Title: Sputum Smear Conversion Time of HIV Infected and Uninfected Patients with Rifampicin and Isoniazid Mycobacterium tuberculosis gene Mutations in Western Kenya
Authors: Shiluli, Clement, Ouma, Collins, Vulule, John, Khayumbi, Jeremiah, Murithi, Wilfred, Musau, Susan, Okumu, Albert
DOI: https://dx.doi.org/10.18535/jmscr/v4i12.28
Background: In 2013, an estimated 9.0 million people developed tuberculosis (TB) and 1.5 million died from the disease, 360 000 of whom were HIV-positive. A major challenge to TB management is the multi-drug resistant (MDR) TB strains and HIV. There are few studies in western Kenya on the specific mutations underlying resistance to rifampicin (RIF) and isoniazid (INH) and the time to sputum smear conversion, especially in HIV-infected patients. Methods: We therefore studied sputum smear conversion time in TB and HIV co-infected patients with previously confirmed rpoB, katG and inhA Mycobacterium tuberculosis gene mutations. Drug sensitivity tests and line probe assays had been performed previously on sputum samples from participating patients. Samples with discordant results were further sequenced to confirm rpoB, katG, and inhA gene mutations that have been associated with RIF and INH mutations. Gene mutations were classified into three categories based on specific codons with mutations on the rpo B, kat G, and in hA genes as follows, MDR-TB, RIF mono-resistant (RMR) TB and isoniazid mono-resistant (INHMR) TB. Ziehl-Neelsen (ZN) microscopy was done on sputum samples from enrolled patients on two occasions; during first and follow-up visits at respective health facilities. The period of follow-up was less than one year. Smear results were available for 16 patients with confirmed drug resistant TB. The smear conversion rate was determined by dividing the number of patients who had a negative smear during follow-up and the number of smear positive patients on first visit and multiplying by 100.Spearman’s correlation coefficient was used to assess the strength of associations between continuous and ordinal variables. Results: The smear conversion rate for participating patients was as follows; RMR-TB = 100%, INHMR-TB = 60% and MDR-TB = 67%.All the patients had positive Mycobacterium tuberculosis cultures. There was positive correlation between follow-up days and ZN smear results, (rs(14) = 0.097, p = 0.721). Conclusion: Sputum smear conversion time can be used in monitoring drug resistant TB in both HIV-infected and -uninfected patients. Keywords: Tuberculosis, HIV, MDR-TB, isoniazid mono resistant, rifampicin mono resistant gene sequencing. 1. WHO. Global Tuberculosis Report 2014. Geneva, Switzerland: World Health Organization.; 2014. 2. KAIS. Kenya AIDS Indicator Survey Annual report. 2013. 3. Jamieson FB, Guthrie JL, Neemuchwala A, Lastovetska O, Melano RG, Mehaffy C. Profiling of rpoB mutations and MICs for rifampin and rifabutin in Mycobacterium tuberculosis. J ClinMicrobiol. 2014 Jun;52(6):2157-62. 4. Quy HT, Cobelens FG, Lan NT, Buu TN, Lambregts CS, Borgdorff MW. Treatment outcomes by drug resistance and HIV status among tuberculosis patients in Ho Chi Minh City, Vietnam.Int J Tuberc Lung Dis. 2006 Jan;10(1):45-51. 5. Sarin R, Singla R, Visalakshi P, Jaiswal A, Puri MM, Khalid UK, et al. Smear microscopy as surrogate for culture during follow up of pulmonary MDR-TB patients on DOTS Plus treatment. Indian J Tuberc. 2010 Jul;57(3):134-40. 6. Gammino VM, Taylor AB, Rich ML, Bayona J, Becerra MC, Bonilla C, et al. Bacteriologic monitoring of multidrug-resistant tuberculosis patients in five DOTS-Plus pilot projects. Int J Tuberc Lung Dis. 2012 Oct;15(10):1315-22. 7. Bawri S, Ali S, Phukan C, Tayal B, Baruwa P. A study of sputum conversion in new smear positive pulmonary tuberculosis cases at the monthly intervals of 1, 2 & 3 month under directly observed treatment, short course (dots) regimen. Lung India. 2008 Jul;25(3):118-23. 8. Telenti A, Honore N, Bernasconi C, March J, Ortega A, Heym B, et al. Genotypic assessment of isoniazid and rifampin resistance in Mycobacterium tuberculosis: a blind study at reference laboratory level. J ClinMicrobiol. 1997 Mar;35(3):719-23. 9. Huyen MN, Cobelens FG, Buu TN, Lan NT, Dung NH, Kremer K, et al. Epidemiology of isoniazid resistance mutations and their effect on tuberculosis treatment outcomes. Antimicrob Agents Chemother. 2013 Aug;57(8):3620-7. 10. Palacios E, Franke M, Munoz M, Hurtado R, Dallman R, Chalco K, et al. HIV-positive patients treated for multidrug-resistant tuberculosis: clinical outcomes in the HAART era. Int J Tuberc Lung Dis. 2012;16(3):348-54. 11. Moh. Guidelines For The Management Of Drug Resistant Tuberculosis In Kenya. 2010. 2010. 12. NLTLD. Annual Report.Ministry of Health, National Leprosy, TB and Lung Disease Program (NLTLD). 2014. 13. Sitienei J, Kipruto H, Mansour O, Ndisha M, Hanson C, Wambu R, et al. Correlates of default from anti-tuberculosis treatment: a case study using Kenya's electronic data system. Int J Tuberc Lung Dis. 2015 Sep;19(9):1051-6. 14. Atif M, Sulaiman SA, Shafie AA, Ali I, Asif M, Babar ZU. Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang, Malaysia. BMC Infect Dis. 2014;14:399. 15. Charles M, Vilbrun SC, Koenig SP, Hashiguchi LM, Mabou MM, Ocheretina O, et al. Treatment outcomes for patients with multidrug-resistant tuberculosis in post-earthquake Port-au-Prince, Haiti. Am J Trop Med Hyg. 2014 Oct;91(4):715-21. 16. Menzies D, Benedetti A, Paydar A, Martin I, Royce S, Pai M, et al. Effect of duration and intermittency of rifampin on tuberculosis treatment outcomes: a systematic review and meta-analysis. PLoS Med. 2009 Sep;6(9):e1000146. Shiluli, Clement School of Public Health and Community Development, Department of Biomedical Sciences and Technology, Maseno University, P.O. Private Bag, Maseno Email: This email address is being protected from spambots. You need JavaScript enabled to view it., Mobile Number+254 723 474 168Abstract
References