Journal Article > LetterFull Text
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Bastard M, Bonnet MMB, du Cros PAK, Khamraev AK, Hayrapetyan A, et al.
Am J Respir Crit Care Med. 2015 February 1; Volume 191 (Issue 3); 355-358.; DOI:10.1164/rccm.201407-1302LE
Journal Article > LetterSubscription Only
N Engl J Med. 2008 November 27; Volume 359 (Issue 22); 2398-400.; DOI:10.1056/NEJMc0805644
Cox HS, Sibilia C, Feuerriegel S, Kalon S, Polonsky JA, et al.
N Engl J Med. 2008 November 27; Volume 359 (Issue 22); 2398-400.; DOI:10.1056/NEJMc0805644
Journal Article > ResearchFull Text
PLOS One. 2018 March 8; Volume 13 (Issue 3); DOI:10.1371/journal.pone.0193491
Bastard M, Sanchez-Padilla E, du Cros PAK, Khamraev AK, Parpieva N, et al.
PLOS One. 2018 March 8; Volume 13 (Issue 3); DOI:10.1371/journal.pone.0193491
The emergence of resistance to anti-tuberculosis (DR-TB) drugs and the HIV epidemic represent a serious threat for reducing the global burden of TB. Although data on HIV-negative DR-TB treatment outcomes are well published, few data on DR-TB outcomes among HIV co-infected people is available despite the great public health importance.
Journal Article > LetterFull Text
Emerg Infect Dis. 2015 September 9; Volume 21 (Issue 11); DOI:10.3201/eid2111.151119
Achar J, Berry C, Herboczek K, Parpieva N, Tillashaykhov M, et al.
Emerg Infect Dis. 2015 September 9; Volume 21 (Issue 11); DOI:10.3201/eid2111.151119
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2016 February 1; Volume 20 (Issue 2); 177-186.; DOI:10.5588/ijtld.15.0962
Bonnet MMB, Bastard M, du Cros PAK, Khamraev AK, Kimenye K, et al.
Int J Tuberc Lung Dis. 2016 February 1; Volume 20 (Issue 2); 177-186.; DOI:10.5588/ijtld.15.0962
BACKGROUND
The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome.
OBJECTIVE
To identify patients at risk of unfavourable outcomes who may benefit from the new drugs.
METHODS
Retrospective cohort study of treatment outcomes involving four to five effective drugs for 15–24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011.
RESULTS
Of 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m2, 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22–20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00–3.62) or OFX (aOR 5.56, 95%CI 2.15–14.37), past incarceration (aOR 1.88, 95%CI 1.11–3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53–6.85), low BMI (aOR 2.22, 95%CI 1.56–3.12) and high bacillary load (aOR 2.32, 95%CI 1.15–4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04–2.28).
CONCLUSION
In our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.
The World Health Organization recommends adding bedaquiline or delamanid to multidrug-resistant tuberculosis (MDR-TB) regimens for which four effective drugs are not available, and delamanid for patients at high risk of poor outcome.
OBJECTIVE
To identify patients at risk of unfavourable outcomes who may benefit from the new drugs.
METHODS
Retrospective cohort study of treatment outcomes involving four to five effective drugs for 15–24 months in programmes in Uzbekistan, Georgia, Armenia, Swaziland and Kenya between 2001 and 2011.
RESULTS
Of 1433 patients, 48.5% had body mass index (BMI) <18.5 kg/m2, 72.9% had a high bacillary load, 16.7% were resistant to two injectables, 2.9% were resistant to ofloxacin (OFX) and 3.0% had extensively drug-resistant TB (XDR-TB). Treatment success ranged from 59.7% (no second-line resistance) to 27.0% (XDR-TB). XDR-TB (aOR 8.16, 95%CI 3.22–20.64), resistance to two injectables (aOR 1.90, 95%CI 1.00–3.62) or OFX (aOR 5.56, 95%CI 2.15–14.37), past incarceration (aOR 1.88, 95%CI 1.11–3.2), history of second-line treatment (aOR 3.24, 95%CI 1.53–6.85), low BMI (aOR 2.22, 95%CI 1.56–3.12) and high bacillary load (aOR 2.32, 95%CI 1.15–4.67) were associated with unfavourable outcomes. Patients started on capreomycin rather than kanamycin were more likely to have an unfavourable outcome (aOR 1.54, 95%CI 1.04–2.28).
CONCLUSION
In our cohort, patients who may benefit from bedaquiline and delamanid represented up to two thirds of all MDR-TB patients.
Journal Article > ResearchFull Text
Health Econ Rev. 2016 July 12; Volume 6 (Issue 1); 28.; DOI: 10.1186/s13561-016-0100-z
Kohler S, Asadov DA, Bründer A, Healy S, Khamraev AK, et al.
Health Econ Rev. 2016 July 12; Volume 6 (Issue 1); 28.; DOI: 10.1186/s13561-016-0100-z
Uzbekistan inherited a hospital-based health system from the Soviet Union. We explore the health system-related challenges faced during the scale-up of ambulatory (outpatient) treatment for drug-susceptible and drug-resistant tuberculosis (TB) in Karakalpakstan in Uzbekistan. Semi-structured interviews were conducted with key informants of the TB services, the ministries of health and finance, and their TB control partners. Structural challenges and resource needs were both discussed as obstacles to the expansion of ambulatory TB treatment. Respondents stated need for revising the financing mechanisms of the TB services to incentivize referral to ambulatory TB treatment. An increased workload and need for transportation in ambulatory TB care were also pointed out by respondents, given the quickly rising outpatient numbers but per capita financing of outpatient care. Policy makers showed strong interest in good practice examples for financing ambulatory-based management of TB in comparable contexts and in guidance for revising the financing of the TB services in a way that strengthens ambulatory TB treatment. To facilitate changing the model of care, TB control strategies emphasizing ambulatory care in hospital-oriented health systems should anticipate health system support and strengthening needs, and provide a plan of action to resolve both. Addressing both types of needs may require not only involving TB control and health financing actors, but also increasing knowledge about viable and tested financing mechanisms that incentivize the adoption of new models of care for TB.
Journal Article > ResearchFull Text
BMC Med. 2016 November 18; Volume 14 (Issue 1); 187.; DOI:10.1186/s12916-016-0723-2
Trauer JM, Achar J, Parpieva N, Khamraev AK, Denholm JT, et al.
BMC Med. 2016 November 18; Volume 14 (Issue 1); 187.; DOI:10.1186/s12916-016-0723-2
BACKGROUND
Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9–11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization.
METHODS
We construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions.
RESULTS
Based on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates.
CONCLUSIONS
In addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable.
Multidrug-resistant tuberculosis (MDR-TB) is a major threat to global TB control. MDR-TB treatment regimens typically have a high pill burden, last 20 months or more and often lead to unsatisfactory outcomes. A 9–11 month regimen with seven antibiotics has shown high success rates among selected MDR-TB patients in different settings and is conditionally recommended by the World Health Organization.
METHODS
We construct a transmission-dynamic model of TB to estimate the likely impact of a shorter MDR-TB regimen when applied in a low HIV prevalence region of Uzbekistan (Karakalpakstan) with high rates of drug resistance, good access to diagnostics and a well-established community-based MDR-TB treatment programme providing treatment to around 400 patients. The model incorporates acquisition of additional drug resistance and incorrect regimen assignment. It is calibrated to local epidemiology and used to compare the impact of shorter treatment against four alternative programmatic interventions.
RESULTS
Based on empirical outcomes among MDR-TB patients and assuming no improvement in treatment success rates, the shorter regimen reduced MDR-TB incidence from 15.2 to 9.7 cases per 100,000 population per year and MDR-TB mortality from 3.0 to 1.7 deaths per 100,000 per year, achieving comparable or greater gains than the alternative interventions. No significant increase in the burden of higher levels of resistance was predicted. Effects are probably conservative given that the regimen is likely to improve success rates.
CONCLUSIONS
In addition to benefits to individual patients, we find that shorter MDR-TB treatment regimens also have the potential to reduce transmission of resistant strains. These findings are in the epidemiological setting of treatment availability being an important bottleneck due to high numbers of patients being eligible for treatment, and may differ in other contexts. The high proportion of MDR-TB with additional antibiotic resistance simulated was not exacerbated by programmatic responses and greater gains may be possible in contexts where the regimen is more widely applicable.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2014 December 1; Volume 18 (Issue 12); DOI:10.5588/ijtld.14.0190
Kohler S, Asadov D, Brunder A, Healy S, Khamraev AK, et al.
Int J Tuberc Lung Dis. 2014 December 1; Volume 18 (Issue 12); DOI:10.5588/ijtld.14.0190
The tuberculosis (TB) control strategy in the Republic of Karakalpakstan, Uzbekistan, is being changed to decentralised out-patient care for most TB patients by the Government of Uzbekistan, in collaboration with the international medical humanitarian organisation Médecins Sans Frontières. Ambulatory treatment of both drug-susceptible and drug-resistant TB from the first day of treatment has been recommended since 2011. Out-patient treatment of TB from the beginning of treatment was previously prohibited. However, the current Uzbek health financing system, which evolved from the Soviet Semashko model, offers incentives that work against the adoption of ambulatory TB treatment. Based on the 'Comprehensive TB Care for All' programme implemented in Karakalpakstan, we describe how existing policies for the allocation of health funds complicate the scale-up of ambulatory-based management of TB.
Journal Article > ResearchFull Text
ERJ Open Res. 2021 February 8; Volume 7 (Issue 1); DOI:10.1183/23120541.00537-2020
du Cros PAK, Khamraev AK, Tigay Z, Abdrasuliev T, Greig J, et al.
ERJ Open Res. 2021 February 8; Volume 7 (Issue 1); DOI:10.1183/23120541.00537-2020
BACKGROUND
In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.
METHODS
Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.
RESULTS
Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression.
CONCLUSION
Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.
In 2016, World Health Organization guidelines conditionally recommended standardised shorter 9–12-month regimens for multidrug-resistant (MDR) tuberculosis (TB) treatment. We conducted a prospective study of a shorter standardised MDR-TB regimen in Karakalpakstan, Uzbekistan.
METHODS
Consecutive adults and children with confirmed rifampicin-resistant pulmonary TB were enrolled between September 1, 2013 and March 31, 2015; exclusions included prior treatment with second-line anti-TB drugs, and documented resistance to ofloxacin or to two second-line injectable agents. The primary outcome was recurrence-free cure at 1 year following treatment completion.
RESULTS
Of 146 enrolled patients, 128 were included: 67 female (52.3%), median age 30.1 (interquartile range 23.8–44.4) years. At the end of treatment, 71.9% (92 out of 128) of patients achieved treatment success, with 68% (87 out of 128) achieving recurrence-free cure at 1 year following completion. Unsuccessful outcomes during treatment included 22 (17.2%) treatment failures with fluoroquinolone-resistance amplification in 8 patients (8 out of 22, 36.4%); 12 (9.4%) lost to follow-up; and 2 (1.5%) deaths. Recurrence occurred in one patient. Fourteen patients (10.9%) experienced serious adverse events. Baseline resistance to both pyrazinamide and ethambutol (adjusted OR 6.13, 95% CI 2.01; 18.63) and adherence <95% (adjusted OR 5.33, 95% CI 1.73; 16.36) were associated with unsuccessful outcome in multivariable logistic regression.
CONCLUSION
Overall success with a standardised shorter MDR-TB regimen was moderate with considerable treatment failure and amplification of fluoroquinolone resistance. When introducing standardised shorter regimens, baseline drug susceptibility testing and minimising missed doses are critical. High rates globally of pyrazinamide, ethambutol and ethionamide resistance raise questions of continued inclusion of these drugs in shorter regimens in the absence of drug susceptibility testing-confirmed susceptibility.