TB Modeling and Translational Epi Group

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- June 2018 -

Impact of Providing Preexposure Prophylaxis for Human Immunodeficiency Virus at Clinics for Sexually Transmitted Infections in Baltimore City: An Agent-based Model. (2018). Kasaie P., Berry SA., Shah MS., Rosenberg ES., Hoover KW., Gift TL., Chesson H., Pennington J., German D., Flynn CP., Beyrer C., Dowdy DW, Sexually transmitted diseases, 45, 791-797

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BACKGROUND: Preexposure prophylaxis (PrEP) greatly reduces the risk of human immunodeficiency virus (HIV) acquisition, but its optimal delivery strategy remains uncertain. Clinics for sexually transmitted infections (STIs) can provide an efficient venue for PrEP delivery. METHODS: To quantify the added value of STI clinic-based PrEP delivery, we used an agent-based simulation of HIV transmission among men who have sex with men (MSM). We simulated the impact of PrEP delivery through STI clinics compared with PrEP delivery in other community-based settings. Our primary outcome was the projected 20-year reduction in HIV incidence among MSM. RESULTS: Assuming PrEP uptake and adherence of 60% each, evaluating STI clinic attendees and delivering PrEP to eligible MSM reduced HIV incidence by 16% [95% uncertainty range, 14%-18%] over 20 years, an impact that was 1.8 (1.7-2.0) times as great as that achieved by evaluating an equal number of MSM recruited from the community. Comparing strategies where an equal number of MSM received PrEP in each strategy (ie, evaluating more individuals for PrEP in the community-based strategy, because MSM attending STI clinics are more likely to be PrEP eligible), the reduction in HIV incidence under the STI clinic-based strategy was 1.3 (1.3-1.4) times as great as that of community-based delivery. CONCLUSIONS: Delivering PrEP to MSM who attend STI clinics can improve efficiency and effectiveness. If high levels of adherence can be achieved in this population, STI clinics may be an important venue for PrEP implementation.

Effect of baseline micronutrient and inflammation status on CD4 recovery post-cART initiation in the multinational PEARLS trial. (2018). Shivakoti R., Ewald ER., Gupte N., Yang WT., Kanyama C., Cardoso SW., Santos B., Supparatpinyo K., Badal-Faesen S., Lama JR., Lalloo U., Zulu F., Pawar JS., Riviere C., Kumarasamy N., Hakim J., Pollard R., Detrick B., Balagopal A., Asmuth DM., Semba RD., Campbell TB., Golub J., Gupta A, Clinical nutrition (Edinburgh, Scotland), 38, 1303-1309

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BACKGROUND & AIMS: Nutritional deficiency and inflammation may impact CD4+ T cell recovery during combination antiretroviral therapy (cART), particularly in resource-limited settings where malnutrition is prevalent. The aim of this study was to investigate the relationship of micronutrient and inflammation biomarkers to CD4 recovery after cART initiation. METHODS: We conducted a secondary analysis of a random sub-cohort sample (n = 270) from a multinational randomized trial of cART regimen efficacy among 1571 cART-naïve adults. We measured pre-cART serum levels of micronutrients (Vitamin A, B(6), B(12), D, total carotenoids, selenium, and iron) and inflammation (C-reactive protein, soluble CD14 (sCD14), IFNγ, TNFα, Interleukin-6, and C-X-C motif chemokine 10 (CXCL10/IP10), EndoCab (IgM)) biomarkers. Biomarker status (i.e. micronutrient deficiency vs. sufficiency and elevated vs. low inflammation) was defined using established cutoffs or quartiles. Mixed-effects linear regression models were used to determine the association of baseline (pre-cART) concentrations of individual biomarkers with CD4 recovery through 96 weeks post-cART initiation. RESULTS: In models adjusting for time-dependent viral load and baseline CD4 count, age, sex, body mass index, country, treatment regimen, anemia and hypoalbuminemia status, pre-cART vitamin D deficiency was associated with lower CD4 recovery (-14.9 cells/mm(3), 95% CI: -27.9, -1.8) compared to sufficiency. In contrast, baseline selenium deficiency (20.8 cells/mm(3), 95% CI: 3.3, 38.3), vitamin A deficiency (35.9 cells/mm(3), 95% CI: 17.6, 54.3) and high sCD14 (23.4 cells/mm(3), 95% CI: 8.9, 37.8) were associated with higher CD4 recovery compared to sufficient/low inflammation status. CONCLUSIONS: In summary, baseline vitamin D deficiency was associated with diminished CD4 recovery after cART initiation; impaired CD4 recovery may contribute to the poor clinical outcomes recently observed in individuals with vitamin D deficiency. Vitamin A, selenium and sCD14 were associated with CD4 recovery but future studies are needed to further explore these relationships.

Would pan-tuberculosis treatment regimens be cost-effective? (2018). Kendall EA., Brigden G., Lienhardt C., Dowdy DW, The Lancet. Respiratory medicine, 6, 486-488

- May 2018 -

Sources of household air pollution and their association with fine particulate matter in low-income urban homes in India. (2018). Elf JL., Kinikar A., Khadse S., Mave V., Suryavanshi N., Gupte N., Kulkarni V., Patekar S., Raichur P., Breysse PN., Gupta A., Golub JE, Journal of exposure science & environmental epidemiology, 28, 400-410

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INTRODUCTION: Household air pollution (HAP) is poorly characterized in low-income urban Indian communities. MATERIALS AND METHODS: A questionnaire assessing sources of HAP and 24 h household concentrations of particulate matter less than 2.5 microns in diameter (PM(2.5)) were collected in a sample of low-income homes in Pune, India. RESULTS: In 166 homes, the median 24 h average concentration of PM(2.5) was 167 μg/m(3) (IQR: 106-294). Although kerosene and wood use were highly prevalent (22% and 25% of homes, respectively), primarily as secondary fuel sources, high PM(2.5) concentrations were also found in 95 (57%) homes reporting LPG use alone (mean 141 μg/m(3); IQR: 92-209). In adjusted linear regression, log PM(2.5) concentration was positively associated with wood cooking fuel (GMR 1.5, 95% CI: 1.1-2.0), mosquito coils (GMR 1.5, 95% CI: 1.1-2.1), and winter season (GMR 1.7, 95% CI: 1.4-2.2). Households in the highest quartile of exposure were positively associated with wood cooking fuel (OR 1.3, 95% CI: 1.1-1.5), incense (OR 1.1, 95% CI: 1.0-1.3), mosquito coils (OR 1.3, 95% CI: 1.1-1.6), and winter season (OR 1.2, 95% CI: 1.1-1.4). DISCUSSION: We observed high concentrations of PM(2.5) and identified associated determinants in urban Indian homes.

- April 2018 -

Transmission of Mycobacterium tuberculosis From Patients Who Are Nucleic Acid Amplification Test Negative. (2018). Xie YL., Cronin WA., Proschan M., Oatis R., Cohn S., Curry SR., Golub JE., Barry CE 3rd., Dorman SE, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 67, 1653-1659

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BACKGROUND: Among adults with signs and symptoms of pulmonary tuberculosis (TB), recognition of transmissible TB has implications for airborne infection isolation and public health activities. Sputum smear-negative TB patients account for around one-fifth of tuberculosis transmission. The tuberculosis transmission risk of TB patients with negative results on nucleic acid amplification test (NAAT) of respiratory specimens has not been established. We sought to estimate the tuberculosis transmission risk of NAAT-negative TB patients. METHODS: We retrospectively reviewed Maryland TB program data collected from 2004 to 2009, during which time NAAT using the Mycobacterium Tuberculosis Direct Test (MTD) was performed routinely. Patients with sputum Mycobacterium tuberculosis (M.tb) isolates having matching genotypes were assigned to clusters. Transmission sequence was approximated by collection order of individuals' first culture-positive specimens. Minimum transmission risks of NAAT (MTD)-negative TB patients and of smear-negative TB patients were estimated based on individuals' positions within clusters. RESULTS: Among 809 patients with culture-confirmed TB, M.tb genotypes were available for 782 (96.7%). For NAA-negative TB patients, the minimum transmission risk estimate was 5.1% (95% CI 0-11.4). For smear-negative TB patients, the minimum transmission risk estimate was 11.2% (95% CI 7.2-15.3). CONCLUSIONS: Minimum transmission risk of NAAT-negative TB patients was lower than that of smear-negative TB patients. However, transmission risk of NAA-negative TB patients appears to not be negligible.

Relevance and acceptability of using the Quantiferon gold test (QGIT) to screen CD4 blood draws for latent TB infection among PLHIV in South Africa: formative qualitative research findings from the TEKO trial. (2018). Kerrigan D., Tudor C., Motlhaoleng K., Lebina L., Qomfu C., Variava E., Chon S., Martinson N., Golub JE, BMC health services research, 18, 288

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BACKGROUND: Tuberculosis (TB) is the leading cause of mortality among people living with HIV (PLHIV), despite the availability of effective preventive therapy. The TEKO trial is assessing the impact of using a blood test, Quantiferon-TB Gold In-Tube Test (QGIT), to screen for latent TB compared to the Tuberculin Screening Test (TST) among PLHIV in South Africa. METHODS: Fifty-six qualitative interviews were conducted with PLHIV and clinical providers participating in the TEKO trial. We explored TB screening, diagnosis, and treatment guidelines and processes and the use of the QGIT to screen for latent TB infection at the time of CD4 blood draw. Thematic content analysis was conducted. RESULTS: Considerable variability in TB screening procedures was documented due to lack of personnel and clarity regarding current national TB guidelines for PLHIV. Few clinics had started using the TST per national guidelines and many patients had never heard of isoniazid preventive therapy (IPT). Nearly all participants supported the idea of latent TB screening using routine blood drawn for CD4 counts. CONCLUSIONS: Findings indicate that screening for latent TB infection using QGIT from blood drawn for CD4 counts among PLHIV is an acceptable approach to increase latent TB detection given the challenges associated with ensuring systematic latent TB screening in overburdened public clinics. TRIAL REGISTRATION: The results presented here were from formative research related to the TEKO trial (Identifier NCT02119130 , registered 10 April 2014).

Cost-effectiveness of Preventive Therapy for Tuberculosis With Isoniazid and Rifapentine Versus Isoniazid Alone in High-Burden Settings. (2018). Johnson KT., Churchyard GJ., Sohn H., Dowdy DW, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 67, 1072-1078

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BACKGROUND: A short-course regimen of 3 months of weekly rifapentine and isoniazid (3HP) has recently been recommended by the World Health Organization as an alternative to at least 6 months of daily isoniazid (isoniazid preventive therapy [IPT]) for prevention of tuberculosis (TB). The contexts in which 3HP may be cost-effective compared to IPT among people living with human immunodeficiency virus are unknown. METHODS: We used a Markov state transition model to estimate the incremental cost-effectiveness of 3HP relative to IPT in high-burden settings, using a cohort of 1000 patients in a Ugandan HIV clinic as an emblematic scenario. Cost-effectiveness was expressed as 2017 US dollars per disability-adjusted life year (DALY) averted from a healthcare perspective over a 20-year time horizon. We explored the conditions under which 3HP would be considered cost-effective relative to IPT. RESULTS: Per 1000 individuals on antiretroviral therapy in the reference scenario, treatment with 3HP rather than IPT was estimated to avert 9 cases of TB and 1 death, costing $9402 per DALY averted relative to IPT. Cost-effectiveness depended strongly on the price of rifapentine, completion of 3HP, and prevalence of latent TB. At a willingness to pay of $1000 per DALY averted, 3HP is likely to be cost-effective relative to IPT only if the price of rifapentine can be greatly reduced (to approximately $20 per course) and high treatment completion (85%) can be achieved. CONCLUSIONS: 3HP may be a cost-effective alternative to IPT in high-burden settings, but cost-effectiveness depends on the price of rifapentine, achievable completion rates, and local willingness to pay.

- March 2018 -

The effect of partner HIV status on motivation to take antiretroviral and isoniazid preventive therapies: a conjoint analysis. (2018). Kim HY., Hanrahan CF., Dowdy DW., Martinson N., Golub J., Bridges JFP, AIDS care, 30, 1298-1305

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Antiretroviral therapy (ART) and isoniazid preventive therapy (IPT) are important to reduce morbidity and mortality among people newly diagnosed of HIV. The successful uptake of ART and IPT requires a comprehensive understanding of patients' motivation to take such therapies. Partners also play an important role in the decision to be initiated and retained in care. We quantified patients' motivation to take preventive therapies (ART and IPT) and compared by partner HIV status among people newly diagnosed of HIV. We enrolled and surveyed adults (≥18 years) with a recent HIV diagnosis (<6 months) from 14 public primary care clinics in Matlosana, South Africa. Participants received eight forced-choice tasks comparing two mutually exclusive sub-sets of seven possible benefits related to preventive therapies. A linear probability model was fitted to estimate the probability of prioritizing each benefit. Tests of concordance were conducted across partner HIV status (no partner, HIV- or unknown, or HIV+). A total of 424 people completed surveys. At the time of interview, 272 (64%) were on ART and 334 (79%) had a partner or spouse. Keeping themselves healthy for their family was the most important motivator to take preventive therapies (p < 0.001). Preventing HIV transmission to partners was also highly prioritized among participants with current partners independent of partner's HIV status (p < 0.001), but it was least prioritized among those without current partners (p = 0.72). Keeping themselves healthy was less prioritized. We demonstrate that social responsibility such as supporting family and preventing HIV transmission to partners may pose greater motivation for ART and IPT initiation and adherence compared to individual health benefits. These messages should be emphasized to provide effective patient-centered care and counseling.

Predictors of isoniazid preventive therapy completion among adults newly diagnosed with HIV in rural Malawi. (2018). Little KM., Khundi M., Barnes GL., Ngwira LG., Nkhoma A., Makombe S., Corbett EL., Chaisson RE., Dowdy DW, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 22, 371-377

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SETTING: To reduce the risk of tuberculosis (TB) among individuals with human immunodeficiency virus (HIV) infection, the World Health Organization recommends at least 6 months of isoniazid preventive therapy (IPT). Completion of IPT remains a major challenge in resource-limited settings. OBJECTIVE: To evaluate predictors of IPT completion in individuals newly diagnosed with HIV. DESIGN: Predictors of IPT completion among adults newly diagnosed with HIV in rural Malawi were evaluated using a multilevel logistic regression model. RESULTS: Of 974 participants who screened negative for active TB and were started on IPT, 732 (75%) completed treatment. Only one IPT-eligible individual refused treatment. Participants who were aged <25 years (compared with those aged 45 years, adjusted OR [aOR] 0.33, 95%CI 0.18-0.60) and male (compared to non-pregnant females, aOR 0.57, 95%CI 0.37-0.88) had lower odds of IPT completion. CONCLUSION: IPT provision at the time of initial HIV diagnosis was highly acceptable in rural Malawi; three quarters of those who initiated IPT successfully completed therapy. We observed lower odds of completion among males and among female participants aged <25 years. Additional efforts may be needed to ensure IPT completion among males and young females who have recently been diagnosed with HIV.

Of Testing and Treatment: Implications of Implementing New Regimens for Multidrug-Resistant Tuberculosis. (2018). Dowdy DW., Theron G., Tornheim JA., Warren R., Kendall EA, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 65, 1206-1211

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A novel, shorter-course regimen for treating multidrug-resistant (MDR) tuberculosis was recently recommended by the World Health Organization. However, the most appropriate use of drug susceptibility testing (DST) to support this regimen is less clear. Implementing countries must therefore often choose between using a standardized regimen despite high levels of underlying drug resistance or require more stringent DST prior to treatment initiation. The former carries a high likelihood of exposing patients to de facto monotherapy with a critical drug class (fluoroquinolones), whereas the latter could exclude large groups of patients from their most effective treatment option. We discuss the implications of this dilemma and argue for an approach that will integrate DST into the delivery of any novel antimicrobial regimen, without excessively stringent requirements. Such guidance could make the novel MDR tuberculosis regimen available to most patients while reducing the risk of generating additional drug resistance.

Tuberculosis Mortality in the United States: Epidemiology and Prevention Opportunities. (2018). Beavers SF., Pascopella L., Davidow AL., Mangan JM., Hirsch-Moverman YR., Golub JE., Blumberg HM., Webb RM., Royce RA., Buskin SE., Leonard MK., Weinfurter PC., Belknap RW., Hughes SE., Warkentin JV., Welbel SF., Miller TL., Kundipati SR., Lauzardo M., Barry PM., Katz DJ., Garrett DO., Graviss EA., Flood JM, Annals of the American Thoracic Society, 15, 683-692

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Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

- February 2018 -

Delay in seeking care for tuberculosis symptoms among adults newly diagnosed with HIV in rural Malawi. (2018). Ngwira LG., Dowdy DW., Khundi M., Barnes GL., Nkhoma A., Choko AT., Murowa M., Chaisson RE., Corbett EL., Fielding K, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 22, 280-286

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SETTING: Ten primary health clinics in rural Thyolo District, Malawi. OBJECTIVE: Tuberculosis (TB) is a common initial presentation of human immunodeficiency virus (HIV) infection. We investigated the time from TB symptom onset to HIV diagnosis to describe TB health-seeking behaviour in adults newly diagnosed with HIV. DESIGN: We asked adults (18 years) about the presence and duration of TB symptoms at the time of receiving a new HIV diagnosis. Associations with delayed health seeking (defined as >30 and >90 days from the onset of TB symptoms) were evaluated using multivariable logistic regression. RESULTS: TB symptoms were reported by 416 of 1265 participants (33%), of whom 36% (150/416) had been symptomatic for >30 days before HIV testing. Most participants (260/416, 63%) were below the poverty line (US$0.41 per household member per day). Patients who first sought care from informal providers had an increased odds of delay of >30 days (adjusted odds ratio [aOR] 1.6, 95%CI 0.9-2.8) or 90 days (aOR 2.0, 95%CI 1.1-3.8). CONCLUSIONS: Delayed health seeking for TB-related symptoms was common. Poverty was ubiquitous, but had no clear relationship to diagnostic delay. HIV-positive individuals who first sought care from informal providers were more likely to experience diagnostic delays for TB symptoms.

What Will It Take to Reduce HIV Incidence in the United States: A Mathematical Modeling Analysis. (2018). Perry A., Kasaie P., Dowdy DW., Shah M, Open forum infectious diseases, 5, ofy008

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BACKGROUND: The National HIV/AIDS Strategy has set ambitious goals to improve the epidemic in the United States. However, there is a paucity of usable program-level benchmarks tied to population-level epidemiologic goals. Our objective was to define tangible benchmarks for annual rates along the care continuum that are likely to translate to meaningful reductions in incidence. METHODS: We used a validated mathematical model of HIV transmission and care engagement to characterize care continuum parameters that would translate into 50% reductions in incidence by 2025, compared with a base case scenario of the current US care continuum. We generated a large pool of simulations in which rates of screening, linkage, and retention in care were varied across wide ranges to evaluate permutations that halved incidence by 2025. RESULTS: Among all simulations, 7% achieved a halving of incidence. It was impossible for our simulations to achieve this target if the annual rate of disengagement from care exceeded 20% per year, even at high rates of care reengagement. When retention in care was 95% per year and people living with HIV (PLWH) out of care reengaged within 1.5 years (on average), the probability of halving incidence by 2025 was approximately 90%. CONCLUSIONS: HIV programs should aim to retain at least 95% of PLWH in care annually and reengage people living with HIV into care within an average of 1.5 years to achieve the goal of halving HIV incidence by 2025.

Risk factors associated with cluster size of Mycobacterium tuberculosis (Mtb) of different RFLP lineages in Brazil. (2018). Peres RL., Vinhas SA., Ribeiro FKC., Palaci M., do Prado TN., Reis-Santos B., Zandonade E., Suffys PN., Golub JE., Riley LW., Maciel EL, BMC infectious diseases, 18, 71

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BACKGROUND: Tuberculosis (TB) transmission is influenced by patient-related risk, environment and bacteriological factors. We determined the risk factors associated with cluster size of IS6110 RFLP based genotypes of Mycobacterium tuberculosis (Mtb) isolates from Vitoria, Espirito Santo, Brazil. METHODS: Cross-sectional study of new TB cases identified in the metropolitan area of Vitoria, Brazil between 2000 and 2010. Mtb isolates were genotyped by the IS6110 RFLP, spoligotyping and RD(Rio). The isolates were classified according to genotype cluster sizes by three genotyping methods and associated patient epidemiologic characteristics. Regression Model was performed to identify factors associated with cluster size. RESULTS: Among 959 Mtb isolates, 461 (48%) cases had an isolate that belonged to an RFLP cluster, and six clusters with ten or more isolates were identified. Of the isolates spoligotyped, 448 (52%) were classified as LAM and 412 (48%) as non-LAM. Our regression model found that 6-9 isolates/RFLP cluster were more likely belong to the LAM family, having the RD(Rio) genotype and to be smear-positive (adjusted OR = 1.17, 95% CI 1.08-1.26; adjusted OR = 1.25, 95% CI 1.14-1.37; crude OR = 2.68, 95% IC 1.13-6.34; respectively) and living in a Serra city neighborhood decrease the risk of being in the 6-9 isolates/RFLP cluster (adjusted OR = 0.29, 95% CI, 0.10-0.84), than in the others groups. Individuals aged 21 to 30, 31 to 40 and > 50 years were less likely of belonging the 2-5 isolates/RFLP cluster than unique patterns compared to individuals < 20 years of age (adjusted OR = 0.49, 95% CI 0.28-0.85, OR = 0.43 95% CI 0.24-0.77and OR = 0. 49, 95% CI 0.26-0.91), respectively. The extrapulmonary disease was less likely to occur in those infected with strains in the 2-5 isolates/cluster group (adjustment OR = 0.45, 95% CI 0.24-0.85) than unique patterns. CONCLUSIONS: We found that a large proportion of new TB infections in Vitoria is caused by prevalent Mtb genotypes belonging to the LAM family and RD(Rio) genotypes. Such information demonstrates that some genotypes are more likely to cause recent transmission. Targeting interventions such as screening in specific areas and social risk groups, should be a priority for reducing transmission.

- January 2018 -

Gender-based violence screening methods preferred by women visiting a public hospital in Pune, India. (2018). Suryavanshi N., Naik S., Waghmare S., Gupte N., Khan S., Mave V., Deluca A., Gupta A., Golub J., Bollinger RC., Shankar A, BMC women's health, 18, 19

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BACKGROUND: Gender-based violence (GBV) is a major global public health concern and is a risk factor for adverse health outcomes. Early identification of GBV is crucial for improved health outcomes. Interactions with health care providers may provide a unique opportunity for routine GBV screening, if a safe, confidential environment can be established. METHODS: Between November 2014 and February 2015, a cross-sectional, observational study was conducted where women were interviewed about their opinions concerning GBV screening in a tertiary health care setting in Pune, India. Trained counsellors interviewed 300 women at different out-patient and in-patient departments using a semi-structured questionnaire. RESULTS: Twenty-three percent of these women reported experiencing GBV in their life. However, 90% of women said they had never been asked about GBV in a health care setting. Seventy-two percent expressed willingness to be asked about GBV by their health care providers, with the preferred provider being nurses or counsellors. More than half (53%) women reported face-to-face interview as the most preferred method for screening. There were no major differences in these preferences by GBV history status. CONCLUSIONS: Our study provides evidence for preferred GBV screening methods and optimal provider engagement as perceived by women attending a public hospital.

Metformin Use Reverses the Increased Mortality Associated With Diabetes Mellitus During Tuberculosis Treatment. (2018). Degner NR., Wang JY., Golub JE., Karakousis PC, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 66, 198-205

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BACKGROUND: The global type 2 diabetes mellitus (DM) epidemic threatens progress made in reducing tuberculosis (TB)-related mortality worldwide. Previous clinical studies have not fully evaluated potential confounding variables in addressing the impact of DM on TB treatment outcomes. The antidiabetic agent metformin regulates autophagy and may play a role as a host-directed therapeutic adjuvant to antitubercular treatment. METHODS: We conducted a retrospective cohort study comprising patients aged ≥13 years undergoing treatment for culture-confirmed, drug-susceptible pulmonary TB. We assessed the effect of DM on mortality during TB treatment and 2-month TB sputum-culture conversion. We also evaluated the effect of metformin use on survival during TB treatment. RESULTS: Among 2416 patients undergoing TB treatment, after adjusting for age, sex, chronic kidney disease, cancer, hepatitis C, tobacco use, cavitary disease, and treatment adherence, patients with DM had 1.91 times higher odds (95% confidence interval [CI], 1.51-2.40) of death during TB treatment than patients without DM, and 1.72 (95% CI, 1.25-2.38) times higher odds of remaining culture-positive at 2 months. Metformin use in patients with DM was significantly associated with decreased mortality during TB treatment (hazard ratio, 0.56 [95% CI, .39-.82]), and metformin users had similar mortality as patients without DM. CONCLUSIONS: This study suggests that despite multiple potential confounding variables, DM poses an increased risk of adverse TB treatment outcomes. There was a significant association between metformin use and decreased mortality during TB treatment, suggesting a potential role for this agent as adjunctive, host-directed therapy.

Brief Report: "Give Me Some Time": Facilitators of and Barriers to Uptake of Home-Based HIV Testing During Household Contact Investigation for Tuberculosis in Kampala, Uganda. (2018). Armstrong-Hough M., Ggita J., Ayakaka I., Dowdy D., Cattamanchi A., Haberer JE., Katamba A., Davis JL, Journal of acquired immune deficiency syndromes (1999), 77, 400-404

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BACKGROUND: Integrating home-based HIV counseling and testing (HCT) with tuberculosis (TB) evaluation could improve the uptake of HIV testing among household contacts of patients with active TB. We sought to identify the facilitators of and barriers to HCT during household contact investigation for TB in Kampala, Uganda. METHODS: We nested semi-structured interviews with 28 household contacts who were offered home-based HCT in a household-randomized trial of home-based strategies for TB contact investigation. Respondents reflected on their experiences of the home visit, the social context of the household, and their decision to accept or decline HIV testing. We used content analysis to identify and evaluate facilitators of and barriers to testing, then categorized the emergent themes using the Capability, Opportunity, Motivation, and Behavior (COM-B) model. RESULTS: Facilitators included a preexisting desire to confirm HIV status or to show support for the index TB patient; a perception that home-based services are convenient; and positive perceptions of lay health workers. Key barriers included fear of results and feeling psychologically unprepared to receive results. The social influence of other household members operated as both a facilitator and a barrier. CONCLUSIONS: Preexisting motivation, psychological readiness to test, and the social context of the household are major contributors to the decision to test for HIV at home. Uptake might be improved by providing normalizing information about HCT before the visit, by offering a second HCT opportunity, by offering self-tests with follow-up counseling, or by introducing HCT using "opt-out" language.

Prevalence of dysglycemia and clinical presentation of pulmonary tuberculosis in Western India. (2018). 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 A., Gupta A., Gupte N., Golub JE, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 21, 1280-1287

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SETTING: Pune, India. OBJECTIVES: To estimate the prevalence and risk factors of pre-diabetes mellitus (DM) and DM, and its associations with the clinical presentation of tuberculosis (TB). DESIGN: Screening for DM was conducted among adults (age  18 years) with confirmed TB between December 2013 and January 2017. We used multinomial regression to evaluate the risk factors for pre-DM (glycated hemoglobin [HbA1c]  5.7-6.5% or fasting glucose 100-125 mg/dl) and DM (HbA1c  6.5% or fasting glucose  126 mg/dl or random blood glucose > 200 mg/dl or self-reported DM history/treatment) and the association of dysglycemia with the severity of TB disease. RESULTS: Among 1793 participants screened, 890 (50%) had microbiologically confirmed TB. Of these, 33% had pre-DM and 18% had DM; 41% were newly diagnosed. The median HbA1c level among newly diagnosed DM was 7.0% vs. 10.3% among known DM (P < 0.001). DM (adjusted OR [aOR] 4.94, 95%CI 2.33-10.48) and each per cent increase in HbA1c (aOR 1.42, 95%CI 1.01-2.01) was associated with >1+ smear grade or 9 days to TB detection. CONCLUSION: Over half of newly diagnosed TB patients had DM or pre-DM. DM and increasing dysglycemia was associated with higher bacterial burden at TB diagnosis, potentially indicating a higher risk of TB transmission to close contacts.

Secondhand Smoke Exposure and Validity of Self-Report in Low-Income Women and Children in India. (2018). Elf JL., Kinikar A., Khadse S., Mave V., Gupte N., Kulkarni V., Patekar S., Raichur P., Cohen J., Breysse PN., Gupta A., Golub JE, Pediatrics, 141, S118-S129

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BACKGROUND: There is limited validation of self-reported measures for secondhand smoke (SHS) exposure in low- and middle-income countries. We evaluated the validity of standard self-reported measures among women and children in urban India. METHODS: Structured questionnaires were administered, and household air and hair samples were analyzed for nicotine concentration. RESULTS: In total, 141 households of 70 child and 71 adult participants were included. Air nicotine was detected in 72 (51%) homes, and 35 (75%) child and 12 (56%) adult participants had detectable hair nicotine. Correlation between air and hair nicotine was significant in children (r = 0.5; P = .0002) but not in adults (r = -0.1; P = .57). Poor correlation was found between self-reported measures of exposure and both air and hair nicotine. No questions were significantly correlated with hair nicotine, and the highest-magnitude correlation with air nicotine was for how often someone smoked inside for adults (r = 0.4; P = .10) and for home preparation of mishri (a smokeless tobacco product prepared for consumption by roasting) for children (r = 0.4; P = .39). The highest value for sensitivity by using air nicotine as the gold standard was for whether people smelled other families preparing mishri (47%; 95% confidence interval: 31-62) and prepared mishri in their own homes (50%; 95% confidence interval: 19-81). CONCLUSIONS: These results raise caution in using or evaluating self-reported SHS exposure in these communities. More appropriate questions for this population are needed, including mishri preparation as a source of SHS exposure.

- December 2017 -

Integrating social justice concerns into economic evaluation for healthcare and public health: A systematic review. (2017). Dukhanin V., Searle A., Zwerling A., Dowdy DW., Taylor HA., Merritt MW, Social science & medicine (1982), 198, 27-35

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Social justice is the moral imperative to avoid and remediate unfair distributions of societal disadvantage. In priority setting in healthcare and public health, social justice reaches beyond fairness in the distribution of health outcomes and economic impacts to encompass fairness in the distribution of policy impacts upon other dimensions of well-being. There is an emerging awareness of the need for economic evaluation to integrate all such concerns. We performed a systematic review (1) to describe methodological solutions suitable for integrating social justice concerns into economic evaluation, and (2) to describe the challenges that those solutions face. To be included, publications must have captured fairness considerations that (a) involve cross-dimensional subjective personal life experience and (b) can be manifested at the level of subpopulations. We identified relevant publications using an electronic search in EMBASE, PubMed, EconLit, PsycInfo, Philosopher's Index, and Scopus, including publications available in English in the past 20 years. Two reviewers independently appraised candidate publications, extracted data, and synthesized findings in narrative form. Out of 2388 publications reviewed, 26 were included. Solutions sought either to incorporate relevant fairness considerations directly into economic evaluation or to report them alongside cost-effectiveness measures. The majority of reviewed solutions, if adapted to integrate social justice concerns, would require their explicit quantification. Four broad challenges related to the implementation of these solutions were identified: clarifying the normative basis; measuring and determining the relative importance of criteria representing that basis; combining the criteria; and evaluating trade-offs. All included solutions must grapple with an inherent tension: they must either face the normative and operational challenges of quantifying social justice concerns or accede to offering incomplete policy guidance. Interdisciplinary research and broader collaborations are crucial to address these challenges and to support due attention to social justice in priority setting.

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