Discordant drug susceptibility for mycobacterium tuberculosis within families.

Children with presumed tuberculosis who are in contact with a multidrug-resistant source case should be treated according to the drug susceptibility of the source case's isolate. However, it is important to obtain a microbiologic diagnosis as it is possible for the child to have a different susceptibility profile to the source case. We present 2 such cases

Original Article Analysis of Isoniazid, Streptomycin and Ethambutol resistance in

Background: Drug-resistant tuberculosis is a major problem worldwide. Based on the knowledge of specific mutations occurring in Mycobacterium tuberculosis genome, drug resistance can be detected earlier. The aim of this study was to determine the prevalence of the most common mutations associated with resistance to Isoniazid (INH), Streptomycin (SM) and Ethambutol (EMB) in Mycobacterium tuberculosis isolates from Morocco in order to select target mutations to develop tests for rapid detection of drug-resistant Mycobacterium tuberculosis Moroccan isolates. Methodology: A total of 199 M. tuberculosis isolates collected from the National Tuberculosis Reference Laboratory in Morocco were subject to katG, inhA, rrs, rpsL and emb mutation analysis by PCR probe-based assay. The genotypic results were then compared to drug susceptibility testing results for the corresponding drugs. Results: Among 66 phenotypically INH resistant isolates, 80.3 % (53/66) were found to be genotypically INH resistant from which 77.3% (51/66) and 3 % (2/66) had respective mutations in katG315 and inhp-15 codons. Of the 58 phenotypically SM resistant isolates, genotypic SM resistance was confirmed in 17.2 % (10/58) cases. Nucleotide mutations at codons 43 and 88 of rpsL gene and at codon 512 of rrs gene were found respectively in 12.1 % (7/58); 1.7 % (1/58) and 3.4 % (2/58) of the phenotypically SM resistant Mycobacterium tuberculosis isolates. Finally, mutations at codon 306 of embB gene were identified in 42.3 % (11/26) of Mycobacterium tuberculosis isolates phenotypically EMB resistant

Beijing and Haarlem Genotypes Are Overrepresented among Children with Drug-Resistant Tuberculosis in the Western Cape Province of South Africa

Drug resistance among children with culture-confirmed tuberculosis (TB) provides an accurate measure of transmitted drug resistance within the community. We describe the genotype diversity in children with culture-confirmed TB and investigate the relationship between genotype and drug resistance. A prospective study was conducted from March 2003 through August 2005 at Tygerberg Children's Hospital, in the Western Cape Province of South Africa. All children (<13 years of age) diagnosed with culture-confirmed TB were included. Genotype analysis and phenotypic drug susceptibility testing were performed on the first culture-positive isolate from each patient. Mutation analysis was performed on all drug-resistant isolates. Spoligotyping was successfully performed on isolates from 391/399 (98%) children diagnosed with culture-confirmed TB. Drug susceptibility testing was also performed on 391 isolates; 49 (12.5%) were resistant to isoniazid, and 20 (5.1%) of these were resistant to both isoniazid and rifampin. Beijing was the most common genotype family, identified in 130/391 (33.2%) cases, followed by LAM in 114/391 (29.2%) cases. The presence of both Beijing and Haarlem genotype families was significantly associated with drug resistance (26/49 [53.1%] versus 113/342 [33.0%]; odds ratio, 1.7; 95% confidence interval, 1.0 to 2.9). The high prevalence of Beijing and LAM in children with culture-confirmed TB reflects considerable transmission of these genotype families within the community. The overrepresentation of Beijing and Haarlem genotype families in children with drug-resistant TB demonstrates their contribution to transmitted drug resistance and their potential importance in the emergent drug-resistant TB epidemic

Drug susceptibility testing using molecular techniques can enhance diagnosis in a community with a high tuberculosis incidence

Background: Sputum samples were collected from tuberculosis patients in a high tuberculosis incidence area in the Western Cape, South Africa. The aim of this study was to evaluate the performance and time to diagnosis of a genotypic drug susceptibility testing method.Methodology: During June 2000 and November 2003, a total of 1,540 samples were sent for drug susceptibility testing (DST) to the national health laboratory services, and of those, a phenotypic DST result was obtained for 1,373 samples whereas a genotypic DST result was obtained for 1,301 of 1,540 samples. Performance-based calculations were done on 1,244 samples for which both a phenotypic and genotypic DST result was available.Results: The reproducibility of the genotypic and phenotypic DST methods was 97% and 95%, respectively. The sensitivity and specificity of the genotypic DST method was 68% and 99% for Isoniazid and 87% and 99% for Rifampicin, respectively. Smear gradation was found to influence the performance of the genotypic DST method. The genotypic DST method gave accurate DST results for 75% of the samples within 20 days (range, 15-25), whereas the phenotypic DST results were only available for 75% of the samples after 38 days (range, 26-115) (p<0.001).Conclusion: This study showed that the genotypic DST could improve tuberculosis control by rapid diagnosis of drug resistant tuberculosis. This finding may have important implications for the control of drug resistant tuberculosis as it may reduce the chance for further transmission events