Nosocomial Transmission of Coronavirus Disease 2019: A Retrospective Study of 66 Hospital-acquired Cases in a London Teaching Hospital.

Coronavirus disease 2019 (COVID-19) can cause deadly healthcare-associated outbreaks. In a major London teaching hospital, 66 of 435 (15%) COVID-19 inpatient cases between 2 March and 12 April 2020 were definitely or probably hospital-acquired, through varied transmission routes. The case fatality was 36%. Nosocomial infection rates fell following comprehensive infection prevention and control measures.

Estimating the Hospital Burden of Norovirus-Associated Gastroenteritis in England and Its Opportunity Costs for Nonadmitted Patients.

Background: Norovirus places a substantial burden on healthcare systems, arising from infected patients, disease outbreaks, beds kept unoccupied for infection control, and staff absences due to infection. In settings with high rates of bed occupancy, opportunity costs arise from patients who cannot be admitted due to beds being unavailable. With several treatments and vaccines against norovirus in development, quantifying the expected economic burden is timely. Methods: The number of inpatients with norovirus-associated gastroenteritis in England was modeled using infectious and noninfectious gastrointestinal Hospital Episode Statistics codes and laboratory reports of gastrointestinal pathogens collected at Public Health England. The excess length of stay from norovirus was estimated with a multistate model and local outbreak data. Unoccupied bed-days and staff absences were estimated from national outbreak surveillance. The burden was valued conventionally using accounting expenditures and wages, which we contrasted to the opportunity costs from forgone patients using a novel methodology. Results: Between July 2013 and June 2016, 17.7% (95% confidence interval [CI], 15.6%‒21.6%) of primary and 23.8% (95% CI, 20.6%‒29.9%) of secondary gastrointestinal diagnoses were norovirus attributable. Annually, the estimated median 290000 (interquartile range, 282000‒297000) occupied and unoccupied bed-days used for norovirus displaced 57800 patients. Conventional costs for the National Health Service reached £107.6 million; the economic burden approximated to £297.7 million and a loss of 6300 quality-adjusted life-years annually. Conclusions: In England, norovirus is now the second-largest contributor of the gastrointestinal hospital burden. With the projected impact being greater than previously estimated, improved capture of relevant opportunity costs seems imperative for diseases such as norovirus.

Long-term outcomes of pneumococcal meningitis in childhood and adolescence.

A vaccine to prevent pneumococcal meningitis (PM) has recently been introduced. However, contemporary data to inform cost-effectiveness analysis and justify its routine use are sparse. We examined the cognitive, educational, psychological and social outcomes of PM in childhood. We completed a population-based case-control study in two regions of the UK. Children and young people currently between 3 and 20 years of age that had been diagnosed with PM ≤14 years of age were identified from active regional surveillance. Controls were siblings or neighbours of similar age. Standardised questionnaires and neuropsychological testing was administered to assess IQ, educational attainments, memory, psychological distress, quality of life and hearing impairment. Data were available on 97 patients and 93 controls. Eighty-four patients had a sibling/neighbour-matched control. Both matched and unmatched analyses were completed, and results of the 84 matched comparisons were highly similar to the unmatched. For the total sample, controls were similar in age, ethnicity and socioeconomic status. Median age at meningitis was 11 months. Median time between meningitis and assessment was 6.0 years. In the matched analysis, partial or profound hearing impairment was reported in 14% of patients and 1% of controls. Patients had significantly lower mean full-scale IQ (p = 0.05), verbal IQ (p = 0.0008), numeracy (p = 0.02), total quality of life (p = 0.04), school functioning (p = 0.005), psychosocial functioning (p = 0.001) and psychological difficulties (p = 0.01). Parents of patients reported greater functional disability (p = 0.008), impairment in all aspects of quality of life (p = 0.001) and psychological difficulties (p < 0.0006). Findings for IQ were not materially different when analyses were repeated only in those without hearing impairment. In multivariate regression analysis that included both case-control status and hearing status, both being a patient (p = 0.001) and having profound hearing impairment (p = 0.001) were independently associated with lower full-scale IQ. Conclusions Pneumococcal meningitis is associated with major sequelae. Our findings strongly support the introduction of pneumococcal conjugate vaccine as part of routine childhood vaccination programmes internationally.

Moving beyond hand hygiene monitoring as a marker of infection prevention performance: Development of a tailored infection control continuous quality improvement tool.

BACKGROUND: Infection control practice compliance is commonly monitored by measuring hand hygiene compliance. The limitations of this approach were recognized in 1 acute health care organization that led to the development of an Infection Control Continuous Quality Improvement tool. METHODS: The Pronovost cycle, Barriers and Mitigation tool, and Hexagon framework were used to review the existing monitoring system and develop a quality improvement data collection tool that considered the context of care delivery. RESULTS: Barriers and opportunities for improvement including ambiguity, consistency and feasibility of expectations, the environment, knowledge, and education were combined in a monitoring tool that was piloted and modified in response to feedback. Local adaptations enabled staff to prioritize and monitor issues important in their own workplace. The tool replaced the previous system and was positively evaluated by auditors. Challenges included ensuring staff had time to train in use of the tool, time to collect the audit, and the reporting of low scores that conflicted with a target-based performance system. CONCLUSIONS: Hand hygiene compliance monitoring alone misses other important aspects of infection control compliance. A continuous quality improvement tool was developed reflecting specific organizational needs that could be transferred or adapted to other organizations.

Health related quality of life in survivors of pneumococcal meningitis.

AIM: To estimate the overall long-term health related quality of life implications of an episode of pneumococcal meningitis in childhood. METHOD: Cases were identified through two regional UK surveillance studies and traced via their general practitioners (GPs) or local hospital paediatrician. Siblings were used as controls where available. Health related quality of life was assessed using the health utilities index (HUI). Mean utility scores were compared between cases and controls and univariate linear regression was used to identify factors that influenced the overall utility scores. RESULTS: HUI data were available for 71 cases and 66 controls. The mean overall utility score for cases 0.774 (95% CI 0.711- 0.837) was significantly lower than for controls 0.866 (95% CI 0.824-0.907) (p-value = 0.0185). Hearing was the most significantly affected health attribute (p-value < 0.006). In cases, males had lower quality of life scores than females (p-value = 0.018), however this was not seen in controls. CONCLUSION: An episode of pneumococcal meningitis results in a long-term decrement in overall health related quality of life and is significantly related to hearing loss.

Validity of hand hygiene compliance measurement by observation: A systematic review.

BACKGROUND: Hand hygiene is monitored by direct observation to improve practice, but this approach can potentially cause information, selection, and confounding bias, threatening the validity of findings. The aim of this study was to identify and describe the potential biases in hand hygiene compliance monitoring by direct observation; develop a typology of biases and propose improvements to reduce bias; and increase the validity of compliance measurements. METHODS: This systematic review of hospital-based intervention studies used direct observation to monitor health care workers' hand hygiene compliance. RESULTS: Seventy-one publications were eligible for review. None was free of bias. Selection bias was present in all studies through lack of data collection on the weekends (n = 61, 86%) and at night (n = 46, 65%) and observations undertaken in single-specialty settings (n = 35, 49%). We observed inconsistency of terminology, definitions of hand hygiene opportunity, criteria, tools, and descriptions of the data collection. Frequency of observation, duration, or both were not described or were unclear in 58 (82%) publications. Observers were trained in 56 (79%) studies. Inter-rater reliability was measured in 26 (37%) studies. CONCLUSIONS: Published research of hand hygiene compliance measured by direct observation lacks validity. Hand hygiene should be measured using methods that produce a valid indication of performance and quality. Standardization of methodology would expedite comparison of hand hygiene compliance between clinical settings and organizations.

Nosocomial transmission of influenza: A retrospective cross-sectional study using next generation sequencing at a hospital in England (2012-2014).

BACKGROUND: The extent of transmission of influenza in hospital settings is poorly understood. Next generation sequencing may improve this by providing information on the genetic relatedness of viral strains. OBJECTIVES: We aimed to apply next generation sequencing to describe transmission in hospital and compare with methods based on routinely-collected data. METHODS: All influenza samples taken through routine care from patients at University College London Hospitals NHS Foundation Trust (September 2012 to March 2014) were included. We conducted Illumina sequencing and identified genetic clusters. We compared nosocomial transmission estimates defined using classical methods (based on time from admission to sample) and genetic clustering. We identified pairs of cases with space-time links and assessed genetic relatedness. RESULTS: We sequenced influenza sampled from 214 patients. There were 180 unique genetic strains, 16 (8.8%) of which seeded a new transmission chain. Nosocomial transmission was indicated for 32 (15.0%) cases using the classical definition and 34 (15.8%) based on genetic clustering. Of the 50 patients in a genetic cluster, 11 (22.0%) had known space-time links with other cases in the same cluster. Genetic distances between pairs of cases with space-time links were lower than for pairs without spatial links (P < .001). CONCLUSIONS: Genetic data confirmed that nosocomial transmission contributes significantly to the hospital burden of influenza and elucidated transmission chains. Prospective next generation sequencing could support outbreak investigations and monitor the impact of infection and control measures.

Colonization and persistence of antibiotic-resistant Enterobacteriaceae strains in infants nursed in two neonatal intensive care units in East London, United Kingdom.

Stool samples were collected from infants nursed in two neonatal intensive care units (NICUs) in East London, United Kingdom. The aim of the study was to determine the incidence of and risk factors for the carriage of multiresistant Enterobacteriaceae strains (MRE; resistant to three or more classes of antibiotic) and the extent of the persistence of resistant strains following discharge. Sixty-two (50%) of 124 infants had acquired MRE by 2 weeks of postnatal age, and 69 (56%) infants had acquired MRE by discharge. The proportions of infants at 2 weeks carrying strains that were resistant to antibiotics were the following: tetracycline, 79%; amoxicillin, 78%; cephalosporins, 31%; trimethoprim, 20%; piperacillin-tazobactam, 11%; chloramphenicol, 9%; and aminoglycoside, 4%. A gestational age of less than 26 weeks was a risk factor for colonization with MRE at discharge, but not at 2 weeks. Analysis within a NICU showed that exposure of an infant to a specific antibiotic in the NICU was not a risk factor for the carriage of a strain resistant to that antibiotic. Estimates of persistence from discharge to 6 months were the following: for tetracycline, 57% (95% confidence intervals [CI], 0.35 to 0.87); chloramphenicol, 49% (95% CI, 0.20 to 0.83); trimethoprim, 45% (95% CI, 0.22 to 0.74); piperacillin-tazobactam, 42% (95% CI, 0.20 to 0.71); and augmentin, 34% (95% CI, 0.11 to 0.66). Strains resistant to cephalosporins or aminoglycosides showed lower levels of persistence. Nine of 34 infants (26.5%) with Escherichia coli and 4 (7.1%) of 56 infants with Klebsiella spp. at discharge carried strains indistinguishable by randomly amplified polymorphic DNA and antibiotic susceptibility patterns at 6 months. MRE were found at high frequency in the infants during their stay in the NICU and persisted in a proportion of infants.

The development of hand hygiene compliance imperatives in an emergency department.

BACKGROUND: Monitoring results showing poor hand hygiene compliance in a major, busy emergency department prompted a quality improvement initiative to improve hand hygiene compliance. PURPOSE: To identify, remove, and reduce barriers to hand hygiene compliance in an emergency department. METHODS: A barrier identification tool was used to identify key barriers and opportunities associated with hand hygiene compliance. Hand hygiene imperatives were developed and agreed on with clinicians, and a framework for monitoring and improving hand hygiene compliance was developed. RESULTS: Barriers to compliance were ambiguity about when to clean hands, the pace and urgency of work in some areas of the department, which left little time for hand hygiene and environmental and operational issues. Sore hands were a problem for some staff. Expectations of compliance were agreed on with staff, and changes were made to remove barriers. A monitoring tool was designed to monitor progress. Gradual improvement occurred in all areas, except in emergency situations, which require further improvement work. CONCLUSIONS: The context of care and barriers to compliance should be reflected in hand hygiene expectations and monitoring. In the emergency department, the requirement to deliver urgent live-saving care can supersede conventional hand hygiene expectations.

Clinical outcomes in children with sickle cell disease living in England: a neonatal cohort in East London.

BACKGROUND AND OBJECTIVES: We investigated outcomes in a UK neonatal cohort as a benchmark for care of children with sickle cell disease (SCD). DESIGN AND METHODS: Two-hundred and fifty-two children (180 with hemoglobin [Hb] SS, 64 with HbSC, and 8 with HbS/beta thalassemia), identified during 1983-2005 by universal birth screening in East London, were followed in a hospital and community-based program which included penicillin V prophylaxis from 3 months of age, 23-valent pneumococcal polysaccharide vaccine from 1993, conjugate pneumococcal vaccine from 2002 and transcranial Doppler screening from 1991. RESULTS: At the end of 2005, there were 2158 patient years of observation. The median age of the patients was 7.8 (interquartile range 3.3-13.0) years, and 2.8% of those enrolled had been lost to follow-up. The estimated survival of children with HbSS at 16 years was 99.0% (95% confidence interval, CI, 93.2 to 99.9%) and pneumococcal sepsis rate was 0.3 (95% CI 0.1-0.8) episodes per 100 patient-years. The risk of overt stroke was 4.3% (95%CI 1.5 to 11.4%) and could be further reduced by transcranial Doppler screening from infancy and transfusing all children with high-risk scans. No deaths, strokes or episodes of pneumococcal sepsis were observed in children with HbSC or HbS/beta thalassemia. The mortality rates from HbSS were significantly lower than those in other reported cohorts. INTERPRETATION AND CONCLUSIONS: Mortality in childhood SCD can virtually be eliminated in a well-resourced health service setting linking community-based care with a specialized, hospital-based center. SCD continues to cause substantial morbidity from acute complications and chronic organ damage. We recommend setting up of clinical networks to optimize the management of SCD.

How mathematical models have helped to improve understanding the epidemiology of infection.

Mathematical models have proved to be useful tools for addressing questions about the process of infection. This is because the model allows the investigation of the mathematical link between invisible events (transmission of infection between individuals) and more visible ones (incidence of clinical infection, seroprevalence data etc.). A useful model is often one that is simple enough to provide answers that are applicable to as general a context as possible, but also complex enough so that it can address the most relevant questions. Thus, relatively simple models of viral (or hospital acquired-) infection were used to establish the existence of critical thresholds of immunisation (or antibiotic usage) coverage, although more complex models were needed for the investigation of the impact of infection control practices within more specific contexts. Mathematical models have the potential to elucidate key determinants of the epidemiology of infectious disease arising in infants nursed in neonatal intensive care units.

Is it exposure to cigarette smoke or to smokers which increases the risk of meningococcal disease in teenagers?

BACKGROUND: Passive smoking appears to increase the risk of meningococcal disease (MD) in adolescents. Whether this effect is attributable to exposure to cigarette smoke or contact with smokers is unknown. METHODS: We conducted a prospective population-based case-control study with age, sex matched-controls in 1:1 matching. Participants were 15-19 year old with MD recruited at hospital admission in six regions (65% of the population of England) from January 1999 through June 2000, and their matched controls. Data on potential risk factors were gathered by confidential interview, including seven passive smoking variables. Factor analysis was performed to assess the dimensionality of the passive smoking exposure variables. The data were analysed with univariate and multivariate conditional logistic regression. RESULTS: 144 case-control pairs were recruited (51% male; median age 17.6). Factor analysis identified two independent factors representing passive smoking (P < 0.01), one associated with 'exposure to smoke', the other with 'smoker contact'. Only smoker contact was a significant risk factor for MD (OR = 1.8; 95% CI 1.0-3.3; P = 0.05). In multivariate analysis this factor was still associated with MD independently of potential confounders such as active smoker status and household crowding. CONCLUSION: Contact with smokers is associated with increased risk of MD in adolescents. This is more likely to be due to higher carriage rates in smokers than to exposure to smoke and emphasizes the importance of public health measures to stop smoking. In epidemiological studies that assess risk from passive smoking, exposure to smoke should be differentiated where possible from contact with smokers.

Survival of medically treated thalassemia patients in Cyprus. Trends and risk factors over the period 1980-2004.

BACKGROUND AND OBJECTIVES: A large number of patients with thalassemia major have been born and treated exclusively in Cyprus. They have been managed according to standard international practice, but few have been transplanted. In 1999, a combination chelation regime with desferrioxamine and deferiprone was introduced. We analyzed survival trends in Cypriots and tried to identify factors associated with prolonged survival. DESIGN AND METHODS: We had incomplete information on births pre-1974 and complete information from 1974 onwards. Clinical data were incomplete pre-1980 and complete thereafter. We analyzed data on 539 patients born after 1960 and followed over the period 1980 to the end of 2004. RESULTS: There were 58 deaths, 31 (53.4%) of which where due to cardiac causes. In the complete birth cohort of 284 patients born after 1974, survival (95% CI) at 10, 20 and 30 years was 100% (0); 98.5% (96.1-99.4) and 92.7% (86.7-96.1) respectively. There was a significant trend of increasing cardiac deaths between 1980 and 2000 (p<0.001) and a decline after 2000 (p=0.06). In multivariate survival analysis, protective effects were found for female sex (hazard ratio, 0.37, 95% CI 0.21-0.66; p<0.001), and post-2000 follow-up (hazard ratio, 0.44, 95% CI 0.20-0.99; p<0.05), but not for genotype, treatment center or birth cohort. INTERPRETATION AND CONCLUSIONS: Most patients born after 1974 survive to at least the age of 30. There has been a marked improvement in survival for patients of all ages since 2000, which may be due to the introduction of combination chelation therapy.

Predicting and preventing post-herpetic neuralgia: are current risk factors useful in clinical practice?

Post-herpetic neuralgia (PHN) following acute herpes zoster remains a significant cause of neuropathic pain especially in the elderly. Early treatment of the zoster rash with antiviral agents, such as aciclovir remains one of the few measures proven to reduce the incidence and duration of PHN albeit only in a subset of patients. It is therefore crucial that the physician who first sees a case of zoster identifies those patients who are most likely to develop long-term pain and treats them accordingly. In particular, prodrugs such as famciclovir and valaciclvoir may be more beneficial in reducing PHN than the shorter acting aciclovir, but can be more expensive. Measures that could be used to predict patients likely to develop PHN would also facilitate the evaluation of early use of antiepileptic, anti-inflammatory and analgesic agents in the prevention of PHN. In a prospective study of 280 herpes zoster (HZ) cases seen by the general practitioner (GP) we evaluated the predictive value of five clinical factors identified in clinical trials as associated with a higher likelihood of PHN. A visual analogue score (VAS) over 5 and/or age over 50 correctly identified all subjects with PHN at 3 and 6 months, respectively. However, the specificity of this prediction was low because as many as 81% and 85% of those aged over 50 recovered within 3 and 6 months, respectively. Better methods are needed to identify patients over 50 at most risk of PHN that enable GPs to better allocate their resources with respect to HZ treatment.

Erythromycin for prokinesis: imprudent prescribing?

Problems with antibiotic resistant bacteria are increasing in the hospital and particularly in the intensive care unit. Methicillin-resistant Staphylococcus aureus, Acinetobacter baumanii and extended spectrum beta-lactamase producing gram-negative bacilli constitute a therapeutic and infection control challenge. Early enteral feeding improves survival in patients in the intensive care unit. Prokinetic agents are routinely used in patients with inappropriate gastrointestinal motility. The use of erythromycin at sub-therapeutic doses as a prokinetic agent is a cause of concern for the following reasons: it can increase the emergence and spread of antibiotic resistance and the likelihood of Clostridium difficile disease. The use of an antibiotic as a prokinetic agent does not constitute prudent antimicrobial prescribing and should be avoided. Alternative agents, whenever possible, should be used.

Diarrhoea in the critically ill is common, associated with poor outcome, and rarely due to Clostridium difficile.

Diarrhoea is common in Intensive Care Unit (ICU) patients, with a reported prevalence of 15-38%. Many factors may cause diarrhoea, including Clostridium difficile, drugs (e.g. laxatives, antibiotics) and enteral feeds. Diarrhoea impacts on patient dignity, increases nursing workload and healthcare costs, and exacerbates morbidity through dermal injury, impaired enteral uptake and subsequent fluid imbalance. We analysed a cohort of 9331 consecutive patients admitted to a mixed general intensive care unit to establish the prevalence of diarrhoea in intensive care unit patients, and its relationship with infective aetiology and clinical outcomes. We provide evidence that diarrhoea is common (12.9% (1207/9331) prevalence) in critically ill patients, independently associated with increased intensive care unit length of stay (mean (standard error) 14.8 (0.26) vs 3.2 (0.09) days, p < 0.001) and mortality (22.0% (265/1207) vs 8.7% (705/8124), p < 0.001; adjusted hazard ratio 1.99 (95% CI 1.70-2.32), p < 0.001) compared to patients without diarrhoea even after adjusting for potential confounding factors, and infrequently caused by infective aetiology (112/1207 (9.2%)) such as Clostridium difficile (97/1048 (9.3%) tested) or virological causes (9/172 (5.7%) tested). Our findings suggest non-infective causes of diarrhoea in ICU predominate and pathophysiology of diarrhoea in critically ill patients warrants further investigation.

Persistent non-gastrointestinal metabolic acidosis in pediatric HIV-1 infection.

OBJECTIVES: To determine the incidence and to identify the clinical parameters associated with non-gastrointestinal renal tubular and high anion gap acidosis in a cohort of HIV-1-infected children. METHODS: Records of 202 HIV-1-infected children were reviewed to identify patients with metabolic acidosis. Serum and urine chemistries of those children with persistent non-gastrointestinal acidosis were then studied prospectively. Serum and urinary anion gaps (SAG and UAG) were calculated. Those with acidosis (group 1) were compared with children without acidosis (group 2). Associations were determined with Pediatric HIV classification, height, weight, antiretroviral therapy, and Pneumocystis carinii pneumonia prophylaxis. RESULTS: Persistent acidosis was noted in 34 out of 202 children (17%): 16 out of 34 (47%, group 1A) had elevated SAG acidosis, and 18 out of 34 (53%) had normal SAG acidosis with a positive UAG (distal renal tubular) acidosis (group 1B). Those with acidifying defects more often received P. carinii pneumonia prophylaxis (P = 0.02 and 0.01 for groups 1 and 1A, respectively) independently of HIV-1 classification. This group was shorter in height than group 2 (P = 0.007). Differences in weight were not significant (P = 0.1). However, acidotic subjects were more immunocompromised than those in group 2 (multivariate P < 0.001 for HIV classification C3). CONCLUSIONS: Elevated SAG acidosis and renal tubular acidosis are not uncommon among HIV-infected children with advanced disease. These disorders may be associated with height growth failure and prophylaxis with sulfur/sulfone containing antibiotics. HIV infection and/or its associated therapies may cause renal tubular damage. The causes of elevated SAG acidosis require further investigation.

Retinoblastoma treated with primary chemotherapy alone: the significance of tumour size, location, and age.

AIMS: To evaluate how tumour size, retinal location, and patient age affect the outcome of retinoblastoma foci treated with chemotherapy. METHODS: Retrospective review of retinoblastoma foci treated with primary chemotherapy alone. Individual tumours were coded with regard to their largest basal diameter, location within the eye (macula, macula to equator, equator to ora serrata), and patient's age at diagnosis. Successfully treated tumours required no further intervention while those requiring additional treatment were coded as failures. RESULTS: 56 (72%) tumours responded successfully to chemotherapy alone while 22 (28%) required additional therapy. 26 of 31 macular tumours (84%) and 30 of 47 extramacular tumours (64%) responded to chemotherapy (p <0.060). Relative to size, 46 of 60 tumours (77%) greater than 2 mm in basal diameter were successfully treated with chemotherapy, while only 10 of 18 tumours (56%) less than or equal to 2 mm responded (p <0.088). Among the eight tumour foci diagnosed in children less than 2 months of age, five (63%) failed to respond to chemotherapy alone (p <0.032). CONCLUSION: Retinoblastoma is more likely to respond to primary chemotherapy if it is located in the macula and if the patient is older than 2 months of age. Tumours measuring less than 2 mm in diameter may be less responsive to this treatment.

Meningococcal W135 carriage; enhanced surveillance amongst east London Muslim pilgrims and their household contacts before and after attending the 2002 Hajj.

BACKGROUND: For two successive years, 2000 and 2001, there was a world-wide outbreak of W135 meningococcal disease amongst pilgrims who attended the Hajj and in their contacts after returning home. METHODS: Beginning January 2002, we offered meningococcal quadrivalent polysaccharide vaccine (against serogroups A, C, Y and W135) to pilgrims and collected a throat swab for meningococcal W135 carriage before and after their pilgrimage. RESULTS: The overall Neisseria meningitidis carriage pre-Hajj was 8.3% and 6.3% post-Hajj. We found W135 carriage rates of 0.8% before and 0.6% after Hajj, respectively. 21% (36/174) of the pilgrims were treated with antibiotics for respiratory illness. CONCLUSION: The carriage of meningococcus W135 among UK pilgrims who visited the Hajj in 2002 was low. This contrasts with another study suggesting pilgrims frequently acquired N. meningitidis W135 carriage during 2001 Hajj. The use of the quadrivalent vaccine may account for this difference.

Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection.

BACKGROUND: Diagnosis of Clostridium difficile infection is controversial because of many laboratory methods, compounded by two reference methods. Cytotoxigenic culture detects toxigenic C difficile and gives a positive result more frequently (eg, because of colonisation, which means that individuals can have the bacterium but no free toxin) than does the cytotoxin assay, which detects preformed toxin in faeces. We aimed to validate the reference methods according to clinical outcomes and to derive an optimum laboratory diagnostic algorithm for C difficile infection. METHODS: In this prospective, multicentre study, we did cytotoxigenic culture and cytotoxin assays on 12,420 faecal samples in four UK laboratories. We also performed tests that represent the three main targets for C difficile detection: bacterium (glutamate dehydrogenase), toxins, or toxin genes. We used routine blood test results, length of hospital stay, and 30-day mortality to clinically validate the reference methods. Data were categorised by reference method result: group 1, cytotoxin assay positive; group 2, cytotoxigenic culture positive and cytotoxin assay negative; and group 3, both reference methods negative. FINDINGS: Clinical and reference assay data were available for 6522 inpatient episodes. On univariate analysis, mortality was significantly higher in group 1 than in group 2 (72/435 [16·6%] vs 20/207 [9·7%], p=0·044) and in group 3 (503/5880 [8·6%], p<0·001), but not in group 2 compared with group 3 (p=0·4). A multivariate analysis accounting for potential confounders confirmed the mortality differences between groups 1 and 3 (OR 1·61, 95% CI 1·12-2·31). Multistage algorithms performed better than did standalone assays. INTERPRETATION: We noted no increase in mortality when toxigenic C difficile alone was present. Toxin (cytotoxin assay) positivity correlated with clinical outcome, and so this reference method best defines true cases of C difficile infection. A new diagnostic category of potential C difficile excretor (cytotoxigenic culture positive but cytotoxin assay negative) could be used to characterise patients with diarrhoea that is probably not due to C difficile infection, but who can cause cross-infection.