Mycobacterium tuberculosis resistance to Isoniazid and Rifampicin in a HIV-1 endemic population in western Kenya in 2012-2014

Title: Mycobacterium tuberculosis resistance to Isoniazid and Rifampicin in a HIV-1 endemic population in western Kenya in 2012-2014

Authors: Clement Shiluli, Collins Ouma, John M. Vulule, Jeremiah Khayumbi, Wilfred Murithi, Susan Musau and Albert Okumu

DOI: https://dx.doi.org/10.18535/jmscr/v4i12.51

Abstract

Background: Mono-resistant and multi-drug resistant tuberculosis (MDR-TB) has been enhanced by delays in the identification of resistant strains. However, resistance gene patterns and the extent of mono-resistant TB and MDR-TB in western Kenya is unknown. The objective of the study was to identify cases of mono-resistant TB and MDR-TB in western Kenya.

Methods: Early morning sputum samples were cultured on Mycobacteria growth indicator tubes (MGIT) and incubated at 37 °C. Drug susceptibility testing (DST) using the SIRE® kit was done on ZN smear positive MGIT tubes and line probe assay (LPA) performed to identify specific mutations on the rpo B, kat G and inh A genes. Mutations on discordant samples were confirmed by sequence analysis.

Results: The rpo B H526Y and the kat G S315T1 mutations were common in HIV positive patients (8 % and 18 % respectively) and that the S3I5T1 and S531L was the most common mutation in MDR-TB strains in both HIV positive and negative patients (5 % and 8 % respectively). Binary logistic regression, indicated that RMR TB is associated with HIV status (P = 0.025).

Conclusions: Our findings showed that there is a potential association between RMR TB and HIV-1 status in western Kenya.

Keywords: Tuberculosis, HIV, Drug susceptibility test, Line Probe Assay, MDR-TB, mono resistant TB.

References

1. World Health Organization, Global Tuberculosis Report 2014. . Geneva, Switzerland: World Health Organization.; 2014 [updated 2014; cited 2016 2 Feb]

2. Drug resistant TB in Kenya Profiles. https://extranet.who.int/sree/Reports?op=Replet&name=/WHO_HQ_Reports/G2/PROD/EXT/TBCountryProfile&ISO2=KE&outtype=pdf; 2016 [updated 2016; cited 2016]

3. Guidelines For The Management Of Drug Resistant Tuberculosis In Kenya. 2010.

4. Huyen MN, Cobelens FG, Buu TN, Lan NT, Dung NH, Kremer K. Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes. Antimicrob Agents Chemother. 2013 Aug;57(8):3620-7.

5. Coovadia YM, Mahomed S, Pillay M, Werner L, Mlisana K. Rifampicin mono-resistance in Mycobacterium tuberculosis in KwaZulu-Natal, South Africa: a significant phenomenon in a high prevalence TB-HIV region. PLoS One. 2013;8(11):e77712.

6. Andrews JR, Shah NS, Gandhi N, Moll T, Friedland G. Multidrug-resistant and extensively drug-resistant tuberculosis: implications for the HIV epidemic and antiretroviral therapy rollout in South Africa. J Infect Dis. 2007 Dec 1;196 Suppl 3:S482-90.

7. Nduba V, Hoog AH, Mitchell E, Onyango P, Laserson K, Borgdorff M. Prevalence of tuberculosis in adolescents, western Kenya: implications for control programs. Int J Infect Dis. 2015 Jun;35:11-7.

8. Kenya AIDS Indicator Survey 2012. In: (NASCOP) NAaSCP, editor.: Republic of Kenya; 2014.

9. Lukoye D, Adatu F, Musisi K, Kasule GW, Were W, Odeke R. Anti-tuberculosis drug resistance among new and previously treated sputum smear-positive tuberculosis patients in Uganda: results of the first national survey. PLoS One. 2013;8(8):e70763.

10. Raizada N, Sachdeva KS, Chauhan DS, Malhotra B, Reddy K, Dave PV. A multi-site validation in India of the line probe assay for the rapid diagnosis of multi-drug resistant tuberculosis directly from sputum specimens. PLoS One. 2014;9(2):e88626.

11. Ling DI, Zwerling AA, Pai M. GenoType MTBDR assays for the diagnosis of multidrug-resistant tuberculosis: a meta-analysis. Eur Respir J. 2008 Nov;32(5):1165-74.

12. Bottger EC, Pletschette M, Andersson D. Drug resistance and fitness in Mycobacterium tuberculosis infection. J Infect Dis. 2005 Mar 1;191(5):823-4; author reply 4.

13. Brossier F, Veziris N, Truffot-Pernot C, Jarlier V, Sougakoff W. Performance of the genotype MTBDR line probe assay for detection of resistance to rifampin and isoniazid in strains of Mycobacterium tuberculosis with low- and high-level resistance. J Clin Microbiol. 2006 Oct;44(10):3659-64.

14. Baker L, Brown T, Maiden MC, Drobniewski F. Silent nucleotide polymorphisms and a phylogeny for Mycobacterium tuberculosis. Emerg Infect Dis. 2004 Sep;10(9):1568-77.

15. Cattamanchi A, Dantes RB, Metcalfe JZ, Jarlsberg LG, Grinsdale J, Kawamura LM. Clinical characteristics and treatment outcomes of patients with isoniazid-monoresistant tuberculosis. Clin Infect Dis. 2009 Jan 15;48(2):179-85.

16. Fenner L, Egger M, Bodmer T, Altpeter E, Zwahlen M, Jaton K. Effect of mutation and genetic background on drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2012 Jun;56(6):3047-53.

17. Gupta A, Nagaraja MR, Kumari P, Singh G, Raman R, Singh SK. Association of MDR-TB isolates with clinical characteristics of patients from Northern region of India. Indian J Med Microbiol. 2014 Jul-Sep;32(3):270-6.

18. Prach LM, Pascopella L, Barry PM, Flood J, Porco TC, Hopewell PC. Rifampin monoresistant tuberculosis and HIV comorbidity in California, 1993-2008: a retrospective cohort study. AIDS. 2013 Oct 23;27(16):2615-22.

19. Ridzon R, Whitney CG, McKenna MT, Taylor JP, Ashkar SH, Nitta AT. Risk factors for rifampin mono-resistant tuberculosis. Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):1881-4.

Corresponding Author

Clement Shiluli

*Correspondence; School of Public Health and Community Development, Department of Biomedical Sciences and Technology, Maseno University, P.O. Box Private Bag, Maseno

Email: This email address is being protected from spambots. You need JavaScript enabled to view it., +254 723 474 168