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Search Results: 1 - 10 of 225271 matches for " Philip C Hopewell "
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Tuberculosis control: how the world has changed since 1990
Hopewell Philip C.
Bulletin of the World Health Organization , 2002,
The High Cost of Free Tuberculosis Services: Patient and Household Costs Associated with Tuberculosis Care in Ebonyi State, Nigeria
Kingsley N. Ukwaja, Isaac Alobu, Chika lgwenyi, Philip C. Hopewell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073134
Abstract: Objective Poverty is both a cause and consequence of tuberculosis. The objective of this study is to quantify patient/household costs for an episode of tuberculosis (TB), its relationships with household impoverishment, and the strategies used to cope with the costs by TB patients in a resource-limited high TB/HIV setting. Methods A cross-sectional study was conducted in three rural hospitals in southeast Nigeria. Consecutive adults with newly diagnosed pulmonary TB were interviewed to determine the costs each incurred in their care-seeking pathway using a standardised questionnaire. We defined direct costs as out-of-pocket payments, and indirect costs as lost income. Results Of 452 patients enrolled, majority were male 55% (249), and rural residents 79% (356), with a mean age of 34 (±11.6) years. Median direct pre-diagnosis/diagnosis cost was $49 per patient. Median direct treatment cost was $36 per patient. Indirect pre-diagnostic and treatment costs were $416, or 79% of total patient costs, $528. The median total cost of TB care per household was $592; corresponding to 37% of median annual household income pre-TB. Most patients reported having to borrow money 212(47%), sell assets 42(9%), or both 144(32%) to cope with the cost of care. Following an episode of TB, household income reduced increasing the proportion of households classified as poor from 54% to 79%. Before TB illness, independent predictors of household poverty were; rural residence (adjusted odds ratio [aOR] 2.8), HIV-positive status (aOR 4.8), and care-seeking at a private facility (aOR 5.1). After TB care, independent determinants of household poverty were; younger age (≤35 years; aOR 2.4), male gender (aOR 2.1), and HIV-positive status (aOR 2.5). Conclusion Patient and household costs for TB care are potentially catastrophic even where services are provided free-of-charge. There is an urgent need to implement strategies for TB care that are affordable for the poor.
Commercial Serological Tests for the Diagnosis of Active Pulmonary and Extrapulmonary Tuberculosis: An Updated Systematic Review and Meta-Analysis
Karen R. Steingart,Laura L. Flores,Nandini Dendukuri,Ian Schiller,Suman Laal,Andrew Ramsay,Philip C. Hopewell,Madhukar Pai
PLOS Medicine , 2011, DOI: 10.1371/journal.pmed.1001062
Abstract: Background Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed an updated systematic review to assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary TB with a focus on the relevance of these tests in low- and middle-income countries. Methods and Findings We used methods recommended by the Cochrane Collaboration and GRADE approach for rating quality of evidence. In a previous review, we searched multiple databases for papers published from 1 January 1990 to 30 May 2006, and in this update, we add additional papers published from that period until 29 June 2010. We prespecified subgroups to address heterogeneity and summarized test performance using bivariate random effects meta-analysis. For pulmonary TB, we included 67 studies (48% from low- and middle-income countries) with 5,147 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (31% to 100%). For anda-TB IgG, the only test with enough studies for meta-analysis, pooled sensitivity was 76% (95% CI 63%–87%) in smear-positive (seven studies) and 59% (95% CI 10%–96%) in smear-negative (four studies) patients; pooled specificities were 92% (95% CI 74%–98%) and 91% (95% CI 79%–96%), respectively. Compared with ELISA (pooled sensitivity 60% [95% CI 6%–65%]; pooled specificity 98% [95% CI 96%–99%]), immunochromatographic tests yielded lower pooled sensitivity (53%, 95% CI 42%–64%) and comparable pooled specificity (98%, 95% CI 94%–99%). For extrapulmonary TB, we included 25 studies (40% from low- and middle-income countries) with 1,809 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (59% to 100%). Overall, quality of evidence was graded very low for studies of pulmonary and extrapulmonary TB. Conclusions Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity. Quality of evidence remains very low. These data informed a recently published World Health Organization policy statement against serological tests. Please see later in the article for the Editors' Summary
Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review
Karen R Steingart,Megan Henry,Suman Laal,Philip C Hopewell,Andrew Ramsay,Dick Menzies,Jane Cunningham,Karin Weldingh,Madhukar Pai
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040202
Abstract: Background The global tuberculosis epidemic results in nearly 2 million deaths and 9 million new cases of the disease a year. The vast majority of tuberculosis patients live in developing countries, where the diagnosis of tuberculosis relies on the identification of acid-fast bacilli on unprocessed sputum smears using conventional light microscopy. Microscopy has high specificity in tuberculosis-endemic countries, but modest sensitivity which varies among laboratories (range 20% to 80%). Moreover, the sensitivity is poor for paucibacillary disease (e.g., pediatric and HIV-associated tuberculosis). Thus, the development of rapid and accurate new diagnostic tools is imperative. Immune-based tests are potentially suitable for use in low-income countries as some test formats can be performed at the point of care without laboratory equipment. Currently, dozens of distinct commercial antibody detection tests are sold in developing countries. The question is “do they work?” Methods and Findings We conducted a systematic review to assess the accuracy of commercial antibody detection tests for the diagnosis of pulmonary tuberculosis. Studies from all countries using culture and/or microscopy smear for confirmation of pulmonary tuberculosis were eligible. Studies with fewer than 50 participants (25 patients and 25 control participants) were excluded. In a comprehensive search, we identified 68 studies. The results demonstrate that (1) overall, commercial tests vary widely in performance; (2) sensitivity is higher in smear-positive than smear-negative samples; (3) in studies of smear-positive patients, Anda-TB IgG by enzyme-linked immunosorbent assay shows limited sensitivity (range 63% to 85%) and inconsistent specificity (range 73% to 100%); (4) specificity is higher in healthy volunteers than in patients in whom tuberculosis disease is initially suspected and subsequently ruled out; and (5) there are insufficient data to determine the accuracy of most commercial tests in smear microscopy–negative patients, as well as their performance in children or persons with HIV infection. Conclusions None of the commercial tests evaluated perform well enough to replace sputum smear microscopy. Thus, these tests have little or no role in the diagnosis of pulmonary tuberculosis. Lack of methodological rigor in these studies was identified as a concern. It will be important to review the basic science literature evaluating serological tests for the diagnosis of pulmonary tuberculosis to determine whether useful antigens have been described but their potential has not been
Correction: Commercial Serological Antibody Detection Tests for the Diagnosis of Pulmonary Tuberculosis: A Systematic Review
Karen R Steingart,Megan Henry,Suman Laal,Philip C Hopewell,Andrew Ramsay,Dick Menzies,Jane Cunningham,Karin Weldingh,Madhukar Pai
PLOS Medicine , 2007, DOI: 10.1371/journal.pmed.0040254
Impact of Isoniazid Resistance-Conferring Mutations on the Clinical Presentation of Isoniazid Monoresistant Tuberculosis
Raymund Dantes, John Metcalfe, Elizabeth Kim, Midori Kato-Maeda, Philip C. Hopewell, Masae Kawamura, Payam Nahid, Adithya Cattamanchi
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0037956
Abstract: Background Specific isoniazid (INH) resistance conferring mutations have been shown to impact the likelihood of tuberculosis (TB) transmission. However, their role in the clinical presentation and outcomes of TB has not been evaluated. Methods We included all cases of culture-confirmed, INH monoresistant tuberculosis reported to the San Francisco Department of Public Health Tuberculosis Control Section from October 1992 through October 2005. For cases with stored culture isolates, we used polymerase chain reaction (PCR) testing and gene sequencing to identify INH resistance-conferring mutations, and compared genotypic and phenotypic characteristics. Results Among 101 consecutive cases of INH monoresistant TB in San Francisco 19 (19%) had isolates with a katG mutation other than S315T; 38 (38%) had isolates with the katG S315T mutation, 29 (29%) had isolates with a inhA-15;c-t promoter mutation, and 15 (15%) had isolates with other mutations. The katG S315T mutation was independently associated with high-level INH resistance (risk ratio [RR] 1.56, 95% confidence interval [CI] 1.07–2.27), and the inhA-15;c-t promoter mutation was inversely associated with high-level INH resistance (RR 0.43, 95% CI 0.21–0.89). However, specific INH resistance-conferring mutations were not associated with the clinical severity or outcomes of INH monoresistant TB cases. Conclusion These data suggest that INH resistance-conferring mutations do not impact the clinical presentation of TB.
Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis
Payam Nahid, Leah G Jarlsberg, Irina Rudoy, Bouke C de Jong, Alon Unger, L Masae Kawamura, Dennis H Osmond, Philip C Hopewell, Charles L Daley
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-1
Abstract: Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.Tuberculosis is a leading cause of death worldwide. According to the World Health Organization (WHO) over 1.7 million people with tuberculosis died in 2008 [1]. Advanced age, male gender, delays in diagnosis and treatment, drug resistance, and co-morbid conditions including HIV co-infection, diabetes, renal disease and COPD, have been associated with increased risk of death in patients with active tuberculosis [2-8]. A substantial proportion of deaths occur during tuberculosis treatment despite patient
Role of interferon-gamma release assays in the diagnosis of pulmonary tuberculosis in patients with advanced HIV infection
Adithya Cattamanchi, Isaac Ssewenyana, J Lucian Davis, Laurence Huang, William Worodria, Saskia den Boon, Samuel Yoo, Alfred Andama, Philip C Hopewell, Huyen Cao
BMC Infectious Diseases , 2010, DOI: 10.1186/1471-2334-10-75
Abstract: We enrolled HIV-infected patients admitted to Mulago Hospital in Kampala, Uganda with cough ≥ 2 weeks. All patients underwent standard medical evaluation. We collected peripheral blood specimens at enrollment and performed a commercial, ELISPOT-based IGRA according to the manufacturer's recommendations. IGRA sensitivity and specificity were determined using mycobacterial culture results as the reference standard.Overall, 236 patients were enrolled. The median CD4+ T-lymphocyte count was 49 cells/μl and 126 (53%) patients were diagnosed with active pulmonary tuberculosis. IGRAs were not performed in 24 (10%) patients due to insufficient mononuclear cell counts. In the remaining 212 patients, results were indeterminate in 54 (25%). IGRAs were positive in 95 of 158 (60%) patients with interpretable results. The proportion of positive test results was similar across CD4+ count strata. IGRA sensitivity was 73% and specificity 54%. IGRA results did not meaningfully alter the probability of active tuberculosis in patients with negative sputum smears.An ELISPOT-based IGRA detected a high prevalence of latent tuberculosis infection in a hospitalized population of tuberculosis suspects with advanced HIV/AIDS but had limited utility for diagnosis of active tuberculosis in a high prevalence setting. Further research is needed to identify stronger and more specific immune responses in patients with active tuberculosis.T-cell interferon-gamma release assays (IGRAs) measure interferon-gamma release by sensitized T-lymphocytes stimulated with Mycobacterium tuberculosis (M. TB)-specific antigens. Though IGRAs are highly accurate for diagnosis of latent tuberculosis infection (LTBI) [1], their use as a diagnostic tool for active tuberculosis (TB) poses several challenges. IGRAs measure the host immune response to M. TB rather than the presence or absence of the organism in clinical specimens. In addition, IGRAs cannot distinguish an immune response to current active TB from an immune
Sensitivity of direct versus concentrated sputum smear microscopy in HIV-infected patients suspected of having pulmonary tuberculosis
Adithya Cattamanchi, David W Dowdy, J Lucian Davis, William Worodria, Samuel Yoo, Moses Joloba, John Matovu, Philip C Hopewell, Laurence Huang
BMC Infectious Diseases , 2009, DOI: 10.1186/1471-2334-9-53
Abstract: We performed a prospective, blinded evaluation of direct and concentrated Ziehl-Neelsen smear microscopy on a single early-morning sputum sample in HIV-infected patients with > 2 weeks of cough hospitalized in Kampala, Uganda. Direct and concentrated smear results were compared with results of Lowenstein-Jensen culture.Of 279 participants, 170 (61%) had culture-confirmed TB. The sensitivity of direct and concentrated smear microscopy was not significantly different (51% vs. 52%, difference 1%, 95% confidence interval (CI): [-7%, 10%], p = 0.88). However, when results of both direct and concentrated smears were considered together, sensitivity was significantly increased compared with either method alone (64%, 95% CI: [56%, 72%], p < 0.01 for both comparisons) and was similar to that of direct smear results from consecutive (spot and early-morning) specimens (64% vs. 63%, difference 1%, 95% CI: [-6%, 8%], p = 0.85). Among 109 patients with negative cultures, one had a positive direct smear and 12 had positive concentrated smears (specificity 99% vs. 89%, difference 10%, 95% CI: [2%, 18%], p = 0.003). Of these 13 patients, 5 (38%) had improved on TB therapy after two months.Sputum concentration did not increase the sensitivity of light microscopy for TB diagnosis in this HIV-infected population. Given the resource requirements for sputum concentration, additional studies using maximal blinding, high-quality direct microscopy, and a rigorous gold standard should be conducted before universally recommending this technique.Direct sputum smear microscopy is the cornerstone of tuberculosis (TB) diagnosis worldwide [1]. Direct smear microscopy is rapid, inexpensive [2-4], highly specific [5-7], and capable of identifying the most infectious cases of TB [7-9], but its sensitivity is limited, particularly in those with human immunodeficiency virus (HIV) co-infection [10-13]. Processing of sputum with subsequent concentration by centrifugation or sedimentation may increase the
Influence of M. tuberculosis Lineage Variability within a Clinical Trial for Pulmonary Tuberculosis
Payam Nahid,Erin E. Bliven,Elizabeth Y. Kim,William R. Mac Kenzie,Jason E. Stout,Lois Diem,John L. Johnson,Sebastien Gagneux,Philip C. Hopewell,Midori Kato-Maeda
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010753
Abstract: Recent studies suggest that M. tuberculosis lineage and host genetics interact to impact how active tuberculosis presents clinically. We determined the phylogenetic lineages of M. tuberculosis isolates from participants enrolled in the Tuberculosis Trials Consortium Study 28, conducted in Brazil, Canada, South Africa, Spain, Uganda and the United States, and secondarily explored the relationship between lineage, clinical presentation and response to treatment. Large sequence polymorphisms and single nucleotide polymorphisms were analyzed to determine lineage and sublineage of isolates. Of 306 isolates genotyped, 246 (80.4%) belonged to the Euro-American lineage, with sublineage 724 predominating at African sites (99/192, 51.5%), and the Euro-American strains other than 724 predominating at non-African sites (89/114, 78.1%). Uneven distribution of lineages across regions limited our ability to discern significant associations, nonetheless, in univariate analyses, Euro-American sublineage 724 was associated with more severe disease at baseline, and along with the East Asian lineage was associated with lower bacteriologic conversion after 8 weeks of treatment. Disease presentation and response to drug treatment varied by lineage, but these associations were no longer statistically significant after adjustment for other variables associated with week-8 culture status.
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