Lessons from a large norovirus outbreak: impact of viral load, patient age and ward design on duration of symptoms and shedding and likelihood of transmission.

BACKGROUND: Hospital norovirus outbreaks cause significant financial and operational disruption which should be minimised by optimal handling of affected areas and use of isolation facilities. AIM: To identify factors associated with increased duration of symptoms and viral excretion and increased probability of transmission. METHODS: Retrospective observational study of a large norovirus outbreak at a UK teaching hospital in the winter of 2009-2010 where patients were diagnosed using a real-time polymerase chain reaction (PCR) assay. FINDINGS: Symptom duration was significantly associated with patient age (Spearman rank correlation coefficient: 0.197; P = 0.002) but not with PCR cycle threshold (C(T)) value. Duration of viral excretion was found to be longer in patients with higher viral loads. Transmission within a ward bay was not significantly associated either with age or with C(T) value but was more likely to occur in some ward blocks than others, which may relate to differences in ward design. Transfer of patients into isolation rooms or cohorted area within two days of symptom onset did not significantly influence probability of onward transmission (52% vs 47%; P = 0.67). CONCLUSIONS: The presented data suggest that C(T) value may guide timing of repeat sample collection if ongoing gastrointestinal symptoms may relate to other pathologies, and that patients developing symptoms of norovirus may remain in their current bay rather than being moved into isolation facilities. The bay or ward should be closed to new admissions but it should be anticipated that duration of symptoms and therefore closure will be longer when the outbreak involves elderly patients.

Contribution of bacteriology and virology in sudden unexpected death in infancy.

OBJECTIVE: To appraise the inter-agency protocol used in sudden unexpected death in infancy (SUDI) cases in South Yorkshire, UK. DESIGN: A retrospective audit of 121 postmortems carried out over a 3-year period was completed to assess adherence to local guidelines introduced in 2005 specifying the required microbiological specimen set to be collected at postmortem in cases of SUDI. Data on organisms isolated was also collated and assessed for significance. SETTING: Sheffield Children's Hospital Histopathology Department is the South Yorkshire referral centre for SUDI. Post-mortem samples were processed by Sheffield Teaching Hospital's microbiology and virology departments. PATIENTS: All postmortems of SUDI in children less than 2 years of age performed between January 2004 and December 2007. RESULTS: 116/121 cases had samples sent for microbiological and/or virological investigation: 90% of cases had a blood culture and 68% had a cerebrospinal fluid sample taken. Of the 116 cases, 49% had a potentially pathogenic organism isolated, 73% had post-mortem flora and 10% had no organisms isolated (32% had both post-mortem flora and a potential pathogen). 27% of cases were found to have middle ear exudate requiring sampling, from 48% of which a potentially pathogenic organism was isolated. CONCLUSIONS: Our finding of a potential pathogen in 57/116 (49%) of our cases, although not necessarily the cause of death, confirms the relevance of performing multisite and virology investigations in all cases of SUDI. Standardised protocols with agreed definitions are necessary for a consistent approach.

Ongoing queries: Interpretation of serology in asymptomatic or atypical chronic Q fever.

Chronic Q fever, predominantly associated with endocarditis, can develop insidiously. Although the diagnosis may be straightforward with a typical clinical presentation, incidental discovery of positive Coxiella burnetii serology poses a difficult clinical challenge. We describe the cases of two such patients and review the literature on the serological diagnosis of chronic Q fever.

Changes in age related seroprevalence of antibody to varicella zoster virus: impact on vaccine strategy.

AIM: To study changes in the seroprevalence of varicella zoster virus (VZV) antibody over the past 25 years with a view to determining the target age group for any future vaccination strategy. METHODS: Stored sera collected from different age groups over a period of 25 years were tested by a commercial VZV IgG enzyme immunoassay at a four year time interval. Data were analysed by logistic regression to investigate the evidence for changes in incidence and hence seroprevalence over that period. RESULTS: There was a significant rise in VZV antibody prevalence in the 1-4 year age group during the study period. CONCLUSIONS: A universal childhood VZV vaccination strategy will need to take account of the increase in incidence of VZV infection in children under the age of 4 years; hence, the suggested target age would be between 12 and 18 months---soon after the disappearance of maternal antibody.

IL-1, IL-6 and TNF-alpha concentrations in the peritoneal fluid of women with pelvic adhesions.

BACKGROUND: Pelvic adhesions are a significant cause of morbidity and are associated with infertility and pain. The three pro-inflammatory cytokines interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF)-alpha are involved in adhesion formation/reformation. METHODS: The concentration of these three cytokines was examined in the peritoneal fluid of women undergoing laparoscopy, in order to examine the factors affecting their concentrations, with specific reference to the presence or absence of adhesions. RESULTS: We found that the concentration of TNF-alpha in the peritoneal fluid was significantly correlated to the menstrual cycle day (P < 0.01), with increasing concentration as the menstrual cycle progressed from the follicular to the luteal phase. In contrast, IL-1 and IL-6 levels did not show any variation throughout the menstrual cycle. Increased TNF-alpha was found in patients with pelvic adhesions compared with those with normal pelvis; the concentration of TNF-alpha was highest in mild compared with severe adhesions. In contrast, IL-1 concentration was higher in the presence of severe adhesions. IL-6 levels were significantly correlated with the grade of endometriosis (P < 0.05), but there were no significant correlations of either TNF-alpha or IL-1 concentrations with the various grades of endometriosis. CONCLUSION: The exact role of TNF-alpha and IL-1 in adhesion formation is still unknown, but the results from this study suggest that their concentration in the peritoneal fluid is associated with the degree of adhesions present.

The prevalence of Chlamydia trachomatis infection in male undergraduates: a postal survey.

OBJECTIVES: To determine the prevalence of Chlamydia trachomatis infection in male undergraduates and to investigate whether prevalence increases with time spent at university. To investigate the feasibility of screening men for C trachomatis by self sampling and posting of urine specimens. METHODS: The study design was a postal survey undertaken by the Department of Genito-Urinary Medicine (GUM) and Student University Health Service (SUHS) in SHEFFIELD: 2607 male undergraduates from the SUHS patient list were invited to participate in the study by providing a first void urine specimen and posting it to the laboratory. The main outcome measure was the detection of C trachomatis infection. RESULTS: 758 students participated in the study, a response rate of 29.1%. Nine students (1.2%) tested positive for C trachomatis. The prevalence of infection in the first, second, and third year of study was 0.7%, 1.5%, and 1.6% of participants respectively. There was no statistically significant difference in prevalence of infection between first and third year students (chi(2) test, p = 0.32). However, students with chlamydia had a higher median age (Mann-Whitney U test, p < or = 0.05). Contact tracing identified four further cases of C trachomatis infection. CONCLUSION: Screening for C trachomatis infection by postal survey is feasible. However, the response rate in this study was poor and the estimated sample size was not reached. Therefore, it has not been possible to determine the true prevalence of infection in this population or to accurately assess changes in prevalence with time spent at university.

Outbreaks of influenza A in nursing homes in Sheffield during the 1997-1998 season: implications for diagnosis and control.

Three recent outbreaks of influenza A in nursing and residential homes in Sheffield were characterized by high attack rates among both residents and staff, and a high mortality rate among residents. The epidemiology of the outbreaks was unusual in that all three occurred towards the end of a quiet influenza season, against a generally low level of community activity, and involved strains of influenza that were not included in the current season's vaccine. The outbreak investigation was aided by the use of a novel rapid diagnostic technique. In future the combination of vaccination, surveillance, rapid diagnosis and new antineuraminidase drugs should improve prospects for control of influenza within closed communities.

Is VZV reactivation a common cause of unexplained unilateral pain? Results of a prospective study of 57 patients.

OBJECTIVE: Pain is a common reason for patients to present to a doctor. Many patients with zoster have seen their doctor with pain during the days before the rash and zoster sine herpete is well described. If early varicella zoster virus (VZV) reactivation could be identified confidently, it could provide an opportunity for early antiviral intervention. This prospective study was performed to assess how often patients presenting to their general practitioner with unilateral pain of no obvious clinical cause proved to have evidence of VZV reactivation. METHODS: Fifty-seven patients were recruited and followed for 28 days; laboratory testing included VZV polymerase chain reaction (PCR) from peripheral blood mononuclear cells, VZV IgG, IgA and IgM. The control group consisted of 81 blood donors. RESULTS: Only two study patients developed the rash of zoster. There was no significant difference in PCR or serological responses between the study group and control group. Clinical characteristics did not enable identification of patients presenting to their doctor with unilateral pain who had prodromal zoster. CONCLUSION: There was no evidence on clinical or laboratory tests used in this study to support the view that reactivation of VZV is a common cause of unexplained unilateral pain.

Failure to find an association between hepatitis C virus and thyroid autoimmunity.

A high frequency of hepatitis C antibodies has been reported from France in patients with autoimmune thyroiditis. Two cases of Hashimoto's thyroiditis in association with chronic active hepatitis and hepatitis C infection have also been reported. We have examined this potential association in 46 patients with autoimmune hypothyroidism and found that 16 apparently had hepatitis C antibodies in one of the two commercially available enzyme-linked immunosorbent assays (ELISA), but all patients were negative in a confirmatory commercially available recombinant immunoblot assay (RIBA-3) indicating that none of the patients were truly positive for hepatitis C antibodies. We also tested sera from 111 patients with proven hepatitis C infection and found no increased prevalence of thyroid autoantibodies. These results suggest that hepatitis C infection is not a risk factor for the development of thyroid autoimmunity in the United Kingdom.

Effect of acyclovir and prednisolone on the serological response in herpes zoster.

The serological response of patients with acute herpes zoster was studied to determine whether a diagnosis could be made on a single serum sample, and whether this response was modified by treatment with antiviral and/or steroid therapy. The patients received one of four regimes of acyclovir and prednisolone, Varicella zoster virus (VZV) IgG, IgM, and IgA responses were measured by commercial and in-house enzyme immunoassays (EIA) using serum samples taken at days 0, 7, and 21 after entry into the study. Samples were also tested for IgM to Epstein-Barr virus (EBV) viral capsid antigen (VCA), and cytomegalovirus (CMV) IgM and for herpes simplex virus (HSV) antibodies by the complement fixation test (CFT). Analysis was carried out on data from 71 patients. VZV IgM was detected in 72%, VZV IgA in 78%, and either VZV IgM or IgA in 88% of patients tested, at some time during the 3-week study period. The optimal time to detect either class of antibody was approximately 1 week after the onset of the vesicular rash, when 85% of patients had one or both classes of acute phase antibody in their serum. There was no evidence of cross reaction with EBV, CMV, or HSV antibodies. Neither treatment with prednisolone nor the length of therapy with acyclovir affected significantly the VZV IgM or IgA responses. Therefore it is possible to make a serological diagnosis of herpes zoster on a single sample, optimally 1 week after the onset of the rash, in patients treated with acyclovir alone or with acyclovir and steroids.

False-positive legionella titres in routine clinical serology testing detected by absorption with campylobacter: implications for the serological diagnosis of legionnaires' disease.

A simple absorption step using blocking fluid prepared from a selected campylobacter strain was introduced in parallel with routine legionella serology tests. Over 12 months, 2716 patients were tested for legionella antibodies by the Indirect Fluorescent Antibody Test of whom 58 (2.1%) had a positive titre (> or = 16) in one or more sera. Campylobacter blocking fluid significantly reduced the legionella titres in 17 of these patients (29%) including four patients with diagnostic serology results (two of whom had pneumonia) and 13 patients with non-diagnostic titres. Absorption with campylobacter however had no effect on the legionella titres in 10 patients with positive serology, in whom legionnaires' disease had been confirmed by culture of Legionella pneumophila from sputum or detection of legionella urinary antigen by ELISA. These results indicate that the serological cross-reaction between legionella and campylobacter is encountered in routine legionella serology tests. The important implications for the diagnosis of legionnaires' disease are discussed.

Gastroenteritis associated with oysters.

An outbreak of gastroenteritis occurred in catering students attending three classes at a Yorkshire college in February 1994. The three classes were held on the Monday, Tuesday, and Thursday of the same week and had identical menus. Thirty-seven of the 90 students were affected. A cohort study, with a 94% response rate, showed a highly significant association of illness with the consumption of raw oysters grown in English coastal waters.

Effect of glycerol on intracellular virus survival: implications for the clinical use of glycerol-preserved cadaver skin.

Glycerol has long been used for the preservation of skin allografts. The antimicrobial activity of glycerol has not been fully documented. This paper reports the results of an investigation of a model studying the effect of glycerol on the inactivation of intracellular viruses. Two viruses--herpes simplex type I (HSV-1) and poliovirus--were cultured within human dermal fibroblasts. These intracellular viruses were incubated with 50 per cent, 85 per cent and 98 per cent glycerol at 4 degrees C and 20 degrees C for 4 weeks. Each week, the cultures in glycerol and controls in fibroblast maintenance medium were assayed for virus infectivity by examining the ability of harvested viruses to infect further fibroblasts. At 4 degrees C, 85 per cent glycerol could not fully inactivate intracellular HSV-I or poliovirus even after 4 weeks; 98 per cent glycerol inactivated intracellular HSV-I (after 3 weeks) but could not fully inactivate intracellular poliovirus after 4 weeks. At 20 degrees C, 85 per cent glycerol inactivated intracellular HSV-I (within 1 week) but could not fully inactivate intracellular poliovirus after 4 weeks; 98 per cent glycerol inactivated intracellular HSV-I (within 1 week) and inactivated intracellular poliovirus (after 2 weeks). It is suggested that, on the basis of this study, glycerol can reduce intracellular virus infectivity but that its effects are very dependent on concentration, time and temperature such that we would recommend that allograft skin be exposed to 98 per cent glycerol for a minimum of at least 4 weeks at a minimum temperature of 20 degrees C before clinical use.

Low incidence of primary infection with toxoplasma among women in Sheffield: a seroconversion study.

OBJECTIVE: To determine the incidence of primary toxoplasma infection in women of childbearing age. DESIGN: A retrospective study of seroconversion on stored pairs of sera taken for routine antenatal testing. SETTING: The antenatal clinics and general practices of Sheffield between July 1989 and October 1992. SUBJECTS: One thousand six hundred and twenty-one women on whom pairs of sera, separated by more than 500 days, had been received. MAIN OUTCOME MEASURE: Rate of primary infection determined by seroconversion as measured by the presence of antibody in the second serum and its absence in the first. RESULTS: Of 1621 women, 160 (9.9%) were initially seropositive. One seroconversion was detected in 2966 woman years of observation for susceptibles. The projected rate for primary infections was 0.23 (95% CI 0.0059-1.3) per 1000 pregnancies. CONCLUSIONS: The rate is much lower than for earlier estimates of incidence in the UK but agrees with a more recent estimate from Sheffield and suggests a falling incidence.

Prolonged cryptosporidiosis during primary HIV infection.

Primary infection with the human immunodeficiency virus causes profound immunosuppression with a decrease in lymphocyte numbers and function. However, this immunosuppression is transient and most individuals regain normal immune function. Infection with opportunist pathogens during the period of immunosuppression is rare. We report a case of severe prolonged cryptosporidiosis complicating primary HIV infection. This has not previously been described. A review of other cases of opportunist infections in primary HIV infection suggests that various pathogens may take advantage of the transient immunosuppression. This has important implications for the diagnosis and management of acute HIV infection, and for the diagnostic criteria currently used for AIDS.

False positive legionella serology in campylobacter infection: campylobacter serotypes, duration of antibody response and elimination of cross-reactions in the indirect fluorescent antibody test.

Sera from 83 patients with campylobacter gastroenteritis were examined for the presence of legionella antibodies by indirect immunofluorescence. Twenty-one patients (25%) had positive titres (> or = 16) including 11 patients with titres of > or = 128. Legionella seropositivity persisted in 5 of 9 patients (55%) studied for 6-9 months. Campylobacter isolates were serotyped by the Penner scheme. Isolates associated with legionella seropositivity included Penner types 1, 2 and 4, the common endemic serotypes in England. Campylobacter blocking fluids were prepared from a range of Penner reference strains. The blocking fluid prepared from Penner type 11 was the most efficient at inhibiting the false-positive legionella titres. Using this absorption step legionella titres were inhibited from 24 of 26 patients (92%) with campylobacter but not from 8 patients with culture-proven legionnaires' disease. We recommend that this method is incorporated into routine diagnostic legionella serology in order to eliminate false-positive reactions due to campylobacter.