Search PubMed⌕ Search

Biomedical subjects

M D Yates

Publications and source records attributed to M D Yates.

At least 19 recordsLinked to original sources

Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC -46A polymorphism.

The present study investigated the prevalence and diagnostic potential of the most commonly reported mutations associated with isoniazid resistance, katG 315Thr, katG 315Asn, inhA -15T, inhA -8A, and the oxyR-ahpC intergenic region, in a population sample of 202 isoniazid-resistant Mycobacterium tuberculosis isolates and 176 randomly selected fully sensitive isolates from England and Wales identified by using a directed oligonucleotide array and limited DNA sequencing. The strains were recovered from patients originating from 29 countries; 41 isolates were multidrug resistant. Mutations affecting katG 315, the inhA promoter, and the oxyR-ahpC intergenic region were found in 62.7, 21.9, and 30% of 169 genotypically distinct isoniazid-resistant isolates, respectively, whereas they were found in 0, 0, and 8% of susceptible strains, respectively. The frequency of mutation at each locus was unrelated to the resistance profile or previous antituberculous drug therapy. The commonest mutation in the oxyR-ahpC intergenic region, ahpC -46A, was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. This proved to be a phylogenetic marker for a subgroup of M. tuberculosis strains originating on the Indian subcontinent, which shared IS6110-based restriction fragment length polymorphism and spoligotype features with the Delhi strain and Central Asian strain CAS1; and this marker is strongly associated with isoniazid resistance and the katG 315Thr mutation. In total, 82.8% of unrelated isoniazid-resistant isolates could be identified by analysis of just two loci: katG 315 and the inhA promoter. Analysis of the oxyR-ahpC intergenic region, although phylogenetically interesting, does not contribute significantly to further identification of isoniazid-resistant isolates.

Antitubercular Agents↗

Outbreak of isoniazid resistant tuberculosis in north London.

BACKGROUND: A description is given of a major outbreak of isoniazid monoresistant tuberculosis (TB) chiefly in north London, including prisons. The earliest case was diagnosed in 1995 with most cases appearing after 1999. METHODS: Confirmation of a local cluster of cases was confirmed by restriction fragment length polymorphism (RFLP IS6110) typing or "rapid epidemiological typing" (RAPET). Further cases were found by retrospective analysis of existing databases, prospective screening of new isolates, and targeted epidemiological case detection including questionnaire analysis. RESULTS: By the end of 2001, 70 confirmed cases in London had been linked with a further 13 clinical cases in contacts and nine epidemiologically linked cases outside London. The epidemic curve suggests that the peak of the outbreak has not yet been reached. Cases in the outbreak largely belong to a social group of young adults of mixed ethnic backgrounds including several individuals from professional/business backgrounds. Compared with other cases of TB reported to the enhanced surveillance scheme in London during 1999-2001, the cases are more likely to be of white (26/70 (37%) v 1308/7666 (17%)) or black Caribbean ethnicity (17/70 (24%) v 312/7666 (4%)), born in the UK (41/70 (59%) v 1335/7666 (17%)), and male (52/70 (74%) v 4195/7666 (55%)). Drug misuse and/or prison detention are factors common to many cases. CONCLUSIONS: The investigation of the outbreak revealed significant problems on an individual patient and population based level including difficulties with contact tracing, compliance, and the risk of developing multidrug resistance. This incident has demonstrated the value of molecular strain typing in investigating an extensive outbreak of TB. This is the first documented outbreak involving a UK prison.

Adolescent↗

Evaluation and utilization as a public health tool of a national molecular epidemiological tuberculosis outbreak database within the United Kingdom from 1997 to 2001.

The aim of this study was to develop a national model and analyze the value of a molecular epidemiological Mycobacterium tuberculosis DNA fingerprint-outbreak database. Incidents were investigated by the United Kingdom PHLS Mycobacterium Reference Unit (MRU) from June 1997 to December 2001, inclusive. A total of 124 incidents involving 972 tuberculosis cases, including 520 patient cultures from referred incidents and 452 patient cultures related to two population studies, were examined by using restriction fragment length polymorphism IS6110 fingerprinting and rapid epidemiological typing. Investigations were divided into the following three categories, reflecting different operational strategies: retrospective passive analysis, retrospective active analysis, and retrospective prospective analysis. The majority of incidents were in the retrospective passive analysis category, i.e., the individual submitting isolates has a suspicion they may be linked. Outbreaks were examined in schools, hospitals, farms, prisons, and public houses, and laboratory cross-contamination events and unusual clinical presentations were investigated. Retrospective active analysis involved a major outbreak centered on a high school. Contact tracing of a teenager with smear-positive pulmonary tuberculosis matched 14 individuals, including members of his class, and another 60 cases were identified in schools clinically and radiologically and by skin testing. Retrospective prospective analysis involved an outbreak of 94 isoniazid-resistant tuberculosis cases in London, United Kingdom, that began after cases were identified at one hospital in January 2000. Contact tracing and comparison with MRU databases indicated that the earliest matched case had occurred in 1995. Subsequently, the MRU changed to an active prospective analysis targeting linked isoniazid-monoresistant isolates for follow up. The patients were multiethnic, born mainly in the United Kingdom, and included professionals, individuals from the music industry, intravenous drug abusers, and prisoners.

Antitubercular Agents↗

Application of a simple multiplex PCR to aid in routine work of the mycobacterium reference laboratory.

A PCR specific for spacer regions 33 and 34 of the direct repeat region of the Mycobacterium tuberculosis complex was developed to complement the biochemical differentiation of M. tuberculosis, Mycobacterium bovis, M. bovis BCG, and Mycobacterium africanum subtypes I and II. In addition, this approach was incorporated into a multiplex PCR that included primers specific for IS6110 and the 65-kDa antigen gene in order to differentiate members of the M. tuberculosis complex from atypical mycobacteria.

DNA, Intergenic↗

Molecular epidemiology of Mycobacterium avium complex isolated from patients with and without AIDS in Brazil and England.

Mycobacterium avium complex (MAC) is ubiquitous throughout the world. It is an opportunistic pathogen in AIDS patients but the number of cases in HIV negative patients is also increasing. The aim of this study was to determine whether patients were being infected with different MAC strains or whether one strain was dominant. DNA obtained from isolates in Brazil and England were compared using pulsed field gel electrophoresis (PFGE). Strains from 22 Brazilian patients clustered into 7 groups but 68/90 patients had a unique strain. In all patients, Brazilian and English, the same strain was isolated repeatedly over time, some over several years. This study shows that it is most likely that Man is infected from the environment and that one strain can survive without change for many years both in the environment and in Man.

AIDS-Related Opportunistic Infections↗

Comparison of three molecular assays for rapid detection of rifampin resistance in Mycobacterium tuberculosis.

Multidrug-resistant Mycobacterium tuberculosis (MDR-TB) is an emerging problem of great importance to public health, with higher mortality rates than drug-sensitive TB, particularly in immunocompromised patients. MDR-TB patients require treatment with more-toxic second-line drugs and remain infectious for longer than patients infected with drug-sensitive strains, incurring higher costs due to prolonged hospitalization. It is estimated that 90% of United Kingdom rifampin-resistant isolates are also resistant to isoniazid, making rifampin resistance a useful surrogate marker for multidrug resistance and indicating that second- and third-line drugs to which these isolates are susceptible are urgently required. Resistance in approximately 95% of rifampin-resistant isolates is due to mutations in a 69-bp region of the rpoB gene, making this a good target for molecular genotypic diagnostic methods. Two molecular assays, INNO-LiPA Rif.TB (Innogenetics, Zwijndrecht, Belgium) and MisMatch Detect II (Ambion, Austin, Tex.), were performed on primary specimens and cultures to predict rifampin resistance, and these methods were compared with the resistance ratio method. A third method, the phenotypic PhaB assay, was also evaluated in comparison to cultures in parallel with the genotypic assays. In an initial evaluation 16 of 16, 15 of 16, and 16 of 16 rifampin-resistant cultures (100, 93.8, and 100%, respectively), were correctly identified by line probe assay (LiPA), mismatch assay, and PhaB assay, respectively. Subsequently 38 sputa and bronchealveolar lavage specimens and 21 isolates were received from clinicians for molecular analysis. For the 38 primary specimens the LiPA and mismatch assay correlated with culture and subsequent identification and susceptibility tests in 36 and 38 specimens (94.7 and 100%), respectively. For the 21 isolates submitted by clinicians, both assays correlated 100% with routine testing.

Antibiotics, Antitubercular↗

Isolation of environmental mycobacteria from clinical specimens in south-east England: 1973-1993.

SETTING: A reference centre for tuberculosis bacteriology serving South-East England. OBJECTIVE: The number of cultures of environmental mycobacteria (EM) submitted to regional and reference laboratories in the UK is increasing, and is adding considerably to the workload of these laboratories. The changing trends in the numbers and nature of EM submitted to the Dulwich Public Health Laboratory Regional Tuberculosis Centre (RTC), have been analysed to establish the nature of the increase. DESIGN: This study is based on all cultures of EM submitted to RTC between 1973 and 1993. The cultures were grouped according to year of first isolation, number of isolates and data supplied by the client laboratories, including age and human immunodeficiency virus (HIV) status of the patients and the anatomical sites from which the mycobacteria were isolated. RESULTS: A total of 9379 EM from 6668 patients was received. Single and multiple isolates were received, respectively, from 4681 and 1192 patients not known to be HIV positive and from 477 and 318 who were known to be HIV positive. The annual number of patients not known to be HIV positive with isolates of probable clinical significance increased steadily from less than 40 in 1973 to over 100 per year since 1990. Isolates of doubtful clinical significance also showed an increase over time. The annual numbers from HIV positive patients increased steeply following the first such isolates in 1984. CONCLUSIONS: The data show that the annual number of isolates of EM from both HIV positive and negative patients is increasing both absolutely and relatively to isolates of Mycobacterium tuberculosis. This trend should be considered when planning the future scope and activities of mycobacterium reference laboratories, including the introduction of new DNA-based diagnostic methods.

Body Fluids↗

Factors determining ethnic differences in the incidence of bacteriologically confirmed genitourinary tuberculosis in south east England.

In South East England, genitourinary (GU) tuberculosis is a much less common manifestation of non-respiratory tuberculosis in patients of Indian subcontinent (ISC) ethnic origin than in those of European ethnic origin. When considered in relation to all bacteriologically confirmed cases of tuberculosis, both respiratory and non-respiratory, the ethnic difference in the occurrence of GU tuberculosis is much less evident, while there is a highly significant excess of other forms of non-respiratory tuberculosis among the ethnic ISC patients. Unlike other forms of non-respiratory tuberculosis, GU disease tends to occur in an older age range in the ethnic ISC population and, when stratified for age, the ethnic difference in the occurrence of this form of tuberculosis is not significant while that of lymph node tuberculosis remains significantly high. Thus, after elimination of the confounding factor of age, the occurrence of GU tuberculosis is very similar in the two ethnic groups while other forms of non-respiratory tuberculosis differ considerably.

Adult↗

A new group (type 3) of Mycobacterium celatum isolated from AIDS patients in the London area.

We describe a new group (type 3) of the recently proposed species Mycobacterium celatum isolated from eight patients with AIDS in London, England. Sequences of genes coding for 16S rRNA (EMBL accession no. Z46664) showed a divergence of 17 bases from M. celatum type 2 reference isolates and a divergence of 7 bases from M. celatum type 1 reference isolates. A reference strain is available (NCTC 12882).

Acquired Immunodeficiency Syndrome↗

Bacteriologically confirmed non-tuberculous mycobacterial lymphadenitis in south east England: a recent increase in the number of cases.

The annual numbers of cases of non-tuberculous mycobacterial lymphadenitis in south east England has increased over the period 1973 to 1993, most notably during the last few years. The most frequent cause is the Mycobacterium avium complex, followed by M malmoense. The reason for the increase is unknown but it could be due to an increased awareness in mycobacterial disease, an external factor such as pollution, or both.

Adolescent↗

Zoonotic aspects of Mycobacterium bovis infection.

The bovine tuberculosis eradication campaigns in many industrially developed countries have led to a huge reduction in the incidence of human tuberculosis caused by Mycobacterium bovis. Overt disease in man may, however, manifest decades after the initial infection and the occurrence of such disease raises several important questions. In particular, it is important to determine whether man-to-man transmission occurs, thereby rendering man a continuing reservoir of infection, and whether, if this is the case, man develops infectious forms of tuberculosis that enable M. bovis to be transmitted back to cattle. Epidemiological studies in South East England indicate that human tuberculosis due to M. bovis is rare and that the incidence is declining. In contrast to earlier days, the lung is now involved in many cases, raising the possibility of transmission of bacilli to other human beings and to cattle by the aerogenous route. No direct evidence of man-to-man transmission of overt disease was found but it is possible that inapparent primary pulmonary infections are occurring and these may proceed to overt post-primary disease in the future. The genito-urinary tract is now the most prevalent site of non-pulmonary lesions and there is firm evidence that this form of tuberculosis poses a hazard to cattle. Though uncommon, human tuberculosis due to M. bovis is still a public health problem of concern to both the medical and veterinary professions and there is a need to maintain careful bacteriological surveillance.

Animals↗

A case report of Mycobacterium chelonae keratitis and a review of mycobacterial infections of the eye and orbit.

Mycobacteria are unusual causes of keratitis and other ocular infections but the outcome of infection is often serious. We report a case of keratitis due to Mycobacterium chelonae, a rapidly growing environmental mycobacterium, in a soft contact-lens wearer, and discuss the difficulty and delay in identifying the organism, twice erroneously identified as Nocardia asteroides on morphological grounds. Despite in vitro susceptibility, the response to anti-bacterial agents was negligible and a second keratoplasty was required after a recurrence of disease at the donor-host junction. We review the role of mycobacteria as the cause of keratitis and other forms of ocular disease.

Adult↗

Single and double drug susceptibility testing of Mycobacterium avium complex and mycobacteria other than the tubercle (MOTT) bacilli by a micro-dilution broth minimum inhibitory concentration (MIC) method.

SETTING: The incidence of Mycobacterioses is increasing annually, especially in patients with AIDS. There is no clear correlation between in vitro drug susceptibility testing of mycobacteria other than the tubercle (MOTT) bacilli and the in vivo response. Although in vitro, MOTT bacilli appear resistant, some patients respond to treatment possibly as a result of a synergistic action between the drugs being used. OBJECTIVE: To produce a simple method to determine which individual drugs or combinations of drugs will be effective in killing the causative organism. DESIGN: A broth microdilution method, using microtitre plates, was used to determine the minimum inhibitory concentration (MIC) of the drugs alone and then in combination. RESULTS: It was found that the MIC values of the test drugs varied between but were constant within each of the species. Mycobacterium xenopi, M. malmoense and M. kansasii showed a large amount of susceptibility while M. avium complex, M. fortuitum and M. chelonae were limited in their response. These results were reproducible. The test was also easy to perform. The drug combination studies showed that each strain of the M. avium complex tested exhibited synergy between different combinations of drugs. CONCLUSION: This method, therefore, can be used to indicate individual or combinations of drugs that will or will not act upon the Mycobacterium species isolated. The method was also very rapid, giving a result within 7 days.

Antibiotics, Antitubercular↗