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<h1 class='titleban'>TB Modeling and Translational Epi Group</h1>
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<h1>Group Publications</h1>
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<div class='abstract_nav'><p>Page Navigation:</p><a href='publication0.html'>1</a><a href='publication1.html'>2</a><a href='publication2.html'>3</a><a href='publication3.html'>4</a><a href='publication4.html'>5</a><a href='publication5.html'>6</a><a class='current'>7</a><a href='publication7.html'>8</a><a href='publication8.html'>9</a><a href='publication9.html'>10</a></div><h2> - November 2018 - </h2><div class='abstract'><p><span class='b'>Simple Inclusion of Complex Diagnostic Algorithms in Infectious Disease Models for Economic Evaluation.</span> (2018). Dodd PJ., Pennington JJ., Bronner Murrison L., Dowdy DW, <span class='i'>Medical decision making : an international journal of the Society for Medical Decision Making</span>, <span class='i'>38</span>, 930-941</p><div><a id='ab_btn_120'>View Abstract Text</a><div id='ab_txt_120' class='hidden_abstract'><p>INTRODUCTION: Cost-effectiveness models for infectious disease interventions often require transmission models that capture the indirect benefits from averted subsequent infections. Compartmental models based on ordinary differential equations are commonly used in this context. Decision trees are frequently used in cost-effectiveness modeling and are well suited to describing diagnostic algorithms. However, complex decision trees are laborious to specify as compartmental models and cumbersome to adapt, limiting the detail of algorithms typically included in transmission models. METHODS: We consider an approximation replacing a decision tree with a single holding state for systems where the time scale of the diagnostic algorithm is shorter than time scales associated with disease progression or transmission. We describe recursive algorithms for calculating the outcomes and mean costs and delays associated with decision trees, as well as design strategies for computational implementation. We assess the performance of the approximation in a simple model of transmission/diagnosis and its role in simplifying a model of tuberculosis diagnostics. RESULTS: When diagnostic delays were short relative to recovery rates, our approximation provided a good account of infection dynamics and the cumulative costs of diagnosis and treatment. Proportional errors were below 5% so long as the longest delay in our 2-step algorithm was under 20% of the recovery time scale. Specifying new diagnostic algorithms in our tuberculosis model was reduced from several tens to just a few lines of code. DISCUSSION: For conditions characterized by a diagnostic process that is neither instantaneous nor protracted (relative to transmission dynamics), this novel approach retains the advantages of decision trees while embedding them in more complex models of disease transmission. Concise specification and code reuse increase transparency and reduce potential for error.</p></div></div></div><div class='abstract'><p><span class='b'>Economic and epidemiologic impact of guidelines for early ART initiation irrespective of CD4 count in Spain.</span> (2018). Kasaie P., Radford M., Kapoor S., Jung Y., Hernandez Novoa B., Dowdy D., Shah M, <span class='i'>PloS one</span>, <span class='i'>13</span>, e0206755</p><div><a id='ab_btn_121'>View Abstract Text</a><div id='ab_txt_121' class='hidden_abstract'><p>INTRODUCTION: Emerging data suggest that early antiretroviral therapy (ART) could reduce serious AIDS and non-AIDS events and deaths but could also increase costs. In January 2016, the Spanish guidelines were updated to recommend ART at any CD4 count. However, the epidemiologic and economic impacts of early ART initiation in Spain remain unclear. METHODS: The Johns Hopkins HIV Economic-Epidemiologic Mathematical Model (JHEEM) was utilized to estimate costs, transmissions, and outcomes in Spain over 20 years. We compared implementation of guidelines for early ART initiation to a counterfactual scenario deferring ART until CD4-counts fall below 350 cells/mm3. We additionally studied the impact of early ART initiation in combination with improvements to HIV screening, care linkage and engagement. RESULTS: Early ART initiation (irrespective of CD4-count) is expected to avert 20,100 [95% Uncertainty Range (UR) 11,100-83,000] new HIV cases over the next two decades compared to delayed ART (28% reduction), at an incremental health system cost of €1.05 billion [€0.66 - €1.63] billion, and an incremental cost-effectiveness ratio (ICER) of €29,700 [€13,700 - €41,200] per QALY gained. Projected ICERs declined further over longer time horizon; e.g., an ICER of €12,691 over 30 years. Furthermore, the impact of early ART initiation was potentiated by improved HIV screening among high-risk individuals, averting an estimated 41,600 [23,200-172,200] HIV infections (a 58% decline) compared to delayed ART. CONCLUSIONS: Recommendations for ART initiation irrespective of CD4-counts are cost-effective and could avert > 30% of new cases in Spain. Improving HIV diagnosis can amplify this impact.</p></div></div></div><div class='abstract'><p><span class='b'>Tuberculosis Incidence Among Populations at High Risk in California, Florida, New York, and Texas, 2011-2015.</span> (2018). Cherng ST., Shrestha S., Reynolds S., Hill AN., Marks SM., Kelly J., Dowdy DW, <span class='i'>American journal of public health</span>, <span class='i'>108</span>, S311-S314</p><div><a id='ab_btn_122'>View Abstract Text</a><div id='ab_txt_122' class='hidden_abstract'><p>OBJECTIVES: To illustrate the magnitude of between-state heterogeneities in tuberculosis (TB) incidence among US populations at high risk for TB that may help guide state-specific strategies for TB elimination. METHODS: We used data from the National Tuberculosis Surveillance System and other public sources from 2011 to 2015 to calculate TB incidence in every US state among people who were non-US-born, had diabetes, or were HIV-positive, homeless, or incarcerated. We then estimated the proportion of TB cases that reflected the difference between each state's reported risk factor-specific TB incidence and the lowest incidence achieved among 4 states (California, Florida, New York, Texas). We reported these differences for the 4 states and also calculated and aggregated across all 50 states to quantify the total percentage of TB cases nationally that reflected between-state differences in risk factor-specific TB incidence. RESULTS: On average, 24% of recent TB incidence among high-risk US populations reflected heterogeneity at the state level. The populations that accounted for the greatest percentage of heterogeneity-reflective cases were non-US-born individuals (51%) and patients with diabetes (24%). CONCLUSIONS: State-level differences in TB incidence among key populations provide clues for targeting state-level interventions.</p></div></div></div><div class='abstract'><p><span class='b'>The Importance of Heterogeneity to the Epidemiology of Tuberculosis.</span> (2018). Trauer JM., Dodd PJ., Gomes MGM., Gomez GB., Houben RMGJ., McBryde ES., Melsew YA., Menzies NA., Arinaminpathy N., Shrestha S., Dowdy DW, <span class='i'>Clinical infectious diseases : an official publication of the Infectious Diseases Society of America</span>, <span class='i'>69</span>, 159-166</p><div><a id='ab_btn_123'>View Abstract Text</a><div id='ab_txt_123' class='hidden_abstract'><p>Although less well-recognized than for other infectious diseases, heterogeneity is a defining feature of tuberculosis (TB) epidemiology. To advance toward TB elimination, this heterogeneity must be better understood and addressed. Drivers of heterogeneity in TB epidemiology act at the level of the infectious host, organism, susceptible host, environment, and distal determinants. These effects may be amplified by social mixing patterns, while the variable latent period between infection and disease may mask heterogeneity in transmission. Reliance on notified cases may lead to misidentification of the most affected groups, as case detection is often poorest where prevalence is highest. Assuming that average rates apply across diverse groups and ignoring the effects of cohort selection may result in misunderstanding of the epidemic and the anticipated effects of control measures. Given this substantial heterogeneity, interventions targeting high-risk groups based on location, social determinants, or comorbidities could improve efficiency, but raise ethical and equity considerations.</p></div></div></div><h2> - October 2018 - </h2><div class='abstract'><p><span class='b'>Projected population-wide impact of antiretroviral therapy-linked isoniazid preventive therapy in a high-burden setting.</span> (2018). Kendall EA., Azman AS., Maartens G., Boulle A., Wilkinson RJ., Dowdy DW., Rangaka MX, <span class='i'>AIDS (London, England)</span>, <span class='i'>33</span>, 525-536</p><div><a id='ab_btn_124'>View Abstract Text</a><div id='ab_txt_124' class='hidden_abstract'><p>OBJECTIVE: Both isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) reduce tuberculosis risk in individuals living with HIV. We sought to estimate the broader, population-wide impact of providing a pragmatically implemented 12-month IPT regimen to ART recipients in a high-burden community. DESIGN: Dynamic transmission model of a tuberculosis (TB)-HIV epidemic, calibrated to site-specific, historical epidemiologic and clinical trial data from Khayelitsha, South Africa. METHODS: We projected the 5-year impact of delivering a 12-month IPT regimen community-wide to 85% of new ART initiators and 15%/year of those already on ART, accounting for IPT-attributable reductions in TB infection, progression, and transmission. We also evaluated scenarios of continuously-delivered IPT, ongoing ART scale-up, and lower tuberculosis incidence. RESULTS: Under historical (early 2010) ART coverage, this ART-linked IPT intervention prevented one tuberculosis case per 18 [95% credible interval (CrI) 11-29] people treated. It lowered TB incidence by a projected 23% (95% CrI 14-30%) among people receiving ART, and by 5.2% (95% CrI 2.9-8.7%) in the total population. Continuous IPT reduced the number needed to treat to prevent one case of TB to 10 (95% CrI 7-16), though it required 74% more person-years of therapy (95% CrI 64-94%) to prevent one TB case, relative to 12-month therapy. Under expanding ART coverage, the tuberculosis incidence reduction achieved by 12-month IPT grew to 7.6% (95% CrI 4.3-12.6%). Effect sizes were similar in a simulated setting of lower TB incidence. CONCLUSIONS: IPT in conjunction with ART reduces tuberculosis incidence among those who receive therapy and has additional impact on tuberculosis transmission in the population.</p></div></div></div><h2> - September 2018 - </h2><div class='abstract'><p><span class='b'>The association of household fine particulate matter and kerosene with tuberculosis in women and children in Pune, India.</span> (2018). Elf JL., Kinikar A., Khadse S., Mave V., Suryavanshi N., Gupte N., Kulkarni V., Patekar S., Raichur P., Paradkar M., Kulkarni V., Pradhan N., Breysse PN., Gupta A., Golub JE, <span class='i'>Occupational and environmental medicine</span>, <span class='i'>76</span>, 40-47</p><div><a id='ab_btn_125'>View Abstract Text</a><div id='ab_txt_125' class='hidden_abstract'><p>OBJECTIVES: Household air pollution (HAP) is a risk factor for respiratory disease, however has yet to be definitively associated with tuberculosis (TB). We aimed to assess the association between HAP and TB. METHODS: A matched case-control study was conducted among adult women and children patients with TB and healthy controls matched on geography, age and sex. HAP was assessed using questionnaires for pollution sources and 24-hour household concentrations of particulate matter <2.5 μm in diameter (PM(2.5)). RESULTS: In total, 192 individuals in 96 matched pairs were included. The median 24-hour time-weighted average PM(2.5) was nearly seven times higher than the WHO's recommendation of 25 µg/m(3), and did not vary between controls (179 µg/m(3); IQR: 113-292) and cases (median 157 µg/m(3); 95% CI 93 to 279; p=0.57). Reported use of wood fuel was not associated with TB (OR 2.32; 95% CI 0.65 to 24.20) and kerosene was significantly associated with TB (OR 5.49, 95% CI 1.24 to 24.20) in adjusted analysis. Household PM(2.5) was not associated with TB in univariate or adjusted analysis. Controlling for PM(2.5) concentration, kerosene was not significantly associated with TB, but effect sizes ranged from OR 4.30 (95% CI 0.78 to 30.86; p=0.09) to OR 5.49 (0.82 to 36.75; p=0.08). CONCLUSIONS: Use of kerosene cooking fuel is positively associated with TB in analysis using reported sources of exposure. Ubiquitously high levels of particulates limited detection of a difference in household PM(2.5) between cases and controls.</p></div></div></div><div class='abstract'><p><span class='b'>Yield and Efficiency of Novel Intensified Tuberculosis Case-Finding Algorithms for People Living with HIV.</span> (2018). Yoon C., Semitala FC., Asege L., Katende J., Mwebe S., Andama AO., Atuhumuza E., Nakaye M., Armstrong DT., Dowdy DW., McCulloch CE., Kamya M., Cattamanchi A, <span class='i'>American journal of respiratory and critical care medicine</span>, <span class='i'>199</span>, 643-650</p><div><a id='ab_btn_126'>View Abstract Text</a><div id='ab_txt_126' class='hidden_abstract'><p>RATIONALE: The recommended tuberculosis (TB) intensified case finding (ICF) algorithm for people living with HIV (symptom-based screening followed by Xpert MTB/RIF [Xpert] testing) is insufficiently sensitive and results in unnecessary Xpert testing. OBJECTIVES: To evaluate whether novel ICF algorithms combining C-reactive protein (CRP)-based screening with urine Determine TB-LAM (TB-LAM), sputum Xpert, and/or sputum culture could improve ICF yield and efficiency. METHODS: We compared the yield and efficiency of novel ICF algorithms inclusive of point-of-care CRP-based TB screening and confirmatory testing with urine TB-LAM (if CD4 count ≤100 cells/μl), sputum Xpert, and/or a single sputum culture among consecutive people living with HIV with CD4 counts less than or equal to 350 cells/μl initiating antiretroviral therapy in Uganda. MEASUREMENTS AND MAIN RESULTS: Of 1,245 people living with HIV, 203 (16%) had culture-confirmed TB including 101 (49%) patients with CD4 counts less than or equal to 100 cells/μl. Compared with the current ICF algorithm, point-of-care CRP-based TB screening followed by Xpert testing had similar yield (56% [95% confidence interval, 49-63] vs. 59% [95% confidence interval, 51-65]) but consumed less than half as many Xpert assays per TB case detected (9 vs. 4). Addition of TB-LAM did not significantly increase diagnostic yield relative to the current ICF algorithm but provided same-day diagnosis for 26% of TB patients with advanced HIV. Addition of a single culture to TB-LAM and Xpert substantially improved ICF yield, identifying 78% of all TB cases. CONCLUSIONS: Point-of-care CRP-based screening can improve ICF efficiency among people living with HIV. Addition of TB-LAM and a single culture to Xpert confirmatory testing could enable HIV programs to increase the speed of TB diagnosis and ICF yield.</p></div></div></div><div class='abstract'><p><span class='b'>COach2Quit: A Pilot Randomized Controlled Trial of a Personal Carbon Monoxide Monitor for Smoking Cessation.</span> (2018). Krishnan N., Elf JL., Chon S., Golub JE, <span class='i'>Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco</span>, <span class='i'>21</span>, 1573-1577</p><div><a id='ab_btn_127'>View Abstract Text</a><div id='ab_txt_127' class='hidden_abstract'><p>INTRODUCTION: Mobile phone-based messaging support and biomarker feedback independently show evidence of increasing an individual's likelihood of quitting smoking. However, the combination of these two strategies to facilitate smoking cessation has not been adequately explored. METHODS: We conducted a randomized controlled trial in Baltimore, Maryland, to assess the efficacy of COach2Quit, a smartphone application that provides exhaled carbon monoxide readings with message support. The primary outcome was self-reported and biochemically verified smoking cessation at 30-day follow-up. Secondary outcomes were reduction in smoking, motivation to quit, and engagement and satisfaction with COach2Quit. An intention-to-treat analysis was conducted. RESULTS: Adult smokers were randomized 1:1 to receive brief advice and COach2Quit (intervention, n = 50) or brief advice only (control, n = 52). Thirteen participants were lost to follow-up. At 30-day follow-up, one participant in each arm quit smoking. Median change in carbon monoxide levels (in parts per million (ppm)) (intervention: -3.0 [interquartile range (IQR) -12.0, 2.0]; control: -2.5 [IQR -9.0, 2.0]) and median change in number of cigarettes smoked per day (intervention: -5.5 [IQR -14.0, -1.0]; control: -6.0 [IQR -10.0, -2.0]) was similar between study arms. There was no significant difference in mean percent change in the Reasons for Quitting scale score (intervention: 6.3 [95% confidence interval = -2.2% to 14.8%]; control: -3.6 [95% confidence interval = -9.2% to 2.1%]). A majority (n = 32, 91%) of participants liked having COach2Quit to help them quit smoking. CONCLUSIONS: There were no significant differences in smoking cessation, smoking reduction, and motivation to quit between study arms. However, high satisfaction with the COach2Quit application indicates its feasibility and acceptability as a smoking cessation tool. IMPLICATIONS: Smoking is the leading preventable cause of morbidity and mortality in the United States. Although counseling and pharmacotherapy are efficacious for smoking cessation, they are not easily accessible or desirable to all smokers, highlighting the need for identifying other interventions. There is evidence for the efficacy of mobile phone-based messaging support for smoking cessation. However, there is limited research on the efficacy of biomarker feedback, much less interventions that combine these two approaches. This research contributes to filling this gap and identifying novel interventions to facilitate smoking cessation.</p></div></div></div><h2> - August 2018 - </h2><div class='abstract'><p><span class='b'>Chest X-ray for tuberculosis preventive therapy: use caution.</span> (2018). Hanrahan C., Dowdy D, <span class='i'>The lancet. HIV</span>, <span class='i'>5</span>, e478-e479</p></div><div class='abstract'><p><span class='b'>Inequalities in HAART uptake and differential survival according to exposure category in Rio de Janeiro, Brazil.</span> (2018). Lima TA., Beyrer C., Golub JE., Mota JCD., Malta MS., Silva CMFPD., Bastos FI, <span class='i'>Cadernos de saude publica</span>, <span class='i'>34</span>, e00009617</p><div><a id='ab_btn_129'>View Abstract Text</a><div id='ab_txt_129' class='hidden_abstract'><p>Despite substantial improvement in prognosis and quality of life among people living with HIV/AIDS (PLWHA) in Brazil, inequalities in access to treatment remain. We assessed the impact of these inequalities on survival in Rio de Janeiro over a 12-year period (2000/11). Data were merged from four databases that comprise the national AIDS monitoring system: SINAN-AIDS (Brazilian Information System for Notificable Diseases; AIDS cases), SISCEL (laboratory tests), SICLOM (electronic dispensing system), and SIM (Brazilian Mortality Information System), using probabilistic linkage. Cox regressions were fitted to assess the impact of HAART (highly active antiretroviral therapy) on AIDS-related mortality among men who have sex with men (MSM), people who inject drugs (PWID), and heterosexuals diagnosed with AIDS, between 2000 and 2011, in the city of Rio de Janeiro, RJ, Brazil. Among 15,420 cases, 60.7% were heterosexuals, 36.1% MSM and 3.2% PWID. There were 2,807 (18.2%) deaths and the median survival time was 6.29. HAART and CD4+ > 200 at baseline were associated with important protective effects. Non-whites had a 33% higher risk of dying in consequence of AIDS than whites. PWID had a 56% higher risk and MSM a 11% lower risk of dying of AIDS than heterosexuals. Non-white individuals, those with less than eight years of formal education, and PWID, were more likely to die of AIDS and less likely to receive HAART. Important inequalities persist in access to treatment, resulting in disparate impacts on mortality among exposure categories. Despite these persistent disparities, mortality decreased significantly during the period for all categories under analysis, and the overall positive impact of HAART on survival has been dramatic.</p></div></div></div><div class='abstract'><p><span class='b'>Effect of Diabetes Mellitus on the Pharmacokinetics and Pharmacodynamics of Tuberculosis Treatment.</span> (2018). Alfarisi O., Mave V., Gaikwad S., Sahasrabudhe T., Ramachandran G., Kumar H., Gupte N., Kulkarni V., Deshmukh S., Atre S., Raskar S., Lokhande R., Barthwal M., Kakrani A., Chon S., Gupta A., Golub JE., Dooley KE, <span class='i'>Antimicrobial agents and chemotherapy</span>, <span class='i'>62</span></p><div><a id='ab_btn_130'>View Abstract Text</a><div id='ab_txt_130' class='hidden_abstract'><p>Diabetes mellitus (DM) and tuberculosis (TB) are two common diseases with increasing geographic overlap and clinical interactions. The effect of DM and hemoglobin A1c (HbA1c) values on the pharmacokinetics (PK) and pharmacodynamics (PD) of anti-TB drugs remains poorly characterized. Newly diagnosed TB patients with and without DM starting fixed-dose, thrice-weekly treatment underwent sampling for PK assessments (predose and 0.5, 2, and 6 h postdose) during the intensive and continuation phases of treatment. The effect of DM and HbA1c values on the maximum concentration (C (max)) of rifampin, isoniazid, and pyrazinamide and the association between drug concentrations and microbiologic and clinical outcomes were assessed. Of 243 patients, 101 had DM. Univariate analysis showed significant reductions in the C (max) of pyrazinamide and isoniazid (but not rifampin) with DM or increasing HbA1c values. After adjusting for age, sex, and weight, DM was associated only with reduced pyrazinamide concentrations (adjusted geometric mean ratio = 0.74, P = 0.03). In adjusted Cox models, female gender (adjusted hazards ratio [aHR] = 1.75, P = 0.001), a lower smear grade with the Xpert assay (aHR = 1.40, P < 0.001), and the pyrazinamide C (max) (aHR = 0.99, P = 0.006) were independent predictors of sputum culture conversion to negative. Higher isoniazid or rifampin concentrations were associated with a faster time to culture conversion in patients with DM only. A pyrazinamide C (max) above the therapeutic target was associated with higher unfavorable outcomes (treatment failure, relapse, death) (odds ratio = 1.92, P = 0.04). DM and higher HbA1c values increased the risk of not achieving therapeutic targets for pyrazinamide (but not rifampin or isoniazid). Higher pyrazinamide concentrations, though, were associated with worse microbiologic and clinical outcomes. DM status also appeared to influence PK-PD relationships for isoniazid and rifampin.</p></div></div></div><h2> - July 2018 - </h2><div class='abstract'><p><span class='b'>Screening for Tuberculosis With Xpert MTB/RIF Assay Versus Fluorescent Microscopy Among Adults Newly Diagnosed With Human Immunodeficiency Virus in Rural Malawi: A Cluster Randomized Trial (Chepetsa).</span> (2018). Ngwira LG., Corbett EL., Khundi M., Barnes GL., Nkhoma A., Murowa M., Cohn S., Moulton LH., Chaisson RE., Dowdy DW, <span class='i'>Clinical infectious diseases : an official publication of the Infectious Diseases Society of America</span>, <span class='i'>68</span>, 1176-1183</p><div><a id='ab_btn_131'>View Abstract Text</a><div id='ab_txt_131' class='hidden_abstract'><p>BACKGROUND: Tuberculosis (TB) remains the leading cause of death among human immunodeficiency virus (HIV)-infected individuals globally. Screening for TB at the point of HIV diagnosis with a high-sensitivity assay presents an opportunity to reduce mortality. METHODS: We performed a cluster randomized trial of TB screening among adults newly diagnosed with HIV in 12 primary health clinics in rural Thyolo, Malawi. Clinics were allocated in a 1:1 ratio to perform either point-of-care Xpert MTB/RIF assay (Xpert) or point-of-care light-emitting diode fluorescence microscopy (LED-FM) for individuals screening positive for TB symptoms. Asymptomatic participants were offered isoniazid preventive therapy in both arms. Investigators, but not clinic staff or participants, were masked to allocation. Our primary outcome was the incidence rate ratio (RR) of all-cause mortality within 12 months of HIV diagnosis. RESULTS: Prevalent TB was diagnosed in 24 of 1001 (2.4%) individuals enrolled in clinics randomized to Xpert, compared with 10 of 841 (1.2%) in clinics randomized to LED-FM. All-cause mortality was 22% lower in the Xpert arm than in the LED-FM arm (6.7 vs 8.6 per 100 person-years; RR, 0.78 [95% confidence interval {CI}, .58-1.06]). A planned subgroup analysis suggested that participants with more advanced HIV (World Health Organization clinical stage 3 or 4) disease had lower mortality in clinics randomized to Xpert than to LED-FM (RR, 0.43 [95% CI, .22-.87]). CONCLUSIONS: In rural Malawi, using point-of-care Xpert MTB/RIF to test symptomatic patients for TB at the time of HIV diagnosis reduced all-cause 12-month mortality among individuals with advanced HIV. CLINICAL TRIALS REGISTRATION: NCT01450085.</p></div></div></div><div class='abstract'><p><span class='b'>Trends in HbA1c levels and implications for diabetes screening in tuberculosis cases undergoing treatment in India.</span> (2018). Gupte AN., Mave V., Meshram S., Lokhande R., Kadam D., Dharmshale S., Bharadwaj R., Kagal A., Pradhan N., Deshmukh S., Atre S., Sahasrabudhe T., Barthwal M., Meshram S., Kakrani A., Kulkarni V., Raskar S., Suryavanshi N., Shivakoti R., Chon S., Selvin E., Gupte N., Gupta A., Golub JE, <span class='i'>The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease</span>, <span class='i'>22</span>, 800-806</p><div><a id='ab_btn_132'>View Abstract Text</a><div id='ab_txt_132' class='hidden_abstract'><p>SETTING: The optimal timing of screening for diabetes mellitus (DM) among tuberculosis (TB) cases is unclear due to the possibility of stress hyperglycemia. DESIGN: We evaluated adult (18 years) pulmonary TB cases at treatment initiation as well as at 3 months, 6 months and 12 months. DM was identified by self-report (known DM) or glycated hemoglobin (HbA1c) 6.5% (new DM). Trends in HbA1c levels during treatment were assessed using non-parametric tests. RESULTS: Of the 392 participants enrolled, 75 (19%) had DM, 30 (40%) of whom had new DM. Of the 45 participants with known DM, respectively 37 (82%) and 40 (89%) received medication to lower glucose levels at treatment initiation and completion; one participant with new DM initiated glucose-lowering medication during follow-up. The median HbA1c level in participants with known, new and no DM was respectively 10.1% (interquartile range [IQR] 8.3-11.6), 8.5% (IQR 6.7-11.5) and 5.6% (IQR 5.3-5.9) at treatment initiation, and 8.7% (IQR 6.8-11.3), 7.1% (IQR 5.8-9.5) and 5.3% (IQR 5.1-5.6) at treatment completion (P < 0.001). Overall, 5 (12%) with known and 13 (43%) with new DM at treatment initiation had reverted to HbA1c < 6.5% by treatment completion (P = 0.003); the majority of reversions occurred during the first 3 months, with no significant reversions beyond 6 months. CONCLUSION: HbA1c levels declined with anti-tuberculosis treatment. Repeat HbA1c testing at treatment completion could reduce the risk of misdiagnosis of DM.</p></div></div></div><div class='abstract'><p><span class='b'>Advancing global health and strengthening the HIV response in the era of the Sustainable Development Goals: the International AIDS Society-Lancet Commission.</span> (2018). Bekker LG., Alleyne G., Baral S., Cepeda J., Daskalakis D., Dowdy D., Dybul M., Eholie S., Esom K., Garnett G., Grimsrud A., Hakim J., Havlir D., Isbell MT., Johnson L., Kamarulzaman A., Kasaie P., Kazatchkine M., Kilonzo N., Klag M., Klein M., Lewin SR., Luo C., Makofane K., Martin NK., Mayer K., Millett G., Ntusi N., Pace L., Pike C., Piot P., Pozniak A., Quinn TC., Rockstroh J., Ratevosian J., Ryan O., Sippel S., Spire B., Soucat A., Starrs A., Strathdee SA., Thomson N., Vella S., Schechter M., Vickerman P., Weir B., Beyrer C, <span class='i'>Lancet (London, England)</span>, <span class='i'>392</span>, 312-358</p></div><div class='abstract'><p><span class='b'>Incipient and Subclinical Tuberculosis: a Clinical Review of Early Stages and Progression of Infection.</span> (2018). Drain PK., Bajema KL., Dowdy D., Dheda K., Naidoo K., Schumacher SG., Ma S., Meermeier E., Lewinsohn DM., Sherman DR, <span class='i'>Clinical microbiology reviews</span>, <span class='i'>31</span></p><div><a id='ab_btn_134'>View Abstract Text</a><div id='ab_txt_134' class='hidden_abstract'><p>Tuberculosis (TB) is the leading infectious cause of mortality worldwide, due in part to a limited understanding of its clinical pathogenic spectrum of infection and disease. Historically, scientific research, diagnostic testing, and drug treatment have focused on addressing one of two disease states: latent TB infection or active TB disease. Recent research has clearly demonstrated that human TB infection, from latent infection to active disease, exists within a continuous spectrum of metabolic bacterial activity and antagonistic immunological responses. This revised understanding leads us to propose two additional clinical states: incipient and subclinical TB. The recognition of incipient and subclinical TB, which helps divide latent and active TB along the clinical disease spectrum, provides opportunities for the development of diagnostic and therapeutic interventions to prevent progression to active TB disease and transmission of TB bacilli. In this report, we review the current understanding of the pathogenesis, immunology, clinical epidemiology, diagnosis, treatment, and prevention of both incipient and subclinical TB, two emerging clinical states of an ancient bacterium.</p></div></div></div><div class='abstract'><p><span class='b'>Prevalence and Correlates of Snuff Use, and its Association With Tuberculosis, Among Women Living With HIV in South Africa.</span> (2018). Elf JL., Variava E., Chon S., Lebina L., Motlhaoleng K., Gupte N., Niaura R., Abrams D., Martinson N., Golub JE, <span class='i'>Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco</span>, <span class='i'>21</span>, 1087-1092</p><div><a id='ab_btn_135'>View Abstract Text</a><div id='ab_txt_135' class='hidden_abstract'><p>INTRODUCTION: A higher proportion of people living with HIV (PLWH) smoke compared to the general population, but little information exists about the prevalence and correlates of smokeless tobacco use among PLWH. In South Africa, dry powdered tobacco is inhaled nasally as snuff. METHODS: A cross-sectional survey among PLWH attending three HIV clinics was conducted. Snuff use was assessed via self-report and urine cotinine. RESULTS: Given the low (3%) prevalence of snuff use among men, analysis was restricted to n = 606 nonsmoking women living with HIV. Half (n = 298, 49%) were snuff users, the majority of whom (n = 244, 84%) had a positive urine cotinine test. In adjusted analysis, snuff use was negatively associated with higher education (relative risk [RR] 0.55; 95% confidence interval [CI]: 0.39, 0.77) and mobile phone ownership (RR 0.83; 95% CI: 0.71, 0.98), and positively associated with ever having tuberculosis (TB) (RR 1.22; 95% CI: 1.03, 1.45). In adjusted analysis, with current TB as the outcome, snuff use was marginally statistically significantly associated with a twofold increase in odds of a current TB diagnosis (odds ratio [OR] 1.99; 95% CI: 0.98, 4.15). DISCUSSION: A high proportion of nonsmoking South African women living with HIV use snuff, which was a risk factor for TB. Additional research is needed to understand the relationship between snuff, TB, and other potential health risks. IMPLICATIONS: PLWH have a higher prevalence of smoking than their seronegative peers, but there is a paucity of research on smokeless tobacco use in this population, especially in low-resource settings. TB is the leading cause of death among PLWH, and with improvements to HIV treatment and care, PLWH are at greater risk of tobacco-related diseases. We report an extremely high prevalence of snuff use among women living with HIV in South Africa. Further, in this population snuff use is positively associated with ever having a TB diagnosis, as well as currently having TB.</p></div></div></div><div class='abstract'><p><span class='b'>What if They Don't Have Tuberculosis? The Consequences and Trade-offs Involved in False-positive Diagnoses of Tuberculosis.</span> (2018). Houben RMGJ., Lalli M., Kranzer K., Menzies NA., Schumacher SG., Dowdy DW, <span class='i'>Clinical infectious diseases : an official publication of the Infectious Diseases Society of America</span>, <span class='i'>68</span>, 150-156</p><div><a id='ab_btn_136'>View Abstract Text</a><div id='ab_txt_136' class='hidden_abstract'><p>To find the millions of missed tuberculosis (TB) cases, national TB programs are under pressure to expand TB disease screening and to target populations with lower disease prevalence. Together with imperfect performance and application of existing diagnostic tools, including empirical diagnosis, broader screening risks placing individuals without TB on prolonged treatment. These false-positive diagnoses have profound consequences for TB patients and prevention efforts, yet are usually overlooked in policy decision making. In this article we describe the pathways to a false-positive TB diagnosis, including trade-offs involved in the development and application of diagnostic algorithms. We then consider the wide range of potential consequences for individuals, households, health systems, and reliability of surveillance data. Finally, we suggest practical steps that the TB community can take to reduce the frequency and potential harms of false-positive TB diagnosis and to more explicitly assess the trade-offs involved in the screening and diagnostic process.</p></div></div></div><div class='abstract'><p><span class='b'>Yield of household contact tracing for tuberculosis in rural South Africa.</span> (2018). Little KM., Msandiwa R., Martinson N., Golub J., Chaisson R., Dowdy D, <span class='i'>BMC infectious diseases</span>, <span class='i'>18</span>, 299</p><div><a id='ab_btn_137'>View Abstract Text</a><div id='ab_txt_137' class='hidden_abstract'><p>BACKGROUND: Efficient and effective strategies for identifying cases of active tuberculosis (TB) in rural sub-Saharan Africa are lacking. Household contact tracing offers a potential approach to diagnose more TB cases, and to do so earlier in the disease course. METHODS: Adults newly diagnosed with active TB were recruited from public clinics in Vhembe District, South Africa. Study staff visited index case households and collected sputum specimens for TB testing via smear microscopy and culture. We calculated the yield and the number of households needed to screen (NHNS) to find one additional case. Predictors of new TB among household contacts were evaluated using multilevel logistic regression. RESULTS: We recruited 130 index cases and 282 household contacts. We identified 11 previously undiagnosed cases of bacteriologically-confirmed TB, giving a prevalence of 3.9% (95% CI: 2.0-6.9%) among contacts, a yield of 8.5 per 100 (95% CI: 4.2-15.1) index cases traced, and NHNS of 12 (95% CI: 7-24). The majority of new TB cases (10/11, 90.9%) were smear negative, culture positive. The presence of TB symptoms was not associated with an increased odds of active TB (aOR: 0.3, 95% CI: 0.1-1.4). CONCLUSIONS: Household contacts of recently diagnosed TB patients in rural South Africa have high prevalence of TB and can be feasibly detected through contact tracing, but more sensitive tests than sputum smear are required. Symptom screening among household contacts had low sensitivity and specificity for active TB in this study.</p></div></div></div><div class='abstract'><p><span class='b'>Maternal priorities for preventive therapy among HIV-positive pregnant women before and after delivery in South Africa: a best-worst scaling survey.</span> (2018). Kim HY., Dowdy DW., Martinson NA., E Golub J., Bridges JFP., Hanrahan CF, <span class='i'>Journal of the International AIDS Society</span>, <span class='i'>21</span>, e25143</p><div><a id='ab_btn_138'>View Abstract Text</a><div id='ab_txt_138' class='hidden_abstract'><p>INTRODUCTION: Pregnant women newly diagnosed with HIV during pregnancy are often lost to follow up and their adherence rates drop after delivery. We quantified changes in priorities related to isoniazid preventive therapy (IPT) and antiretroviral therapy (ART) among pregnant women living with HIV. METHODS: We enrolled pregnant women recently diagnosed with HIV from 14 primary health clinics during pregnancy and followed them after delivery in Matlosana, South Africa. Best-worst scaling (BWS) was used to determine the women's priorities out of 11 attributes related to preventive therapy in the ante- versus postpartum periods. Aggregate BWS scores were calculated based on the frequency with which participants selected each attribute as the best or worst among five options (across multiple choice sets). Individual BWS scores were also calculated and rescaled from 0 (always selected as worst) to 10 (always selected as best), and changes in BWS scores in the ante- versus postpartum periods were compared, using a paired t-test. Factors associated with the changes in BWS scores were examined in multiple linear regressions. Spearman's rho was used to compare the ranking of attributes. RESULTS: Out of a total of 204 participants, 154 (75.5%) completed the survey in the postpartum at the median 15 (IQR: 11 to 27) weeks after delivery. Trust in healthcare providers was most highly prioritized both in the ante- (individual BWS Score = 7.34, SE = 0.13) and postpartum periods (BWS = 7.21 ± 0.11), followed by living a long life (BWS = 6.77 ± 0.09 in the ante- vs. BWS = 6.86 ± 0.10 in the postpartum). Prevention for infants' health was more prioritized in the post- (BWS = 6.54 ± 0.09) versus antepartum periods (BWS = 6.11 ± 0.10) (p = 0.05). This change was associated with IPT initiation at enrolment (regression coefficient = 0.78 ± 0.33, p = 0.001). Difficulty in daily pill-uptake was significantly more prioritized in the postpartum (BWS = 5.03 ± 0.11) than in the antepartum (BWS = 4.43 ± 0.10) (p < 0.01). Transportation cost and worry about side effects of pills were least prioritized. Overall ranking of attributes was similar in both time periods (spearman's rho = 0.90). CONCLUSIONS: Comprehensive interventions to build trust in healthcare providers and support adherence may increase uptake of preventive therapy. Counselling needs to emphasize medication benefits for both maternal and infant health among HIV-positive pregnant women.</p></div></div></div><h2> - June 2018 - </h2><div class='abstract'><p><span class='b'>A systematic review of the effectiveness of smoking cessation interventions among patients with tuberculosis.</span> (2018). Whitehouse E., Lai J., Golub JE., Farley JE, <span class='i'>Public health action</span>, <span class='i'>8</span>, 37-49</p><div><a id='ab_btn_139'>View Abstract Text</a><div id='ab_txt_139' class='hidden_abstract'><p>Smoking is a significant risk factor for morbidity and mortality, particularly among patients with tuberculosis (TB). Although smoking cessation is recommended by the World Health Organization and the International Union Against Tuberculosis and Lung Disease, there has been no published evaluation of smoking cessation interventions among people with TB. The purpose of this review was to synthesize the evidence on interventions and suggest practice, research and policy implications. A systematic review of the literature identified 14 peer-reviewed studies describing 13 smoking cessation interventions between 2007 and 2017. There were five randomized controlled trials, three non-randomized interventions, and five prospective cohort studies. The primary types of interventions were brief advice (n = 9), behavioral counseling (n = 4), medication (n = 3), and community-based care (n = 3). A variety of health care workers (HCWs) implemented interventions, from physicians, nurses, clinic staff, community health workers (CHWs), as did family members. There was significant heterogeneity of design, definition of smoking and smoking abstinence, and implementation, making comparison across studies difficult. Although all smoking interventions increased smoking cessation between 15% and 82%, many studies had a high risk for bias, including six without a control group. The implementing personnel did not make a large difference in cessation results, suggesting that national TB programs may customize according to their needs and limitations. Family members may be important supporters/advocates for cessation. Future research should standardize definitions of smoking and cessation to allow comparisons across studies. Policy makers should encourage collaboration between tobacco and TB initiatives and develop smoking cessation measures to maximize results in low-resource settings.</p></div></div></div><div class='abstract_nav'><p>Page Navigation:</p><a href='publication0.html'>1</a><a href='publication1.html'>2</a><a href='publication2.html'>3</a><a href='publication3.html'>4</a><a href='publication4.html'>5</a><a href='publication5.html'>6</a><a class='current'>7</a><a href='publication7.html'>8</a><a href='publication8.html'>9</a><a href='publication9.html'>10</a></div>
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