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M.Tuberculosis Multi-Drug Resistance

#KR-1596


Detection of Multi-Drug Resistance of M.Tuberculosis by Biochips in Pulmonary TB Patients in Penitentiary Facilities and Their Households

Tech Area / Field

  • BIO-MIB/Microbiology/Biotechnology

Status
8 Project completed

Registration date
14.12.2007

Completion date
03.09.2012

Senior Project Manager
Genisaretskaya S V

Leading Institute
National Center of Cardiology and Internal Medicine, Kyrgyzstan, Bishkek

Supporting institutes

  • National Center of Phthisiology, Kyrgyzstan, Bishkek

Collaborators

  • Forschungszentrum Borstel / National Reference Center for Mycobacteria, Germany, Borstel

Project summary

The goal f the project is to increase efficiency of preventive TB control actions through early MDR-TB detection by bio-chips analysis in pulmonary TB patients of the penitentiary system and the households of them.

According to the World Health Organization, TB morbidity in Kyrgyzstan has reached the epidemic scale. Specialists make such conclusions when TB incidences constitute 50 per 100 000 population. In the republic, this rate equals to 122,3 (2006). One of the main sources of TB are facilities of penitentiary system, where for many years TB morbidity rate has been remaining higher than in entire population. In Kyrgyzstan, 3830 TB cases per 100 000 population were registered in the penitentiary system in 2002, 2947 cases - in 2003, and 2875 - in 2004 (the World Bank Report #56, 2005). According to the data of the Republican Center of Information and Epidemiology of the National Center of Phthisiology (NCP), morbidity rate in 2006 was 1995,8 per 100 000 inmates, and mortality rate in 2006 was 505,5 per 100 000 of incarcerated people.

Being infected or sick, prisoners cause a risk for a prison personnel and visiting people and after release – in particular for the households of them and the community as a whole. It has been noted that during declaration of big amnesties in the republic, morbidity rate in drug resistant TB cases goes up. Children staying in the pesthole of drug resistant TB are at high risk. A profound effect of the TB infection source on TB morbidity rate among children is evidenced by the fact that alarming data exists in places of TB pesthole (Mamytova N.B. et al, 1999, 2000, Galieva R.Sh. et al., 2001, Kurmanova N.K. et al, 2002, 2006). Compared to the situation in 1994, when morbidity rate among children from the source of TB infection was 431,3 per 100 000 contacts, that rate has currently increased by 3,5 times. At present, morbidity rate among children remains high. In 2006, there were 44, 1 incidences per 100 000 children.

As per the data of the Children’s Department of the National Phthisiology Center (NCP) (2003-2004), contacts with TB parents were found in 73% of TB children. But for all that, children were in close contact with parents in 60,1% of cases. The cases of the so-called “family TB” became frequent. It’s when in one family several children infected by their parents get sick with TB at one and the same time. The rate of TB children among all TB cases ranged from 15,0% up to 22% for different years (1997-2002).

Performance of the drug sensitivity test of MT to anti-TB drugs in children is complicated in children, particularly of a preschool age, due to sputum collection difficulties (they swallow up sputum). As a result of that, MT is identified by a standard microscopic examination only in 2-3% of TB children. The rest of them become suspected for drug resistant TB when positive clinical-and-roentgen course of the disease is lacking and the disease is progressing on the background of chemotherapy when other factors negatively affecting treatment efficiency being excluded.

Nowadays, identification of drug resistance in adult members of the family is of very important for TB prevention in children. Chemoprophylaxis efficiency in children depends much on drug resistance of MT in the source of infection. Qualitatively performed chemoprophylaxis decreases the risk of TB among children by 5-8 times (Yanchenko E.N. et al., 1987, Ovsyankina E.S. et al., 2006).

Children and teenagers from the pesthole resistant to anti-TB drugs in the source of infection get sick with TB by 3, 4 times higher than those from the pesthole where susceptibility to anti-TB drugs is preserved (Ovsyankina E.S. et al., 2006). This fact is an evidence of a high epidemic threat of the pesthole with drug resistant MT in the source of infection.

Nowadays, culture examination is a commonly accepted “golden standard” for testing drug susceptibility of MT. However, culture examination does not produce rapid results due to a long length of time required for analysis and that complicates timely performance of chemoprophylaxis and chemotherapy.

At present, molecular-genetic methods as an alternative technique are widely used along with culture examinations to test MT susceptibility to antibiotics. The latest one is a rapid analysis system “MDR TB-biochip” developed at the V.A. Engelgard Molecular Biology Institute of RAS (Moscow, Russia). The principle advantage of the biochip analysis is a direct detection of MT DNA in contrast to culture examination and a possibility for a rapid (within 3 days) detection of MT susceptibility to basic first-line anti-TB drugs: rifampicin (R) and isoniazid (H) per mutation in genes rpoB, katG, inhA, ahpC (Mikhailovich, V. et al. 2001).

However, irrespective of an obvious advantage, biochip analysis is not commonly recognized and requires standardization relative to commonly accepted culture examination.

At the TB Scientific-Research Institute of RAMS (Russian Academy of Medical Sciences), both the biochip analysis results and the results of commonly recognized culture examination of drug susceptibility to rifampicin and isoniazid were compared. The sensitivity and specificity of the biochip technique constituted 88,9% and 94,3%, and per the data of the Moscow City Scientific Center - 97,8 и 90,6%, correspondingly.

Under the ISTC KRN#861 project, we have also compared the results of 745 biochip analysis with the culture examination results performed at the National Center of Phthisiology in Bishkek city. Per our results, sensitivity and specificity of the biochip analysis were 87% and 92%, and prognostic significance of the positive and negative result was - 94,7 and 90%, correspondingly.

According to the international procedures, none of the diagnostic techniques, biochip analysis included, can be recognized as a standard technique and applied in a wide laboratory practice, if a compulsory comparison with the results of the commonly accepted and certified International Reference Laboratory is lacking.

Considering the above sited, it is offered in this project to evaluate the diagnostic value of the biochip analysis in comparison with the results of the standard culture examination performed by the National Reference Center for Mycobacteria in Borstel, Germany. The results of the biochip analysis and culture examination will be compared by a blind method taking one and the same sputum smear sample in Bishkek and Borstel cities. To compare the results of biochip analysis and culture examination, 300 sputum smear samples of pulmonary TB patients will be tested. Sputum samples of 150 new detected TB patients and 150 sputum samples of patients treated before will be compared. As a result of the comparison of biochip analysis and culture examination, susceptibility and specificity will be evaluated by a four-field table and that will enable to assess how well the results of the MDR-TB detection by a biochip analysis coincides with a commonly used standard technique for diagnosing drug resistant strains of MT.

Our jointly developed project will contribute to the standardization of the biochip analysis technique for implementation in the penitentiary system laboratory services and health facilities of Kyrgyzstan for early detection and timely isolation of drug resistant TB patients.


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