Multidrug resistance emerging in North London outbreak.
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Disease Outbreaks↗
Biomedical subjects
H Maguire
Publications and source records attributed to H Maguire.
Epidemiology and response to the growing problem of tuberculosis in London.
As in other countries with low tuberculosis incidence, tuberculosis in England and Wales tends to be concentrated in some subgroups of the population, and is mainly a problem in large cities. In 2003, almost half of all tuberculosis cases reported in England and Wales were from London, where the incidence was almost five times higher than in the rest of England and Wales. While the highest proportion of cases occur in foreign born patients, evidence from a large outbreak of drug resistant tuberculosis points to ongoing active transmission among marginalised groups including homeless people, hard drug users, and prisoners. Increasing rates of disease and levels of drug resistance, combined with a concentration of disease in hard-to-reach risk groups now present a major challenge to tuberculosis control in the city. To respond to the changing epidemiology observed in recent years, treatment and control services are being reconfigured, surveillance has been improved with the implementation of the London TB register, and the utility of mobile digital x ray screening for at risk populations such as homeless people and prisoners is being evaluated. However, tuberculosis in London is not yet under control and more needs to be done. Services must adapt to the needs of those groups now most affected. This will require continued improvements to surveillance and monitoring, combined with improved access to care, better case detection, rapid diagnosis and active social support for people undergoing treatment.
Journal Article↗
Large outbreak of measles in London: reversal of health inequalities.
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Child↗
The public health response to a case of Lassa fever in London in 2000.
OBJECTIVES: Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. METHODS: Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. RESULTS: Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. CONCLUSIONS: If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.
Communicable Disease Control↗
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↗
Surveillance of antenatal infections--HIV, hepatitis B, syphilis and rubella susceptibility in London.
London has relatively high rates of HIV, hepatitis B and syphilis, and has the potential for undiagnosed infection in pregnancy. As part of a drive to improve HIV testing in pregnancy, surveillance of a number of antenatal infections has been carried out in London's 30 maternity units since 2000. Infection screening rates rose from 89% in 2000 to 94% in 2002, and HIV screening rates increased from 66% to 86%. During 2002, 115,230 women booked for antenatal care; 998 were HBsAg positive (about ten in 1000), 452 were HIV positive (five in 1,000), 412 tested positive for syphilis (four in 1000), and 3,929 were susceptible to rubella (36 in 1000). The main burden of infection was concentrated in a few geographic areas. Worryingly the majority of women found to be HIV positive were diagnosed by antenatal screening and not before.
Disease Susceptibility↗
Estimation of the rate of unrecognized cross-contamination with mycobacterium tuberculosis in London microbiology laboratories.
Isolates from patients with confirmed tuberculosis from London were collected over 2.5 years between 1995 and 1997. Restriction fragment length polymorphism (RFLP) analysis was performed by the international standard technique as part of a multicenter epidemiological study. A total of 2,779 samples representing 2,500 individual patients from 56 laboratories were examined. Analysis of these samples revealed a laboratory cross-contamination rate of between 0.54%, when only presumed cases of cross-contamination were considered, and 0.93%, when presumed and possible cases were counted. Previous studies suggest an extremely wide range of laboratory cross-contamination rates of between 0.1 and 65%. These data indicate that laboratory cross-contamination has not been a common problem in routine practice in the London area, but in several incidents patients did receive full courses of therapy that were probably unnecessary.
Bacterial Typing Techniques↗
Resurgence of paediatric tuberculosis in London.
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Adolescent↗
Molecular epidemiology of tuberculosis in London 1995-7 showing low rate of active transmission.
BACKGROUND: Tuberculosis notification rates for London have risen dramatically in recent years. Molecular typing of Mycobacterium tuberculosis has contributed to our understanding of the epidemiology of tuberculosis throughout the world. This study aimed to assess the degree of recent transmission of M tuberculosis in London and subpopulations of the community with high rates of recent transmission. METHODS: M tuberculosis isolates from all persons from Greater London diagnosed with culture positive tuberculosis between 1 July 1995 and 31 December 1997 were genetically fingerprinted using IS6110 restriction fragment length polymorphism (RFLP) typing. A structured proforma was used during record review of cases of culture confirmed tuberculosis. Cluster analysis was performed and risk factors for clustering were examined in a univariate analysis followed by a logistic regression analysis with membership of a cluster as the outcome variable. RESULTS: RFLP patterns were obtained for 2042 isolates with more than four copies of IS6110; 463 (22.7%) belonged to 169 molecular clusters, which ranged in size from two (65% of clusters) to 12 persons. The estimated rate of recent transmission was 14.4%. Young age (0-19 years) (odds ratio (OR) 2.65, 95% confidence interval (CI) 1.59 to 4.44), birth in the UK (OR 1.55, 95% CI 1.04 to 2.03), black Caribbean ethnic group (OR 2.19, 95% CI 1.15 to 4.16), alcohol dependence (OR 2.33, 95% CI 1.46 to 3.72), and streptomycin resistance (OR 1.82, 95% CI 1.15 to 2.88) were independently associated with an increased risk of clustering. CONCLUSIONS: Tuberculosis in London is largely caused by reactivation or importation of infection by recent immigrants. Newly acquired infection is also common among people with recognised risk factors. Preventative interventions and early diagnosis of immigrants from areas with a high incidence of tuberculosis, together with thorough contact tracing and monitoring of treatment outcome among all cases of tuberculosis (especially in groups at higher risk of recent infection), remains most important.
Adolescent↗
Induction of potent Th1-type immune responses from a novel DNA vaccine for West Nile virus New York isolate (WNV-NY1999).
West Nile virus (WNV) is a vectorborne pathogen that induces brain inflammation and death. Recently, confirmed cases of infection and deaths have occurred in the United States Mid-Atlantic region. In this study, a DNA vaccine encoding the WNV capsid protein was constructed, and the in vivo immune responses generated were investigated in DNA vaccine-immunized mice. Antigen-specific humoral and cellular immune responses were observed, including a potent induction of antigen-specific Th1 and cytotoxic T lymphocyte responses. Strong induction of Th1-type immune responses included high levels of antigen-specific elaboration of the Th1-type cytokines interferon-gamma and interleukin-2 and beta-chemokines RANTES (regulated upon activation, normal T cell-expressed and secreted) and macrophage inflammatory protein-1beta. Dramatic infiltration of CD4 and CD8 T cells and macrophages also was observed at the muscle injection site. These results support the potential utility of this method as a tool for developing immunization strategies for WNV and other emerging pathogens.
Animals↗
Anti-idiotypic antibody (ab2) vaccines: coupling of Ab2 BR3E4 to KLH increases humoral and/or cellular immune responses in animals and colorectal cancer patients.
The colorectal carcinoma (CRC)-associated CO17-1A/GA733 antigen (Ag) has been the target of a phase II/III randomized trial of passive immunotherapy with monoclonal antibody CO17-1A (Ab1), and phase I active immunotherapy trials with polyclonal anti-idiotypic antibodies (Ab2) mimicking the CO17-1A or GA733 epitope of the Ag. However, monoclonal rat Ab2 BR3E4 directed against Ab1 CO17-1A was superior to polyclonal Ab2 in inducing antigen-specific humoral and cellular immune responses in mice and rabbits. Various forms of Ab2 BR3E4, i.e., BR3E4-F(ab')2 precipitated with aluminum-hydroxide (alum), BR3E4-F(ab')2 coupled to KLH and precipitated or non-precipitated with alum, and BR3E4-IgG in alum or incomplete Freund's adjuvant were compared for their capacity to induce in rabbits anti-anti-idiotypic antibodies (Ab3) that specifically bind to the CO17-1A Ag. BR3E4-F(ab')2 coupled to KLH and precipitated with alum was shown to induce the highest Ab3 titers, followed by Ab2 BR3E4-IgG in alum. Therefore Ab2 BR3E4 as intact IgG (IgG group) or as F(ab')2 coupled to KLH (KLH group), was administered in a phase I trial to 45 patients with CRC, stage Dukes'D (UICC stage IV), with the goal to modulate patients' immune responses to their tumors. Fifteen of 23 patients in the IgG group developed Ab3 binding specifically to Ab2, and in four of these patients the Ab3 also specifically bound to Ag-positive CRC cells. Lymphoproliferative responses to Ab2 and/or GA733-2E Ag stimulation were observed in three of these patients. Eighteen of the 22 KLH group patients tested developed Ab3 and the Ab3 bound specifically to CRC cells in eight patients. Five of the 15 KLH group patients tested developed lymphoproliferative responses to Ab2 and/or GA733-2E Ag. Thus, there was a trend for the KLH group demonstrating higher immune response rates than the IgG group. Clinical responses were rare in these patients with liver metastases.
Animals↗
Evidence base of incubation periods, periods of infectiousness and exclusion policies for the control of communicable diseases in schools and preschools.
BACKGROUND: The optimal control of communicable diseases requires accurate information on incubation periods, periods of infectiousness and the effectiveness of exclusion. We collected the available evidence for a wide range of infections and infestations and produced evidence-based guidelines for their control in schools and preschools. METHODS: A thorough MEDLINE literature search was conducted on the incubation period, period of infectiousness and effectiveness of exclusion for 41 infections. The quality of the information obtained was indicated by levels of evidence. The information was used to produce guidelines on exclusion, and the recommendations were graded according to the levels of evidence available. Grades A, B and C represented strongly, reasonably and poorly evidence-based recommendations, respectively. RESULTS: The quality of data obtained was highly variable. Information on incubation periods was obtained for all 41 infections and was generally of good quality. Information on periods of infectiousness and effectiveness of exclusion was of a lesser quality and was found for only 11 and 4 conditions, respectively. There were 3 Grade A, 17 Grade B and 21 Grade C recommendations on exclusion. Examples of exclusion periods include: 5 days for chickenpox, measles, mumps, rubella, pertussis and scarlet fever; and 24 h from the cessation of diarrhea for most gastrointestinal diseases In contrast to existing guidelines exclusion was not recommended for school age children with hepatitis A. CONCLUSIONS: We have been able to present the best available data on the incubation periods and periods of infectiousness of 41 childhood infections. It was possible to produce strongly or reasonably evidence-based guidelines on exclusion periods for approximately one-half of the infections.
Child↗
An outbreak of hepatitis A among young men associated with having sex in public venues.
An increase in hepatitis A virus (HAV) infection was noted among young men in the former Thames regions during 1997. A retrospective case-control study, using a standardised questionnaire at interview, was conducted in the area most affected (London and East Sussex) to investigate the hypothesis that this increase was mainly among homosexual men and to establish the risk factors associated with transmission. Forty-eight cases and 161 controls completed questionnaires. Forty-one cases (85%) described their sexuality as homosexual (p < 0.0001). Cases were more likely than controls to have eaten shellfish (Odds Ratio (OR) 2.4; 95% Confidence Interval (CI) 1.16, 5.04) during the two months before onset of illness. Cases had more sexual partners (p = 0.015), and more casual sexual partners (p = 0.007) than controls. Cases were more likely to have had sex in a gay sauna (OR 3.5; 95% CI 1.53, 8.30), or in a gay club, pub or disco (OR 2.9; 95 CI 1.29, 6.63) than controls. After adjusting for confounding factors, cases were more likely to have eaten shellfish (adjusted [adj] OR 3.0; 95% CI 1.33, 6.59) and to have had sex in a gay sauna (adj OR 3.9; 95% CI 1.42, 10.59). Public health messages need to inform homosexual men about recognised risk factors such as eating shellfish and travel abroad to endemic areas, as well as sexual risks. Homosexual men can benefit from hepatitis A vaccine. We would suggest that in an outbreak situation men who have multiple anonymous partners and have sex in public venues should be targeted as a priority for health education and immunisation.
Adolescent↗
Increasing gonorrhoea reports--not only in London.
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Adolescent↗
Hospital outbreak of Salmonella virchow possibly associated with a food handler.
A foodborne outbreak of salmonella infection at a private hospital in London in 1994 was found to be associated with eating turkey sandwiches prepared by a food handler. One patient, nine staff, and a foodhandler's baby were confirmed to have Salmonella enterica serotype virchow, phage type 26 infection. The attack rate was estimated to be 5% among the approximately 200 patients and staff at risk. A food handler reportedly became ill days after, but her baby days before, the first hospital case. Although it appeared to be a single outbreak, antibiogram analysis, supplemented by plasmid profile typing, demonstrated that there were two strains of S. virchow involved, one with resistance to sulphonamides and trimethoprim and a second sensitive to these antimicrobial drugs. Mother and child had different strains. The investigation demonstrated the importance of full phenotypic characterization of putative outbreak strains including antimicrobial susceptibility testing. Outbreaks of foodborne infection in hospitals are preventable and are associated with high attack rates and disruption of services. There is a need for good infection control policies and training of all staff involved in patient care as well as in catering services. Consultants in Communicable Disease (CCDCs) should include private hospitals in their outbreak control plans. Good working relations between Infection Control Doctors (ICDs) in the private health sector and their local CCDCs are important if outbreaks are to be properly investigated.
Adult↗
Antimicrobial activities of synthetic bismuth compounds against Clostridium difficile.
Clostridium difficile is a major nosocomial pathogen responsible for pseudomembranous colitis and many cases of antibiotic-associated diarrhea. Because of potential relapse of disease with current antimicrobial therapy protocols, there is a need for additional and/or alternative antimicrobial agents for the treatment of disease caused by C. difficile. We have synthesized a systematic series of 14 structurally simple bismuth compounds and assessed their biological activities against C. difficile and four other gastrointestinal species, including Helicobacter pylori. Here, we report on the activities of six compounds that exhibit antibacterial activities against C. difficile, and some of the compounds have MICs of less than 1 microgram/ml. Also tested, for comparison, were the activities of bismuth subcitrate and ranitidine bismuth citrate obtained from commercial sources. C. difficile and H. pylori were more sensitive both to the synthetic bismuth compounds and to the commercial products than were Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis, and the last three species were markedly resistant to the commercial bismuth salts. Testing with human foreskin fibroblast cells revealed that some of the synthetic compounds were more cytotoxic than others. Killing curves for C. difficile treated with the more active compounds revealed rapid death, and electron microscopy showed that the bismuth of these compounds was rapidly incorporated by C. difficile. Energy dispersive spectroscopy X-ray microanalysis of C. difficile cells containing electron-dense material confirmed the presence of internalized bismuth. Internalized bismuth was not observed in C. difficile treated with synthetic bismuth compounds that lacked antimicrobial activity, which suggests that the uptake of the metal is required for killing activity. The nature of the carrier would seem to determine whether bismuth is transported into susceptible bacteria like C. difficile.
Anti-Bacterial Agents↗
Incidence of gonorrhoea diagnosed in GUM clinics in South Thames (west) region.
OBJECTIVES: To describe the incidence of gonorrhoea diagnosed in genitourinary medicine (GUM) clinics in South Thames (West) between 1995 and 1996, and how it changed among population subgroups. SETTINGS AND SUBJECTS: Cases of uncomplicated and complicated gonorrhoea diagnosed at 13 GUM clinics in the former South Thames West (STW) Regional Health Authority that reported disaggregate data to the South Thames GUM Clinic Collaborative STD Surveillance Scheme. METHODS: Annual incidence rates (per 100,000) of gonorrhoea diagnoses by sex, age group, ethnic group, area of residence, and year were calculated. Poisson regression models were used to calculate risk ratios (RR) to describe the key differences in the variation of gonorrhoea cases by these variables. Relative differences in the incidence of diagnosed gonorrhoea between 1995 and 1996 were investigated by including an interaction between year and the other variables (age group, sex, ethnic group, region) and testing whether any were significant using a likelihood ratio test. RESULTS: Area of residence, sex, age group, and ethnic group were key predictors of the rates of diagnosed gonorrhoea. The risk ratio for gonorrhoea (after adjustment for the other variables) was: 13 times higher among blacks than the white population; twice as high in inner London compared with outer London; and three times lower in the "shire" region compared with outer London. The rate of diagnosed gonorrhoea was significantly higher in the black population in the shire region than the inner London white population. The rate of gonorrhoea diagnosed by GUM clinics from 1995 to 1996 almost doubled in the white population aged 15-44 years, from 16 cases per 100,000 to 30 cases per 100,000 (adjusted RR 2.0, 95% CI 1.6 to 2.4), whereas increased rates in the black and Asian/other ethnic groups were not statistically significant (adjusted RR 1.1, 95% CI 0.9 to 1.4; and 1.4, 95% CI 0.7 to 2.7 respectively). CONCLUSION: The observed increase in gonorrhoea between 1995 and 1996 occurred mostly among heterosexual white men and women. Overall, the rates of gonorrhoea among young people, especially in the black population and in inner London represent a significant public health problem that may merit further targeted interventions, the effectiveness of which could be monitored through further development of routine surveillance data.
Adolescent↗
Outbreak of hepatitis B in an acupuncture clinic.
A retrospective cohort serological study identified five confirmed cases of acute hepatitis B virus (HBV) infection in three and a half years at an acupuncture clinic in London. These cases made up 1.7% of those treated by an acupuncturist who was a hepatitis B 'e' antigen (HBeAg) carrier. Virus subtyping and polymerase chain reaction--single strand conformation polymorphism assay (PCR-SSCPA) showed that strains of virus from the acupuncturist and two of the five patients for whom it was possible to perform the test were indistinguishable. Nine other patients who attended the same acupuncturist had antibody to the hepatitis B core antigen but had other risk factors for HBV infection. No obvious mode of transmission was identified but cross contamination of needles could not be ruled out in two cases. The fifth case was exposed to HBV after disposable needles were introduced. Routine immunisation of acupuncturists against HBV is recommended.
Acupuncture Therapy↗