In 1981, R. Edgar Hope-Simpson proposed that a ‘seasonal stimulus’ intimately associated with solar radiation explained the remarkable seasonality of epidemic influenza. Solar radiation triggers robust seasonal vitamin D production in the skin; vitamin D deficiency is common in the winter, and activated vitamin D, 1,25(OH)2D, a steroid hormone, has profound effects on human immunity. 1,25(OH)2D acts as an immune system modulator, preventing excessive expression of inflammatory cytokines and increasing the ‘oxidative burst’ potential of macrophages. Perhaps most importantly, it dramatically stimulates the expression of potent anti-microbial peptides, which exist in neutrophils, monocytes, natural killer cells, and in epithelial cells lining the respiratory tract where they play a major role in protecting the lung from infection. Volunteers inoculated with live attenuated influenza virus are more likely to develop fever and serological evidence of an immune response in the winter. Vitamin D deficiency predisposes children to respiratory infections. Ultraviolet radiation (either from artificial sources or from sunlight) reduces the incidence of viral respiratory infections, as does cod liver oil (which contains vitamin D). An interventional study showed that vitamin D reduces the incidence of respiratory infections in children. We conclude that vitamin D, or lack of it, may be Hope-Simpson's ‘seasonal stimulus’.

We reviewed the epidemiological and microbiological characteristics of 89 reported outbreaks of waterborne infectious intestinal disease affecting 4321 people in England and Wales over the period 1992–2003. Public water supplies were implicated in 24 outbreaks (27%), private water supplies in 25 (28%), swimming pools in 35 (39%) and other sources in five outbreaks (6%). Cryptosporidium was implicated in 69% of outbreaks, Campylobacter sp. in 14%, Giardia in 2%, E. coli O157 in 3% and Astrovirus in 1%. From 2000, there was a consistent decline in the number of outbreaks of waterborne disease associated with public water supplies. The incidence rate of outbreaks in recipients of private water supplies may be as high as 35 times the rate in those receiving public water supplies (1830 vs. 53 per million population). Private water suppliers need to be aware of the importance of adequate treatment and the prevention of faecal contamination of storage water. Swimming-pool operators need to ensure chlorination and in particular adequate filtration measures are in place.

Despite the importance of lower respiratory-tract infection (LRI) in causing hospitalizations in elderly patients ([ges ]65 years of age) and recent advances in vaccine development, a complete picture of the causative organisms is not available. All hospital discharge diagnoses (ICD-10 code) for LRI in elderly patients in England during 1995–1998 were reviewed. Using known seasonality in potential causative agents of LRI, the contribution of different respiratory pathogens to hospitalizations coded as ‘unspecified LRI’ was estimated by multiple linear regression analysis. Ninety-seven per cent of 551633 LRI-associated diagnoses had no specific organism recorded. From the statistical model the estimated proportions of admissions attributable to different pathogens were applied to calculate estimated hospitalization rates: 93·9 hospitalizations/10000 population aged [ges ]65 years due to S. pneumoniae, 22·9 to influenza virus, 22·3 to H. influenzae, 17·0 to whooping cough, and 12·8 to respiratory syncytial virus. There is enormous potential to improve health using existing vaccines and those under development.

Although mixing patterns are crucial in dynamic transmission models of close contact infections, they are largely estimated by intuition. Using a convenience sample (n=73), we tested self-evaluation and prospective diary surveys with a web-based interface, in order to obtain social contact data. The number of recorded contacts was significantly (P<0·01) greater on workdays (18·1) vs. weekend days (12·3) for conversations, and vice versa for touching (5·4 and 7·2 respectively). Mixing was highly assortative with age for both (adults contacting other adults vs. 0- to 5-year-olds, odds ratio 8·9–10·8). Respondents shared a closed environment significantly more often with >20 other adults than with >20 children. The difference in number of contacts per day was non-significant between self-evaluation and diary (P=0·619 for conversations, P=0·125 for touching). We conclude that self-evaluation could yield similar results to diary surveys for general or very recent mixing information. More detailed data could be collected by diary, at little effort to respondents.

A case-control study was undertaken in an acute district general hospital to identify risk factors for hospital-acquired bacteraemia caused by methicillin-resistant Staphylococcus aureus (MRSA). Cases of hospital-acquired MRSA bacteraemia were defined as consecutive patients from whom MRSA was isolated from a blood sample taken on the third or subsequent day after admission. Controls were randomly selected from patients admitted to the hospital over the same time period with a length of stay of more than 2 days who did not have bacteraemia. Data on 42 of the 46 cases of hospital-acquired bacteraemia and 90 of the 92 controls were available for analysis. There were no significant differences in the age or sex of cases and controls. After adjusting for confounding factors, insertion of a central line [adjusted odds ratio (aOR) 35·3, 95% confidence interval (CI) 3·8–325·5] or urinary catheter (aOR 37·1, 95% CI 7·1–193·2) during the admission, and surgical site infection (aOR 4·3, 95% CI 1·2–14·6) all remained independent risk factors for MRSA bacteraemia. The adjusted population attributable fraction, showed that 51% of hospital-acquired MRSA bacteraemia cases were attributable to a urinary catheter, 39% to a central line, and 16% to a surgical site infection. In the United Kingdom, measures to reduce the incidence of hospital-acquired MRSA bacteraemia in acute general hospitals should focus on improving infection control procedures for the insertion and, most importantly, care of central lines and urinary catheters.

Co-circulation of respiratory syncytial virus (RSV) and influenza has made the partitioning of morbidity and mortality from each virus difficult. Given the interaction between chronic obstructive lung disease (COPD) and pneumonia, often one can be mistaken for the other. Multivariate time-series methodology was applied to examine the impact of RSV and influenza on hospital admissions for bronchiolitis, pneumonia, and COPD. The Granger Causality Test, used to determine the causal relationship among series, showed that COPD and pneumonia are not influenced by RSV (P=0·2999 and 0·7725), but RSV does influence bronchiolitis (P=0·0001). Influenza was found to influence COPD, pneumonia, and bronchiolitis (P<0·0001). The use of multivariate time series and Granger causality applied to epidemiological data clearly illustrates the significant contribution of influenza and RSV to morbidity in the population.

Nasopharyngeal carriage of potential pathogens was studied in 425 healthy 3- to 6-year-old children attending 16 day-care centres (DCCs) in nine Czech cities during the winter 2004–2005. The overall carriage of pathogens was 62·8% (Streptococcus pneumoniae, 38·1%; Haemophilus influenzae, 24·9%; Moraxella catarrhalis, 22·1%; Staphylococcus aureus, 16%). An age-related downward trend was observed for colonization with respiratory pathogens in contrast to Staph. aureus whose carriage was significantly higher among older children. The following serotypes of colonizing S. pneumoniae were the most predominant: 23F (20·6%), 6A (15·1%), 6B (12·7%), 18C (7·8%), 15B and 19F (6% each). The majority (94·3%) of H. influenzae isolates were non-typable; among capsulated isolates, serotype b was not found. Decreased susceptibility to penicillin was determined in 3% of pneumococci; 4·6% of H. influenzae strains and 85·1% of M. catarrhalis strains produced β-lactamase. As for non-β-lactam antibiotics, pneumococci resistant to trimethoprim–sulphamethoxazole were the most common (15·7%) among the attendees.

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.

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.

Studying the epidemiology of pertussis and impact of differing vaccine schedules is difficult because of differing methods of case ascertainment. The advent of internationally standardized serological diagnosis for recent infection has allowed comparison of age-specific pertussis infection among European countries and was applied in Australia at the time of a major national epidemic. In 1997 and 1998, a nationally representative serum bank using residual sera from diagnostic laboratories was established. Measurement of pertussis toxin (PT) IgG level was conducted by a reference laboratory using an enzyme-linked immunosorbent assay standardized for a number of European countries. A titre of 125 EU/ml was interpreted as indicative of recent pertussis infection. The serological data were correlated with age, gender, region and disease epidemiology in Australia. The highest prevalence of recent pertussis infection was in the 5–9 years age group, and the lowest in 1–4 and 25–64 years age groups. In the 5–14 years age group, 29·7% (5–9 years) and 14·6% (10–14 years) of the sample had serological evidence of recent infection, correlating with the pattern of epidemic notifications. The 15- to 24-year-olds had similar high titres but the same notification rate as 25- to 44-year-olds, suggesting ascertainment bias may result in under-notification in the former age group. The prevalence of high titres observed was up to 20-fold higher than some European countries during a similar time period. Although vaccination has reduced the transmission of pertussis in the youngest and most vulnerable age group, pertussis is still endemic in Australia, particularly in older children and the elderly. The Australian vaccination schedule has been changed in an attempt to address this problem, by spacing doses more widely, with the fifth dose at 15–17 years of age. Seroepidemiology for pertussis offers the potential to compare patterns of pertussis between countries and examine the impact of vaccine schedule changes independent of notification and diagnostic bias.

Leptospirosis is one of the most commonly encountered zoonoses in both Australia and the rest of the world. The incidence of leptospirosis in Queensland over the 7-year study period (1998–2004) was 3·1/100000 population. Enhanced surveillance questionnaires were used to collect patient data and facilitate an epidemiological investigation of leptospirosis in Queensland. Farming occupations comprised the majority of occupational exposure cases, however, recreational exposure accounted for 18% of the 883 cases. Rainfall and the presence of animal hosts had the most influence on the incidence of leptospirosis. Several trends in serovar numbers over this period are noted, in particular the emergence of L. borgpetersenii serovar Arborea, which accounted for 22% of all leptospirosis cases in Australia and 68% of South-East Queensland cases in 2004. Assessment of epidemiological trends in leptospirosis is important to obtain directed public health intervention and outcomes in the reduction of leptospirosis cases.

Between 28 November 2003 and 23 February 2004, 4343 cases and 154 deaths from cholera (case-fatality rate 3·5%) were reported in Lusaka, Zambia. A case-control study was conducted in February 2004 to assess potential transmission routes and prevention strategies. Consumption of raw vegetables was significantly associated with cholera [adjusted odds ratio (aOR) 4·7, 95% confidence interval (CI) 1·7–13, P=0·003). Consumption of a local sardine-like fish was protective (aOR 0·3, 95% CI 0·1–0·7, P=0·008). Hand soap was present in 90% of control homes and 58% of case homes. Observed hand soap was a strongly protective factor (aOR 0·1, 95% CI 0·04–0·4, P=0·001). No water source or treatment practice was significantly associated with cholera. This study documents the importance of foodborne transmission of cholera, illustrates the protective role of hand washing in an epidemic setting, and identifies a novel possible protective factor, a local fish, which warrants further research.

Dispersed community outbreaks of Shigella sonnei have occurred cyclically among traditionally observant Jews in the United States. In February 2000, we investigated a S. sonnei outbreak in one Jewish community in New York City. To determine risk factors for introduction of infection into households, we conducted a cohort study of households to compare risk factors for illness among primary subjects within households and age-matched well siblings. Isolates were subtyped by pulsed-field gel electrophoresis (PFGE). We used a random effects model to assess extra-household vs. intra-household transmission in households with multiple ill household members. Daycare or pre-school attendance [matched odds ratio (mOR) 16·1, P<0·001] and age <60 months (mOR 6·3, P<0·001) were independently associated with index subject illness. Outbreak isolates were closely related by PFGE analysis to the strain previously observed in Jewish community outbreaks. The random effects model strongly indicated that multiple illnesses in a single household are due to secondary transmission. Disease containment efforts should focus on reducing Shigella transmission in childcare settings and within homes.

Ninety-seven isolates of Shigella flexneri from children seeking medical care from three sites in Egypt were characterized. Overall, 46·4% of children (median age 17 months) were febrile or reported blood in their stools, 25·8% were dehydrated and 16·5% were admitted to hospital. Serotypes 2a (37·1%), 1b (18·6%), 1c (17·5%), and 6 (15·5%) comprised over 88·7% of the total isolates. We observed marked resistance to ampicillin (87·6%), tetracycline (84·5%) and trimethoprim–sulfamethoxazole (63·9%). Pulsed-field electrophoresis grouped the majority of isolates within a serotype together, separately from isolates of an alternative serotype. The set gene was present in all serogroup 2a isolates, however, the sen gene was detected in every isolate. Our results show S. flexneri 1c has emerged as a dominant S. flexneri serotype in Egypt. Development and application of a Shigella vaccine should consider the diversity of Shigella serotypes within a geographical region prior to administration.

A total of 113 strains of Shigella dysenteriae type 2 isolated from patients attending the Dhaka diarrhoea treatment centre of ICDDR,B: Centre for Health and Population Research during the period 1999–2004 were studied. Serotype of the isolates was confirmed using commercially available antisera. Except for arabinose fermentation, all the strains had similar biochemical reactions. More than 60% of the strains were sensitive to commonly used antibiotics; only 6% (n=7) of the strains were resistant to nalidixic acid, and none of the strains were resistant to mecillinam and ciprofloxacin. All strains were invasive as demonstrated by the presence of a 140 MDa plasmid, ial, sen and ipaH genes, Congo Red absorption ability and by the Sereny test performed on representative strains. Plasmid patterns were heterogeneous but more than 50% of strains were confined to a single pattern. All strains possessed a 1·6 MDa plasmid and 87% of the strains contained a 4 MDa plasmid. Middle-range plasmids (90 MDa to 30 MDa) present in 36% of the strains were not associated with antibiotic resistance. All the strains were clustered within a single type with four subtypes by pulsed-field gel electrophoresis while ribotyping patterns of all the strains were identical.

Salmonella Mississippi infections are very common in Australia's island state – Tasmania – with an annual rate of 17 cases/100000 population. A case-control study conducted during 2001–2002 found single variable associations with indirect exposure to many native animal species, untreated drinking water, travelling within the state, hand–mouth behaviours and contact with pet faeces. No associations were detected with farm animal or pet species or with any food. Indirect contact with native birds, untreated drinking water and travel within the state remained significant predictors of infection in the final model with population attributable fractions of 0·57 and 0·54 for native animals and untreated drinking water respectively. In Tasmania, Australian wildlife species are the likely reservoir for S. Mississippi, contaminating land and water environments. To decrease infection rates requires treatment of water supplies, particularly private rainwater collection systems and advising people to wash their hands after being outdoors and prior to eating.

In The Netherlands, a national programme for the surveillance of zoonotic bacteria in farm animals has been operative since 1997. We describe the results of the surveillance of Salmonella spp. in flocks of laying hens and broilers and of Campylobacter spp. in broiler flocks in the period 1999–2002. The prevalence of Salmonella spp. in laying-hen flocks has significantly decreased from 21·1% in 1999 to 13·4% in 2002. This decreasing trend might indicate that the control measures taken by the poultry industry were effective. S. Enteritidis was the predominant serovar in laying hens accounting for one third of the positive flocks. Although prevalence estimates for Salmonella spp. in broiler flocks did not yield a significant decreasing trend in 1999–2002, a decrease in Salmonella prevalence to 11% was measured in 2002. During the study period, S. Paratyphi B var. Java emerged in broilers to become the predominant serovar in 2002 accounting for one third of the positive flocks. The prevalence of Campylobacter spp. in broiler flocks did not increase nor decrease continuously between 1999 and 2002, which roughly corresponds with the monitoring results from the poultry industry. In this period, the estimated flock prevalence roughly averaged around 20%, with C. jejuni being the predominant species. The approach of monitoring presented in this paper can serve as a blueprint for monitoring schemes in farm animal populations to be developed in the context of the EC Zoonoses Directive.

In the summer of 2001 an outbreak of Escherichia coli O157 gastroenteritis affected staff and residents of a care home for the elderly in the West Midlands, UK. E. coli O157 phage type 2 was isolated from faeces in eight patients and 12 staff members. Thirty-five staff and 40 residents met the case definition for clinical gastrointestinal infection. Serological testing identified a further 14 possible cases of infection amongst asymptomatic staff and residents. The outbreak was atypical, as the disease seemed to be milder than has been observed in past outbreaks in similar settings. The index case, a member of staff, developed bloody diarrhoea and haemolytic–uraemic syndrome (HUS), but only one resident developed bloody diarrhoea and required hospitalization. No deaths occurred, despite the high-risk nature of the affected population. The source of the outbreak could not be identified. The prolonged nature of the outbreak and observed lapses in infection control practices indicated that person-to-person spread was the likely route of transmission. This outbreak illustrates the importance of observing appropriate infection control measures in the institutions providing residential and nursing care to the elderly.

The antimicrobial resistance profiles of Campylobacter isolates recovered from a range of retail food samples (n=374) and humans (n=314) to eight antimicrobial compounds were investigated. High levels of resistance in food C. jejuni isolates were observed for ceftiofur (58%), ampicillin (25%) and nalidixic acid (17%) with lower levels observed for streptomycin (7·9%) and chloramphenicol (8·3%). A total of 80% of human C. jejuni isolates were resistant to ceftiofur, while 17% showed resistance to ampicillin and nalidixic acid, 8·6% to streptomycin and 4·1% to chloramphenicol. Resistance to clinically relevant antimicrobials such as erythromycin, ciprofloxacin and tetracycline was 6·7, 12, and 15% respectively for all food isolates and was similar to corresponding resistance prevalences observed for human isolates, where 6·4, 12 and 13% respectively were found to be resistant. Comparisons of C. jejuni isolates in each location showed a high degree of similarity although some regional variations did exist. Comparison of total C. jejuni and C. coli populations showed minor differences, with C. jejuni isolates more resistant to ampicillin and ceftiofur. Multidrug resistance patterns showed some profiles common to human and clinical isolates.