Diversity of Mycobacterium tuberculosis strains in Nairobi, Kenya

Setting: Tuberculosis (TB) patients attending 16 public health facilities in Nairobi, Kenya. Objective: To determine the Mycobacterium tuberculosis (M.tuberculosis) strain families circulating in Nairobi, Kenya. Methods: Sputum specimens from consecutive new and previously treated smear positive pulmonary TB patients were collected between February and August 2010 and cultured on Lowenstein9Jensen media. Spoligotyping was done on DNA extracted from the first isolate of each patient. The international spoligotype data base (SpolDB4) was used to group isolates into strain families. Results: Fourty seven different strain families were identified from 536 isolates. The principal groups were; CAS1_KILI 96/536 (17%), T1 69/536 (12%), Beijing 65/536 (12%), LAM9 46/536 (9% ), LAM3 & S/Conversant 37/536 (7% ), LAM11_ZWE 26/536 (5%), CAS1_DELHI 24/536 (4%) and T2 24/536 (4%). Others identified and are found in the SpolDB4 were 113/536 (21%). A possible new M.tuberculosis strain family was identified with 21/536 (4%) isolates which was designated as Nairobi subtype. Others identified not previously included in the SpolDB4 accounted for 15/536 (3%). Conclusion: We found a diverse array of M.tuberculosis strain families which could be indicative of a cosmopolitant polulation with frequent migration that may suggest that the dorminant strain families may have been present in the population for an extended period of time or on going transmision of closely related strains families. The emergence of the Beijing strains poses a serious threat to TB control due to its high virulence and frequent association with multidrug resistance. We therefore call for strenghthening efforts on early case finding through enhanced public health education campains and provision of accessible diagnostic services with enhanced treatment compliance

inhA promoter mutations: A gateway to extensively drug-resistant tuberculosis in South Africa?

SETTING: Western Cape and Eastern Cape Provinces, South Africa. OBJECTIVE: To assess the potential association between the evolution of extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis and mutations in the inhA promoter or the katG gene. DESIGN: Analysis of the frequency distribution of isoniazid (INH) resistance conferring mutations in a population sample of drug-resistant isolates of M. tuberculosis. RESULTS: In the Western Cape and Eastern Cape Provinces, the percentage of isolates exhibiting inhA promoter mutations increased significantly from respectively 48.4% and 62.4% in multidrug-resistant tuberculosis (MDR-TB) isolates to 85.5% and 91.9% in XDR isolates. Data from the Western Cape revealed that significantly more XDR-TB isolates showed mutations in the inhA promoter than in katG (85.5% vs. 60.9%, P < 0.01), while the respective proportions were equal for INH-resistant non-MDR-TB isolates (∼30%). CONCLUSIONS: inhA promoter mutations are strongly associated with XDR-TB in South Africa. We suggest that this is due to the dual resistance to ethionamide and (low-dose) INH conferred by inhA promoter mutations. The use of molecular probe assays such as the Geno-Type® MTBDRplus assay, which allows the detection of inhA promoter mutations, could enable treatment regimens to be adjusted depending on the pharmacogenetic properties of the mutations detected. © 2011 The Union.Articl

Population structure of multi- and extensively drug-resistant Mycobacterium tuberculosis strains in South Africa

Genotyping of multidrug-resistant (MDR) Mycobacterium tuberculosis strains isolated from tuberculosis (TB) patients in four South African provinces (Western Cape, Eastern Cape, KwaZulu-Natal, and Gauteng) revealed a distinct population structure of the MDR strains in all four regions, despite the evidence of substantial human migration between these settings. In all analyzed provinces, a negative correlation between strain diversity and an increasing level of drug resistance (from MDR-TB to extensively drug-resistant TB [XDR-TB]) was observed. Strains predominating in XDR-TB in the Western and Eastern Cape and KwaZulu-Natal Provinces were strongly associated with harboring an inhA promoter mutation, potentially suggesting a role of these mutations in XDR-TB development in South Africa. Approximately 50% of XDR-TB cases detected in the Western Cape were due to strains probably originating from the Eastern Cape. This situation may illustrate how failure of efficient health care delivery in one setting can burden health clinics in other areas. Copyright © 2012, American Society for Microbiology. All Rights Reserved

Higgs boson potential at colliders: Status and perspectives

International audienceThis document summarises the current theoretical and experimental status of the di-Higgs boson production searches, and of the direct and indirect constraints on the Higgs boson self-coupling, with the wish to serve as a useful guide for the next years. The document discusses the theoretical status, including state-of-the-art predictions for di-Higgs cross sections, developments on the effective field theory approach, and studies on specific new physics scenarios that can show up in the di-Higgs final state. The status of di-Higgs searches and the direct and indirect constraints on the Higgs self-coupling at the LHC are presented, with an overview of the relevant experimental techniques, and covering all the variety of relevant signatures. Finally, the capabilities of future colliders in determining the Higgs self-coupling are addressed, comparing the projected precision that can be obtained in such facilities. The work has started as the proceedings of the Di-Higgs workshop at Colliders, held at Fermilab from the 4th to the 9th of September 2018, but it went beyond the topics discussed at that workshop and included further developments. FERMILAB-CONF-19-468-E-T, LHCHXSWG-2019-00