摘要 :
An outbreak of isoniazid-resistant tuberculosis first identified in London has now been ongoing for 20 years, making it the largest drug-resistant outbreak of tuberculosis documented to date worldwide. We identified culture-confir...
展开
An outbreak of isoniazid-resistant tuberculosis first identified in London has now been ongoing for 20 years, making it the largest drug-resistant outbreak of tuberculosis documented to date worldwide. We identified culture-confirmed cases with indistinguishable molecular strain types and extracted demographic, clinical, microbiological and social risk factor data from surveillance systems. We summarised changes over time and used kernel-density estimation and k-function analysis to assess geographic clustering. From 1995 to 2014, 508 cases were reported, with a declining trend in recent years. Overall, 70% were male (n?=?360), 60% born in the United Kingdom (n?=?306), 39% white (n?=?199), and 26% black Caribbean (n?=?134). Median age increased from 25 years in the first 5 years to 42 in the last 5. Approximately two thirds of cases reported social risk factors: 45% drug use (n?=?227), 37% prison link (n?=?189), 25% homelessness (n?=?125) and 13% alcohol dependence (n?=?64). Treatment was completed at 12 months by 52% of cases (n?=?206), and was significantly lower for those with social risk factors (p?0.05), but increased over time for all patients (p?0.05). The outbreak remained focused in north London throughout. Control of this outbreak requires continued efforts to prevent and treat further active cases through targeted screening and enhanced case management. Keywords: tuberculosis, antimicrobial resistance, outbreaks, typing, geographic information system – GIS, social risk factorsIntroductionIncidence rates of tuberculosis have fallen in many European countries in recent years, but were increasing until 2009 in England and Wales, and have since remained relatively high [1]. In 2014, 6,520 cases were reported in England (12/100,000 inhabitants) and 115 in Wales (4/100,000). The highest incidence rate (30/100,000) was reported in London, where 39% of cases in England resided [2]. Multidrug-resistant (MDR) disease poses a particular threat to tuberculosis control as it cannot be managed using standard treatment regimens. Resistance to a single first-line drug is a precursor for development of MDR-tuberculosis, and isoniazid resistance is the most commonly identified form of resistance worldwide [3].In England and Wales, 6–7% of cases with drug-susceptibility results are resistant to isoniazid [2], and in 2013, 7% of isoniazid-resistant tuberculosis cases in England had a strain type known to be associated with an ongoing outbreak [4]. This outbreak was first identified in 2000 at a hospital in north London where three young men were diagnosed with an identical strain type of the Euro-American lineage within a week. Retrospective strain typing of isolates available at the time identified a further 15 cases, with the first case dating back to 1995 [5]. Cases have since been ascertained prospectively, and the outbreak now spans 20 years [6].Epidemiological characteristics of this ongoing outbreak were last described for cases up to 2006 [7]. These cases have previously been shown to include a high proportion of young males, particularly of white or black Caribbean ethnicity, who were born in the United Kingdom (UK) and lived in north London. Cases were also significantly more likely to present with social risk factors including imprisonment, unemployment, drug use or sex work [5,7,8]. An Outbreak Control Committee (OCC) established in 2000 recommended action on interagency working, improved identification and management of cases including use of directly observed therapy (DOT) and contact tracing, and improved control in prisons [9].As cases continue to be reported 20 years since the first identified case, this cluster now represents one of the largest documented outbreaks worldwide of drug-resistant tuberculosis. In this study, we aimed to describe the evolution of the outbreak in time and space and discuss implications for future tuberculosis control.MethodsOutbreak case definition and data sourcesCases were defined as individuals diagnosed from 1995 to 2014 in England and Wales with a Mycobacterium tuberculosis isolate that was indistinguishable from the outbreak strain. Following identification of the outbreak in January 2000, cases were ascertained prospectively by strain typing of all isoniazid-resistant isolates from patients resident in, or with known epidemiological links to, London. Prior to 2000, cases were ascertained retrospectively through review of microbiological databases and strain typing of identified isolates [7]. From 2010 onwards, strain typing was conducted on all tuberculosis isolates in England and Wales, regardless of links to London.The outbreak strain was initially characterised using restriction fragment length polymorphism (RFLP) analysis and before 2000, the isolates selected for typing were those of isoniazid monoresistant organisms cultured at four laboratories serving the area where first cases were reported. After 2000 all such strains across London were RFLP-typed,
收起