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Tommie C. Victor

Bio: Tommie C. Victor is an academic researcher from Stellenbosch University. The author has contributed to research in topics: Mycobacterium tuberculosis & Tuberculosis. The author has an hindex of 36, co-authored 69 publications receiving 4415 citations. Previous affiliations of Tommie C. Victor include University of Cape Town & National Research Foundation of South Africa.


Papers
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Journal ArticleDOI
TL;DR: The results suggests the existence of fine geographical genetic clines within MTC populations, that could mirror the passed and present Homo sapiens sapiens demographical and mycobacterial co-evolutionary history whose structure could be further reconstructed and modelled, thereby providing a large-scale conceptual framework of the global TB Epidemiologic Network.
Abstract: Background The Direct Repeat locus of the Mycobacterium tuberculosis complex (MTC) is a member of the CRISPR (Clustered regularly interspaced short palindromic repeats) sequences family. Spoligotyping is the widely used PCR-based reverse-hybridization blotting technique that assays the genetic diversity of this locus and is useful both for clinical laboratory, molecular epidemiology, evolutionary and population genetics. It is easy, robust, cheap, and produces highly diverse portable numerical results, as the result of the combination of (1) Unique Events Polymorphism (UEP) (2) Insertion-Sequence-mediated genetic recombination. Genetic convergence, although rare, was also previously demonstrated. Three previous international spoligotype databases had partly revealed the global and local geographical structures of MTC bacilli populations, however, there was a need for the release of a new, more representative and extended, international spoligotyping database.

1,042 citations

Journal Article
TL;DR: A two-step, multiplex polymerase chain reaction (PCR) method based on genomic regions of difference allowed for rapid differentiation of members of the Mycobacterium tuberculosis complex, making it suitable for routine laboratories and surveillance purposes.
Abstract: Differentiation of members of the Mycobacterium tuberculosis complex by conventional mycobacteriological methods is time consuming, making surveillance of species-specific disease difficult A two-step, multiplex polymerase chain reaction (PCR) method based on genomic regions of difference (RD1, RD1(mic), RD2(seal), RD4, RD9 and RD12) was developed for the differentiation of M canettii, M tuberculosis, M africanum, M microti, M pinnipedii, M caprae, M bovis and M bovis BCG The size of the respective multiplex PCR amplification products corresponded to the presence of the different M tuberculosis complex members This method allows for rapid differentiation, making it suitable for routine laboratories and surveillance purposes

279 citations

Journal ArticleDOI
TL;DR: The tubercle bacillus has become a central player in the epidemiology of diarrheal disease and its role in this disease has become increasingly important in the management of infectious disease outbreaks.
Abstract: Since the discovery of the tubercle bacillus by Robert Koch in 1882 ([110][1]), a greater understanding of the dynamics and survival mechanisms of this pathogen has led to more questions than answers. Despite stringent control strategies and many advances in our knowledge of the epidemiology of

239 citations

Journal ArticleDOI
TL;DR: A role for rpoC mutations in the transmission of multidrug-resistant tuberculosis is supported and illustrates how epistatic interactions between drug resistance-conferring mutations, compensatory mutations, and different strain genetic backgrounds might influence compensatory evolution in drug-resistant M. tuberculosis.
Abstract: Rifampin resistance in clinical isolates of Mycobacterium tuberculosis arises primarily through the selection of bacterial variants harboring mutations in the 81-bp rifampin resistance-determining region of the rpoB gene. While these mutations were shown to infer a fitness cost in the absence of antibiotic pressure, compensatory mutations in rpoA and rpoC were identified which restore the fitness of rifampin-resistant bacteria carrying mutations in rpoB. To investigate the epidemiological relevance of these compensatory mutations, we analyzed 286 drug-resistant and 54 drug-susceptible clinical M. tuberculosis isolates from the Western Cape, South Africa, a high-incidence setting of multidrug-resistant tuberculosis. Sequencing of a portion of the RpoA-RpoC interaction region of the rpoC gene revealed that 23.5% of all rifampin-resistant isolates tested carried a nonsynonymous mutation in this region. These putative compensatory mutations in rpoC were associated with transmission, as 30.8% of all rifampin-resistant isolates with an IS6110 restriction fragment length polymorphism (RFLP) pattern belonging to a recognized RFLP cluster harbored putative rpoC mutations. Such mutations were present in only 9.4% of rifampin-resistant isolates with unique RFLP patterns (P < 0.01). Moreover, these putative compensatory mutations were associated with specific strain genotypes and the rpoB S531L rifampin resistance mutation. Among isolates harboring this rpoB mutation, 44.1% also harbored rpoC mutations, while only 4.1% of the isolates with other rpoB mutations exhibited mutations in rpoC (P < 0.001). Our study supports a role for rpoC mutations in the transmission of multidrug-resistant tuberculosis and illustrates how epistatic interactions between drug resistance-conferring mutations, compensatory mutations, and different strain genetic backgrounds might influence compensatory evolution in drug-resistant M. tuberculosis.

190 citations

Journal ArticleDOI
TL;DR: The binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of Mycobacterium tuberculosis, having important implications for molecular epidemiologic strain tracking and for the application of spolgotype data to phylogenetic analysis of M. tuberculosis isolates.
Abstract: The direct repeat (DR) region has been determined to be an important chromosomal domain for studying the evolution of Mycobacterium tuberculosis. Despite this, very little is known about microevolutionary events associated with clonal expansion and how such events influence the interpretation of both restriction fragment length polymorphism (RFLP) and spoligotype data. This study examined the structure of the DR region in three independently evolving lineages of M. tuberculosis with a combination of DR-RFLP, spoligotyping, and partial DNA sequencing. The results show that the duplication of direct variable repeat (DVR) sequences and single-nucleotide polymorphisms is rare; conversely, the deletion of DVR sequences and IS6110-mediated mutation is observed frequently. Deletion of either single or contiguous DVR sequences was observed. The deletion of adjacent DVR sequences occurred in a dependent manner rather than as an accumulation of independent events. Insertion of IS6110 into either the direct repeat or spacer sequences influenced the spoligotype pattern, resulting in apparent deletion of DVR sequences. Homologous recombination between adjacent IS6110 elements led to extensive deletion in the DR region, again demonstrating a dependent evolutionary mechanism. Different isolates from the same strain family and isolates from different strain families were observed to converge to the same spoligotype pattern. In conclusion, the binary data of the spoligotype are unable to provide sufficient information to accurately establish genotypic relationships between certain clinical isolates of M. tuberculosis. This has important implications for molecular epidemiologic strain tracking and for the application of spoligotype data to phylogenetic analysis of M. tuberculosis isolates.

162 citations


Cited by
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TL;DR: The current level of understanding of the pathogenesis of the diarrheagenic E. coli strains is discussed and how their pathogenic schemes underlie the clinical manifestations, diagnostic approach, and epidemiologic investigation of these important pathogens are described.
Abstract: Escherichia coli is the predominant nonpathogenic facultative flora of the human intestine. Some E. coli strains, however, have developed the ability to cause disease of the gastrointestinal, urinary, or central nervous system in even the most robust human hosts. Diarrheagenic strains of E. coli can be divided into at least six different categories with corresponding distinct pathogenic schemes. Taken together, these organisms probably represent the most common cause of pediatric diarrhea worldwide. Several distinct clinical syndromes accompany infection with diarrheagenic E. coli categories, including traveler’s diarrhea (enterotoxigenic E. coli), hemorrhagic colitis and hemolytic-uremic syndrome (enterohemorrhagic E. coli), persistent diarrhea (enteroaggregative E. coli), and watery diarrhea of infants (enteropathogenic E. coli). This review discusses the current level of understanding of the pathogenesis of the diarrheagenic E. coli strains and describes how their pathogenic schemes underlie the clinical manifestations, diagnostic approach, and epidemiologic investigation of these important pathogens.

4,863 citations

01 Jan 2002
TL;DR: The postmortem observations of Green, published in the Lancet in 1836, were the first to describe the distinct pathological features of tuberculous meningitis and set it apart from the other recognised causes of ‘acute hydrocephalus’ (Green 1836).
Abstract: INTRODUCTION The postmortem observations of Green, published in the Lancet in 1836, were the fi rst to describe the distinct pathological features of tuberculous meningitis and set it apart from the other recognised causes of ‘acute hydrocephalus’ (Green 1836). The challenge for the physician then lay in distinguishing the disease before death, and delivering the grave prognosis. Thomas Mann captures the full horror of this process in Dr Faustus as the helpless Dr Kurbis presides over the agonizing death of a small child from tuberculous meningitis: The whole thing lasted scarcely two weeks, including the earliest signs that all was not quite well with the child; from the beginnings no one – I believe no one at all – even dreamed of the horror to come ... Kurbis tested the child’s eyes, the pupils of which were tiny and showed a tendency to squint. The pulse raced. Muscular contractions developed, and an incipient rigidity of the neck. It was cerebrospinal meningitis, infl ammation of the meninges. The good man pronounced the name with a deprecating movement of the head shoulderwards, probably in the hope that they might not know the almost complete powerlessness of medical science in the face of this onslaught. Tuberculous meningitis was invariably fatal before the advent of anti-tuberculosis chemotherapy. Therefore, the need to diagnose the disorder became a priority after streptomycin was found to reduce mortality of tuberculous meningitis by one third in 1948 (MRC 1948). Progress was rapid over the next 5 years: adding para-aminosalicylic acid to streptomycin reduced mortality to 30%, and the addition of isoniazid to both of these compounds lowered the mortality still more to Robert Koch: photograph taken in the 1880s, around the time of his discovery of the tubercle bacillus (or ‘bacille Koch’, as it is still called in Vietnam).

1,579 citations

Journal ArticleDOI
TL;DR: Mycotoxins have various acute and chronic effects on humans and animals depending on species and susceptibility of an animal within a species, and ruminants have, however, generally been more resistant to the adverse effects of mycotoxin.

1,542 citations

Journal ArticleDOI
TL;DR: It is hypothesized that the healthy mucosa is capable of holding back fecal bacteria and that this function is profoundly disturbed in patients with IBD, suggesting that the changes in the mucosal flora in IBD are not secondary to inflammation, but a result of a specific host response.

1,346 citations

Journal ArticleDOI
TL;DR: A discriminatory subset of 15 loci with the highest evolutionary rates was defined that concentrated 96% of the total resolution obtained with the full 24-locus set, and its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing.
Abstract: Molecular typing based on 12 loci containing variable numbers of tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTRs) has been adopted in combination with spoligotyping as the basis for large-scale, high-throughput genotyping of Mycobacterium tuberculosis. However, even the combination of these two methods is still less discriminatory than IS6110 fingerprinting. Here, we define an optimized set of MIRU-VNTR loci with a significantly higher discriminatory power. The resolution and the stability/robustness of 29 loci were analyzed, using a total of 824 tubercle bacillus isolates, including representatives of the main lineages identified worldwide so far. Five loci were excluded for lack of robustness and/or stability in serial isolates or isolates from epidemiologically linked patients. The use of the 24 remaining loci increased the number of types by 40%—and by 23% in combination with spoligotyping—among isolates from cosmopolitan origins, compared to those obtained with the original set of 12 loci. Consequently, the clustering rate was decreased by fourfold—by threefold in combination with spoligotyping—under the same conditions. A discriminatory subset of 15 loci with the highest evolutionary rates was then defined that concentrated 96% of the total resolution obtained with the full 24-locus set. Its predictive value for evaluating M. tuberculosis transmission was found to be equal to that of IS6110 restriction fragment length polymorphism typing, as shown in a companion population-based study. This 15-locus system is therefore proposed as the new standard for routine epidemiological discrimination of M. tuberculosis isolates and the 24-locus system as a high-resolution tool for phylogenetic studies.

1,270 citations