The cost of hospital care for management of invasive group A streptococcal infections in England.

The objective of this study was to estimate the direct financial costs of hospital care for management of invasive group A streptococcal (GAS) infections using hospital records for cases diagnosed in England. We linked laboratory-confirmed cases (n = 3696) identified through national surveillance to hospital episode statistics and reimbursement codes. From these codes we estimated the direct hospital costs of admissions. Almost all notified invasive GAS cases (92% of 3696) were successfully matched to a primary hospital admission. Of these, secondary admissions (within 30 days of primary admission) were further identified for 593 (17%). After exclusion of nosocomial cases (12%), the median costs of primary and secondary hospital admissions were estimated by subgroup analysis as £1984-£2212 per case, totalling £4·43-£6·34 million per year in England. With adjustment for unmatched cases this equated to £4·84-£6·93 million per year. Adults aged 16-64 years accounted for 48% of costs but only 40% of cases, largely due to an increased number of surgical procedures. The direct costs of hospital admissions for invasive GAS infection are substantial. These estimated costs will contribute to a full assessment of the total economic burden of invasive GAS infection as a means to assess potential savings through prevention measures.

Mortality in patients with meticillin-resistant Staphylococcus aureus bacteraemia, England 2004-2005.

A population-based study was undertaken to determine the short term risk of death in English patients diagnosed with meticillin-resistant Staphylococcus aureus (MRSA) bacteraemia. All patients with an MRSA-positive blood culture taken in 2004 and 2005 in England identified through routine surveillance were matched to the national registry of deaths. The study found an overall case fatality (all-cause) within 7 days of MRSA-positive blood culture diagnosis of 20%, rising to 38% within 30 days. Risk of death was highest on the day subsequent to the blood specimen being drawn (4%). Seven-day case fatality rates in women were 16% higher than for men (odds ratio: 1.16; 95% confidence interval: 1.04-1.29), although no significant difference was discernable by day 30. Risk of death increased with rising age, with 28% (425/1513) of patients aged ≥85 years dying within 7 days and 57% (859/1513) within 30 days. A seasonal pattern in case fatality rates was evident, highest in the winter and lowest in the summer. The age-standardised mortality ratios within the first week were 180 and 225 times as high for men and women, respectively, as for the general population. This declined rapidly after 10 weeks to approximately 9 for both sexes. An estimated 5.53 deaths per 100,000 population followed MRSA bacteraemia in 2004 and 2005, although no inference on causality or attributable mortality could be made through this study. The stable, elevated risk of death observable after 10 weeks compared with that in the general population gave an indication of the background risk of death unrelated to MRSA infection.

Enhanced surveillance of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland.

OBJECTIVE: To determine the incidence and demographic features of methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia in children in the UK and Ireland and to characterise MRSA isolated from cases. DESIGN: Prospective surveillance study. SETTING: Children aged <16 years hospitalised with bacteraemia due to MRSA. METHODS: Cases were ascertained by active surveillance involving paediatricians reporting to the British Paediatric Surveillance Unit and by routine laboratory surveillance. Patient characteristics were obtained using questionnaires sent to reporting paediatricians. MRSA isolates were characterised using molecular and phenotypic techniques including antimicrobial susceptibility testing. RESULTS: 265 episodes of MRSA bacteraemia were ascertained, involving 252 children. The overall incidence rate was 1.1 per 100 000 child population per year (95% CI 0.9 to 1.2): 61% of the children were aged <1 year (a rate of 9.7 cases per 100 000 population per year (95% CI 8.2 to 11.4)) and 35% were <1 month. Clinical data were obtained from 115 cases. The clinical presentation varied, with fever present in only 16% of neonates compared with 72% of older children. A history of invasive procedure was common, with 32% having had intravascular lines and 13% having undergone surgery. 62% of patients for whom data were available were receiving high-dependency care (46% in SCBU/NICU and 16% in PICU). Of 93 MRSA isolates studied, 73% belonged to epidemic strains widely associated with nosocomial infection in the UK and Ireland. CONCLUSIONS: MRSA bacteraemia in children was relatively uncommon and was predominantly seen in very young children, often those receiving neonatal or paediatric intensive care. Bacteraemia predominantly involved well-documented epidemic strains of MRSA associated with nosocomial infection.

A methodological approach to investigating a nationwide clinical specimen contamination problem in England.

Outbreaks of pseudo-infection due to contamination of specimens have been described, often as localised incidents. From August 2006, several English hospital laboratories began to refer an unusually high number of isolates of the fungus Paecilomyces variotii from clinical specimens to the national mycology reference laboratory for microbiological testing. We describe the methods used during the outbreak investigation in order to provide infection control specialists with an overview of how such national incidents may be investigated. We surveyed the hospitals reporting the contamination problem and conducted microbiological and environmental sampling. We applied analytical epidemiology to supply chain data, comparing the supply lines of key equipment to affected and unaffected hospitals in England. The survey was useful to describe procedures and equipment in use in the hospitals reporting the problem. The microbiological aspects of the investigation helped us understand how the fungal spores were distributed in the hospital environment. In the supply chain investigation we used data that was previously only used for logistical purposes. Overall the investigation was methodologically challenging, with no existing protocol to guide the investigators. To our knowledge, this is a novel approach to the investigation of such a widespread contamination problem, affecting geographically disparate hospitals at the same time.

Group B streptococcal disease in infants: a case control study.

OBJECTIVES: To describe and quantify the maternal and neonatal factors associated with Group B streptococcus (GBS) disease in infants <90 days of age. SETTING: Neonatal Units in London, Oxford, Portsmouth and Bristol. PATIENTS: Cases were infants <90 days of age with invasive GBS disease diagnosed between 2000 and 2003, and controls were healthy infants born in the same hospital and in the same birth weight category. MAIN OUTCOME MEASURES: Demographic and clinical data on the mother, baby, birth and neonatal stay. RESULTS: 138 cases and 305 controls were recruited. The majority of cases (74%) presented in the first week of life (early onset, EO); most on day 1 (89%). 65% of EO cases had one or more clinical risk factors (prematurity, prolonged rupture of membranes (PROM), known maternal GBS carriage, fever during labour). A multivariable logistic regression analysis found that the strongest independent associations with GBS disease were known maternal carriage of GBS (odds ratio (OR) 6.9), maternal infection in the peripartum period (OR 4.2) and maximum temperature in labour (OR 2.2 per degrees C). GBS disease was associated with twice the likelihood of PROM and fetal tachycardia (p = 0.05 and 0.07 respectively). EO cases had lower Apgar scores and were more likely to have respiratory distress and convulsions, and to require tube feeding than controls. They spent longer in hospital than controls, requiring longer stays at all levels of care. CONCLUSIONS: Independent of birth weight, a number of maternal, birth and neonatal factors are significantly associated with GBS disease. The management of babies with GBS disease results in an appreciable use of hospital resources.

Increase in invasive group A streptococcal infections in England, Wales and Northern Ireland, 2008-9.

Increases in invasive and non-invasive group A streptococcal diseases are currently being seen in the United Kingdom. National enhanced surveillance is being launched to examine the clinical presentations, risk factors, outcome and clustering patterns of cases to further inform public health management strategies.

Epidemic of severe Streptococcus pyogenes infections in injecting drug users in the UK, 2003-2004.

During the late 1990s, increases in referrals to the national reference laboratory of Streptococcus pyogenes isolates from injecting drug users (IDUs) with severe soft tissue infection indicated an emerging problem in the UK, later confirmed during the 2003-2004 European enhanced surveillance (Strep-EURO) programme. In light of these findings, further analyses were undertaken in an attempt to understand the reasons behind this increase in referrals. Single and multivariable analyses were undertaken to compare clinical, microbiological and demographic characteristics of IDUs diagnosed with severe S. pyogenes infection during the 2003-2004 enhanced surveillance study with those of other cases arising during this same period. Temporal and spatial analyses were undertaken for IDUs to identify clustering, as a means of understanding the transmission dynamics underpinning this increase. Infections in IDUs were spread across the UK, with some concentration in northern England and London. IDUs presented with a wide range of clinical manifestations, including pneumonia, which was found to be significantly more common in IDUs (OR 3.00) than in other cases. Marked differences in type distributions were found between IDUs and other cases, in particular the concentration of emm/M83 (22% of IDUs, 2% of non-IDUs). These findings indicate that an epidemic of severe S. pyogenes infections in IDUs occurred in the UK, peaking in 2003. The explanation for this rise remains unclear.

Candida parapsilosis infection in very low birthweight infants.

In a UK national surveillance study, we found that Candida parapsilosis accounted for one quarter of all cases of invasive fungal infection in very low birthweight infants. C parapsilosis was associated with fewer deep-seated infections than C albicans, but mortality was similar. Ongoing surveillance is needed to monitor the epidemiology of invasive fungal infection in very low birthweight infants.

Invasive fungal infection in very low birthweight infants: national prospective surveillance study.

OBJECTIVE: To describe the epidemiology of invasive fungal infection in very low birthweight (VLBW: <1500 g) infants in the United Kingdom. DESIGN: National prospective surveillance study between February 2003 and February 2004 using the British Paediatric Surveillance Unit reporting system reconciled with cases identified through routine laboratory reporting to the Health Protection Agency (England, Wales, and Northern Ireland), the Scottish Centre for Infection and Environmental Health, and the UK Mycology Reference Laboratory. RESULTS: Ninety four confirmed cases of invasive fungal infection were identified during the surveillance period giving an incidence of estimated annual incidence of 10.0 (95% confidence interval (CI) 8.0 to 12.0) cases per 1000 VLBW live births. Eighty one (86%) of the infants were of extremely low birth weight (ELBW: <1000 g), incidence 21.1 (95% CI 16.5 to 25.7) per 1000 ELBW live births. Candida species, predominantly C albicans and C parapsilosis, were isolated in 93% of cases. Most organisms were isolated from the bloodstream and urinary tract. Death occurred in 41% of the infected infants before 37 weeks postconceptional age. CONCLUSIONS: The incidence of invasive fungal infection in VLBW and ELBW infants in the United Kingdom is lower than reported in previous studies from tertiary centres in North America and elsewhere. The associated late neonatal and post-neonatal death rates are substantially higher than expected in infants without invasive fungal infection. These data may inform decisions about the evaluation and use of antifungal infection control strategies.

The epidemiology of severe Streptococcus pyogenes associated disease in Europe.

Several European countries reported outbreaks of severe disease caused by Streptococcus pyogenes in the late 1980s. This marked a departure from the previous decades, where very few such outbreaks were noted. These changes in disease occurrence formed part of a global phenomenon, the reasons for which have yet to be explained. Results of surveillance activities for invasive S. pyogenes infection within Europe over the past fifteen years identified further increases in many countries. However, variations in surveillance methods between countries preclude robust comparisons being made, illustrating the need for a unified surveillance strategy across Europe. This was finally embodied in the Strep-EURO programme, introduced in 2002.

Invasive group A streptococcal disease: should close contacts routinely receive antibiotic prophylaxis?

Group A streptococci (Streptococcus pyogenes) causes a wide range of illnesses from non-invasive disease--eg, pharyngitis--to more severe invasive infections--eg, necrotising fasciitis and toxic shock-like syndrome. There remains uncertainty about the risk of secondary cases of invasive disease occurring among close contacts of an index case and how best to manage that risk. We do not consider that currently available evidence justifies the routine administration of chemoprophylaxis to close contacts. We suggest that the appropriate response should be to routinely inform all household contacts of a patient with invasive group A streptococcal disease about the clinical manifestations of invasive disease and to seek immediate medical attention if they develop such symptoms.

The epidemiology of severe Streptococcus pyogenes associated disease in Europe.

Several European countries reported outbreaks of severe disease caused by Streptococcus pyogenes in the late 1980s. This marked a departure from the previous decades, where very few such outbreaks were noted. These changes in disease occurrence formed part of a global phenomenon, the reasons for which have yet to be explained. Results of surveillance activities for invasive S. pyogenes infection within Europe over the past fifteen years identified further increases in many countries. However, variations in surveillance methods between countries preclude robust comparisons being made, illustrating the need for a unified surveillance strategy across Europe. This was finally embodied in the Strep-EURO programme, introduced in 2002.

Emergence of methicillin resistant Staphylococcus aureus (MRSA) bacteraemia among children in England and Wales, 1990-2001.

Methicillin resistant Staphylococcus aureus (MRSA) is now a major cause of adult bacteraemia. All reports of Staphylococcus aureus bacteraemia to the Health Protection Agency were analysed from 1990 to 2001. There were 376 cases of MRSA bacteraemia in children <15 years over this time. The proportion of Staphylococcus aureus bacteraemia due to MRSA increased steadily from 0.9% in 1990 to 13% in 2000. The proportion was higher in infants. MRSA bacteraemia is now a serious problem in children in England and Wales. More data on the risk factors for acquisition and spread of MRSA in children are required.

Emerging trends in the epidemiology of invasive mycoses in England and Wales (1990-9).

Invasive fungal infections are becoming an increasing public health problem owing to the growth in numbers of susceptible individuals. Despite this, the profile of mycoses remains low and there is no surveillance system specific to fungal infections currently existing in England and Wales. We analysed laboratory reports of deep-seated mycoses made to the Communicable Disease Surveillance Centre between 1990 and 1999 from England and Wales. A substantial rise in candidosis was seen during this period (6.76-13.70 reports per million population/year), particularly in the older age groups. Rates of cryptococcosis in males fluctuated over the decade but fell overall (1.05-0.66 per million population/year), whereas rates of female cases gradually rose up until 1998 (0.04-0.41 per million population/year). Reports of Pneumocystis carinii in men reduced substantially between 1990 and 1999 (2.77-0.42 per million population/year) but showed little change in women. Reports of aspergillosis fluctuated up until 1996, after which reports of male and female cases rose substantially (from 0.08 for both in 1996 to 1.92 and 1.69 per million population/year in 1999 for males and females respectively), largely accounted for by changes in reporting practice from one laboratory. Rates of invasive mycoses were generally higher in males than females, with overall male-to-female rate ratios of 1.32 (95% CI 1.25-1.40) for candidosis, 1.30 (95% CI 1.05-1.60) for aspergillosis, 3.99 (95% CI 2.93-5.53) for cryptococcosis and 4.36 (95% CI 3.47-5.53) for Pneumocystis carinii. The higher male than female rates of reports is likely to be a partial reflection of HIV epidemiology in England and Wales, although this does not fully explain the ratio in infants and older age groups. Lack of information on underlying predisposition prevents further identification of risk groups affected. Whilst substantial under-reporting of Pneumocystis carinii and Cryptococcus species was apparent, considerable numbers of superficial mycoses were misreported indicating a need for clarification of reporting guidelines. Efforts to enhance comprehensive laboratory reporting should be undertaken to maximize the utility of this approach for surveillance of deep-seated fungal infections.

The national CD4 surveillance scheme for England and Wales.

This paper describes a national surveillance scheme, began in 1995, designed to monitor immunosuppression associated with HIV infection in adults in England and Wales. Currently 60 out of 64 (94%) laboratories performing CD4 cell counts participate in the scheme. The database contains over 42,000 patient records with over 300,000 counts, taken between April 1984 and March 2000. Approximately half of the patient records in the CD4 database match with patient records in the UK database of diagnosed HIV infections; a large proportion of the unmatched patients in the CD4 database may not be HIV-infected. Close to 50% of both men who have sex with men and injecting drug users and two-thirds of those who acquired their infection heterosexually had CD4 cell counts below 350 cells/mm3 at the time of HIV diagnosis. The National CD4 Surveillance Scheme provides important information regarding the epidemiology of HIV infection such as the changes in patterns of early and late diagnosis. It should continue to be used in conjunction with the other HIV surveillance systems to present as complete a picture of the epidemic as possible.

Failure to vaccinate current injecting drug users against hepatitis B in England and Wales.

In most industrialised countries the elimination of hepatitis B infection is highly reliant on effective vaccine delivery to injecting drug users. This paper highlights the very poor vaccine coverage achieved in England and Wales in the ten years since this problem was officially recognised and targeted. This is despite the existence of a comprehensive and well-utilised network of specialist services for injecting drug users.

Poor hepatitis B vaccine coverage in injecting drug users: England, 1995 and 1996.

Self-reported data on vaccination status collected in 1995 and 1996 from seven of the 39 drug agencies in England that took part in the unlinked anonymous HIV prevalence monitoring programme of injecting drug users were analysed to estimate hepatitis B vaccine coverage in this population. Twenty-seven per cent (374/1366) of injecting drug users (IDUs) reported vaccination against hepatitis B and 13% (172) reported having received three doses of vaccine. Eighteen per cent of the IDUs who reported vaccination (66/374) were found to have a marker in their saliva of past/current hepatitis B infection (antibody to hepatitis B core (anti-HBc)) compared with 23% (232/992) of those unvaccinated. Over half (760/1366) of all IDUs tested reported not having been vaccinated against hepatitis B were negative for anti-HBc, and therefore remained susceptible to infection. Targeted vaccination for IDUs against hepatitis B in England has had little success so far, suggesting that enhanced or alternative strategies need to be adopted.

The risk of infection with HIV and hepatitis B in individuals who inject steroids in England and Wales.

Data on injecting anabolic steroid users, within the national Unlinked Anonymous HIV Prevalence Monitoring Survey of injecting drug users (IDUs) were analysed to determine their risk of acquiring blood borne viruses. One hundred and forty-nine participants who had injected anabolic steroids in the previous month were identified from 1991-6, contributing 1.4% of all participation episodes in the survey. Rates of needle and syringe sharing by steroid users were low. Three of the 149 (2.0%) had anti-HBc and none had anti-HIV in their salivary specimens. The prevalence of anti-HBc in steroid injectors was significantly lower than in heroin injectors, 275/1509 (18%) (P < 0.001), or in amphetamine injectors, 28/239 (12%) (P < 0.001). The risk of blood borne virus transmission amongst these steroid injectors is low, probably due to hygienic use of injecting equipment and low levels of sharing. It is important to distinguish steroid injectors from other IDUs because they are a distinct group in terms of lifestyle and injecting practice.