Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11-1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions.

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.

Challenges in engaging the private sector for tuberculosis prevention and care in Nigeria: a mixed methods study.

OBJECTIVES: This study aimed to assess the practices of private practitioners regarding tuberculosis (TB), and to ascertain factors related to the low contribution of private healthcare providers to TB prevention and care in Nigeria. DESIGN: This is a mixed methods study comprising a quantitative retrospective review and qualitative study. SETTING: Private health facilities (HF) in Oyo State and the Federal Capital Territory (FCT), Nigeria. PARTICIPANTS: We used routinely collected data on patients with tuberculosis (TB) notified between 1 January 2017 and 31 December 2018. In-depth interviews were also conducted with the clinical staff of the facilities. PRIMARY AND SECONDARY OUTCOME MEASURES: The study outcomes are practices of TB case notification and treatment outcome, as well as the barriers and enablers of TB notification. RESULTS: A total of 13 (11.0%) out of 118 private HF were designated as 'engaged' TB care facilities in Oyo State and none (0%) of the 198 private HF in the FCT held this designation. From the 214 patients with presumptive TB, 75 (35%) were diagnosed with TB, 42 (56%) had a bacteriological test done, 12 (16%) had an X-ray of the chest alone and 21 (28%) had other non-specific investigations. Most patients diagnosed were referred to a public HF, while 19 (25%) patients were managed at the private HF. Among them, 2 (10.5%) patients were treated with unconventional regimens, 4 (21%) were cured, 2 (11%) died, 3 (16%) lost to follow-up and 10 (53%) were not evaluated. The general practitioners did not have up-to-date knowledge of TB with a majority not trained on TB. Most referred patients with presumptive and confirmed TB to the public sector without feedback and were unclear regarding diagnostic algorithm and relevant tests to confirm TB. CONCLUSION: Most private facilities were not engaged to provide TB services although with knowledge and practice gaps. The study has been used to develop plans for strategic engagement of the private sector in Nigeria.

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys.

Background: Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods: In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings: We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%-56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27-2.40) and symptomatic TB (OR 1.49, 95% CI 1.34-1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17-2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55-1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70-3.62) for subclinical TB and OR 1.43, 95% CI 0.59-3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0-85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation: Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB. Funding: None.

Budgetary impact of using BPaL for treating extensively drug-resistant tuberculosis.

INTRODUCTION: Bedaquiline, pretomanid and linezolid (BPaL) is a new all oral, 6-month regimen comprised of bedaquiline, the new drug pretomanid and linezolid, endorsed by the WHO for use under operational research conditions in patients with extensively drug-resistant tuberculosis (XDR-TB). We quantified per-patient treatment costs and the 5-year budgetary impact of introducing BPaL in Indonesia, Kyrgyzstan and Nigeria. METHODS: Per-patient treatment cost of BPaL regimen was compared head-to-head with the conventional XDR-TB treatment regimen for respective countries based on cost estimates primarily assessed using microcosting method and expected frequency of each TB service. The 5-year budget impact of gradual introduction of BPaL against the status quo was assessed using a Markov model that represented patient's treatment management and outcome pathways. RESULTS: The cost per patient completing treatment with BPaL was US$7142 in Indonesia, US$4782 in Kyrgyzstan and US$7152 in Nigeria - 57%, 78% and 68% lower than the conventional regimens in the respective countries. A gradual adoption of the BPaL regimen over 5 years would result in an 5-year average national TB service budget reduction of 17% (US$128 780) in XDR-TB treatment-related expenditure in Indonesia, 15% (US$700 247) in Kyrgyzstan and 32% (US$1 543 047) in Nigeria. CONCLUSION: Our study demonstrates that the BPaL regimen can be highly cost-saving compared with the conventional regimens to treat patients with XDR-TB in high drug-resistant TB burden settings. This supports the rapid adoption of the BPaL regimen to address the significant programmatic and clinical challenges in managing patients with XDR-TB in high DR-TB burden countries.

Assessment of GeneXpert MTB/RIF Performance by Type and Level of Health-Care Facilities in Nigeria.

SETTING: Nigeria adopted GeneXpert MTB Rif as a primary diagnostic tool were available and accessible since 2016. The current geographical coverage of GeneXpert machines by LGAs stands at 48%, with a varied access and utilization. OBJECTIVES: To assess the association between the type and level of health facilities implementing GeneXpert MTB/Rif and performance outcome of the machines in Nigeria. STUDY DESIGN: Retrospective secondary data analysis of GeneXpert performance for 2017 from GXAlert database. The independent variables were type and levels of health care facilities, and dependent variables were GeneXpert performance (utilization, successful test, error rates, MTB detected, and Rifampicin resistance detected). RESULTS: Only 366 health care facilities are currently implementing and reporting GeneXpert performance, the distribution is 86.9% and 13.1% public and private health care facilities respectively, and only 6.3% of the facilities are primary health care. Of 354,321 test conducted in 2017, 91.5% were successful, and among unsuccessful test 6.8% were errors. The yield was 16.8% MTB detected (54,713) among which 6.8% had Rif resistance. The GeneXpert utilization rate was higher among private health care facilities (55.8%) compared to 33.3% among public health care facilities. There was a statistically significant difference in the number of successful test between public and private health facility-based machines as determined by one-way ANOVA (F(1,2) = 21.81, P = 0.02) and between primary, secondary and tertiary level health facility-based machines (F(1,2) = 41.24, P < 0.01). CONCLUSION: Nigeria with very low TB coverage should rapidly scale-up and decentralize GeneXpert services to the private sector.