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26 result(s)
Journal Article > ResearchFull Text

Second-line drug-resistant TB and associated risk factors in Karakalpakstan, Uzbekistan

IJTLD OPEN. 1 September 2024; Volume 1 (Issue 9); 391-397.; DOI:10.5588/ijtldopen.24.0351
Moe S, Azamat I, Allamuratova S, Oluya M, Khristusev A,  et al.
IJTLD OPEN. 1 September 2024; Volume 1 (Issue 9); 391-397.; DOI:10.5588/ijtldopen.24.0351

BACKGROUND

Drug-resistant TB (DR-TB) remains a major public health threat. In 2022, Uzbekistan reported 2,117 cases of DR-TB, with 69% tested for fluoroquinolone resistance. Limited information is available on the prevalence of resistance to bedaquiline, linezolid, and fluoroquinolone, which are key components of the all-oral treatment regimen for rifampicin-resistant TB in Uzbekistan.


METHODS

A retrospective study was conducted using extensive programmatic data from 2019 to 2023 in Uzbekistan. We assessed second-line drug-resistant TB (SLDR-TB) rates using phenotypic drug susceptibility testing (pDST). Demographic and clinical characteristics associated with SLDR-TB were analysed using multivariable logistic regression models based on the Allen-Cady approach.


RESULTS 

In total, 2,405 patients with TB who had undergone pDST were included (median age 40 years, 47% female). The overall SLDR-TB resistance rate was 24% (95% CI 22-26). Prevalence of resistance to bedaquiline, linezolid, moxifloxacin, levofloxacin, and amikacin were respectively 3.1%, 0.8%, 15%, 13%, and 12%. Risk factors for SLDR-TB were resistance to rifampicin and/or isoniazid, exposure to clofazimine, retreatment status, contact with drug-susceptible TB case or DR-TB case, and diabetes.


CONCLUSIONS

The high prevalence of SLDR-TB is of major concern, emphasising the need for baseline pDST in RR-TB treatment. Identified risk factors can aid early detection of at-risk individuals and inform clinical practice.

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Journal Article > ResearchFull Text

Primary bedaquiline resistance in Karakalpakstan, Uzbekistan

Int J Tuberc Lung Dis. 1 May 2023; Volume 27 (Issue 5); 381-386.; DOI:10.5588/ijtld.22.0536
Moe S, Rekart ML, Hernandez D, Sholpan A, Ismailov A,  et al.
Int J Tuberc Lung Dis. 1 May 2023; Volume 27 (Issue 5); 381-386.; DOI:10.5588/ijtld.22.0536
BACKGROUND:
Bedaquiline (BDQ) is widely used in the treatment of rifampicin-resistant TB (RR-TB). However, resistance to BDQ is now emerging. There are no standardised regimens for BDQ-resistant TB. This study aims to share experience in managing primary BDQ-resistant TB.

METHODS:
We performed a retrospective study of patients treated for RR-TB in Karakalpakstan, Uzbekistan, from January 2017 to March 2022. We identified patients with resistance to BDQ with no history of BDQ exposure. We describe baseline characteristics, treatment and follow-up of these patients.

RESULTS:
Twelve of the 1,930 patients (0.6%) had baseline samples resistant to BDQ with no history of BDQ exposure, 75% (9/12) of whom had been previously treated for TB. Ten (83.3%) were resistant to fluoroquinolones; respectively 66% and 50% had culture conversion by Month 3 and Month 6. The interim
treatment outcomes were as follows: unfavourable treatment outcomes (3/12, 25%), favourable outcomes (2/12, 17%); the remaining seven (58%) were continuing treatment.

CONCLUSIONS:
A large proportion of the cases had previously been treated for TB and had TB resistant to quinolone.
Both patients who had not experienced culture conversion by Month 3 had an unfavourable treatment outcome. Therefore, we recommend monthly monitoring of culture status for patients on treatment regimens for BDQ resistance.
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Journal Article > ResearchAbstract Only

Costs and import costs of past, present, and future TB drug regimens: a case study for Karakalpakstan, Uzbekistan

J Public Health (Oxf.). 23 November 2022; Online ahead of print; fdac124.; DOI:10.1093/pubmed/fdac124
Kohler S, Sitali N, Achar J, Paul N
J Public Health (Oxf.). 23 November 2022; Online ahead of print; fdac124.; DOI:10.1093/pubmed/fdac124
BACKGROUND
Tuberculosis (TB) drugs and their import are costly. We assessed how shorter TB drug regimens, which were non-inferior or superior in recent TB trials, can affect the costs for purchasing and importing TB drugs.

METHODS
We estimated the drug costs and import costs of 39 longer and shorter TB drug regimens using TB drug prices from the Global Drug Facility and import cost estimates for a TB program in Karakalpakstan, Uzbekistan. Drug regimens from recent TB trials were compared with TB drug regimens following present or past World Health Organization recommendations.

RESULTS
We estimated an import cost of $4.19 and a drug cost of $43 per standard 6-month drug-sensitive (DS)-TB regimen. A new 17-week DS-TB regimen from the TBTC Study 31 currently requires more tablets and is more expensive to import ($6.08) and purchase ($233). The TB program can substantially decrease import costs ($2.26–14) and drug costs ($391–2308) per multidrug-resistant (MDR)-TB regimen when using new 6-month or shorter drug regimens from the Nix-TB, NExT, TB PRACTECAL, ZeNix, or BEAT TB trials instead of 9–20-month regimens with import costs of $9.96–507 and drug costs of $354–15 028. For a commonly used 20-month all-oral, bedaquiline-containing MDR-TB regimen, we estimated costs of $41 for drug import and $1773 for drug purchase.

CONCLUSIONS
The implementation of a new and shorter DS-TB regimen may increase the costs for drug purchase and import. The implementation of new and shorter MDR-TB regimens may decrease the costs for drug purchase and/or drug import.
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Journal Article > ResearchFull Text

Acquired bedaquiline resistance in Karakalpakstan, Uzbekistan

Int J Tuberc Lung Dis. 1 July 2022; Volume 26 (Issue 7); 658-663.; DOI:10.5588/ijtld.21.0631
Nair P, Hasan T, Zaw KK, Allamuratova S, Ismailov A,  et al.
Int J Tuberc Lung Dis. 1 July 2022; Volume 26 (Issue 7); 658-663.; DOI:10.5588/ijtld.21.0631
BACKGROUND
The WHO recommends the use of bedaquiline (BDQ) in longer, as well as shorter, multidrug-resistant TB (MDR-TB) treatment regimens. However, resistance to this new drug is now emerging. We aimed to describe the characteristics of patients in Karakalpakstan, Uzbekistan, who were treated for MDR-TB and acquired BDQ resistance during treatment.

METHODS
We performed a retrospective study of routinely collected data for patients treated for MDR-TB in Karakalpakstan between January 2015 and December 2020. We included patients on BDQ-containing regimens with baseline susceptibility to BDQ who developed BDQ resistance at any point after treatment initiation. Patients resistant to BDQ at baseline or with no confirmed susceptibility to BDQ at baseline were excluded.

RESULTS:
Of the 523 patients who received BDQ-containing regimens during the study period, BDQ resistance was detected in 31 patients (5.9%); 20 patients were excluded-16 with no prior confirmation of BDQ susceptibility and 4 who were resistant at baseline. Eleven patients with acquired BDQ resistance were identified. We discuss demographic variables, resistance profiles, treatment-related variables and risk factors for unfavourable outcomes for these patients.

CONCLUSION
Our programmatic data demonstrated the acquisition of BDQ resistance during or subsequent to receiving a BDQ-containing regimen in a patient cohort from Uzbekistan. We highlight the need for individualised treatment regimens with optimised clinical and laboratory follow up to prevent resistance acquisition.
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Journal Article > ResearchFull Text

Impact of pyrazinamide resistance on multidrug-resistant tuberculosis in Karakalpakstan, Uzbekistan

Int J Tuberc Lung Dis. 1 May 2018; Volume 22 (Issue 5); 544-550.; DOI:10.5588/ijtld.17.0483
Kuhlin J, Smith C, Khaemraev A, Tigay Z, Parpieva N,  et al.
Int J Tuberc Lung Dis. 1 May 2018; Volume 22 (Issue 5); 544-550.; DOI:10.5588/ijtld.17.0483
SETTING
The World Health Organization (WHO) recommends the inclusion of pyrazinamide (PZA) in treatment regimens for multidrug-resistant tuberculosis (MDR-TB) unless resistance has been confirmed.

OBJECTIVE
To investigate the association between PZA susceptibility and MDR-TB treatment outcome among patients treated with a PZA-containing regimen and whether the duration of the intensive phase of the PZA-containing regimen affected treatment outcome.

DESIGN
We conducted a retrospective cohort study including all eligible MDR-TB patients starting treatment in 2003-2013 in the TB programme in Karakalpakstan, Uzbekistan. PZA drug susceptibility testing (DST) using liquid culture was performed, and outcomes were classified according to the WHO 2013 definitions.

RESULTS
Of 2446 MDR-TB patients included, 832 (34.0%) had an available baseline PZA DST result, 612 (73.6%) of whom were PZA-resistant. We found no association between treatment success and PZA susceptibility (adjusted odds ratio [aOR] 0.86, 95%CI 0.51-1.44, P = 0.6) in patients treated with PZA. Furthermore, among patients with no baseline PZA DST result, no evidence was seen of an association between treatment success and PZA treatment duration (aOR 0.86, 95%CI 0.49-1.51, P = 0.6).

CONCLUSION
Treatment of MDR-TB with a standard PZA regimen does not appear to improve treatment outcomes, regardless of PZA susceptibility or duration of treatment.
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Journal Article > ResearchFull Text

Outcomes with a shorter multidrug-resistant tuberculosis regimen from Karakalpakstan, Uzbekistan

ERJ Open Res. 8 February 2021; 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. 8 February 2021; 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.
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Journal Article > ResearchFull Text

Assessment of dietary exposure to some persistent organic pollutants in the Republic of Karakalpakstan of Uzbekistan

Environ Health Perspect. 1 August 2003; Volume 111 (Issue 10); 1306-1311.; DOI:10.1289/ehp.5907
Muntean N, Jermini M, Small I, Falzon D, Fürst P,  et al.
Environ Health Perspect. 1 August 2003; Volume 111 (Issue 10); 1306-1311.; DOI:10.1289/ehp.5907
A 1999 study heightened long-standing concerns over persistent organic pollutant contamination in the Aral Sea area, detecting elevated levels in breast milk and cord blood of women in Karakalpakstan (western Uzbekistan). These findings prompted a collaborative research study aimed at linking such human findings with evidence of food chain contamination in the area. An international team carried out analyses of organochlorine and organophosphate pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs) on samples of 12 foods commonly produced and consumed in Karakalpakstan. Analysis consistently detected long-lasting organochlorine pesticides and their metabolites in all foods of animal origin and in some vegetables such as onions and carrots--two low-cost components of many traditional dishes. Levels of PCBs were relatively low in all samples except fish. Analyses revealed high levels of PCDDs and PCDFs (together often termed "dioxins") in sheep fat, dairy cream, eggs, and edible cottonseed oil, among other foodstuffs. These findings indicate that food traditionally grown, sold, and consumed in Karakalpakstan is a major route of human exposure to several persistent toxic contaminants, including the most toxic of dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD). Intake estimations demonstrate that consumption of even small amounts of locally grown food may expose consumers to dioxin levels that considerably exceed the monthly tolerable dioxin intake levels set by the World Health Organization. Data presented in this study allow a first assessment of the risk associated with the consumption of certain food products in Karakalpakstan and highlight a critical public health situation.More
Journal Article > ResearchFull Text

Programme costs of longer and shorter tuberculosis drug regimens and drug import: a modelling study for Karakalpakstan, Uzbekistan

ERJ Open Res. 21 March 2022; Volume 8 (Issue 1); 00622-2021.; DOI:10.1183/23120541.00622-2021
Kohler S, Sitali N, Achar J, Paul N
ERJ Open Res. 21 March 2022; Volume 8 (Issue 1); 00622-2021.; DOI:10.1183/23120541.00622-2021
BACKGROUND
The introduction of new and often shorter tuberculosis (TB) drug regimens affects the cost of TB programmes.

METHODS
We modelled drug purchase and import costs for 20-month, 9-month and 4- to 6-month TB drug regimens based on 2016-2020 treatment numbers from a TB programme in Karakalpakstan, Uzbekistan, and 2021 Global Drug Facility prices.

RESULTS
On average, 2225±374 (±sd) people per year started TB treatment, 30±2.1% of whom were diagnosed with drug-resistant forms of TB. Transitioning from a 6-month to a 4-month drug-susceptible (DS)-TB drug regimen increased the TB programme's annual DS-TB drug cost from USD 65±10 K to USD 357±56 K (p<0.001) and its drug import cost from USD 6.4±1.0 K to USD 9.3±1.4 K (p=0.008). Transitioning from a 20-month all-oral multidrug-resistant (MDR)-TB drug regimen to a 9-month MDR-TB drug regimen with an injectable antibiotic decreased the TB programme's annual MDR-TB drug cost from USD 1336±265 K to USD 266±53 K (p<0.001) and had no significant effect on the drug import cost (USD 28±5.5 K versus USD 27±5.4 K; p=0.88). Purchasing (USD 577±114 K) and importing (USD 3.0±0.59 K) the 6-month all-oral MDR-TB drug regimen cost more than procuring the 9-month MDR-TB drug regimen but less than the 20-month all-oral MDR-TB drug regimen (both p<0.01).

CONCLUSION
Introducing new and shorter TB drug regimens could increase the cost of TB programmes with low drug resistance rates and decrease the cost of TB programmes with high drug resistance rates.
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Journal Article > ResearchFull Text

A framework for assessing import costs of medical supplies and results for a tuberculosis program in Karakalpakstan, Uzbekistan

Health data sci. 25 August 2021; Volume 2021; DOI:10.34133/2021/9813732
Kohler S, Sitali N, Paul N
Health data sci. 25 August 2021; Volume 2021; DOI:10.34133/2021/9813732

BACKGROUND

Import of medical supplies is common, but limited knowledge about import costs and their structure introduces uncertainty to budget planning, cost management, and cost-effectiveness analysis of health programs. We aimed to estimate the import costs of a tuberculosis (TB) program in Uzbekistan, including the import costs of specific imported items.


METHODS

We developed a framework that applies costing and cost accounting to import costs. First, transport costs, customs-related costs, cargo weight, unit weights, and quantities ordered were gathered for a major shipment of medical supplies from the Médecins Sans Frontières (MSF) Procurement Unit in Amsterdam, the Netherlands, to a TB program in Karakalpakstan, Uzbekistan, in 2016. Second, air freight, land freight, and customs clearance cost totals were estimated. Third, total import costs were allocated to different cargos (standard, cool, and frozen), items (e.g., TB drugs), and units (e.g., one tablet) based on imported weight and quantity. Data sources were order invoices, waybills, the local MSF logistics department, and an MSF standard product list.


RESULTS

The shipment contained 1.8 million units of 85 medical items of standard, cool, and frozen cargo. The average import cost for the TB program was 9.0% of the shipment value. Import cost varied substantially between cargos (8.9–28% of the cargo value) and items (interquartile range 4.5–35% of the item value). The largest portion of the total import cost was caused by transport (82–99% of the cargo import cost) and allocated based on imported weight. Ten (14%) of the 69 items imported as standard cargo were associated with 85% of the standard cargo import cost. Standard cargo items could be grouped based on contributing to import costs predominantly through unit weight (e.g., fluids), imported quantity (e.g., tablets), or the combination of unit weight and imported quantity (e.g., items in powder form).


CONCLUSIONS

The cost of importing medical supplies to a TB program in Karakalpakstan, Uzbekistan, was sizable, variable, and driven by a subset of imported items. The framework used to measure and account import costs can be adapted to other health programs.

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Journal Article > ResearchFull Text

'They prefer hidden treatment': anti-tuberculosis drug-taking practices and drug regulation in Karakalpakstan

Int J Tuberc Lung Dis. 1 August 2016; Volume 20 (Issue 8); 1084-1090.; DOI:10.5588/ijtld.15.0815
Stringer B, Lowton K, Tillashaikhov M, Parpieva N, Ulmasova D,  et al.
Int J Tuberc Lung Dis. 1 August 2016; Volume 20 (Issue 8); 1084-1090.; DOI:10.5588/ijtld.15.0815
SETTING
The joint Médecins Sans Frontières/Ministry of Health Multidrug-Resistant Tuberculosis (MDR-TB) Programme, Karakalpakstan, Uzbekistan.

OBJECTIVE
Uzbekistan has high rates of MDR-TB. We aimed to understand patients' and prescribers' attitudes to anti-tuberculosis drug prescription, regulation and drug-taking behaviour.

METHODS
Participants (12 patients, 12 practitioners) were recruited purposively. Data were gathered qualitatively using field notes and in-depth interviews and analysed thematically.

FINDINGS
Our analysis highlighted two main themes. First, shame and stigma were reported to increase the likelihood of self-treatment and incorrect use of anti-tuberculosis drugs, most commonly at the initial stages of illness. A health system failure to promote health information was perceived, leading to wrong diagnoses and inappropriate therapies. Motivated by shame, patients hid their condition by resorting to drug treatment options outside the programme, compounding the risk of chaotic management and dissemination of erroneous information through lay networks. Second, positive influences on treatment were reported through patients, practitioners and peers working effectively together to deliver the correct information and support, which acted to normalise TB, reduce stigma and prevent misuse of anti-tuberculosis drugs.

CONCLUSION
Effective case finding, patient support and community education strategies are essential. Patients, practitioners and peers working together can help reduce stigma and prevent misuse of anti-tuberculosis drugs.
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