Human Tuberculosis Cases Research Articles

Status and Public Health Significance of Mycobacterium bovis in Ethiopia

Infectious diseases, accounting for 30-50% of the total annual losses, remain a major impediment to Ethiopia’s livestock economy. Cattle, other domesticated animals, and some free-range or captive wildlife species are all susceptible to the infectious disease known as bovine tuberculosis, which is caused by the Mycobacterium bovis (M. bovis). It is typically distinguished by the development of tubercle-like nodular granulomas. The bovine tuberculosis-diseased animal loses 10-25% of their productive efficiency; direct losses due to the infection become evident by a decrease in 10-18% milk and a 15% reduction in meat production. During the final stages of tuberculosis, severe emaciation and acute respiratory distress might happen. It affects animal production, but it also significantly affects public health. Human infection due to M. bovis is thought to be mainly through the drinking of contaminated or unpasteurized raw milk and undercooked meat. It is estimated that M. bovis causes 10-15% of human cases of tuberculosis in countries. This indicated that tuberculosis in both humans and animals is endemic in Ethiopia. Reporting the status of tuberculosis in animals and humans is so dynamic.

Genetic Diversity and Population Structure of Mycobacterium bovis at the Human-Animal-Ecosystem Interface in France: "A One Health Approach".

Mycobacterium bovis infects cattle and wildlife, and also causes a small proportion of tuberculosis cases in humans. In most European countries, M. bovis infections in cattle have been drastically reduced, but not eradicated. Here, to determine the M. bovis circulation within and between the human, cattle, and wildlife compartments, we characterized by spoligotyping and mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) typing the genetic diversity of M. bovis isolates collected from humans, cattle, and wildlife in France from 2000 to 2010. We also assessed their genetic structure within and among the different host groups, and across time and space. The M. bovis genetic structure and its spatiotemporal variations showed different dynamics in the human and animal compartments. Most genotypes detected in human isolates were absent in cattle and wildlife isolates, possibly because in patients, M. bovis infection was contracted abroad or was the reactivation of an old lesion. Therefore, they did not match the genetic pool present in France during the study period. However, some human-cattle exchanges occurred because some genotypes were common to both compartments. This study provides new elements for understanding M. bovis epidemiology in France, and calls for increased efforts to control this pathogen worldwide.

Zoonotic Importance of Bovine Tuberculosis in Ethiopia: An Overview

Bovine tuberculosis (BTB) is an important zoonotic disease that affects both domestic animals as well as humans in many countries of the world. The disease is caused by Mycobacterium bovis, which is responsible for 10–15% of human tuberculosis cases. BTB poses an occupational health hazard to the cattle owners, butchers, animal attendants, and veterinarians. The source of infection is exogenous and the respiratory tract is considered the chief portal of entry of the organism. The mode of spread of bacteria is aerogenous. BTB is endemic in Ethiopia, and it is mostly transmitted to people through the consumption of unpasteurized contaminated milk. Miliary tubercular lesions, chronic cough, blockages of the airways, alimentary system, or blood vessels, and lymph node enlargement are all symptoms of tuberculosis. Single intradermal or comparative intradermal tuberculin tests are useful delayed-type hypersensitivity tools for diagnosing tuberculosis in live animals. It is also employed in tuberculosis eradication programs and international trade activity. Vaccination of calves with an attenuated BTB strain known as Bacillus of Calmette and Guerin, as well as testing and culling, is significant measures in the prevention and control of BTB in endemic areas like Ethiopia. The proper pasteurization of milk before human consumption is a significant measure to reduce the public health risk posed by BTB.

Monitoring IgG against Mycobacterium tuberculosis proteins in an Asian elephant cured of tuberculosis that developed from long-term latency

Tuberculosis (TB) is fatal in elephants, hence protecting elephants from TB is key not only in the conservation of this endangered animal, but also to prevent TB transmission from elephants to humans. Most human TB cases arise from long-term asymptomatic infections. Significant diagnostic challenges remain in the detection of both infection and disease development from latency in elephants due to their huge bodies. In this study, we assessed cryopreserved sera collected for over 16 years, from the first Japanese treatment case of elephant TB. Semi-quantification of IgG levels to 11 proteins showed high detection levels of 3 proteins, namely ESAT6/CFP10, MPB83 and Ag85B. The level of IgG specific to these 3 antigens was measured longitudinally, revealing high and stable ESAT6/CFP10 IgG levels regardless of onset or treatment. Ag85B-specifc IgG levels were largely responsive to onset or treatment, while those of MPB83 showed intermediate responses. These results suggest that ESAT6/CFP10 is immunodominant in both asymptomatic and symptomatic phases, making it useful in the detection of infection. On the other hand, Ag85B has the potential to be a marker for the prediction of disease onset and in the evaluation of treatment effectiveness in elephants.

Polyresistant Mycobacterium bovis Infection in Human and Sympatric Sheep, Spain, 2017-2018.

The main etiologic agent of tuberculosis (TB) in livestock is Mycobacterium bovis; human TB cases caused by M. bovis are rare. Analysis of a TB outbreak caused by polyresistant M. bovis involving a human and sympatric sheep in Spain suggests local circulation of drug-resistant M. bovis strains among livestock.

Spatial and temporal analyses of culls due to bovine tuberculosis in slaughterhouses of Minas Gerais state, Brazil, 2008 to 2012

ABSTRACT: The application of spatial and temporal analysis in epidemiology aims to understand the causes and consequences of spatial and temporal heterogeneity in studies of infectious diseases. Bovine tuberculosis (bTB) is a chronic and progressive infectious disease caused by Mycobacterium bovis and is an important zoonosis worldwide. The aim of this study was to conduct spatial and temporal analyses of a secondary database of bTB-positive cases registered by the Federal Inspection Service in two slaughterhouses from the West of Minas mesoregion of Minas Gerais state, Brazil, from 2008 to 2012 and to suggest its use in epidemiological surveillance. The culled cattle with bTB macroscopic lesions during post mortem inspection were considered positive in this study. The data used were the positive cases registered on the “Sistema de Informações Gerenciais do Serviço de Inspeção Federal” (SIG/SIF - Management Information System of the Federal Inspection Service) of the “Ministério da Agricultura, Pecuária e Abastecimento” (MAPA - Ministry of Agriculture, Livestock and Supplies), the number of animals slaughtered monthly and their municipalities of origin, per slaughterhouse. The prevalence (%) of cases per cattle slaughtered was calculated, and the relationship between these cases of bTB and cases of human tuberculosis (hTB) and the GDP per capita of the mesoregions comprising the municipalities surveyed was evaluated. The prevalence was 1,030 cases of bTB (0.28%). The lowest case numbers and prevalence rates were obtained in 2010, while the highest rates were observed in 2011. Slaughterhouse 1 showed stationarity, while Slaughterhouse 2 showed an increasing annual trend for data since October 2009. A statistical correlation between the numbers of cases of bovine and human TB (p=0.006, r=0.148) was observed. The prevalence for Slaughterhouses 1 and 2 were not correlated (p>0.05). The municipalities of origin demonstrated randomness in their spatial distribution. SIG/SIF-MAPA may be used for the analysis of spatial and temporal distribution to contribute to the monitoring of animal health services with information on the prevalence of culling for bTB in the West of Minas, South/Southwest of Minas, Campo das Vertentes and Zona da Mata mesoregions of Minas Gerais, Brazil.

Zoonotic tuberculosis in nomadic pastoral communities in Nigeria: Risk routes for transmission, socio-cultural drivers and public health implications

Background: Bovine tuberculosis (bTB) is a zoonotic disease, caused by Mycobacterium bovis, a member of Mycobacterium tuberculosis complex. M. bovis causes 5–7% of human tuberculosis cases in Africa. To achieve the World Health Organization's “END-TB” goal by 2035, surveillance system that encompasses livestock herders’ knowledge about bTB epidemiology is required. Study objectives were: to assess pastoralists’ knowledge-attitude-practices regarding bTB, zoonotic transmission risk routes, and estimate its prevalence in lactating pastoral cow herds. We hypothesized that socio-cultural practices cannot influence bTB occurrence in pastoral communities. Methods and materials: Interview-questionnaire based cross-sectional study was conducted on 600 randomly selected herd owners in nomadic pastoral communities of north-central Nigeria in 2018. Also, 196 lactating Zebu cows were systematic randomly selected for raw milk collection in targeted herds. Milk samples were examined for acid-fast bacilli using Ziehl-Neelsen microscopic evaluation in a biosafety laboratory level II. Descriptive, unvariate and multivariable logistic regressions models were performed at 95% confidence level. Results: An 8.7% (11/196) prevalence of red rod-like tubercle bacilli was obtained. About 90% (538/600) of selected pastoralists participated. Majority (63.9%) of respondents had no formal education. Only 24.7% of them mentioned bTB to be zoonotic. Only 18.8% of participants practiced adequate boiling of raw milk before consumption as preventive measures. Risk routes for bTB zoonotic transmission were: consumption of raw milk and milk products (p < 0.001); contacts with infected udder and co-habitation with infected cows (p = 0.001); and aerosols of milk with viable M. bovis during milking and discarded infected milk in the environment (p < 0.001). Socio-cultural drivers associated with zoonotic tuberculosis occurrence in nomadic pastoral communities were: extensive husbandry system (p < 0.001), culture of borrowing/loaning cattle (p = 0.001), culture of giving out cattle as gift/payment for dowry (p = 0.001), high herds density sharing common watering points (p < 0.001) and introduction of new cattle into herd without quarantine (p = 0.001). Conclusion: This study revealed pastoralists’ low knowledge and practices regarding zoonotic tuberculosis. The challenging gaps call for health education of vulnerable populations. Tuberculosis surveillance and control programmes take identified bTB risk transmission routes and social drivers into consideration, in line with ‘One Health’ approach, will assure food safety, food security, public and environmental health in Africa.

First isolation of Mycobacterium bovis SIT 482 BOV from beef cattle in Turkey

Bovine tuberculosis is a zoonotic disease which should be emphasized in our country as in many countries. A large number of genotypes have been revealed by spoligotyping method of M. bovis in the world. M. bovis SIT 482. BOV is one of these genotypes and it is also M. bovis genotype in which BCG vaccine is administered in humans. The BCG vaccine is obtained through multiple passages of this genotype. However, this genotype, like other genotypes, can cause serious infections in humans and animals. There are data on the isolation of M. bovis SIT 482 BOV from animal and human tuberculosis cases in the world. In our country, the isolation of this genotype has been reported only in humans and no data have been found in the animals. In this study, M. bovis SIT 482. BOV was isolated from the samples of six cattle with internal organ samples obtained from licensed slaughterhouses in Aksaray. While isolation is carried out with BACTEC MGIT 960 liquid media, spoligotyping was carried out according to the manufacturer’s with kit (Isogen LifeScience, The Netherlands). This study aims to report M. bovis SIT 482 BOV from cattle in Turkey for the first time, to draw attention a very limited number reported in M. bovis cases in Turkey, highlight the importance of genotyping of tuberculosis factors and contribute to epidemiological studies. These and similar studies will contribute to the creation of genetic maps for eradication of M. bovis from cattle in our country. The study was also conducted to investigate whether M. bovis SIT 482. BOV isolated from cattle in Aksaray province is BCG strain or another strain giving the same pattern.

Strong homology between SARS-CoV-2 envelope protein and a Mycobacterium sp. antigen allows rapid diagnosis of Mycobacterial infections and may provide specific anti-SARS-CoV-2 immunity via the BCG vaccine

The vaccine BCG has been reported to offer protection against SARS-CoV-2 infection. It has been hypothesized this is based on nonspecific enhancement of innate immunity. This study addressed whether there is strong homology between a SARS-CoV-2 capsid protein and a Mycobacterium bovis protein that would allow for stronger, more specific immune protection. The study also showed the utility of immunohistochemistry in the diagnostic pathology laboratory for elucidating this information. Immunohistochemistry documented that an antibody directed against the SARS-CoV-2 envelope, but not the spike or membrane proteins, strongly cross hybridized to 11/11 Mycobacterial species tested, including M. bovis. BlastP analysis showed high homology of the SARS-CoV-2 envelope protein with 12 consecutive amino acids of the protein LytR C, which is a consensus protein unique to Mycobacteria. Six additional cases of human tuberculosis with few organisms showed that the viral envelope specific antibody (5/6) was more accurate than the AFB stain (2/6) for diagnostic purposes. These data indicate BCG vaccination induces a specific immunity against SARS CoV-2 that targets the viral envelope protein that is essential for infectivity. Thus, a concurrent booster or first use of the BCG vaccine may reduce the severity of the current COVID-19 pandemic. The data also suggests the value of using the SARS-CoV-2 envelope antibody in the diagnosis of Mycobacterial infections in formalin fixed, paraffin embedded tissues by the diagnostic pathologist.

Reconsidering Mycobacterium bovis as a proxy for zoonotic tuberculosis: a molecular epidemiological surveillance study

SummaryBackgroundZoonotic tuberculosis is defined as human infection with Mycobacterium bovis. Although globally, India has the largest number of human tuberculosis cases and the largest cattle population, in which bovine tuberculosis is endemic, the burden of zoonotic tuberculosis is unknown. The aim of this study was to obtain estimates of the human prevalence of animal-associated members of the Mycobacterium tuberculosis complex (MTBC) at a large referral hospital in India.MethodsWe did a molecular epidemiological surveillance study of 940 positive mycobacteria growth indicator tube (MGIT) cultures, collected from patients visiting the outpatient department at Christian Medical College (Vellore, India) with suspected tuberculosis between Oct 1, 2018, and March 31, 2019. A PCR-based approach was applied to subspeciate cultures. Isolates identified as MTBC other than M tuberculosis or as inconclusive on PCR were subject to whole-genome sequencing (WGS), and phylogenetically compared with publicly available MTBC sequences from south Asia. Sequences from WGS were deposited in the National Center for Biotechnology Information Sequence Read Archive, accession number SRP226525 (BioProject database number PRJNA575883).FindingsThe 940 MGIT cultures were from 548 pulmonary and 392 extrapulmonary samples. A conclusive identification was obtained for all 940 isolates; wild-type M bovis was not identified. The isolates consisted of M tuberculosis (913 [97·1%] isolates), Mycobacterium orygis (seven [0·7%]), M bovis BCG (five [0·5%]), and non-tuberculous mycobacteria (15 [1·6%]). Subspecies were assigned for 25 isolates by WGS, which were analysed against 715 MTBC sequences from south Asia. Among the 715 genomes, no M bovis was identified. Four isolates of cattle origin were dispersed among human sequences within M tuberculosis lineage 1, and the seven M orygis isolates from human MGIT cultures were dispersed among sequences from cattle.InterpretationM bovis prevalence in humans is an inadequate proxy of zoonotic tuberculosis. The recovery of M orygis from humans highlights the need to use a broadened definition, including MTBC subspecies such as M orygis, to investigate zoonotic tuberculosis. The identification of M tuberculosis in cattle also reinforces the need for One Health investigations in countries with endemic bovine tuberculosis.FundingBill & Melinda Gates Foundation, Canadian Institutes for Health Research.

The paleopathological evidence on the origins of human tuberculosis: a review

SummaryTuberculosis (TB) has been one of the most important infectious diseases affecting mankind and still represents a plague on a global scale. In this narrative review the origins of tuberculosis are outlined, according to the evidence of paleopathology. In particular the first cases of human TB in ancient skeletal remains are presented, together with the most recent discoveries resulting from the paleomicrobiology of the tubercle bacillus, which provide innovative information on the history of TB. The paleopathological evidence of TB attests the presence of the disease starting from Neolithic times. Traditionally, it was thought that TB has a zoonotic origin, being acquired by humans from cattle during the Neolithic revolution. However, the biomolecular studies proposed a new evolutionary scenario demonstrating that human TB has a human origin. The researches show that the disease was present in the early human populations of Africa at least 70000 years ago and that it expanded following the migrations of Homo sapiens out of Africa, adapting to the different human groups. The demographic success of TB during the Neolithic period was due to the growth of density and size of the human host population, and not the zoonotic transfer from cattle, as previously hypothesized. These data demonstrate a long coevolution of the disease and its human host. Understanding the changes of TB through time thanks to the advances in the field of paleopathology can help to solve the present problems and understand the future evolution of TB.

Farmer and veterinarian attitudes towards the risk of zoonotic Mycobacterium bovis infection in Northern Ireland

Based on a qualitative social science research methodology using semi-structured interviews, this paper examines the attitudes of farmers and veterinarians in Northern Ireland around the risk of acquiring tuberculosis caused...

Retrospective Analysis of Archived Pyrazinamide Resistant Mycobacterium tuberculosis Complex Isolates from Uganda-Evidence of Interspecies Transmission.

The contribution of Mycobacterium bovis to the proportion of tuberculosis cases in humans is unknown. A retrospective study was undertaken on archived Mycobacterium tuberculosis complex (MTBC) isolates from a reference laboratory in Uganda to identify the prevalence of human M. bovis infection. A total of 5676 isolates maintained in this repository were queried and 136 isolates were identified as pyrazinamide resistant, a hallmark phenotype of M. bovis. Of these, 1.5% (n = 2) isolates were confirmed as M. bovis by using regions of difference PCR analysis. The overall size of whole genome sequences (WGSs) of these two M. bovis isolates were ~4.272 Mb (M. bovis Bz_31150 isolated from a captive chimpanzee) and 4.17 Mb (M. bovis B2_7505 from a human patient), respectively. Alignment of these genomes against 15 MTBC genome sequences revealed 7248 single nucleotide polumorphisms (SNPs). Theses SNPs were used for phylogenetic analysis that indicated a strong relationship between M. bovis and the chimpanzee isolate (Bz_31150) while the other M. bovis genome from the human patient (B2_7505) analyzed did not cluster with any M. bovis or M. tuberculosis strains. WGS analysis also revealed multidrug resistance genotypes; these genomes revealed pncA mutations at positions H57D in Bz_31150 and B2_7505. Phenotypically, B2_7505 was an extensively drug-resistant strain and this was confirmed by the presence of mutations in the major resistance-associated proteins for all anti-tuberculosis (TB) drugs, including isoniazid (KatG (S315T) and InhA (S94A)), fluoroquinolones (S95T), streptomycin (rrs (R309C)), and rifampin (D435Y, a rare but disputed mutation in rpoB). The presence of these mutations exclusively in the human M. bovis isolate suggested that these occurred after transmission from cattle. Genome analysis in this study identified M. bovis in humans and great apes, suggesting possible transmission from domesticated ruminants in the area due to a dynamic and changing interface, which has created opportunity for exposure and transmission.

A Nonribosomal Peptide Synthase Gene Driving Virulence in Mycobacterium tuberculosis.

Nonribosomal peptide synthases produce short peptides in a manner that is distinct from classical mRNA-dependent ribosome-mediated translation. The Mycobacterium tuberculosis genome harbors a nonribosomal peptide synthase gene, nrp, which is part of a gene cluster proposed to be involved in the biosynthesis of isonitrile lipopeptides. Orthologous clusters are found in other slow-growing pathogenic mycobacteria and actinomycetes. To probe the role of the nrp gene in infection, we generated an nrp deletion mutant in M. tuberculosis H37Rv and tested its virulence in immunocompetent (C57BL/6) mice. The nrp mutant strain displayed lower initial growth rates in the lungs and a defective dissemination to the spleens of infected mice. Mice infected with the mutant strain also survived for twice as long as those infected with wild-type M. tuberculosis and, remarkably, showed subdued pathology, despite similar bacterial loads at later stages of infection. The differences in the course of infection between wild-type and nrp mutant strains were accompanied by distinct dynamics of the immune response. Most strikingly, the nrp mutant was highly attenuated in immunodeficient (SCID-, recombination activating 2 [RAG2]-, and gamma interferon [IFN-γ]-deficient) mice, suggesting that macrophages control the nrp mutant more efficiently than they control the wild-type strain. However, in the presence of IFN-γ, both strains were equally controlled. We propose that the nrp gene and its associated cluster are drivers of virulence during the early stages of infection.IMPORTANCE Over 10 million people developed tuberculosis (TB) in 2016, and over 1.8 million individuals succumbed to the disease. These numbers make TB the ninth leading cause of death worldwide and the leading cause from a single infectious agent. Therefore, finding novel therapeutic targets in Mycobacterium tuberculosis, the pathogen that causes most cases of human TB, is critical. In this study, we reveal a novel virulence factor in M. tuberculosis, the nrp gene. The lack of nrp highly attenuates the course of M. tuberculosis infection in the mouse model, which is particularly relevant in immune-deficient hosts. This is very relevant as TB is particularly incident in immune-suppressed individuals, such as HIV patients.

Genotyping and rifampicin and isoniazid resistance in Mycobacterium bovis strains isolated from the lymph nodes of slaughtered cattle

In developing nations, 10–20% of the human cases of tuberculosis are caused by Mycobacterium bovis. However, this percentage may be underestimated because most laboratories in developing countries do not routinely perform mycobacterial cultures, and only a few have the systems in place to identify M. bovis. There are few studies investigating genotypic diversity and drug resistance in M. bovis from animal and/or human infections.The genotypic diversity of M. bovis strains obtained from bovine lymph nodes were investigated by spacer oligonucleotide typing (spoligotyping) and mycobacterial interspersed repetitive unit–variable-number tandem repeat typing (MIRU-VNTR). The phenotypic resistance to isoniazid and rifampicin and MIC values of the isolates were determined using the resazurin microtiter assay plate method (REMA). The evaluation of the possible genetic basis for such resistance was performed with GenoType MTBDRplus. Sixty-seven isolates were obtained, of which 11 (16%) were MDR-TB, 8 (12%) were isoniazid-resistant, and 2 (3%) were rifampicin-resistant. Mutations associated with drug resistance were not found. Genotyping techniques enabled the grouping of the strains into 12 clusters and 21 isolates with unique profiles.The high frequency of M. bovis reinforces the impact of the pathogen as a major causal agent of bovine tuberculosis in the study area. The resistance of the strains to drugs used for first-line treatment of human tuberculosis raises public health concerns. Further studies are required to elucidate the basis of drug resistance and genotypic diversity in M. bovis.

Tuberculosis and One Health - What is in a Name?

Most control programs for bovine tuberculosis include reporting to both veterinary and public health authorities, and measures to prevent transmission from animals to humans. On the other hand, reporting of human cases to veterinary authorities is rare, unless an animal source is suspected. Exchange of data and strategic discussions between veterinary and public health authorities would strengthen tuberculosis surveillance in both animal and human populations. A One Health approach is clearly warranted for tuberculosis. The disease has similarly serious consequences for humans and a broad range of animal species, and it has been strongly advocated as a One Health issue (1). Yet, tuberculosis cases in humans and animals are commonly treated as separate problems (2, 3). Tuberculosis is caused by bacteria within the Mycobacterium tuberculosis complex (MTBC). “Bovine tuberculosis” usually means infection in cattle with Mycobacterium bovis (3, 4). However, this definition may be too restrictive, and the term bovine tuberculosis has been proposed to signify infection in cattle with any bacteria in the MTBC (5, 6). Similarly, “human tuberculosis” usually refers to infection in humans with M. tuberculosis, while “zoonotic tuberculosis” refers to human infection with M. bovis (7). However, for control and monitoring purposes, as well as a One Health approach, it would be preferable to use the terms “human tuberculosis” and “bovine tuberculosis” for infection with all bacteria within the MTBC in humans and cattle, respectively. Consequently, infections in other host species could be named after the host species, complemented by specifying the infecting bacterial species. In the following, the term “tuberculosis” is used for infection with bacteria within the MTBC, regardless of host species.

Development of an in vitro model of the early-stage bovine tuberculous granuloma using Mycobacterium bovis-BCG

Mycobacterium bovis causes 3.1% of human tuberculosis cases, as described by the World Health Organisation. In cattle, this organism causes bovine tuberculosis (BTB) which can have a prevalence of up to 39.5% in some developing countries. In developed countries, although the prevalence of BTB has been reduced through eradication programmes, complete eradication has in some cases proved elusive, with prevalences in cattle of 0.5% in the Republic of Ireland and of 4.3% in the UK. As the tuberculous granuloma is the fundamental lesion that reflects the pathogenesis, immune control and progression of BTB, we aimed to develop an in vitro model of the early-stage bovine tuberculous granuloma, in order to model the early stages of BTB, while also reducing the use of experimentally infected animals. In vitro models of human and ovine mycobacterial granulomas have previously been developed; however, so far, there is no model for the BTB granuloma. As the disease in cattle differs in a number of ways from that in other species, we consider this to be a significant gap in the tools available to study the pathogenesis of BTB. By combining bovine monocyte-derived macrophages infected with M. bovis-BCG and autologous lymphocytes we have developed an early-stage tuberculous bovine granuloma model. In the model, 3D cell aggregations formed a spherical-shape that grew for up to 11 days post-infection. This bovine tuberculous granuloma model can aid in the study of such lesion development, and in comparative studies of pathogenesis, such as, for example, the question of mycobacterial latency in bovine tuberculosis.

The bacterial and host factors associated with extrapulmonary dissemination of Mycobacterium tuberculosis.

With high morbidity and mortality worldwide, tuberculosis (TB) is still an important public health threat. The majority of human TB cases are caused by Mycobacterium tuberculosis. Although pulmonary TB is the most common presentation, M. tuberculosis can disseminate into other organs and causes extrapulmonary TB (EPTB). The dissemination of bacteria from the initial site of infection to other organs can lead to fatal diseases, such as miliary and meningeal TB. Thoroughly understanding the mechanisms and pathways of dissemination would develop therapies to prevent the lethal prognosis of EPTB (miliary and meningeal TB) and vaccines to promote the development of adaptive immunity. This review focuses on risk factors of EPTB, bacterial and host genes involved in EPTB, and potential mechanisms of M. tuberculosis extrapulmonary dissemination.

Zoonotic tuberculosis caused by Mycobacterium bovis, Central province, Iran

Background and Objectives: Although Mycobacterium tuberculosis (M. tuberculosis) causes most cases of human tuberculosis (TB), Mycobacterium bovis (M. bovis) is an important cause of TB infections in certain populations. Identification of M. bovis as a member of M. tuberculosis complex could be valuable in term of public health control measures. In search for cases of zoonotic TB we have performed an 18-month molecular epidemiology study on all patients presenting pulmonary tuberculosis admitted to public hospitals in Markazi province, central Iran. Materials and Methods: Only one Mycobacterium bovis isolate was detected among 42 M. tuberculosis isolates that were successfully collected during the research. Identified as M. bovis by phenotypic tests, PCR-RFLP for OxyR gene of this isolate coupled with findings of PGRS-RFLP and also DR-RFLP genotyping demonstrated an entirely different strain to those previously reported from animal hosts in Iran. Results: Considering the very homogenous population of M. bovis in Iran, and the patient's age, 75, we assume this isolate displays activation of an earlier exposure to M. bovis during the patient's life. Conclusion: Besides, our data suggest a low contribution of M. bovis in human TB in the region and possibly in the whole country.

Molecular characterization of Mycobacterium bovis isolates from patients with tuberculosis in Baja California, Mexico

The incidence of tuberculosis (TB) from Mycobacterium bovis in humans is likely to be underestimated and in some cases even ignored in most developing countries. This may be due to the difficulty of differentiating TB caused by either Mycobacteriumtuberculosis or M. bovis.Our objectives were to determine the prevalence of M. bovis human disease among the patients referred for study to the Tuberculosis Laboratory of the Tijuana General Hospital in Baja California, Mexico and to characterize molecularly the clinical isolates using 8 loci of MIRU-VNTR.A cross-sectional analysis of all culture-proven cases of tuberculosis was conducted during the period from January 1, 2011 through June 30, 2013. Clinical isolates that exhibited resistance to pyrazinamide (Z) were submitted for molecular analysis.A total of 2699 clinical samples were cultured during the study period and 600 (22%) that tested positive were processed for drug susceptibility for first line drugs. Sixty-four (10.7%) of the tested isolates tested were resistant to Z, and 27 (4.5%) of those were subsequently identified molecularly as M. bovis. Three of the M. bovis isolates were polyresistant to Z, isoniazid (H), ethambutol (E) and rifampicin (R) (Z+H+E, Z+E and Z+R); the rest were only resistant only to Z. VNTR typing, based on the 8 VNTR loci commonly tested for M.bovis, detected 12 allelic profiles (genotypes).The real burden of M. bovis cases among the total reported human tuberculosis cases can only be known from especially designed studies in which, during a specific period, all specimens submitted to tuberculosis diagnosis in one or more laboratories are cultured on the appropriate media and the isolated mycobacteria are analyzed to differentiate M. bovis from M. tuberculosis and other Mycobacterium species.