Akujobi CN, Okoro CE, Anyabolu AE, Okonkwo RC, Onwunzo MC and Chukwuka CP.

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Akujobi CN, Okoro CE, Anyabolu AE, Okonkwo RC, Onwunzo MC and Chukwuka CP

 Tuberculosis (TB) is the most common opportunistic infection in Human Immunodeficiency Virus (HIV)-infected patients. 1  HIV-infected patients are known to have 10% risk of reactivation of TB per year. 2  They are more likely to die from TB than HIV negative patients. 3

 In Sub-Saharan Africa, 30% of HIV-infected patients who are diagnosed with TB die 12 months after the initiation of treatment. 4,5  Nigeria has a HIV prevalence of 3.6% and has the world’s third largest TB burden.  It is also known that 26% of TB patients in Nigeria have HIV co-infection 7.

 Multi Drug resistant Tuberculosis (MDR-TB) is tuberculosis that is resistant to at least the first line anti-TB drugs, Rifampicin and Isoniazid. 8  The emergence of Multi Drug Resistant tuberculosis (MDR-TB) is of concern to both patients and clinicians because of the attendant increased mortality and morbidity.

 To determine the prevalence of MDR-TB among HIV seropositive and seronegative patients receiving treatment in Nnamdi Azikiwe University Teaching Hospital (NAUTH), Nnewi, Anambra State, South Eastern Nigeria.

 The study population included:-  HIV seropositive and  HIV seronegative TB patients receiving anti- Kochs therapy from January 2012 to June 2014.

 Sputum samples of TB patients were collected using the Directly Observed Treatment Short Course (DOTs) strategy specification.  This involves collecting three (03) samples: (1) on the spot assessment of patients, (2) Another sample early morning next day (3) A third sample as the patient submits the second sample. Samples are labeled 1,2, and 3 with patient’s identification parameters.

 Specimens were processed using the Ziehl- Neelsen staining method, fluorescent staining technique and confirmed using the Gene Xpert by Cepheid, especially HIV positive cases with cough.  The positive TB cases were referred to the DOTs clinic where they were commenced on anti-Kochs treatment with the Intensive phase using Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol for two months

 After the intensive phase of therapy, a repeat sputum microscopy was done to determine if the patient still had open TB, before continuation phase was started with Rifampicin and Isoniazid.   In patients who still had open TB, resistance was suspected and their samples were sent for Gene Xpert confirmation. (Category 1 failure)  (Gene Xpert confirms Tuberculosis infection but most importantly, it confirms resistance to Rifampicin).

 At the completion of treatment i.e. after 6 months of anti-Kochs administration, the patients were rechecked to ascertain if they were cured.  Any patient who still had a positive sputum sample was classified as Category 2 failure.

 Out of 732 diagnosed TB patients seen between 2012 till date, only six (6) had MDR-TB (0.82%). Five (5) of the 6 were HIV-negative while only one (1) patient was HIV-positive.  Of these 6 MDR-TB patients, two (2) have been completely treated, two (2) have died, one (1) patient is still receiving treatment while the other person is not on treatment because of the cost.

 In Nnamdi Azikiwe University Teaching Hospital, the anti-Kochs regimen used is 2 months intensive treatment phase with Rifampicin, Isoniazid, Pyrazinamide and Ethambutol, followed by 4 months continuation phase using Rifampicin and Isoniazid.  It is expected that by the end of the two months intensive phase of treatment, patients with open TB who adhered strictly to treatment should no longer have open TB.

 The conventional methods of detecting resistance involves growth/culture of Mycobacterium tuberculosis on liquid or solid culture medium and drug susceptibility testing. 10

 They should no longer have the bacilli in their sputum. A re-check of the sputum is done at this stage to know those who have responded well to treatment.  Patients who still have open TB are classified as treatment Category 1 failure.  Their sputum samples are further subjected to resistance testing using Gene Xpert which detects rifampicin resistance and may not detect isoniazid mono resistance.

 The prevalence of MDR-TB in the study was 0.82%. This is much less than what other researchers found. Dinic et al had 5.5% 11 in treatment naïve patients while Uzoewulu et al had 8%. 12  This could be due to the fact that Nnewi is an urban city and the teaching hospital is situated there so there is better access to medical care.  It is also pertinent to mention here that patients were closely observed/monitored during treatment.

 The result shows that most of the patients were Category 2 failure, and there was poor compliance to treatment irrespective of their HIV status.   It is important to note that although TB is a common opportunistic infection in HIV patients, HIV itself does not predispose to MDR-TB so long as the patient complies with anti-Kochs regimen

 MDR-TB poses a challenge in the management of HIV/TB co-infection because of poor treatment outcomes, higher treatment costs, lack of adequate treatment centers.  Prevention still remains the better option.  All hands must be on deck to prevent or reduce MDR-TB by monitoring TB patients on treatment. As is usually said “DOT the I’s and Cross the T’s” to prevent resistance.

 Only smear AFB and Gene Xpert testing were employed in the study.  DST was not done due to unavailability of culture centres, but the future work would incorporate that and others.  The study did not separate patients into those already on treatment and treatment naïve.

1.Sant’Anna FM, Velasque L, Costa MJ, Schmaltz CA, Morgado MG, Louren ḉ o MC, Grinsztejn B, Rolla VC. Effectiveness of highly active antiretroviral therapy (HAART) used concomitantly with rifampicin in patients with tuberculosis and AIDS. Brazilian Journal Of Infectious Diseases; 13:26-34.

2.Mark Gladwin, Bill Trattler. Clinical microbiology made ridiculously simple. Edition Page Selwyn PA, Sckell BM, Alcabes P, Friedland GH, Klein RS, Schoenbaum EE. High risk of active tuberculosis in HIV-infected drug users with cutaneous anergy. JAMA Jul ;268(4):504-9.

4. Harries AD et al. Deaths from tuberculosis in sub-Saharan African countries with a high prevalence of HIV-1. Lancet May 12;357(9267): Whalen CC et al. Impact of pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study in Uganda. AIDS Jun 16;14(9):

6.Federal Ministry of Health, Nigeria. Technical report: National HIV Seroprevalence Sentinel Survey, p World Health Organization. Global tuberculosis control: WHO report,2010.

8.Hirpa S, Medhin G, Girma B, Melese M, Mekonen A, Suarez P and Ameni G Determinants of Multidrug resistant tuberculosis in Patients who underwent first- line treatment in Addis Ababa: a case control study. BioMed Central Public Health. 13:782

9.World Health Organization (WHO): Drug- resistant tuberculosis now at record levels. int/mediacentre/news/releases/2010/drug_resi stant_tb_ /en/ int/mediacentre/news/releases/2010/drug_resi stant_tb_ /en/ 10.World Health Organization. The global MDR-TB and XDR-TB response plan

11.Dinic L et al. Genetic determinants of drug- resistant tuberculosis among HIV- infected patients in Nigeria. J Clin Microbiol Sep;50(9): doi: /JCM Uzoewulu NG, Ibeh IN, Lawson L, Umenyonu N, et al. (2014) Drug Resistant Mycobacterium tuberculosis in Tertiary Hospital South East, Nigeria. J Med Microb Diagnosis; 3:141. doi: /

13. Affolabi D, Adjagba OABG, Tanimomo- Kledjo B, Gninafon M, Anagonou SY, Portaels F. Antituberculosis drug resistance among new and previously treated pulmonary tuberculosis patients in Cotonou, Benin. Int J Tuberc Lung Dis. 2007;11(11):

14. Diandé S, Sangaré L, Kouanda S, Dingtoumda BI, Traoré AS. Drug Resistance of Mycobacterium tuberculosis Complex among Newly Diagnosed Tuberculosis Cases in Burkina Faso. WAJM. 2009;28(6): Sangaré L, Diandé S, Badoum G, Dingtoumda B, Traoré AS. Anti-tuberculosis drug resistance in new and previously treared pulmonary tuberculosis cases in Burkina Faso. Int J Tuberc Lung Dis. 2010;14(11): (Study 1)

16.Berhan A, Berhan Y, Yizengaw D. A meta- alysis of drug resistant tuberculosis in Sub- Saharan Africa: how strongly associated with previous treatment and HIV co-infection? Ethiop J Health Sci Nov;23(3):

Thank you.