Multi Drug Resistant Tuberculosis (MDR-TB) Among HIV-Positive Patients in A Tertiary Health Institution in South Eastern Nigeria
Tuberculosis (TB) is the most common opportunistic infection in HumanImmunodeficiencyVirus (HIV)-infected patients.1HIV-infectedpatients are known tohave 10% risk of reactivation of TB per year.2They are morelikely to die fromTBthan HIV negativepatients.3
InSub-SaharanAfrica, 30% of HIV-infected patients who are diagnosed with TB die 12 months after the initiation oftreatment.4,5Nigeriahasa HIVprevalence of 3.6% and has the world’s third largest TB burden.It isalso known that 26% of TB patients in Nigeria have HIV co-infection7.
MultiDrug resistant Tuberculosis (MDR-TB) is tuberculosis that is resistant to at least the first line anti-TB drugs,Rifampicinand Isoniazid.8The emergence of Multi Drug Resistant tuberculosis (MDR-TB) is of concern to both patients and clinicians because of the attendant increased mortality and morbidity.
Todetermine the prevalence of MDR-TB among HIVseropositiveandseronegativepatients receiving treatment in Nnamdi Azikiwe University Teaching Hospital (NAUTH),Nnewi,AnambraState,South EasternNigeria.
The study population included:-HIV seropositive andHIVseronegativeTB patients receivinganti-Kochstherapy from January 2012 toJune 2014.
Materials and method
Sputum samples of TB patients were collected using theDirectlyObservedTreatmentShortCourse(DOTs)strategy specification.Thisinvolves collecting three (03)samples: (1) onthe spot assessment of patients,(2) Anothersample early morning nextday(3) A thirdsample as the patient submits the second sample. Samples are labeled 1,2, and 3 with patient’s identification parameters.
Specimens were processed using theZiehl-Neelsenstaining method, fluorescent staining technique and confirmed using the GeneXpertbyCepheid, especially HIV positive cases with cough.ThepositiveTB cases werereferred to the DOTs clinic where they were commenced on anti-Kochstreatment with the Intensive phase using Rifampicin, Isoniazid, Pyrazinamide, andEthambutolfor two months
After the intensive phase of therapy, a repeat sputum microscopy was done to determine if the patient still had openTB, before continuation phase was started with Rifampicin andIsoniazid.Inpatients who still had open TB, resistance was suspected and their samples were sent for GeneXpertconfirmation.(Category 1 failure)(GeneXpertconfirms Tuberculosis infection but most importantly, it confirms resistance to Rifampicin).
At the completion of treatment i.e. after 6 months of anti-Kochsadministration, 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) ofthe 6wereHIV-negativewhile only one(1) patient wasHIV-positive.Of these 6 MDR-TB patients, two (2) havebeen 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.
InNnamdiAzikiweUniversity Teaching Hospital, theanti-Kochsregimen used is 2 months intensive treatment phase with Rifampicin, Isoniazid, Pyrazinamide andEthambutol, followed by 4 months continuation phase using Rifampicin andIsoniazid.Itis expected that by the end of thetwomonths intensive phase of treatment, patients with open TB who adhered strictly to treatment shouldno longer have open TB.
The conventional methods of detecting resistance involves growth/culture ofMycobacterium tuberculosison liquid or solid culturemedium and drug susceptibility testing.10
They shouldno longer have the bacilli in theirsputum. A re-checkof the sputum is done at this stage to know those who have responded well to treatment.Patientswho still have open TB are classified as treatment Category 1 failure.Theirsputum samples are further subjected to resistance testing using GeneXpertwhich 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.Dinicet al had 5.5%11in treatment naïve patients whileUzoewuluet al had 8%.12This could be due to the fact thatNnewiis an urban city andthe teachinghospital 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 wereCategory2 failure, and there was poor compliance to treatment irrespective oftheir HIVstatus.Itis important to note thatalthough TBis a common opportunistic infection in HIV patients, HIV itself does not predispose to MDR-TB so long as the patientcomplieswithanti-Kochsregimen13-16.
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 GeneXperttesting were employed in the study.DST was not done due to unavailability of culturecentres, 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’AnnaFM,VelasqueL,CostaMJ,SchmaltzCA,MorgadoMG,LourenḉoMC,GrinsztejnB, RollaVC.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, BillTrattler. Clinical microbiologymade ridiculouslysimple. Edition 3. 2006. Page 134.3. Selwyn PA,SckellBM,AlcabesP,FriedlandGH, Klein RS,SchoenbaumEE.High risk of active tuberculosis inHIV-infecteddrug users with cutaneousanergy.JAMA. 1992 Jul 22-29;268(4):504-9.
Harries AD et al.Deathsfrom tuberculosis in sub-Saharan African countries with a high prevalence of HIV-1.Lancet. 2001 May 12;357(9267):1519-23.5 Whalen CC et al.Impactof pulmonary tuberculosis on survival of HIV-infected adults: a prospective epidemiologic study inUganda. AIDS. 2000 Jun 16;14(9):1219-28.
6. FederalMinistry ofHealth, Nigeria. Technical report: NationalHIVSeroprevalenceSentinelSurvey,2010. p1-110.7. WorldHealthOrganization. Globaltuberculosis control: WHOreport,2010.
8.HirpaS,MedhinG,GirmaB,MeleseM,MekonenA, Suarez P andAmeniG .2013. Determinants of Multidrug resistant tuberculosis in Patients who underwent first-line treatment in Addis Ababa: a case control study.BioMedCentral Public Health. 13:782
9. WorldHealth Organization (WHO): Drug-resistant tuberculosis now at recordlevels.http://www.who-int/mediacentre/news/releases/2010/drug_resistant_tb_20100318/en/10. WorldHealthOrganization.The global MDR-TB and XDR-TB response plan.2007.
11.DinicL et al. Genetic determinants of drug- resistant tuberculosis among HIV-infected patients in Nigeria. JClinMicrobiol.2012 Sep;50(9):2905-9.doi: 10.1128/JCM.00982-1212.UzoewuluNG,IbehIN, LawsonL,UmenyonuN,et al. (2014) Drug ResistantMycobacterium tuberculosisin Tertiary HospitalSouthEast,Nigeria.J MedMicrobDiagnosis;3:141.doi: 10.4172/2161-0703.1000141
13.AffolabiD,AdjagbaOABG,Tanimomo-KledjoB,GninafonM,AnagonouSY,PortaelsF.Antituberculosisdrug resistance among new and previously treated pulmonary tuberculosis patients inCotonou, Benin.IntJTubercLung Dis. 2007;11(11):1221-1224.
DiandéS,SangaréL,KouandaS,DingtoumdaBI,TraoréAS. Drug Resistance ofMycobacterium tuberculosisComplex among Newly Diagnosed Tuberculosis Cases in Burkina Faso. WAJM. 2009;28(6):353-357..SangaréL,DiandéS,BadoumG,DingtoumdaB,TraoréAS. Anti-tuberculosis drug resistance in new and previouslytrearedpulmonary tuberculosis cases in Burkina Faso.IntJTubercLung Dis. 2010;14(11):1424-1429. (Study 1)
16.BerhanA,BerhanY,YizengawD. A meta-alysisof drugresistant tuberculosis in Sub-Saharan Africa: how strongly associated with previous treatment and HIV co-infection? Ethiop J Health Sci. 2013 Nov;23(3):271-82.