Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-23 (of 23 Records) |
Query Trace: Cavanaugh JS[original query] |
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Quantification of multidrug-resistant M. tuberculosis bacilli in sputum during the first 8 weeks of treatment
Smith-Jeffcoat SE , Eisenach KD , Joloba M , Ssengooba W , Namaganda C , Nsereko M , Okware B , Cavanaugh JS , Cegielski JP . Int J Tuberc Lung Dis 2022 26 (11) 1058-1064 SETTING: Mulago Hospital, Kampala, Uganda.OBJECTIVE: To quantify Mycobacterium tuberculosis in sputum during the first 8 weeks of pulmonary multidrug-resistant TB (MDR-TB) treatment.DESIGN: We enrolled consecutive adults with pulmonary MDR-TB treated according to national guidelines. We collected overnight sputum samples before treatment and weekly. Sputum samples were cultured on Middlebrook 7H11S agar to measure colony-forming units per mL (cfu/mL) and in MGIT™ 960™ media to measure time to detection (TTD). Linear mixed-effects regression was used to estimate the relational change in log(10) cfu/mL and TTD.RESULTS: Twelve adults (median age: 27 years) were enrolled. Half were women, and two-thirds were HIV-positive. At baseline, median log(10) cfu/mL was 5.1, decreasing by 0.29 log(10) cfu/mL/week. The median TTD was 116.5 h, increasing in TTD by 36.97 h/week. The weekly change was greater in the first 2 weeks (-1.04 log(10) cfu/mL/week and 120.02 h/week) than in the remaining 6 weeks (-0.17 log(10) cfu/mL/week and 26.11 h/week).CONCLUSION: Serial quantitative culture measures indicate a slow, uneven rate of decline in sputum M. tuberculosis over 8 weeks of standardized pulmonary MDR-TB treatment. |
Implementing TB preventive treatment within differentiated HIV service delivery models in global programs
Boyd AT , Moore B , Shah M , Tran C , Kirking H , Cavanaugh JS , Al-Samarrai T , Pathmanathan I . Public Health Action 2020 10 (3) 104-110 Global HIV program stakeholders, including the US President's Emergency Plan for AIDS Relief (PEPFAR), are undertaking efforts to ensure that eligible people living with HIV (PLHIV) receiving antiretroviral treatment (ART) receive a course of TB preventive treatment (TPT). In PEPFAR programming, this effort may require providing TPT not only to newly diagnosed PLHIV as part of HIV care initiation, but also to treatment-experienced PLHIV stable on ART who may not have been previously offered TPT. TPT scale-up is occurring at the same time as a trend to provide more person-centered HIV care through differentiated service delivery (DSD). In DSD, PLHIV stable on ART may receive less frequent clinical follow-up or receive care outside the traditional clinic-based model. The misalignment between traditional delivery of TPT and care delivery in innovative DSD may require adaptations to TPT delivery practices for PLHIV. Adaptations include components of planning and operationalization of TPT in DSD, such as determination of TPT eligibility and TPT initiation, and clinical management of PLHIV while on TPT. A key adaptation is alignment of timing and location for TPT and ART prescribing, monitoring, and dispensing. Conceptual examples of TPT delivery in DSD may help program managers operationalize TPT in HIV care. |
Case series of glans injuries during voluntary medical male circumcision for HIV prevention - eastern and southern Africa, 2015-2018
Lucas TJ , Toledo C , Davis SM , Watts DH , Cavanaugh JS , Kiggundu V , Thomas AG , Odoyo-June E , Bonnecwe C , Maringa TH , Martin E , Juma AW , Xaba S , Balachandra S , Come J , Canda M , Nyirenda R , Msungama W , Odek J , Lija GJI , Mlanga E , Zulu JE , O'Bra H , Chituwo O , Aupokolo M , Mali DA , Zemburuka B , Malaba KD , Ntsuape OC , Hines JZ . BMC Urol 2020 20 (1) 45 BACKGROUND: Male circumcision confers partial protection against heterosexual HIV acquisition among men. The President's Emergency Plan for AIDS Relief (PEPFAR) has supported > 18,900,000 voluntary medical male circumcisions (VMMC). Glans injuries (GIs) are rare but devastating adverse events (AEs) that can occur during circumcision. To address this issue, PEPFAR has supported multiple interventions in the areas of surveillance, policy, education, training, supply chain, and AE management. METHODS: Since 2015, PEPFAR has conducted surveillance of GIs including rapid investigation by the in-country PEPFAR team. This information is collected on standardized forms, which were reviewed for this analysis. RESULTS: Thirty-six GIs were reported from 2015 to 2018; all patients were < 15 years old (~ 0.7 per 100,000 VMMCs in this age group) with a decreasing annual rate (2015: 0.7 per 100,000 VMMCs; 2018: 0.4 per 100,000 VMMC; p = 0.02). Most (64%) GIs were partial or complete amputations. All amputations among 10-14 year-olds occurred using the forceps-guided (FG) method, as opposed to the dorsal-slit (DS) method, and three GIs among infants occurred using a Mogen clamp. Of 19 attempted amputation repairs, reattached tissue was viable in four (21%) in the short term. In some cases, inadequate DS method training and being overworked, were found. CONCLUSION: Following numerous interventions by PEPFAR and other stakeholders, GIs are decreasing; however, they have not been eliminated and remain a challenge for the VMMC program. Preventing further cases of complete and partial amputation will likely require additional interventions that prevent use of the FG method in young patients and the Mogen clamp in infants. Improving management of GIs is critical to optimizing outcomes. |
Tuberculosis preventive treatment scale-up among antiretroviral therapy patients - 16 countries supported by the U.S. President's Emergency Plan for AIDS Relief, 2017-2019
Melgar M , Nichols C , Cavanaugh JS , Kirking HL , Surie D , Date A , Ahmedov S , Maloney S , Fukunaga R . MMWR Morb Mortal Wkly Rep 2020 69 (12) 329-334 Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS(dagger) Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality. |
Policies, practices and barriers to implementing tuberculosis preventive treatment-35 countries, 2017
Surie D , Interrante JD , Pathmanathan I , Patel MR , Anyalechi G , Cavanaugh JS , Kirking HL . Int J Tuberc Lung Dis 2019 23 (12) 1308-1313 BACKGROUND: Tuberculosis preventive treatment (TPT) reduces the development of tuberculosis (TB) disease and mortality in people living with human immunodeficiency virus (HIV) infection. Despite this known effectiveness, global uptake of TPT has been slow. We aimed to assess current status of TPT implementation in countries supported by the US President's Emergency Plan for AIDS Relief (PEPFAR).METHODS: We surveyed TB-HIV program staff at US Centers for Disease Control and Prevention (CDC) country offices in 42 PEPFAR-supported countries about current TPT policies, practices, and barriers to implementation. Surveys completed from July to December 2017 were analyzed.RESULTS: Of 42 eligible PEPFAR-supported countries, staff from 35 (83%) CDC country offices completed the survey. TPT was included in national guidelines in 33 (94%) countries, but only 21 (60%) reported nationwide programmatic TPT implementation. HIV programs led TPT implementation in 20/32 (63%) countries, but TB programs led drug procurement in 18/32 (56%) countries. Stock outs were frequent, as 21/28 (75%) countries reported at least one isoniazid stock out in the previous year.CONCLUSION: Despite widespread inclusion of TPT in guidelines, programmatic TPT implementation lags. Successful scale-up of TPT requires uninterrupted drug supply chains facilitated by improved leadership and coordination between HIV and TB programs. |
TB preventive therapy for people living with HIV: Key considerations for scale-up in resource-limited settings
Pathmanathan I , Ahmedov S , Pevzner E , Anyalechi G , Modi S , Kirking H , Cavanaugh JS . Int J Tuberc Lung Dis 2018 22 (6) 596-605 Tuberculosis (TB) is the leading cause of death for persons living with the human immunodeficiency virus (PLHIV). TB preventive therapy (TPT) works synergistically with, and independently of, antiretroviral therapy to reduce TB morbidity, mortality and incidence among PLHIV. However, although TPT is a crucial and costeffective component of HIV care for adults and children and has been recommended as an international standard of care for over a decade, it remains highly underutilized. If we are to end the global TB epidemic, we must address the significant reservoir of tuberculous infection, especially in those, such as PLHIV, who are most likely to progress to TB disease. To do so, we must confront the pervasive perception that barriers to TPT scale-up are insurmountable in resource-limited settings. Here we review available evidence to address several commonly stated obstacles to TPT scale-up, including the need for the tuberculin skin test, limited diagnostic capacity to reliably exclude TB disease, concerns about creating drug resistance, suboptimal patient adherence to therapy, inability to monitor for and prevent adverse events, a 'one size fits all' option for TPT regimen and duration, and uncertainty about TPT use in children, adolescents, and pregnant women. We also discuss TPT delivery in the era of differentiated care for PLHIV, how best to tackle advanced planning for drug procurement and supply chain management, and how to create an enabling environment for TPT scale-up success. |
Evaluation of automated molecular testing rollout for tuberculosis diagnosis using routinely collected surveillance data - Uganda, 2012-2015
Scott C , Walusimbi S , Kirenga B , Joloba M , Winters M , Abdunoor N , Bain R , Alexander H , Shinnick T , Toney S , Odeke R , Mwangi C , Birabwa E , Dejene S , Mugabe F , YaDiul M , Cavanaugh JS . MMWR Morb Mortal Wkly Rep 2017 66 (12) 339-342 In 2012, Uganda introduced the use of GeneXpert MTB/RIF (Cepheid, Sunnyvale CA), a sensitive, automated, real-time polymerase chain reaction-based platform for tuberculosis (TB) diagnosis, for programmatic use among children, adults with presumptive human immunodeficiency virus (HIV)-associated TB, and symptomatic persons at risk for rifampicin (RIF)-resistant TB. The effect of using the platform's Xpert MTB/RIF assay on TB care and control was assessed using routinely collected programmatic data; in addition, a retrospective review of district quarterly summaries using abstracted TB register data from purposively selected facilities in the capital city of Kampala was conducted. Case notification rates were calculated and nonparametric statistical methods were used for analysis. No statistically significant differences were observed in case notification rates before and after the Xpert MTB/RIF assay became available, although four of 10 districts demonstrated a statistically significant difference in bacteriologically confirmed TB. Once the GeneXpert MTB/RIF platform is established and refined, a more comprehensive evaluation should be conducted. |
Susceptibilities of MDR Mycobacterium tuberculosis isolates to unconventional drugs compared with their reported pharmacokinetic/pharmacodynamic parameters
Cavanaugh JS , Jou R , Wu MH , Dalton T , Kurbatova E , Ershova J , Cegielski JP . J Antimicrob Chemother 2017 72 (6) 1678-1687 Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment. The resazurin microdilution assay was performed to determine MICs of trimethoprim/sulfamethoxazole, mefloquine, thioridazine, clofazimine, amoxicillin/clavulanate, meropenem/clavulanate, nitazoxanide, linezolid and oxyphenbutazone. Isoniazid was used for validation. We calculated the MIC 50 and MIC 90 as the MICs at which growth of 50% and 90% of isolates was inhibited, respectively. Results: The MIC 50 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.2/4; mefloquine, 8; thioridazine, 4; clofazimine, 0.25; amoxicillin/clavulanate, 16/8; meropenem/clavulanate, 1/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 40. The MIC 90 s, in mg/L, for initial isolates were as follows: trimethoprim/sulfamethoxazole, 0.4/8; mefloquine, 8; thioridazine, 8; clofazimine, 0.5; amoxicillin/clavulanate, 32/16; meropenem/clavulanate, 8/2.5; nitazoxanide, 16; linezolid, 0.25; and oxyphenbutazone, 60. By comparison, the MIC 90 of isoniazid was >4 mg/L, as expected. There was no evidence that previous treatment affected susceptibility to any drug. Conclusions: Most drugs demonstrated efficacy against M. tuberculosis . When these MICs are compared with the published pharmacokinetic/pharmacodynamic profiles of the respective drugs in humans, trimethoprim/sulfamethoxazole, meropenem/clavulanate, linezolid, clofazimine and nitazoxanide appear promising and warrant further clinical investigation. |
Comparison of sputum-culture conversion for Mycobacterium bovis and M. tuberculosis
Scott C , Cavanaugh JS , Silk BJ , Ershova J , Mazurek GH , LoBue PA , Moonan PK . Emerg Infect Dis 2017 23 (3) 456-462 Current US guidelines recommend longer treatment for tuberculosis (TB) caused by pyrazinamide-resistant organisms (e.g., Mycobacterium bovis) than for M. tuberculosis TB. We compared treatment response times for patients with M. bovis TB and M. tuberculosis TB reported in the United States during 2006-2013. We included culture-positive, pulmonary TB patients with genotyping results who received standard 4-drug treatment at the time of diagnosis. Time to sputum-culture conversion was defined as time between treatment start date and date of first consistently culture-negative sputum. We analyzed 297 case-patients with M. bovis TB and 30,848 case-patients with M. tuberculosis TB. After 2 months of treatment, 71% of M. bovis and 65% of M. tuberculosis TB patients showed conversion of sputum cultures to negative. Likelihood of culture conversion was higher for M. bovis than for M. tuberculosis, even after controlling for treatment administration type, sex, and a composite indicator of bacillary burden. |
Multidrug-resistant tuberculosis in Bangladesh: Results from a sentinel surveillance system
Banu S , Rahman MT , Ahmed S , Khatun R , Ferdous SS , Hosen B , Rahman MM , Ahmed T , Cavanaugh JS , Heffelfinger JD . Int J Tuberc Lung Dis 2017 21 (1) 12-17 and i BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to successful TB control. The 2010-2011 Bangladesh Drug Resistance Survey (DRS) showed MDR-TB prevalence to be 7% overall, 1.4% in new and 28.5% in previously treated patients. We aimed to determine the rate of MDR-TB in selected sentinel sites in Bangladesh. METHODS: Fourteen hospitals from the seven divisions in Bangladesh were selected as sentinel surveillance sites. Newly registered TB patients were systematically enrolled from August 2011 to December 2014. Sputum specimens were processed for culture and drug susceptibility testing by the proportion method using Lowenstein-Jensen medium. RESULTS: Specimens from 1906 (84%) of 2270 enrolled patients were analysed. Isolates from 61 (3.2%) were identified as having MDR-TB. The proportion of MDR-TB was 2.3% among new and 13.8% among previously treated TB patients (P < 0.001). The overall proportion of MDR-TB was 3.2%:3.5% in males and 2.3% in females; by age, the MDR-TB rate was highest (5.2%) in those aged ≥65 years. CONCLUSIONS: The high proportion of MDR-TB among new patients found in this sentinel surveillance significantly differs from that reported in the DRS. While the sentinel surveillance sites were not designed to be nationally representative, it is worrying to observe a higher number of MDR-TB cases among new patients. |
Performance of clinical screening algorithms for tuberculosis intensified case finding among people living with HIV in western Kenya
Modi S , Cavanaugh JS , Shiraishi RW , Alexander HL , McCarthy KD , Burmen B , Muttai H , Heilig CM , Nakashima AK , Cain KP . PLoS One 2016 11 (12) e0167685 OBJECTIVE: To assess the performance of symptom-based screening for tuberculosis (TB), alone and with chest radiography among people living with HIV (PLHIV), including pregnant women, in Western Kenya. DESIGN: Prospective cohort study. METHODS: PLHIV from 15 randomly-selected HIV clinics were screened with three clinical algorithms [World Health Organization (WHO), Ministry of Health (MOH), and "Improving Diagnosis of TB in HIV-infected persons" (ID-TB/HIV) study], underwent chest radiography (unless pregnant), and provided two or more sputum specimens for smear microscopy, liquid culture, and Xpert MTB/RIF. Performance of clinical screening was compared to laboratory results, controlling for the complex design of the survey. RESULTS: Overall, 738 (85.6%) of 862 PLHIV enrolled were included in the analysis. Estimated TB prevalence was 11.2% (95% CI, 9.9-12.7). Sensitivity of the three screening algorithms was similar [WHO, 74.1% (95% CI, 64.1-82.2); MOH, 77.5% (95% CI, 68.6-84.5); and ID-TB/HIV, 72.5% (95% CI, 60.9-81.7)]. Sensitivity of the WHO algorithm was significantly lower among HIV-infected pregnant women [28.2% (95% CI, 14.9-46.7)] compared to non-pregnant women [78.3% (95% CI, 67.3-86.4)] and men [77.2% (95% CI, 68.3-84.2)]. Chest radiography increased WHO algorithm sensitivity and negative predictive value to 90.9% (95% CI, 86.4-93.9) and 96.1% (95% CI, 94.4-97.3), respectively, among asymptomatic men and non-pregnant women. CONCLUSIONS: Clinical screening missed approximately 25% of laboratory-confirmed TB cases among all PLHIV and more than 70% among HIV-infected pregnant women. National HIV programs should evaluate the feasibility of laboratory-based screening for TB, such as a single Xpert MTB/RIF test for all PLHIV, especially pregnant women, at enrollment in HIV services. |
Human tuberculosis caused by Mycobacterium bovis in the United States, 2006-2013.
Scott C , Cavanaugh JS , Pratt R , Silk BJ , LoBue P , Moonan PK . Clin Infect Dis 2016 63 (5) 594-601 BACKGROUND: Using genotyping techniques that have differentiated Mycobacterium bovis from M. tuberculosis since 2005, we review the epidemiology of human TB caused by M. bovis in the United States and validate previous findings nationally. METHODS: All TB cases with a genotyped M. tuberculosis complex isolate reported during 2006-2013 in the United States were eligible for analysis. We used binomial regression to identify characteristics independently associated with M. bovis disease using adjusted prevalence ratios (aPRs) and corresponding 95% confidence intervals (95%CI). RESULTS: During 2006-2013, the annual percentages of TB cases attributable to M. bovis remained consistent nationally (range: 1.3-1.6%) among all TB cases (n=59,273). Compared with adults 25-44 years of age, infants 0-4 years (aPR 1.9, 95% CI 1.4-2.8) and children 5-14 years (aPR 4.0, 95% CI 3.1-5.3) had higher prevalences of M. bovis disease. Patients who were foreign-born (aPR 1.4, 95% CI 1.2-1.7), Hispanic (aPR 3.9, 95% CI 3.0-5.0), female (aPR 1.4, 95% CI 1.3-1.6),), and resided in U.S.-Mexico border counties (aPR 2.0, 95% CI 1.7-2.4) also had higher M. bovis prevalences. Exclusively extrapulmonary disease (aPR 3.7, 95% CI 3.3-4.2) or disease that was both pulmonary and extrapulmonary (aPR 2.4, 95% CI 2.1-2.9) were associated with a higher prevalence of M. bovis disease CONCLUSIONS: Children, foreign-born persons, Hispanics, and women are disproportionately affected by M. bovis, which was independently associated with extrapulmonary disease. Targeted prevention efforts aimed at Hispanic mothers and caregivers are warranted. |
Comparative yield of different diagnostic tests for tuberculosis among people living with HIV in Western Kenya
Cavanaugh JS , Modi S , Musau S , McCarthy K , Alexander H , Burmen B , Heilig CM , Shiraishi RW , Cain K . PLoS One 2016 11 (3) e0152364 BACKGROUND: Diagnosis followed by effective treatment of tuberculosis (TB) reduces transmission and saves lives in persons living with HIV (PLHIV). Sputum smear microscopy is widely used for diagnosis, despite limited sensitivity in PLHIV. Evidence is needed to determine the optimal diagnostic approach for these patients. METHODS: From May 2011 through June 2012, we recruited PLHIV from 15 HIV treatment centers in western Kenya. We collected up to three sputum specimens for Ziehl-Neelsen (ZN) and fluorescence microscopy (FM), GeneXpert MTB/RIF (Xpert), and culture, regardless of symptoms. We calculated the incremental yield of each test, stratifying results by CD4 cell count and specimen type; data were analyzed to account for complex sampling. RESULTS: From 778 enrolled patients, we identified 88 (11.3%) laboratory-confirmed TB cases. Of the 74 cases who submitted 2 specimens for microscopy and Xpert testing, ZN microscopy identified 25 (33.6%); Xpert identified those plus an additional 18 (incremental yield = 24.4%). Xpert testing of spot specimens identified 48 (57.0%) of 84 cases; whereas Xpert testing of morning specimens identified 50 (66.0%) of 76 cases. Two Xpert tests detected 22/24 (92.0%) TB cases with CD4 counts <100 cells/muL and 30/45 (67.0%) of cases with CD4 counts ≥100 cells/mul. CONCLUSIONS: In PLHIV, Xpert substantially increased diagnostic yield compared to smear microscopy and had the highest yield when used to test morning specimens and specimens from PLHIV with CD4 count <100 cells/muL. TB programs unable to replace smear microscopy with Xpert for all symptomatic PLHIV should consider targeted replacement and using morning specimens. |
Tuberculosis screening outcomes for newly diagnosed persons living with HIV, Nyanza Province, Kenya, 2009
Burmen B , Modi S , Cavanaugh JS , Muttai H , McCarthy KD , Alexander H , Cain K . Int J Tuberc Lung Dis 2016 20 (1) 79-84 SETTING: Fifteen human immunodeficiency virus (HIV) clinics in Nyanza Region, Western Kenya. OBJECTIVE: To describe routine tuberculosis (TB) screening and diagnostic practices among newly enrolled people living with HIV (PLHIV) prior to the implementation of World Health Organization recommended TB intensified case finding. DESIGN: Retrospective chart abstraction of PLHIV aged 7 years who were newly enrolled in HIV care in July and August 2009, and who had not received antiretroviral treatment in the preceding 2 years or been diagnosed with TB in the previous year. Factors associated with evidence of TB diagnostic evaluation among symptomatic PLHIV were assessed. RESULTS: Of 1020 patients included in the analysis, 995 (98%) were screened for TB at enrolment and 613 (62%) reported TB symptoms. Ninety-six (16%) patients with symptoms had evidence of referral for TB diagnostic evaluation, including patients at large clinics, those with advanced HIV disease and those reporting multiple TB symptoms. Among the 43 (45%) with documented evaluation results, 26 (60%) were diagnosed with TB. CONCLUSION: Although most PLHIV were screened for TB, very few underwent an evaluation, and the proportion diagnosed with TB was very low. Efforts to improve TB screening should focus on standardizing the intensified case finding algorithm and linkage to, and adequate infrastructure for, TB diagnostic evaluation. |
Evaluation of community-based treatment for drug-resistant tuberculosis in Bangladesh
Cavanaugh JS , Kurbatova E , Alami NN , Mangan J , Sultana Z , Ahmed S , Begum V , Sultana S , Daru P , Ershova J , Golubkov A , Banu S , Heffelfinger JD . Trop Med Int Health 2015 21 (1) 131-139 OBJECTIVE: Drug-resistant tuberculosis (TB) threatens global TB control because it is difficult to diagnose and treat. Community-based programmatic management of drug-resistant TB (cPMDT) has made therapy easier for patients, but data on these models are scarce. Bangladesh initiated cPMDT in 2012, and in 2013 we sought to evaluate program performance. METHODS: In this retrospective review, we abstracted demographic, clinical, microbiologic and treatment outcome data for all patients enrolled in the cPMDT program over six months in three districts of Bangladesh. We interviewed a convenience sample of patients about their experience in the program. RESULTS: Chart review was performed on 77 patients. Sputum smears and cultures were done, on average, once every 1.35 and 1.36 months, respectively. Among 74 initially culture-positive patients, 70 (95%) converted their cultures and 69 (93%) patients converted the cultures before the sixth month. Fifty-two (68%) patients had evidence of screening for adverse events. We found written documentation of musculoskeletal complaints for 16 (21%) patients, gastrointestinal adverse events for 16 (21%), hearing loss for eight (10%) and psychiatric events for four (5%) patients; conversely, on interview of 60 patients, 55 (92%) reported musculoskeletal complaints, 54 (90%) reported nausea, 36 (60%) reported hearing loss, and 36 (60%) reported psychiatric disorders. CONCLUSIONS: The cPMDT program in Bangladesh appears to be programmatically feasible and clinically effective; however, inadequate monitoring of adverse events raises some concern. As the program is brought to scale nationwide, renewed efforts at monitoring adverse events should be prioritized. This article is protected by copyright. All rights reserved. |
Association between Mycobacterium tuberculosis complex phylogenetic lineage and acquired drug resistance
Yuen CM , Kurbatova EV , Click ES , Cavanaugh JS , Cegielski JP . PLoS One 2013 8 (12) e83006 BACKGROUND: Development of resistance to antituberculosis drugs during treatment (i.e., acquired resistance) can lead to emergence of resistant strains and consequent poor clinical outcomes. However, it is unknown whether Mycobacterium tuberculosis complex species and lineage affects the likelihood of acquired resistance. METHODS: We analyzed data from the U.S. National Tuberculosis Surveillance System and National Tuberculosis Genotyping Service for tuberculosis cases during 2004-2011 with assigned species and lineage and both initial and final drug susceptibility test results. We determined univariate associations between species and lineage of Mycobacterium tuberculosis complex bacteria and acquired resistance to isoniazid, rifamycins, fluoroquinolones, and second-line injectables. We used Poisson regression with backward elimination to generate multivariable models for acquired resistance to isoniazid and rifamycins. RESULTS: M. bovis was independently associated with acquired resistance to isoniazid (adjusted prevalence ratio = 8.46, 95% CI 2.96-24.14) adjusting for HIV status, and with acquired resistance to rifamycins (adjusted prevalence ratio = 4.53, 95% CI 1.29-15.90) adjusting for homelessness, HIV status, initial resistance to isoniazid, site of disease, and administration of therapy. East Asian lineage was associated with acquired resistance to fluoroquinolones (prevalence ratio = 6.10, 95% CI 1.56-23.83). CONCLUSIONS: We found an association between mycobacterial species and lineage and acquired drug resistance using U.S. surveillance data. Prospective clinical studies are needed to determine the clinical significance of these findings, including whether rapid genotyping of isolates at the outset of treatment may benefit patient management. |
Epidemiology of pyrazinamide-resistant tuberculosis in the United States, 1999-2009
Kurbatova EV , Cavanaugh JS , Dalton T , Click E , Cegielski JP . Clin Infect Dis 2013 57 (8) 1081-93 BACKGROUND: Pyrazinamide (PZA) is essential in tuberculosis (TB) treatment. We describe the prevalence, trends and predictors of PZA resistance in Mycobacterium tuberculosis complex (MTBC) in the U.S. METHODS: We analyzed culture-positive MTBC cases with reported drug susceptibility tests (DST) for PZA in 38 jurisdictions routinely testing for PZA susceptibility from 1999-2009. National TB Genotyping Service data for 2004-2009 were used to distinguish Mycobacterium tuberculosis from Mycobacterium bovis and determine phylogenetic lineage. RESULTS: Overall 2.7% (2,167/79,321) of MTBC cases had PZA resistance, increasing annually from 2.0% to 3.3% during 1999-2009 (P<0.001), largely due to an increase in PZA monoresistance. PZA-monoresistant MTBC (versus drug-susceptible) was associated with age 0-24 years (adjusted prevalence ratio [aPR]=1.50, 95% CI 1.31-1.71), Hispanic ethnicity (aPR=3.52, 2.96-4.18), HIV infection (aPR=1.43, 1.15-1.77), extrapulmonary disease (aPR=3.02, 2.60-3.52), and normal chest radiograph (aPR=1.88, 1.63-2.16), and inversely associated with Asian (aPR=0.59, 0.47-0.73) and Black (aPR=0.37, 0.29-0.49) race. Among multidrug-resistant (MDR) cases 38.0% were PZA-resistant; PZA resistance in MDR MTBC was associated with female sex (aPR=1.25, 1.08-1.46) and previous TB diagnosis (aPR=1.37, 1.16-1.62). Of 28,080 cases with genotyping data, 925 (3.3%) had PZA resistance; 465/925 (50.3%) were M. bovis. In non-MDR M. tuberculosis cases, PZA resistance was higher in the Indo-Oceanic than the East Asian lineage (2.2% versus 0.9%; respectively; aPR=2.26, 1.53-3.36), but in MDR cases it was lower in the Indo-Oceanic lineage (22.0% versus 43.4%, respectively; aPR=0.54, 0.32-0.90). CONCLUSIONS: Specific human and mycobacterial characteristics were associated with pyrazinamide-resistant MTBC, reflecting both specific subgroups of the population and phylogenetic lineages of the mycobacteria. |
Epidemiology of smear-negative pulmonary tuberculosis in the United States, 1993-2008
Shah NS , Cavanaugh JS , Pratt R , Cain KP , Wells C , Laserson K , Nelson L . Int J Tuberc Lung Dis 2012 16 (9) 1234-40 BACKGROUND: Smear-negative tuberculosis (TB) is difficult to diagnose and has been associated with poor treatment outcomes and excessive mortality, particularly in high human immunodeficiency virus (HIV) prevalent settings. However, few studies have used mycobacterial culture to rigorously confirm all smear-negative TB cases in a population-based cohort. DESIGN: We included all culture-confirmed, pulmonary TB cases reported to the US National TB Surveillance System from 1993 to 2008. We analyzed smear-negative TB risk factors and survival, as compared to smear-positive TB. We calculated prevalence ratios (PRs) and adjusted for confounders (aPR). RESULTS: From 1993 to 2008, 159,121 cases of culture-confirmed pulmonary TB were reported in the United States, of which 58,786 (37%) were sputum smear-negative. Smear-negative TB cases were more likely to be foreign-born (aPR 1.10, 95%CI 1.08-1.12), incarcerated (aPR 1.52, 95%CI 1.48-1.56) or HIV-infected (aPR 1.27, 95%CI 1.24-1.30). Hispanics and non-Hispanic Blacks were less likely to have smear-negative TB (respectively aPR 0.87, 95%CI 0.85-0.89 and aPR 0.90, 95%CI 0.89-0.92). Smear-negative TB cases had lower mortality (aRR 0.78, 95%CI 0.74-0.81), independent of HIV status. CONCLUSION: Smear-negative TB represents a large proportion of TB cases in the United States, and occurs more often among persons in groups more likely to undergo TB screening. The lower mortality may indicate earlier TB detection, and underscores the need for continued vigilance in screening of high-risk persons. |
Survival among patients with HIV infection and smear-negative pulmonary tuberculosis - United States, 1993-2006
Cavanaugh JS , Shah NS , Cain KP , Winston CA . PLoS One 2012 7 (10) e47855 BACKGROUND: In patients with HIV and tuberculosis (TB) in resource-constrained settings, smear-negative disease has been associated with higher mortality than smear-positive disease. Higher reported mortality may be due to misdiagnosis, diagnostic delays, or because smear-negative disease indicates more advanced immune suppression. METHODS: We analyzed culture-confirmed, pulmonary TB among patients with TB and HIV in the United States from 1993-2008 to calculate prevalence ratios (PRs) for smear-negative disease by demographic and clinical characteristics. Allowing two years for treatment outcome to be reported, we determined hazard ratios (HRs) for survival by smear status, adjusted for significant covariates on patients before 2006. RESULTS: Among 16,710 cases with sputum smear results, 6,739 (39%) were sputum smear-negative and 9,971 (58%) were sputum smear-positive. The prevalence of smear-negative disease was lower in male patients (PR: 0.89, 95% confidence interval [CI]: 0.86-0.93) and in those who were homeless (PR: 0.92, CI: 0.87-0.97) or used alcohol excessively (PR: 0.91, CI: 0.87-0.95), and higher in persons diagnosed while incarcerated (PR: 1.20, CI: 1.13-1.27). Patients with smear-negative disease had better survival compared to patients with smear-positive disease, both before (HR: 0.82, CI: 0.75-0.90) and after (HR: 0.81, CI: 0.71-0.92) the introduction of combination anti-retroviral therapy. CONCLUSIONS: In the United States, smear-negative pulmonary TB in patients with HIV was not associated with higher mortality, in contrast to what has been documented in high TB burden settings. Smear-negative TB can be routinely and definitively diagnosed in the United States, whereas high-burden countries often rely solely on AFB-smear microscopy. This difference could contribute to diagnostic and treatment delays in high-burden countries, possibly resulting in higher mortality. |
Outcomes and follow-up of patients treated for multidrug-resistant tuberculosis in Orel, Russia, 2002-2005
Cavanaugh JS , Kazennyy BY , Nguyen ML , Kiryanova EV , Vitek E , Khorosheva TM , Nemtsova E , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (8) 1069-74 SETTING: Multidrug-resistant tuberculosis (MDR-TB) treatment facility, Orel Oblast, Russian Federation. OBJECTIVES: To determine factors associated with poor outcome and to document status of patients after recording of TB outcomes. DESIGN: Retrospective review of prospective single cohort. RESULTS: Among 192 patients, factors significantly associated with poor outcome in multivariate analysis include three or more treatment interruptions during the intensive phase of therapy and alcohol or drug addiction (adjusted OR [aOR] 2.1, 95%CI 1.0-4.3 and aOR 1.9, 95%CI 1.0-3.7). Previous treatment was associated with poor outcome, but only among smear-positive patients (aOR 3.1, 95%CI 1.3-7.3). Ten patients (5%) developed extensively drug-resistant TB (XDR-TB) during treatment; of 115 patients with at least 6 months of follow-up data after outcomes were recorded, 13 (11%) developed XDR-TB. CONCLUSION: Interventions focused on supporting patient adherence during the intensive phase of treatment; the management of drug and alcohol addiction should be developed and studied. A substantial proportion of patients developed XDR-TB during and after treatment. Longer term follow-up data of patients treated for MDR-TB are needed to better inform programmatic policy. |
An outbreak of tuberculosis among adults with mental illness
Cavanaugh JS , Powell K , Renwick OJ , Davis KL , Hilliard A , Benjamin C , Mitruka K . Am J Psychiatry 2012 169 (6) 569-75 In August 2008, a resident at a Florida assisted living facility for adults with mental illness was diagnosed with infectious pulmonary tuberculosis (TB). From October 2008 to May 2009, 14 additional residents and three nonresidents were diagnosed with TB. The index patient was contagious for approximately 8 months before he was diagnosed in August 2008. He first sought medical attention for a cough and general malaise in April 2008, at a local psychiatric hospital where he felt comfortable receiving care because of his frequent previous hospitalizations there. He was evaluated by an internist and admitted for acute psychiatric decompensation for 8 days to a locked ward that held approximately 25 patients. Although cough was documented on admission, medical records did not reveal any detail on how the patient described his symptoms, and further evaluation was not performed at that time. During the course of his infectious period, the patient did not seek treatment at a medical facility for his worsening TB symptoms. He was held for one night in a one-person cell at the county jail and was hospitalized three more times at the psychiatric hospital for stays ranging from 2 to 8 days. He was assessed by an internist at each admission, and a cough was documented in each admission note. When the patient was hospitalized for the fourth time at the psychiatric facility in August 2008, a provider noted that his cough had persisted and ordered chest radiography, which revealed evidence of a cavitary lesion suggestive of pulmonary TB. The patient was transferred to a medical hospital, where sputum smear microscopy was positive for acid-fast bacilli, and confirmatory testing revealed Mycobacterium tuberculosis. After 2 weeks of TB treatment, the patient left against medical advice and returned to the assisted living facility. Three days later, supervisors from the assisted living facility brought him to another medical hospital for admission under direct one-to-one observation. He attempted to leave the hospital multiple times, requiring transfer to an isolation unit at the local jail and then to the A.G. Holley State Hospital, a Department of Health facility specializing in tuberculosis, in accordance with Florida state law permitting the involuntary examination and treatment of persons with mental illness who may be a harm to others, such as patients who have dangerous infectious diseases like tuberculosis. |
Rifampicin-resistant Mycobacterium tuberculosis: susceptibility to isoniazid and other anti-tuberculosis drugs
Kurbatova EV , Cavanaugh JS , Shah NS , Wright A , Kim H , Metchock B , Van Deun A , Barrera L , Boulahbal F , Richter E , Martin-Casabona N , Arias F , Zemanova I , Drobniewski F , Santos Silva A , Coulter C , Lumb R , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (3) 355-357 Based on data from 14 Supranational Tuberculosis (TB) Reference Laboratories worldwide, the proportion of rifampicin (RMP) resistant isolates that were isoniazid (INH) susceptible by phenotypic drug susceptibility testing varied widely (0.5-11.6%). RMP-resistant isolates that were INH-susceptible had significantly lower rates of resistance to other first- and second-line anti-tuberculosis drugs (except rifabutin) compared to multidrug-resistant isolates. RMP resistance is not a lways a good proxy for a presumptive diagnosis of multidrug-resistant TB, which has implications for use of molecular assays that identify only RMP resistanceassociated DNA mutations. (2012 The Union.) |
Global isoniazid resistance patterns in rifampin-resistant and rifampin-susceptible tuberculosis
Smith SE , Kurbatova EV , Cavanaugh JS , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (2) 203-205 Following the World Health Organization's endorsement of the Xpert((R)) MTB/RIF assay, which rapidly and simultaneously diagnoses tuberculosis (TB) and detects resistance to rifampin (RMP), the question arises to what extent RMP resistance is an adequate marker for multidrug-resistant TB (MDR-TB). A retrospective analysis of data from >81 countries and subnational settings demonstrated that >40% of RMP-resistant isolates from new TB cases did not display resistance to isoniazid (INH) in settings with relatively low MDR-TB prevalence (one third of all countries and subnational settings). Results indicated the need for INH susceptibility testing in addition to RMP susceptibility testing. |
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