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The authors report the results of a survey on the possible role of human Mycobacterium in the ganglio-pulmonary tuberculosis of bovines. 232 bovines seized in the abattoirs of Algiers over a period of 8 months were concerned by this work. The results obtained showed that microscopic examination was negative in 50% of cases. This result was expected as ganglionary lesions are paucibacillary. Cultures were also negative in 50% of cases, 25% of them were contaminated. 50% rate of positive cultures was obtained when Loewenstein-Jensen medium with 1% pyruvate was used. Morphological and biochemical identification showed that out of 113 strains, 7 were Mycobacterium tuberculosis (6.2%). In seems therefore that Mycobacterium tuberculosis, human pathogen, is also pathogenic for bovines. Its frequent occurrence could be explained by the high prevalence of human tuberculosis in Algeria.
PURPOSE: We evaluated the performance of the Abbott RealTime Mycobacterium tuberculosis (MTB) PCR (RT MTB) on bronchoscopic specimens using conventional culture as the reference standard in a low-Tuberculosis (TB) prevalence setting. METHODS: A total of 6,988 specimens (4,682 bronchial aspirates [BAS] and 2,306 bronchoalveolar lavages [BAL]) from 4,118 patients with suspected pulmonary TB were included. When BAS and BAL specimens from the same bronchoscopy procedure were available, these were mixed 1:1 prior to culture inoculation and PCR testing. Following processing, specimens were inoculated into a Löwenstein-Jensen and a Bactec MGIT 960 tube and incubated at 37 °C for 3 months and at 35 °C for 8 weeks, respectively. RT MTB was performed as indicated by the manufacturer. RT MTB targets the insertion sequence IS6110 and the protein antigen B (PAB) gene, both highly conserved within the Mycobacterium tuberculosis complex. Whole genome Next generation sequencing of clinical MTBC isolates was performed when indicated. RESULTS: Among the 104 culture-positive specimens, 84 (1.2%) were detected by PCR. Additionally, 16 specimens (0.3% of all samples), from 16 patients, were PCR-positive despite negative culture results. Conversely, 20 specimens (0.4% of all samples), from 19 patients, were culture-positive but not detected by PCR. No significant differences were found between PCR-positive and PCR-negative specimens with respect to the number of IS6110 copies per isolate or PAB gene sequences (P = 0.69). Finally, there were 4,683 specimens (97.4%) from the remaining 4,014 patients tested PCR-negative/Culture-negative. Following the resolution of discrepancies based on clinical grounds the sensitivity and specificity of RT MTB were 83.9% (CI 95%, 76.0-90.0) and 99.9% (CI 95%, 99.9-99.9), respectively. These results exceed the minimum performance requirements defined in the WHO Target Product Profiles for molecular TB diagnostics. Although RT MTB is not a point-of-care test but rather a moderate-complexity automated NAAT, it is recommended by WHO as part of the Abbott RealTime MTB/MTB RIF-INH testing algorithm, in which MTBC detection by RT MTB is followed by reflex testing with the MTB RIF/INH assay for detection of rifampicin and isoniazid resistance. CONCLUSION: RT MTB shows a good performance on bronchoscopic specimens.
Evidence suggests that in humans tuberculous disease usually arises at apical or subapical sites in the lungs seeded as a consequence of an early bacillemic phase of the infection. This study examined the fate of bacilli transported via the bloodstream to metastatic sites in the lungs of guinea pigs after aerosol infection with approximately two viable virulent Mycobacterium tuberculosis. The results revealed that, even after logarithmic-phase multiplication of bacilli in primary lesions had been terminated, bacilli seeded via the bloodstream to metastatic sites in the lung were able to multiply. These observations, made in an animal model that mimics the conditions under which tuberculosis develops in human subjects, challenge the relevance of systemic macrophage activation in experimental airborne tuberculosis in guinea pigs.
Tuberculosis (TB) is a deadly disease that claims the lives of over a million people each year worldwide. The Bacille Calmette-Guérin vaccine has long been used to protect against TB, but it produces variable effects across different populations and fails to protect against adult pulmonary TB. Therefore, there is an urgent need for alternative vaccines that can offer better protection. We have developed a strategy for the rational deletion of virulence-related genes in Mycobacterium tuberculosis (Mtb) to create hyperattenuation that also enhances immunogenicity. Previously, we generated both single (∆fbpA) and double knockout (DKO) (∆fbpA-∆sapM) mutants of Mtb and assessed their immunogenicity and efficacy using mice. Herein, we have created triple knockout (TKO) and quadruple knockout (QKO) strains to enhance the immunogenicity and safety of the DKO strain by deleting the zmp1 and dosR genes. The resulting TKO strains, TKO-Z (∆fbpA-∆sapM-∆zmp1) and TKO-D (∆fbpA-∆sapM-∆dosR), and the QKO strain (∆fbpA-∆sapM-∆zmp1-∆dosR), were evaluated for their immunogenicity and safety in mice. Whereas TKO-Z and QKO strains exhibited superior immunogenicity compared to the DKO strain, their protective efficacy in mice was comparable. However, survival studies involving SCID mice indicated that the QKO strain was highly attenuated. Therefore, rational deletion of genes in Mtb seems to be an innovative approach for developing safer and more efficacious vaccines against TB.
The Mycobacterium tuberculosis complex (MTBC) phylogenetic lineages 1-4 (L1-L4) are the main causes of human tuberculosis (TB). Until now, most of the focus in the TB field has been on MTBC L2 and L4, as these two lineages are geographically widespread and have been repeatedly associated with multidrug resistance. By comparison, MTBC L1 has received little attention, partially because of its restricted geographical range that mainly includes low- to middle-income countries in South and Southeast Asia, and East Africa. However, recent estimates indicate that MTBC L1 is in fact the most common cause of human TB in terms of absolute numbers of TB patients, particularly among several high TB burden countries. As more L1 strains are being sampled in L1-endemic countries, the high genetic diversity of this geographically restricted MTBC lineage is slowly uncovered. This discovery has also impacted L1 nomenclature, which has been modified as new distinct L1 clades were identified. In parallel to the genomic discoveries ushered by progress in whole genome sequencing, clinical researchers have also studied several phenotypes that better describe L1 TB disease. L1 strains have been shown to have increased vulnerability to oxidative stress, which was associated with decreased virulence in animal and in vitro models. L1 infection also shows possible association with extrapulmonary TB and asymptomatic TB. However, despite belonging to the same lineage, L1 strains display phenotypic diversity that can be attributed to high within-lineage genetic diversity and possibly the interaction of different L1 genotypes with different human host genotypes. Among the clinical phenotypes that show heterogeneity are bacterial factors, immune profiles, and clinical virulence. The traditional view regarding the reduced transmissibility in L1 is now being challenged by new data indicating that L1 may be as transmissible as L2 or L4. Lastly, although historically referred to as being negatively associated with drug resistance, there is indication that the contribution of L1 to TB drug resistance is significant and that it may evolve drug resistance in ways distinct from those of other MTBC lineages.
A rigimen of rifampicin plus isoniazid, supplemented in the first two months by ethambutol or streptomycin, was given for six, nine, twelve, or eighteen months in a controlled study of 696 patients with culture-positive pulmonary tuberculosis. The results obtained in the thirty-three months since the start of treatment when all the patients in the six-month and nine-month groups had completed at least two years and those in the twelve-month group had completed twenty-one months of post-chemotherapy follow-up revealed no relapses among patients receiving nine months chemotherapy and a 1% relapse-rate in the twelve-month group. The same regimen given for only six months resulted in a relapse-rate of 5% during the subsequent twenty-seven months. There were adverse effects with streptomycin but not with ethambutol. It is concluded that treatment with rifampicin plus isoniazid for nine months, supplemented by ethambutol in a dose of 25 mg/kg for the first two months, is now acceptable as standard chemotherapy for pulmonary tuberculosis in Britain.
Spoligotyping was undertaken in 65 multiple-drug-resistant Mycobacterium tuberculosis isolates from Bombay, India. The spoligotype patterns showed seven closely related clusters, a cluster with 2 Beijing-like isolates, and unique spoligotypes (43%). Of the clusters, one with 29% of all the isolates suggested transmission of a dominant resistant clone.
Genitourinary tuberculosis should be managed on an outpatient basis, patients being seen once a week. The treatment of choice is a short-course regimen comprising 2 months of either three or fours drugs - streptomycin, rifampicin, isoniazid, and pyrazinamide - followed by isoniazid and rifampicin three times a week for either 2 or 4 months, depending on the severity of the lesion. Patients should be followed-up, normally for one year, and be told to report to their doctors if they have any recurrence of urinary symptoms. However, if they have renal calcification they should be followed-up as for any other case of calcification and seen annually for at least 10 years. Surgery still has an important part to play in the present management. Radical surgery, nearly always nephrectomy or epididymectomy, should be carried out when there are destructive lesions. Reconstructive surgery, mainly the the repair of strictures at the lower end of the ureter and bladder augmentation for a small fibrotic bladder, is frequently required. Both radical and reconstructive surgery should be carried out in the first 2 months of intensive chemotherapy. There is no reason now why all patients should not be able to return to a normal efficient life - free from all association with the disease - not later than 4 months after the start of treatment.
Humoral immune response of patients with newly detected, bacteriologically confirmed pulmonary tuberculosis was determined prior to initiation of chemotherapy. Correlation with the extent of the disease was studied. A significant rise in the IgA and IgG levels in the serum was observed, the increase in the IgA levels correlated with the extent of the disease. In tuberculous patients elevated levels of anti-OT (ppd) antibodies were found by haemaggluination, but no marked correlation was observed with the extent of the disease. There was no interrelationship between the IgA or IgG increase and that of specific anti-OT (PPD) antibodies. The importance of the mentioned findings is discussed.
The results of short courses of chemotherapy using rifampicin plus isoniazid, supplemented for the first two months by streptomycin or ethambutol, in patients with newly diagnosed pulmonary tuberculosis, have been studied. 174 patients with little or no cavitation received six months chemotherapy. 1 (0.6%) failed to convert to culture negative during treatment and 5 (3%) relapsed in the twelve months after the end of treatment. In 177 patients with similar disease, twelve months chemotherapy was 100% effective in rendering the sputum culture negative and in preventing relapse in the six months after the end of treatment. 151 patients with more extensive cavitation received chemotherapy for nine months; this was 100% effective in sputum conversion and in preventing relapse in the nine months after the end of treatment. In 155 patients with similar disease, the eighteen-month regimen was uniformly successful in sputum conversion. The rifampicin plus isoniazed regimen was well tolerated, producing adverse effects which warranted withdrawal from the study in only 3.6% of patients. Comparison of ethambutol with streptomycin as a third drug given for the first eight weeks showed no significant difference in the rate of sputum conbersion nor in the incidence of relapse. Streptomycin produced significant adverse effects in 8% of patients whilst ethambutol caused none. Chemotherapy with rifampicin plus isoniazed for nine months, supplemented initially by ethambutol, is more acceptable than standard chemotherapy for eighteen months, is highly effective in sputum conversion, and has resulted in no relapses over a nine-month follow-up period. Further follow-up is being continued to confirm that relapse does not occur.
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