IMPLEMENTATION OF DIRECTLY OBSERVED TREATMENT ONMULTI-DRUG RESISTANT TUBERCULOSIS PATIENTS IN YEREVAN, ARMENIA

Abstract



Tuberculosis (TB) is one of the important public health problems globally [31,p.5]. Multi- Drug Resistant tuberculosis (MDR-TB) is fetching more concern nowadays, owing to its intensive medical care requirement [30, p.5, 20, p.5]. The low and middle-income countries are the most victims [31, p.5]. As, Armenia is classified as one of the middle-income countries it is included in the WHO’s TB risk regions with 3495 TB cases [33, p.5, 1, p.3].Though the morbidity and mortality rate of TB incidence in Armenia is reducing, it was reported that 9.4% of all TB cases in the country were MDR-TB, in 2016 [17, p.5, 26, p.5]. The development of MDR in the country can be narrowed down to definite causes, notably, non-adherence to the treatment strategy leading to development of re-infection with drug resistance, poor awareness programs, poor quality of drugs, treatment plan, co-morbidities, and socio-economic status [9, p.4, 10, p.4, 22, p.5]. With increasing global MDR-TB cases at an alarming rate, WHO has developed and adopted Directly Observed Treatment (DOT) strategy [32, p.5]. Georgia, the neighbor of Armenia sharing its geographical and socio-economic situation as a post-Soviet country, has employed DOT in treatment of MDR-TB and showing hopeful results of treating the disease [14, p.4].With addition of newly developed drugs and revised DOT strategy, Armenia can provide better treatment to TB patients, ensuring comfortable post disease period and making way to the eradication of the disease [3, p.4, 25, p.5]. Tuberculosis (TB) is one of the top 10 causes of death globally [31, p. 5]. Tuberculosis been known to man-kind for around 4000 years [35, p.5].Development of resistance to antibiotic medications is usual and in the case of Mycobacterium tuberculosis is no different [13, p. 4].It is believed that the drug resistance formed was due to antibiotic abuse and improper medical interventions, which lead to spontaneous chromosomal mutation in the causative bacteria [13, p. 4]. Drug Resistant-TB (DR-TB) is classified as mono-drug resistant TB, poly-drug resistant TB, multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) [19, p. 5]. Further, poor TB awareness national program, unsupervisedtreatment, lead to failure of treatment and development of drug resistance [5, p. 4]. In 2017, 121 countries have reported WHO of at least one XDR-TB case in their country [30 ,p. 5]. TB disease manifestation is mainly seen in the lungs but also in other organ systems when the disease takes severe course. Chest pain, hemoptysis, chronic cough, fatigue or general weakness, fever, weight lossand night-sweats are the main clinical signs and symptoms of pulmonary TB [35, p. 5]. A non-drug resistant TB can be treated in around 6 months with first line treatment medications, but some strains of Mycobacterium develop mono- and multi-drug resistance which may require severe treatment for up to 18 months [11, p. 4]. In the 1960s, it was believed that TB was not a public health issue and that in future the disease would be eradicated completely [16, p. 4]. But to the surprise of public health professionals, TB became a concern in 1980s with intensifying epidemic of the acquired immune deficiency syndrome (AIDS) and the development of drug-resistant forms of TB Mycobacterium [18, p. 8]. Magnitude of the problem: оnly in 2016, 10.4 million people were reported to be affected with TB globally, and 1.7 million died, out of which 0.4% were HIV infected and low- and middle- income countries contributed around 95% of all TB deaths [31, p. 5]. Armenia is classified as one of the middle-income countries, but performing better in economic growth that its peers [33, p. 5]. In 2016, MDR and Rifampicin Resistance TB (RR-TB) caused 240,000 deaths, where most cases and deaths were reported from Asia [30,p. 5, 20, p. 8]. It was reported that in 2016, there were 600,000 new cases with rifampicin (first-line drug) resistance, out of which 490,000 had multi- drug resistance worldwide [31, p. 5]. TB as a public health problem in Armenia remains alarming, with an estimated incidence rate of 44 new cases per 100,000 in 2016 [27, p. 5]. TB morbidity in Armenia saw a decline from 47.6 in 2007 to 23.1 per 100,000 in 2017 [17, p. 5]. The TB mortality rate was also reduced from 5.4 to 1.8 per 100,000 during the same period [17,p. 5].WHO statistics infers that in Armenia, 9.4% of all TB cases reported to have MDR-TB [25, p.5]. While global prevalence of MDR-TB in 2016 was estimated to be 11% among new and 47% among previously treated cases [30, p. 5].Globally, TB incidence is sinking at about 2% per year. But this needs to be accelerated to a 4-5% declineto reach ‘The 2020 milestones of the End TB Strategy’[27, p. 5]. Several factors have been identified for the development of MDR, include non-adherence to therapy, lack of direct observed treatment, improper drug supplies, poor quality of drugs, easy accessibility of anti-TB drugs without prescription, poor medical management, and poorly-managed national control programs [9, p. 4,10, p. 4]. A study identified that age 18 to 45 years, education at secondary school level, service field and business as profession, smoking history, and type-2 diabetes as risk factors ofcomorbidities [10, p. 4]. The existence of MDR-TB is mainly attributable to human factors such as errors and delay in medical interventions that predispose for development of drug resistance, alsogenetics and genetic factorsare also believed to be one of the important contributors [22, p. 5]. A study conducted in the country of Georgia, a neighboring nation, sharing the geographical and economic situation to Armenia, revealed that MDR-TB were noted mostly in patients who did not adhere to strategy during intensive and continuous therapeutic processes [14, p. 4]. This led to disturbance of TB bacterial death and growth cycles, causing discrete mutations of different independent genes to accrue [14, p. 4]. Further, a study in other setting detailed that MDR-TB cases were prevalent among the older age [4,p.4]. Furthermore, majority of the global MDR-TB cases were from low socio-economic groups [7, p.4, 6,p.4]. In Armenia, the most TB cases were reported from the Shirak region, which is considered as the poorest region of the country and the Yerevan city as the ‘average’ [23, p.5]. Another significant key determinant for TB in Armenia, is the success rate of treatment for sputum smear-positive cases has never reached WHO’s target of 85% in the pastdecade and half [8, p.4]. Recommended interventions: WHO recommends the adoption of DOT approach to tackle the predicament situation of rising MDR-TB and in the TB treatment [32, p.5]. In DOT, the chemotherapeutic interventions are carried in attendance of a health care professional at prescribed time to ensure proper and precise following of treatment plan [24, p.5]. Implementation of DOT has been a revolution in the TB control Globally, it has become the basis in the treatment of tuberculosis [29, p.5]. China [34, p.9], Bangladesh [12, p.4] and Georgia [14, p.4] have employed the DOT program and have seen promising results. There has been steady increase in the number of countries adopting WHO’s DOT strategy [29, p.5]. In the last 15 years, around 35 million TB patients were cured, and around 8 million deaths were prevented with DOTS adoption worldwide [21, p.5]. For the first time in five decades, two new drugs, Bedaquiline and delamanid, have been developed and approved to have ‘WHO interim policy guidance’ for their usage for MDR-TB treatment [3, p.4]. A cohort study of effective treatment using four to five drugs for 15-24 months in Armenia, Georgia, Swaziland, Uzbekistan and Kenya between 2001 and 2011 was conducted [2, p. 4]. Two thirds of all MDR-TB Patients who benefited from bedaquiline and delamanid were involved in the study [2, p. 4].WHO devised five priorities on MDR-TB intervention and prevention strategy such asensuring good access MDR-TB care, implementing control measures on disease transmission, providing immediate access to effective treatment, strong commitment from government and politics sector [20, p. 5].The advantages of DOT overweigh its disadvantage and all key determinant problems were met [15, p.4]. Treatment of drug susceptible TB conducted by national TB programs (NTPs) using standard four drug therapies and DOT strategy has led to relapse-free cure rates over 95% and declines in TB incidence [13, p. 4]. As reported on June 2017, 55 countries had imported delamanidand89 countries started using bedaquiline [30, p. 5]. These new medicines were provisionally agreed to be used in the treatment of MDR-TB by stringent regulatory authorities in recent years [30, p. 5].“To ensure the expansion of the Stop TB Strategy in Armenia, the Minister of Health took over the management of the National Tuberculosis Program (NTP) in 2010” [28, p. 5].

R S Sankaran

Yerevan State Medical University after Mkhitar Heratsi

L G Gevorgyan

Yerevan State Medical University after Mkhitar Heratsi

  1. Andreasyan D, Bazarchyan A, Simonyan S, et al. Statistical Year Book. Yerevan; 2017. [Internet-resource] http://nih.am/assets/pdf/atvk/14c0b8ed94657718a8658fb0f8ae2ff6.pdf (Date: 12.11.2018).
  2. Bonnet M, Bastard M, du Cros P, et al. Identification of patients who could benefit from bedaquiline or delamanid: a multisite MDR-TB cohort study. International Journal of Tuberculosisa and Lung Diseases.2016; 20(2):177- 186.
  3. Brigden G, Hewison C, Varaine F. New developments in the treatment of drug-resistant tuberculosis: clinical utility of bedaquiline and delamanid. Infectionand Drug Resistance. 2015;8:367-378.
  4. Caminero JA. Likelihood of generating MDR-TB and XDR-TB under adequate National Tuberculosis Control Programme implementation. I n t e r n a t i o n a l Journal of Tuberculosis and Lung Diseases.2008;12(8):869-877.
  5. Caminero JA. Multidrug-resistant tuberculosis: epidemiology, risk factors and case finding State of the art series. Drug-resistant tuberculosis. International Journal of Tuberculosis and Lung Diseases.2010; 14(4): 382-390.
  6. Chen S, Huai P, Wang X, et al. Risk factors for multidrug resistance among previously treated patients with tuberculosis in eastern China: a case-control study. International Journal of Infectious Diseases.2013;17(12):1116-1120.
  7. Daniel O, Osman E. Prevalence and risk factors associated with drug resistant TB in South
  8. West Nigeria. Asian Pacific Journal of Tropical Medicine. 2011;4(2):148-151.
  9. Dikran R B, Karapet D, Andre B, et al. Tuberculosis treatment and Smoking, Armenia, 2014-2016. Journal of Clinical Tuberculosis and Other Mycobacterial Diseases.2017;8(1):1-5.
  10. Espinal MA, Laserson K, Camacho M, et al. Determinants of drug-resistant tuberculosis: analysis of 11 countries. International Journal of Tuberculosis and Lung Diseases.2001;5:887-893.
  11. Farmer P, Bayona J, Becerra M. Multidrug resistant tuberculosis and the need for biosocial perspectives. International Journal of Tuberculosis and Lung Diseases2001;5:885-886.
  12. Iseman MD. Treatment of Multidrug-Resistant Tuberculosis. New England Journal of Medicine.1993;329(11): 784-791.
  13. Kumaresan JA, Ahsan Ali AK, Parkkali LM. Tuberculosis control in Bangladesh: success of the DOTS strategy. International Journal of Tuberculosis and Lung Diseases.1998;2(12):992-998. [Internet-resource] http://www.ncbi.nlm.nih.gov/pubmed/9869115. (Date: 12.11.2018).
  14. Kurz SG, Furin JJ, Bark CM. Drug resistant tuberculosis: challenges and progress. Infectious Disease Clinics of North America.2016;30(2):509-522.
  15. Lomtadze N, Aspindzelashvili R, Janjgava M, et al. Prevalence and Risk Factors for Multidrug-Resistant Tuberculosis in Republic of Georgia:Population Based Study. International Journal of Tuberculosis and Lung Diseases.2009;13(1):68-73.
  16. Murali MS, Sajjan BS. DOTS strategyforcontroloftuberculosisepidemic.Indian Journal of Medical Sciences.2002;56(1):16-18.
  17. Myers JA. Can tuberculosis be eradicated? Diseases of the Chest. 1963;43:327- 329.
  18. National Tuberculosis Program of Armenia database. [Internet-resource] http:// www.ntp.am/hy/statistics. (Date: 12.11.2018).
  19. Nguyen L.Antibiotic resistance mechanisms in M. tuberculosis: an update. Archives of Toxicology.2016;90(7):1585-1604.
  20. Nune T, Ruzanna G, Hripsime M, et al. Center for health services research anddevelopment, American university of Armenia. Operational research on working migrants and TB in Armenia. 2012. [Internet-resource] http:// chsr.aua.am/files/2014/02/TB_Migrant_report_ English.pdf. (Date:12.11.2018).
  21. Panda S, Swaminathan S, Hyder KA, et al. Drug resistance in malaria, tuberculosis, and HIV in South East Asia: biology, programme, and policy considerations. The British Medical Journal.2017;358:j3545. doi: 10.1136/bmj.j3545.
  22. Ramakant B. 36 million people with TB cured.World Health Organization:Geneva;2009. http://www. weeklyblitz.net/363,Published on 3-Mar-2010.
  23. Sharma SK, Mohan A. Multidrug- resistant tuberculosis: a menace that threatens to destabilize tuberculosis control.Chest. 2006;130(1):261-72.
  24. Truzyan N, Grigoryan R, Martirosyan H, et al. Operational Research on Investigation of TB Risk Factors in Armenia. 2012:77. [Internet-resource] http://chsr.aua.am/ files/2014/02/Risk-Factors_Report_English.pdf. (Date: 12.11.2018).
  25. Volmink J, Garner P. Directly observed therapy for treating tuberculosis. In: Volmink J, ed. Cochrane Database of Systematic Reviews. Chichester, UK: John Wiley & Sons, Ltd; 2006.
  26. WHO. Blueprint on People- Centered Model of TB Care, 2017. Performance- Based Financing Manual for Primary Health Care Facilities. Approved by the Republic of Armenia Minister of Health order N 262-A of Feb-12-2013.
  27. WHO. Country Profile, Armenia. [Internet-resource] https://extranet.who.int/ sreeReports. (Date: 12.11.2018).
  28. WHO, GlobalTB Report 2017. [Internet-resource] http://www.who.int/tb/ publications/global_report/en. (Date: 12.11.2018).
  29. WHO. Epidemiological profile: 2010 Tuberculosis country work summary Armenia. 9 December 2011.
  30. WHO. Global tuberculosis control 2009: epidemiology, strategy, financing: WHO report 2009. Geneva; 2009. p. 303. (WHO/HTM/ TB/2009.411).
  31. WHO. Multidrug-resistant tuberculosis (MDR-TB) 2017 update. [Internet- resource] http://www.who.int/tb/challenges/ mdr/MDR-RR_TB_factsheet_2017.pdf(Date: 12.11.2018).
  32. WHO. Tuberculosis. [Internet- resource] http://www.who.int/tb/en. Accessed on Sept-10-2018. (Date: 12.11.2018).
  33. WHO. What is DOTS (Directly Observed Treatment, Short Course). [Internet- resource] http://www.searo.who.int/tb/topics/ what_dots/en/. Published on July 12, 2017. (Date: 12.11.2018).
  34. World Bank. Armenia-April,2018 update. [Internet-resource] http://www.worldbank. org /en /cou nt r y/ar menia /over view( Date: 12.11.2018).
  35. World Health Organization. WPRO, Tuberculosis in China. WPRO. 2017. [Internet-resource] http://www.wpro.who.int/ china/mediacentre/factsheets/tuberculosis/en. (Date: 12.11.2018).
  36. Zaman K. Tuberculosis: a global health problem. Journal of Health, Population and Nutrition.2010;28(2):111-113.

Views

Abstract - 6

PDF (Russian) - 4

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies