Rifampicin mono-resistance in Mycobacterium tuberculosis in KwaZulu-Natal, South Africa: a significant phenomenon in a high prevalence TB-HIV region.
METHODS
The dual epidemics of HIV-TB including MDR-TB are major contributors to high morbidity and mortality rates in South Africa. Rifampicin (RIF) resistance is regarded as a proxy for MDR-TB. Currently available molecular assays have the advantage of rapidly detecting resistant strains of MTB, but the GeneXpert does not detect isoniazid (INH) resistance and the GenoTypeMTBDRplus(LPA) assay may underestimate resistance to INH. Increasing proportions of rifampicin mono-resistance resistance (RMR) have recently been reported from South Africa and other countries.


OBJECTIVE
This laboratory based study was conducted at NHLS TB Laboratory, Durban, which is the reference laboratory for culture and susceptibility testing in KwaZulu-Natal. We retrospectively determined, for the period 2007 to 2009, the proportion of RMR amongst Mycobacterium tuberculosis (MTB) isolates, that were tested for both RIF and INH, using the gold standard of culture based phenotypic drug susceptibility testing (DST). Gender and age were also analysed to identify possible risk factors for RMR.


METHODS
MTB culture positive sputum samples from 16,748 patients were analysed for susceptibility to RIF and INH during the period 2007 to 2009. RMR was defined as MTB resistant to RIF and susceptible to INH. For the purposes of this study, only the first specimen from each patient was included in the analysis.


RESULTS
RMR was observed throughout the study period. The proportion of RMR varied from a low of 7.3% to a high of 10.0% [overall 8.8%]. Overall, males had a 42% increased odds of being RMR as compared to females. In comparison to the 50 plus age group, RMR was 37% more likely to occur in the 25-29 year age category.


CONCLUSIONS
We report higher proportions of RMR ranging from 7.3% to 10% [overall 8.8%] than previously reported in the literature. To avoid misclassification of RMR, detected by the GeneXpert, as MDR-TB, culture based phenotypic DST must be performed on a second specimen, as recommended by the SA NDOH TB guidelines as well as WHO. We suggest that two sputum samples should be obtained at the first visit. The second sputum sample should be stored at 4°C. The latter sample is then readily available for performing additional DST (phenotypic or genotypic) for 2nd lines drugs, resulting in a decreased waiting period for DST results to become available.
National Health Laboratory Services, University of KwaZulu-Natal, Durban, South Africa ; Medical Microbiology Department, University of KwaZulu-Natal, Durban, South Africa.
Yacoob Mahomed
YM
Coovadia
Sharana
S
Mahomed
Melendhran
M
Pillay
Lise
L
Werner
Koleka
K
Mlisana
D000293:Adolescent; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000494:pharmacology* / Q000627:therapeutic use; D060085:Coinfection / Q000453:epidemiology*; D024881:Drug Resistance, Bacterial; D005260:Female; D015658:HIV Infections / Q000453:epidemiology*; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D015995:Prevalence; D012189:Retrospective Studies; D012293:Rifampin / Q000494:pharmacology* / Q000627:therapeutic use; D012307:Risk Factors; D013019:South Africa / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology; D055815:Young Adult
D000904:Antibiotics, Antitubercular; D012293:Rifampin