Tuberculosis drug resistance in Bamako, Mali, from 2006 to 2014.

BACKGROUND: Although Drug resistance tuberculosis is not a new phenomenon, Mali remains one of the "blank" countries without systematic data. METHODS: Between 2006 and 2014, we enrolled pulmonary TB patients from local TB diagnostics centers and a university referral hospital in several observational cohort studies. These consecutive patients had first line drug susceptibility testing (DST) performed on their isolates. A subset of MDR was subsequently tested for second line drug resistance. RESULTS: A total of 1186 mycobacterial cultures were performed on samples from 522 patients, including 1105 sputa and 81 blood samples, yielding one or more Mycobacterium tuberculosis complex (Mtbc) positive cultures for 343 patients. Phenotypic DST was performed on 337 (98.3%) unique Mtbc isolates, of which 127 (37.7%) were resistant to at least one drug, including 75 (22.3%) with multidrug resistance (MDR). The overall prevalence of MDR-TB was 3.4% among new patients and 66.3% among retreatment patients. Second line DST was available for 38 (50.7%) of MDR patients and seven (18.4%) had resistance to either fluoroquinolones or second-line injectable drugs. CONCLUSION: The drug resistance levels, including MDR, found in this study are relatively high, likely related to the selected referral population. While worrisome, the numbers remained stable over the study period. These findings prompt a nationwide drug resistance survey, as well as continuous surveillance of all retreatment patients, which will provide more accurate results on countrywide drug resistance rates and ensure that MDR patients access appropriate second line treatment.

Performance comparison of a pair of Lowenstein-Jensen media supplemented with pyruvate or glycerol, and the combination of both supplements in a single Lowenstein-Jensen medium for the growth support of the Mycobacterium Tuberculosis complex.

OBJECTIVE/BACKGROUND: To evaluate the performance of Lowenstein-Jensen medium (LJ) supplemented with pyruvate and glycerol (LJPG), compared with LJ supplemented with pyruvate (LJP) or glycerol (LJG) for the support of mycobacterial growth. METHOD: This study used 100 Ziehl-Neelsen-confirmed positive mycobacterium growth indicator tube 960 culture samples that were obtained from clinical samples during routine diagnosis. All cultures were inoculated in parallel on LJG/LJP and on LJGP, which were incubated and read weekly for the evidence of growth. The mycobacterial recovery rate, contamination rate, and time to detection were compared. RESULT: The recovery rate for LJG/LJP and for LJPG was 90% (90 samples) and 88% (88 samples), respectively (kappa p-value, 0.9). There was no significant difference in the contamination rate, which was 8% (8 samples) for LJG/LJP and 9% (9 samples) for LJPG. Mycobacterial growth was faster in LJPG (1.6weeks) than in LJG/LJP (2weeks). CONCLUSION: A single LJPG slope was not significantly different, compared with the usual pair of LJG or LJP slopes. This is a promising new culturing approach that could be used in Mycobacterium africanum-endemic in West African countries. It significantly reduces labor time and consumable costs and more quickly detects the M. tuberculosis complex.

Drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis in Ibadan, Nigeria.

BACKGROUND: Information on TB drug resistance profiles and its' associated risk factors are scarce in Nigeria despite the large burden of disease in the country. The study was designed to report drug resistance profiles of new- and previously treated patients with pulmonary tuberculosis (TB) in Ibadan, Nigeria. METHOD: Sputum from consenting pulmonary TB patients were collected and cultured for Mycobacterium tuberculosis (Mtb) at the TB laboratory of the University College Hospital, Ibadan, Nigeria using standard method. Mtb were stored and sent for drug susceptibility testing against first and second-line anti-TB drugs at the MRC Unit, The Gambia and at the Institute of Tropical Medicine, Antwerp, Belgium using BACTEC MGIT 960 and proportion method on solid medium respectively. RESULTS: Of 238 Mtb collected, 124 (52.1%) were viable, 102 (59.65%) non-viable while 12 (7.02%) were contaminated. About half (58.87%) of the Mtb were from previously treated patients, 40 (32.26%) were from new patients while treatment history of 1.1 (8.87%) were unknown. Forty-seven (37.90%) of the 124 Mtb. tested were multidrug resistant (MDR) out of which, 40 (85.10%) were from previously treated patients.. HIV prevalence was 8.69%. Of the 17 MDR-TB from previously treated cases tested for second-line drugs, four (23.53%) were resistant to fluoroquinolones or injectable agents, 13 (76.47%) were susceptible while none was resistant to both of these classes of drugs. CONCLUSION: MDR-TB in Ibadan already demonstrates resistance to second line anti-TB drugs hence management of MDR-TB patients should be strengthened to prevent emergence of extensively drug-resistant TB (XDR-TB).

Essential role of choline for pneumococcal virulence in an experimental model of meningitis.

OBJECTIVES: The goal of the present study was to elucidate the contribution of the newly recognized virulence factor choline to the pathogenesis of Streptococcus pneumoniae in an animal model of meningitis. RESULTS: The choline containing strain D39Cho(-) and its isogenic choline-free derivative D39Cho(-)licA64--each expressing the capsule polysaccharide 2--were introduced intracisternally at an inoculum size of 10(3) CFU into 11 days old Wistar rats. During the first 8 h post infection both strains multiplied and stimulated a similar immune response that involved expression of high levels of proinflammatory cytokines, the matrix metalloproteinase 9 (MMP-9), IL-10, and the influx of white blood cells into the CSF. Virtually identical immune response was also elicited by intracisternal inoculation of 10(7) CFU equivalents of either choline-containing or choline-free cell walls. At sampling times past 8 h strain D39Cho(-) continued to replicate accompanied by an intense inflammatory response and strong granulocytic pleiocytosis. Animals infected with D39Cho(-) died within 20 h and histopathology revealed brain damage in the cerebral cortex and hippocampus. In contrast, the initial immune response generated by the choline-free strain D39Cho(-)licA64 began to decline after the first 8 h accompanied by elimination of the bacteria from the CSF in parallel with a strong WBC response peaking at 8 h after infection. All animals survived and there was no evidence for brain damage. CONCLUSION: Choline in the cell wall is essential for pneumococci to remain highly virulent and survive within the host and establish pneumococcal meningitis.