From August 2002 to February 2003 25 cases of hepatitis A were notified from one town in Jutland. The first cases were children of three families who returned from an endemic country. The infection spread subsequently in the local community and within households. A case-control study among household index cases showed that hepatitis A was associated with contact to a case in an after-school group (OR 29·6) and with contact to a case household member in a school class or day-care centre group (OR 9·5). From a serosurvey it was estimated that for each notified patient approximately one additional infection has occurred in the households. The infection was imported by children of immigrants, born in Denmark, returning from a visit to friends and relatives in the high-incidence country of origin of their parents and was then propagated through contact between children in after-school groups, schools and their families. Immunoprophylaxis should be given to children prior to visits to friends and relatives in endemic countries and to case contacts.

The development of second-generation rotavirus vaccines requires knowledge of baseline incidence rates for intussusception in infants prior to vaccine introduction. To obtain such estimates we reviewed clinical records in a hospital that served as the major provider of paediatric beds in a local community in the northern part of Japan. During the 25-year period (1978–2002), there were 91 hospitalizations due to radiologically confirmed intussusception in children <5 years of age, of which 45% were <1 year of age. Assuming that all children with intussusception in the area had been admitted to this hospital, there were an average of 185 and 78 hospitalizations per 100 000 person-years for children <1 year old and 5 years old respectively. There was period-to-period variability with no long-term secular trend in the incidence of intussusception. The incidence rate in Japan was among the highest thus far reported, providing further evidence of geographic variability.

The lymphocyte profile of 521 HIV-infected subjects hospitalized at Jackson Memorial (2001–2002) was compared across main respiratory diseases. Study data included medical history and all laboratory evaluations performed during hospitalization. Community-acquired pneumonias (CAP, 52%), Pneumocystis jiroveci pneumonia (PCP, 24%), tuberculosis (TB, 9%) and non-tuberculous mycobacterial diseases (NTM, 12%) were the most frequent causes of admission. Patients hospitalized with PCP and NTM exhibited the lowest CD4 counts (P=0·003). PCP patients had the highest B-cell percentages (P=0·04). CAP patients had the highest CD8 and CD4 percentages and the lowest percentage of Natural Killer (NK) cells and viral burdens. TB patients exhibited the lowest NK-cell (11·4±6·3) and B-cell percentages (13·6±12) and the highest CD8 (59±14) percentage. NTM patients, in contrast, had the highest NK-cell percentages of the groups (19·1±11·6, P=0·01). Additionally, immune responses associated with respiratory pathogens differed in HIV-infected patients with CD4+ cells above and below 200 counts.

A growing number of publications are recommending annual influenza vaccination of healthy children and adults. However, the long-term consequences of repeated influenza vaccination are unknown. We used a simple model of recurrent influenza infection to assess the likely impact of various repeated influenza vaccination scenarios. The model was based on a Markovian framework and was fitted on annual incidence rates of influenza infection by age. We found that natural influenza infection reduced the risk of being re-infected by 15·4% (95% confidence interval 7·1–23·0). Various scenarios of repeated influenza vaccination were then simulated and compared with a reference scenario where vaccination is given from age 65 years onwards. We show that repeated vaccination at a young age substantially increases the risk of influenza in older age, by a factor ranging between 1·2 (vaccination after 50 years) to 2·4 (vaccination from birth). These findings have important implications for influenza vaccination policies.

A nationwide study was undertaken to determine the susceptibility to penicillin and serotypes of Streptococcus pneumoniae in Japan. S. pneumoniae was isolated from 114 adult patients with community-acquired pneumonia over 22 months at 20 hospitals and medical centres in different regions in Japan. All but five isolates were from sputum. Forty-eight isolates (42·1%) were susceptible, 40 (35·1%) showed intermediate resistance (MIC, 0·12–1·0 μg/ml) and 26 (22·8%) were resistant (MIC, [ges ]2·0 μg/ml) to penicillin G. All isolates were susceptible to ceftriaxone (breakpoint 1 μg/ml), imipenem (4 μg/ml) and vancomycin (4 μg/ml). Most were resistant to erythromycin, clarithromycin and azithromycin; only two were resistant to levofloxacin. Differences were found in the distribution of serotypes among isolates showing susceptibility to penicillin (predominant types 3, 6B, and 19F), intermediate resistance (6B, 14, 19F, and 23F) and full resistance (19F and 23F). PFGE typing showed that 14 of the 25 strains of serotype 19F had a single DNA profile, pattern A, a pattern closely similar to that of the Taiwan multidrug-resistant 19F clone. Twelve pattern A strains were not susceptible to penicillin but carried the macrolide resistance gene mef(A). The DNA profiles of the 15 strains of 23F were also heterogeneous but six were highly similar (pattern b) yet distinct from the Spanish multidrug-resistant 23F clone although possibly related to the Taiwan multidrug-resistant 23F clone. The pattern b strains were not susceptible to penicillin and also harboured either mef(A) or erm(B). Our results indicate that multidrug-resistant pneumococci are spreading rapidly in Japan. Efforts to prevent the spread of the pandemic multidrug-resistant serotypes should be intensified.

In September 2000, haemolytic uraemic syndrome (HUS) was diagnosed in a 10-month-old child with a prodromal history of vomiting and diarrhoea (non-bloody). Investigation revealed that a self-limiting gastrointestinal illness (mean duration 48 h) had occurred among immediate and extended family in the 2 weeks prior to the child's admission. The epidemiology of the illness suggested person-to-person spread. Five children (close family contacts) had E. coli O26 verocytotoxin (VT1 and VT2) isolated from stools. Stool culture and serology from the index case were negative for shiga toxin-producing E. coli (STEC) organisms. Control measures in accordance with the Public Health Laboratory Service (PHLS), verocytotoxogenic organisms (VTEC) guidelines were applied to prevent further spread among the extended family and contacts. Despite detailed food and environmental exposure histories, the source of the illness was not identified. This incident highlights the importance of investigation of cases of post-diarrhoeal HUS, for potential shiga toxin E. coli aetiology.

In the rapidly developing city of Almaty, Kazakhstan, rates of hepatitis A have fallen, but no data on prevalence of antibody to hepatitis A virus (anti-HAV) exist with which to interpret incidence data. In the autumn of 2001, we determined the anti-HAV prevalence among household and school contacts of hepatitis A cases. For contacts aged 0–4 years, 5–9 years, 10–14 years, 15–19 years, or 20–30 years, immune prevalences were 9, 12, 33, 33 and 77% respectively, among immediate-family household contacts and 15, 28, 49, 52 and 77% respectively, among community contacts. Child community contacts were more likely to be immune than their immediate-family household counterparts (odds ratio 2·0, 95% confidence interval 1·3–3·2). Almaty is experiencing an epidemiological shift in hepatitis A incidence. Feasible and effective prevention strategies using hepatitis A vaccine should be explored.

Worldwide, early detection systems have been used in public health to aid the timely detection of increases in disease reporting that may be indicative of an outbreak. To date, their application to animal surveillance has been limited and statistical methods to analyse human health data have not been viewed as being applicable for animal health surveillance data. This issue was investigated by developing an early detection system for Salmonella disease in British livestock. We conclude that an early detection system, as for public health surveillance, can be an effective tool for enhanced surveillance. In order to implement this system in the future and extend it for other data types, we provide recommendations for improving the current data collection process. These recommendations will ensure that quality surveillance data are collected and used effectively to monitor disease in livestock populations.

A number of outbreaks and pseudo-outbreaks have been associated with contaminated rinse water in endoscope washer-disinfectors. Health Technical Memorandum 2030 specifies that final rinse water should be ‘bacteria-free’. In this study, results of rinse-water testing from 20 endoscopy units were reviewed over a 4-month period. Over 60% of samples were of an unsatisfactory quality (i.e. not bacteria-free) and none of the endoscopy units consistently achieved sterile water throughout the study period. Poor microbiology results caused anxiety to endoscopy staff and infection control teams who had to decide whether or not to take washer-disinfectors out of use, possibly resulting in delays to medical procedures. There was no common policy on how to react to poor results, with staff at each unit developing their own action levels. Here, it is suggested that future guidelines would be of more practical use if they specified a series of action levels of increasing severity based on the bacterial count in a water sample.

This study investigates the distribution of pulsed-field gel electrophoresis (PFGE) profiles within Salmonella enterica serotype Enteritidis phage type (PT) 4 and S. Typhimurium definitive phage type (DT) 104, from cases of human infection in nine European countries from 2000 to 2004. Isolates were subtyped using standardized methods and gel images submitted by each participating country to the coordinating centre (Health Protection Agency Centre for Infections, London, UK), where they were entered into a central database, developed within BioNumerics software, and designated using an agreed nomenclature. S. Enteritidis PT4 (n=3637) was differentiated into 38 different profiles. Simpson's index of diversity (D) of profiles ranged from 0·2 to 0·4. Profile SENTXB.0001 represented at least 80% of all profiles in each country. S. Typhimurium DT104 (n=1202) was differentiated into 28 different profile types. Simpson's D was at least 0·6 in all countries except in Austria and Italy. In both these countries over 74% of S. Typhimurium DT104 profiles were STYMXB.0013. Profile STYMXB.0061, was predominant in Denmark, Spain, Finland and England & Wales where it represented between 36% and 45% of profiles. Profile STYMXB.0001 represented nearly half of all profiles in Scotland and 23% in England & Wales. PFGE is proving useful for further discrimination within S. Enteritidis PT4 and S. Typhimurium DT104. Ascertainment of international outbreaks involving common serotypes and phage types may be increased by the timely pooling of PFGE profiles within a central database readily accessible to all participating countries.

At the University Hospital of Besançon (département of Doubs, France), an unusually high number of patients were hospitalized for hepatitis A during the 1999–2000 period, some of whom had not travelled abroad. This prompted us to conduct an investigation on a population basis and search for clusters of cases possibly related to local sources of contamination. Accordingly, case definition was restricted to autochthonous cases. During the 1999–2002 period, 45 autochthonous cases were classified as possibly originating from local environmental sources. A space–time scan statistic detected one most likely cluster (standardized incidence ratio 20·63, 95% confidence interval 10·6–37·1), consisting of 11 persons (of whom five children had attended the same swimming pool). It remained significant in a sensitivity analysis, strongly supporting the hypothesis of an environmental source of contamination. This study reveals the necessity of regular surveillance for hepatitis A and raises the issue of virological surveys of pool waters.

The antibiogram pattern and seasonal distribution of Salmonella serotypes were analysed retrospectively over a 6-year period from January 1999 to December 2004. Blood cultures received in the Bacteriology Laboratory were processed by standard procedures and the Salmonella spp. isolates were identified with specific antisera and standard biochemical tests. Antimicrobial susceptibility testing was carried out by a standard disc diffusion method and the minimum inhibitory concentration (MIC) of ciprofloxacin for 332 representative Salmonella isolates was determined by E test. Salmonella Typhi (75·7%) was the predominant serotype among 830 Salmonella spp. isolated during the study period followed by S. Paratyphi A (23·8%). The maximum number of enteric fever cases occurred during April–June (dry season) followed by July–September (monsoon season). There was a decrease in multidrug-resistant (MDR) S. Typhi, but MDR S. Paratyphi A isolates increased. There was also a dramatic increase in nalidixic acid-resistant isolates. All isolates were susceptible to third-generation cephalosporins and ciprofloxacin except one S. Typhi strain which demonstrated high-level ciprofloxacin resistance with a MIC of 16 μg/ml. A knowledge of the seasonal distribution and antibiotic resistance pattern of Salmonella in a particular geographical region is helpful in the delineation of appropriate control measures required for prevention of enteric fever.

The objectives of these studies were to analyse the effect of mass influenza immunization in children on the morbidity of unvaccinated non-institutionalized elderly during an influenza epidemic. A mass vaccination campaign with vaccine was conducted in children aged 3–6 years attending kindergartens (57·4% of 6374) and aged 7–17 years attending schools (72% of 34 237) in two communities of the Moscow region. The clinical effectiveness of vaccination was 60·9% for kindergartens and 68·8% for schools. There were 3·4 times fewer episodes of influenza-like illnesses and 1·7–2·6 fewer episodes in all seven diseases which are possible complications of influenza out of the 10 evaluated diseases in 158 451 unvaccinated non-institutionalized elderly people during the influenza epidemic compared with the control communities. The differences were found to be statistically significant. Mass vaccination of children attending child institutions brought about a significant reduction of both influenza-like illnesses in children and influenza-associated illnesses in unvaccinated non-institutionalized elderly persons living in the home setting.

A total of 293 meningococcal disease (McD) patients from Western Norway hospitalized during 1985–2002 were examined for risk factors related to death. The case-fatality rate (CFR) increased from 4% during 1985–1993 to 17% during 1994–2002. We analysed the phenotypic and genotypic characteristics of the meningococcal patient isolates, with the aim of identifying whether highly virulent meningococcal strains contributed to the increased CFR. The Norwegian epidemic strain B:15:P1.7,16/ST-32 complex was overall the most common phenotype/genotype (n=75) and caused most deaths (n=9; CFR 12·0%). However, fatality was significantly associated with disease caused by serogroup C meningococcal strains; C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains, which had the highest CFRs of 21·1% and 18·2% respectively. Serogroup B strains of the ST-32 complex differing by serotype and/or serosubtype from the epidemic strain had a CFR of 5·1%, while the CFR of disease caused by other strains (all phenotypes and genotypes pooled) was 2·2%. The distribution of phenotypes/clonal complexes varied significantly between 1985–1993 and 1994–2002 (P<0·001); B:15/ST-32 complex strains decreased whereas both C:15:P1.7,16/ST-32 complex strains and strains with other phenotypes/clonal complexes increased. Our results indicate that C:15:P1.7,16/ST-32 and C:2a/ST-11 complex strains were highly virulent strains and contributed to the high CFR of McD in patients from Western Norway. To reduce fatality, rapid identification of such virulent strains is necessary. In addition, early and specific measures should include public information, vaccination of populations at risk of disease and carriage eradication, when clustering of patients occurs.

One hundred and eighteen Neisseria meningitidis isolates were recovered from patients with invasive meningococcal disease in Portugal, over one year. Our study was undertaken to evaluate antimicrobial susceptibility, serogroup, serotype and genotype of isolates. One quarter (24·6%) of the isolates showed moderate resistance to penicillin and 47·4% were resistant to sulphadiazine. The two most common serosubtypes were C:2b:P1.5,2 (31·3%) and B:4:P1.15 (3·4%). Half (53·6%) of the isolates with moderate resistance to penicillin were phenotype C:2b:P1.5,2 (n=14), C:2b:P1.2 (n=1) or C:2b:NST (n=1); Pulsed-field gel electrophoresis (PFGE) showed that all these isolates were genetically related. Multilocus sequence typing (MLST) analysis of representative clones from each PFGE pattern showed the predominance of the ST-8 complex/cluster A4 among N. meningitidis with moderate resistance to penicillin. This clonal complex has been principally found in Southern Europe. The apparent emergence and dissemination of the hypervirulent ST-8 complex/cluster A4 among serogroup C strains increases the need for a continued surveillance of antimicrobial susceptibility of meningococci and of genotypic markers in Portugal.

Salmonella enterica serovar Enteritidis (SE) is a major foodborne pathogen primarily causing human infection through contaminated chicken eggs. To understand how SE survives in chicken egg albumen, we systematically and quantitatively analysed the survival properties of SE in egg albumen and identified factors affecting its survival. Survival assays of SE in egg indicate that egg albumen restricted the growth of SE. A major factor that controlled SE's growth in egg albumen was iron restriction, since egg albumen supplemented with iron allowed SE to grow, and iron acquisition mutants of SE showed decreased survival in egg albumen. In addition, low pH of albumen, high concentrations of bacteria and low incubation temperatures of bacteria with albumen facilitates the survival of SE. Our results suggest that egg albumen uses multiple mechanisms to control SE including iron limitation, surface interaction and possible enzymatic activities.

In summer 2004, an outbreak caused by Salmonella enterica serovar Enteritidis phage type 13 (S. Enteritidis PT13) was recorded in the Czech Republic. As well being a relatively rare phage type the strain was also ampicillin resistant. Outbreak (n=39) and pre-outbreak isolates (n=13) were characterized by pulsed-field gel electrophoresis (PFGE), β-lactamase gene polymerase chain reaction and plasmid profile. The majority of outbreak isolates (n=37) were identical in XbaI PFGE profile, and two other outbreak isolates each differed from this profile by one or two fragments respectively. The pre-outbreak isolates were uniform in PFGE profile but distinct from the outbreak strain. Ampicillin resistance was confirmed to be encoded by the blaTEM gene located on the TnA transposon. This gene was readily transferable to a S. Enteritidis recipient strain and was associated with the transfer of a 200-kb plasmid. Our results indicate that all S. Enteritidis PT13 tested from 2004 belonged to a single outbreak strain which prior to 2004 had not been recognized in the Czech Republic.

We conducted a prospective, cohort study at two affiliated level III neonatal intensive care units to evaluate the effect of a closed drug-delivery system on the incidence of nosocomial and catheter-related bloodstream infections (CRBSI) in infants. A total of 300 infants (n=150 at each site) were enrolled over a 4-year study period. There was no difference in the rate of CRBSI per 1000 catheter days between the two sites (16·2±39 vs. 8·9±24, P=0·054, 95% CI−14·8 to 0·13). Infants at site A (closed drug-delivery system) had a higher rate of infectious nosocomial respiratory complications per 100 hospital days than infants at site B (open delivery system) (1·1±2·2 vs. 0·5±1·5, P=0·009), however, there was no difference in the overall number of confirmed or suspected nosocomial infection events per patient between study sites. Logistic regression revealed that the number of additional peripheral catheters, gestational age and duration of parenteral nutrition all significantly contributed to the risk of developing one or more CRSBI. The closed drug-delivery system failed to reduce the incidence of CRBSI or overall rate of nosocomial infections in premature infants.

We conducted a prospective birth cohort study in rural Sudan to assess measles virus (MV)-specific antibody levels at different time points in infancy. Dried blood spots were collected on filter paper at birth (cord blood) and at ages 6, 12 and 24 months (heel-prick). Maternally derived MV-specific antibody levels were high in cord blood samples, but at the age of 6 months had dropped below cut-off values in half of the infants. By extrapolation it was concluded that the current Expanded Programme of Immunization (EPI) target age for measles vaccination of 9 months was an appropriate choice for this area. At the age of 24 months acquired MV-specific antibodies were detected in 65–85% of the cohort, which corresponded well with the 79% of infants reported to be vaccinated by this age. This study demonstrates the usefulness of filter paper blood samples for seroepidemiological studies in developing countries.

This study analysed the role of several risk factors for hospitalization due to community-acquired, respiratory syncytial virus (RSV) infection. The risk factors detected in infants hospitalized for RSV infection in the first 24 months of life were compared with those in the general infant population in our region. There were 361 episodes of hospitalization in 357 infants. Eighty per cent of the infants did not present underlying conditions for severe RSV infection and only 10 (3%) were candidates for palivizumab prophylaxis. In multivariate analysis, birthweight of <2500 g was independently associated with hospitalization for RSV infection and was the most commonly detected medical risk factor. Other risk factors were maternal age at delivery <25 years, birth in the second half of the year, prematurity, suburban residence and congenital heart disease. In conclusion, together with well-known risk factors, we found that low birthweight was an independent factor for severe RSV infection.