Part of tuberculosis (TB) patients were missed if symptomatic screening was based on the main TB likely symptoms. This study conducted to compare the yield and relative costs of different TB screening algorithms in active case-finding in the whole population in China.The study population was screened based on the TB likely symptoms through a face-to-face interview in selected 27 communities from 10 counties of 10 provinces in China. If the individuals had any of the enhanced TB likely symptoms, both chest X-ray and sputum tests were carried out for them furtherly. We used the McNemar test to analyze the difference in TB detection among four algorithms in active case-finding. Of four algorithms, two were from WHO recommendations including 1a/1c, one from China National Tuberculosis Program, and one from this study with the enhanced TB likely symptoms. Furthermore, a two-way ANOVA analysis was performed to analyze the cost difference in the performance of active case-finding adjusted by different demographic and health characteristics among different algorithms.Algorithm with the enhanced TB likely symptoms defined in this study could increase the yield of TB detection in active case-finding, compared with algorithms recommended by WHO (p < 0.01, Kappa 95% CI: 0. 93-0.99) and China NTP (p = 0.03, Kappa 95% CI: 0.96-1.00). There was a significant difference in the total costs among different three algorithms WHO 1c/2/3 (F = 59.13, p < 0.01). No significant difference in the average costs for one active TB case screened and diagnosed through the process among Algorithms 1c/2/3 was evident (F = 2.78, p = 0.07). The average costs for one bacteriological positive case through algorithm WHO 1a was about two times as much as the costs for one active TB case through algorithms WHO 1c/2/3.Active case-finding based on the enhanced symptom screening is meaningful for TB case-finding and it could identify more active TB cases in time. The findings indicated that this enhanced screening approach cost more compared to algorithms recommend by WHO and China NTP, but the increased yield resulted in comparative costs per patient. And it cost much more that only smear/bacteriological-positive TB cases are screened in active case-finding.© 2021. The Author(s).

To compare two community screening tests for TB: sputum examination using Xpert MTB/RIF and chest radiography (CXR). Men aged ≥15 years and women aged >45 years living in 96 sub-communes in Ca Mau, Viet Nam, were invited to provide a single sputum specimen that was tested using Xpert. Participants were also invited to attend a nearby location for digital radiography. Participants whose sputum was Xpert MTB-positive or whose CXR was reported as 'consistent with TB´ were requested to provide two further sputum specimens for culture. The sensitivities of the two tests for detecting TB (defined as sputum culture-positive for ) were compared. There were 72 985 eligible participants, of whom 57 597 (78.9%) participated in Xpert screening, 12 752 (17.5%) had CXR and 11 235 (15.4%) had both tests. We estimated that there were 59 cases of TB, of whom 20 were Xpert MTB-positive (programmatic sensitivity 34.0%) and 47 had CXR reported as 'consistent with TB´ (sensitivity 80.0%, < 0.0001). In community-wide screening for TB, CXR is more sensitive than a single spontaneously expectorated sputum sample tested using Xpert, but it has a substantially lower participation rate.

There are no published data on the critical review of chest X-ray (CXR) findings of children in the context of community-based contact screening.To describe the quality, findings and inter-observer agreement of CXRs in child TB contacts in Indonesia.We performed antero-posterior (AP) and lateral CXR in children who had had close contact with a pulmonary TB case. The CXRs were interpreted independently by four reviewers.A total of 530 CXRs of 265 children were reviewed. Most (63%) of the children were asymptomatic at the time of CXR. Only 60% of the CXRs were reported as moderate to good quality by all reviewers, and inter-observer agreement on quality was slight to moderate (weighted κ = 0.16-0.35) for AP view. The majority of the CXRs were reported as normal (range 65-77%), with fair to moderate inter-observer agreement (κ = 0.25-0.46). Hilar lymphadenopathy (6-16%) was the most common CXR abnormality reported with poor inter-observer agreement (κ = -0.03 to 0.25).The CXRs of child TB contacts investigated in the community were characterised by low quality, low agreement and low yield. Our findings support guidelines that CXR is not routinely indicated in asymptomatic child TB contacts in this setting.

To determine interobserver agreement between paediatric radiologists interpreting tuberculosis (TB) screening chest radiographs (CXR) in children in the UK, and the TB detection rate.A retrospective review was undertaken of electronic request, notes, and CXRs (>7 years) in children exposed to an infectious case of TB and new entrants to the UK, at a tertiary children's hospital. Included were those with positive Mantoux/interferon gamma release assay (IGRA), positive culture, or high clinical suspicion of TB. CXR reports were categorised as normal, abnormal without features of TB, or abnormal with features of pulmonary TB. Three paediatric radiologists from a dedicated paediatric radiology department evaluated available CXRs, aware of the TB screening indication, using a published CXR reporting tool and blinded to the initial CXR report and to each other. A majority decision was collated, and considered lymphadenopathy and miliary nodules as diagnostic of primary TB. Interobserver agreement was calculated using Cohen's kappa.One hundred and forty-eight children underwent TB screening with a CXR. One hundred and twenty-five had available CXR reports and case notes, which indicated 20/125 (16%) had CXR features of TB. One hundred and twenty-one of the 125 had CXRs available to for panel review. Twenty of these 121 (17%) yielded a majority decision of pulmonary TB. Inter-reader agreement was moderate in all aspects (kappa 0.4-0.6).The high percentage of pulmonary TB on CXR (16% original reports; 17% by panel review) suggests that it is worthwhile investigating childhood TB contacts; however, the routine use and recommendation for CXR is questionable because of only moderate interpretation reliability (kappa 0.5), even by experts.Copyright © 2020 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Systematic screening for active pulmonary tuberculosis (PTB) is recommended for high-risk populations, including people living with the human immunodeficiency virus (PLHIV); however, currently recommended TB screening tools are inadequate for most high-burden settings.To determine whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active PTB.We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (10 mg/l cut-off point) for culture-positive PTB. Pooled diagnostic accuracy estimates were generated using random-effects meta-analysis for out-patients and in-patients, and for pre-specified subgroups based on HIV status and test indication.We identified nine unique studies enrolling 1793 adults from out-patient (five studies, 1121 patients) and in-patient settings (five studies, 672 patients), 72% of whom had confirmed HIV infection. Among out-patients, CRP had high sensitivity (93%, 95%CI 88-98) and moderate specificity (60%, 95%CI 40-75) for active PTB. Specificity was lowest among in-patients (21%, 95%CI 6-52) and highest among out-patients undergoing TB screening (range 58-81%). There was no difference in summary estimates by HIV status.CRP, which is available as a simple, inexpensive and point-of-care test, can be used to screen PLHIV presenting for routine HIV/AIDS (acquired immune-deficiency syndrome) care for active TB.

There is an urgent need for more accurate screening tests for tuberculosis(TB). We assessed the diagnostic accuracy of C-reactive protein (CRP) as a screening test for active TB in HIV-infected ambulatory adults.CRP levels were measured in blood collected at the time of HIV testing.Diagnostic accuracy of CRP for pulmonary TB was calculated (reference standard: TB culture), compared to the WHO 4-symptom screen, consisting of cough, fever, night sweats, and weight loss. Diagnostic accuracy was also calculated for CRP in a larger cohort of HIV-infected adults with a positive symptom screen (reference standard: clinical or microbiological TB).Among 425 HIV-infected outpatients systematically tested for pulmonary TB, TB culture was positive in 42 (10%), 279 (66%) had at least one TB-related symptom and 197 (46%) had a CRP more than 5 mg/l. The sensitivity of CRP and the TB symptom screen to detect TB was the same [90.5%; 95% confidence interval 77.4-97.3] but specificity of CRP was higher than for the TB symptom screen (58.5% vs. 37.1%, P < 0.001). Of persons with no symptoms and normal CRP, 99 (98%) had no TB. In another cohort of 749 patients presenting with at least one TB-related symptom and clinically evaluated, CRP had a sensitivity of 98.7% and specificity of 48.3%.In HIV-infected outpatients, CRP was as sensitive but substantially more specific than TB symptom screening. Use of CRP as a screening tool to exclude active TB could identify the same number of HIV-associated TB cases, but reduce the use of diagnostic sputum testing in TB-endemic regions.

Contact tracing is a key element in England's 2015 collaborative TB strategy, although proposed indicators of successful contact tracing remain undescribed.We conducted descriptive and multivariable analyses of contact tracing of TB cases in London between 1 July 2012 and 31 December 2015 using cohort review data from London's TB Register, identifying characteristics associated with improved indicators and yield.Of the pulmonary TB cases notified, 60% (2716/4561) had sufficient information for inclusion. Of these, 91% (2481/2716) had at least 1 contact (median: 4/case (IQR: 2-6)) identified, with 86% (10 251/11 981) of these contacts evaluated. 4.1% (177/4328), 1.3% (45/3421) and 0.70% (51/7264) of evaluated contacts of pulmonary smear-positive, pulmonary smear-negative and non-pulmonary cases, respectively, had active disease. Cases who were former prisoners or male were less likely to have at least one contact identified than those never imprisoned or female, respectively. Cases diagnosed at clinics with more directly observed therapy or social workers were more likely to have one or more contacts identified. Contacts screened at a different clinic to their index case or of male index cases were less likely to be evaluated than those screened at the same clinic or of women, respectively; yield of active disease was similar by sex. 10% (490/4850) of evaluated child contacts had latent TB infection.These are the first London-wide estimates of TB contact tracing indicators which are important for monitoring the strategy's success and informing risk assessment of index cases. Understanding why differences in indicators occur between groups could improve contact tracing outcomes.Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Contact investigation is an important and effective active case-finding strategy, but there is a lack of research on congregate settings in countries with an intermediate incidence. This study determined the incidence of and risk factors for tuberculosis (TB) development after exposure in congregate settings. This retrospective cohort study included 116,742 contacts identified during the investigation of 2,609 TB cases diagnosed from January to December 2015. We searched the Korean National Tuberculosis Surveillance System TB registry to identify contacts that developed active TB during follow-up until May 2018. During the mean observation period of 2.9 years, 499 of 116,742 contacts (0.4%) developed new active TB. From these contacts, 404 (81.0%) developed TB within 2 years after exposure. The 2-year Kaplan-Meier cumulative risk for TB was the highest in contacts aged ≥65 years [1%; 95% confidence interval (CI), 0.8-1.3]. Contacts with LTBI who completed chemoprophylaxis exhibited a lower risk of active TB development than those without chemoprophylaxis (adjusted hazard ratio, 0.16; 95% CI, 0.08-0.29). Aggressive contact investigation is effective for the early detection and prevention of TB in congregate settings. The risk of progression to active TB among contacts with LTBI can be minimised by the completion of chemoprophylaxis.

A recurrent tuberculosis (TB) episode results from exogenous reinfection or relapse after cure. The use of genotyping allows the distinction between both.We did a systematic review and meta-analysis, using four databases to search for studies in English, French and Spanish published between 1 January 1980 and 30 September 2020 that assessed recurrences after TB treatment success and/or differentiated relapses from reinfections using genotyping. We calculated person years of follow-up and performed random-effects model meta-analysis for estimating pooled recurrent TB incidence rates and proportions of relapses and reinfections. We performed subgroup analyses by clinical-epidemiological factors and by methodological study characteristics.The pooled recurrent TB incidence rate was 2.26 per 100 person years at risk (95% CI 1.87 to 2.73; 145 studies). Heterogeneity was high (I=98%). Stratified pooled recurrence rates increased from 1.47 (95% CI 0.87 to 2.46) to 4.10 (95% CI 2.67 to 6.28) per 100 person years for studies conducted in low versus high TB incidence settings. Background HIV prevalence, treatment drug regimen, sample size and duration of follow-up contributed too. The pooled proportion of relapses was 70% (95% CI 63% to 77%; I²=85%; 48 studies). Heterogeneity was determined by background TB incidence, as demonstrated by pooled proportions of 83% (95% CI 75% to 89%) versus 59% (95% CI 42% to 74%) relapse for studies from settings with low versus high TB incidence, respectively.The risk of recurrent TB is substantial and relapse is consistently the most frequent form of recurrence. Notwithstanding, with increasing background TB incidence the proportion of reinfections increases and the predominance of relapses among recurrences decreases.CRD42018077867.© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.

The resurgence of tuberculosis (TB) in western countries has been attributed to the HIV epidemic, immigration, and drug resistance. Multidrug resistant tuberculosis (MDR-TB) is caused by the transmission of multidrug resistant Mycobacterium tuberculosis strains in new cases, or by the selection of single drug resistant strains induced by previous treatment. The aim of this report is to determine risk factors for MDR-TB in Europe.A systematic review was conducted of published reports of risk factors associated with MDR-TB in Europe. Meta-analysis, meta-regression, and sub-grouping were used to pool risk estimates of MDR-TB and to analyse associations with age, sex, immigrant status, HIV status, occurrence year, study design, and area of Europe.Twenty nine papers were eligible for the review from 123 identified in the search. The pooled risk of MDR-TB was 10.23 times higher in previously treated than in never treated cases, with wide heterogeneity between studies. Study design and geographical area were associated with MDR-TB risk estimates in previously treated patients; the risk estimates were higher in cohort studies carried out in western Europe (RR 12.63; 95% CI 8.20 to 19.45) than in eastern Europe (RR 8.53; 95% CI 6.57 to 11.06). National estimates were possible for six countries. MDR-TB cases were more likely to be foreign born (odds ratio (OR) 2.46; 95% CI 1.86 to 3.24), younger than 65 years (OR 2.53; 95% CI 1.74 to 4.83), male (OR 1.38; 95% CI 1.16 to 1.65), and HIV positive (OR 3.52; 95% CI 2.48 to 5.01).Previous treatment was the strongest determinant of MDR-TB in Europe. Detailed study of the reasons for inadequate treatment could improve control strategies. The risk of MDR-TB in foreign born people needs to be re-evaluated, taking into account any previous treatment.

To investigate the extent to which relapse and other previously treated tuberculosis (TB) contribute to the notified TB burden in South Africa. We conducted an ecological analysis at the level of the 52 South African health districts using national electronic TB register data. We included all bacteriologically confirmed TB cases treated for presumed drug-susceptible TB in 2011. Treatment history information was based on recorded patient categories (new vs. retreatment). Relapse and other previously treated TB cases constituted between 7.6% and 40% (median 17%, interquartile range 12-22) of all bacteriologically confirmed TB cases in the 52 South African districts. Multivariable analysis suggested that districts with higher proportions of previously treated TB cases had higher TB case notification rates (< 0.001), lower estimates of antenatal human immunodeficiency virus (HIV) prevalence in the district population (< 0.001) as well as lower HIV co-infection rates (< 0.001) among new TB cases. Relapse and other previously treated TB cases contributed substantially to the notified TB burden in several South African health districts, particularly those with high case notification rates and lower antenatal HIV prevalence. Additional efforts to prevent TB among previously treated people, such as strengthening treatment monitoring and/or secondary preventive therapy, should be considered.

Tens of millions of children are exposed to Mycobacterium tuberculosis globally every year; however, there are no contemporary estimates of the risk of developing tuberculosis in exposed children. The effectiveness of contact investigations and preventive therapy remains poorly understood.In this systematic review and meta-analysis, we investigated the development of tuberculosis in children closely exposed to a tuberculosis case and followed for incident disease. We restricted our search to cohort studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase electronic databases. Individual-participant data and a pre-specified list of variables were requested from authors of all eligible studies. These included characteristics of the exposed child, the index case, and environmental characteristics. To be eligible for inclusion in the final analysis, a dataset needed to include: (1) individuals below 19 years of age; (2) follow-up for tuberculosis for a minimum of 6 months; (3) individuals with household or close exposure to an individual with tuberculosis; (4) information on the age and sex of the child; and (5) start and end follow-up dates. Studies assessing incident tuberculosis but without dates or time of follow-up were excluded. Our analysis had two primary aims: (1) estimating the risk of developing tuberculosis by time-period of follow-up, demographics (age, region), and clinical attributes (HIV, tuberculosis infection status, previous tuberculosis); and (2) estimating the effectiveness of preventive therapy and BCG vaccination on the risk of developing tuberculosis. We estimated the odds of prevalent tuberculosis with mixed-effects logistic models and estimated adjusted hazard ratios (HRs) for incident tuberculosis with mixed-effects Poisson regression models. The effectiveness of preventive therapy against incident tuberculosis was estimated through propensity score matching. The study protocol is registered with PROSPERO (CRD42018087022).In total, study groups from 46 cohort studies in 34 countries-29 (63%) prospective studies and 17 (37%) retrospective-agreed to share their data and were included in the final analysis. 137 647 tuberculosis-exposed children were evaluated at baseline and 130 512 children were followed for 429 538 person-years, during which 1299 prevalent and 999 incident tuberculosis cases were diagnosed. Children not receiving preventive therapy with a positive result for tuberculosis infection had significantly higher 2-year cumulative tuberculosis incidence than children with a negative result for tuberculosis infection, and this incidence was greatest among children below 5 years of age (19·0% [95% CI 8·4-37·4]). The effectiveness of preventive therapy was 63% (adjusted HR 0·37 [95% CI 0·30-0·47]) among all exposed children, and 91% (adjusted HR 0·09 [0·05-0·15]) among those with a positive result for tuberculosis infection. Among all children <5 years of age who developed tuberculosis, 83% were diagnosed within 90 days of the baseline visit.The risk of developing tuberculosis among exposed infants and young children is very high. Most cases occurred within weeks of contact investigation initiation and might not be preventable through prophylaxis. This suggests that alternative strategies for prevention are needed, such as earlier initiation of preventive therapy through rapid diagnosis of adult cases or community-wide screening approaches.National Institutes of Health.Copyright © 2020 Elsevier Ltd. All rights reserved.

Tuberculosis (TB) remains one of the world's most lethal infectious diseases. Preventive and control strategies among other high-risk groups, such as the elderly population, continues to be a challenge. Clinical features of TB in older adults may be atypical and confused with age-related diseases. Diagnosis and management of TB in the elderly person can be difficult; treatment can be associated with adverse drug reactions. This article reviews the current global epidemiology, pathogenesis, clinical characteristics, diagnosis, management, and prevention of Mycobacterium tuberculosis infection in community-dwelling and institutionalized aging adults.Copyright © 2016 Elsevier Inc. All rights reserved.

China is facing challenges of the shifting presentation of tuberculosis (TB) from younger to elderly due to an ageing population, longer life expectancy and reactivation disease. However, the burden of elderly TB and influence factors are not yet clear. To fill the gap, we generated a cohort study to measure the magnitude of TB incidence and associated factors among the elderly population aged 65 years and above in China.In this cohort established in 2013 through a prevalence survey conducted in selected sites, a total of 34 076 elderlies without TB were enrolled into two-year follow-up. We used both active and passive case findings to find out all TB patients among them. The person-year (PY) incidence rates for both bacteriologically positive TB and active TB were calculated. Cox proportional regression model was performed to test effect of risk factors, and the population attributable fraction (PAF) of each risk factor contributing to incident TB among elderlies was calculated.Over the two-year follow-up period, a total of 215 incident active TB were identified, 62 of which were bacteriologically positive. The incidence rates for active TB and bacteriologically positive TB were 481.8 per 100 000 PY (95% CI: 417.4-546.2 per 100 000 PY) and 138.9 per 100 000 PY (95% CI: 104.4-173.5 per 100 000 PY), respectively. Incident cases detected by active case finding were significantly higher (P < 0.001). Male, non-Han nationality, previously treated TB, ex/current smoker and body mass index (BMI) < 18.5 presented as independent predictors for developing TB disease. For developing bacteriologically positive TB, the biggest contribution was from self-reported ex or current smoker (18.06%). And, for developing active TB, the biggest contribution was from non-Han nationality (35.40%), followed by male (26.80%) and age at 75 years and above (10.85%).Ageing population in China had a high TB incidence rate and risk to develop TB disease, implying that National TB Program (NTP) needs to prioritize for elderly. Active case finding should be applied capture more active TB cases among this particular population, especially for male, non-Han nationality, and those with identified risk factors.

To assess the feasibility and results of screening of patients with DM for TB in routine community health services in China.Agreement on how to screen patients with DM for TB and monitor and record the results was obtained at a stakeholders meeting. Subsequent training was carried out for staff at 10 community health centres, with activities implemented from June 2013 to April 2014. Patients with DM were screened for TB at each clinical visit using a symptom-based enquiry, and those positive to any symptom were referred to the TB clinic for TB investigation.A total of 2942 patients with DM visited these ten clinics. All patients received at least one screening for TB. Two patients were identified as already known to have TB. In total, 278 (9.5% of those screened) who had positive TB symptoms were referred for TB investigations and 209 arrived at the TB centre or underwent a chest radiograph for TB investigation. One patient (0.5% of those investigated) was newly diagnosed with active TB and was started on anti-TB treatment. The TB case notification rate of those screened was 102/100,000.This pilot project shows it is feasible to carry out TB screening among patients with DM in community settings, but further work is needed to better characterise patients with DM at higher risk of TB. This may require a more targeted approach focused on high-risk groups such as those with untreated DM or poorly controlled hyperglycaemia.© 2015 John Wiley & Sons Ltd.

To assess the yield of finding additional TB or diabetes mellitus (DM) cases through systematic screening and to determine the effectiveness of preventive TB therapy in people with DM.We systematically reviewed studies that had screened for active TB or implemented preventive therapy for TB among people with DM, and those that screened for DM among patients with TB. We searched published literature through PubMed and EMBASE and included studies that reported the number of TB cases identified among people with DM; the number of DM cases identified among patients with TB, or the relative incidence of TB between people with DM who received a TB prophylaxis and those who did not. We assessed the yield of screening by estimating the prevalence of TB or DM in each study, the prevalence ratio and difference where comparison populations were available, and the number of persons to screen to detect an additional case of TB or DM.Twelve studies on screening for TB in people with DM and 18 studies on screening for DM in patients with TB met our inclusion criteria. Screening for TB in persons with DM demonstrated that TB prevalence in this population is high, ranging from 1.7% to 36%, and increasing with rising TB prevalence in the underlying population as well as with DM severity. Screening patients with TB for DM also yielded high prevalences of DM ranging from 1.9% to 35%. Two studies examining the role of TB preventive therapy in people with DM did not provide sufficient details for clear evidence of the effectiveness.Active screening leads to the detection of more TB and DM with varying yield. This review highlights the need for further research in screening and preventive therapy.© 2010 Blackwell Publishing Ltd.