Bacteriologically-confirmed Tuberculosis Research Articles

Iterative evaluation of mobile computer-assisted digital chest x-ray screening for TB improves efficiency, yield, and outcomes in Nigeria.

Wellness on Wheels (WoW) is a model of mobile systematic tuberculosis (TB) screening of high-risk populations combining digital chest radiography with computer-aided automated detection (CAD) and chronic cough screening to identify presumptive TB clients in communities, health facilities, and prisons in Nigeria. The model evolves to address technical, political, and sustainability challenges. Screening methods were iteratively refined to balance TB yield and feasibility across heterogeneous populations. Performance metrics were compared over time. Screening volumes, risk mix, number needed to screen (NNS), number needed to test (NNT), sample loss, TB treatment initiation and outcomes. Efforts to mitigate losses along the diagnostic cascade were tracked. Persons with high CAD4TB score (≥80), who tested negative on a single spot GeneXpert were followed-up to assess TB status at six months. An experimental calibration method achieved a viable CAD threshold for testing. High risk groups and key stakeholders were engaged. Operations evolved in real time to fix problems. Incremental improvements in mean client volumes (128 to 140/day), target group inclusion (92% to 93%), on-site testing (84% to 86%), TB treatment initiation (87% to 91%), and TB treatment success (71% to 85%) were recorded. Attention to those as highest risk boosted efficiency (the NNT declined from 8.2 ± SD8.2 to 7.6 ± SD7.7). Clinical diagnosis was added after follow-up among those with ≥ 80 CAD scores and initially spot -sputum negative found 11 additional TB cases (6.3%) after 121 person-years of follow-up. Iterative adaptation in response to performance metrics foster feasible, acceptable, and efficient TB case-finding in Nigeria. High CAD scores can identify subclinical TB and those at risk of progression to bacteriologically-confirmed TB disease in the near term.

Deep learning and radiomics of longitudinal CT scans for early prediction of tuberculosis treatment outcomes

BackgroundTo predict tuberculosis (TB) treatment outcomes at an early stage, prevent poor outcomes ofdrug-resistant tuberculosis(DR-TB) and interrupt transmission. MethodsAn internal cohort for model development consists of 204 bacteriologically-confirmed TB patients who completed anti-tuberculosis treatment, with one pretreatment and two follow-up CT images (612 scans). Three radiomics feature-based models (RM) with multiple classifiers of Bagging, Random forest and Gradient boosting and two deep-learning-based models (i.e., supervised deep-learning model, SDLM; weakly supervised deep-learning model, WSDLM) are developed independently. Prediction scores of RM and deep-learning models with respectively highest performance are fused to create new fusion models under different fusion strategies. An additional independent validation was conducted on the external cohort comprising 80 patients (160 scans). ResultsFor RM scheme, 16 optimal radiomics features are finally selected using longitudinal scans. The AUCs of RM for Bagging, Random forest and Gradient boosting were 0.789, 0.773 and 0.764 in the internal cohort and 0.840, 0.834 and 0.816 in the external cohort, respectively. For deep learning-based scheme, AUCs of SDLM and WSDLM were 0.767 and 0.661 in the internal cohort, and 0.823 and 0.651 in the external. The fusion model yields AUCs from 0.767 to 0.802 in the internal cohort, and from 0.831 to 0.857 in the external cohort. ConclusionsFusion of radiomics features and deep-learning model may have the potential to predict early failure outcome of DR-TB, which may be combined to help prevent poor TB treatment outcomes.

Prevalence of bacteriologically-confirmed pulmonary tuberculosis in urban Blantyre, Malawi 2019-20: Substantial decline compared to 2013-14 national survey.

Recent evidence shows rapidly changing tuberculosis (TB) epidemiology in Southern and Eastern Africa, with need for subdistrict prevalence estimates to guide targeted interventions. We conducted a pulmonary TB prevalence survey to estimate current TB burden in Blantyre city, Malawi. From May 2019 to March 2020, 115 households in middle/high-density residential Blantyre, were randomly-selected from each of 72 clusters. Consenting eligible participants (household residents ≥ 18 years) were interviewed, including for cough (any duration), and offered HIV testing and chest X-ray; participants with cough and/or abnormal X-ray provided two sputum samples for microscopy, Xpert MTB/Rif and mycobacterial culture. TB disease prevalence and risk factors for prevalent TB were calculated using complete-case analysis, multiple imputation, and inverse probability weighting. Of 20,899 eligible adults, 15,897 (76%) were interviewed, 13,490/15,897 (85%) had X-ray, and 1,120/1,394 (80%) sputum-eligible participants produced at least one specimen, giving 15,318 complete cases (5,895, 38% men). 29/15,318 had bacteriologically-confirmed TB (189 per 100,000 complete-case (cc) / 150 per 100,000 with inverse weighting (iw)). Men had higher burden (cc: 305 [95% CI:144-645] per 100,000) than women (cc: 117 [95% CI:65-211] per 100,000): cc adjusted odds ratio (aOR) 2.70 (1.26-5.78). Other significant risk factors for prevalent TB on complete-case analysis were working age (25-49 years) and previous TB treatment, but not HIV status. Multivariable analysis of imputed data was limited by small numbers, but previous TB and age group 25-49 years remained significantly associated with higher TB prevalence. Pulmonary TB prevalence for Blantyre was considerably lower than the 1,014 per 100,000 for urban Malawi in the 2013-14 national survey, at 150-189 per 100,000 adults, but some groups, notably men, remain disproportionately affected. TB case-finding is still needed for TB elimination in Blantyre, and similar urban centres, but should focus on reaching the highest risk groups, such as older men.

Where are the missing people affected by tuberculosis? A programme review of patient-pathway and cascade of care to optimise tuberculosis case-finding, treatment and prevention in Cambodia

BackgroundCambodia has achieved great success in tuberculosis (TB) control in the past decade. Nevertheless, people with TB are missed by the health systems at different stages of the care pathway....

Accuracy of computer-aided chest X-ray in community-based tuberculosis screening: Lessons from the 2016 Kenya National Tuberculosis Prevalence Survey.

Community-based screening for tuberculosis (TB) could improve detection but is resource intensive. We set out to evaluate the accuracy of computer-aided TB screening using digital chest X-ray (CXR) to determine if this approach met target product profiles (TPP) for community-based screening. CXR images from participants in the 2016 Kenya National TB Prevalence Survey were evaluated using CAD4TBv6 (Delft Imaging), giving a probabilistic score for pulmonary TB ranging from 0 (low probability) to 99 (high probability). We constructed a Bayesian latent class model to estimate the accuracy of CAD4TBv6 screening compared to bacteriologically-confirmed TB across CAD4TBv6 threshold cut-offs, incorporating data on Clinical Officer CXR interpretation, participant demographics (age, sex, TB symptoms, previous TB history), and sputum results. We compared model-estimated sensitivity and specificity of CAD4TBv6 to optimum and minimum TPPs. Of 63,050 prevalence survey participants, 61,848 (98%) had analysable CXR images, and 8,966 (14.5%) underwent sputum bacteriological testing; 298 had bacteriologically-confirmed pulmonary TB. Median CAD4TBv6 scores for participants with bacteriologically-confirmed TB were significantly higher (72, IQR: 58-82.75) compared to participants with bacteriologically-negative sputum results (49, IQR: 44-57, p<0.0001). CAD4TBv6 met the optimum TPP; with the threshold set to achieve a mean sensitivity of 95% (optimum TPP), specificity was 83.3%, (95% credible interval [CrI]: 83.0%-83.7%, CAD4TBv6 threshold: 55). There was considerable variation in accuracy by participant characteristics, with older individuals and those with previous TB having lowest specificity. CAD4TBv6 met the optimal TPP for TB community screening. To optimise screening accuracy and efficiency of confirmatory sputum testing, we recommend that an adaptive approach to threshold setting is adopted based on participant characteristics.

Neighbourhood prevalence-to-notification ratios for adult bacteriologically-confirmed tuberculosis reveals hotspots of underdiagnosis in Blantyre, Malawi.

Local information is needed to guide targeted interventions for respiratory infections such as tuberculosis (TB). Case notification rates (CNRs) are readily available, but systematically underestimate true disease burden in neighbourhoods with high diagnostic access barriers. We explored a novel approach, adjusting CNRs for under-notification (P:N ratio) using neighbourhood-level predictors of TB prevalence-to-notification ratios. We analysed data from 1) a citywide routine TB surveillance system including geolocation, confirmatory mycobacteriology, and clinical and demographic characteristics of all registering TB patients in Blantyre, Malawi during 2015-19, and 2) an adult TB prevalence survey done in 2019. In the prevalence survey, consenting adults from randomly selected households in 72 neighbourhoods had symptom-plus-chest X-ray screening, confirmed with sputum smear microscopy, Xpert MTB/Rif and culture. Bayesian multilevel models were used to estimate adjusted neighbourhood prevalence-to-notification ratios, based on summarised posterior draws from fitted adult bacteriologically-confirmed TB CNRs and prevalence. From 2015-19, adult bacteriologically-confirmed CNRs were 131 (479/371,834), 134 (539/415,226), 114 (519/463,707), 56 (283/517,860) and 46 (258/578,377) per 100,000 adults per annum, and 2019 bacteriologically-confirmed prevalence was 215 (29/13,490) per 100,000 adults. Lower educational achievement by household head and neighbourhood distance to TB clinic was negatively associated with CNRs. The mean neighbourhood P:N ratio was 4.49 (95% credible interval [CrI]: 0.98-11.91), consistent with underdiagnosis of TB, and was most pronounced in informal peri-urban neighbourhoods. Here we have demonstrated a method for the identification of neighbourhoods with high levels of under-diagnosis of TB without the requirement for a prevalence survey; this is important since prevalence surveys are expensive and logistically challenging. If confirmed, this approach may support more efficient and effective targeting of intensified TB and HIV case-finding interventions aiming to accelerate elimination of urban TB.

Spatially targeted digital chest radiography to reduce tuberculosis in high-burden settings: A study of adaptive decision making

BackgroundSpatially-targeted approaches to screen for tuberculosis (TB) could accelerate TB control in high-burden populations. We aimed to estimate gains in case-finding yield under an adaptive decision-making approach for spatially-targeted, mobile digital chest radiography (dCXR)-based screening in communities with varying levels of TB prevalence. MethodsWe used a Monte-Carlo simulation model to simulate a spatially-targeted screening intervention in 24 communities with TB prevalence estimates derived from a large community-randomized trial. We implemented a Thompson sampling algorithm to allocate screening units based on Bayesian probabilities of local TB prevalence that are continuously updated during weekly screening rounds. Four mobile units for dCXR-based screening and subsequent Xpert Ultra-based testing were allocated among the communities during a 52-week period. We estimated the yield of bacteriologically-confirmed TB per 1000 screenings comparing scenarios of spatially-targeted and untargeted resource allocation. ResultsWe estimated that under the untargeted scenario, an expected 666 (95% uncertainty interval 522–825) TB cases would be detected over one year, equivalent to 8.9 (7.5–10.3) per 1000 individuals screened. Allocating the screening units to the communities with the highest (prior-year) cases notification rates resulted in an expected 760 (617−926) TB cases detected, 10.1 (8.6–11.8) per 1000 screened. Adaptive, spatially-targeted screening resulted in an expected 1241 (995–1502) TB cases detected, 16.5 (14.5–18.7) per 1000 screened. Numbers of dCXR-based screenings needed to detect one additional TB case declined during the first 12–14 weeks as a result of Bayesian learning. ConclusionWe introduce a spatially-targeted screening strategy that could reduce the number of screenings necessary to detect additional TB in high-burden settings and thus improve the efficiency of screening interventions. Empirical trials are needed to determine whether this approach could be successfully implemented.

Tuberculosis prevalence and associated factors among persons with diabetes mellitus after intensified case finding in three West African countries.

BackgroundTo determine the prevalence of tuberculosis (TB) and associated factors in persons with diabetes mellitus (DM) in Benin, Guinea and Senegal.Patients and MethodA cross-sectional study was conducted in the largest DM center in each country. Participants systematically underwent clinical screening and chest radiography. Participants who were symptomatic or with abnormal radiography underwent bacteriological investigations (sputum smear, Xpert MTB/RIF and culture) on sputum. Participants with no TB at enrolment were re-examined for TB six months later. Logistic regression was performed to identify factors associated with TB.ResultsThere were 5,870 DM patients: 1,881 (32.0%) in Benin, 1,912 (32.6%) in Guinea and 2,077 (35.4%) in Senegal. Out of these, 114 had bacteriologically-confirmed TB, giving a pooled prevalence of 1.9% (95%CI=1.6-2.3). TB prevalence was 0.5% (95%CI=0.3-1.0), 2.4% (95%CI=1.8-3.2) and 2.8% (95%CI=2.2-3.6), respectively, in Benin, Guinea and Senegal. Factors associated with an increased odds of TB diagnosis were a usual residence in Guinea (aOR=2.62;95%CI=1.19-5.77; p=0.016) or in Senegal (aOR=3.73;95%CI=1.85-7.51; p<0.001), the age group of 35-49 years (aOR=2.30;95%CI=1.11-4.79; p=0.025), underweight (aOR=7.34;95%CI=4.65-11.57; p<0.001) and close contact with a TB case (aOR=2.27;95%CI=1.37-3.76; p=0.002). Obesity was associated with lower odds of TB (aOR=0.20; 95%CI=0.06-0.65; p=0.008).ConclusionTB is prevalent among DM patients in Benin, Guinea and Senegal and higher than among the general population. The findings support the need for intensified case finding in DM patients in order to ensure systematic early detection of TB during the routine consultation process.

Standard dose raltegravir or efavirenz-based antiretroviral treatment for patients co-infected with HIV and tuberculosis (ANRS 12 300 Reflate TB 2): an open-label, non-inferiority, randomised, phase 3 trial

In patients co-infected with HIV and tuberculosis, antiretroviral therapy options are limited due to drug-drug interactions with rifampicin. A previous phase 2 trial indicated that raltegravir 400 mg twice a day or efavirenz 600 mg once a day might have similar virological efficacy in patients given rifampicin. In this phase 3 trial, we assessed the non-inferiority of raltegravir to efavirenz. We did a multicentre, open-label, non-inferiority, randomised, phase 3 trial at six sites in Côte d'Ivoire, Brazil, France, Mozambique, and Vietnam. We included antiretroviral therapy (ART)-naive adults (aged ≥18 years) with confirmed HIV-1 infection and bacteriologically confirmed or clinically diagnosed tuberculosis who had initiated rifampicin-containing tuberculosis treatment within the past 8 weeks. Using computerised random numbers, we randomly assigned participants (1:1; stratified by country) to receive raltegravir 400 mg twice daily or efavirenz 600 mg once daily, both in combination with tenofovir and lamivudine. The primary outcome was the proportion of patients with virological suppression at week 48 (defined as plasma HIV RNA concentration <50 copies per mL). The prespecified non-inferiority margin was 12%. The primary outcome was assessed in the intention-to-treat population, which included all randomly assigned patients (excluding two patients with HIV-2 infection and one patient with HIV-1 RNA concentration of <50 copies per mL at inclusion), and the on-treatment population, which included all patients in the intention-to-treat population who initiated treatment and were continuing allocated treatment at week 48, and patients who had discontinued allocated treatment due to death or virological failure. Safety was assessed in all patients who received at least one dose of the assigned treatment regimen. This study is registered with ClinicalTrials.gov, NCT02273765. Between Sept 28, 2015, and Jan 5, 2018, 460 participants were randomly assigned to raltegravir (n=230) or efavirenz (n=230), of whom 457 patients (230 patients in the raltegravir group; 227 patients in the efavirenz group) were included in the intention-to-treat analysis and 410 (206 patients in the raltegravir group; 204 patients in the efavirenz group) in the on-treatment analysis. At baseline, the median CD4 count was 103 cells per μL and median plasma HIV RNA concentration was 5·5 log10 copies per mL (IQR 5·0-5·8). 310 (68%) of 457 participants had bacteriologically-confirmed tuberculosis. In the intention-to-treat population, at week 48, 140 (61%) of 230 participants in the raltegravir group and 150 (66%) of 227 patients in the efavirenz had achieved virological suppression (between-group difference -5·2% [95% CI -14·0 to 3·6]), thus raltegravir did not meet the predefined criterion for non-inferiority. The most frequent adverse events were HIV-associated non-AIDS illnesses (eight [3%] of 229 patients in the raltegravir group; 21 [9%] of 230 patients in the efavirenz group) and AIDS-defining illnesses (ten [4%] patients in the raltegravir group; 13 [6%] patients in the efavirenz group). 58 (25%) of 229 patients in raltegravir group and 66 (29%) of 230 patients in the efavirenz group had grade 3 or 4 adverse events. 26 (6%) of 457 patients died during follow-up: 14 in the efavirenz group and 12 in the raltegravir group. In patients with HIV given tuberculosis treatment, non-inferiority of raltegravir compared with efavirenz was not shown. Raltegravir was well tolerated and could be considered as an option, but only in selected patients. National French Agency for AIDS Research, Ministry of Health in Brazil, Merck. For the Portuguese and French translations of the abstract see Supplementary Materials section.

Molecular Detection of Mycobacterium tuberculosis in Oral Mucosa from Patients with Presumptive Tuberculosis.

Tuberculosis (TB) diagnosis is increasingly based on the detection of Mycobacterium tuberculosis complex (MTBC) DNA in sputum using molecular diagnostic tests as the first test for diagnosis. However, sputum can be difficult to obtain in children, patients without productive cough, and the elderly and approaches testing non-sputum samples are needed. We evaluated whether TB can be detected from the oral mucosa of patients with TB. Adults with presumptive TB were examined using culture, Xpert MTB/RIF, smear microscopy and X-Rays. Oral mucosa swabs collected on PrimeStore-MTM, stored at room temperature if tested within 30 days or at −20 °C if examined at a later time. RT-PCR was performed to detect M. tuberculosis DNA. Eighty patients had bacteriologically-confirmed TB, 34 had bacteriologically-negative TB (negative tests but abnormal X-rays) and 152 were considered not to have TB (not TB). Oral swabs RT-PCR were positive in 29/80 (36.3%) bacteriologically-confirmed, 9/34 (26.5%) bacteriologically-negative and 29/152 (19.1%) not TB. The yield varied among samples stored for less and more than 30 days (p = 0.013) from 61% (11/18) and 29% (18/62) among bacteriologically confirmed, and 30.8% (4/13) and 23.8% (5/21) among bacteriologically-negative participants. Among not TB patients, the specificity was 80.9% (123/152), being 78.3% (18/23) among samples stored less than 30 days and 81.4% (105/129) among samples stored for more than 30 days (p = 0.46). The detection of M. tuberculosis in oral mucosa samples is feasible, but storage conditions may affect the yield.

Active tuberculosis risk associated with malignancies: an 18-year retrospective cohort study in Korea

BackgroundActive tuberculosis (TB) develops in approximately 10% of people with a latent tuberculosis infection (LTBI). TB guidelines recommend that LTBI screening and treatments target high-risk patients. Malignancies are not universally considered a high-risk factor for active TB. This study aimed to determine the degrees to which active TB risk was associated with various cancers in a Korean population.MethodsThis study involved patients aged ≥20 years who were diagnosed with cancer at Ulsan University Hospital (UUH) from January 2000 to December 2014 and individuals who visited UUH for health screening and were age- and sex-matched randomly with cases in a 1:2 ratio. Using retrospective cohort study, the development of bacteriologically confirmed TB (BCTB) within 3 years after enrollment was investigated. The relative risks of BCTB were estimated using incidence rate ratios (IRRs) and a Poisson regression analysis.ResultsDuring the study period, 380 of 34,783 cancer patients and 79 of 69,566 control subjects developed BCTB, yielding respective incidence rates of 535 and 37/100,000 person-years, respectively. In all cancer cases, the IRR of BCTB was 14.30, and especially high rates were associated with the following cancers: esophageal cancer (74.72), multiple myeloma (70.76), lung cancer (50.35), pancreatic cancer (46.04), leukemia (40.45), head and neck cancer (24.60), and lymphoma (22.67).ConclusionsThe incidence of active TB was higher in cancer patients than in control subjects. In particular, lung cancer, esophageal cancer, pancreatic cancer, hematologic malignancy and head and neck cancer were identified as high-risk factors for active TB, as indicated by IRRs of 20-75. These findings suggest that patients with high-risk cancers should be targeted for LTBI screening and treatment.

Detection of spleen abscesses facilitates diagnosis of melioidosis in Malaysian children

ObjectivesMelioidosis is associated with extremely high case fatality ratios. The aim of this study was to determine whether detection of abdominal visceral abscesses can facilitate diagnosis of melioidosis in children. MethodsWe conducted a retrospective analysis of all children who had liver and/or spleen abscesses on abdominal ultrasonography admitted to Bintulu Hospital in Sarawak, Malaysia, from January 2014 until December 2018. ResultsFifty-three children had liver and/or spleen abscesses. Spleen abscesses were present in 48 (91%) cases; liver abscesses in 15 (28%). Melioidosis was confirmed by culture in 9 (17%) children; small occult splenic abscesses were present in all cases. In 78% of these cases, the lesions were detected before any positive culture (or serology) results were available. Four (8%) children had bacteriologically-confirmed tuberculosis. Two (4%) had Staphylococcus aureus infection. Of the remaining 38 (72%) culture-negative cases, 36 (95%) had clinical and imaging characteristics similar to that of children with culture-confirmed melioidosis and improved with empirical melioidosis antibiotic therapy. ConclusionsA large number of children in Bintulu Hospital in Sarawak, Malaysia, were found to have spleen abscesses. Melioidosis was the most common etiology identified in these children. Abdominal ultrasonography is extremely useful in facilitating the diagnosis of pediatric melioidosis.

Performance of metabonomic serum analysis for diagnostics in paediatric tuberculosis

We applied a metabonomic strategy to identify host biomarkers in serum to diagnose paediatric tuberculosis (TB) disease. 112 symptomatic children with presumptive TB were recruited in The Gambia and classified as bacteriologically-confirmed TB, clinically diagnosed TB, or other diseases. Sera were analysed using 1H nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS). Multivariate data analysis was used to distinguish patients with TB from other diseases. Diagnostic accuracy was evaluated using Receiver Operating Characteristic (ROC) curves. Model performance was tested in a validation cohort of 36 children from the UK. Data acquired using 1H NMR demonstrated a sensitivity, specificity and Area Under the Curve (AUC) of 69% (95% confidence interval [CI], 56–73%), 83% (95% CI, 73–93%), and 0.78 respectively, and correctly classified 20% of the validation cohort from the UK. The most discriminatory MS data showed a sensitivity of 67% (95% CI, 60–71%), specificity of 86% (95% CI, 75–93%) and an AUC of 0.78, correctly classifying 83% of the validation cohort. Amongst children with presumptive TB, metabolic profiling of sera distinguished bacteriologically-confirmed and clinical TB from other diseases. This novel approach yielded a diagnostic performance for paediatric TB comparable to that of Xpert MTB/RIF and interferon gamma release assays.

Pre-treatment loss to follow-up and treatment delay among bacteriologically-confirmed tuberculosis patients diagnosed in Mandalay Region, Myanmar

BackgroundPre-treatment loss to follow-up (PTLFU) among tuberculosis (TB) patients is a global public health problem, because such patients are highly infectious and experience high mortality. There is no published evidence on this issue from Myanmar.ObjectiveTo determine PTLFU and treatment delays (> 7 days duration between the date of diagnosis and starting anti-TB treatment) and their associated demographic, clinical, and health system-related factors among bacteriologically confirmed (sputum smear-positive and/or Xpert-positive) TB patients diagnosed in public health facilities of the Mandalay Region between January and June 2017.MethodThis was a cohort study involving secondary analysis of routine programme data. Every bacteriologically confirmed TB patient in the laboratory register was tracked for at least 3 months in the treatment register. Patients neither found in the treatment register nor referred out for treatment were considered PTLFU.ResultsOf the 1365 bacteriologically confirmed patients diagnosed, 1051 (77%) started on anti-TB treatment, 200 (15.6%) were referred for treatment to health facilities outside the study area, and 114 (8.4%, 95% CI 7.0%–9.9%) did not initiate anti-TB treatment (PTLFU). PTLFU was significantly higher in those with TB/HIV co-infected (18%), sputum smear-negative but Xpert MTB-positive patients (31%), and patients diagnosed at a moderate- or high-volume facility (> 50 patients tested form TB during the study period) (~ 10%). Of the 940 patients with dates recorded, 46 (5%) had a treatment delay of more than 7 days. Patients aged 45–64 years had higher risk of treatment delay compared to those aged 15–44 years. About 97% of records did not have a phone number recorded.ConclusionPTLFU and treatment delay were relatively low in the Mandalay Region. While this is reassuring, urgent steps must be taken to address those that are lost, which includes improving documentation of phone numbers to improve ‘trackability’, instituting proactive measures to trace patients lost in the care pathway, and introducing an indicator in the national tuberculosis programme (NTP) monthly report to monitor and review PTLFU. Patient subgroups with higher PTLFU should receive priority attention.

Population-Based Tuberculosis Disease Prevalence Survey in Ghana: The Role and Lessons Learnt from the Laboratory

Background: Bacteriologically-confirmed tuberculosis (TB) cases used in calculating TB prevalence in a country are obtained through laboratory examination of sputum specimens. Objective: This article describes laboratory processing of specimens, results overview, conclusions and key lessons learnt from the perspective of laboratory personnel involved in the conduct of TB disease prevalence survey in Ghana in 2013. Methods: Symptoms screening and Chest X-ray suggestive of TB were used to select participants who produced sputum to confirm TB cases using microscopy, culture and Xpert® MTB/RIF assay (GeneXpert). Results: A total of 15,935 single and paired sputum specimens were received from eligible participants. About half of Ziehl-Nielsen (129/263) and Auramine O (122/246) stained smear positives were scanty positive. Culture positivity rate for Mycobacterium tuberculosis complex was 266/14,994 (1.7%) and 100/15,179 (0.7%) in Mycobacterial Growth Indicator Tube (MGIT) and Lowenstein-Jensen (LJ) media respectively; while non-tuberculous mycobacterium was 294/14,994 (1.96%) and 167/15,179 (1.1%). Total contamination rates in MGIT (5.4%) were higher than in LJ (1.7%). Prevalence of smear positive TB and bacteriologically confirmed TB among adult population (≥15 years) was estimated at 111 (95% CI: 76 - 145) and 356 (95% CI: 288 - 425) per 100,000 population respectively. Conclusions and Lessons Learnt: Direct supervision of specimen collection by well-trained laboratory personnel, timely transportation of specimens from field to laboratory, prompt specimen processing and use of electronic data management systems are essential for a reliable TB disease prevalence survey data. More importantly, strengthening human and logistical capacity of the laboratory must be of utmost priority.

Yield of household contact tracing for tuberculosis in rural South Africa

BackgroundEfficient and effective strategies for identifying cases of active tuberculosis (TB) in rural sub-Saharan Africa are lacking. Household contact tracing offers a potential approach to diagnose more TB cases, and to do so earlier in the disease course.MethodsAdults newly diagnosed with active TB were recruited from public clinics in Vhembe District, South Africa. Study staff visited index case households and collected sputum specimens for TB testing via smear microscopy and culture. We calculated the yield and the number of households needed to screen (NHNS) to find one additional case. Predictors of new TB among household contacts were evaluated using multilevel logistic regression.ResultsWe recruited 130 index cases and 282 household contacts. We identified 11 previously undiagnosed cases of bacteriologically-confirmed TB, giving a prevalence of 3.9% (95% CI: 2.0–6.9%) among contacts, a yield of 8.5 per 100 (95% CI: 4.2–15.1) index cases traced, and NHNS of 12 (95% CI: 7–24). The majority of new TB cases (10/11, 90.9%) were smear negative, culture positive. The presence of TB symptoms was not associated with an increased odds of active TB (aOR: 0.3, 95% CI: 0.1–1.4).ConclusionsHousehold contacts of recently diagnosed TB patients in rural South Africa have high prevalence of TB and can be feasibly detected through contact tracing, but more sensitive tests than sputum smear are required. Symptom screening among household contacts had low sensitivity and specificity for active TB in this study.

Detection of Apparent Cell-free M. tuberculosis DNA from Plasma

New diagnostics are needed to improve clinicians’ ability to detect tuberculosis (TB) disease in key populations such as children and persons living with HIV and to rapidly detect drug resistance. Circulating cell-free DNA (ccfDNA) in plasma is a diagnostic target in new obstetric and oncologic applications, but its utility for diagnosing TB is not known. Here we show that Mycobacterium tuberculosis complex DNA can be detected in plasma of persons with sputum smear-positive TB, even in the absence of mycobacteremia. Among 40 participants with bacteriologically-confirmed smear-positive TB disease who had plasma tested by quantitative PCR (qPCR), 18/40 (45%) had a positive result on at least one triplicate reaction. Our results suggest that plasma DNA may be a useful target for improving clinicians’ ability to diagnose TB. We anticipate these findings to be the starting point for optimized methods of TB ccfDNA testing and sequence-based diagnostic applications such as molecular detection of drug resistance.

Prevalence and Incidence of Smear-Positive Pulmonary Tuberculosis in the Hetosa District of Arsi Zone, Oromia Regional State of Central Ethiopia

BackgroundThe real burden of smear-positive (PTB+) and bacteriologically confirmed tuberculosis (BCTB) in Ethiopia is not known. Thus, the aim of this community-based study was to measure the prevalence and incidence of tuberculosis in the Hetosa District of Oromia Region, Ethiopia.MethodsFirst, a population-based cross-sectional survey was conducted on a total of 33,073 individuals aged ≥ 15 years to determine the prevalence of PTB+ and BCTB cases. Then, in order to determine the incidence, a prospective follow-up was carried out on 32,800 individuals found to be either free from symptoms suggestive of TB (SSTB) during the baseline survey or had symptoms suggestive of TB but yielded negative bacteriological examination results. We identified 1,041 presumptive TB cases at the baseline survey, and 1,468 in the follow-up study. Each participants with cough of more than two weeks were provided spot and morning sputum samples for acid-fast bacilli sputum microscopy and culture.ResultsAt the baseline survey, 43 BCTB cases were identified. Thirty six of these were both smear- and culture-positive while seven were only culture-positive. In the follow-up study, however, 76 BCTB cases were diagnosed and 70 of these were found to be both smear- and culture-positive while six were culture-positive only. The adjusted prevalence of PTB+ and BCTB in the study area was 109 and 132/100,000 persons, respectively. Moreover, the incidences of PTB+ and BCTB were 214 and 232/100,000 persons per year (py), respectively. The ratio of the passive to active case finding was 1:0.96 (45/43). For every TB case identified through the existing passive case diagnosis, there was an almost equal number (0.96) of undiagnosed infectious TB cases in the community. A family history of TB contact was independently associated with a high risk of TB (TB prevalence, AOR, 13; 95% CI: 6.55–15.33) and (TB incidence, aIRR 4.11, 95% CI: 2.18–7.77).Conclusions and recommendationsThe prevalence and incidence of smear-positive and bacteriologically confirmed TB cases were high in the study area. For every case of smear-positive TB receiving treatment, there was an almost equal (0.96) number of undetected infectious bacteriologically confirmed TB case in the community. The high proportion of undetected infectious TB cases in the community could possibly be due to the sub-optimal performance of Directly Observed Treatment Short-course (DOTS) in detecting 70% of infectious TB cases, as well as attaining a cure rate of 85% in the study area. Family history of TB contact has substantaially increased the risk of developing the disease, and there is a need to improve ways of identifying TB cases and intensify mechanisms of tracing contacts among household members of PTB+ cases.

Demographic and microbial characteristics of extrapulmonary tuberculosis cases diagnosed in Malatya, Turkey, 2001-2007

BackgroundExtrapulmonary tuberculosis (EPTB) has an increasing rate in Turkey. The reason remains largely unknown. A better understanding of the demographic and microbial characteristics of EPTB in the Turkish population would extend the knowledgebase of EPTB and allow us to develop better strategies to control tuberculosis (TB).MethodsWe retrospectively evaluated clinical and laboratory data of 397 bacteriologically-confirmed TB cases diagnosed during an eight year-period using by chi-square analysis and multivariate logistic regression model.ResultsOf the 397 study patients, 103 (25.9%) had EPTB and 294 (74.1%) had pulmonary tuberculosis (PTB). The most commonly seen two types of EPTB were genitourinary TB (27.2%) and meningeal TB (19.4%). TB in bone/joints, pleural cavity, lymph nodes, skin, and peritoneal cavity occurred at a frequency ranging from 9.7% to 10.7%. The age distribution was significantly different (P < 0.01) between PTB and EPTB, with patients older than 45 years tending to have an increased risk of EPTB. Furthermore, the distribution of different types of EPTB differed significantly among age groups (P = 0.03). Meningeal and bone and/or joint TB were more commonly observed among the male patients, while lymphatic, genitourinary, and peritoneal TB cases were more frequently seen among females. Unique strain infection was statistically significantly associated with EPTB (OR: 2.82, 95% CI [1.59, 5.00])ConclusionsEPTB accounted for a significant proportion of TB cases in Malatya, Turkey between 2001 and 2007. The current study has provided an insight into the dynamics of EPTB in Malatya, Turkey. However, the risk factors for having EPTB in Malatya, Turkey remain to be assessed in future studies using population-based or randomly selected sample.

Nontuberculous mycobacterial infections among patients suspected of pulmonary tuberculosis

The purpose of this study was to present a retrospective analysis of the frequency of nontuberculous mycobacteria (NTM)-related pulmonary infections among the AFB-positive and/or culture-positive patients in the Warsaw region who were suspected of tuberculosis (TB) and hospitalized in the university hospital between 1999 and 2005. All the AFB-positive pulmonary samples were examined with a molecular method using the Amplicor MTB test (Roche) for detection of Mycobacterium tuberculosis complex, and all mycobacterial isolates were speciated by high performance liquid chromatography (HPLC) analysis of mycolic acids. Patients who met clinical, radiological, and bacteriological criteria of mycobacteriosis were classified according to the American Thoracic Society (ATS) guidelines for diagnosis of NTM related disease. Among the 445 smear-positive or/and culture-positive patients, 142 subjects (31.9%) were found to be infected with M. tuberculosis. Among 303 non-TB patients, mycobacteriosis was found in 27 (8.9%) subjects. The frequency of NTM-related lung disease as compared to the bacteriologically-confirmed lung TB was estimated at 1:5. The rapid, precise methods of NTM speciation are necessary for progress in diagnostics of NTM related diseases.