A rare case of spinal tuberculosis due to Mycobacterium bovis. Is zoonotic tuberculosis underdiagnosed?

We report a rare presentation of Pott's disease caused by M. bovis, suggesting transmission from infected cattle, and only the second case described so far in scientific reports. Noteworthy of this case was that the strain was only isolated on Stonebrink medium, a sodium pyruvate-containing culture medium for the isolation of mycobacteria. This medium is frequently ignored in diagnostic laboratories and in the laboratory manuals of most international health organizations. In general laboratories use a culture medium that contains glycerol, a carbon substrate considered inhibitory for the growth of M. bovis. The use of glycerol-containing medium therefore likely contributes towards underestimating zoonotic tuberculosis. Our case suggests that, in order to improved surveillance efforts for zoonotic TB and increase the notification rate for M. bovis to human TB, the use of pyruvate-containing media should be promoted, particularly in developing countries with a high prevalence of bovine TB, but also through the World Health Organization' (WHO) End TB Strategy and the Roadmap for Zoonotic TB.

Mycobacterium tuberculosis population structure and molecular epidemiological analysis in Sucre municipality, Miranda state, Venezuela / Estructura poblacional y análisis epidemiológico molecular de Mycobacterium tuberculosis en el municipio Sucre, estado Miranda, Venezuela

Sucre municipality is a large, densely populated marginal area in the eastern part of Caracas, Venezuela that consistently has more cases of tuberculosis than other municipalities in the country. To identify the neighborhoods in the municipality with the highest prevalence of tuberculosis, and determine whether the Mycobacterium tuberculosis strain distribution in this municipality is different from that previously found in the western part of Caracas and the rest of Venezuela, we collected data on all tuberculosis cases in the municipality diagnosed in 2005-6. We performed two separate molecular epidemiological studies, spoligotyping 44 strains in a first study, and spoligotyping 131 strains, followed by MIRU-VNTR 15 on 21 clustered isolates in the second. With spoligotyping, the most common patterns were Shared International Type SIT17 (21%); SIT42 (15%); SIT93 (11%); SIT20 (7%); SIT53 (6%), a distribution similar to other parts of Venezuela, except that SIT42 and SIT20 were more common. MIRU-VNTR 15 showed that six of seven SIT17 strains examined belonged to a large cluster previously found circulating in Venezuela, but all of the SIT42 strains were related to a cluster centered in the neighborhoods of Unión and Maca, with a MIRU-VNTR pattern not previously seen in Venezuela. It appears that a large percentage of the tuberculosis in the Sucre municipality is caused by the active transmission of two strain families centered within distinct neighborhoods, one reflecting communication with the rest of the country, and the other suggesting the insular, isolated nature of some sectors.

El municipio Sucre es un área densamente poblada del este de Caracas, Venezuela, con más casos de tuberculosis que otros municipios del país. Para establecer las áreas en el municipio Sucre con la mas alta prevalencia de tuberculosis y determinar sí la distribución de cepas de Mycobacterium tuberculosis es diferente de las encontradas previamente en el Oeste de Caracas y el resto de Venezuela, se recolectaron los datos de todos los casos diagnosticados de tuberculosis en el municipio en el 2005-6. Además, se aplicaron dos estudios de epidemiología molecular, el primero con 44 aislados en 2006 y el segundo con 131 aislados del 2006 al 2011, todos caracterizados por spoligotyping. Fue aplicada la técnica MIRU VNTR15 sobre 21 aislados agrupados. Con spoligotyping, los patrones encontrados fueron SIT17 (21%); SIT42 (15%); SIT93 (11%); SIT20 (7%); SIT53 (6%), presentando una distribución similar en otras partes de Venezuela, con la diferencia de que el SIT42 y el SIT20 fueron comunes en el municipio. MIRU VNTR15 mostró que seis de las siete cepas SIT17 pertenecían a un gran grupo encontrado previamente en Venezuela, mientras las cepas SIT42, estaban relacionados a un grupo concentrado en los Barrios Unión y Maca, con un patrón MIRU VNTR no visto previamente en Venezuela. Los resultados indicarían que un gran porcentaje de tuberculosis en el municipio Sucre es causada por transmisión activa de dos familias, una reflejando comunicación con el resto del país, y otra sugiriendo que es un aislado propio de algunos Barrios del municipio.

Agreement between QuantiFERON®-TB Gold In-Tube and the tuberculin skin test and predictors of positive test results in Warao Amerindian pediatric tuberculosis contacts.

BACKGROUND: Interferon-gamma release assays have emerged as a more specific alternative to the tuberculin skin test (TST) for detection of tuberculosis (TB) infection, especially in Bacille Calmette-Guérin (BCG) vaccinated people. We determined the prevalence of Mycobacterium tuberculosis infection by TST and QuantiFERON®-TB Gold In-Tube (QFT-GIT) and assessed agreement between the two test methods and factors associated with positivity in either test in Warao Amerindian children in Venezuela. Furthermore, progression to active TB disease was evaluated for up to 12 months. METHODS: 163 HIV-negative childhood household contacts under 16 years of age were enrolled for TST, QFT-GIT and chest X-ray (CXR). Follow-up was performed at six and 12 months. Factors associated with TST and QFT-GIT positivity were studied using generalized estimation equations logistic regression models. RESULTS: At baseline, the proportion of TST positive children was similar to the proportion of children with a positive QFT-GIT (47% vs. 42%, p = 0.12). Overall concordance between QFT-GIT and TST was substantial (kappa 0.76, 95% CI 0.46-1.06). Previous BCG vaccination was not associated with significantly increased positivity in either test (OR 0.68, 95% CI 0.32-1.5 for TST and OR 0.51, 95% CI 0.14-1.9 for QFT-GIT). Eleven children were diagnosed with active TB at baseline. QFT-GIT had a higher sensitivity for active TB (88%, 95% CI 47-98%) than TST (55%, 95% CI 24-83%) while specificities were similar (respectively 58% and 55%). Five initially asymptomatic childhood contacts progressed to active TB disease during follow-up. CONCLUSION: Replacement of TST by the QFT-GIT for detection of M. tuberculosis infection is not recommended in this resource-constrained setting as test results showed substantial concordance and TST positivity was not affected by previous BCG vaccination. The QFT-GIT had a higher sensitivity than the TST for the detection of TB disease. However, the value of the QFT-GIT as an adjunct in diagnosing TB disease is limited by a high variability in QFT-GIT results over time.

Molecular characterisation of Mycobacterium tuberculosis isolates in the First National Survey of Anti-tuberculosis Drug Resistance from Venezuela.

BACKGROUND: Molecular typing of Mycobacterium tuberculosis strains has become a valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of outbreaks, tracking of epidemics, identification of genotypes and transmission events among patients who would have remained undetected by conventional contact investigation. This is the first genetic biodiversity study of M. tuberculosis in Venezuela. Thus, we investigated the genetic patterns of strains isolated in the first survey of anti-tuberculosis drug-resistance realised as part of the Global Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD). RESULTS: Clinical isolates (670/873) were genotyped by spoligotyping. The results were compared with the international spoligotyping database (SpolDB4). Multidrug resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped 82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs) specific to Venezuela were identified. Eight new inter-regional clusters were created. The Beijing genotype was not found. The genetic network shows that the Latin American and Mediterranean family constitutes the backbone of the genetic TB population-structure in Venezuela, responsible of >60% of total TB cases studied. MDR was 0.5% in never treated patients and 13.5% in previously treated patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of the MDR strains, respectively. Two clusters were found to be identical by the four different analysis methods, presumably representing cases of recent transmission of MDR tuberculosis. CONCLUSION: This study gives a first overview of the M. tuberculosis strains circulating in Venezuela during the first survey of anti-tuberculosis drug-resistance. It may aid in the creation of a national database that will be a valuable support for further studies.