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.

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.

Effect of patient-delivered household contact tracing and prevention for tuberculosis: A household cluster-randomised trial in Malawi.

BACKGROUND: Household contact tracing provides TB screening and TB preventive therapy (TPT) to contacts at high risk of TB disease. However, it is resource intensive, inconvenient, and often poorly implemented. We investigated a novel model aiming to improve uptake. METHODS: Between May and December 2014, we randomised patient with TB who consented to participate in the trial to either standard of care (SOC) or intervention (PACTS) arms. Participants randomised to PACTS received one screening/triage tool (adapted from WHO integrated management of adolescent and adult illnesses [IMAI] guidelines) and sputum pots for each reported household contact. The tool guided participants through symptom screening; TPT (6-months of isoniazid) eligibility; and sputum collection for contacts. Patients randomised to SOC were managed in accordance with national guidelines, that is, they received verbal instruction on who to bring to clinics for investigation using national guidelines. MAIN OUTCOME AND MEASURES: The primary outcome was the proportion of adult contacts receiving treatment for TB within 3 months of randomisation. Secondary outcomes were the proportions of child contacts under age 5 years (U5Y) who were commenced on, and completed, TPT. Data were analyzed by logistic regression with random effects to adjust for household clustering. RESULTS: Two hundred and fourteen index TB participants were block-randomized from two sites (107 PACTS, reporting 418 contacts; and 107 SOC, reporting 420 contacts). Overall, 62.8% of index TB participants were HIV-positive and 52.1% were TB culture-positive. 250 otherwise eligible TB patients declined participation and 6 households (10 PACTS, 6 SOC) were lost to follow-up and were not included in the analysis. By three months, nine contacts (PACTS: 6, [1.4%]; SOC: 3, [0.7%]) had TB diagnosed, with no difference between groups (adjusted odds ratio [aOR]: 2.18, 95% CI: 0.60-7.95). Eligible PACTS contacts (37/96, 38.5%) were more likely to initiate TPT by 3-months compared to SOC contacts (27/101, 26.7%; aOR 2.27, 95% CI: 1.04-4.98). U5Y children in the PACTS arm (47/81 58.0%) were more likely to have initiated TPT before the 3-month visit compared to SOC children (36/89, 41.4%; aOR: 2.31, 95% CI: 1.05-5.06). CONCLUSIONS AND RELEVANCE: A household-centred patient-delivered symptom screen and IPT eligibility assessment significantly increased timely TPT uptake among U5Y children, but did not significantly increase TB diagnosis. This model needs to be optimized for acceptability, given low participation, and investigated in other low resource settings. CLINICAL TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: ISRCTN81659509 https://www.isrctn.com/ISRCTN81659509?q=&filters=conditionCategory:Respiratory,recruitmentCountry:Malawi,ageRange:Mixed&sort=&offset=1&totalResults=1&page=1&pageSize=10&searchType=basic-search. 19 July 2012.

"Are we getting the biometric bioethics right?" - the use of biometrics within the healthcare system in Malawi.

Biometrics is the science of establishing the identity of an individual based on their physical attributes. Ethical concerns surrounding the appropriate use of biometrics have been raised, especially in resource-poor settings. A qualitative investigation was conducted to explore biometrics clients (n = 14), implementers (n = 12) and policy makers as well as bioethicists (n = 4) perceptions of the ethical aspects of implementing biometrics within the healthcare system in Malawi. Informed use, privacy and confidentiality as well as perceptions of benefits and harms were identified as major issues in the application of biometrics. Implementation of biometrics within the healthcare system in Malawi poses a range of potential ethical issues and practical challenges that impact on equitable uptake. There is a need for more research to explore the benefits and harms of biometrics in practice. Improved community engagement and sensitization should be a required component of biometrics introduction in Malawi.

Post-test adverse psychological effects and coping mechanisms amongst HIV self-tested individuals living in couples in urban Blantyre, Malawi.

INTRODUCTION: Mandatory face-to-face counselling is necessary during HIV testing but difficult to implement within the context of HIV self-testing. We investigated adverse psychological effects and coping mechanisms following HIV-positive and HIV-discordant test results amongst self-tested individuals living in couples in urban Blantyre, Malawi. METHODS: Qualitative data from 35 in-depth interviews with self-tested individuals living in couples for more than 3 months were collected and analysed using thematic content analysis. RESULTS: Adverse psychological effects seemed to mostly occur among individuals learning for the first-time that they were HIV-positive or living in HIV-discordant relationship. Irrespective of test outcomes, women living in couples expressed difficulty making important decisions about the future of their relationships while men seemed to shoulder the emotional burden associated with feeling or being seen as responsible for introducing HIV into the relationship. Post-test psychosocial support and ascertained positive behaviour change of the perceived index partner allowed some couples to overcome adverse psychological effects linked to test results. CONCLUSION: Self-tested individuals living in couples may lack collective coping capability to collaboratively manage post-test adverse events after new HIV-positive or HIV-discordant results. Psychosocial support seemed to enable couples to foster both an individual and a collective ability to manage adverse psychological effects within the context of a couple. More research is needed to ascertain the magnitude of the deficiency of collective coping competency in couples following an HIV test.

The Sensitivity and Specificity of Loop-Mediated Isothermal Amplification (LAMP) Assay for Tuberculosis Diagnosis in Adults with Chronic Cough in Malawi.

BACKGROUND: Current tuberculosis diagnostics lack sensitivity, and are expensive. Highly accurate, rapid and cheaper diagnostic tests are required for point of care use in low resource settings with high HIV prevalence. OBJECTIVE: To investigate the sensitivity and specificity, and cost of loop-mediated isothermal amplification (LAMP) assay for tuberculosis diagnosis in adults with chronic cough compared to Xpert® MTB/RIF, fluorescence smear microscopy. METHODS: Between October 2013 and March 2014, consecutive adults at a primary care clinic were screened for cough, offered HIV testing and assessed for tuberculosis using LAMP, Xpert® MTB/RIF and fluorescence smear microscopy. Sensitivity and specificity (with culture as reference standard), and costs were estimated. RESULTS: Of 273 adults recruited, 44.3% (121/273) were HIV-positive and 19.4% (53/273) had bacteriogically confirmed tuberculosis. The sensitivity of LAMP compared to culture was 65.0% (95% CI: 48.3% to 79.4%) with 100% (95% CI: 98.0% to 100%) specificity. The sensitivity of Xpert® MTB/RIF (77.5%, 95% CI: 61.5% to 89.2%) was similar to that of LAMP, p = 0.132. The sensitivity of concentrated fluorescence smear microscopy with routine double reading (87.5%, 95% CI: 73.2% to 95.8%) was higher than that of LAMP, p = 0.020. All three tests had high specificity. The lowest cost per test of LAMP was at batch size of 14 samples (US$ 9.98); this was lower than Xpert® MTB/RIF (US$ 13.38) but higher than fluorescence smear microscopy (US$ 0.65). CONCLUSION: The sensitivity of LAMP was similar to Xpert® MTB/RIF but lower than fluorescence smear microscopy; all three tests had high specificity. These findings support the Malawi policy that recommends a combination of fluorescence smear microscopy and Xpert® MTB/RIF prioritised for people living with HIV, already found to be smear-negative, or being considered for retreatment of tuberculosis.