Research Roadmap for Tuberculosis Transmission Science: Where Do We Go From Here and How Will We Know When We're There? (2017). Auld SC., Kasmar AG., Dowdy DW., Mathema B., Gandhi NR., Churchyard GJ., Rustomjee R., Shah NS, The Journal of infectious diseases, 216, S662-S668
High rates of tuberculosis transmission are driving the ongoing global tuberculosis epidemic, and there is a pressing need for research focused on understanding and, ultimately, halting transmission. The ongoing tuberculosis-human immunodeficiency virus (HIV) coepidemic and rising rates of drug-resistant tuberculosis in parts of the world add further urgency to this work. Success in this research will require a concerted, multidisciplinary effort on the part of tuberculosis scientists, clinicians, programs, and funders and must span the research spectrum from biomedical sciences to the social sciences, public health, epidemiology, cost-effectiveness analyses, and operations research. Heterogeneity of tuberculosis disease, both among individual patients and among communities, poses a substantial challenge to efforts to interrupt transmission. As such, it is likely that effective interventions to stop transmission will require a combination of approaches that will vary across different epidemiologic settings. This research roadmap summarizes key gaps in our current understanding of transmission, as laid out in the preceding articles in this series. We also hope that it will be a call to action for the global tuberculosis community to make a sustained commitment to tuberculosis transmission science. Halting transmission today is an essential step on the path to end tuberculosis tomorrow.
Designing and Evaluating Interventions to Halt the Transmission of Tuberculosis. (2017). Dowdy DW., Grant AD., Dheda K., Nardell E., Fielding K., Moore DAJ, The Journal of infectious diseases, 216, S654-S661
To reduce the incidence of tuberculosis, it is insufficient to simply understand the dynamics of tuberculosis transmission. Rather, we must design and rigorously evaluate interventions to halt transmission, prioritizing those interventions most likely to achieve population-level impact. Synergy in reducing tuberculosis transmission may be attainable by combining interventions that shrink the reservoir of latent Mycobacterium tuberculosis infection (preventive therapy), shorten the time between disease onset and treatment initiation (case finding and diagnosis), and prevent transmission in key settings, such as the built environment (infection control). In evaluating efficacy and estimating population-level impact, cluster-randomized trials and mechanistic models play particularly prominent roles. Historical and contemporary evidence suggests that effective public health interventions can halt tuberculosis transmission, but an evidence-based approach based on knowledge of local epidemiology is necessary for success. We provide a roadmap for designing, evaluating, and modeling interventions to interrupt the process of transmission that fuels a diverse array of tuberculosis epidemics worldwide.
Measuring success: The challenge of social protection in helping eliminate tuberculosis. (2017). Shete PB., Dowdy DW, PLoS medicine, 14, e1002419
In this Perspective on the research article by William Rudgard and colleagues, Priya Shete and coauthor discuss the challenges of measuring the impact of social protection programs such as cash transfers.
Drop-out from the tuberculosis contact investigation cascade in a routine public health setting in urban Uganda: A prospective, multi-center study. (2017). Armstrong-Hough M., Turimumahoro P., Meyer AJ., Ochom E., Babirye D., Ayakaka I., Mark D., Ggita J., Cattamanchi A., Dowdy D., Mugabe F., Fair E., Haberer JE., Katamba A., Davis JL, PloS one, 12, e0187145
SETTING: Seven public tuberculosis (TB) units in Kampala, Uganda, where Uganda's national TB program recently introduced household contact investigation, as recommended by 2012 guidelines from WHO. OBJECTIVE: To apply a cascade analysis to implementation of household contact investigation in a programmatic setting. DESIGN: Prospective, multi-center observational study. METHODS: We constructed a cascade for household contact investigation to describe the proportions of: 1) index patient households recruited; 2) index patient households visited; 3) contacts screened for TB; and 4) contacts completing evaluation for, and diagnosed with, active TB. RESULTS: 338 (33%) of 1022 consecutive index TB patients were eligible for contact investigation. Lay health workers scheduled home visits for 207 (61%) index patients and completed 104 (50%). Among 287 eligible contacts, they screened 256 (89%) for symptoms or risk factors for TB. 131 (51%) had an indication for further TB evaluation. These included 59 (45%) with symptoms alone, 58 (44%) children <5, and 14 (11%) with HIV. Among 131 contacts found to be symptomatic or at risk, 26 (20%) contacts completed evaluation, including five (19%) diagnosed with and treated for active TB, for an overall yield of 1.7%. The cumulative conditional probability of completing the entire cascade was 5%. CONCLUSION: Major opportunities exist for improving the effectiveness and yield of TB contact investigation by increasing the proportion of index households completing screening visits by lay health workers and the proportion of at-risk contacts completing TB evaluation.
Linking Individual Natural History to Population Outcomes in Tuberculosis. (2017). Salvatore PP., Proaño A., Kendall EA., Gilman RH., Dowdy DW, The Journal of infectious diseases, 217, 112-121
BACKGROUND: Substantial individual heterogeneity exists in the clinical manifestations and duration of active tuberculosis. We sought to link the individual-level characteristics of tuberculosis disease to observed population-level outcomes. METHODS: We developed an individual-based, stochastic model of tuberculosis disease in a hypothetical cohort of patients with smear-positive tuberculosis. We conceptualized the disease process as consisting of 2 states-progression and recovery-including transitions between the 2. We then used a Bayesian process to calibrate the model to clinical data from the prechemotherapy era, thus identifying the rates of progression and recovery (and probabilities of transition) consistent with observed population-level clinical outcomes. RESULTS: Observed outcomes are consistent with slow rates of disease progression (median doubling time: 84 days, 95% uncertainty range 62-104) and a low, but nonzero, probability of transition from disease progression to recovery (median 16% per year, 95% uncertainty range 11%-21%). Other individual-level dynamics were less influential in determining observed outcomes. CONCLUSIONS: This simplified model identifies individual-level dynamics-including a long doubling time and low probability of immune recovery-that recapitulate population-level clinical outcomes of untreated tuberculosis patients. This framework may facilitate better understanding of the population-level impact of interventions acting at the individual host level.
Current and future trends in tuberculosis incidence in New York City: a dynamic modelling analysis. (2017). Fojo AT., Stennis NL., Azman AS., Kendall EA., Shrestha S., Ahuja SD., Dowdy DW, The Lancet. Public health, 2, e323-e330
BACKGROUND: After steady decline since the 1990s, tuberculosis (TB) incidence in New York City (NYC) and the United States (US) has flattened. The reasons for this trend and the implications for the future trajectory of TB in the US remain unclear. METHODS: We developed a compartmental model of TB in NYC, parameterized with detailed epidemiological data. We ran the model under five alternative scenarios representing different explanations for recent declines in TB incidence. We evaluated each scenario's relative likelihood by comparing its output to available data. We used the most likely scenarios to explore drivers of TB incidence and predict future trajectories of the TB epidemic in NYC. FINDINGS: Demographic changes and declining TB transmission alone were insufficient to explain recent trends in NYC TB incidence. Only scenarios that assumed contemporary changes in TB dynamics among the foreign-born - a declining rate of reactivation or a decrease in imported subclinical TB - could accurately describe the trajectory of TB incidence since 2007. In those scenarios, the projected decline in TB incidence from 2015 to 2025 varied from minimal [2·0%/year (95% credible interval 0·4-3·5%)] to similar to 2005 to 2009 trends [4·4%/year (2·5-6·4%)]. The primary factor differentiating optimistic from pessimistic projections was the degree to which improvements in TB dynamics among the foreign-born continued into the coming decade. INTERPRETATION: Further progress against TB in NYC requires additional focus on the foreign-born population. Absent additional intervention in this group, TB incidence may not decline further.
Prevalence and Correlates of Smoking Among People Living With HIV in South Africa. (2017). Elf JL., Variava E., Chon S., Lebina L., Motlhaoleng K., Gupte N., Niaura R., Abrams D., Golub JE., Martinson N, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 20, 1124-1131
INTRODUCTION: Smoking likely exacerbates comorbidities which people living with HIV (PLWH) are predisposed. We assessed prevalence and correlates of smoking among PLWH in South Africa, which has 7 million PLWH but inadequate reporting of smoking. METHODS: A cross-sectional survey was conducted among randomly selected adults with HIV infection in Klerksdorp, South Africa. Current smoking was assessed by questionnaire, exhaled carbon monoxide (eCO), and urine cotinine. RESULTS: Of 1210 enrolled adults, 753 (62%) were women. In total, 409 (34%) self-reported ever smoking: 301 (74%) were current and 108 (26%) were former smokers. Using eCO and urine cotinine tests, 239 (52%) men and 100 (13%) women were defined as current smokers. Nearly all smokers (99%) were receiving ART, and had a median (IQR) CD4 count of 333 cells/μL (181-534), viral load of 31 IU/mL (25-4750), and BMI of 21 kg/m2 (19-24). Adjusted analysis among men showed higher odds of smoking with marijuana use (OR = 7.5, 95% CI = 4.1 to 14.6). Among women, 304 (43%) reported using snuff, compared to only 11 (3%) of men, and snuff use was inversely associated with smoking (OR = 0.1; 95% CI = 0.05 to 0.2). A subset of participants (n = 336) was asked about alcohol use, which was positively associated with smoking for men (OR = 8.1, 95% CI = 2.8 to 25.9) and women (OR = 8.5, 95% CI = 2.9 to 26.8). CONCLUSION: Smoking prevalence among PLWH in South Africa is alarmingly high. Prevention and cessation strategies that consider marijuana and alcohol use are needed. IMPLICATIONS: As long-term HIV care continues to improve, more people living with HIV (PLWH) will die of diseases, including tuberculosis, for which smoking plays an important causal role. The prevalence of smoking is markedly higher among PLWH in high-resource settings, but data for Africa and other low-resource settings that shoulder the brunt of the HIV epidemic has previously not been well documented. We report an alarmingly high prevalence of smoking among PLWH in South Africa, particularly among men, and a strong association between current smoking and use of other substances.
Preventing tuberculosis in people with HIV-no more excuses. (2017). Chaisson RE., Golub JE, The Lancet. Global health, 5, e1048-e1049
Applying the Care Group model to tuberculosis control: findings from a community-based project in Mozambique. (2017). Brown A., Ernst P., Cambule A., Morrow M., Dortzbach D., Golub JE., Perry HB, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 21, 1086-1093
BACKGROUND: We describe the effectiveness of an innovative community-based social mobilization approach called Care Groups to improve the effectiveness of the national tuberculosis (TB) program by increasing TB testing and improving treatment outcomes in six districts of rural Mozambique. METHODS: The Care Group approach, which was implemented in a population of 218 191, enabled a facilitator to meet every 6 months with 10-12 community health volunteers (forming a Care Group) to share key TB messages and then for them to convey these messages over the subsequent 6 months to 10-12 households. Three household surveys were performed over 5 years to measure population-level changes in knowledge and behaviors. Data from village TB, laboratory, and district registers were also used to monitor activities and outcomes. RESULTS: There were substantial improvements in TB-related knowledge and behaviors in the number of patients initiating treatment, in the percentage of patients receiving directly observed treatment, in treatment success, and in TB-related mortality. CONCLUSION: Care Groups are uniquely suited to address some of the challenges of TB control. This project sheds light on a new strategy for engaging communities to address not only TB, but other health priorities as well.
Factors associated with pulmonary impairment in HIV-infected South African adults. (2017). Gupte AN., Wong ML., Msandiwa R., Barnes GL., Golub J., Chaisson RE., Hoffmann CJ., Martinson NA, PloS one, 12, e0184530
BACKGROUND: HIV-infected individuals have increased risk of developing obstructive lung disease (OLD). Studies from developed countries report high viral load, low CD4 counts, and anti-retroviral therapy (ART) to be associated with OLD; but these findings may not be generalizable to populations in resource-limited settings. METHODS: We conducted a prospective cohort study of lung function in 730 HIV-infected black South African adults. Pre-bronchodilator spirometry was performed at enrollment and repeated annually for three years. Logistic regression models were used to identify factors associated with OLD, defined as FEV1/FVC<0.70, at enrollment. Excess annual declines in FEV1 and FVC were modelled as the product-term of follow-up time and exposures using random effects regression. RESULTS: Median (IQR) age at enrollment was 36 (32-41) years, 85% were female and 30% ever-smoked with a median (IQR) exposure of 3 (1-6) pack-years. Median (IQR) CD4 count and viral load at enrollment were 372 (261-518) cells/mm3 and 2655 (91-13,548) copies/mL respectively. Overall, 25% were receiving ART at enrollment, 16% of whom reported at least 6 months of ART receipt. OLD was found in 35 (5%) at enrollment. Increasing age (aOR = 2.08 per 10-years [95%CI 1.22-3.57], p = 0.007), current smoking (aOR = 3.55 [95%CI 1.20-10.53], p = 0.02), and CRP (aOR = 1.01 per unit-increase [95%CI 1.00-1.03], p = 0.04) were significantly associated with OLD at enrollment; while increasing CD4 count (aOR = 1.02 per-100 cells/mm3 [95%CI 0.85-1.22], p = 0.82), viral load (aOR = 0.67 per log-increase [95%CI 0.43-1.10], p = 0.12) and receipt of ART (aOR = 0.57 [95%CI 0.18-1.75], p = 0.32) were not. The median (IQR) follow-up time was 18 (12-24) months. Participants with a history of tuberculosis (TB) had a 35 mL (95%CI 2-68, p = 0.03) and 57 mL (95%CI 19-96, p = 0.003) per year excess loss of FEV1 and FVC respectively. CONCLUSION: Prevalent OLD was associated with older age, current smoking and higher CRP levels, but not CD4 counts and ART, in HIV-infected South African adults. Better understanding of the long-term effects of TB, smoking and inflammation on lung function in HIV-infected populations is urgently needed.
Point-of-care C-reactive protein-based tuberculosis screening for people living with HIV: a diagnostic accuracy study. (2017). Yoon C., Semitala FC., Atuhumuza E., Katende J., Mwebe S., Asege L., Armstrong DT., Andama AO., Dowdy DW., Davis JL., Huang L., Kamya M., Cattamanchi A, The Lancet. Infectious diseases, 17, 1285-1292
BACKGROUND: Symptom-based screening for tuberculosis is recommended for all people living with HIV. This recommendation results in unnecessary Xpert MTB/RIF testing in many individuals living in tuberculosis-endemic areas and thus poor implementation of intensified case finding and tuberculosis preventive therapy. Novel approaches to tuberculosis screening are needed to help achieve global targets for tuberculosis elimination. We assessed the performance of C-reactive protein (CRP) measured with a point-of-care assay as a screening tool for active pulmonary tuberculosis. METHODS: For this prospective study, we enrolled adults (aged ≥18 years) living with HIV with CD4 cell count less than or equal to 350 cells per μL who were initiating antiretroviral therapy (ART) from two HIV/AIDS clinics in Uganda. CRP concentrations were measured at study entry with a point-of-care assay using whole blood obtained by fingerprick (concentration ≥10 mg/L defined as screen positive for tuberculosis). Sputum samples were collected for Xpert MTB/RIF testing and culture. We calculated the sensitivity and specificity of point-of-care CRP and WHO symptom-based screening in reference to culture results. We repeated the sensitivity analysis with Xpert MTB/RIF as the reference standard. FINDINGS: Between July 8, 2013, and Dec 15, 2015, 1237 HIV-infected adults were enrolled and underwent point-of-care CRP testing. 60 (5%) patients with incomplete or contaminated cultures were excluded from the analysis. Of the remaining 1177 patients (median CD4 count 165 cells per μL [IQR 75-271]), 163 (14%) had culture-confirmed tuberculosis. Point-of-care CRP testing had 89% sensitivity (145 of 163, 95% CI 83-93) and 72% specificity (731 of 1014, 95% CI 69-75) for culture-confirmed tuberculosis. Compared with WHO symptom-based screening, point-of-care CRP testing had lower sensitivity (difference -7%, 95% CI -12 to -2; p=0·002) but substantially higher specificity (difference 58%, 95% CI 55 to 61; p<0·0001). When Xpert MTB/RIF results were used as the reference standard, sensitivity of point-of-care CRP and WHO symptom-based screening were similar (94% [79 of 84] vs 99% [83 of 84], respectively; difference -5%, 95% CI -12 to 2; p=0·10). INTERPRETATION: The performance characteristics of CRP support its use as a tuberculosis screening test for people living with HIV with CD4 count less than or equal to 350 cells per μL who are initiating ART. HIV/AIDS programmes should consider point-of-care CRP-based tuberculosis screening to improve the efficiency of intensified case finding and increase uptake of tuberculosis preventive therapy. FUNDING: National Institutes of Health; President's Emergency Plan for AIDS Relief; University of California, San Francisco, Nina Ireland Program for Lung Health.
Modelling the social and structural determinants of tuberculosis: opportunities and challenges. (2017). Pedrazzoli D., Boccia D., Dodd PJ., Lönnroth K., Dowdy DW., Siroka A., Kimerling ME., White RG., Houben RMGJ, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 21, 957-964
INTRODUCTION: Despite the close link between tuberculosis (TB) and poverty, most mathematical models of TB have not addressed underlying social and structural determinants. OBJECTIVE: To review studies employing mathematical modelling to evaluate the epidemiological impact of the structural determinants of TB. METHODS: We systematically searched PubMed and personal libraries to identify eligible articles. We extracted data on the modelling techniques employed, research question, types of structural determinants modelled and setting. RESULTS: From 232 records identified, we included eight articles published between 2008 and 2015; six employed population-based dynamic TB transmission models and two non-dynamic analytic models. Seven studies focused on proximal TB determinants (four on nutritional status, one on wealth, one on indoor air pollution, and one examined overcrowding, socio-economic and nutritional status), and one focused on macro-economic influences. CONCLUSIONS: Few modelling studies have attempted to evaluate structural determinants of TB, resulting in key knowledge gaps. Despite the challenges of modelling such a complex system, models must broaden their scope to remain useful for policy making. Given the intersectoral nature of the interrelations between structural determinants and TB outcomes, this work will require multidisciplinary collaborations. A useful starting point would be to focus on developing relatively simple models that can strengthen our knowledge regarding the potential effect of the structural determinants on TB outcomes.
Correction: Optimal costs of HIV pre-exposure prophylaxis for men who have sex with men. (2017). McKenney J., Chen A., Hoover KW., Kelly J., Dowdy D., Kasaie P., Sullivan PS., Rosenberg ES, PloS one, 12, e0182593
[This corrects the article DOI: 10.1371/journal.pone.0178170.].
Qualitative Exploration of a Smoking Cessation Trial for People Living With HIV in South Africa. (2017). Krishnan N., Gittelsohn J., Ross A., Elf J., Chon S., Niaura R., Martinson N., Golub JE, Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 20, 1117-1123
INTRODUCTION: In South Africa, people living with HIV have a high prevalence of smoking, which undermines the beneficial effects of antiretroviral therapy. However, little is known about barriers to smoking cessation and what interventions work for people living with HIV in this setting. METHODS: A randomized trial comparing intensive anti-smoking counseling versus counseling and nicotine replacement therapy was recently concluded in Klerksdorp, South Africa. In a post-trial follow-up, 23 in-depth interviews with patients and one focus group discussion with counselors from the trial were conducted. A codebook was developed and codes were applied to the transcripts, which were analyzed using a thematic analysis. RESULTS: Barriers at the economic, social/interpersonal, and individual levels induced stress, which hindered smoking cessation. Economic stressors included unemployment and poverty. Social or interpersonal stressors were lack of social support for quitting smoking and lack of social support due to having HIV. Individual stressors were traumatic life events. Alcohol was used to cope with stress and frequently co-occurred with smoking. Managing cravings was a barrier unrelated to stress. Participants proposed income and employment opportunities, group counseling, and more frequent counseling as solutions to address stressors at different levels. Nicotine replacement therapy was helpful to mitigate cravings. CONCLUSIONS: Future smoking cessation interventions need to target barriers at multiple levels. Increasing the supply and duration of nicotine replacement therapy may increase its effectiveness. Other behavioral approaches such as group counseling or peer counseling could hold promise in this setting but need to be tested for efficacy through randomized controlled trials. IMPLICATIONS: To our knowledge, this is the first qualitative study examining barriers to smoking cessation for people living with HIV in South Africa. Smoking is highly prevalent among people with HIV in South Africa and cessation interventions are urgently needed. A better understanding of barriers to smoking cessation that people with HIV face will lead to the development of contextually appropriate interventions. This study also provides feedback on interventions from a recently concluded smoking cessation randomized trial and will help guide the design of future smoking cessation trials.
Feasibility of a streamlined tuberculosis diagnosis and treatment initiation strategy. (2017). Shete PB., Nalugwa T., Farr K., Ojok C., Nantale M., Howlett P., Haguma P., Ochom E., Mugabe F., Joloba M., Chaisson LH., Dowdy DW., Moore D., Davis JL., Katamba A., Cattamanchi A, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 21, 746-752
OBJECTIVE: To assess the feasibility of a streamlined strategy for improving tuberculosis (TB) diagnostic evaluation and treatment initiation among patients with presumed TB. DESIGN: Single-arm interventional pilot study at five primary care health centers of a streamlined, SIngle-saMPLE (SIMPLE) TB diagnostic evaluation strategy: 1) examination of two smear results from a single spot sputum specimen using light-emitting diode fluorescence microscopy, and 2) daily transportation of smear-negative sputum samples to Xpert® MTB/RIF testing sites. RESULTS: Of 1212 adults who underwent sputum testing for TB, 99.6% had two smears examined from the spot sputum specimen. Sputum was transported for Xpert testing within 1 clinic day for 83% (907/1091) of the smear-negative patients. Of 157 (13%) patients with bacteriologically positive TB, 116 (74%) were identified using sputum smear microscopy and 41 (26%) using Xpert testing of smear-negative samples. Anti-tuberculosis treatment was initiated in 142 (90%) patients with bacteriologically positive TB, with a median time to treatment of 1 day for smear-positive patients and 6 days for smear-negative, Xpert-positive patients. CONCLUSION: The SIMPLE TB strategy led to successful incorporation of Xpert testing and rapid treatment initiation in the majority of patients with bacteriologically confirmed TB in a resource-limited setting.
Cost-effectiveness of triage testing for facility-based systematic screening of tuberculosis among Ugandan adults. (2017). Murray M., Cattamanchi A., Denkinger C., Van't Hoog A., Pai M., Dowdy D, BMJ global health, 1, e000064
BACKGROUND: Systematic screening is often proposed as a way to improve case finding for tuberculosis (TB), but the cost-effectiveness of specific strategies for systematic screening remains poorly studied. METHODS: We constructed a Markov-based decision analytic model to analyse the cost-effectiveness of triage testing for TB in Uganda, compared against passive case detection with Xpert MTB/RIF. We assumed a triage algorithm whereby all adults presenting to healthcare centres would be screened for cough, and those with cough of at least 2 weeks would receive the triage test, with positive triage results confirmed by Xpert MTB/RIF. We adopted the perspective of the TB control sector, using a primary outcome of the cost per year of life gained (YLG) over a lifetime time horizon. RESULTS: Systematic screening in a population with a 5% underlying prevalence of TB was estimated to cost US$610 per YLG (95% uncertainty range US$200-US$1859) with chest X-ray (CXR) (US$5 per test, specificity 0.67), or US$588 (US$221-US$1746) with C reactive protein (CRP) (US$3 per test, specificity 0.59). In addition to the cost and specificity of the triage test, cost-effectiveness was most sensitive to the underlying prevalence of TB, monthly risk of mortality in people with untreated TB and the proportion of patients with TB who would be treated in the absence of systematic screening. CONCLUSIONS: To optimise the cost-effectiveness of facility-based systematic screening of TB with a triage test, it must be carried out in a high-risk population, or use triage tests that are cheaper or more specific than CXR or CRP.
Tuberculosis screening among persons with diabetes mellitus in Pune, India. (2017). Mave V., Nimkar S., Prasad H., Kadam D., Meshram S., Lokhande R., Gupte N., Jain D., Gupta A., Golub JE, BMC infectious diseases, 17, 388
BACKGROUND: Diabetes mellitus (DM) increases tuberculosis (TB) risk, and there is increasing concern over the public health implications of the convergence of these two epidemics. Screening for TB among people with DM is now recommended in India. METHODS: People with DM seeking care at a large public sector tertiary care hospital clinic in Pune, India, were screened for TB from June 2015 to May 2016. All consenting people with DM were screened for TB at each clinic visit using a five-item, WHO-recommended questionnaire and those with TB symptoms and/or risk factors were tested for active TB using sputum smear microscopty, Xpert® MTB/RIF and TB culture. Categorical data and continuous variables were summarized using descriptive statistics. The x (2) test or Wilcoxon rank-sum test was used to ascertain significant associations between categorical and continuous variables, respectively. RESULTS: Among 630 adults approached for screening, median age was 60 (interquartile range (IQR), 57-64) years and 350 (56%) were females. Median hemoglobin A1c (HbA1c) was 8.7% (IQR, 6.7-9.9) and 444 (70.5%) were poorly controlled DM (HbA1c > 7). Forty-four (7%) had prior history of TB but the proportion with TB risk factors at screening was low (<5%). While 18% of participants reported any TB symptoms, none of these patients were diagnosed with culture confirmed TB. CONCLUSIONS: Our study failed to yield any active TB cases using a WHO-recommended questionnaire among people with DM. High TB risk populations among people with DM must be identified if TB screening is to be feasible in settings such as India where the DM epidemic continues to rise.
Optimal costs of HIV pre-exposure prophylaxis for men who have sex with men. (2017). McKenney J., Chen A., Hoover KW., Kelly J., Dowdy D., Sharifi P., Sullivan PS., Rosenberg ES, PloS one, 12, e0178170
INTRODUCTION: Men who have sex with men (MSM) are disproportionately affected by HIV due to their increased risk of infection. Oral pre-exposure prophylaxis (PrEP) is a highly effictive HIV-prevention strategy for MSM. Despite evidence of its effectiveness, PrEP uptake in the United States has been slow, in part due to its cost. As jurisdictions and health organizations begin to think about PrEP scale-up, the high cost to society needs to be understood. METHODS: We modified a previously-described decision-analysis model to estimate the cost per quality-adjusted life-year (QALY) gained, over a 1-year duration of PrEP intervention and lifetime time horizon. Using updated parameter estimates, we calculated: 1) the cost per QALY gained, stratified over 4 strata of PrEP cost (a function of both drug cost and provider costs); and 2) PrEP drug cost per year required to fall at or under 4 cost per QALY gained thresholds. RESULTS: When PrEP drug costs were reduced by 60% (with no sexual disinhibition) to 80% (assuming 25% sexual disinhibition), PrEP was cost-effective (at <$100,000 per QALY averted) in all scenarios of base-case or better adherence, as long as the background HIV prevalence was greater than 10%. For PrEP to be cost saving at base-case adherence/efficacy levels and at a background prevalence of 20%, drug cost would need to be reduced to $8,021 per year with no disinhibition, and to $2,548 with disinhibition. CONCLUSION: Results from our analysis suggest that PrEP drug costs need to be reduced in order to be cost-effective across a range of background HIV prevalence. Moreover, our results provide guidance on the pricing of generic emtricitabine/tenofovir disoproxil fumarate, in order to provide those at high risk for HIV an affordable prevention option without financial burden on individuals or jurisdictions scaling-up coverage.
Improving active case finding for tuberculosis in South Africa: informing innovative implementation approaches in the context of the Kharitode trial through formative research. (2017). Kerrigan D., West N., Tudor C., Hanrahan CF., Lebina L., Msandiwa R., Mmolawa L., Martinson N., Dowdy D, Health research policy and systems, 15, 42
BACKGROUND: Tuberculosis (TB) is the leading infectious killer worldwide, with approximately 1.8 million deaths in 2015. While effective treatment exists, implementation of active case finding (ACF) methods to identify persons with active TB in a timely and cost-effective manner continues to be a major challenge in resource-constrained settings. Limited qualitative work has been conducted to gain an in-depth understanding of implementation barriers. METHODS: Qualitative research was conducted to inform the development of three ACF strategies for TB to be evaluated as part of the Kharitode cluster-randomised trial being conducted in a rural province of South Africa. This included 25 semi-structured in-depth interviews among 8 TB patients, 7 of their household members and 10 clinic health workers, as well as 4 focus group discussions (2 rural and 2 main town locations) with 6-8 participants each (n = 27). Interviews and focus group discussions explored the context, advantages and limitations, as well as the implications of three ACF methods. Content analysis was utilised to document salient themes regarding their feasibility, acceptability and potential effectiveness. RESULTS: Study participants (TB patients and community members) reported difficulty identifying TB symptoms and seeking care in a timely fashion. In turn, all stakeholder groups felt that more proactive case finding strategies would be beneficial. Clinic-based strategies (including screening all patients regardless of visit purpose) were seen as the most acceptable method based on participants' preference ranking of the ACF strategies. However, given the resource constraints experienced by the public healthcare system in South Africa, many participants doubted whether it would be the most effective strategy. Household outreach and incentive-based strategies were described as promising, but participants reported some concerns (e.g. stigma in case of household-based and ethical concerns in the case of incentives). Participants offered insights into how to optimise each strategy, tailoring implementation to community needs (low TB knowledge) and realities (financial constraints, transport, time off from work). CONCLUSIONS: Findings suggest different methods of TB ACF are likely to engage different populations, highlighting the utility of a comprehensive approach. TRIAL REGISTRATION: Clinicaltrials.gov ( NCT02808507 ). Registered June 1, 2016. The participants in this formative study are not trial participants.
Reply to Anthony et al., "Protecting Pyrazinamide, a Priority for Improving Outcomes in Multidrug-Resistant Tuberculosis Treatment". (2017). Fofana MO., Dowdy DW, Antimicrobial agents and chemotherapy, 61