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Search Results: 1 - 10 of 133094 matches for " David W. Dowdy "
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The persistence of tuberculosis in the age of DOTS: reassessing the effect of case detection
Dowdy,David W; Chaisson,Richard E;
Bulletin of the World Health Organization , 2009, DOI: 10.1590/S0042-96862009000400015
Abstract: objective: to investigate whether short-term annual declines of 5-10% in the incidence of tuberculosis (tb) can be sustained over the long term by maintaining high case detection rates (cdrs). methods: we constructed a compartmental difference-equation model of a tb epidemic in a hypothetical population of constant size with a treatment success rate of 85%. the impact of cdr on tb incidence was then investigated by generating an equilibrium population with no tb case detection and increasing the smear-positive cdr under two scenarios: (i) rapid expansion by 10% per year to a cdr of 80% after 8 years, and (ii) gradual expansion by 1% per year to a cdr of 90% after 90 years. the model was applied in two hypothetical populations: one without hiv and the other with a stable hiv incidence representative of the african region. the cdr for smear-negative tb was assumed to be a constant fraction of the smear-positive cdr. findings: in the absence of a tb control programme, the projected annual incidence of tb was 513 cases per 100 000 population, with a point prevalence of 1233 per 100 000 and an annual tb-specific mortality rate of 182 per 100 000. immediately increasing the tb cdr from 0% to 70% caused a 74% reduction in tb incidence within 10 years. however, once case detection stabilized at any constant level < 80%, projected tb incidence also stabilized. ten years after a cdr of 70% was reached, the annual decline in tb incidence was < 1.5%, regardless of how rapidly case detection was scaled up and despite wide variation of all model parameters. conclusion: while improved cdrs have a dramatic short-term effect on tb incidence, maintaining those rates, even at current target levels, may not reduce long-term incidence by more than 1-2% per year. tb control programmes and researchers should vigorously pursue improvements in case detection, regardless of current cdrs.
Is Scale-Up Worth It? Challenges in Economic Analysis of Diagnostic Tests for Tuberculosis
David W. Dowdy ,Adithya Cattamanchi,Karen R. Steingart,Madhukar Pai
PLOS Medicine , 2011, DOI: 10.1371/journal.pmed.1001063
Abstract:
Serological Testing Versus Other Strategies for Diagnosis of Active Tuberculosis in India: A Cost-Effectiveness Analysis
David W. Dowdy,Karen R. Steingart,Madhukar Pai
PLOS Medicine , 2011, DOI: 10.1371/journal.pmed.1001074
Abstract: Background Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown. Methods and Findings Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses. Conclusions In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests. Please see later in the article for the Editors' Summary
Do We Need to Detect Isoniazid Resistance in Addition to Rifampicin Resistance in Diagnostic Tests for Tuberculosis?
Claudia M. Denkinger, Madhukar Pai, David W. Dowdy
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0084197
Abstract: Background Multidrug-resistant tuberculosis (MDR-TB) is resistant to both rifampicin (RIF) and isoniazid (INH). Whereas many TB diagnostics detect RIF-resistance, few detect INH-monoresistance, which is common and may increase risk of acquired MDR-TB. Whether inclusion of INH-resistance in a first-line rapid test for TB would have an important impact on MDR-TB rates remains uncertain. Methods We developed a transmission model to evaluate three tests in a population similar to that of India: a rapid molecular test for TB, the same test plus RIF-resistance detection (“TB+RIF”), and detection of RIF and INH-resistance (“TB+RIF/INH”). Our primary outcome was the prevalence of INH-resistant and MDR-TB at ten years. Results Compared to the TB test alone and assuming treatment of all diagnosed MDR cases, the TB+RIF test reduced the prevalence of MDR-TB among all TB cases from 5.5% to 3.8% (30.6% reduction, 95% uncertainty range, UR: 17–54%). Despite using liberal assumptions about the impact of INH-monoresistance on treatment outcomes and MDR-TB acquisition, expansion from TB+RIF to TB+RIF/INH lowered this prevalence only from 3.8% to 3.6% further (4% reduction, 95% UR: 3–7%) and INH-monoresistant TB from 15.8% to 15.1% (4% reduction, 95% UR: (-8)-19%). Conclusion When added to a rapid test for TB plus RIF-resistance, detection of INH-resistance has minimal impact on transmission of TB, MDR-TB, and INH-monoresistant TB.
Population-Level Impact of Active Tuberculosis Case Finding in an Asian Megacity
David W. Dowdy, Ismat Lotia, Andrew S. Azman, Jacob Creswell, Suvanand Sahu, Aamir J. Khan
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077517
Abstract: Background The potential population-level impact of private-sector initiatives for tuberculosis (TB) case finding in Southeast Asia remains uncertain. In 2011, the Indus Hospital TB Control Program in Karachi, Pakistan, undertook an aggressive case-finding campaign that doubled notification rates, providing an opportunity to investigate potential population-level effects. Methods We constructed an age-structured compartmental model of TB in the intervention area. We fit the model using field and literature data, assuming that TB incidence equaled the estimated nationwide incidence in Pakistan (primary analysis), or 1.5 times greater (high-incidence scenario). We modeled the intervention as an increase in the rate of formal-sector TB diagnosis and evaluated the potential impact of sustaining this rate for five years. Results In the primary analysis, the five-year intervention averted 24% (95% uncertainty range, UR: 18-30%) of five-year cumulative TB cases and 52% (95% UR: 45-57%) of cumulative TB deaths. Corresponding reductions in the high-incidence scenario were 12% (95% UR: 8-17%) and 27% (95% UR: 21-34%), although the absolute number of lives saved was higher. At the end of five years, TB notification rates in the primary analysis were below their 2010 baseline, incidence had dropped by 45%, and annual mortality had fallen by 72%. About half of the cumulative impact on incidence and mortality could be achieved with a one-year intervention. Conclusions Sustained, multifaceted, and innovative approaches to TB case-finding in Asian megacities can have substantial community-wide epidemiological impact.
Population-Level Impact of Same-Day Microscopy and Xpert MTB/RIF for Tuberculosis Diagnosis in Africa
David W. Dowdy, J. Lucian Davis, Saskia den Boon, Nicholas D. Walter, Achilles Katamba, Adithya Cattamanchi
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0070485
Abstract: Objective To compare the population-level impact of two World Health Organization-endorsed strategies for improving the diagnosis of tuberculosis (TB): same-day microscopy and Xpert MTB/RIF (Cepheid, USA). Methods We created a compartmental transmission model of TB in a representative African community, fit to the regional incidence and mortality of TB and HIV. We compared the population-level reduction in TB burden over ten years achievable with implementation over two years of same-day microscopy, Xpert MTB/RIF testing, and the combination of both approaches. Findings Same-day microscopy averted an estimated 11.0% of TB incidence over ten years (95% uncertainty range, UR: 3.3%–22.5%), and prevented 11.8% of all TB deaths (95% UR: 7.7%–27.1%). Scaling up Xpert MTB/RIF to all centralized laboratories to achieve 75% population coverage had similar impact on incidence (9.3% reduction, 95% UR: 1.9%–21.5%) and greater effect on mortality (23.8% reduction, 95% UR: 8.6%–33.4%). Combining the two strategies (i.e., same-day microscopy plus Xpert MTB/RIF) generated synergistic effects: an 18.7% reduction in incidence (95% UR: 5.6%–39.2%) and 33.1% reduction in TB mortality (95% UR: 18.1%–50.2%). By the end of year ten, combining same-day microscopy and Xpert MTB/RIF could reduce annual TB mortality by 44% relative to the current standard of care. Conclusion Scaling up novel diagnostic tests for TB and optimizing existing ones are complementary strategies that, when combined, may have substantial impact on TB epidemics in Africa.
Population-Level Impact of Shorter-Course Regimens for Tuberculosis: A Model-Based Analysis
Mariam O. Fofana, Gwenan M. Knight, Gabriela B. Gomez, Richard G. White, David W. Dowdy
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096389
Abstract: Despite current control efforts, global tuberculosis (TB) incidence is decreasing slowly. New regimens that can shorten treatment hold promise for improving treatment completion and success, but their impact on population-level transmission remains unclear. Earlier models projected that a four-month regimen could reduce TB incidence by 10% but assumed that an entire course of therapy must be completed to derive any benefit. We constructed a dynamic transmission model of TB disease calibrated to global estimates of incidence, prevalence, mortality, and treatment success. To account for the efficacy of partial treatment, we used data from clinical trials of early short-course regimens to estimate relapse rates among TB patients who completed one-third, one-half, two-thirds, and all of their first-line treatment regimens. We projected population-level incidence and mortality over 10 years, comparing standard six-month therapy to hypothetical shorter-course regimens with equivalent treatment success but fewer defaults. The impact of hypothetical four-month regimens on TB incidence after 10 years was smaller than estimated in previous modeling analyses (1.9% [95% uncertainty range 0.6–3.1%] vs. 10%). Impact on TB mortality was larger (3.5% at 10 years) but still modest. Transmission impact was most sensitive to the proportion of patients completing therapy: four-month therapy led to greater incidence reductions in settings where 25% of patients leave care (“default”) over six months. Our findings remained robust under one-way variation of model parameters. These findings suggest that novel regimens that shorten treatment duration may have only a modest effect on TB transmission except in settings of very low treatment completion.
Rapid Molecular Testing for TB to Guide Respiratory Isolation in the U.S.: A Cost-Benefit Analysis
Alexander J. Millman, David W. Dowdy, Cecily R. Miller, Robert Brownell, John Z. Metcalfe, Adithya Cattamanchi, J. Lucian Davis
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0079669
Abstract: Background Respiratory isolation of inpatients during evaluation for TB is a slow and costly process in low-burden settings. Xpert MTB/RIF (Xpert) is a novel molecular test for tuberculosis (TB) that is faster and more sensitive but substantially more expensive than smear microscopy. No previous studies have examined the costs of molecular testing as a replacement for smear microscopy in this setting. Methods We conducted an incremental cost–benefit analysis comparing the use of a single negative Xpert versus two negative sputum smears to release consecutive adult inpatients with presumed TB from respiratory isolation at an urban public hospital in the United States. We estimated all health-system costs and patient outcomes related to Xpert implementation, diagnostic evaluation, isolation, hospitalization, and treatment. We performed sensitivity and probabilistic uncertainty analyses to determine at what threshold the Xpert strategy would become cost-saving. Results Among a hypothetical cohort of 234 individuals undergoing evaluation for presumed active TB annually, 6.4% had culture-positive TB. Compared to smear microscopy, Xpert reduced isolation bed utilization from an average of 2.7 to 1.4 days per patient, leading to a 48% reduction in total annual isolation bed usage from 632 to 328 bed-days. Xpert saved an average of $2,278 (95% uncertainty range $1582–4570) per admission, or $533,520 per year, compared with smear microscopy. Conclusions Molecular testing for TB could provide substantial savings to hospitals in high-income countries by reducing respiratory isolation usage and overall length of stay.
The Importance of Implementation Strategy in Scaling Up Xpert MTB/RIF for Diagnosis of Tuberculosis in the Indian Health-Care System: A Transmission Model
Henrik Salje,Jason R. Andrews,Sarang Deo,Srinath Satyanarayana,Amanda Y. Sun,Madhukar Pai ? ,David W. Dowdy
PLOS Medicine , 2014, DOI: 10.1371/journal.pmed.1001674
Abstract: Background India has announced a goal of universal access to quality tuberculosis (TB) diagnosis and treatment. A number of novel diagnostics could help meet this important goal. The rollout of one such diagnostic, Xpert MTB/RIF (Xpert) is being considered, but if Xpert is used mainly for people with HIV or high risk of multidrug-resistant TB (MDR-TB) in the public sector, population-level impact may be limited. Methods and Findings We developed a model of TB transmission, care-seeking behavior, and diagnostic/treatment practices in India and explored the impact of six different rollout strategies. Providing Xpert to 40% of public-sector patients with HIV or prior TB treatment (similar to current national strategy) reduced TB incidence by 0.2% (95% uncertainty range [UR]: ?1.4%, 1.7%) and MDR-TB incidence by 2.4% (95% UR: ?5.2%, 9.1%) relative to existing practice but required 2,500 additional MDR-TB treatments and 60 four-module GeneXpert systems at maximum capacity. Further including 20% of unselected symptomatic individuals in the public sector required 700 systems and reduced incidence by 2.1% (95% UR: 0.5%, 3.9%); a similar approach involving qualified private providers (providers who have received at least some training in allopathic or non-allopathic medicine) reduced incidence by 6.0% (95% UR: 3.9%, 7.9%) with similar resource outlay, but only if high treatment success was assured. Engaging 20% of all private-sector providers (qualified and informal [providers with no formal medical training]) had the greatest impact (14.1% reduction, 95% UR: 10.6%, 16.9%), but required >2,200 systems and reliable treatment referral. Improving referrals from informal providers for smear-based diagnosis in the public sector (without Xpert rollout) had substantially greater impact (6.3% reduction) than Xpert scale-up within the public sector. These findings are subject to substantial uncertainty regarding private-sector treatment patterns, patient care-seeking behavior, symptoms, and infectiousness over time; these uncertainties should be addressed by future research. Conclusions The impact of new diagnostics for TB control in India depends on implementation within the complex, fragmented health-care system. Transformative strategies will require private/informal-sector engagement, adequate referral systems, improved treatment quality, and substantial resources. Please see later in the article for the Editors' Summary
Impact and Cost-Effectiveness of Culture for Diagnosis of Tuberculosis in HIV-Infected Brazilian Adults
David W. Dowdy, Maria C. Louren?o, Solange C. Cavalcante, Valeria Saraceni, Bonnie King, Jonathan E. Golub, David Bishai, Betina Durovni, Richard E. Chaisson, Susan E. Dorman
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0004057
Abstract: Background Culture of Mycobacterium tuberculosis currently represents the closest “gold standard” for diagnosis of tuberculosis (TB), but operational data are scant on the impact and cost-effectiveness of TB culture for human immunodeficiency (HIV-) infected individuals in resource-limited settings. Methodology/Principal Findings We recorded costs, laboratory results, and dates of initiating TB therapy in a centralized TB culture program for HIV-infected patients in Rio de Janeiro, Brazil, constructing a decision-analysis model to estimate the incremental cost-effectiveness of TB culture from the perspective of a public-sector TB control program. Of 217 TB suspects presenting between January 2006 and March 2008, 33 (15%) had culture-confirmed active tuberculosis; 23 (70%) were smear-negative. Among smear-negative, culture-positive patients, 6 (26%) began TB therapy before culture results were available, 11 (48%) began TB therapy after culture result availability, and 6 (26%) did not begin TB therapy within 180 days of presentation. The cost per negative culture was US$17.52 (solid media)–$23.50 (liquid media). Per 1,000 TB suspects and compared with smear alone, TB culture with solid media would avert an estimated eight TB deaths (95% simulation interval [SI]: 4, 15) and 37 disability-adjusted life years (DALYs) (95% SI: 13, 76), at a cost of $36 (95% SI: $25, $50) per TB suspect or $962 (95% SI: $469, $2642) per DALY averted. Replacing solid media with automated liquid culture would avert one further death (95% SI: ?1, 4) and eight DALYs (95% SI: ?4, 23) at $2751 per DALY (95% SI: $680, dominated). The cost-effectiveness of TB culture was more sensitive to characteristics of the existing TB diagnostic system than to the accuracy or cost of TB culture. Conclusions/Significance TB culture is potentially effective and cost-effective for HIV-positive patients in resource-constrained settings. Reliable transmission of culture results to patients and integration with existing systems are essential.
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