We describe the identification of, and risk factors for, the single most prevalent Mycobacterium tuberculosis strain in the West Midlands region of the UK. Two retrospective epidemiological investigations were also undertaken using univariable and multivariable logistic regression analysis. A second more detailed investigation analyzed a cohort of 82 patients resident in Wolverhampton between and The continued consistent presence of the Mercian strain suggests ongoing community transmission.
Whilst ificant associations have been found, there may be other common risk factors yet Looking for sex san West midlands be identified. Future investigations should focus on targeting the relevant risk groups and elucidating the biological factors that mediate continued transmission of this strain. This is an open-access article distributed under the terms of the Creative Commons Attributionwhich permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
The Department of Health had no role in study de, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist. DNA fingerprinting of Mycobacterium tuberculosis has a key role in TB control and cluster investigation as the molecular data obtained can be used to direct and focus public health control efforts . For example, DNA fingerprinting enhanced the investigation of a large outbreak in North London where many of the epidemiological links would not have been established by routine contact tracing or traditional epidemiological investigations alone . Large-scale studies of M. The of cases of tuberculosis in the UK has consistently increased each year since the late s with 8, cases There were 1, clinical cases Birmingham is the largest city in the West Midlands with a rate Looking for sex san West midlands There were We analyzed all M.
We then examined the geographical distribution and epidemiological characteristics of cases infected with this strain in the West Midlands region, and in the city of Wolverhampton, which was found to have the highest proportion of patients with this strain. The setting for this study was the West Midlands region of the UK. This region had a total population of 5. The city of Birmingham has the largest population in the West Midlands with one million inhabitants .
Prospective universal DNA fingerprinting was undertaken between and with retrospective genotyping carried out on strains isolated before Retrospective observational epidemiological investigations were undertaken within one city and on a regional scale.
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From onwards, all M. The most recent complete calendar year available for molecular and epidemiological data analysis was For M. Spoligotyping was carried out to identify the global strain family that the most prevalent strain is part of. Spoligotyping was performed using the Luminex Multianalyte Profiling System as ly described .
Spoligotype families were ased by comparison to the international SpolDB4 database . Patients with M. The HPA Enhanced Tuberculosis Surveillance System contains molecular, pathological, and treatment data on all notified cases of tuberculosis in England including culture-confirmed cases and clinically diagnosed cases. All patients with strain typing data were selected for comparison. More specific analysis of patient residence was undertaken by analyzing patient location within one of 33 Local Authority regions in the West Midlands.
Local Authorities are administrative regions that are based on city or county boundaries. Laboratory records of patients with the most prevalent strain were used to map patient residential location using postcode within the West Midlands. When it became apparent that there was a cohort of patients in Wolverhampton with an indistinguishable MIRU-VNTR profile, a retrospective review of patient case notes and interview of specialist tuberculosis nurses who were involved with the care of these patients was undertaken for culture-positive patients resident in Wolverhampton diagnosed with the same indistinguishable MIRU-VNTR profile between June and February to identify common factors and potential epidemiological links.
These patients were compared to culture-positive cases diagnosed with other strains in A questionnaire was deed to collect comprehensive epidemiologic information including demographic characteristics, clinical history, predisposing risk factors and evidence of contact with patients with active disease caused by any strain.
Information was also obtained on occupational, social and recreational history, compliance with tuberculosis treatment and change in weight after eight weeks treatment. Chest radiographs of all patients were reviewed for the presence of cavitation.
Proportions calculated from epidemiological data obtained from the West Midlands regional and Wolverhampton city datasets were compared using Pearson's chi-squared test with Fisher's exact test where necessary. All cases with missing values for the variables examined were excluded from the multivariate model with patients infected by the Mercian strain and 1, patients in the control group included.
Differences in proportions between entries with complete data for each variable and missing data for at least one variable was analysed. A univariate analysis of the epidemiological investigation of patients resident in Wolverhampton was undertaken using EpiData Analysis v2. This report details the current status of the investigation into the most prevalent strain in the West Midlands, which has been undertaken as part of normal public health practice by microbiologists, respiratory physicians, and public health teams.
Therefore, specific ethical approval was not required.
Between and4, isolates were typed from 31 referring laboratories in the West and East Midlands. This profile was identified soon after universal prospective DNA fingerprinting was initiated in and has been consistently identified since then Figure 1. The HPA UK Mycobacterium tuberculosis Strain Typing Database was interrogated to analyze the national distribution of the most prevalent strain in the West Midlands with a total of isolates identified across the UK between and Figure 2 shows the geographical mapping of in the West Midlands between and The city of Wolverhampton where the focused epidemiological investigation was undertaken is highlighted in yellow.
Retrospective typing of stored M. A selection of 10 strains from five different locations isolated between and were analyzed by the optimal 24 MIRU-VNTR loci set and spoligotyping. All 10 strains were indistinguishable at each of the 24 loci and possessed an indistinguishable spoligotype octal type which is shared type ST and is a member of the Clade X1 global clade.
Investigation of the global SpolDB4 database revealed that only 3 strains with this shared type have been identified. Each horizontal lane is an example of an individual M. The 8 th IS fragment was identified in an isolate from Wolverhampton in There were 2, tuberculosis patients with other strain types notified in the West Midlands between and Patient characteristics identified as risk factors ificant in a univariate analysis Table 1 and Table S1 for all epidemiological variables were residence in the West Midlands West Health Looking for sex san West midlands Unit Area and then specifically residence in Wolverhampton, UK-born, and Black Caribbean or White ethnic group.
ificant negative associations were identified with age not greater than 65 years old, the Black African ethnic group or extra-pulmonary disease. There were no statistically ificant differences between patients with complete data for each variable compared to those with missing data in both this analysis and the following city-wide epidemiological investigation.
The Mercian strain in Wolverhampton was ificantly associated with white UK-born patients who presented with cavitations on chest X-ray and produced smear positive specimens Table 2 and Table S2 for all epidemiological variables. Patients infected with the Mercian strain continued to experience weight loss at 8 weeks after starting anti-tubercular chemotherapy.
However, there was no ificant difference between treatment completion rates after 12 months. ificant social factors detected were evidence of excess alcohol intake and cannabis use. We describe here the identification of the most prevalent M. Regional, national, and global genotyping databases provided evidence that this strain was restricted to the West Midlands region in England. Regional data showed that this strain primarily infected UK-born, Black Caribbean patients less than 65 years old.
The regional and Wolverhampton epidemiological investigations presented in this report identified ificant associations for the Mercian strain. However, they do not provide a full explanation of why the Mercian strain is more prevalent compared to other strains in the West Midlands.
Drug and alcohol use were identified as ificant social factors in Wolverhampton. Alcohol and drug use have been identified as ificant associations in ly reported tuberculosis outbreaks particularly in low-incidence countries  — . The cumulative of cases and continuing presence of the Mercian strain does not follow a typical point-source outbreak pattern.
The ificant association with younger Looking for sex san West midlands suggests that cases caused by the Mercian strain have arisen as a result of recent transmission and not re-activation in older patients. A possible transmission scenario is that after the initial emergence of the Mercian strain there have been several independent clusters of transmission each with their own common social link.
This has resulted in a large, complex social network where transmission persists and the complete transmission scenario is yet to be fully elucidated. Both epidemiological investigations presented in this report were retrospective and did not involve direct patient interviews. The Mercian strain continues to be identified in the West Midlands which means that enhanced epidemiological knowledge could be obtained by prospectively investigating social links as each new patient is diagnosed.
Investigation of potential factors which may cause a delay in diagnosis should be investigated as well. The data presented by us identified the infected patient population and also important common social factors. The exact interaction of patient population and social factors should be investigated further to identify and fully understand any confounding factors.
It must be noted that the Wolverhampton epidemiological investigation applied a detailed questionnaire that was only used in this location. Patients with the Mercian strain in Birmingham and Coventry might differ in their use of drugs and alcohol.
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The from the Wolverhampton and region-wide analysis do not concord exactly as different ethnic population groups were identified as at highest risk: the White population in Wolverhampton but the Black Caribbean group across the West Midlands.
Detection of this strain was only possible with the commencement of universal prospective typing of all M. Only with universal prospective DNA fingerprinting was the full extent of the Mercian strain in the West Midlands fully characterized.
Since the Mercian strain is not a drug-resistant strain without associated phenotypic properties that could differentiate it from other M. The patient population in which the Mercian strain has been identified is different to the UK-wide situation for TB as the majority of patients diagnosed each year in the UK are not born in the UK and originate from the Indian Sub-Continent .