National Center for Tuberculosis Problems

Almaty, Kazakhstan

National Center for Tuberculosis Problems

Almaty, Kazakhstan
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Hermosilla S.,Columbia University | You P.,Columbia University | Aifah A.,Columbia University | Abildayev T.,National Center for Tuberculosis Problems | And 8 more authors.
PLoS ONE | Year: 2017

Background Sputum smear-positive tuberculosis (TB) patients have a high risk of transmission and are of great epidemiological and infection control significance. Little is known about the smearpositive populations in high TB burden regions, such as Kazakhstan. The objective of this study is to characterize the smear-positive population in Kazakhstan and identify associated modifiable risk factors. Methods Data on incident TB cases' (identified between April 2012 and March 2014) socio-demographic, risk behavior, and comorbidity characteristics were collected in four regions of Kazakhstan through structured survey and medical record review. We used multivariable logistic regression to determine factors associated with smear positivity. Results Of the total sample, 193 (34.3%) of the 562 study participants tested smear-positive. In the final adjusted multivariable logistic regression model, sex (adjusted odds ratio (aOR) = 2.0, 95% CI:1.3-3.1, p < 0.01), incarceration (aOR = 3.6, 95% CI:1.2-11.1, p = 0.03), alcohol dependence (aOR = 2.6, 95% CI:1.2-5.7, p = 0.02), diabetes (aOR = 5.0, 95% CI:2.4-10.7, p < 0.01), and physician access (aOR = 2.7, 95% CI:1.3-5.5p < 0.01) were associated with smear-positivity. Conclusions Incarceration, alcohol dependence, diabetes, and physician access are associated with smear positivity among incident TB cases in Kazakhstan. To stem the TB epidemic, screening, treatment and prevention policies should address these factors. © 2017 Hermosilla et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Kayukova L.A.,Bekturov Institute of Chemical Sciences | Orazbaeva M.A.,Bekturov Institute of Chemical Sciences | Bismilda V.L.,National Center for Tuberculosis Problems | Chingisova L.T.,National Center for Tuberculosis Problems
Pharmaceutical Chemistry Journal | Year: 2010

The search for new tuberculostatics is an important task for medicinal chemistry. A series of new O-aroyl-β-(4-phenylpiperazin-1-yl) propioamidoximes were synthesized and tested in vitro for antituberculosis activity. The synthesis of the target substances consists of 3-4 steps. In the first step, β-(4-phenylpiperazin1-yl)propionitrile was obtained in 79% yield; the second step yields β-(4-phenylpiperazin-1-yl)propioamidoxime in 75% yield. Subsequent aroylation of this amidoxime by substituted benzoic acid chlorides in the presence of Et3N leads to the target O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes in 61-93% yields. Hydrochlorides of the O-aroylated products were obtained in 72-94% yields by the action of ethereal HCl on solutions of the bases. PMR spectra of hydrochlorides of the O-aroylated products show evidence of slow inversion of the heterocycle at the β-position and coordination of HCl at the N1 atom of the 4-phenylpiperazine fragment. Some bases and hydrochlorides of O-aroyl-β-(4-phenylpiperazin-1-yl)propioamidoximes exhibited interesting antituberculosis properties when tested in vitro on sensitive, resistant, and multi-drug resistant strains of M. tuberculosis. © 2010 Springer Science+Business Media, Inc.

Tursynbayeva A.,National Center for Tuberculosis Problems | Tursynbayeva A.,KNCV Tuberculosis Foundation | Idrissova M.,KNCV Tuberculosis Foundation | Markabaeva T.,National Center for Tuberculosis Problems | And 7 more authors.
Open Infectious Diseases Journal | Year: 2013

In Kazakhstan, tuberculosis (TB) patients are screened for human immunodeficiency virus (HIV), and HIVinfected individuals are screened for active TB. However, there is no exchange of case-based information between the TB and HIV/AIDS programs. To assess the proportion of co-infected patients registered as such in both registers and to assess reasons for patients missing in either register, we compared 2009 data from the TB and HIV/AIDS registers from two areas in Kazakhstan. Almaty city and the adjacent Almaty oblast, represent 22% of the country's population. Also, co-infected patients as well as a number of HIV-infected individuals were interviewed. In total, 85 patients diagnosed with TB and HIV were registered, of whom 73 were registered in the TB register, 79 in the HIV/AIDS register, and 67 in both registers. In the TB register, twelve patients were wrongly recorded as HIV negative. Only 9 (11%) out of the 82 patients who started treatment (three died shortly after diagnosis) had been prescribed antiretroviral treatment. In conclusion, gaps and mistakes with regard to TB/HIV patients were identified in both registers. Collaboration between the TB and HIV/AIDS centers was strengthened, which includes routine monitoring of TB/HIV diagnoses and treatment. This should lead to improved quality of care for TB/HIV patients and an improved insight in TB/HIV epidemiology. © Tursynbayeva et al.; Licensee Bentham Open.

Sengstake S.,Royal Tropical Institute | Bablishvili N.,National Center for Tuberculosis and Lung Diseases | Schuitema A.,Royal Tropical Institute | Bzekalava N.,National Center for Tuberculosis and Lung Diseases | And 14 more authors.
BMC Genomics | Year: 2014

Background: Multiplex ligation-dependent probe amplification (MLPA) is a powerful tool to identify genomic polymorphisms. We have previously developed a single nucleotide polymorphism (SNP) and large sequence polymorphisms (LSP)-based MLPA assay using a read out on a liquid bead array to screen for 47 genetic markers in the Mycobacterium tuberculosis genome. In our assay we obtain information regarding the Mycobacterium tuberculosis lineage and drug resistance simultaneously. Previously we called the presence or absence of a genotypic marker based on a threshold signal level. Here we present a more elaborate data analysis method to standardize and streamline the interpretation of data generated by MLPA. The new data analysis method also identifies intermediate signals in addition to classification of signals as positive and negative. Intermediate calls can be informative with respect to identifying the simultaneous presence of sensitive and resistant alleles or infection with multiple different Mycobacterium tuberculosis strains.Results: To validate our analysis method 100 DNA isolates of Mycobacterium tuberculosis extracted from cultured patient material collected at the National TB Reference Laboratory of the National Center for Tuberculosis and Lung Diseases in Tbilisi, Republic of Georgia were tested by MLPA. The data generated were interpreted blindly and then compared to results obtained by reference methods. MLPA profiles containing intermediate calls are flagged for expert review whereas the majority of profiles, not containing intermediate calls, were called automatically. No intermediate signals were identified in 74/100 isolates and in the remaining 26 isolates at least one genetic marker produced an intermediate signal.Conclusion: Based on excellent agreement with the reference methods we conclude that the new data analysis method performed well. The streamlined data processing and standardized data interpretation allows the comparison of the Mycobacterium tuberculosis MLPA results between different experiments. All together this will facilitate the implementation of the MLPA assay in different settings. © 2014 Sengstake et al.

Van Den Hof S.,KNCV Tuberculosis Foundation | Van Den Hof S.,Amsterdam Institute for Global Health and Development | Tursynbayeva A.,National Center for Tuberculosis Problems | Tursynbayeva A.,KNCV Tuberculosis Foundation | And 5 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2013

SETTING: Kazakhstan is a country with a low HIV/ AIDS (human immunodeficiency virus/acquired immunedeficiency syndrome) burden, but a high prevalence of multidrug-resistant tuberculosis (MDR-TB). METHODS: We describe the epidemiology of multidrug resistance and HIV among TB patients, using the 2007- 2011 national electronic TB register. RESULTS: HIV test results were available for 97.2% of TB patients. HIV prevalence among TB patients increased from 0.6% in 2007 to 1.5% in 2011. Overall, 41.6% of patients had a positive smear at diagnosis, 38.6% a positive culture and 51.7% either a positive smear or culture. Drug susceptibility testing (DST) results were available for 92.7% of culture-positive cases. Socio-economic factors independently associated with both HIV and MDR-TB were urban residency, drug use, homelessness and a history of incarceration. In adjusted analysis, HIV positivity was not associated with MDRTB (OR 1.0, 95%CI 0.86-1.2). Overall, among TB patients with DST and HIV test results available, 65.0% were positive for neither HIV nor MDR-TB, 33.5% only for MDR-TB, 0.9% only for HIV and 0.6% for both HIV and MDR-TB. Among injection drug users, 12.5% were positive for HIV and MDR-TB. CONCLUSION: We showed increasing HIV prevalence among TB patients in Kazakhstan. HIV was not an independent risk factor for MDR-TB, but risk factors were largely overlapping and we did identify subgroups at particular risk of HIV-MDR-TB co-infection, notably drug users. Enhanced efforts are necessary to provide care to these socially vulnerable populations. © 2013 The Union.

Klinkenberg E.,KNCV Tuberculosis Foundation | Klinkenberg E.,University of Amsterdam | Van Den Hof S.,KNCV Tuberculosis Foundation | Van Den Hof S.,University of Amsterdam | And 7 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2012

In Kenya and Kazakhstan, integration of human immunodeficiency virus (HIV) testing results into the routine surveillance of multidrug-resistant tuberculosis (MDRTB) proved feasible and useful. The integration process improved overall data quality and data validation capacity, and integrated data are a useful addition to routine cohort and treatment outcome data. Besides their importance for individual patient care, they provide trends on the association of MDR-TB and HIV in the routine programme setting. They also form a useful epidemiological basis for more specific studies, such as on nosocomial outbreaks. Whether the system itself is sensitive enough to monitor possible outbreaks needs further investigation. © 2012 The Union.

Kuranov A.B.,National Center for Biotechnology | Kozhamkulov U.A.,National Center for Biotechnology | Vavilov M.N.,Chelyabinsk State University | Belova E.S.,National Center for Tuberculosis Problems | And 4 more authors.
Tissue Antigens | Year: 2014

The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Some studies have reported that HLA class II genes play a strong role in severe cases of pulmonary tuberculosis (PTB) in several populations. Thus the aim of the study was to compare the HLA-class II alleles of patients with drug resistant tuberculosis with those of healthy controls from the same ethnic group in Kazakhstan. The aim of the present study was to evaluate the correlation of HLA-class II alleles by patients with drug resistant tuberculosis and the healthy controls of the same ethnic group in Kazakhstan. The HLA-class II alleles of 76 patients with tuberculosis (TB) and 157 healthy volunteers were investigated using sequence-based typing (SBT)-method. HLA-DQA1*03:02 HLA-DRB1*08:01 and DRB1*08:03 occurred more frequently (P=0.05) in patients with drug resistant tuberculosis than in controls. We observed a possible association between certain HLA alleles and TB that are specific for the Kazakh population. Further studies are needed to confirm our findings using a larger number of patients with drug resistant tuberculosis. © 2014 John Wiley & Sons A/S.

Kozhamkulov U.,National Center for Biotechnology | Akhmetova A.,National Center for Biotechnology | Rakhimova S.,National Center for Biotechnology | Belova E.,National Center for Tuberculosis Problems | And 6 more authors.
Japanese Journal of Infectious Diseases | Year: 2011

Kazakhstan is one of the 14 countries with a high rate of morbidity due to multidrugresistant tuberculosis (MDR TB) in WHO European region. The aim of our study was to characterize mutations associated with drug resistance to rifampicin and isoniazid in Mycobacterium tuberculosis isolates from Kazakhstan. M. tuberculosis strains were isolated from TB patients in different regions of Kazakhstan. A drug susceptibility test was performed on Lowenstein-Jensen medium using the absolute concentration method. Sequencing analysis was performed of the rpoB rifampicin resistance-determining region and the katG gene, the oxyR-ahpC intergenic region, and the inhA promoter region in 259 MDR M. tuberculosis isolates, in 51 isoniazid-resistant isolates, and in 13 rifampicin-resistant isolates. The mutational analysis revealed that the most frequent mutations associated with rifampicin and isoniazid resistance in M. tuberculosis are the substitutions at codons 531 (82.7%) and 315 (98.4%) in the rpoB and kat G genes, espectively. In addition, we have found mutations with lower frequency at codons 526 (8.4%), 533 (1.5%), and 516 (1.1%) in the rpoB gene. In 6.2% of the isolates, no mutations were found in the rpoB gene. The findings of this study provide useful data for a better understanding of the mutation spectrum of isoniazid and rifampicin resistance among strains isolated from patients in Kazakhstan. Our results are also useful for the development of diagnostic tests of MDR M. tuberculosis.

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