Comparative Modeling of Tuberculosis Epidemiology and Policy Outcomes in California. (2019). Menzies NA., Parriott A., Shrestha S., Dowdy DW., Cohen T., Salomon JA., Marks SM., Hill AN., Winston CA., Asay GR., Barry P., Readhead A., Flood J., Kahn JG., Shete PB, American journal of respiratory and critical care medicine, 201, 356-365
Rationale: Mathematical modeling is used to understand disease dynamics, forecast trends, and inform public health prioritization. We conducted a comparative analysis of tuberculosis (TB) epidemiology and potential intervention effects in California, using three previously developed epidemiologic models of TB.Objectives: To compare the influence of various modeling methods and assumptions on epidemiologic projections of domestic latent TB infection (LTBI) control interventions in California.Methods: We compared model results between 2005 and 2050 under a base-case scenario representing current TB services and alternative scenarios including: 1) sustained interruption of Mycobacterium tuberculosis (Mtb) transmission, 2) sustained resolution of LTBI and TB prior to entry of new residents, and 3) one-time targeted testing and treatment of LTBI among 25% of non-U.S.-born individuals residing in California.Measurements and Main Results: Model estimates of TB cases and deaths in California were in close agreement over the historical period but diverged for LTBI prevalence and new Mtb infections-outcomes for which definitive data are unavailable. Between 2018 and 2050, models projected average annual declines of 0.58-1.42% in TB cases, without additional interventions. A one-time LTBI testing and treatment intervention among non-U.S.-born residents was projected to produce sustained reductions in TB incidence. Models found prevalent Mtb infection and migration to be more significant drivers of future TB incidence than local transmission.Conclusions: All models projected a stagnation in the decline of TB incidence, highlighting the need for additional interventions including greater access to LTBI diagnosis and treatment for non-U.S.-born individuals. Differences in model results reflect gaps in historical data and uncertainty in the trends of key parameters, demonstrating the need for high-quality, up-to-date data on TB determinants and outcomes.
Clinical Consequences of Using an Indeterminate Range for Early Infant Diagnosis of HIV: A Decision Model. (2019). Salvatore P., Johnson K., Vojnov L., Doherty M., Dowdy D, Journal of acquired immune deficiency syndromes (1999), 82, 287-296
BACKGROUND: To minimize false-positive diagnoses of HIV in exposed infants, the World Health Organization recommends confirmatory testing for all infants initiating antiretroviral therapy (ART). In settings where confirmatory testing is not feasible or intermittently performed, clinical decisions may be aided by semi-quantitative cycle thresholds (Cts) that identify positive results most likely to be false-positive. METHODS: We developed a decision analysis model of HIV-exposed infants in sub-Saharan Africa to estimate the clinical consequences of deferring ART for infants with weakly positive ("indeterminate") results. We assessed the degree to which "indeterminate" results may reduce the number of infants starting ART unnecessarily while missing a small number of HIV-infected infants. Our primary outcome was the ratio of averted unnecessary ART regimens to additional HIV-related deaths (due to false-negative diagnosis) at different Ct cutoffs. RESULTS: The clinical consequences of adopting an indeterminate range varied with the prevalence of HIV and Ct cutoff. Considering a Ct cutoff ≥33, adopting an indeterminate range could prevent a median of 1.4 infants from receiving ART unnecessarily (95% UR: 1.0-2.0) for each additional HIV-related death. This ratio could be improved by prioritizing infants with indeterminate results for confirmatory testing [median 8.8 (95% UR: 6.0-13.3)] and by adopting a higher cutoff [median 82.3 (95% UR: 49.0-155.8) with Ct ≥36]. CONCLUSIONS: When implemented in settings where confirmatory testing is not universal, the benefits of classifying weakly positive results as "indeterminate" may outweigh the risks. Accordingly, the World Health Organization has recommended Ct values ≥33 be considered indeterminate for infant HIV diagnosis.
Ending the Human Immunodeficiency Virus Epidemic: Towards an Evidence-Based Approach. (2019). Fojo AT., Dowdy DW, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 69, 2199-2200
Guidance for Studies Evaluating the Accuracy of Tuberculosis Triage Tests. (2019). Nathavitharana RR., Yoon C., Macpherson P., Dowdy DW., Cattamanchi A., Somoskovi A., Broger T., Ottenhoff THM., Arinaminpathy N., Lonnroth K., Reither K., Cobelens F., Gilpin C., Denkinger CM., Schumacher SG, The Journal of infectious diseases, 220, S116-S125
Approximately 3.6 million cases of active tuberculosis (TB) go potentially undiagnosed annually, partly due to limited access to confirmatory diagnostic tests, such as molecular assays or mycobacterial culture, in community and primary healthcare settings. This article provides guidance for TB triage test evaluations. A TB triage test is designed for use in people with TB symptoms and/or significant risk factors for TB. Triage tests are simple and low-cost tests aiming to improve ease of access and implementation (compared with confirmatory tests) and decrease the proportion of patients requiring more expensive confirmatory testing. Evaluation of triage tests should occur in settings of intended use, such as community and primary healthcare centers. Important considerations for triage test evaluation include study design, population, sample type, test throughput, use of thresholds, reference standard (ideally culture), and specimen flow. The impact of a triage test will depend heavily on issues beyond accuracy, primarily centered on implementation.
Adherence to tuberculosis preventive therapy measured by urine metabolite testing among people with HIV. (2019). Kendall EA., Durovni B., Martinson NA., Cavalacante S., Masonoke K., Saraceni V., Lebina L., Efron A., Cohn S., Chon S., Chaisson RE., Dowdy DW., Golub JE, AIDS (London, England), 34, 63-71
OBJECTIVES: Tuberculosis preventive therapy for people living with HIV is effective, widely recommended, and increasingly prescribed, but completion rates are less than ideal, and adherence is not typically monitored. We sought to quantify adherence to isoniazid preventive therapy using a urine metabolite assay. DESIGN: Two cross-sectional surveys. SETTING: Rio de Janeiro, Brazil, 2008-2009; and Northwest Province, South Africa, 2018-2019. PARTICIPANTS: Two hundred and three Brazilian and 93 South African patients attending HIV clinics with active prescriptions for isoniazid preventive therapy MAIN OUTCOME MEASURES:: Self-reported isoniazid adherence, paired with semiquantitative measurement of urine isoniazid metabolites. RESULTS: By self-report, 90% of patients [95% confidence interval (CI) 86-93%] reported having taken a dose of isoniazid on the day of enrollment or the preceding day, and 91% (95% CI 87-94%) reported missing an average of one dose or fewer per week. By urine testing, only 65% (95% CI 59-70%) of all patients, and 69% (95% CI 63-74%) of those who reported having taken isoniazid on the current or preceding day, had detectable urine metabolites (expected in 95% of patients at 24 h). Longer time since starting preventive therapy was independently associated with a negative urine test for isoniazid metabolites (adjusted prevalence ratio 1.11 per month of isoniazid, 95% CI 1.05-1.18). CONCLUSION: Adherence to isoniazid preventive therapy among patients with HIV in Brazil and South Africa is inadequate, is overestimated by self-report, and declines with time on treatment. Shorter regimens for TB preventive therapy may improve adherence and completion, but adherence support for all patients may be necessary.
Promoting Tuberculosis Preventive Therapy for People Living with HIV in South Africa: Interventions Hindered by Complicated Clinical Guidelines and Imbalanced Patient-Provider Dynamics. (2019). Jarrett BA., Woznica DM., Tilchin C., Mpungose N., Motlhaoleng K., Golub JE., Martinson NA., Hanrahan CF, AIDS and behavior, 24, 1106-1117
Isoniazid preventive therapy (IPT) reduces the risk of active tuberculosis among people living with HIV, but implementation of IPT in South Africa and elsewhere remains slow. The objective of this study was to examine both nurse perceptions of clinical mentorship and patient perceptions of in-queue health education for promoting IPT uptake in Potchefstroom, South Africa. We measured adoption, fidelity, acceptability, and sustainability of the interventions using both quantitative and qualitative methods. Adoption, fidelity, and acceptability of the interventions were moderately high. However, nurses believed they could not sustain their increased prescriptions of IPT, and though many patients intended to ask nurses about IPT, few did. Most patients attributed their behavior to an imbalance of patient-provider power. National IPT guidelines should be unambiguous and easily implemented after minimal training on patient eligibility and appropriate medication durations, nurse-patient dynamics should empower the patient, and district-level support and monitoring should be implemented.
Estimating the impact of a novel drug regimen for treatment of tuberculosis: a modeling analysis of projected patient outcomes and epidemiological considerations. (2019). Kendall EA., Malhotra S., Cook-Scalise S., Denkinger CM., Dowdy DW, BMC infectious diseases, 19, 794
BACKGROUND: Regimens that could treat both rifampin-resistant (RR) and rifampin-susceptible tuberculosis (TB) while shortening the treatment duration have reached late-stage clinical trials. Decisions about whether and how to implement such regimens will require an understanding of their likely clinical impact and how this impact depends on local epidemiology and implementation strategy. METHODS: A Markov state-transition model of 100,000 representative South African adults with TB was used to simulate implementation of the regimen BPaMZ (bedaquiline, pretomanid, moxifloxacin, and pyrazinamide), either for RR-TB only or universally for all patients. Patient outcomes, including cure rates, time with active TB, and time on treatment, were compared to outcomes under current care. Sensitivity analyses varied the drug-resistance epidemiology, rifampin susceptibility testing practices, and regimen efficacy. RESULTS: Using BPaMZ exclusively for RR-TB increased the proportion of all RR-TB that was cured by initial treatment from 60 ± 1% to 67 ± 1%. Expanding use of BPaMZ to all patients increased cure of RR-TB to 89 ± 1% and cure of all TB from 87.3 ± 0.1% to 89.5 ± 0.1%, while shortening treatment by 1.9 months/person. In sensitivity analyses, reducing the coverage of rifampin susceptibility testing resulted in lower projected proportions of patients cured under all regimen scenarios (current care, RR-only BPaMZ, and universal BPaMZ), compared to the proportions projected using South Africa's high coverage; however, this reduced coverage resulted in greater expected incremental benefits of universal BPaMZ implementation, both when compared to RR-only BPaMZ implementation and when compared to to current care under the same low rifampin susceptibility testing coverage. In settings with higher RR-TB prevalence, the benefits of BPaMZ were magnified both for RR-specific and universal BPaMZ implementation. CONCLUSIONS: Novel regimens such as BPaMZ could improve RR-TB outcomes and shorten treatment for all patients, particularly with universal use. Decision-makers weighing early options for implementing such regimens at scale will want to consider the expected impact on patient outcomes and on the burden of treatment in their local context.
Tuberculosis fatality rates in the city of Campinas - São Paulo, Brazil, from 2001 to 2009. (2019). Oliveira HB., Marin-Léon L., Saita NM., Golub JE, Revista brasileira de epidemiologia = Brazilian journal of epidemiology, 22, e190043
INTRODUCTION: The mortality rate among tuberculosis patients (TB fatality) has been attributed to irregular chemotherapy, delay in diagnosis, multidrug resistance, and HIV coinfection. OBJECTIVE: To analyze TB fatality rates by sex, clinical presentation and HIV coinfection in Campinas, São Paulo, Brazil. METHODS: Cohorts of residents in the city of Campinas who either died during treatment for tuberculosis or had the disease confirmed after death were divided into three intervals: 2001-2003, 2004-2006, and 2007-2009. Data were obtained from the database of the Tuberculosis Surveillance System of the University of Campinas, and notifications were gathered through TB-WEB Health São Paulo Secretary. Statistical significance was determined using a chi-square test, considering p < 0.05. RESULTS: Between 2001 and 2009, 3,416 TB patients were diagnosed: 2,827 (82.8%) were new TB cases and 589 (17.2%) were retreatments. Between the first and second triennium, the number of new patients decreased by 18%, and 23% among retreatments. Between the second and third intervals, the reduction was 5% and 21%, respectively. General case fatality rate declined from 11.4% to 9.9% across intervals, and was most significant among patients that had previously abandoned treatment (17.3% to 5.1%). Fatality rates among patients coinfected with TB-AIDS were 2-3 times that of patients not infected with TB-AIDS throughout the intervals. Fatality between the first and third triennium among TB-AIDS co-infected patients declined (24.8% to 19.5%), while increasing slightly among non-AIDS TB patients (7.3% to 8%) during this period. CONCLUSION: Though mortality among TB-AIDS patients declined from 2001-2009, rates among non-AIDS TB remained stagnant. Improved TB diagnosis and treatment is needed to further decrease TB mortality in Campinas.
Mobile phone access and comfort: implications for HIV and tuberculosis care in India and South Africa. (2019). Cox SN., Elf JL., Lokhande R., Ogale YP., DiAndreth L., Dupuis E., Milovanovic M., Mpungose N., Mave V., Suryavanshi N., Gupta A., Martinson N., Golub JE., Mathad JS, The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease, 23, 865-872
SETTING: India and South Africa shoulder the greatest burden of tuberculosis (TB) and human immunodeficiency virus (HIV) infection respectively, but care retention is suboptimal.OBJECTIVE: We conducted a study in Pune, India, and Matlosana, South Africa, 1) to identify the factors associated with mobile phone access and comfort of use, 2) to assess access patterns.DESIGN: A cross-sectional study assessed mobile phone access, and comfort; a longitudinal study assessed access patterns.RESULTS: We enrolled 261 participants: 136 in India and 125 in South Africa. Between 1 week and 6 months, participant contact decreased from 90% (n = 122) to 57% (n = 75) in India and from 93% (n = 116) to 70% (n = 88) in South Africa. In the latter, a reason for a clinic visit for HIV management was associated with 63% lower odds of contact than other priorities (e.g., diabetes mellitus, maternal health, TB). In India, 57% (n = 78) reported discomfort with texting; discomfort was higher in the unemployed (adjusted OR [aOR] 4.97, 95%CI 1.12-22.09) and those aged ≥35 years (aOR 1.10, 95%CI 1.04-1.16) participants, but lower in those with higher education (aOR 0.04, 95% CI 0.01-1.14). In South Africa, 91% (n = 114) reported comfort with texting.CONCLUSION: Mobile phone contact was poor at 6 months. While mHealth could transform TB-HIV care, alternative approaches may be needed for certain subpopulations.
Informing decision-making for universal access to quality tuberculosis diagnosis in India: an economic-epidemiological model. (2019). Sohn H., Kasaie P., Kendall E., Gomez GB., Vassall A., Pai M., Dowdy D, BMC medicine, 17, 155
BACKGROUND: India and many other high-burden countries have committed to providing universal access to high-quality diagnosis and drug susceptibility testing (DST) for tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster diagnosis and reduce losses to follow-up (LTFU). METHODS: We generated functions to evaluate the costs of centralized and decentralized molecular testing for tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. RESULTS: Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] - $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. CONCLUSIONS: Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for tuberculosis.
Home-based tuberculosis contact investigation in Uganda: a household randomised trial. (2019). Davis JL., Turimumahoro P., Meyer AJ., Ayakaka I., Ochom E., Ggita J., Mark D., Babirye D., Okello DA., Mugabe F., Fair E., Vittinghoff E., Armstrong-Hough M., Dowdy D., Cattamanchi A., Haberer JE., Katamba A, ERJ open research, 5
INTRODUCTION: The World Health Organization (WHO) recommends household tuberculosis (TB) contact investigation in low-income countries, but most contacts do not complete a full clinical and laboratory evaluation. METHODS: We performed a randomised trial of home-based, SMS-facilitated, household TB contact investigation in Kampala, Uganda. Community health workers (CHWs) visited homes of index patients with pulmonary TB to screen household contacts for TB. Entire households were randomly allocated to clinic (standard-of-care) or home (intervention) evaluation. In the intervention arm, CHWs offered HIV testing to adults; collected sputum from symptomatic contacts and persons living with HIV (PLWHs) if ≥5 years; and transported sputum for microbiologic testing. CHWs referred PLWHs, children <5 years, and anyone unable to complete sputum testing to clinic. Sputum testing results and/or follow-up instructions were returned by automated SMS texts. The primary outcome was completion of a full TB evaluation within 14 days; secondary outcomes were TB and HIV diagnoses and treatments among screened contacts. RESULTS: There were 471 contacts of 190 index patients allocated to the intervention and 448 contacts of 182 index patients allocated to the standard-of-care. CHWs identified 190/471 (40%) intervention and 213/448 (48%) standard-of-care contacts requiring TB evaluation. In the intervention arm, CHWs obtained sputum from 35/91 (39%) of sputum-eligible contacts and SMSs were sent to 95/190 (50%). Completion of TB evaluation in the intervention and standard-of-care arms at 14 days (14% versus 15%; difference -1%, 95% CI -9% to 7%, p=0.81) and yields of confirmed TB (1.5% versus 1.1%, p=0.62) and new HIV (2.0% versus 1.8%, p=0.90) diagnoses were similar. CONCLUSIONS: Home-based, SMS-facilitated evaluation did not improve completion or yield of household TB contact investigation, likely due to challenges delivering the intervention components.
Smoking, alcohol use disorder and tuberculosis treatment outcomes: A dual co-morbidity burden that cannot be ignored. (2019). Thomas BE., Thiruvengadam K., S R., Kadam D., Ovung S., Sivakumar S., Bala Yogendra Shivakumar SV., Paradkar M., Gupte N., Suryavanshi N., Dolla CK., Gupte AN., Kohli R., Pradhan N., Sivaramakrishnan GN., Gaikwad S., Kagal A., Dhanasekaran K., Deluca A., Golub JE., Mave V., Chandrasekaran P., Gupta A, PloS one, 14, e0220507
BACKGROUND: More than 20% of tuberculosis (TB) disease worldwide may be attributable to smoking and alcohol abuse. India is the second largest consumer of tobacco products, a major consumer of alcohol particularly among males, and has the highest burden of TB globally. The impact of increasing tobacco dose, relevance of alcohol misuse and past versus current or never smoking status on TB treatment outcomes remain inadequately defined. METHODS: We conducted a multi-centric prospective cohort study of newly diagnosed adult pulmonary TB patients initiated on TB treatment and followed for a minimum of 6 months to assess the impact of smoking status with or without alcohol abuse on treatment outcomes. Smokers were defined as never smokers, past smokers or current smokers. Alcohol Use Disorder Identification Test (AUDIT) scores were used to assess alcohol misuse. The association between smoking status and treatment outcomes was assessed in univariate and multivariate random effects poisson regression models. RESULTS: Of 455 enrolled, 129 (28%) had a history of smoking with 94 (20%) current smokers and 35 (8%) past smokers. Unfavourable treatment outcomes were significantly higher among past and current smokers as compared to never smokers. Specifically, the risk of treatment failure was significantly higher among past smokers (aIRR = 2.66, 95% CI: 1.41-4.90, p = 0.002), recurrent TB among current smokers (aIRR = 2.94, 95% CI: 1.30-6.67, p = 0.010) and death among both past (2.63, 95% CI: 1.11-6.24, p = 0.028) and current (aIRR = 2.59, 95% CI: 1.29-5.18, p = 0.007) smokers. Furthermore, the combined effect of alcohol misuse and smoking on unfavorable treatment outcomes was significantly higher among past smokers (aIRR: 4.67, 95% CI: 2.17-10.02, p<0.001) and current smokers (aIRR: 3.58, 95% CI: 1.89-6.76, p<0.001). CONCLUSION: Past and current smoking along with alcohol misuse have combined effects on increasing the risk of unfavourable TB treatment outcomes. Innovative interventions that can readily address both co-morbidities are urgently needed.
Seventy Years of Tuberculosis Prevention: Efficacy, Effectiveness, Toxicity, Durability, and Duration. (2019). Salazar-Austin N., Dowdy DW., Chaisson RE., Golub JE, American journal of epidemiology, 188, 2078-2085
Tuberculosis (TB) has been a leading infectious cause of death worldwide for much of human history, with 1.6 million deaths estimated in 2017. The Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health has played an important role in understanding and responding to TB, and it has made particularly substantial contributions to prevention of TB with chemoprophylaxis. TB preventive therapy is highly efficacious in the prevention of TB disease, yet it remains underutilized by TB programs worldwide despite strong evidence to support its use in high-risk groups, such as people living with HIV and household contacts, including those under 5 years of age. We review the evidence for TB preventive therapy and discuss the future of TB prevention.
Empiric treatment of pulmonary TB in the Xpert era: Correspondence of sputum culture, Xpert MTB/RIF, and clinical diagnoses. (2019). Kendall EA., Kamoga C., Kitonsa PJ., Nalutaaya A., Salvatore PP., Robsky K., Nakasolya O., Mukiibi J., Isooba D., Cattamanchi A., Kato-Maeda M., Katamba A., Dowdy DW, PloS one, 14, e0220251
BACKGROUND: Clinical tuberculosis diagnosis and empiric treatment have traditionally been common among patients with negative bacteriologic test results. Increasing availability of rapid molecular diagnostic tests, including Xpert MTB/RIF and the new Xpert Ultra cartridge, may alter the role of empiric treatment. METHODS: We prospectively enrolled outpatients age > = 15 who were evaluated for pulmonary tuberculosis at three health facilities in Kampala, Uganda. Using sputum mycobacterial culture, interviews, and clinical record abstraction, we estimated the accuracy of clinical diagnosis relative to Xpert and sputum culture and assessed the contribution of clinical diagnosis to case detection. RESULTS: Over a period of 9 months, 99 patients were diagnosed with pulmonary tuberculosis and subsequently completed sputum culture; they were matched to 196 patients receiving negative tuberculosis evaluations in the same facilities. Xpert was included in the evaluation of 291 (99%) patients. Compared to culture, Xpert had a sensitivity of 92% (95% confidence interval 83-97%) and specificity of 95% (92-98%). Twenty patients with negative Xpert were clinically diagnosed with tuberculosis and subsequently had their culture status determined; two (10%) were culture-positive. Considering all treated patients regardless of Xpert and culture data completeness, and considering treatment initiations before a positive Xpert (N = 4) to be empiric, 26/101 (26%) tuberculosis treatment courses were started empirically. Compared to sputum smear- or Xpert-positive patients with positive cultures, empirically-treated, Xpert-negative patients with negative cultures had higher prevalence of HIV (67% versus 37%), shorter duration of cough (median 4 versus 8 weeks), and lower inflammatory markers (median CRP 7 versus 101 mg/L). CONCLUSION: Judged against sputum culture in a routine care setting of high HIV prevalence, the accuracy of Xpert was high. Clinical judgment identified a small number of additional culture-positive cases, but with poor specificity. Although clinicians should continue to prescribe tuberculosis treatment for Xpert-negative patients whose clinical presentations strongly suggest pulmonary tuberculosis, they should also carefully consider alternative diagnoses.
Infection free "resisters" among household contacts of adult pulmonary tuberculosis. (2019). Mave V., Chandrasekaran P., Chavan A., Shivakumar SVBY., Danasekaran K., Paradkar M., Thiruvengadam K., Kinikar A., Murali L., Gaikwad S., Hanna LE., Kulkarni V., Pattabiraman S., Suryavanshi N., Thomas B., Kohli R., Sivaramakrishnan GN., Pradhan N., Bhanu B., Kagal A., Golub J., Gandhi N., Gupte A., Gupte N., Swaminathan S., Gupta A, PloS one, 14, e0218034
Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (<5mm TST and <0.35IU/mL QFT-GIT), underwent follow-up testing at 4-6 and/or 12 months. We defined persons with persistently negative LTBI tests at both baseline and followup as pLTBI- and resisters as those who had a high exposure to TB using a published score and remained pLTBI-. We calculated the proportion of resisters overall and resisters with complete absence of response to LTBI tests (0mm TST and/or QFT-GIT <0.01 IU/ml). Using random effects Poisson regression, we assessed factors associated with pLTBI-. Of 799 HHCs in 355 households, 67 (8%) were pLTBI- at 12 months; 52 (6.5%) pLTBI- in 39 households were resisters. Complete absence of response to LTBI tests was found in 27 (53%) resisters. No epidemiological characteristics were associated with the pLTBI- phenotype. LTBI free resisters among HHC exist but are uncommon and are without distinguishing epidemiologic characteristics. Assessing the genetic and immunologic features of such resister individuals is likely to elucidate mechanisms of protective immunity to TB.
Formative research for an mHealth program to improve the HIV care continuum in South Africa. (2019). DiAndreth L., Krishnan N., Elf JL., Cox S., Tilchin C., Nthulana M., Jarrett B., Kronis N., Dupuis E., Motlhaoleng K., Chon S., Martinson N., Golub JE, AIDS care, 32, 744-748
In South Africa, high attrition rates throughout the care continuum present major barriers to controlling the HIV epidemic. Mobile health (mHealth) interventions may provide innovative opportunities for efficient healthcare delivery and improving retention in care. In this formative research, we interviewed 11 patients and 28 healthcare providers in North West Province, South Africa, to identify perceived benefits, concerns and suggestions for a future mHealth program to deliver HIV Viral Load and CD4 Count test results directly to patients via mobile phone. Thematic analysis found that reduced workload for providers, reduced wait times for patients, potential expanded uses and patient empowerment were the main perceived benefits of an mHealth program. Perceived concerns included privacy, disseminating distressing results through text messages and patients' inability to interpret results. Participants felt that an mHealth program should complement face-to-face interactions and educational information to interpret results is needed. Providers identified logistical considerations and suggested protocols be developed. An mHealth program to deliver HIV test results directly to patients could mitigate multiple barriers to care but needs to be tested for efficacy. Concerns identified by patients and providers must be addressed in designing the program to successfully integrate with health facility workflow and ensure its sustainability.
High risk for latent tuberculosis infection among medical residents and nursing students in India. (2019). Kinikar A., Chandanwale A., Kadam D., Joshi S., Basavaraj A., Pardeshi G., Girish S., Shelke S., DeLuca A., Dhumal G., Golub J., Lokhande N., Gupte N., Gupta A., Bollinger R., Mave V, PloS one, 14, e0219131
Defining occupational latent tuberculosis infection (LTBI) risk among healthcare workers is needed to support implementation of prevention guidelines. Prospective cohort study of 200 medical residents and nursing students in India was conducted May 2016-December 2017. Tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) were performed at study entry and 12 months. Primary outcome was incident LTBI (≥10mm TST induration and/or ≥0.35IU/mL QFT-GIT) at 12 months; secondary outcomes included baseline LTBI prevalence and risk factors for incident and prevalent LTBI using Poisson regression. Among 200, [90 nursing students and 110 medical residents], LTBI prevalence was 30% (95% CI, 24-37); LTBI incidence was 26.8 (95% CI, 18.6-37.2) cases per 100 person-years and differed by testing method (28.7 [95% CI, 20.6-38.9] vs 17.4 [95% CI, 11.5-25.4] cases per 100 person-years using TST and QFT-GIT, respectively). Medical residents had two-fold greater risk of incident LTBI than nursing students (Relative Risk, 2.16; 95% CI, 1.05-4.42). During study period 6 (3%) HCWs were diagnosed with active TB disease. Overall, median number of self-reported TB exposures was 5 (Interquartile Range, 1-15). Of 60 participants with prevalent and incident LTBI who were offered free isoniazid preventive therapy (IPT), only 2 participants initiated and completed IPT. High risk for LTBI was noted among medical residents compared to nursing students. Self-reported TB exposure is underreported, and uptake of LTBI prevention therapy remains low. New approaches are needed to identify HCWs at highest risk for LTBI.
A Systematic Review to Evaluate the Association between Clean Cooking Technologies and Time Use in Low- and Middle-Income Countries. (2019). Simkovich SM., Williams KN., Pollard S., Dowdy D., Sinharoy S., Clasen TF., Puzzolo E., Checkley W, International journal of environmental research and public health, 16
Interventions implementing clean fuels to mitigate household air pollution in low- and middle-income countries have focused on environmental and health outcomes, but few have evaluated time savings. We performed a systematic review, searching for studies of clean fuel interventions that measured time use. A total of 868 manuscripts were identified that met the search criteria, but only 2 met the inclusion criteria. Both were cross-sectional and were conducted in rural India. The first surveyed the female head of household (141 using biogas and 58 using biomass) and reported 1.2 h saved per day collecting fuel and 0.7 h saved cooking, resulting in a combined 28.9 days saved over an entire year. The second surveyed the head of household (37 using biogas and 68 using biomass, 13% female) and reported 1.5 h saved per day collecting fuel, or 22.8 days saved over a year. Based on these time savings, we estimated that clean fuel use could result in a 3.8% or 4.7% increase in daily income, respectively, not including time or costs for fuel procurement. Clean fuel interventions could save users time and money. Few studies have evaluated this potential benefit, suggesting that prospective studies or randomized controlled trials are needed to adequately measure gains.
Impact and Effectiveness of State-Level Tuberculosis Interventions in California, Florida, New York, and Texas: A Model-Based Analysis. (2019). Shrestha S., Cherng S., Hill AN., Reynolds S., Flood J., Barry PM., Readhead A., Oxtoby M., Lauzardo M., Privett T., Marks SM., Dowdy DW, American journal of epidemiology, 188, 1733-1741
The incidence of tuberculosis (TB) in the United States has stabilized, and additional interventions are needed to make progress toward TB elimination. However, the impact of such interventions depends on local demography and the heterogeneity of populations at risk. Using state-level individual-based TB transmission models calibrated to California, Florida, New York, and Texas, we modeled 2 TB interventions: 1) increased targeted testing and treatment (TTT) of high-risk populations, including people who are non-US-born, diabetic, human immunodeficiency virus (HIV)-positive, homeless, or incarcerated; and 2) enhanced contact investigation (ECI) for contacts of TB patients, including higher completion of preventive therapy. For each intervention, we projected reductions in active TB incidence over 10 years (2016-2026) and numbers needed to screen and treat in order to avert 1 case. We estimated that TTT delivered to half of the non-US-born adult population could lower TB incidence by 19.8%-26.7% over a 10-year period. TTT delivered to smaller populations with higher TB risk (e.g., HIV-positive persons, homeless persons) and ECI were generally more efficient but had less overall impact on incidence. TTT targeted to smaller, highest-risk populations and ECI can be highly efficient; however, major reductions in incidence will only be achieved by also targeting larger, moderate-risk populations. Ultimately, to eliminate TB in the United States, a combination of these approaches will be necessary.
Treatment of latent infection to achieve tuberculosis elimination in low-incidence countries. (2019). Campbell JR., Dowdy D., Schwartzman K, PLoS medicine, 16, e1002824
In a Perspective for the Tuberculosis Special Issue, Kevin Schwartzman and colleagues discuss the choices and implications for personal versus public health benefits when pursuing tuberculosis elimination in low-incidence countries.