Predominance of the Mycobacterium tuberculosis Beijing strain amongst children from a high tuberculosis burden township in South Africa.

The objective was to determine the molecular epidemiology and drug susceptibility patterns of Mycobacterium tuberculosis (MTB) of children and their household contacts (HHC) in Umlazi, a high TB-burden township in South Africa. Sixty eight MTBRifPLUS positive TB-infected children (TIC) (≤14 years) and 111 HHC were enrolled. Drug susceptibility testing (DST) was performed on sputum samples using the proportion method and GenoType® MTBDR. Genotyping of MTB was conducted using IS6110-restriction fragment length polymorphism (RFLP) and spoligotyping. Rifampicin (RIF) susceptibility was observed in 67/68 TIC. GenoType® MTBDRplus and phenotypic DST identified drug resistant strains in five of 16 culture-confirmed TIC. The Beijing strain was identified in six and the F15/LAM4/KZN strain in one of the 13 TIC respectively. Four patients with unknown RFLP strains belonged to spoligoclades S, T1, T3 variant and X2. The S-lineage and an unknown strain were identified in two HHC. MDR-TB and pre-XDR-TB were identified in one HHC each. Household transmission could not be determined as none of the culture-confirmed TIC resided with the six culture-confirmed contacts. The predominance of the hypervirulent Beijing strain and presence of drug-resistant strains must be considered in the implementation of effective TB control strategies and development of efficacious vaccines.

Laboratory diagnosis of tuberculous meningitis in human immunodeficiency virus-seropositive patients: Correlation with the uniform case definition.

BACKGROUND: Laboratory confirmation of the diagnosis of tuberculous meningitis (TBM) has always been problematic. Using the uniform case definition suggested by Marais et al., we determined the sensitivity of a variety of laboratory tests. METHODS: Human immunodeficiency virus (HIV)-seropositive patients suspected of having subacute meningitis were included in the study. Using the uniform case definition, patients were divided into possible and probable cases of TBM. The following specific tests were done on the cerebrospinal fluid (CSF): layered Ziehl-Neelsen (ZN) staining, CSF culture and a panel of nucleic acid amplification tests (NAAT) consisting of the GenoType MTBDRplus assay, Cepheid Xpert MTB/RIF, the MTB Q-PCR Alert (Q-PCR) and the loop-mediated isothermal amplification (LAMP) assay. The sensitivity of each test was compared to the case definition and to each other. RESULTS: A total of 68 patients were evaluated. Using the uniform case definition only, without any of the specific laboratory tests, there were 15 probable cases (scores > 12) and 53 possible cases (scores 6-11) of TBM. When the uniform case definition was tested against any laboratory test, 12 of the 15 (80%) probable cases and 26 of the 53 (49.1%) possible cases had laboratory confirmation. When each test was compared to any other test, the sensitivities for the Xpert MTB/RIF, GenoType MTBDRplus, CSF culture, Q-PCR, LAMP and ZN layering were 63.2 (46.0-78.2), 76.3 (59.8-88.6), 65.7 (47.8-80.9), 81.1 (64.8-92.0), 70.3 (53.0-84.1) and 55.6 (38.1-72.1), respectively. CONCLUSION: In this study, the GenoType MTBDRplus and the Q-PCR tests performed better than the Xpert MTB/RIF. Because the Xpert MTB/RIF is not good enough to 'rule out' TBM, a negative result should be followed up by another NAAT, such as the GenoType MTBDRplus or Q-PCR. The LAMP assay may be considered as the first test in resource-poor settings. At the time of the study, we did not have access to the Xpert MTB/RIF Ultra, which has now been recommended by the World Health Organization as the test of first choice. However, even this test has a similar limitation as the Xpert MTB/RIF, with two recent studies showing variable results.

Incidence and Geographic Distribution of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal Province, South Africa.

South Africa is experiencing a widespread drug-resistant tuberculosis epidemic, although data are limited regarding the current situation. This study finds that the extensively drug-resistant tuberculosis (XDR-TB) incidence in KwaZulu-Natal increased to 3.5 cases/100,000 (776 cases) in 2011-2012. XDR-TB cases are widely distributed geographically, with the majority of districts experiencing a rise in incidence.