Spatial distribution of TB among individuals with a history of incarceration. (2021). Robsky KO., Mukiibi J., Nalutaaya A., Kitonsa PJ., Isooba D., Nakasolya O., Baik Y., Kamoga CE., Kendall EA., Katamba A., Dowdy DW, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 25, 513-515
A systematic review of the number needed to screen for active TB among people living with HIV. (2021). Chaisson LH., Naufal F., Delgado-Barroso P., Alvarez-Manzo HS., Robsky KO., Miller CR., Golub JE., Shapiro AE, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 25, 427-435
BACKGROUND: Systematic screening for active TB is recommended for all people living with HIV (PLWH); however, case detection remains poor globally. We investigated the yield of active case finding (ACF) by calculating the number needed to screen (NNS) to detect a case of active TB among PLWH.METHODS: We identified studies reporting ACF for TB among PLWH published from November 2010 to February 2020. We calculated crude NNS for Xpert- or culture-confirmed TB and weighted mean NNS stratified by screening approach, population/risk group, and country TB burden.RESULTS: Of the 27,221 abstracts screened, we identified 58 studies eligible for inclusion, including 5 in low/moderate TB incidence settings and 53 in medium/high incidence settings. Populations screened for TB included inpatients, outpatients not receiving antiretroviral therapy (ART), outpatients receiving ART, those with CD4 < 200 cells/µL, children aged ≤15 years, pregnant PLWH, and PLWH in prisons. Screening tools included symptom-based screening, chest X-ray, C-reactive protein levels, and Xpert. The weighted mean NNS varied across groups but was consistently low, ranging from 4 among inpatients in moderate/high TB burden settings to 137 among pregnant PLWH in moderate/high TB burden settings.CONCLUSIONS: ACF is a high yield intervention among PLWH. Approaches to screening should be tailored to local epidemiological and health-system contexts, and sensitive screening tools such as Xpert should be implemented where feasible.
Design and execution of a public randomization ceremony to enhance stakeholder engagement within a cluster randomized trial to improve tuberculosis diagnosis in Uganda. (2021). Reza TF., Nalugwa T., Nantale M., Adams K., Fielding K., Nakaweesa A., Oyuku D., Nabwire S., Musinguzi J., Ojok C., Babirye D., Ackerman SL., Handley MA., Kityamuwesi A., Dowdy DW., Moore DAJ., Davis JL., Turyahabwe S., Katamba A., Cattamanchi A, Contemporary clinical trials communications, 22, 100707
Public randomization ceremonies have been proposed as a strategy to strengthen stakeholder engagement and address concerns and misconceptions associated with trial randomization. However, there are few published examples that describe how to conduct a public randomization ceremony with meaningful stakeholder engagement or how such ceremonies impact stakeholder perceptions about randomization and the randomization process. Cluster randomization for the GeneXpert Performance Evaluation for Linkage to Tuberculosis Care (XPEL-TB) trial was conducted at a public randomization ceremony attended by 70 stakeholders in Kampala, Uganda. Presentations given by the Acting Assistant Commissioner from the Uganda National Tuberculosis and Leprosy Programme and trial investigators emphasized how the trial aimed to further national TB goals, as well as how stakeholders contributed to the intervention design. The purpose and process of randomization were described using simple text and visuals. Randomization was an interactive activity that required participation of stakeholders from each trial site. A survey administered to stakeholders at the end of the ceremony suggested high comprehension of randomization (98%), trust in the randomization process (96%), and satisfaction with randomization outcomes (96%). Public randomization ceremonies should be considered more routinely to engage stakeholders in and address potential concerns about the fairness and impartiality of the randomization process for community-based trials.
Characterization of geographic mobility among participants in facility- and community-based tuberculosis case finding in urban Uganda. (2021). Robsky KO., Isooba D., Nakasolya O., Mukiibi J., Nalutaaya A., Kitonsa PJ., Kamoga C., Baik Y., Kendall EA., Katamba A., Dowdy DW, PloS one, 16, e0251806
BACKGROUND: International and internal migration are recognized risk factors for tuberculosis (TB). Geographic mobility, including travel for work, education, or personal reasons, may also play a role in TB transmission, but this relationship is poorly defined. We aimed to define geographic mobility among participants in facility- and community-based TB case finding in Kampala, Uganda, and to assess associations between mobility, access to care, and TB disease. METHODS: We included consecutive individuals age ≥15 years diagnosed with TB disease through either routine health facility practices or community-based case finding (consisting of door-to-door testing, venue-based screening, and contact investigation). Each case was matched with one (for community-based enrollment) or two (health facility enrollment) TB-negative controls. We conducted a latent class analysis (LCA) of eight self-reported characteristics to identify and define mobility; we selected the best-fit model using Bayesian Information Criterion. We assessed associations between mobility and TB case status using multivariable conditional logistic regression. RESULTS: We enrolled 267 cases and 432 controls. Cases were more likely than controls to have been born in Kampala (p<0.001); there was no difference between cases and controls for remaining mobility characteristics. We selected a two-class LCA model; the "mobile" class was perfectly correlated with a single variable: travel (>3 km) from residence ≥2 times per month. Mobility was associated with a 28% reduction in odds of being a TB case (adjusted matched odds ratio 0.72 [95% confidence interval 0.49, 1.06]). CONCLUSION: Frequency of out-of-neighborhood travel is an easily measured variable that correlates closely with predicted mobility class membership. Mobility was associated with decreased risk of TB disease; this may be in part due to the higher socioeconomic status of mobile individuals in this population. However, more research is needed to improve assessment of mobility and understand how mobility affects disease risk and transmission.
Digital adherence technology for tuberculosis treatment supervision: A stepped-wedge cluster-randomized trial in Uganda. (2021). Cattamanchi A., Crowder R., Kityamuwesi A., Kiwanuka N., Lamunu M., Namale C., Tinka LK., Nakate AS., Ggita J., Turimumahoro P., Babirye D., Oyuku D., Berger C., Tucker A., Patel D., Sammann A., Turyahabwe S., Dowdy D., Katamba A, PLoS medicine, 18, e1003628
BACKGROUND: Adherence to and completion of tuberculosis (TB) treatment remain problematic in many high-burden countries. 99DOTS is a low-cost digital adherence technology that could increase TB treatment completion. METHODS AND FINDINGS: We conducted a pragmatic stepped-wedge cluster-randomized trial including all adults treated for drug-susceptible pulmonary TB at 18 health facilities across Uganda over 8 months (1 December 2018-31 July 2019). Facilities were randomized to switch from routine (control period) to 99DOTS-based (intervention period) TB treatment supervision in consecutive months. Patients were allocated to the control or intervention period based on which facility they attended and their treatment start date. Health facility staff and patients were not blinded to the intervention. The primary outcome was TB treatment completion. Due to the pragmatic nature of the trial, the primary analysis was done according to intention-to-treat (ITT) and per protocol (PP) principles. This trial is registered with the Pan African Clinical Trials Registry (PACTR201808609844917). Of 1,913 eligible patients at the 18 health facilities (1,022 and 891 during the control and intervention periods, respectively), 38.0% were women, mean (SD) age was 39.4 (14.4) years, 46.8% were HIV-infected, and most (91.4%) had newly diagnosed TB. In total, 463 (52.0%) patients were enrolled on 99DOTS during the intervention period. In the ITT analysis, the odds of treatment success were similar in the intervention and control periods (adjusted odds ratio [aOR] 1.04, 95% CI 0.68-1.58, p = 0.87). The odds of treatment success did not increase in the intervention period for either men (aOR 1.24, 95% CI 0.73-2.10) or women (aOR 0.67, 95% CI 0.35-1.29), or for either patients with HIV infection (aOR 1.51, 95% CI 0.81-2.85) or without HIV infection (aOR 0.78, 95% CI 0.46-1.32). In the PP analysis, the 99DOTS-based intervention increased the odds of treatment success (aOR 2.89, 95% CI 1.57-5.33, p = 0.001). The odds of completing the intensive phase of treatment and the odds of not being lost to follow-up were similarly improved in PP but not ITT analyses. Study limitations include the likelihood of selection bias in the PP analysis, inability to verify medication dosing in either arm, and incomplete implementation of some components of the intervention. CONCLUSIONS: 99DOTS-based treatment supervision did not improve treatment outcomes in the overall study population. However, similar treatment outcomes were achieved during the control and intervention periods, and those patients enrolled on 99DOTS achieved high treatment completion. 99DOTS-based treatment supervision could be a viable alternative to directly observed therapy for a substantial proportion of patients with TB. TRIAL REGISTRATION: Pan-African Clinical Trials Registry (PACTR201808609844917).
Diabetes Mellitus and Tuberculosis Treatment Outcomes in Pune, India. (2021). Mave V., Gaikwad S., Barthwal M., Chandanwale A., Lokhande R., Kadam D., Dharmshale S., Bharadwaj R., Kagal A., Pradhan N., Deshmukh S., Atre S., Sahasrabudhe T., Meshram S., Kakrani A., Kulkarni V., Raskar S., Suryavanshi N., Kornfeld H., Dooley KE., Chon S., Gupte A., Gupta A., Gupte N., Golub JE, Open forum infectious diseases, 8, ofab097
BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) disease. Knowledge of the impact of DM on TB treatment outcomes is primarily based on retrospective studies. METHODS: We conducted a prospective cohort study of new pulmonary TB patients with and without DM (TB-DM and TB only) in India. The association of DM with a composite unfavorable TB treatment outcome (failure, recurrence, mortality) over 18 months was determined, and the effect of DM on all-cause mortality and early mortality (death during TB treatment) was assessed. RESULTS: Of 799 participants, 574 (72%) had TB only and 225 (28%) had TB-DM. The proportion of patients with DM who experienced the composite outcome was 20%, as compared with 21% for TB-only participants (adjusted hazard ratio [aHR], 1.13; 95% CI, 0.75-1.70). Mortality was higher in participants with DM (10% vs 7%), and early mortality was substantially higher among patients with DM (aHR, 4.36; 95% CI, 1.62-11.76). CONCLUSIONS: DM was associated with early mortality in this prospective cohort study, but overall unfavorable outcomes were similar to participants without DM. Interventions to reduce mortality during TB treatment among people with TB-DM are needed.
Quantifying geographic heterogeneity in TB incidence and the potential impact of geographically targeted interventions in South and North City Corporations of Dhaka, Bangladesh: a model-based study. (2021). Shrestha S., Reja M., Gomes I., Baik Y., Pennington J., Islam S., Jamil Faisel A., Cordon O., Roy T., Suarez PG., Hussain H., Dowdy DW, Epidemiology and infection, 149, e106
In rapidly growing and high-burden urban centres, identifying tuberculosis (TB) transmission hotspots and understanding the potential impact of interventions can inform future control and prevention strategies. Using data on local demography, TB reports and patient reporting patterns in Dhaka South City Corporation (DSCC) and Dhaka North City Corporation (DNCC), Bangladesh, between 2010 and 2017, we developed maps of TB reporting rates across wards in DSCC and DNCC and identified wards with high rates of reported TB (i.e. 'hotspots') in DSCC and DNCC. We developed ward-level transmission models and estimated the potential epidemiological impact of three TB interventions: active case finding (ACF), mass preventive therapy (PT) and a combination of ACF and PT, implemented either citywide or targeted to high-incidence hotspots. There was substantial geographic heterogeneity in the estimated TB incidence in both DSCC and DNCC: incidence in the highest-incidence wards was over ten times higher than in the lowest-incidence wards in each city corporation. ACF, PT and combined ACF plus PT delivered to 10% of the population reduced TB incidence by a projected 7%-9%, 13%-15% and 19%-23% over five years, respectively. Targeting TB hotspots increased the projected reduction in TB incidence achieved by each intervention 1.4- to 1.8-fold. The geographical pattern of TB notifications suggests high levels of ongoing TB transmission in DSCC and DNCC, with substantial heterogeneity at the ward level. Interventions that reduce transmission are likely to be highly effective and incorporating notification data at the local level can further improve intervention efficiency.
Evaluating the effects of two alcohol reduction counseling interventions on intimate partner violence perpetration: secondary analysis of a three-arm randomized controlled trial among Vietnamese men with HIV. (2021). Hershow RB., Reyes HLMN., Ha TV., Chander G., Mai NVT., Sripaipan T., Dowdy DW., Latkin C., Hutton HE., Pettifor A., Maman S., Frangakis C., Go VF, Addiction (Abingdon, England)
BACKGROUND AND AIMS: Evidence suggests that alcohol reduction interventions decrease intimate partner violence (IPV) perpetration, although this remains untested in low- and middle-income countries and among men with human immunodeficiency virus (HIV). This study evaluates the effectiveness of alcohol reduction counseling interventions on IPV perpetration among men on anti-retroviral therapy (ART) and tests whether alcohol use explains the intervention effects. DESIGN: Secondary analysis of data from a three-arm randomized controlled trial among ART patients with hazardous alcohol use. Participants were recruited from March 2016 to May 2017. SETTING: Thai Nguyen, Vietnam. PARTICIPANTS, INTERVENTIONS AND COMPARATORS: Male participants (n = 426). Participants received a two-session brief intervention (BI), a six-session combined intervention (CoI) or the standard of care (SOC), comprising alcohol treatment referrals. Alcohol reduction counseling interventions were guided by cognitive-behavioral therapy and motivational enhancement therapy delivered by psychosocial counselors over 3 months. MEASUREMENTS: IPV perpetration was measured using the shortened Conflict Tactics Scale 2 and alcohol use was measured using timeline followback. FINDINGS: BI and CoI participants reported reduced IPV perpetration at 3 months compared with SOC participants [BI: adjusted odds ratio (aOR) = 0.27, 95% confidence interval (CI) = 0.11, 0.65; CoI: aOR = 0.50, 95% CI = 0.22, 1.13]; the association was only significant for the BI group. Intervention effects were not sustained at 6 and 12 months. There was little evidence that alcohol use acted as a mediator (indirect effect, BI: aOR = 0.84, 95% CI = 0.63, 1.04; indirect effect, CoI: aOR = 0.86, 95% CI = 0.66, 1.03). CONCLUSIONS: Among Vietnamese men receiving anti-retroviral therapy, alcohol reduction counseling interventions appeared to reduce intimate partner violence perpetration immediately post-intervention, but reductions were not sustained at 6 and 12 months and were not explained by alcohol reduction.
Ethical Implications of eHealth Tools for Delivering STI/HIV Laboratory Results and Partner Notifications. (2021). Godongwana M., Chewparsad J., Lebina L., Golub J., Martinson N., Jarrett BA, Current HIV/AIDS reports, 18, 237-246
PURPOSE OF REVIEW: eHealth tools are increasingly utilized for communication with patients. Although efficacious and cost-effective, these tools face several barriers that challenge their ethical use in sexual health. We reviewed literature from the past decade to pick illustrative studies of eHealth tools that deliver results of laboratory tests for sexually transmitted infections, including the human immunodeficiency virus, as well as partner notifications. We describe ethical implications for such technologies. RECENT FINDINGS: Our review found that despite widespread research on the use of eHealth tools in delivering laboratory results and partner notifications, these studies rarely measured or reported on the ethical implications. Such implications can be organized according to the four major principles in bioethics: beneficence, patient autonomy, non-maleficence, and justice. The beneficence of eHealth typically measures efficacy in comparison to existing standards of care. Patient autonomy includes the ability to opt in or out of eHealth tools, right-based principles of consent, and sovereignty over healthcare data. To adhere to the principle of non-maleficence, relevant harms must be identified and measured-such as unintentional disclosure of illness, sexual orientation, or sexual activity. Justice must also be considered to accommodate all users equally, irrespective of their literacy level, with easy-to-use platforms that provide clear messages. Based on case studies from this review, we developed a list of recommendations for the ethical development and evaluation of eHealth platforms to deliver STI/HIV results to patients and notifications to partners.
Measuring health-care delays among privately insured patients with tuberculosis in the USA: an observational cohort study. (2021). El Halabi J., Palmer N., McDuffie M., Golub JJ., Fox K., Kohane I., Farhat MR, The Lancet. Infectious diseases
BACKGROUND: A high index of suspicion is needed to initiate appropriate testing for tuberculosis due to its protean symptoms, yet health-care providers in low-incidence settings are becoming less familiar with the disease as rates decline. We aimed to estimate delays in tuberculosis diagnosis and treatment at the US national level between 2008 and 2016. METHODS: In this retrospective observational cohort study, we repurposed private insurance claims data provided by Aetna (Connecticut, USA), to measure health-care delays in tuberculosis diagnosis in the USA in 2008-16. Active tuberculosis was determined by diagnosis codes and the filling of anti-tuberculosis treatment prescriptions. Health-care delays were defined as the duration between the first health-care visit for a tuberculosis symptom and the initiation of anti-tuberculosis treatment. We assessed if delays varied over time, and by patient and system variables, using multivariable regression. We estimated household tuberculosis transmission and respiratory complications after treatment initiation. FINDINGS: We confirmed 738 active tuberculosis cases (incidence 1·45 per 100 000 person-years) with a median health-care delay of 24 days (IQR 10-45). Multivariable regression analysis showed that longer delays were associated with older age (8·4% per 10 year increase [95% CI 4·0 to 13·1]; p<0·0086) and non-HIV immunosuppression (19·2% [15·1 to 60·0]; p=0·0432). Presenting with three or more symptoms was associated with a shorter delay (-22·5% [-39·1 to -2·0]; p=0·0415), relative to presenting with one symptom, as did use of chest imaging (-24·9% [-37·9 to -8·9]; p<0·0098), tuberculosis nucleic acid amplification tests (-19·2% [-32·7 to -3·1]; p=0·0241), and care by a tuberculosis specialist provider (-17·2% [-33·1 to -22·3]; p<0·0087). Longer delays were associated with an increased rate of respiratory complications even after controlling for patient characteristics, and an increased rate of secondary tuberculosis among dependents. INTERPRETATION: In the USA, the median health-care delay for privately insured patients with tuberculosis exceeds WHO-recommended levels of 21 days (3 weeks). The results suggest the need for health-care provider education on best practices in tuberculosis diagnosis, including the use of molecular tests and the maintenance of a high index of suspicion for the disease. FUNDING: US National Institutes of Health.
Community-based active case-finding interventions for tuberculosis: a systematic review. (2021). Burke RM., Nliwasa M., Feasey HRA., Chaisson LH., Golub JE., Naufal F., Shapiro AE., Ruperez M., Telisinghe L., Ayles H., Corbett EL., MacPherson P, The Lancet. Public health, 6, e283-e299
BACKGROUND: Community-based active case-finding interventions might identify and treat more people with tuberculosis disease than standard case detection. We aimed to assess whether active case-finding interventions can affect tuberculosis epidemiology in the wider community. METHODS: We did a systematic review by searching PubMed, Embase, Scopus, and Cochrane Library for studies that compared tuberculosis case notification rates, tuberculosis disease prevalence, or tuberculosis infection prevalence or incidence in children, between populations exposed and unexposed to active case-finding interventions. We included studies published in English between Jan 1, 1980, and April 13, 2020. Studies of active case-finding in the general population, in populations perceived to be at high risk for tuberculosis, and in closed settings were included, whereas studies of tuberculosis screening at health-care facilities, among household contacts, or among children only, and studies that screened fewer than 1000 people were excluded. To estimate effectiveness, we extracted or calculated case notification rates, prevalence of tuberculosis disease, and incidence or prevalence of tuberculosis infection in children, and compared ratios of these outcomes between groups that were exposed or not exposed to active case-finding interventions. RESULTS: 27 883 abstracts were screened and 988 articles underwent full text review. 28 studies contributed data for analysis of tuberculosis case notifications, nine for prevalence of tuberculosis disease, and two for incidence or prevalence of tuberculosis infection in children. In one cluster-randomised trial in South Africa and Zambia, an active case-finding intervention based on community mobilisation and sputum drop-off did not affect tuberculosis prevalence, whereas, in a cluster-randomised trial in Vietnam, an active case-finding intervention based on sputum tuberculosis tests for everyone reduced tuberculosis prevalence in the community. We found inconsistent, low-quality evidence that active case-finding might increase the number of cases of tuberculosis notified in populations with structural risk factors for tuberculosis. INTERPRETATION: Community-based active case-finding for tuberculosis might be effective in changing tuberculosis epidemiology and thereby improving population health if delivered with high coverage and intensity. If possible, active case-finding projects should incorporate a well designed, robust evaluation to contribute to the evidence base and help elucidate which delivery methods and diagnostic strategies are most effective. FUNDING: WHO Global TB Programme.
Effectiveness of low-dose theophylline for the management of biomass-associated COPD (LODOT-BCOPD): study protocol for a randomized controlled trial. (2021). Siddharthan T., Pollard SL., Jackson P., Robertson NM., Wosu AC., Rahman N., Padalkar R., Sekitoleko I., Namazzi E., Alupo P., Hurst JR., Kalyesubula R., Dowdy D., Wise R., Barnes PJ., Checkley W., Kirenga B, Trials, 22, 213
BACKGROUND: COPD is a leading cause of death globally, with the majority of morbidity and mortality occurring in low- and middle-income country (LMIC) settings. While tobacco-smoke exposure is the most important risk factor for COPD in high-income settings, household air pollution from biomass smoke combustion is a leading risk factor for COPD in LMICs. Despite the high burden of biomass smoke-related COPD, few studies have evaluated the efficacy of pharmacotherapy in this context. Currently recommended inhaler-based therapy for COPD is neither available nor affordable in most resource-limited settings. Low-dose theophylline is an oral, once-a-day therapy, long used in high-income countries (HICs), which has been proposed for the management of COPD in LMICs in the absence of inhaled steroids and/or bronchodilators. The Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD) trial investigates the clinical efficacy and cost-effectiveness of low-dose theophylline for the management of biomass-related COPD in a low-income setting. METHODS: LODOT-BCOPD is a randomized, double-blind, placebo-controlled trial to test the efficacy of low-dose theophylline in improving respiratory symptoms in 110 participants with moderate to severe COPD in Central Uganda. The inclusion criteria are as follows: (1) age 40 to 80 years, (2) full-time resident of the study area, (3) daily biomass exposure, (4) post-bronchodilator FEV(1)/FVC below the 5th percentile of the Global Lung Initiative mixed ethnic reference population, and (5) GOLD Grade B-D COPD. Participants will be randomly assigned to receive once daily low-dose theophylline (200 mg ER, Unicontin-E) or placebo for 52 weeks. All participants will receive education about self-management of COPD and rescue salbutamol inhalers. We will measure health status using the St. George's Respiratory Questionnaire (SGRQ) and quality of life using the EuroQol-5D (EQ-5D) at baseline and every 6 months. In addition, we will assess household air pollution levels, serum inflammatory biomarkers (fibrinogen, hs-CRP), and theophylline levels at baseline, 1 month, and 6 months. The primary outcome is change in SGRQ score at 12 months. Lastly, we will assess the cost-effectiveness of the intervention by calculating quality-adjusted life years (QALYs) from the EQ-5D. TRIAL REGISTRATION: ClinicalTrials.gov NCT03984188 . Registered on June 12, 2019 TRIAL ACRONYM: Low-dose Theophylline for the Management of Biomass-Associated COPD (LODOT-BCOPD).
Cost-effectiveness of universal HIV testing and treatment: where next? (2021). Nachega JB., Borre ED., Dowdy DW., Chanda-Kapata P., Cleary S., Geng EH, The Lancet. Global health, 9, e573-e574
Reply to Pierce: Subclinical Tuberculosis: Some Flies in the Ointment. (2021). Kendall EA., Shrestha S., Dowdy DW, American journal of respiratory and critical care medicine, 203, 1328-1329
Infection status of contacts is not associated with severity of TB in the index case. (2021). Baik Y., Nalutaaya A., Kitonsa PJ., Dowdy DW., Katamba A., Kendall EA, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 25, 237-240
Unhealthy alcohol use independently associated with unfavorable TB treatment outcomes among Indian men. (2021). Cox SR., Gupte AN., Thomas B., Gaikwad S., Mave V., Padmapriyadarsini C., Sahasrabudhe TR., Kadam D., Gupte N., Hanna LE., Kagal A., Paradkar M., Thiruvengadam K., Jain D., Atre S., Sekar K., Raskar S., Shivakumar SVBY., Santhappan R., Deshmukh S., Pradhan N., Kulkarni V., Kakrani A., Barthwal MS., Sawant T., DeLuca A., Suryavanshi N., Chander G., Bollinger R., Golub JE., Gupta A, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 25, 182-190
BACKGROUND: Approximately 10% of incident TB cases worldwide are attributable to alcohol. However, evidence associating alcohol with unfavorable TB treatment outcomes is weak.METHODS: We prospectively evaluated men (≥18 years) with pulmonary TB in India for up to 24 months to investigate the association between alcohol use and treatment outcomes. Unhealthy alcohol use was defined as a score of ≥4 on the Alcohol Use Disorders Identification Test-Concise (AUDIT-C) scale at entry. Unfavorable TB treatment outcomes included failure, recurrence, and all-cause mortality, analyzed as composite and independent endpoints.RESULTS: Among 751 men, we identified unhealthy alcohol use in 302 (40%). Median age was 39 years (IQR 28-50); 415 (55%) were underweight (defined as a body mass index [BMI] <18.5 kg/m²); and 198 (26%) experienced an unfavorable outcome. Unhealthy alcohol use was an independent risk factor for the composite unfavorable outcome (adjusted incidence rate ratio [aIRR] 1.47, 95% CI 1.05-2.06; P = 0.03) and death (aIRR 1.90, 95% CI 1.08-3.34; P = 0.03), specifically. We found significant interaction between AUDIT-C and BMI; underweight men with unhealthy alcohol use had increased risk of unfavorable outcomes (aIRR 2.22, 95% CI 1.44-3.44; P < 0.001) compared to men with BMI ≥18.5 kg/m² and AUDIT-C <4.CONCLUSION: Unhealthy alcohol use was independently associated with unfavorable TB treatment outcomes, highlighting the need for integrating effective alcohol interventions into TB care.
Determining the value of TB active case-finding: current evidence and methodological considerations. (2021). Sohn H., Sweeney S., Mudzengi D., Creswell J., Menzies NA., Fox GJ., MacPherson P., Dowdy DW, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 25, 171-181
Active case-finding (ACF) is an important component of the End TB Strategy. However, ACF is resource-intensive, and the economics of ACF are not well-understood. Data on the costs of ACF are limited, with little consistency in the units and methods used to estimate and report costs. Mathematical models to forecast the long-term effects of ACF require empirical measurements of the yield, timing and costs of case detection. Pragmatic trials offer an opportunity to assess the cost-effectiveness of ACF interventions within a 'real-world´ context. However, such analyses generally require early introduction of economic evaluations to enable prospective data collection on resource requirements. Closing the global case-detection gap will require substantial additional resources, including continued investment in innovative technologies. Research is essential to the optimal implementation, cost-effectiveness, and affordability of ACF in high-burden settings. To assess the value of ACF, we must prioritize the collection of high-quality data regarding costs and effectiveness, and link those data to analytical models that are adapted to local settings.
Quantifying the potential value of antigen-detection rapid diagnostic tests for COVID-19: a modelling analysis. (2021). Ricks S., Kendall EA., Dowdy DW., Sacks JA., Schumacher SG., Arinaminpathy N, BMC medicine, 19, 75
BACKGROUND: Testing plays a critical role in treatment and prevention responses to the COVID-19 pandemic. Compared to nucleic acid tests (NATs), antigen-detection rapid diagnostic tests (Ag-RDTs) can be more accessible, but typically have lower sensitivity and specificity. By quantifying these trade-offs, we aimed to inform decisions about when an Ag-RDT would offer greater public health value than reliance on NAT. METHODS: Following an expert consultation, we selected two use cases for analysis: rapid identification of people with COVID-19 amongst patients admitted with respiratory symptoms in a 'hospital' setting and early identification and isolation of people with mildly symptomatic COVID-19 in a 'community' setting. Using decision analysis, we evaluated the health system cost and health impact (deaths averted and infectious days isolated) of an Ag-RDT-led strategy, compared to a strategy based on NAT and clinical judgement. We adopted a broad range of values for 'contextual' parameters relevant to a range of settings, including the availability of NAT and the performance of clinical judgement. We performed a multivariate sensitivity analysis to all of these parameters. RESULTS: In a hospital setting, an Ag-RDT-led strategy would avert more deaths than a NAT-based strategy, and at lower cost per death averted, when the sensitivity of clinical judgement is less than 90%, and when NAT results are available in time to inform clinical decision-making for less than 85% of patients. The use of an Ag-RDT is robustly supported in community settings, where it would avert more transmission at lower cost than relying on NAT alone, under a wide range of assumptions. CONCLUSIONS: Despite their imperfect sensitivity and specificity, Ag-RDTs have the potential to be simultaneously more impactful, and have a lower cost per death and infectious person-days averted, than current approaches to COVID-19 diagnostic testing.
Cost-effectiveness of scaling up short course preventive therapy for tuberculosis among children across 12 countries. (2021). Jo Y., Gomes I., Flack J., Salazar-Austin N., Churchyard G., Chaisson RE., Dowdy DW, EClinicalMedicine, 31, 100707
BACKGROUND: While household contact investigation is widely recommended as a means to reduce the burden of tuberculosis (TB) among children, only 27% of eligible pediatric household contacts globally received preventive treatment in 2018. We assessed the cost-effectiveness of household contact investigation for TB treatment and short-course preventive therapy provision for children under 15 years old across 12 high TB burden countries. METHODS: We used decision analysis to compare the costs and estimated effectiveness of three intervention scenarios: (a) status quo (existing levels of coverage with isoniazid preventive therapy), (b) contact investigation with treatment of active TB but no additional preventive therapy, and (c) contact investigation with TB treatment and provision of short-course preventive therapy. Using country-specific demographic, epidemiological and cost data from the literature, we estimated annual costs (in 2018 USD) and the number of TB cases and deaths averted across 12 countries. Incremental cost effectiveness ratios were assessed as cost per death and per disability-adjusted life year [DALY] averted. FINDINGS: Our model estimates that contact investigation with treatment of active TB and provision of preventive therapy could be highly cost-effective compared to the status quo (ranging from $100 per DALY averted in Malawi to $1,600 in Brazil; weighted average $383 per DALY averted [uncertainty range: $248 - $1,130]) and preferred to contact investigation without preventive therapy (weighted average $751 per DALY averted [uncertainty range: $250 - $1,306]). Key drivers of cost-effectiveness were TB prevalence, sensitivity of TB diagnosis, case fatality for untreated TB, and cost of household screening. INTERPRETATION: Based on this modeling analysis of available published data, household contact investigation with provision of short-course preventive therapy for TB has a value-for-money profile that compares favorably with other interventions. FUNDING: Unitaid (2017-20-IMPAACT4TB).
Patient choice improves self-efficacy and intention to complete tuberculosis preventive therapy in a routine HIV program setting in Uganda. (2021). Lim RK., Semitala FC., Atuhumuza E., Sabiti L., Namakula-Katende J., Muyindike WR., Kamya MR., Dowdy D., Cattamanchi A, PloS one, 16, e0246113
A 12-dose weekly regimen of rifapentine plus isoniazid (3HP) is recommended for the prevention of active tuberculosis (TB); however, it is unclear whether 3HP should be provided by directly observed therapy (DOT) or self-administered therapy (SAT). In addition, the introduction of patient informed choice between delivery modalities may have a positive impact on factors leading to treatment completion. The authors randomized 252 participants with HIV to a hypothetical scenario of providing preventive therapy by either DOT or an informed choice between DOT and SAT. Out of 104 participants who were randomized to a choice between DOT and SAT, 103 chose therapy by SAT. Participants rated their level of confidence and intention to complete therapy. Compared to those assigned to the DOT scenario, patients assigned to the choice scenario expressed greater confidence and intention to complete preventive therapy. Convenience and travel required to complete 3HP therapy were important factors in deciding between delivery modalities. Those assigned to DOT identified more barriers to completing therapy than those given a choice. Empowering patients to make informed decisions about how they receive TB preventive therapy may improve completion rates.