N. Shetty

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

Summary 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. Funding Department of Health and Health Protection Agency, UK.

Evaluation of microbicidal activity of a new disinfectant: Sterilox 2500 against Clostridium difficile spores, Helicobacter pylori, vancomycin resistant Enterococcus species, Candida albicans and several Mycobacterium species

The microbicidal activity of a new disinfectant Sterilox, a super-oxidized water, containing a mixture of oxidizing substances, was tested against Clostridium difficile spores, Helicobacter pylori, vancomycin resistant Enterococcus species, Candida albicans and several Mycobacterium species using membrane filters. All tests were performed in duplicate with and without added horse serum at 1% and 5% v/v. Distilled water, 0.35% peracetic acid (Nu-Cidex) and 2% glutaraldehyde were included as controls. Sterilox: spore suspension (9:1 v/v) achieved log10 kill of > 5 with 5% horse serum in 2 min against H. pylori, vancomycin resistant Enterococcus species, C. albicans and four atypical Mycobacterium species: M. avium, M. chelonei, M. xenopi and M. smegmatis. Sporicidal activity of Sterilox against Clostridium difficile was markedly diminished in the presence of 5% horse serum. Sterilox may be an effective alternative in endoscopy units, as it is a potent microbicidal agent and the manufacturer claims it is not corrosive to metal and is nontoxic to biological tissues.

Healthcare-associated infections in neonatal units: lessons from contrasting worlds.

Summary Neonatal intensive care units are vulnerable to outbreaks and sporadic incidents of healthcare-associated infections (HAIs). The incidence and outcome of these infections are determined by the degree of immaturity of the neonatal immune system, invasive procedures involved, the aetiological agent and its antimicrobial susceptibility pattern and, above all, infection control policies practised by the unit. It is important to raise awareness of infection control practices in resource-limited settings, since overdependence upon antimicrobial agents and co-existing lack of awareness of infection control is encouraging the emergence of multi-drug-resistant nosocomial pathogens. We reviewed 125 articles regarding HAIs from both advanced and resource-limited neonatal units in order to study risk factors, aetiological agents, antimicrobial susceptibility patterns and reported successes in infection control interventions. The articles include surveillance studies, outbreaks and sporadic incidents. Gram-positive cocci, viruses and fungi predominate in reports from the advanced units, while Gram-negative enteric rods, non-fermenters and fungi are commonly reported from resource-limited settings. Antimicrobial susceptibility patterns from surveillance studies determined the empirical therapy used in each neonatal unit. Most outbreaks, irrespective of the technical facilities available, were traced to specific lack of infection control practices. We discuss infection control interventions, with special emphasis on their applicability in resource-limited settings. Cost-effective measures for implementing these interventions, with particular reference to the recognition of the role of the microbiologist, the infection control team and antibiotic policies are presented.

Seroprevalence and risk factors for toxoplasmosis among antenatal women in London: a re-examination of risk in an ethnically diverse population

Background: Primary infection with Toxoplasma gondii in pregnancy can result in miscarriage, hydrocephalus, cerebral calcification and chorioretinitis in the newborn. The objective of our study was to evaluate seroprevalence of and analyse risk factors for toxoplasmosis in antenatal women from 2006 to 2008 in an ethnically diverse population of Central London to re-examine the need for a screening policy. Methods: We performed serum IgG estimations to T. gondii using a commercial kit, and analysed risk factors for acquisition using a questionnaire. Results: Seroprevalence for T. gondii was 17.32% in 2610 samples tested. In all, 67.7% were of UK origin (seroprevalence: 11.9%) and were significantly non-immune to T. gondii (OR: 0.38, 95% CI: 0.31–0.47; P < 0.0001). Risk factors for seroprevalence included African/Afro-Caribbean (OR: 2.67, 95% CI: 1.83–3.88; P < 0.001; seroprevalence: 31.5%), Middle eastern (OR: 3.12, 95% CI: 1.62–5.99; P ≤ 0.001; seroprevalence: 34.8%) and mixed (OR: 1.75, 95% CI: 1.16–2.63; P = 0.007; seroprevalence: 23.3%) ethnic groups; eating undercooked meat (OR: 1.64, 95% CI: 1.29–2.08; P ≤ 0.001; seroprevalence: 20.2%) and drinking unpasteurised milk (OR: 1.38, 95% CI: 1.01–1.88; P = 0.05; seroprevalence: 23.1%). There was no association with pet cats or eating unpasteurised cheeses and antibody responses. Conclusion: Low national prevalence of toxoplasma seroconversion and congenital disease would likely not justify screening in the UK. Individual risk assessment is recommended in ethnically diverse urban areas where populations with relatively high seroprevalence and parasite-associated risk factors exist together with an indigenous population with low prevalence. One universal screening policy based on the indigenous prevalence and risk factors may not be suitable for all.

London 2012 Olympic and Paralympic Games: public health surveillance and epidemiology.

Summary Mass gatherings are regarded as potential risks for transmission of infectious diseases, and might compromise the health system of countries in which they are hosted. The evidence for increased transmission of infectious diseases at international sporting mass gatherings that attract many visitors from all over the world is not clear, and the evidence base for public health surveillance, epidemiology, and response at events such as the Olympics is small. However, infectious diseases are a recognised risk, and public health planning is, and should remain, a crucial part of the overall planning of sporting events. In this Series paper, we set out the planning and the surveillance systems that were used to monitor public health risks during the London 2012 Olympic and Paralympic Games in the summer of 2012, and draw attention to the public health issues—infectious diseases and chemical, radiation, and environmental hazards—that arose. Although the absolute risk of health-protection problems, including infectious diseases, at sporting mass gatherings is small, the need for reassurance of the absence of problems is higher than has previously been considered; this could challenge conventional public health surveillance systems. Recognition of the limitations of health-surveillance systems needs to be part of the planning for future sporting events.

Emerging, Novel, and Known Influenza Virus Infections in Humans

Influenza viruses continue to cause yearly epidemics and occasional pandemics in humans. In recent years, the threat of a possible influenza pandemic arising from the avian influenza A(H5N1) virus has prompted the development of comprehensive pandemic preparedness programs in many countries. The recent emergence of the pandemic influenza A(H1N1) 2009 virus from the Americas in early 2009, although surprising in its geographic and zoonotic origins, has tested these preparedness programs and revealed areas in which further work is necessary. Nevertheless, the plethora of epidemiologic, diagnostic, mathematical and phylogenetic modeling, and investigative methodologies developed since the severe acute respiratory syndrome outbreak of 2003 and the subsequent sporadic human cases of avian influenza have been applied effectively and rapidly to the emergence of this novel pandemic virus. This article summarizes some of the findings from such investigations, including recommendations for the management of patients infected with this newly emerged pathogen.

Features of the new pandemic influenza A/H1N1/2009 virus: virology, epidemiology, clinical and public health aspects.

Purpose of review The emergence of the pandemic A/H1N1/2009 influenza virus has enabled preexisting pandemic influenza plans to be put into action. This review examines the clinical and public health impact of this new virus. Recent findings Although early figures suggested that this pandemic virus was causing higher morbidity and mortality than seasonal influenza viruses, subsequent studies have found it to cause milder disease in most cases. Yet, there are some groups with increased risk of serious disease from this new pathogen. The widespread use of antiviral agents, prophylactically and therapeutically, has led to the sporadic emergence of drug resistance, though this is still rare. Nonpharmacological public health interventions for containment and mitigation have been relatively ineffective in limiting the rapid, global spread of this pathogen. Recently, the focus has been on the manufacture and distribution of various specific vaccines against this new virus, and the care of severely ill patients admitted to intensive care. Summary As this virus continues to infect new members of the global population, it may eventually become just one of the annual circulating seasonal influenza viruses. Until then, it will be prudent to continue to monitor it closely for any signs of enhanced transmissibility and virulence.

The use of povidone iodine in exit site care for patients undergoing continuous peritoneal dialysis (CAPD).

Exit site infection is a major risk factor for the development of peritonitis in continuous ambulatory peritoneal dialysis. The frequency of infection can be reduced by scrupulous exit site care with or without topical antiseptics. A randomized trial was performed of 149 catheters in 130 patients to assess any additional benefits conferred by the use of povidine iodine dry powder spray at dressing changes over an existing strict protocol of exit care. Exit infections occurred in 14 (18%) of 77 patients using spray and in 15 (21%) of 72 patients not using spray. The risk of peritonitis was also similar in each group. The proportion of infections caused by Staphylococcus aureus was reduced in the spray group, but those caused by Pseudomonas aeruginosa were increased. Rash occurred in 6% of those using the spray. The use of the spray did not therefore seem justified.

Assessment of environmental contamination and environmental decontamination practices within an Ebola holding unit, Freetown, Sierra Leone

Evidence to inform decontamination practices at Ebola holding units (EHUs) and treatment centres is lacking. We conducted an audit of decontamination procedures inside Connaught Hospital EHU in Freetown, Sierra Leone, by assessing environmental swab specimens for evidence of contamination with Ebola virus by RT-PCR. Swabs were collected following discharge of Ebola Virus Disease (EVD) patients before and after routine decontamination. Prior to decontamination, Ebola virus RNA was detected within a limited area at all bedside sites tested, but not at any sites distant to the bedside. Following decontamination, few areas contained detectable Ebola virus RNA. In areas beneath the bed there was evidence of transfer of Ebola virus material during cleaning. Retraining of cleaning staff reduced evidence of environmental contamination after decontamination. Current decontamination procedures appear to be effective in eradicating persistence of viral RNA. This study supports the use of viral swabs to assess Ebola viral contamination within the clinical setting. We recommend that regular refresher training of cleaning staff and audit of environmental contamination become standard practice at all Ebola care facilities during EVD outbreaks.

Microbiological aspects of public health planning and preparedness for the 2012 Olympic Games.

Although communicable diseases have hitherto played a small part in illness associated with Olympic Games, an outbreak of infection in a national team, Games venue or visiting spectators has the potential to disrupt a global sporting event and distract from the international celebration of athletic excellence. Preparation for hosting the Olympic Games includes implementation of early warning systems for detecting emerging infection problems. Ensuring capability for rapid microbiological diagnoses to inform situational risk assessments underpins the ability to dispel rumours. These are a prelude to control measures to minimize impact of any outbreak of infectious disease at a time of intense public scrutiny. Complex multidisciplinary teamwork combined with laboratory technical innovation and efficient information flows underlie the Health Protection Agencys preparation for the London 2012 Olympic and Paralympic Games. These will deliver durable legacies for clinical and public health microbiology, outbreak investigation and control in the coming years.