Last data update: Jun 03, 2024. (Total: 46935 publications since 2009)
Records 1-30 (of 31 Records) |
Query Trace: Ershova J [original query] |
---|
Tuberculosis preventive treatment uptake among adults living with human immunodeficiency virus: Analysis of Zimbabwe population-based human immunodeficiency virus impact assessment 2020
Maphosa T , Mirkovic K , Weber RA , Musuka G , Mapingure MP , Ershova J , Laws R , Dobbs T , Coggin W , Sandy C , Apollo T , Mugurungi O , Melchior M , Farahani MS . Int J STD AIDS 2024 9564624241239186 BACKGROUND: Tuberculosis remains the leading cause of death by an infectious disease among people living with HIV (PLHIV). TB Preventive Treatment (TPT) is a cost-effective intervention known to reduce morbidity and mortality. We used data from ZIMPHIA 2020 to assess TPT uptake and factors associated with its use. METHODOLOGY: ZIMPHIA a cross-sectional household survey, estimated HIV treatment outcomes among PLHIV aged ≥15 years. Randomly selected participants provided demographic and clinical information. We applied multivariable logistic regression models using survey weights. Variances were estimated via the Jackknife series to determine factors associated with TPT uptake. RESULTS: The sample of 2419 PLHIV ≥15 years had 65% females, 44% had no primary education, and 29% lived in urban centers. Overall, 38% had ever taken TPT, including 15% currently taking TPT. Controlling for other variables, those screened for TB at last HIV-related visit, those who visited a TB clinic in the previous 12 months, and those who had HIV viral load suppression were more likely to take TPT. CONCLUSION: The findings show suboptimal TPT coverage among PLHIV. There is a need for targeted interventions and policies to address the barriers to TPT uptake, to reduce TB morbidity and mortality among PLHIV. |
The economic burden of households affected by tuberculosis in Brazil: First national survey results, 2019-2021
Noia Maciel EL , Negri Ldsa , Guidoni LM , Fregona GC , Johansen FDC , Sanchez MN , Moreira Adsr , Diaz-Quijano FA , Tonini M , Zandonade E , Ershova J , Nguhiu P , Baena IG . PLoS One 2023 18 (12) e0287961 BACKGROUND: One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. METHODS: A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. RESULTS: We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). CONCLUSIONS: Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil. |
National tuberculosis prevalence surveys in Africa, 2008-2016: an overview of results and lessons learned
Law I , Floyd K , African TB Prevalence Survey Group , Bloss E , Ershova J , Moonan PK . Trop Med Int Health 2020 25 (11) 1308-1327 OBJECTIVE AND METHODS: Worldwide, tuberculosis (TB) is the leading cause of death from a single infectious agent. In many countries, national TB prevalence surveys are the only way to reliably measure the burden of TB disease and can also provide other evidence to inform national efforts to improve TB detection and treatment. Our objective was to synthesise the results and lessons learned from national surveys completed in Africa between 2008 and 2016, to complement a previous review for Asia. RESULTS: Twelve surveys completed in Africa were identified: Ethiopia (2010-2011), Gambia (2011-2013), Ghana (2013), Kenya (2015-2016), Malawi (2013-2014), Nigeria (2012), Rwanda (2012), Sudan (2013-2014), Tanzania (2011-2012), Uganda (2014-2015), Zambia (2013-2014) and Zimbabwe (2014). The eligible population in all surveys was people aged ≥15 years who met residency criteria. In total 588 105 individuals participated, equivalent to 82% (range 57-96%) of those eligible. The prevalence of bacteriologically confirmed pulmonary TB disease in those ≥15 years varied from 119 (95% CI 79-160) per 100 000 population in Rwanda and 638 (95% CI 502-774) per 100 000 population in Zambia. The male:female ratio was 2.0 overall, ranging from 1.2 (Ethiopia) to 4.1 (Uganda). Prevalence per 100 000 population generally increased with age, but the absolute number of cases was usually highest among those aged 35-44 years. Of identified TB cases, 44% (95% CI 40-49) did not report TB symptoms during screening and were only identified as eligible for diagnostic testing due to an abnormal chest X-ray. The overall ratio of prevalence to case notifications was 2.5 (95% CI 1.8-3.2) and was consistently higher for men than women. Many participants who did report TB symptoms had not sought care; those that had were more likely to seek care in a public health facility. HIV prevalence was systematically lower among prevalent cases than officially notified TB patients with an overall ratio of 0.5 (95% CI 0.3-0.7). The two main study limitations were that none of the surveys included people <15 years, and 5 of 12 surveys did not have data on HIV status. CONCLUSIONS: National TB prevalence surveys implemented in Africa between 2010 and 2016 have contributed substantial new evidence about the burden of TB disease, its distribution by age and sex, and gaps in TB detection and treatment. Policies and practices to improve access to health services and reduce under-reporting of detected TB cases are needed, especially among men. All surveys provide a valuable baseline for future assessment of trends in TB disease burden. |
Implementation of a methodological protocol for the national survey on tuberculosis catastrophic costs in Brazil
Maciel ELN , Negri Ldsa , Guidoni LM , Fregona GC , Loureiro RB , Daré IB , Prado TND , Sanchez MN , Diaz-Quijano FA , Tonini M , Zandonade E , Baena IG , Ershova J . Rev Soc Bras Med Trop 2023 56 e0493 The World Health Organization (WHO) has set goals to end the tuberculosis (TB) pandemic by 2035, that is, to reduce the incidence to less than 10 cases per 100,000 inhabitants and the mortality rate by 95%. Although TB is a disease affecting people of all socioeconomic classes, it is mainly found in marginalized and vulnerable populations 1 . In 2019, before the onset of the coronavirus disease 2019 pandemic (COVID-19), 10 million people were diagnosed with TB worldwide, 7.1 million were reported to public health services, and 1.4 million died of the disease, including 20,800 people with human immunodeficiency virus (HIV) 2 , 3 . |
Implementing tuberculosis patient cost surveys in resource-constrained settings: lessons from Tanzania
Kilale AM , Makasi C , Majaha M , Manga CD , Haule S , Hilary P , Kimbute O , Kitua S , Jani B , Range N , Ngowi B , Nkiligi E , Matechi E , Muhandiki W , Mahamba V , Mutayoba B , Ershova J . BMC Public Health 2022 22 (1) 2187 Tuberculosis (TB) disproportionally affects persons and families who are economically and socially disadvantaged. Therefore, a patient cost survey was conducted in Tanzania to evaluate the costs incurred by patients and their households before and after the diagnosis of TB. It was the first survey in Tanzania to ascertain baseline information and experience for subsequent surveys. This paper aims to share the experience encountered during the survey to ensure a standardized approach and elimination of potential barriers for the implementation of future surveys. A total of 777 TB patients from 30 clusters selected based on probability proportional to the size were interviewed during the study period. As the sample size was calculated based on notification data from the previous year, some health facilities experienced an inadequate number of TB patients during the study to meet the allocated cluster size for the survey. Most facilities had poor recording and recordkeeping in TB registers where deaths were not registered, and some patients had not been assigned district identification numbers. Fixed days for TB drug refills in health facilities affected the routine implementation of the survey as the interviews were conducted when patients visited the facility to pick up the drugs. Tablets used to collect data failed to capture the geographic location in some areas. The households of TB patients lost to follow-up and those who had died during TB treatment were not included in the survey. When planning and preparing for patient costs surveys, it is important to consider unforeseen factors which may affect planned activities and findings. During the survey in Tanzania, the identified challenges included survey logistics, communications, patient enrollment, and data management issues. To improve the quality of the findings of future surveys, it may be reasonable to revise survey procedures to include households of TB patients who were lost to follow-up and those who died during TB treatment; the households of such patients may have incurred higher direct and indirect costs than households whose patient was cured as a result of receiving TB treatment. |
The economic burden of TB faced by patients and affected families in Papua New Guinea
Ershova J . Int J Tuberc Lung Dis 2022 26 (10) 934-941 BACKGROUND The costs associated with TB disease can be catastrophic for patients, affecting health and socioeconomic outcomes. Papua New Guinea (PNG) is a high TB burden country and the costs associated with TB are unknown.METHODS We undertook a national survey of TB patients to determine the magnitude of costs associated with TB in PNG, the proportion of households with catastrophic costs and cost drivers. We used a cluster sampling approach and recruited TB patients from health facilities. Descriptive statistics were used to analyse the costs and cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs.RESULTS We interviewed 1,000 TB patients; 19 (1.9%) of them had multidrug-resistant TB (MDR-TB). Costs due to TB were attributable to income loss (64.4%), non-medical (29.9%) and medical (5.7%) expenses. Catastrophic costs were experienced by 33.9% (95% CI 31.0-36.9) of households and were associated with MDR-TB (aOR 4.47, 95% CI 1.21-16.50), hospitalization (aOR 3.94, 95% CI 2.69-5.77), being in the poorest (aOR 3.52, 95% CI 2.43-5.10) or middle wealth tertiles (aOR 1.51, 95% CI 1.03-2.21) or being employed (aOR 2.02, 95% CI 1.43-2.89).CONCLUSION The costs due to TB disease were catastrophic for one third of TB-affected households in PNG. Current support measures could be continued, while new cost mitigation interventions may be considered where needed. |
The second national anti-tuberculosis drug resistance survey in Tanzania, 2017-2018
Mutayoba BK , Ershova J , Lyamuya E , Hoelscher M , Heinrich N , Kilale AM , Range NS , Ngowi BJ , Ntinginya NE , Mfaume SM , Nkiligi E , Doulla B , Lyimo J , Kisonga R , Kingalu A , Lema Y , Kondo Z , Pletschette M . Trop Med Int Health 2022 27 (10) 891-901 OBJECTIVE: To determine the levels and patterns of resistance to first- and second-line anti-tuberculosis (TB) drugs among new and previously treated sputum smear positive pulmonary TB (PTB) patients. METHODS: We conducted a nationally representative cross-sectional facility-based survey in June 2017-July 2018 involving 45 clusters selected based on probability proportional to size. The survey aimed to determine the prevalence of anti-TB drug resistance and associated risk factors among smear positive PTB patients in Tanzania. Sputum samples were examined using smear microscopy, Xpert MTB/RIF, culture and drug susceptibility testing (DST). Logistic regression was used to account for missing data and sampling design effects on the estimates and their standard errors. RESULTS: We enrolled 1557 TB patients, including 1408 (90.4%) newly diagnosed and 149 (9.6%) previously treated patients. The prevalence of multidrug-resistant TB (MDR-TB) was 0.85% [95% confidence interval (CI): 0.4-1.3] among new cases and 4.6% (95% CI: 1.1-8.2) among previously treated cases. The prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) was 1.7% among new TB patients and 6.5% among those previously treated. Drug resistance to all first-line drugs was similar (0.1%) in new and previously treated patients. None of the isolates displayed poly-resistance or extensively drug-resistant TB (XDR-TB). The only risk factor for MDR-TB was history of previous TB treatment (odds ratio = 5.7, 95% CI: 1.9-17.2). CONCLUSION: The burden of MDR-TB in the country was relatively low with no evidence of XDR-TB. Given the overall small number of MDR-TB cases in this survey, it will be beneficial focusing efforts on intensified case detection including universal DST. |
Economic burden of tuberculosis in Tanzania: a national survey of costs faced by tuberculosis-affected households
Ershova J . BMC Public Health 2022 22 (1) 600 BACKGROUND: Although tuberculosis (TB) care is free in Tanzania, TB-associated costs may compromise access to services and treatment adherence resulting in poor outcomes and increased risk of transmission in the community. TB can impact economically patients and their households. We assessed the economic burden of TB on patients and their households in Tanzania and identified cost drivers to inform policies and programs for potential interventions to mitigate costs. METHODS: We conducted a nationally representative cross-sectional survey using a standard methodology recommended by World Health Organization. TB patients of all ages and with all types of TB from 30 clusters across Tanzania were interviewed during July - September 2019. We used the human capital approach to assess the indirect costs and a threshold of 20% of the household annual expenditure to determine the proportion of TB-affected households experiencing catastrophic cost. We descriptively analyzed the cost data and fitted multivariable logistic regression models to identify potential predictors of catastrophic costs. RESULTS: Of the 777 TB-affected households, 44.9% faced catastrophic costs due to TB. This proportion was higher (80.0%) among households of patients with multi-drug resistant TB (MDR-TB). Overall, cost was driven by income loss while accessing TB services (33.7%), nutritional supplements (32.6%), and medical costs (15.1%). Most income loss was associated with hospitalization and time for picking up TB drugs. Most TB patients (85.9%) reported worsening financial situations due to TB, and over fifty percent (53.0%) borrowed money or sold assets to finance TB treatment. In multivariable analysis, the factors associated with catastrophic costs included hospitalization (adjusted odds ratio [aOR] = 34.9; 95% confidence interval (CI):12.5-146.17), living in semi-urban (aOR = 1.6; 95% CI:1.0-2.5) or rural areas (aOR = 2.6; 95% CI:1.8-3.7), having MDR-TB (aOR = 3.4; 95% CI:1.2-10.9), and facility-based directly-observed treatment (DOT) (aOR = 7.2; 95% CI:2.4-26.6). CONCLUSION: We found that the cost of TB care is catastrophic for almost half of the TB-affected households in Tanzania; our findings support the results from other surveys recently conducted in sub-Saharan Africa. Collaborative efforts across health, employment and social welfare sectors are imperative to minimize household costs due to TB disease and improve access to care, patient adherence and outcomes. |
Impact of GeneXpert MTB/RIF® on treatment initiation and outcomes of RIF-resistant and RIF-susceptible TB patients in Vladimir TB dispensary, Russia.
Ershova JV , Volchenkov GV , Somova TR , Kuznetsova TA , Kaunetis NV , Kaminski D , Demikhova OV , Chernousova LN , Vasilyeva IA , Kerr EM , Cegielski JP , Kurbatova EV . BMC Infect Dis 2020 20 (1) 543 BACKGROUND: The main advantage of GeneXpert MTB/RIF® (Xpert) molecular diagnostic technology is the rapid detection of M.tuberculosis DNA and mutations associated with rifampicin (RIF) resistance for timely initiation of appropriate treatment and, consequently, preventing further transmission of the disease. We assessed time to treatment initiation and treatment outcomes of RIF-resistant and RIF-susceptible TB patients diagnosed and treated in Vladimir TB Dispensary, Russia in 2012, before and after implementation of GeneXpert MTB/RIF® diagnostic technology. METHODS: All adult patients suspected of having TB during February-December 2012 underwent a clinical examination, chest x-ray, microscopy, culture, and phenotypic drug susceptibility testing (DST). Starting August 2012 Xpert diagnostic technology became available in the facility. We used logistic regression to compare treatment outcomes in pre-Xpert and post-Xpert periods. Kaplan-Meier curves and log-rank test were used to compare the time to treatment initiation between the groups. RESULTS: Of 402 patients screened for TB during February-December 2012, 338 were diagnosed with TB (280 RIF-susceptible, 58 RIF-resistant). RIF-resistant patients in the post-Xpert group started treatment with second-line drugs (SLD) earlier than those in pre-Xpert group (median 11 vs. 37 days, Log-rank p = 0.02). The hazard ratio for time to SLD treatment initiation was significantly higher in post-Xpert group (HR:2.06; 95%CI:1.09,3.89) compared to pre-Xpert group. Among the 53/58 RIF-resistant TB patients with available treatment outcome, 28 (53%) had successful outcomes (cured/completed treatment) including 15/26 (58%) in post-Xpert group versus 13/27 (48%) in pre-Xpert group. The observed difference, however, was not statistically significant (OR:0.69; 95%CI:0.23,2.06). Among RIF-susceptible TB cases time to treatment initiation was not significantly different between the groups (2 vs. 3 days, Log-rank p = 0.73). Of 252/280 RIF-susceptible TB cases with treatment outcome, 199 (79%) cases had successful outcome including 94/114 (82%) in post-Xpert group versus 105/138 (76%) in pre-Xpert group (OR:0.68; 95%CI:0.36,1.26). CONCLUSION: We observed that availability of Xpert for initial diagnosis significantly reduced the time to SLD treatment for RIF-resistant patients in the Vladimir TB Dispensary. Although implementation of rapid diagnostics did not improve treatment outcomes, early diagnosis of MDR-TB is important for selection of appropriate treatment regimen and prevention of transmission of drug-resistant strains of TB. |
Pre-treatment loss to follow-up among children with multidrug-resistant tuberculosis in South Africa, 2008-2010
Moore BK , Erasmus L , Ershova J , Smith SE , Ndjeka N , Podewils LJ . PLoS One 2020 15 (4) e0230504 Multidrug-resistant (MDR) TB is more difficult to diagnose and treat compared with drug-susceptible TB. Young children are at greater risk of severe TB disease and death when treatment is delayed compared to adults. We sought to describe characteristics of children (<13 years) diagnosed with MDR TB between 2008-2010 in three South African provinces and assess factors associated with pre-treatment loss to follow-up. We matched laboratory and medical records at treatment facilities to identify pre-treatment loss and examined demographic and clinical characteristics for association with loss. Categorical variables were examined for association using Pearson's x2 or Fisher's exact test, employing Bonferroni correction for multiple pairwise comparisons. Between 2008-2010, 156 children were diagnosed with laboratory-confirmed MDR TB. Only 44% (n = 69) were documented as having received treatment. Young children (<2 years) (47/59, 80%), children with extrapulmonary (EP) TB (27/34, 79%), and children diagnosed at general hospitals (60/97, 62%) were most likely to be lost before treatment. Children most vulnerable to death from TB are most likely to be lost before treatment, possibly leading to underestimates of disease burden, case notifications, and poor outcomes among this population. Point-of-care diagnosis and robust follow-up may reduce pre-treatment loss in this population. |
Isoniazid- and Rifampin-Resistance Mutations Associated with Resistance to Second-line Drugs and with Sputum Culture Conversion.
Click ES , Kurbatova E , Alexander H , Dalton TL , Chen MP , Posey JE , Ershova JJ , Cegielski P . J Infect Dis 2020 221 (12) 2072-2082 BACKGROUND: Mutations in the genes inhA, katG and rpoB confer resistance to anti-tuberculosis (TB) drugs isoniazid and rifampin. We questioned whether specific mutations in these genes were associated with different clinical and microbiological characteristics. METHODS: In a multi-country prospective cohort study of MDR-TB, we identified inhA, katG and rpoB mutations in sputum isolates using the Hain MTBDRplus line probe assay. For specific mutations, we performed bivariate analysis to determine relative risk of baseline or acquired resistance to other TB drugs. We compared time-to-sputum-culture-conversion (TSCC) using Kaplan-Meier curves and stratified Cox regression. RESULTS: In total, 447 participants enrolled January 2005-December 2008 from seven countries were included. Relative to rpoB S531L, isolates with rpoB D516V had less cross-resistance to rifabutin, increased baseline resistance to other drugs, and increased acquired fluoroquinolone resistance.Relative to mutation of katG only, mutation of inhA promoter and katG was associated with increased acquired fluoroquinolone resistance and slower TSCC (125.5 vs. 89.0 days). CONCLUSIONS: Specific mutations in inhA and katG are associated with differences in resistance to other drugs and TSCC. Molecular testing may make it possible to tailor treatment and assess additional drug resistance risk according to specific mutation profile. |
Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study
Sharma A , Hill A , Kurbatova E , van der Walt M , Kvasnovsky C , Tupasi TE , Caoili JC , Gler MT , Volchenkov GV , Kazennyy BY , Demikhova OV , Bayona J , Contreras C , Yagui M , Leimane V , Cho SN , Kim HJ , Kliiman K , Akksilp S , Jou R , Ershova J , Dalton T , Cegielski P . Lancet Infect Dis 2017 17 (7) 707-715 BACKGROUND: Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are emerging worldwide. The Green Light Committee initiative supported programmatic management of drug-resistant tuberculosis in 90 countries. We used estimates from the Preserving Effective TB Treatment Study to predict MDR and XDR tuberculosis trends in four countries with a high burden of MDR tuberculosis: India, the Philippines, Russia, and South Africa. METHODS: We calibrated a compartmental model to data from drug resistance surveys and WHO tuberculosis reports to forecast estimates of incident MDR and XDR tuberculosis and the percentage of incident MDR and XDR tuberculosis caused by acquired drug resistance, assuming no fitness cost of resistance from 2000 to 2040 in India, the Philippines, Russia, and South Africa. FINDINGS: The model forecasted the percentage of MDR tuberculosis among incident cases of tuberculosis to increase, reaching 12.4% (95% prediction interval 9.4-16.2) in India, 8.9% (4.5-11.7) in the Philippines, 32.5% (27.0-35.8) in Russia, and 5.7% (3.0-7.6) in South Africa in 2040. It also predicted the percentage of XDR tuberculosis among incident MDR tuberculosis to increase, reaching 8.9% (95% prediction interval 5.1-12.9) in India, 9.0% (4.0-14.7) in the Philippines, 9.0% (4.8-14.2) in Russia, and 8.5% (2.5-14.7) in South Africa in 2040. Acquired drug resistance would cause less than 30% of incident MDR tuberculosis during 2000-40. Acquired drug resistance caused 80% of incident XDR tuberculosis in 2000, but this estimate would decrease to less than 50% by 2040. INTERPRETATION: MDR and XDR tuberculosis were forecast to increase in all four countries despite improvements in acquired drug resistance shown by the Green Light Committee-supported programmatic management of drug-resistant tuberculosis. Additional control efforts beyond improving acquired drug resistance rates are needed to stop the spread of MDR and XDR tuberculosis in countries with a high burden of MDR tuberculosis. FUNDING: US Agency for International Development and US Centers for Disease Control and Prevention, Division of Tuberculosis Elimination. |
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. |
The burden of drug-resistant tuberculosis in Papua New Guinea: Results of a large population-based survey
Aia P , Kal M , Lavu E , John LN , Johnson K , Coulter C , Ershova J , Tosas O , Zignol M , Ahmadova S , Islam T . PLoS One 2016 11 (3) e0149806 BACKGROUND: Reliable estimates of the burden of multidrug-resistant tuberculosis (MDR-TB) are crucial for effective control and prevention of tuberculosis (TB). Papua New Guinea (PNG) is a high TB burden country with limited information on the magnitude of the MDR-TB problem. METHODS: A cross-sectional study was conducted in four PNG provinces: Madang, Morobe, National Capital District and Western Province. Patient sputum samples were tested for rifampicin resistance by the Xpert MTB/RIF assay and those showing the presence of resistance underwent phenotypic susceptibility testing to first- and second-line anti-TB drugs including streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, ofloxacin, amikacin, kanamycin and capreomycin. RESULTS: Among 1,182 TB patients enrolled in the study, MDR-TB was detected in 20 new (2.7%; 95% confidence intervals [CI] 1.1-4.3%) and 24 previously treated (19.1%; 95%CI: 8.5-29.8%) TB cases. No case of extensively drug-resistant TB (XDR-TB) was detected. Thirty percent (6/20) of new and 33.3% (8/24) of previously treated cases with MDR-TB were detected in a single cluster in Western Province. CONCLUSION: In PNG the proportion of MDR-TB in new cases is slightly lower than the regional average of 4.4% (95%CI: 2.6-6.3%). A large proportion of MDR-TB cases were identified from a single hospital in Western Province, suggesting that the prevalence of MDR-TB across the country is heterogeneous. Future surveys should further explore this finding. The survey also helped strengthening the use of smear microscopy and Xpert MTB/RIF testing as diagnostic tools for TB in the country. |
Association between regimen composition and treatment response in patients with multidrug-resistant tuberculosis: A prospective cohort study
Yuen CM , Kurbatova EV , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Ershova J , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Vasilyeva IA , Dalton T , Cegielski JP . PLoS Med 2015 12 (12) e1001932 BACKGROUND: For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen. METHODS AND FINDINGS: We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph. In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen). The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse. CONCLUSIONS: MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens. |
Epidemiology of primary multidrug-resistant tuberculosis, Vladimir Region, Russia
Ershova JV , Volchenkov GV , Kaminski DA , Somova TR , Kuznetsova TA , Kaunetis NV , Cegielski JP , Kurbatova EV . Emerg Infect Dis 2015 21 (11) 2048-51 We studied the epidemiology of drug-resistant tuberculosis (TB) in Vladimir Region, Russia, in 2012. Most cases of multidrug-resistant TB (MDR TB) were caused by transmission of drug-resistant strains, and >33% were in patients referred for testing after mass radiographic screening. Early diagnosis of drug resistance is essential for preventing transmission of MDR TB. |
Multidrug-resistant tuberculosis treatment outcomes in relation to treatment, initial and acquired second-line drug resistance
Cegielski JP , Kurbatova E , van der Walt M , Brand J , Ershova J , Tupasi T , Campos Caoili J , Dalton T , Contreras C , Yagui M , Bayona J , Kvasnovsky C , Leimane V , Kuksa L , Chen MP , Via LE , Hwang SH , Wolfgang M , Volchenkov GV , Somova T , Smith SE , Akksilp S , Wattanaamornkiet W , Kim HJ , Kim CK , Kazennyy BY , Khorosheva T , Kliiman K , Viiklepp P , Jou R , Huang AS , Vasilyeva IA , Demikhova OV . Clin Infect Dis 2015 62 (4) 418-430 BACKGROUND: Resistance to second-line drugs (SLD) develops during treatment of multidrug-resistant (MDR) tuberculosis (TB), but the impact on treatment outcome has not been determined. OBJECTIVES: To determine the relationship with treatment outcomes of (1) initial versus acquired drug resistance and (2) treatment regimens. METHODS: MDR-TB patients starting SLD treatment were enrolled in a prospective cohort study. Sputum cultures were analyzed at a central reference laboratory. We compared subjects with successful and poor treatment outcomes in terms of (1) initial and acquired resistance to fluoroquinolones and second-line injectables (SLI), and (2) treatment regimens. RESULTS: Of 1,244 MDR-TB patients, 973 (78.2%) had known outcomes and 232 (18.6%) were lost to follow-up. Among those with known outcomes, treatment succeeded in 85.8% with plain MDR-TB, 69.7% with initial resistance to either a fluoroquinolone or SLI, 37.5% with acquired resistance to a fluoroquinolone or SLI, 29.3% with initial XDR-TB, and 13.0% with acquired XDR-TB (P<0.0001 for trend). In contrast, among those with known outcomes, treatment success increased stepwise from 41.6% to 92.3% as the number of proven effective drugs increased from ≤1 to ≥5 (P<0.0001 for trend); while acquired drug resistance decreased from 12%-16% range, depending on the drug, down to 0%-2% (P<0.0001 for trend). In multivariable analysis, the adjusted odds of treatment success decreased 0.62-fold (CL 0.56,0.69) for each increment in drug resistance and increased 2.1-fold (1.40,3.18) for each additional effective drug, controlling for differences between programs and patients. Specific treatment, patient and program variables were also associated with treatment outcome. CONCLUSION: Increasing drug resistance was associated in a logical stepwise manner with poor treatment outcomes. Acquired resistance was worse than initial resistance to the same drugs. Increasing numbers of effective drugs, specific drugs, and specific program characteristics were associated with better outcomes and less acquired resistance. |
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. |
Antituberculosis drug resistance survey in Lesotho, 2008-2009: lessons learned
Maama-Maime LB , Mareka M , Ershova JV , Tlali TE , Kao K , Phalatse M , Polansky L , Beres LK , Letsie M , Holtz TH . PLoS One 2015 10 (7) e0133808 SETTING: Drug resistance is an increasing threat to tuberculosis (TB) control worldwide. The World Health Organization advises monitoring for drug resistance, with either ongoing surveillance or periodic surveys. METHODS: The antituberculosis drug resistance survey was conducted in Lesotho in 2008-2009. Basic demographic and TB history information was collected from individuals with positive sputum smear results at 17 diagnostic facilities. Additional sputum sample was sent to the national TB reference laboratory for culture and drug susceptibility testing. RESULTS: Among 3441 eligible smear-positive persons, 1121 (32.6%) were not requested to submit sputum for culture. Among 2320 persons submitted sputum, 1164 (50.2%) were not asked for clinical information or did not have valid sputum samples for testing. In addition, 445/2320 (19.2%) were excluded from analysis because of other laboratory or data management reasons. Among 984/3441 (28.6%) persons who had data available for analysis, MDR-TB was present in 24/773 (3.1%) of new and 25/195 (12.8%) of retreatment TB cases. Logistical, operational and data management challenges affected survey results. CONCLUSION: MDR-TB is prevalent in Lesotho, but limitations reduced the reliability of our findings. Multiple lessons learned during this survey can be applied to improve the next drug resistance survey in Lesotho and other resource constrained countries may learn how to avoid these bottlenecks. |
Additional drug resistance of multidrug-resistant tuberculosis in patients in 9 countries
Kurbatova EV , Dalton T , Ershova J , Tupasi T , Caoili JC , Van Der Walt M , Kvasnovsky C , Yagui M , Bayona J , Contreras C , Leimane V , Via LE , Kim H , Akksilp S , Kazennyy BY , Volchenkov GV , Jou R , Kliiman K , Demikhova OV , Cegielski JP . Emerg Infect Dis 2015 21 (6) 977-83 Data from a large multicenter observational study of patients with multidrug-resistant tuberculosis (MDR TB) were analyzed to simulate the possible use of 2 new approaches to treatment of MDR TB: a short (9-month) regimen and a bedaquiline-containing regimen. Of 1,254 patients, 952 (75.9%) had no resistance to fluoroquinolones and second-line injectable drugs and thus would qualify as candidates for the 9-month regimen; 302 (24.1%) patients with resistance to a fluoroquinolone or second-line injectable drug would qualify as candidates for a bedaquiline-containing regimen in accordance with published guidelines. Among candidates for the 9-month regimen, standardized drug-susceptibility tests demonstrated susceptibility to a median of 5 (interquartile range 5-6) drugs. Among candidates for bedaquiline, drug-susceptibility tests demonstrated susceptibility to a median of 3 (interquartile range 2-4) drugs; 26% retained susceptibility to <2 drugs. These data may assist national TB programs in planning to implement new drugs and drug regimens. |
Risk factors for acquisition of drug resistance during multidrug-resistant tuberculosis treatment, Arkhangelsk Oblast, Russia, 2005-2010
Smith SE , Ershova J , Vlasova N , Nikishova E , Tarasova I , Eliseev P , Maryandyshev AO , Shemyakin IG , Kurbatova E , Cegielski JP . Emerg Infect Dis 2015 21 (6) 1002-11 Acquired resistance to antituberculosis drugs decreases effective treatment options and the likelihood of treatment success. We identified risk factors for acquisition of drug resistance during treatment for multidrug-resistant tuberculosis (MDR TB) and evaluated the effect on treatment outcomes. Data were collected prospectively from adults from Arkhangelsk Oblast, Russia, who had pulmonary MDR TB during 2005-2008. Acquisition of resistance to capreomycin and of extensively drug-resistant TB were more likely among patients who received <3 effective drugs than among patients who received >3 effective drugs (9.4% vs. 0% and 8.6% vs. 0.8%, respectively). Poor outcomes were more likely among patients with acquired capreomycin resistance (100% vs. 25.9%), acquired ofloxacin resistance (83.6% vs. 22.7%), or acquired extensive drug resistance (100% vs. 24.4%). To prevent acquired drug resistance and poor outcomes, baseline susceptibility to first- and second-line drugs should be determined quickly, and treatment should be adjusted to contain >3 effective drugs. |
Epidemiology of drug-resistant tuberculosis among children and adolescents in South Africa, 2005-2010
Moore BK , Anyalechi E , van der Walt M , Smith S , Erasmus L , Lancaster J , Morris S , Ndjeka N , Ershova J , Ismail N , Burton D , Menzies H . Int J Tuberc Lung Dis 2015 19 (6) 663-9 OBJECTIVE: To describe the demographic and clinical characteristics of children and adolescents diagnosed with resistance to any anti-tuberculosis drug (drug-resistant tuberculosis; DR-TB) in South Africa. DESIGN: We retrospectively reviewed medical records of all children (<13 years) and adolescents (13 to <18 years) with DR-TB at specialty hospitals in four South African provinces from 2005 to 2010. RESULTS: During the review period, 774 children and adolescents (median age 11.3 years) were diagnosed with DR-TB at selected facilities. A high proportion of patients had a history of previous TB treatment (285/631; 45.2%), human immunodeficiency virus (HIV) infection (375/685; 54.7%), contact with a TB case (347/454; 76.4%), and smear-positive (443/729; 60.8%), cavitary (253/680, 38.7%) disease. Eighty-two per cent of patients with HIV infection received antiretroviral therapy. Of 626 patients diagnosed with multidrug-resistant TB (MDR-TB), 561 (89.6%) received a regimen consistent with national guidelines; the median length of treatment was 22 months (IQR 16-25). Among 400 patients with any DR-TB and a known outcome, 20.3% died during treatment. CONCLUSION: Pediatric DR-TB in these provinces is characterized by complex clinical features at diagnosis, with one in five children dying during treatment. History of previous treatment and contact with a TB patient indicate opportunities for earlier diagnosis and treatment to improve outcomes. |
Sputum culture conversion as a prognostic marker for end-of-treatment outcome in patients with multidrug-resistant tuberculosis: a secondary analysis of data from two observational cohort studies
Kurbatova EV , Cegielski JP , Lienhardt C , Akksilp R , Bayona J , Becerra MC , Caoili J , Contreras C , Dalton T , Danilovits M , Demikhova OV , Ershova J , Gammino VM , Gelmanova I , Heilig CM , Jou R , Kazennyy B , Keshavjee S , Kim HJ , Kliiman K , Kvasnovsky C , Leimane V , Mitnick CD , Quelapio I , Riekstina V , Smith SE , Tupasi T , van der Walt M , Vasilyeva IA , Via LE , Viiklepp P , Volchenkov G , Walker AT , Wolfgang M , Yagui M , Zignol M . Lancet Respir Med 2015 3 (3) 201-9 BACKGROUND: Sputum culture conversion is often used as an early microbiological endpoint in phase 2 clinical trials of tuberculosis treatment on the basis of its assumed predictive value for end-of-treatment outcome, particularly in patients with drug-susceptible tuberculosis. We aimed to assess the validity of sputum culture conversion on solid media at varying timepoints, and the time to conversion, as prognostic markers for end-of-treatment outcome in patients with multidrug-resistant (MDR) tuberculosis. METHODS: We analysed data from two large cohort studies of patients with MDR tuberculosis. We defined sputum culture conversion as two or more consecutive negative cultures from sputum samples obtained at least 30 days apart. To estimate the association of 2 month and 6 month conversion with successful treatment outcome, we calculated odds ratios (ORs) and 95% CIs with random-effects multivariable logistic regression. We calculated predictive values with bivariate random-effects generalised linear mixed modelling. FINDINGS: We assessed data for 1712 patients who had treatment success, treatment failure, or who died. Among patients with treatment success, median time to sputum culture conversion was significantly shorter than in those who had poor outcomes (2 months [IQR 1-3] vs 7 months [3 to ≥24]; log-rank p<0.0001). Furthermore, conversion status at 6 months (adjusted OR 14.07 [95% CI 10.05-19.71]) was significantly associated with treatment success compared with failure or death. Sputum culture conversion status at 2 months was significantly associated with treatment success only in patients who were HIV negative (adjusted OR 4.12 [95% CI 2.25-7.54]) or who had unknown HIV infection (3.59 [1.96-6.58]), but not in those who were HIV positive (0.38 [0.12-1.18]). Thus, the overall association of sputum culture conversion with a successful outcome was substantially greater at 6 months than at 2 months. 2 month conversion had low sensitivity (27.3% [95% confidence limit 16.6-41.4]) and high specificity (89.8% [82.3-94.4]) for prediction of treatment success. Conversely, 6 month sputum culture conversion status had high sensitivity (91.8% [85.9-95.4]), but moderate specificity (57.8% [42.5-71.6]). The maximum combined sensitivity and specificity for sputum culture conversion was reached between month 6 and month 10 of treatment. INTERPRETATION: Time to sputum culture conversion, conversion status at 6 months, and conversion status at 2 months in patients without known HIV infection can be considered as proxy markers of end-of-treatment outcome in patients with MDR tuberculosis, although the overall association with treatment success is substantially stronger for 6 month than for 2 month conversion status. Investigators should consider these results regarding the validity of sputum culture conversion at various timepoints as an early predictor of treatment efficacy when designing phase 2 studies before investing substantial resources in large, long-term, phase 3 trials of new treatments for MDR tuberculosis. FUNDING: US Agency for International Development, US Centers for Disease Control and Prevention, Division of Intramural Research of the US National Institute of Allergy and Infectious Diseases, Korea Centers for Disease Control and Prevention. |
Extensive drug resistance acquired during treatment of multidrug-resistant tuberculosis
Cegielski JP , Dalton T , Yagui M , Wattanaamornkiet W , Volchenkov GV , Via LE , Van Der Walt M , Tupasi T , Smith SE , Odendaal R , Leimane V , Kvasnovsky C , Kuznetsova T , Kurbatova E , Kummik T , Kuksa L , Kliiman K , Kiryanova EV , Kim H , Kim CK , Kazennyy BY , Jou R , Huang WL , Ershova J , Erokhin VV , Diem L , Contreras C , Cho SN , Chernousova LN , Chen MP , Caoili JC , Bayona J , Akksilp S . Clin Infect Dis 2014 59 (8) 1049-63 INTRODUCTION: Increasing access to drugs for the treatment of multidrug-resistant (MDR) tuberculosis (TB) is crucial but could lead to increasing resistance to these same drugs. In 2000, the international Green Light Committee (GLC) initiative began to increase access while attempting to prevent acquired resistance. SUBJECTS AND METHODS: To assess the GLC's impact, we followed adults with pulmonary MDRTB from the start to the end of treatment with monthly sputum cultures, drug susceptibility testing, and genotyping. We compared the frequency and predictors of acquired resistance to second-line drugs (SLD) in nine countries that volunteered to participate, five countries that met GLC criteria and four countries that did not apply to the GLC. RESULTS: In total, 832 subjects were enrolled. Of those without baseline resistance to specific SLDs, 68 (8.9%) acquired extensively drug-resistant (XDR) TB, 79 (11.2%) acquired fluoroquinolone (FQ) resistance, and 56 (7.8%) acquired resistance to second-line injectable drugs (SLI). The relative risk (95% confidence interval) of acquired resistance was lower at GLC-approved sites: 0.27 (0.16,0.47) for XDRTB, 0.28 (0.17,0.45) for FQ, and 0.15 (0.06,0.39) to 0.60 (0.34,1.05) for three different SLI. The risk increased as the number of potentially effective drugs decreased. Controlling for baseline drug resistance and differences between sites, the odds ratios were 0.21 (0.07,0.62) for acquired XDRTB and 0.23 (0.09,0.59) for acquired FQ resistance. CONCLUSIONS: Treatment of MDRTB involves substantial risk of acquired resistance to SLD, increasing as baseline drug resistance increases. The risk was significantly lower in programs documented by the GLC to meet specific standards. |
Mortality among tuberculosis patients with acquired resistance to second-line anti-tuberculosis drugs - United States, 1993-2008
Ershova JV , Kurbatova EV , Moonan PK , Cegielski JP . Clin Infect Dis 2014 59 (4) 465-72 BACKGROUND: Resistance to second-line anti-tuberculosis drugs (SLD) severely compromises treatment options of drug-resistant tuberculosis (TB). We assessed the association between acquisition of resistance (AR) to second-line injectable drugs (SLI) or fluoroquinolones (FQ) and mortality among TB cases confirmed by positive culture results with available initial and final drug susceptibility test (DST) results. METHODS: We analyzed data from U.S. National TB Surveillance System, 1993-2008. Acquired resistance was defined as drug susceptibility at initial DST but resistance to the same drug at final DST. We compared survival with Kaplan-Meier curves and analyzed the association between AR and mortality using a univariate extended Cox proportional hazards model adjusted for age. RESULTS: Of 2,329 cases with both initial and final DST to SLI, 49 (2.1%) acquired resistance; 13/49 (26.5%) had treatment terminated by death versus 222 (10.0%) of those without AR to SLI (P<0.001). Of 1,187 cases with both initial and final DST to FQ, 32 (2.8%) acquired resistance; 12/32 (37.5%) had treatment terminated by death versus 121 (10.9%) of those without AR to FQ (P=0.001). Controlling for age, mortality was significantly greater among cases with AR to SLD than among cases without AR (adjusted hazard ratio (aHR)[SLI], 2.8; 95% confidence interval (CI),1.4-5.4; aHR[FQ], 1.9; 95% CI,1.0-3.5). MDR TB at treatment initiation, positive HIV status, and extrapulmonary disease were also significantly associated with mortality. CONCLUSION: Mortality was significantly greater among TB cases with AR to SLD. Providers should consider AR to SLD early in treatment, monitor DST results, and avoid premature deaths. |
Evaluation of adherence to national treatment guidelines among tuberculosis patients in three provinces of South Africa
Ershova JV , Podewils LJ , Bronner E , Stockwell HG , Dlamini S , Mametja LD . S Afr Med J 2014 104 (5) 362-368 BACKGROUND: Standardised tuberculosis (TB) treatment through directly observed therapy (DOT) is available in South Africa, but the level of adherence to standardised TB treatment and its impact on treatment outcomes is unknown. OBJECTIVES: To describe adherence to standardised TB treatment and provision of DOT, and analyse its impact on treatment outcome. METHODS: We utilised data collected for an evaluation of the South African national TB surveillance system. A treatment regimen was considered appropriate if based on national treatment guidelines. Multivariate log-binomial regression was used to evaluate the association between treatment regimens, including DOT provision, and treatment outcome. RESULTS: Of 1 339 TB cases in the parent evaluation, 598 (44.7%) were excluded from analysis owing to missing outcome or treatment information. The majority (697, 94.1%) of the remaining 741 patients received an appropriate TB regimen. Almost all patients (717, 96.8%) received DOT, 443 (59.8%) throughout the treatment course and 274 (37.0%) during the intensive (256, 34.6%) or continuation (18, 2.4%) phase. Independent predictors of poor outcome were partial DOT (adjusted risk ratio (aRR) 3.1, 95% confidence interval (CI) 2.2 - 4.3) and previous treatment default (aRR 2.3, 95% CI 1.1 - 4.8). CONCLUSION: Patients who received incomplete DOT or had a history of defaulting from TB treatment had an increased risk of poor outcomes. |
Performance of Cepheid (R) Xpert MTB/RIF (R) and TB-Biochip (R) MDR in two regions of Russia with a high prevalence of drug-resistant tuberculosis
Kurbatova EV , Kaminski DA , Erokhin VV , Volchenkov GV , Andreevskaya SN , Chernousova LN , Demikhova OV , Ershova JV , Kaunetis NV , Kuznetsova TA , Larionova EE , Smirnova TG , Somova TR , Vasilieva IA , Vorobieva AV , Zolkina SS , Cegielski JP . Eur J Clin Microbiol Infect Dis 2013 32 (6) 735-43 The purpose of this study was to assess the performance of Cepheid(R) Xpert MTB/RIF(R) ("Xpert") and TB-Biochip(R) MDR ("TB-Biochip"). Sputum specimens from adults with presumptive tuberculosis (TB) were homogenized and split for: (1) direct Xpert and microscopy, and (2) concentration for Xpert, microscopy, culture [Lowenstein-Jensen (LJ) solid media and Mycobacteria Growth Indicator Tube(R) (MGIT)], indirect drug susceptibility testing (DST) using the absolute concentration method and MGIT, and TB-Biochip. In total, 109 of 238 (45.8 %) specimens were culture-positive for Mycobacterium tuberculosis complex (MTBC), and, of these, 67 isolates were rifampicin resistant (RIF-R) by phenotypic DST and 64/67 (95.5 %) were isoniazid resistant (INH-R). Compared to culture of the same specimen, a single direct Xpert was more sensitive for detecting MTBC [95.3 %, 95 % confidence interval (CI), 90.0-98.3 %] than direct (59.6 %, 95 % CI, 50.2-68.5 %) or concentrated smear (85.3 %, 95 % CI, 77.7-91.1 %) or LJ culture (80.8 %, 95 % CI, 72.4-87.5 %); the specificity was 86.0 % (95 % CI, 78.9-91.3 %). Compared with MGIT DST, Xpert correctly identified 98.2 % (95 % CI, 91.5-99.9 %) of RIF-R and 95.5 % (95 % CI, 85.8-99.2 %) of RIF-susceptible (RIF-S) specimens. In a subset of 104 specimens, the sensitivity of TB-Biochip for MTBC detection compared to culture was 97.3 % (95 % CI, 91.0-99.5 %); the specificity was 78.1 % (95 % CI, 61.5-89.9 %). TB-Biochip correctly identified 100 % (95 % CI, 94.2-100 %) of RIF-R, 94.7 % (95 % CI, 76.7-99.7 %) of RIF-S, 98.2 % (95 % CI, 91.4-99.9 %) of INH-R, and 78.6 % (95 % CI, 52.1-94.2 %) of INH-S specimens compared to MGIT DST. Xpert and Biochip were similar in accuracy for detecting MTBC and RIF resistance compared to conventional culture methods. |
Impact of rapid drug susceptibility testing for tuberculosis: program experience in Lima, Peru
Shin SS , Asencios L , Yagui M , Yale G , Suarez C , Bayona J , Bonilla C , Jave O , Contreras CC , Atwood S , Blaya JA , Ershova J , Cegielski JP . Int J Tuberc Lung Dis 2012 16 (11) 1538-43 SETTING: Programmatic implementation of decentralized rapid drug susceptibility testing (DST) in Lima, Peru. OBJECTIVE: Pre-post analysis compared time to diagnosis, treatment outcome and survival among patients tested with direct nitrate reductase assay (NRA) vs. indirect conventional methods. DESIGN: From 2005 to 2009, we prospectively followed all patients referred for DST before (control) and after (intervention) NRA implementation. Among those referred for DST, NRA was used for smear-positive samples of patients with no prior history of multidrug resistance or treatment for multidrug-resistant tuberculosis (TB). Data were abstracted from patient charts and laboratory registers. Endpoints were favorable outcomes, time to result and time to death. RESULTS: Of those patients who met the criteria for NRA, 740 underwent NRA and 621 underwent conventional DST. NRA yielded test results for 78.4% of cases vs. 68.8% for conventional DST (P < 0.0001); the median time to result was 44 vs. 133 days, respectively (adjusted HR 0.64, 95%CI 0.56-0.73). Among individuals without previous anti-tuberculosis treatment, NRA was associated with a favorable treatment outcome (adjusted OR 1.39, 95%CI 1.01-1.90) and prolonged survival (adjusted HR 0.53, 95%CI 0.31-0.90). CONCLUSION: Direct NRA significantly shortened time to test result and improved treatment outcomes and survival in certain groups. |
Acquired resistance to second-line drugs among persons with tuberculosis in the United States
Ershova JV , Kurbatova EV , Moonan PK , Cegielski JP . Clin Infect Dis 2012 55 (12) 1600-7 BACKGROUND: Acquired resistance to second-line drugs (SLD) is a problem in treating patients with drug-resistant tuberculosis (TB) worldwide. The objectives of this study were to identify risk factors for acquired resistance (AR) to injectable SLD and fluoroquinolones in the US National TB Surveillance System, 1993-2008. METHODS: We selected cases with initial and final drug susceptibility test (DST) results reported. We defined AR as resistance at the final DST but susceptibility to the same drug at the initial DST. We analyzed AR using 2-way frequency tables and multivariable logistic regression. RESULTS: Baseline prevalence of multidrug-resistant (MDR) and extensively drug-resistant (XDR)TB was 12.6% (1864/14,770) and 0.38% (56/14,770), respectively. Of 2,274 individuals without initial resistance to injectable SLD, 49 (2.2%) acquired resistance. Of 1,141 initially susceptible to fluoroquinolones, 32 (2.8%) acquired resistance. AR to injectable SLD was associated with age group 25-44 years (adjusted Odds Ratio [aOR], 2.7; 95% confidence interval [CI], 1.2-6.3), positive HIV status (aOR, 2.5; 95% CI, 1.3-4.7), MDR at treatment initiation (aOR, 5.5; 95% CI, 2.9-10.5), and treatment with any SLD (aOR, 2.4; 95% CI,1.2-4.7). AR to fluoroquinolones was associated with MDR TB at treatment initiation (aOR, 6.5; 95% CI, 2.9-14.6). CONCLUSION: Among patients with initial and final DST reported, risk factors for AR to injectable SLD included age, positive HIV status, MDR TB and initial treatment with any SLD, while the only predictor for AR to fluoroquinolones was MDR TB at treatment initiation. Providers should consider monitoring SLD DST for MDR TB patients in the indicated subgroups. |
- Page last reviewed:Feb 1, 2024
- Page last updated:Jun 03, 2024
- Content source:
- Powered by CDC PHGKB Infrastructure