Uptake and Completion of Tuberculosis Preventive Treatment Using 12-Dose, Weekly Isoniazid-Rifapentine Regimen in Bangladesh: A Community-Based Implementation Study.

BACKGROUND: The United Nations high-level meeting (UNHLM) pledged to enroll 30 million in tuberculosis preventive treatment (TPT) by 2022, necessitating TPT expansion to all at tuberculosis (TB) risk. We assessed the uptake and completion of a 12-dose, weekly isoniazid-rifapentine (3HP) TPT regimen. METHODS: Between February 2018 and March 2019 in Dhaka, community-based TPT using 3HP targeted household contacts of 883 confirmed drug-sensitive pulmonary TB patients. Adhering to World Health Organization guidelines, contacts underwent active TB screening before TPT initiation. RESULTS: Of 3193 contacts who were advised health facility visits for screening, 67% (n = 2149) complied. Among these, 1804 (84%) received chest X-rays. Active TB was diagnosed in 39 (2%) contacts; they commenced TB treatment. Over 97% of 1216 contacts began TPT, with completion rates higher among females, those with more education and income, non-slum residents, and those without 3HP-related adverse events. Adverse events, mainly mild, occurred in 5% of participants. CONCLUSIONS: The 3HP regimen, with its short duration, self-administered option, and minimal side effects, achieved satisfactory completion rates. A community-focused TPT approach is feasible, scalable nationally, and aligns with UNHLM targets.

Improving Tuberculosis Case Detection in Children: Summary of Innovations and Findings From 18 Countries.

Despite a growing focus on the plight of tuberculosis (TB) among children, 56% of the 1.2 million children who develop TB annually are not detected and notified. TB REACH is a platform of the Stop TB Partnership that supports innovative interventions to improve TB case detection and preventative treatment. We present summary findings from 27 TB REACH-supported projects in 18 countries. Interventions were designed around intensified case-finding approaches (facility-based systematic screening and contact investigation), capacity building (including decentralized care delivery and supported decision-making), and improving diagnostic methods (ie, introduction of alternative respiratory specimens and new tools to aid the diagnosis). These interventions were evaluated on how they worked to identify children with TB, prevent further transmission of TB among children, and strengthen the health system involved with childhood TB care. Overall, 13 715 children were detected with TB, improving case notifications by 34%. In addition, nearly 5000 eligible contacts were enrolled on TB preventive treatment through these interventions. Focusing efforts and funding on childhood TB can produce marked improvements in case detection.

A Multi-Faceted Approach to Tuberculosis Active Case Finding among Remote Riverine Communities in Southern Nigeria.

Nigeria accounts for 11% of the worldwide gap between estimated and reported individuals with tuberculosis (TB). Hard-to-reach communities on the Southern Nigeria coast experience many difficulties accessing TB services. We implemented an active case finding (ACF) intervention in Akwa Ibom and Cross River states utilizing three approaches: house-to-house/tent-to-tent screening, community outreach and contact investigation. To evaluate the impact, we compared TB notifications in intervention areas to baseline and control population notifications, as well as to expected notifications based on historical trends. We also gathered field notes from discussions with community volunteers who provided insights on their perspectives of the intervention. A total of 509,768 individuals were screened of which 12,247 (2.4%) had TB symptoms and 11,824 (96.5%) were tested. In total, 1015 (8.6%) of those identified as presumptive had confirmed TB-98.2% initiated treatment. Following implementation, TB notifications in intervention areas increased by 112.9% compared to baseline and increased by 138.3% when compared to expected notifications based on historical trends. In contrast, control population notifications increased by 101% and 49.1%, respectively. Community volunteers indicated a preference for community outreach activities. Multi-faceted, community-based interventions in Nigeria's coastal areas successfully increase TB detection for communities with poor access to health services.

Factors Affecting Motivation among Key Populations to Engage with Tuberculosis Screening and Testing Services in Northwest Tanzania: A Mixed-Methods Analysis.

In northwest Tanzania, many artisanal small-scale miners (ASMs) and female sex workers (FSWs) live in informal communities surrounding mines where tuberculosis (TB) is highly prevalent. An active case finding (ACF) intervention to increase TB case notification was undertaken in two districts. Alongside this, a study was implemented to understand engagement with the intervention through: (1) quantitative questionnaires to 128 ASMs and FSWs, who either engaged or did not engage in the ACF intervention, to assess their views on TB; (2) qualitative interviews with 41 ASMs and FSWs, 36 community health workers (CHWs) and 30 community stakeholders. The mean perceived severity of TB score was higher in the engaged than in the non-engaged group (p = 0.01). Thematic analysis showed that health-seeking behaviour was similar across both groups but that individuals in the non-engaged group were more reluctant to give sputum samples, often because they did not understand the purpose. CHWs feared contracting TB on the job, and many noted that mining areas were difficult to access without transportation. Community stakeholders provided various recommendations to increase engagement. This study highlights reasons for engagement with a large-scale ACF intervention targeting key populations and presents insights from implementers and stakeholders on the implementation of the intervention.

An evaluation of automated chest radiography reading software for tuberculosis screening among public- and private-sector patients.

Computer-aided reading (CAR) of medical images is becoming increasingly common, but few studies exist for CAR in tuberculosis (TB). We designed a prospective study evaluating CAR for chest radiography (CXR) as a triage tool before Xpert MTB/RIF (Xpert).Consecutively enrolled adults in Dhaka, Bangladesh, with TB symptoms received CXR and Xpert. Each image was scored by CAR and graded by a radiologist. We compared CAR with the radiologist for sensitivity and specificity, area under the receiver operating characteristic curve (AUC), and calculated the potential Xpert tests saved.A total of 18 036 individuals were enrolled. TB prevalence by Xpert was 15%. The radiologist graded 49% of CXRs as abnormal, resulting in 91% sensitivity and 58% specificity. At a similar sensitivity, CAR had a lower specificity (41%), saving fewer (36%) Xpert tests. The AUC for CAR was 0.74 (95% CI 0.73-0.75). CAR performance declined with increasing age. The radiologist grading was superior across all sub-analyses.Using CAR can save Xpert tests, but the radiologist's specificity was superior. Differentiated CAR thresholds may be required for different populations. Access to, and costs of, human readers must be considered when deciding to use CAR software. More studies are needed to evaluate CAR using different screening approaches.

Effect of active case finding on prevalence and transmission of pulmonary tuberculosis in Dhaka Central Jail, Bangladesh.

BACKGROUND: Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. METHODS: The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). RESULTS: A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as 'modern' and 100 (30%) strains as 'ancestral'. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. CONCLUSIONS: Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh.

Quantitative drug-susceptibility in patients treated for multidrug-resistant tuberculosis in Bangladesh: implications for regimen choice.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) treatment in Bangladesh is empiric or based on qualitative drug-susceptibility testing (DST) by comparative growth in culture media with and without a single drug concentration. METHODS: Adult patients were enrolled throughout Bangladesh during the period of 2011-2013 at MDR-TB treatment initiation. Quantitative DST by minimum inhibitory concentration (MIC) testing for 12 first and second-line anti-TB drugs was compared to pretreatment clinical characteristics and treatment outcomes. MIC values at or one dilution lower than the resistance breakpoint used for qualitative DST were categorized as borderline susceptible, and MIC values one or two dilutions greater as borderline resistant. RESULTS: Seventy-four patients were enrolled with a mean age of 35 ± 15 years, and 51 (69%) were men. Of the rifampin isolates with MIC >1.0 µg/ml, 12 (19%) were fully susceptible or borderline susceptible to rifabutin (MIC ≤ 0.5 µg/ml). Amikacin was fully susceptible in 73 isolates (99%), but kanamycin in only 54 (75%) (p<0.001). Ofloxacin was borderline susceptible in 64%, and fully susceptible in only 14 (19%) compared to 60 (81%) of isolates fully susceptible for moxifloxacin (p<0.001). Kanamycin non-susceptibility and receipt of the WHO Category IV regimen trended with interim treatment failure: adjusted odd ratios respectively of 5.4 [95% CI 0.82-36.2] (p = 0.08) and 7.2 [0.64-80.7] (p = 0.11). CONCLUSIONS: Quantitative MIC testing could impact MDR-TB regimen choice in Bangladesh. Comparative trials of higher dose or later generation fluoroquinolone, within class change from kanamycin to amikacin, and inclusion of rifabutin appear warranted.

Epidemiology of tuberculosis in an urban slum of Dhaka City, Bangladesh.

BACKGROUND: The objectives of this study were to assess the tuberculosis (TB) burden and to provide an insight into the type of circulating M. tuberculosis species in urban slums of Bangladesh. We also aimed to test the feasibility of a larger transmission study in this setting. METHODS: This cross-sectional study was conducted in an urban slum of Dhaka city. The household members were actively screened to assess the presence of TB-related signs and symptoms; cough ≥ 3 weeks and body mass index (BMI) <17 kg/m(2). Sputum specimens from suspects were collected for acid fast bacilli (AFB) microscopy, culture and drug susceptibility testing. Genotyping of M. tuberculosis was done using spoligotyping and variable number tandem repeats of mycobacterial interspersed repetitive units typing. RESULTS: Among 9,877 adult screened for pulmonary TB (PTB), 25 were positive for AFB on microscopy and/or culture and the prevalence of new PTB cases was estimated to be 253/100,000. Only one child TB case was diagnosed among 5,147 child screened. Out of 26 cases, 21(81%) had cough for several duration and 5(19%) did not present with cough at the time of screening. One multidrug resistant case was found. Fifty two percent of all TB cases had BMI <17 kg/m2 (p = <0.001). Among the 20 analyzed isolates, 13 different spoligotype patterns were identified in which 5 clusters contained 12 strains and 8 strains had unique pattern. CONCLUSIONS: The study revealed high prevalence of TB in urban slums. Screening using low BMI can be beneficial among risk group population. It is important to conduct larger study to validate clinical variables like cough <3 weeks and low BMI to define TB suspect and also to investigate the transmission of TB in slum settings.

Comparison of direct versus concentrated smear microscopy in detection of pulmonary tuberculosis.

BACKGROUND: Sputum smear microscopy is fast and inexpensive technique for detecting tuberculosis (TB) in high incidence areas but has low sensitivity. Physical and chemical sputum processing along with centrifugation have been found to show promise in overcoming this limitation. Our objective was to compare the sensitivity of smear microscopy obtained with smears made directly from respiratory specimens to those from concentrated specimens. METHODS: By active screening, 915 TB suspects were identified from Dhaka Central Jail and sputum specimens were aseptically collected. Direct smears were prepared by taking a small portion of the purulent part of the sputum with a sterile loop. The specimens were then processed by a standard N-acetyl-L-cysteine-NaOH digestion-decontamination method to prepare concentrated specimens. Both smears were then air dried, heat fixed, and stained by the Ziehl-Neelsen staining technique. The stained slides were examined under oil immersion and were graded following International Union Against Tuberculosis and Lung Diseases guidelines. All the specimens were inoculated into Lowenstein-Jensen (L-J) media and culture results were considered as gold standard to calculate sensitivity. RESULTS: Of 915 specimens, 73 (8%) specimens were positive both on direct and concentrated methods, one sample was positive on direct microscopy but was negative on concentrated method. An extra 14 (1.5%) samples were positive on concentrated method which were negative on direct smear. In L-J media 105 specimens were found positive for TB bacilli and of them, 74 (70.5%) and 87 (82.9%) were positive in direct and concentrated smear, respectively. The sensitivity of direct and concentrated smear microscopy was different when using positive culture as the gold standard (71% vs. 83%). CONCLUSIONS: The results showed that concentrated technique increases the sensitivity of microscopy up to 12%. Therefore, the national programs in high TB burden countries may consider incorporating the technique into their guidelines at least in the district and higher level laboratories to improve case finding strategy.

Yield of two consecutive sputum specimens for the effective diagnosis of pulmonary tuberculosis.

BACKGROUND: From long instances, it is debatable whether three sputum specimens are required for the diagnosis of pulmonary tuberculosis (TB) or TB can be diagnosed effectively using two consecutive sputum specimens. This study was set out to evaluate the significance of examining multiple sputum specimens in diagnosis of TB. METHODS: We retrospectively reviewed the acid-fast bacillus (AFB) smear and culture results of three consecutive days' sputum specimens from 413 confirmed TB patients which were detected as part of a larger active case finding study in Dhaka Central Jail, the largest correctional facility in Bangladesh. RESULTS: AFB was detected from 81% (n = 334) patients, of which 89% (n = 297) were diagnosed from the first and additional 9% (n = 30) were from the second sputum specimen. M. tuberculosis growth was observed for 406 patients and 85% (n = 343) were obtained from the first sputum and additional 10% (n = 42) were from the second one. The third specimen didn't show significant additional diagnostic value for the detection of AFB by microscopy or growth of the M. tuberculosis. CONCLUSIONS: We concluded from our study results that examining two consecutive sputum specimens is sufficient enough for the effective diagnosis of TB. It can also decrease the laboratory workload and hence improve the quality of work in settings with high TB burden like Bangladesh.

Multidrug-resistant tuberculosis in admitted patients at a tertiary referral hospital of Bangladesh.

BACKGROUND: This study was set out to investigate the magnitude, patterns and molecular characterization of drug-resistant Mycobacterium tuberculosis strains at a tertiary referral hospital in Bangladesh. METHODS: Pulmonary tuberculosis (TB) patients admitted at National Institute of Diseases of the Chest and Hospital from February 2002 to September 2005 with or without previous history of TB and/or other complications were randomly interviewed. Among 265 participants enrolled, M. tuberculosis isolates from 189 patients were finally tested for susceptibility to rifampicin (RMP), isoniazid (INH), ethambutol (ETM) and streptomycin (STM). Genotyping of M. tuberculosis was done using deletion analysis and spoligotyping. RESULTS: Eighty-eight percent (n = 167) of the patients had history of previous anti-TB treatment while the remaining 12% were new TB cases. Of the 189 isolates, 9% were fully susceptible to the first line anti-TB drugs and 73.5% were multi-drug resistant TB. Other susceptibility results showed 79.4%, 77.2%, 76.7% and 78.8% resistance to INH, RMP, ETM and STM respectively. Multi-drug resistance was significantly higher among the 130 (78%) patients with previous history of anti-tuberculosis treatment (95% confidence interval, p = 0.001). Among the 189 analyzed isolates, 69% were classified as "modern" M. tuberculosis strains (i.e. TbD1- strains, lacking the M. tuberculosis-deletion region TbD1), whereas the remaining 31% were found to belong to the "ancestal" TbD1+ M. tuberculosis lineages. One hundred and five different spoligotype patterns were identified in which 16 clusters contained 100 strains and 89 strains had unique pattern. Strains with a spoligotype characteristic for the "Beijing" cluster were predominant (19%) and most of these strains (75%) were multi-drug resistant (MDR). CONCLUSIONS: A high level of drug resistance observed among the re-treatment patients poses a threat of transmission of resistant strains to susceptible persons in the community. Proper counseling of patients and attention towards the completion of the anti-TB treatment is needed.