessen some of the anxieties expressed by participants. Patient and public involvement is essential to improve informed consent and institutional trust. Publisher PDF

Background\ud \ud Tuberculosis (TB) is a disease of public health concern, with a varying distribution across settings depending on socio-economic status, HIV burden, availability and performance of the health system. Ethiopia is a country with a high burden of TB, with regional variations in TB case notification rates (CNRs). However, TB program reports are often compiled and reported at higher administrative units that do not show the burden at lower units, so there is limited information about the spatial distribution of the disease. We therefore aim to assess the spatial distribution and presence of the spatio-temporal clustering of the disease in different geographic settings over 10 years in the Sidama Zone in southern Ethiopia.\ud \ud Methods\ud \ud A retrospective space–time and spatial analysis were carried out at the kebele level (the lowest administrative unit within a district) to identify spatial and space-time clusters of smear-positive pulmonary TB (PTB). Scan statistics, Global Moran’s I, and Getis and Ordi (Gi*) statistics were all used to help analyze the spatial distribution and clusters of the disease across settings.\ud \ud Results\ud \ud A total of 22,545 smear-positive PTB cases notified over 10 years were used for spatial analysis. In a purely spatial analysis, we identified the most likely cluster of smear-positive PTB in 192 kebeles in eight districts (RR= 2, p

The GeneXpert MTB/RIF assay (Xpert) is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. The objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (PTB) by offering Xpert to smear-negative patients in a low-HIV burden setting with noMycobacterium tuberculosis(M.tb.) culture facilities. Patients routinely presenting with symptoms suggestive of PTB with negative smears were offered single Xpert test on a fee-paying basis. Data were retrospectively reviewed to determine case detection in patients tested from February to December 2013. Symptoms associated with a positive test were analysed to determine if refinement of clinical criteria would reduce unnecessary testing. 258 smear-negative patients were included andM.tb.was detected in 55 (21.32%,n=55/258). Using standard clinical assessment for selection, testing 5 patients detected one case of smear-negative PTB. These results demonstrate that fee-paying Xpert service in low-income setting can increase TB case confirmation substantially and further systematic studies of health economic implications should be conducted to determine optimal implementation models to increase access to Xpert in low- and middle-income countries.

Background.Delay in pulmonary tuberculosis (PTB) diagnosis is one of the major factors that affect outcome and threatens continued spread of tuberculosis. This study aimed at determining factors associated with delayed PTB diagnosis among human immunodeficiency virus (HIV) infected individuals.Methods.A retrospective observational study was done using clinic records of HIV-infected PTB suspects attending an HIV/AIDS clinic at Tintswalo rural hospital in South Africa (SA) between January 2006 and December 2007. Using routine clinic registers, 480 records were identified.Results.PTB diagnosis delay was found among 77/176 (43.8%) of the patients diagnosed with PTB. The mean delay of PTB diagnosis was 170.6 days; diagnosis delay ranged 1–30 days in 27 (35.1%) patients, 31–180 days in 24 (33.8%) patients; 24 (31.2%) patients remained undiagnosed for ≥180 days. Independent factors associated with delayed diagnosis were: older age >40 years (Odds Ratio (OR) 3.43, 95% CI 1.45–8.08) and virological failure (OR 2.72, 95% CI 1.09–6.74).Conclusion.There is a considerable delayed PTB diagnosis among HIV-infected patients in rural SA. Older patients as well as patients with high viral load are at a higher risk of PTB diagnosis delay. Therefore efforts to reduce PTB diagnosis delay need to emphasised.

This study, nested within a clinical trial, by Luis Cuevas and colleagues finds that LED-FM microscopy has higher sensitivity but lower specificity than Zn microscopy for detecting tuberculosis in sputum samples., Background The diagnosis of tuberculosis (TB) in resource-limited settings relies on Ziehl-Neelsen (ZN) smear microscopy. LED fluorescence microscopy (LED-FM) has many potential advantages over ZN smear microscopy, but requires evaluation in the field. The aim of this study was to assess the sensitivity/specificity of LED-FM for the diagnosis of pulmonary TB and whether its performance varies with the timing of specimen collection. Methods and Findings Adults with cough ≥2 wk were enrolled consecutively in Ethiopia, Nepal, Nigeria, and Yemen. Sputum specimens were examined by ZN smear microscopy and LED-FM and compared with culture as the reference standard. Specimens were collected using a spot-morning-spot (SMS) or spot-spot-morning (SSM) scheme to explore whether the collection of the first two smears at the health care facility (i.e., “on the spot”) the first day of consultation followed by a morning sample the next day (SSM) would identify similar numbers of smear-positive patients as smears collected via the SMS scheme (i.e., one on-the-spot-smear the first day, followed by a morning specimen collected at home and a second on-the-spot sample the second day). In total, 529 (21.6%) culture-positive and 1,826 (74.6%) culture-negative patients were enrolled, of which 1,156 (49%) submitted SSM specimens and 1,199 (51%) submitted SMS specimens. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. Using two LED-FM or two ZN smears per patient was 72.8% (385/529, 95% CI 68.8%–76.5%) and 65.8% (348/529, 95% CI 61.6%–69.8%) sensitive (p, Editors' Summary Background Tuberculosis is a global public health problem. Every year, about 1.7 million people die from this contagious bacterial infection, and about 9 million new cases occur, mainly in low- and middle-income countries. Mycobacterium tuberculosis, which causes tuberculosis, is spread in airborne droplets when people with the disease cough or sneeze, and usually infects the lungs (pulmonary tuberculosis). Symptoms of tuberculosis include a persistent cough, weight loss, and night sweats. Because tuberculosis is easily transmitted and potentially deadly, it is important that it is diagnosed quickly and accurately and immediately treated. The “gold standard” diagnostic test for tuberculosis is mycobacterial culture (in liquid or solid medium), in which laboratory technicians try to grow M. tuberculosis from sputum (mucus brought up from the lungs by coughing). However, this test is expensive, so most patients suspected of having pulmonary tuberculosis in resource-limited countries are investigated using sputum smear microscopy. In this cheaper but less sensitive test, sputum samples are “smeared” onto microscope slides, stained with Ziehl-Neelsen (ZN) dye, and then examined with a microscope for the presence of M. tuberculosis. Why Was This Study Done? With smear microscopy, multiple samples have to be examined to increase the test's sensitivity (the proportion of patients with culture-positive tuberculosis that the test detects). Because each smear examination takes up to 10 minutes, tuberculosis diagnosis with ZN smear microscopy creates a large laboratory workload. A variant form of smear microscopy—light-emitting-diode fluorescence microscopy (LED-FM)—could reduce this workload. With LED-FM, smears stained with a fluorescent dye can be examined in a quarter of the time it takes to examine ZN smears. In this study, the researchers evaluate the sensitivity and specificity (the proportion of people with a negative smear among people without tuberculosis; a high specificity indicates a low false-positive rate) of LED-FM using samples collected in a trial undertaken in four resource-limited countries (Ethiopia, Nepal, Nigeria, and Yemen) to investigate two schemes for sputum sample collection. In the spot-morning-spot (SMS) scheme, patients provide an on-the-spot specimen at their initial consultation, a specimen collected at home the next morning, and a second on-the-spot sample when they deliver their morning specimen. In the spot-spot-morning (SSM) scheme, patients provide two on-the-spot samples during their first clinic visit and a sample collected at home the next morning. What Did the Researchers Do and Find? In the main trial, the researchers collected sputum samples using the SMS or SSM scheme from 6,627 patients with a cough lasting more than two weeks. For their investigation of LED-FM, they examined nearly 2,400 samples (half SSM and half SMS specimens, about a quarter of which were tuberculosis culture-positive) with both ZN smear microscopy and LED-FM and determined the sensitivity and specificity of both tests—with one, two, or three sputum samples per patient—relative to mycobacterial solid culture. Single LED-FM smears had higher sensitivity but lower specificity than single ZN smears. The sensitivities of two LED-FM and two ZN smears were 72.8% and 65.8%, respectively; the specificities of these tests were 90.9% and 98.0%. The sensitivities of three LED-FM and three ZN smears were 77% and 70.5%, respectively; the specificities of these tests were 88.1% and 96.5%. The sensitivity and specificity of both tests was similar for samples collected using the SMS and the SSM schemes. What Do These Findings Mean? These findings show that in the resource-limited countries included in this trial, LED-FM has a higher sensitivity but lower specificity than ZN smear microscopy. The researchers calculate that in this study the accuracy of three LED-FM examinations was 85% (2,017 out of 2,355 patients were correctly classified as infected or uninfected), whereas the accuracy of three ZN smears was 91.8%. Thus, although LED-FM should identify more people with tuberculosis than ZN smear microscopy, because of its lower specificity, its use might also lead to more people without tuberculosis being needlessly treated for the disease. Nevertheless, provided that the introduction of LED-FM is accompanied by appropriate training and performance monitoring, LED-FM is an attractive potential tool for the laboratory diagnosis of tuberculosis that, together with a move towards the collection of two on-the-spot smears in a single clinic visit, could ensure that poor patients have access to timely tuberculosis diagnosis and prompt treatment. Additional Information Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001057. Details of the parent trial in which the samples used in this study were collected are available in a PLoS Medicine Research Article by Cuevas et al. The World Health Organization provides information on all aspects of tuberculosis, including information on tuberculosis diagnostics; recent WHO policy statements on diagnosis of tuberculosis are available; the Stop TB Partnership provides information on global tuberculosis control (some information in several languages) The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis MedlinePlus has links to further information about tuberculosis (in English and Spanish) A new Web site dedicated to the discussion and optimization of smear microscopy has recently been launched

Background: Confirmation of pulmonary tuberculosis (PTB) in young children is difficult as they seldom expectorate sputum.\ud Aim: To compare sputa obtained by nasopharyngeal aspiration and by sputum induction for staining and culture of Mycobacterium tuberculosis.\ud Patients and methods: Patients from Mulago Hospital, Kampala with symptoms suggestive of PTB were considered for inclusion in the study. Those with a positive tuberculin test and/ or a chest radiograph compatible with tuberculosis were recruited. Infection with human immunodeficiency virus (HIV) was confirmed by duplicate enzyme-labelled immunosorbent assay or in children,15 months by polymerase chain reaction (PCR). Direct PCR was undertaken on 82 nasopharyngeal aspirates.\ud Results: Of 438 patients referred, 94 were recruited over a period of 5 months. Median (range) age was 48 (4-144) months. Of 63 patients tested, 69.8% were infected with HIV. Paired and uncontaminated culture results were available for 88 patients and smear results for 94 patients. Nasopharyngeal aspirates were smear-positive in 8.5% and culture-positive in 23.9%. Induced sputa were smear-positive in 9.6% and culture positive in 21.6%. Overall, 10.6% were smear-positive, 25.5% were culture-positive and 26.6% had smear and/or culture confirmed tuberculosis. Direct PCR on nasopharyngeal aspirates had a sensitivity of 62% and specificity of 98% for confirmation of culture-positive tuberculosis.\ud Conclusions: Nasopharyngeal aspiration is a useful, safe and low-technology method for confirmation of PTB and, like sputum induction, can be undertaken in outpatient clinics.

Contains fulltext : 96579.pdf (Publisher’s version ) (Open Access) BACKGROUND: More than 50 million people around the world are investigated for tuberculosis using sputum smear microscopy annually. This process requires repeated visits and patients often drop out. METHODS AND FINDINGS: This clinical trial of adults with cough >/=2 wk duration (in Ethiopia, Nepal, Nigeria, and Yemen) compared the sensitivity/specificity of two sputum samples collected "on the spot" during the first visit plus one sputum sample collected the following morning (spot-spot-morning [SSM]) versus the standard spot-morning-spot (SMS) scheme. Analyses were per protocol analysis (PPA) and intention to treat (ITT). A sub-analysis compared just the first two smears of each scheme, spot-spot and spot-morning. In total, 6,627 patients (3,052 SSM/3,575 SMS) were enrolled; 6,466 had culture and 1,526 were culture-positive. The sensitivity of SSM (ITT, 70.2%, 95% CI 66.5%-73.9%) was non-inferior to the sensitivity of SMS (PPA, 65.9%, 95% CI 62.3%-69.5%). Similarly, the specificity of SSM (ITT, 96.9%, 95% CI 93.2%-99.9%) was non-inferior to the specificity of SMS (ITT, 97.6%, 95% CI 94.0%-99.9%). The sensitivity of spot-spot (ITT, 63.6%, 95% CI 59.7%-67.5%) was also non-inferior to spot-morning (ITT, 64.8%, 95% CI 61.3%-68.3%), as the difference was within the selected -5% non-inferiority limit (difference ITT = 1.4%, 95% CI -3.7% to 6.6%). Patients screened using the SSM scheme were more likely to provide the first two specimens than patients screened with the SMS scheme (98% versus 94.2%, p

INTRODUCTION: Pulmonary tuberculosis (PTB) remains an important risk factor for chronic lung disease (CLD) in sub-Saharan Africa (sSA), but our understanding of the nature of post-TB lung damage, its evolution over time, and the associated morbidity remains limited. This information is needed to inform clinical care and health system approaches to the management of those surviving PTB disease.\ud \ud METHODS: A general review of the literature on CLDs in sSA, TB disease and epidemiology, and post-TB lung damage and its associated morbidity were completed, followed by a systematic review of the prevalence and pattern of post-TB structural lung pathology. Primary data presented in this thesis were drawn from two studies based in urban Blantyre, Malawi.\ud The first was a cross-sectional survey of respiratory abnormalities amongst adults in the community which was completed as part of the Burden of Obstructive Lung Disease (BOLD) initiative. The second was a prospective cohort study of HIV-positive and negative adults completing treatment for PTB which aimed to describe a) the prevalence of respiratory pathology at TB treatment completion using symptoms, quality of life scores, spirometry and high-resolution CT imaging, and b) the relationships between post-TB lung damage at treatment completion and adverse outcomes over 1-year of followup.\ud \ud RESULTS: The systematic review identified 39 studies of variable quality describing post-TB structural lung damage. A lack of prospective data, and data from sSA and HIV-positive groups was noted. Few studies related structural damage to symptoms, spirometry, or morbidity. The BOLD data estimated a high burden of respiratory symptoms and abnormal spirometry amongst adults aged ≥18 years in urban Blantyre: 11.8% reported ≥1 symptom, and 4.8% had airway obstruction. The prevalence of the low-FVC pattern of abnormal spirometry varied according to the reference range used for standardisation, from 9.0% (local reference range) to 38.6% (NHANES III reference range). A considerable burden of residual lung pathology was seen amongst 405 adults completing treatment for PTB in Blantyre: 60.7% had ongoing weekly/monthly respiratory symptoms, and 34.2% of participants had abnormal spirometry at PTB treatment completion. Participants had a median of 1.4 lobes of abnormal parenchyma on CT imaging. Moderate-severe bronchiectasis was seen in 44%, and 9.6% had ≥1 ‘destroyed’ lobe. The burden of pathology was lower in HIV-positive vs. HIV-negative adults, but patterns of abnormality were similar. The odds of ongoing respiratory symptoms or an impaired quality of life at 1-year were over three-fold higher amongst those with both extensive structural damage and abnormal spirometry at PTB treatment completion.\ud \ud CONCLUSION: Post-TB lung damage is a common but neglected form of CLD amongst both HIV-positive and negative adults in Malawi, and occurs against a high background prevalence of respiratory symptoms and abnormal spirometry in the community. Severe forms are associated with considerable ongoing morbidity including persistent symptoms and reduced quality of life. Further work is required to understand the range of patterns of post-TB lung damage, and their relationship with long-term outcomes such as respiratory exacerbations and mortality. However, this is a neglected population and interventions to maximise their health following PTB treatment completion are required.