Epidemiology and Infection

Published by Cambridge University Press (CUP)
Online ISSN: 1469-4409
Print ISSN: 0950-2688
SUMMARY Clostridium difficile infection has gained importance in recent years as a result of the rapid spread of epidemic strains, including hypervirulent strains. This study reports the molecular epidemiology of C. difficile obtained from hospitalized patients in Chile. Seven hundred and nineteen isolates of toxigenic C. difficile from 45 hospitals across the country were characterized through toxin profile, pulsed-field gel electrophoresis (PFGE), and sequencing of the tcdC gene. In addition, polymerase chain reaction (PCR) ribotyping and multilocus sequence typing (MLST) were performed on a subset of selected strains. PFGE typing of 719 isolates of C. difficile produced 60 PFGE patterns (subtypes). Subtype 1 was predominant (79% of isolates) and related to the hypervirulent strain (NAP1). Subtype 1 showed 73% relatedness with nine other subtypes, which had a similar tcdC deletion. Subtype 1 corresponded to ribotype 027 and ST1. This report shows the wide dissemination of the hypervirulent strain NAP1/027/ST1 in Chile.
Southern hybridization analysis of genomic DNA from Cs-Kunz SL2840 (lane 1), Cs-non-K 999 \ 94 (lane 2), and Choleraesuis var. Decatur SARB 5 (lane 3) digested with Pvu II and probed by the PCR-generated 550 bp internal fragment of the 16S rrn gene. These most common ribotypes were termed Ia, IIa, and IIIa, respectively. 
Ribotypes of the five O6,7 : c : 1,5 Salmonella groups. Computer generated lane map (Image Master 1D, Pharmacia) of the 16 rrn gene profiles observed in Pvu II digests among the 67 strains analysed. 
Sixty-seven strains of the five described Salmonella serotypes having antigens 6,7[ratio]c[ratio]1,5, that is S. enterica serotype Choleraesuis sensu stricto, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C, and Typhisuis, were examined for 16S rrn profile ribotype, presence of IS200 and phenotypic characters, including rate of change of flagellar-antigen phase and nutritional character. Choleraesuis sensu stricto and its Kunzendorf variant had related but distinct ribotypes. Therefore, ribotyping appears to be a suitable method for differentiating Choleraesuis non-Kunzendorf from Choleraesuis var. Kunzendorf. Some strains of Paratyphi C had 16S profiles that resembled that of Choleraesuis non-Kunzendorf, while others resembled that of Choleraesuis var. Kunzendorf. The Typhisuis profiles were like those of Choleraesuis non-Kunzendorf, while the Choleraesuis var. Decatur profiles were unlike those of any of the other four groups. Furthermore, IS200 fingerprinting discriminated between Choleraesuis var. Decatur and the other strains with antigenic formula O6,7[ratio]c[ratio]1,5, and comparison of IS200 patterns showed a high degree of genetic divergence within Choleraesuis var. Decatur. Our findings show that ribotyping and IS200 fingerprinting, combined with classical microbiological methods, distinguish the groups Choleraesuis non-Kunzendorf, Choleraesuis var. Kunzendorf, Choleraesuis var. Decatur, Paratyphi C and Typhisuis.
The present study was undertaken to investigate the frequency of the nasal carrier rate of Staphylococcus aureus. The investigation was performed on 104 healthy persons. The total number of swabs performed was 1498 and this resulted in isolation of 522 S. aureus strains. All strains have been identified, tested for antibiotic susceptibility, and phage-typed. The carrier-index (number of positive swabs/number of total swabs for each individual person) was compared with different sampling and culturing methods, phage type, age, and resistance to antibiotics. There was statistical difference in carrier rate according to sex (P < 0.05). Among the 104 persons 15 (14.4%) were persistent carriers, 17 (16.3%) intermittent carriers, 55 (52.9%) occasional carriers and 17 (16.3%) non-carriers. Among intermittent and occasional carriers the phage-type distribution was different from the S. aureus strains isolated from Danish hospitalized patients in 1992, while the persistent carriers had similar phage-type distribution.
Between 1 August and 15 September 2000, 361 cases of Salmonella enterica serotype Typhimurium definitive phage type (DT) 104, resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, spectinomycin and tetracycline (R-type ACSSuSpT), were identified in England and Wales residents. Molecular typing of 258 isolates of S. Typhimurium DT104 R-type ACSSuSpT showed that, although isolates were indistinguishable by pulsed-field gel electrophoresis, 67% (174/258) were characterized by a particular plasmid profile. A statistically significant association between illness and consumption of lettuce away from home was demonstrated (OR = 7.28; 95% CI=2.25-23.57; P=0.0006) in an unmatched case-control study. Environmental investigations revealed that a number of food outlets implicated in the outbreak had common suppliers of salad vegetables. No implicated foods were available for microbiological testing. An environmental audit of three farms that might have supplied salad vegetables to the implicated outlets did not reveal any unsafe agricultural practices. The complexity of the food supply chain and the lack of identifying markers on salad stuffs made tracking salad vegetables back to their origin extremely difficult in most instances. This has implications for public health since food hazard warnings and product withdrawal are contingent on accurate identification of the suspect product.
Neighbour-joining tree constructed based on the composite sequence of seven housekeeping gene fragments. Bootstraps were generated using 1000 replicates. BJ, Beijing ; SD, Shandong ; GZ, Guangzhou ; j , new sequence types. 
The phylogenetic and epidemic relationships of 104 clinical isolates of Clostridium difficile from three hospitals of different geographical and population sources in China were investigated by multilocus sequence typing. Twenty-two sequence types (STs) were identified, four of which, ST117, ST118, ST119 and ST129, were novel. No geographically specific and host population-specific phylogenetic lineages were found and there was no correlation between geographical origin or host population and strain genotype. ST37 was the dominant type in our survey but the four novel STs underline the high genetic diversity and unique polymorphisms in C. difficile from China.
Ten most common profile types within S . Enteritidis PT4. 
Diversity of profiles of S. Enteritidis PT4 and S. Typhimurium DT104 within each country
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 and 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 and 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.
An outbreak of echovirus 11 infection was observed in a children's home that housed 16 children. Nine children younger than 1 year shared a large room on the first floor, which contained a large basin. Three of them presented with aseptic meningitis with CSF and stool samples positive for echovirus 11. The other six infants who shared the room were asymptomatic but their stools were positive for echovirus 11. Seven infants aged 1-2 years stayed on the second floor and were asymptomatic. One of them had positive stool culture for echovirus 11. No virus was isolated from stool samples taken from the 26 staff members. However, serology was suggestive for recent echovirus 11 infection in seven asymptomatic staff members. All seven worked either exclusively on the first floor or alternately on both floors. Our survey demonstrated that echovirus 11 may spread very efficiently in children's homes. The rate of meningitis in the infected infants was 30% while all the recently infected adults were asymptomatic.
Phenotypes/clonal complexes of patient strains related to case-fatality rates (CFR) and time period 
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.
Agarose gel electrophoresis showing PCR ampli fi cation products ( a ) IS 1001 , ( b ) IS 1002 , respectively. The fi rst lane represents the positive control, B. parapertussis B0024. Lanes 2 – 7 are some of the representative B. parapertussis isolates collected during December 2009 – January 2010. 
Summary of B. parapertussis isolates and affected clinical cases
SUMMARY Pertussis or whooping cough is a highly contagious community disease mainly caused by Bordetella pertussis and B. parapertussis. We report a minor outbreak of whooping cough (2009-2010) in symptomatic subjects from Bisham, near Swat, Khyber Pukhtoonkhawa province, Pakistan. Interestingly, our results show that all the culture-positive isolates (n = 21) collected from children (average age 3·46 years), were identified as B. parapertussis after routine identification tests and PCR IS481, IS1001 and IS1002. Furthermore, in the affected patients, none had received immunization with diphtheria-pertussis-tetanus (DTPw) vaccine. Therefore, the possibility of the re-emergence of the disease due to limitation of basic health services as a result of the political unrest due to the 9/11 situation is also examined. Moreover, we discuss the importance of vaccinating both adults and children with DTPwPaw vaccine containing both organisms for better protection.
SUMMARY Influenza surveillance in Danish intensive care units (ICUs) was performed during the 2009/10 and 2010/11 influenza seasons to monitor the burden on ICUs. All 44 Danish ICUs reported aggregate data for incidence and point prevalence, and case-based demographical and clinical parameters. Additional data on microbiological testing, vaccination and death were obtained from national registers. Ninety-six patients with influenza A(H1N1)pdm09 were recorded in 2009/10; 106 with influenza A and 42 with influenza B in 2010/11. The mean age of influenza A patients was higher in 2010/11 than in 2009/10, 53 vs. 44 years (P=0·004). No differences in other demographic and clinical parameters were detected between influenza A and B patients. In conclusion, the number of patients with severe influenza was higher in Denmark during the 2010/11 than the 2009/10 season with a shift towards older age groups in influenza A patients. Influenza B caused severe illness and needs consideration in clinical and public health policy.
SUMMARY In this study we collected and analysed data of the severe burn patients at our institution over an 11-year period in order to shed light on the controversial role of bloodstream infection (BSI) as a predictive factor for mortality in this burn population. The factors examined were age, total body surface area, smoke inhalation, presence of BSI, and BSI with resistant bacteria. In total 1081 burn patients were hospitalized from 2001 to 2011, of whom 4% died. We focused here on 158 severe burn patients, 74 of whom developed BSI, and 35 who died. Using univariate analysis, it appeared that the BSI group had a threefold greater chance of mortality compared to the non-BSI group. Patients with a Ryan score 3 had a 100% chance of mortality and those with a score 0 had 0%. Thus, focusing only on Ryan score 1 and score 2 patients, BSI did not contribute to mortality, nor was it shown to contribute to mortality in a multivariate analysis in which the score and BSI were included together. When BSI did occur, it predicted longer hospitalization periods. We conclude that BSI predicts longer length of hospitalization stay but does not contribute to the prediction of mortality beyond that offered by the Ryan score in a severe burn population.
Numbers of cultured meningococcal isolates and incidence of notified cases of IMD in Victoria, 1994-2000. Incidence per 105 values include cases diagnosed on clinical criteria alone, in addition to those confirmed by microbial culture.
Comparison of the frequency of PFGE pattern A and B serogroup C isolates with all other serogroup C isolates, 1996-2000. The category ' Other restriction patterns ' includes PFGE patterns C-F and any remaining patterns exhibited by serogroup C isolates.
Cases of serogroup B and C meningococcal disease in Victoria by age group, 1999–2000. Serogroup C (other restriction patterns) includes all serogroup C isolates except those giving macrorestriction pattern A. 
In the years 1999-2000, there was an increase in the incidence of meningococcal disease in Victoria, largely caused by Neisseria meningitidis serogroup C. This change was associated with a shift in age distribution of cases, with relatively more disease appearing in the 15-29 year age group, and with 40/58 serogroup C isolates in 2000 exhibiting a new macrorestriction pattern (pattern A). Thirty-four of 52 pattern A isolates tested displayed the novel phenotype C:2a:P1.4, and were consistently porA VR type P1.7-2,4 by DNA sequencing. Nine of 10 representative pattern A isolates analysed displayed a housekeeping gene allele profile (ST-11) that is characteristic of the electrophoretic type (ET)-15 variant that has caused outbreaks in Canada, the Czech Republic and Greece. Meningococci belonging to the ST-11 complex that were isolated in Victoria prior to 1999 did not display either restriction pattern A or PorA VR type P1.7-2,4.
Alignment of VNTR VC5 locus of eight V. cholera strains. The DNA fragments of 198 bp contain eight repeats of the motif GATAATCCA (in blue), while the smaller fragments of 138 bp have three repeats. These amplicons with deviation on the allele size have a 15-bp deletion (in yellow) below the VNTR. 
Genetic relationship between 111 V. cholerae strains was analysed by creating a minimum spanning tree. The 111 strains were clustered based on the differences in the phenotypic and genetic markers. Each circle in the tree represents a different type. Circles are divided according the number of strains with a certain type. The species with different serogroups are represented by different colours, as indicated. The thickness of the lines indicate the genetic distance ; solid and thin lines represent single and double locus variants, respectively ; dotted lines indicate the most probable connection between two types differing by more than two locus variants ; the length of the branches is proportional to the distance between the types. 
Discrimination indices of individual or combined typing methods for Vibrio cholerae
A total of 111 clinical and environmental O1, O139 and non-O1/O139 Vibrio cholerae strains isolated between 1978 and 2008 from different geographical areas were typed using a combination of methods: antibiotic susceptibility, biochemical test, serogroup, serotype, biotype, sequences containing variable numbers of tandem repeats (VNTRs) and virulence genes ctxA and tcpA amplification. As a result of the performed typing work, the strains were organized into four clusters: cluster A1 included clinical O1 Ogawa and O139 serogroup strains (ctxA(+) and tcpA(+)); cluster A2 included clinical non-O1/O139 strains (ctxA(-) and tcpA(-)), as well as environmental O1 Inaba and non-O1/O139 strains (ctxA(-) and tcpA(-)/tcpA(+)); cluster B1 contained two clinical O1 strains and environmental non-O1/O139 strains (ctxA(-) and tcpA(+)/tcpA(-)); cluster B2 contained clinical O1 Inaba and Ogawa strains (ctxA(+) and tcpA(+)). The results of this work illustrate the advantage of combining several typing methods to discriminate between clinical and environmental V. cholerae strains.
(Reprinted from: Hayes W. The discovery of pneumococcal type transformation: an appreciation. J Hyg 1966; 64 : 177–184.) Griffith F. The significance of pneumococcal types. J Hyg 1928; 27 : 113–159.
SUMMARY The influence of an immunosuppressive cytokine, interleukin-10 (IL-10), on the outcome of hepatitis C virus (HCV) infection has been increasingly reported recently. A number of polymorphisms appear to control the level of IL-10 production. Among them, -592C/A, -819C/T and -1082G/A in the IL-10 gene are three most studied single nucleotide polymorphisms. To provide a more definitive conclusion about their association with the risk of HCV infection, a meta-analysis was performed by combining and summarizing a total of 17 studies. A biological justification for the choice of genetic model was provided. The results indicated no significant association between these IL-10 polymorphisms and the susceptibility to HCV infection [-592C/A: odds ratio (OR) 0·99, 95% confidence interval (CI) 0·78-1·25; -819C/T: OR 0·90, 95% CI 0·69-1·18; -1082G/A: OR 1·34, 95% CI 0·90-2·00]. However, this analysis did not account for the possible risk modifications by other factors, such as ethnicity and virus persistence. Therefore, the effects of ethnicity and virus persistence were investigated using Bayesian meta-regression and subgroup analysis. Finally, an extended case-control association study was conducted in a Chinese population involving 1140 subjects. Both serum level and genotype data of IL-10 -1082G/A were determined. As a result, a low prevalence of G allele was observed. Significantly higher IL-10 production was observed in HCV patients, especially patients with the GG genotype.
Parameters relating to sexual behaviour [14, 15] 
Prevalence of hepatitis B markers in the UK 
Complex hepatitis B (HBV) epidemiology makes it difficult to evaluate and compare effectiveness of different immunization policies. A method for doing so is presented using a mathematical model of HBV transmission dynamics which can represent universal infant and adolescent vaccination strategies and those targeted at genito-urinary (GU) clinic attenders and infants born to infectious mothers. Model structure, epidemiological underpinning, and parameterization, are described. Data from the UK National Survey of Sexual Attitudes and Lifestyles is used to define patterns of sexual activity and GU clinic attendance; data deficiencies are discussed, in particular that of UK seroprevalence of HBV markers stratified by age, sex, and risk factors. General model predictions of endemic HBV marker prevalence in homosexual and heterosexual populations seem consistent with published UK data. The simulations exhibit non-linearities in the impact of different vaccination strategies. Estimated number of carriers prevented per vaccine dose for each strategy provides a measure of costs and benefits, varying temporally over the course of a programme, and with level of vaccine coverage. Screening before vaccination markedly increases payback per dose in homosexuals but not in heterosexuals; mass infant vaccination gives the poorest effectiveness ratio and vaccination of infants after antenatal screening the best; in general, increasing vaccine coverage yields lower pay-back per dose. The model provides a useful framework for evaluating costs and benefits of immunization programmes, but for precise quantitative comparison more UK epidemiological data is urgently needed.
An outbreak of Salmonella typhimurium DT 124 infection which affected 101 people in England in December 1987 and January 1988 was detected through surveillance of laboratory reports from medical microbiology laboratories of the NHS and PHLS. Within 1 week of noting the increase in reports, epidemiological and microbiological investigations identified a small German salami stick as the vehicle of infection and the product was withdrawn from sale. The epidemiological investigation highlighted the occurrence of a long incubation period, bloody diarrhoea. Prompt recognition and investigation of the outbreak prevented further cases of severe infection.
Demographic and clinical characteristics of 128 patients with severe influenza A(H7N9) infection, Zhejiang, China
SUMMARY No published studies have discussed details of the prognosis and survival of patients with severe avian influenza A(H7N9) infection. In this study we analysed 128 laboratory-confirmed cases of severe H7N9 infection in Zhejiang province, the most affected region during the H7N9 epidemic in mainland China. We found that an increase in patient age by 5 years was associated with a 1·41 [95% confidence interval (CI) 1·19-1·67] times odds ratio for fatality. In addition, the time interval between the first clinical visit after symptom onset and hospital admission was inversely associated with survival time since admission. Of the 47 patients who died of the disease, when the time interval between the first clinical visit and hospital admission increased by 1 day, the duration of survival was 0·78 times (95% CI 0·62-0·98) as long. Our results suggest that patients with severe influenza H7N9 infection at older ages were at a higher risk of fatality, and that a delay in hospital admission was associated with more rapid death. More studies are required to corroborate our major findings.
Foot-and-mouth disease virus (FMDV) can be spread by a variety of mechanisms, including wind. Simulation models, developed to predict the risk of airborne spread, have played an important part in decision making in some outbreaks. The amount of airborne virus excreted as well as the minimal infectious dose (MID) of FMDV for different species are important determinants of airborne spread. The objective of this study was to obtain data for the O1 Lausanne, O SKR 2000 and O UKG 2001 strains of FMDV to enhance the capability of such models. Pigs were exposed to naturally generated aerosols of the three strains using an experimental design which delivered high doses of the two strains O1 Lausanne and O SKR 2000 over a short period, or of the O UKG 2001 strain over an extended period. The average excretion of the O1 Lausanne strain was 10(6.4) TCID50 per pig per hour. The excretion of the O SKR 2000 strain averaged 10(5.8) and the O UKG 2001 strain 10(6.1) TCID per pig per 24 h. The results show that the previous estimate of 'above' 800 TCID50 as the MID50 for the O1 Lausanne strain is a considerable under-estimate and that the real dose may be as high as 6000 TCID50. A dose of around 650 TCID50 of the O SKR 2000 strain failed to infect any pigs. Thus, the aerosol MID50 for pigs for this isolate is at least 1000 TCID50 and likely to be as high or higher than the O1 Lausanne strain. The exposure of pairs of recipient pigs kept physically separated from donor pigs in a series of rooms to aerosol exposure doses of the O UKG 2001 strain of around 50 TCID50 per min for 24-48 h failed to infect any of eight pigs. Thus, the present experiment confirms our previous findings that pigs, compared to cattle and sheep, are relatively resistant to infection with airborne FMDV.
SUMMARY A retrospective case-control study of patients who had undergone cataract extraction at a Spanish hospital over a 13-year period was conducted to identify the risk factors for developing post-operative endophthalmitis (POE). During the study period, the type of antibiotic prophylaxis was changed from subconjunctival gentamicin to the addition of both vancomycin and gentamicin to the irrigating solution. The overall incidence of POE was 0·19% (35 cases/18 287 operations). For the period prior to the change in antibiotic prophylaxis, the incidence rate of POE was 3·4 cases/1000 operations while in the latter period the incidence rate decreased to 0·34 cases/1000 operations. All patients who presented a virulent microorganism had a final visual acuity worse than 20/200. The only significant risk factor identified was the type of prophylaxis used (odds ratio 1·97, 95% confidence interval 0·94-4·14, P = 0·07). There were no significant differences between cases and controls although choice of surgeon approached significance.
Relative hazards (and 95% confidence intervals) of progression to AIDS, death or a CD4 count of 0 05 x 109/l associated with CMV positivity unadjusted for other factors, and with CMV positivity after adjustment for patients' age at seroconversion and most recent CD4 count 
Relative hazards (and 95% confidence intervals) of death associated with CMV status. Baseline dates are defined as the date on which the CD4 count first fell below certain levels. Relative hazards for CMV status are adjusted for age at baseline 
The effect of prior infection with cytomegalovirus (CMV) on progression of HIV disease in a cohort of 111 men with haemophilia was studied after 13 years follow-up. The relative hazards associated with CMV positivity on progression to AIDS, death and a CD4 count of 0.05 x 10(9)/l were 2.28, 2.42 and 2.34, respectively. CMV seropositive patients were significantly older than the seronegative and this was controlled for by using a Cox proportional hazards model. The relative hazards for the three endpoints decreased to 1.89, 1.82 and 1.93 respectively and were marginally non-significant (P = 0.05, 0.08 and 0.08 for the three endpoints respectively). We conclude that this cohort continues to show evidence of a 'co-factor' effect associated with prior infection with CMV which is confounded by age but not completely explained by age differences. The potential biological significance of these results is discussed in the context of recent controlled clinical trials which show a survival benefit from long-term high-dose acyclovir, a drug with activity in vivo against CMV and other herpesviruses.
Clinical features in 128 patients with aseptic meningitis 
Laboratory findings in blood and CSF samples (n=128) 
Odds ratios of parameters in patients as compared to controls in case control study 
Until recently, echovirus 13 has been a very rare cause of aseptic meningitis. We investigated an outbreak of echovirus 13 in central Israel during the summer of 2000 using a prospective case control study and a retrospective study. Echovirus 13 was isolated from 79 cerebrospinal fluid (CSF) specimens from different medical centres in central Israel. Patients' ages ranged from 10 days to 41 years (95% < 15 years, M/F ratio 62/38). A total of 128 patients with clinical aseptic meningitis were admitted to the Department of Pediatrics during the outbreak (aged 10 days to 18 years, mean 5.4 years), and 58 CSF samples were processed for viral cultures. Thirty of them did not grow any virus, 26 samples yielded echovirus 13, and 2 samples echovirus 7. The clinical features of patients with echovirus 13 in the CSF were similar to those in whom no virus was isolated or those infected with other enteroviral strains except for higher rate of fever on admission, and prolonged time with fever following the diagnosis in the echovirus 13 patients. CSF cell count varied from 4 to 2,333 cells/mm3 with polymorphonuclears (PMN) predominant in 90% of our patients. In a case-control study there was no significant difference between patients and matched controls with regard to parameters such as: day care attendance, recreation in summer camp, swimming pools and at the beach, and consumption of tap water. All the patients in our series recovered fully with no neurological abnormalities. The illness caused by echovirus 13 was benign and involved mainly patients younger than 15 year of age. Several features that characterized this outbreak include relatively high WBC in the blood and a minent CSF PMN response.
Number of echovirus 13 and echovirus 30 isolates during the period 1988-2000 in Spain. 
Temporal distribution of echovirus 13 in the Autonomous Communities of Spain during the year 2000 
Number of echovirus 13 isolates (135) in different Autonomous Communities of Spain in the year 2000. 
Incidence of echovirus 13 during the years 2000 and 2001 in different countries 
Echoviruses are the commonest cause of aseptic meningitis (AM). Echovirus type 13 (EV-13) was the second enterovirus serotype associated with different local outbreaks of AM in Spain between February and October 2000. It was the first time that an epidemic AM caused by this virus was recognized in Spain. The index case appeared in the Canary Islands (Canarias). The EV-13 virus was isolated from 135 patients, predominantly from cerebrospinal fluid (CSF). All isolates were from children under 13 years. The age specific peak incidence was in infants under 1 year. Most patients had fever, headache and other meningeal signs. This enterovirus serotype, not previously detected in Spain, caused severe illness with a high attack rate.
Population attributable risk (PAR) of exposures associated with campylobacteriosis. Calculated from case control study on sporadic campylobacteriosis conducted in Denmark 1 May 1996 to 12 May 1997 
Risk factors for campylobacter infections identified in case-control studies, 1979-98 
A case control study comprising 282 cases and 319 matched controls was conducted in Denmark during 1996-7. Two estimates of the odds ratio (OR) were determined for each risk factor with and without 'protective factors' fitted into the final model. Consumption of undercooked poultry (OR 4.5; 8.2), consumption of red meat at a barbecue (OR 2.3; 4.1), consumption of grapes (OR 1.6; 2.8) and drinking unpasteurized milk (OR 2.3; 11.8) were identified as risk factors in both models. Frequent consumption of pork chops (OR 4.4) and daily contact with domestic animals and pets were identified as risk factors in one of the two models only. Finally, foreign travel was found to be a significant risk factor (OR 2.5). Seasonal and regional interaction was observed for several risk factors and the time elapsed from interviewing of cases to interviewing of controls seemed to influence the effect of certain seasonal dependent risk factors.
Sociodemographic characteristics and H. pylori prevalence of the index children
Family members' participation and H. pylori serostatus stratified by the serostatus of the index children
Family and index child characteristics as risk factors for H. pylori infection in the index children
H. pylori serostatus in different categories of family members as risk factors for the infection in the index children
This study aimed to disentangle the independent contributions of Helicobacter pylori infections in mothers, fathers and siblings to the risk for the infection in the 11-13 years age group. Index children from a cross-sectional Stockholm school survey and their family members completed questionnaires and contributed blood samples. H. pylori serostatus was determined with an enzyme-linked immunosorbent assay and immunoblot. Fifty-four seropositive and 108 seronegative index children were included and 480 out of 548 family members contributed blood. In multivariate logistic regression modelling, having an infected mother (OR 11.6, 95% CI 2.0-67.9) or at least one infected sibling (OR 8.1, 95% CI 1.8-37.3) were risk factors for index child infection, whilst the influence of infected fathers was non-significant. Birth in high-prevalence countries was an independent risk factor (OR 10.4, 95% CI 3.4-31.3). H. pylori infections in mothers and siblings and birth in high-prevalence countries stand out as strong markers of infection risk amongst children in Sweden.
Household characteristics 
Frequency of H. pylori infection among 241 children in extended-family homes 
Odds of H. pylori infection accounting for infection status and familial relationship of other children in the household 
Odds of H. pylori infection for only children living with at least one sibling and one non-sibling, accounting for infection status and familial relationship of other children in the household 
Helicobacter pylori is transmitted within households and high concordance is observed among siblings. To better understand the contributions of close interpersonal contact and family relatedness to transmission, we compared concordance of H. pylori infection among 241 sibling and non-sibling children aged 2-18 years in 68, predominantly low-income, Hispanic households with at least two nuclear families. Prevalence of H. pylori infection was 24%. Compared to children with no infected siblings or non-siblings and adjusting for age, odds of H. pylori infection were 1.2 (95% CI 0.52-2.9), 3.2 (95% CI 1.14-9.1), and 9.4 (95% CI 3.1-28.5) for children residing with at least one infected non-sibling, one infected sibling, and with at least one infected sibling and non-sibling, respectively. The study further implicates intersibling transmission as a pathway for H. pylori infection in childhood. In addition, living with a non-sibling in extended-family homes may contribute to infection risk but only in households with prevalent H. pylori infection within all family groups.
Fig. Hepatitis A cases for the period 1998–2002 in Barcelona. Hepatitis A is a notifiable disease. Weeks 1–52 (1998) ; weeks 53–104 (1999); weeks 105–156 (2000) ; weeks 157–208 (2001); weeks 209–260 (2002). Raw sewage sampling started at week 25 with a gap between weeks 133–152. Asterisks denote positive detection of HAV in raw sewage.  
Fig. Hepatitis A cases for the period 1998-2002 in Barcelona. Hepatitis A is a notifiable disease. Weeks 1-52 (1998) ; weeks 53-104 (1999); weeks 105-156 (2000) ; weeks 157-208 (2001); weeks 209-260 (2002). Raw sewage sampling started at week 25 with a gap between weeks 133-152. Asterisks denote positive detection of HAV in raw sewage.
Molecular methods for the detection and typing of hepatitis A virus (HAV) strains in sewage were applied to determine its distribution in Cairo and Barcelona. The study revealed the occurrence of different patterns of hepatitis A endemicity in each city. The circulating strains characterized, whether in Cairo or Barcelona, were genotype IB. The effects of a child vaccination programme and the increase in the immigrant population on the overall hepatitis A occurrence in Barcelona were evaluated. While vaccination contributed to a significant decrease in the number of clinical cases, the huge recent immigration flow has probably been responsible for the re-emergence of the disease in the last year of study, in the form of small outbreaks among the non-vaccinated population.
To investigate whether single nucleotide polymorphisms (SNPs) in Toll-like receptors (TLRs) 3 and 9 affect the susceptibility of hepatitis B virus (HBV) intrauterine transmission, we genotyped 399 neonates for TLR3 (c.1377C/T) [rs3775290] and TLR9 (G2848A) [rs352140] using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). A femoral venous blood sample was obtained from these subjects. Hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) were measured using chemiluminescence immunoassay kits and hepatitis B virus DNA (HBV DNA) levels were determined by fluorescence quantitative PCR assay. Our results showed that when adjusting for maternal HBeAg, maternal HBV DNA and mode of delivery, allele ‘T’ for SNP c.1377C/T was significantly associated with HBV intrauterine transmission susceptibility [adjusted OR (aOR) 0·55, 95% confidence interval (CI) 0·34–0·91, P = 0·020] and the TT genotype decreased the risk of HBV intrauterine transmission (aOR 0·28, 95% CI 0·09–0·91, P = 0·033). Allele ‘A’ for SNP G2848A was significantly associated with HBV intrauterine transmission susceptibility (aOR 0·62, 95% CI 0·39–1·00, P = 0·048) and the GA genotype protected neonates from HBV intrauterine transmission (aOR 0·45, 95% CI 0·22–0·93, P = 0·031). The TLR3 (c.1377C/T) and TLR9 (G2848A) polymorphisms may be relevant for HBV intrauterine transmission susceptibility, although the reduction in risk to HBV intrauterine transmission is modest and the biological mechanism of the observed association merits further investigation.
Plasmid profile analysis by agarose gel electrophoresis was performed on 42 drug resistant strains of Shigella boydii serotypes 1-5, 8, 10, 12-14, collected between 1974 and 1985 from endemic cases of shigellosis in Ethiopia, and their Escherichia coli K12 transconjugants. Resistance factors (R factors) were further characterized by incompatibility testing. Patterns of small plasmids, less than 15 kb, were similar within each of the individual S. boydii serotypes. Plasmids of about 3.3-3.7 kb were found in all strains of serotypes 2 and 4. Plasmids of about 4.3-4.6 kb were found in about 86% of strains. Serotypes 1, 2 and 3 were characterized by plasmids of about 5.6-5.7 kb. The 6.4-6.7 kb plasmid was found consistently in serotypes 1, 2, 3, 5, 8, 12 and 13 which were resistant to SSu or had an SSu resistance component in their phenotypes. Large plasmids (155-186 kb) were found in most S. boydii strains. Conjugative drug resistance plasmids, most often coding for three or less drugs, were found in about 26% of drug resistant strains. R-factors, coding for AT resistance (in types 2 and 8), and ASSuT resistance (in type 4), were compatible with all reference plasmids tested. Plasmids belonging to incompatibility groups X and N were found in serotypes 5 and 10, respectively.
Seasonal distribution of cases of rotavirus gastroenteritis detected in children under 15 in Donostialdea and Tolosaldea (Gipuzkoa, Basque Country, Spain) in 1984–97 (n l 3637). Cases occurring in cold months (December–May) are shown in white and cases occurring in warm months (June–November) are shown in black.  
Distribution and annual incidence by age of the patients with rotairus gastroenteritis detected in Donostialdea and Tolosaldea (Gipuzkoa, Basque Country, Spain) in 1984–90 and 1991–7 1984–90 1991–7 
Monthly distribution of children with gastroenteritis (oerall and rotairus) in the two time periods studied (1984–90 and 1991–7) 1984–90 1991–7 
Over a 14-year period (1984-97) the presence of rotavirus in stool samples from children under 15 years with acute gastroenteritis was studied by enzymoimmunoanalysis. Serotyping (G1-G4) was performed using monoclonal antibodies. A total of 17,348 children under 15 were investigated. Rotavirus was detected in 3637 (21.0%) specimens, 74.6% of which were from children younger than 2 years old. G1 and G4 were the most frequent serotypes. In 1991-7, the minimum incidence of rotavirus gastroenteritis in children under 4 years of age was 21.7 cases/1000 children/year. By the age of 5 years, at least 1 out of 11.3 children and probably 1 out of every 5-6 children in this area had experienced an episode of rotavirus gastroenteritis that required medical care. In the 1984-90 period a clear seasonality was not observed but in the second period of the study (1991-7), seasonality was marked, with peak activity in winter.
Passive immunity against measles decreases during the first months of life. The objective of this study was to determine titres of measles antibodies in children aged 9-14 months and their mothers before vaccination, and the children's response to vaccination. Blood samples were collected by capillary puncture before and 28 days after vaccination. Samples were obtained between February and June 2007 during an ongoing measles outbreak. Titres of specific measles IgG antibodies were determined by enzyme-linked immunosorbent assay. Seroconversion was defined as the presence of antibodies after vaccination in subjects without antibodies before vaccination. Maternal antibodies were present in 37·7% of all 69 children included and in 45·1% of children aged 9 months. Of the 51 children in whom a second sample was obtained, 31 (60·8%) were seronegative before vaccination and 61·3% seroconverted. Interference of maternal antibodies was 30%. Advancing the first dose of measles vaccination from 15 to 12 months is a correct strategy, given the increase in the time of susceptibility of infants to measles.
Seventy-five clinical isolates of Pseudomonas aeruginosa collected in a tertiary teaching hospital in Thailand were investigated for susceptibility to antimicrobials including imipenem. Metallo-β-lactamase (MBL) enzymes were detected by E-test MBL assay and PCR; class 1 integron genes were also detected by PCR. Strains positive for bla(IMP) and bla(VIM) genes were further characterized by DNA sequencing and examined for clonality by pulsed-field gel electrophoresis. High rates of resistance to anti-pseudomonal agents were found. MBL enzymes were found in 13 (17·3%) strains and 24 (32%) carried class 1 integron genes. Twelve of the latter strains harboured the bla(IMP-14) gene and one strain the bla(VIM-2) gene. All of the IMP-14 strains were identical or closely related suggesting clonal dissemination of these genes.
Distribution of S. Dublin temporal antibody profiles (TAP) in 14 Danish dairy herds. TAP1, Persistently high antibody levels ; TAP2, recently increased antibody levels ; TAP3, fluctuating or moderately high antibody levels ; TAP4, recent low antibody levels. 
Temporal antibody profile (TAP) criteria and distributions of animals, observations, faecal culture-positive observations and age in 14 dairy herds that were endemically infected with S. Dublin in Denmark between 2000 and 2002 
SUMMARY This longitudinal field study investigated the hypothesis that persistently high antibody levels indicate a high risk of Salmonella Dublin shedding in animals in 14 endemically infected dairy herds. A hierarchical multivariable logistic regression was used to analyse 6614 paired faecal cultures and four types of temporal antibody profiles from cattle aged ≥180 days. Age and repeated measurements on animals nested within herds were taken into account. Overall, the prevalence of faecal shedders was low (0·3% and 2·8% in the lowest and highest risk groups, respectively). An important predictor of faecal shedding was young age. There was a significant, but modest increase in risk in cattle with persistently high or recently increased antibody levels, but no difference between these two groups. Contrary to previous recommendations, the detection of carriers by the use of repeated antibody testing is not likely to be a plausible control option in most Salmonella Dublin-infected dairy herds.
Examination of a selection of serum samples from adults from two regions of England showed that 50% of men in the 16-24 years and over 55 years age groups had high titres of antibody to diphtheria toxin (DT). In contrast, only 11% of women aged 16 to over 55 years had high titres of antibody to DT. All human antisera with high anti-DT titres reacted with a synthetic peptide (SP) corresponding to the amino acids 141-157 of DT fragment A, with sera from men aged 35 to over 55 years showing the highest titres. High antibody titres to fragment A paralleled those to SP in both sexes. Titres of antibody to DT fragment B were highest in individuals with high titres to DT. In sera from both sexes immunoglobulin G1 was the predominant subclass reactive with all three antigens. However, both IgG1 and IgG4 and to a lesser extent IgG2 and IgG3 were present in immunoglobulin concentrates.
Food poisoning due to Salmonella typhimurium phage type 141 was unusual in the Sheffield area before 1984. The sudden increase in incidence of this phage type during 1984 and 1985, and its causative role in several small outbreaks in this period have been investigated. Epidemiological and laboratory investigations suggested that hens' eggs were the most likely source of S. typhimurium phage type 141.
Among the 81 cultures of Salmonella typhimurium of phage type 141 examined, 72 had been isolated from Sheffield incidents in 1984-5 and 9 were Scottish isolates from 1986-7. All of these cultures from diverse sources belonged to primary biotype 31; 79 were of full biotype 31beg and 2 anaerogenic cultures were of full biotype 31begj. This is the first known occasion on which an epidemic strain of S. typhimurium of phage type/biotype 141/31beg has been implicated in outbreaks of human or animal infection in the UK. Because previous epidemic strains of S. typhimurium of phage type 141 in the UK belonged to biotypes 1f and 9f which are phylogenetically unrelated to biotype 31beg, the likely origin of this most recent epidemic S. typhimurium strain of phage type/biotype 141/31beg is discussed.
A total of 150 patients were treated for tetanus in the tetanus ward of the J. J. Hospital, Bombay, between October 1983 and January 1986. The complications of tetanus and the mode of management in the presence of restricted resources are outlined. Intensive care, proper nutrition, early tracheostomy and ventilator support in severe tetanus were chiefly responsible for an overall reduction in mortality from 30 to 12%. The mortality in severe tetanus was reduced from 70 to 23%. Sudden death due to unexpected cardiac arrest was an important complication in severe tetanus. We observed that an abrupt marked rise in rectal temperature ( > 107 °F, 41·7 °C), if undetected, could lead to sudden circulatory collapse and death. Well-marked hypoxaemia was observed in all patients with severe tetanus, and was related to ventilation perfusion inequalities and to an increase in the true venous admixture (increased Q s /Q t )in the lungs. Bronchopulmonary infections and the adult respiratory distress syndrome added significantly to morbidity and mortality. Autonomic cardiovascular disturbances included bradycardia alternating with tachycardia, and hypertension which was either labile, paroxysmal or sustained. Persistent hypotension was of ominous significance. Amongst numerous complications involving other systems, sepsis and septic shock were associated with a high mortality.
Verotoxin neutralisation titres (NT50) and E. coli 0 157 LPS antibodies in patients with acute HUS and controls No. positive/no. examined (percent) 
To assess the importance of infection by Verotoxin (VT) producing Escherichia coli (VTEC) in children with HUS in Central Europe, stool and/or serum samples obtained from 147 patients from 28 paediatric centres were prospectively examined for the presence of VTEC and the kinetics of faecal VT titres (FVT), and for VT neutralization titres and antibodies against E. coli O 157 lipopolysaccharide, respectively. Ninety-two percent of the patients had classic (enteropathic) HUS (E+ HUS). Evidence of VTEC infection was obtained in 86% of them. VTEC/FVT were identified in 55/118 E+ cases (47%). A prominent feature was the frequent isolation of sorbitol-fermenting, VT2-producing E. coli O 157.H-.VT1 (C600/H19) was neutralized by 9%, and VT2 (C600/933W) by 99% of the initial serum samples from E+ patients, compared to 3% (VT1) and 100% (VT2) from age-related controls. Fourfold titre rises against VT1 and/or VT2 were observed in 13/70 (19%), and significantly elevated O 157 LPS IgM and/or IgA antibodies in 106/128 (83%) of the E+ patients. The ubiquitous VT2 neutralizing principle in the serum of HUS patients as of healthy controls warrants further investigations.
Food-specific attack rates for foods consumed at christening party 
A point source outbreak of haemorrhagic colitis due to Escherichia coli O 157.H7 producing verocytotoxin (VT), took place following a christening party in Birmingham in June 1987. Twenty-six people were affected, six were admitted to hospital and one developed haemolytic uraemic syndrome: there were no deaths. VT + E. coli O 157.H7 was isolated from 13 (57%) of 23 faecal specimens from affected people and from 3 (9%) of 33 specimens from asymptomatic people. Free VT was detected in the faeces of one further asymptomatic person. Illness was associated with eating turkey-roll sandwiches (P less than 0.001) suggesting that cold meats might be an important source of infection.
Using DNA probes specific for the genes encoding Vero cytotoxins 1 and 2 in hybridization experiments on faecal samples, Vero cytotoxin-producing Escherichia coli (VTEC) of serogroup O 157 were detected in 21 of 63 cases of haemorrhagic colitis, 9 of 31 cases of non-bloody diarrhoea and 14 of 68 cases of haemolytic uraemic syndrome. Compared with these results sorbitol-MacConkey agar in conjunction with a specific O 157 antiserum gave a sensitivity of 62% in haemorrhagic colitis, 56% in non-bloody diarrhoea and 57% in haemolytic uraemic syndrome. The specificity of this method was 100% in all three groups. This demonstrates that sorbitol-MacConkey agar is a useful screening method for the detection of VTEC of serogroup O 157 when used in conjunction with a specific homologous antiserum. However, this method does not detect VTEC belonging to other serogroups and such strains were found, particularly in cases of haemolytic uraemic syndrome.
Percentage of cases and controls eating food Odds ratio (lower 
Percentage of cases and controls preparing food 
The first recognized outbreak of haemorrhagic colitis due to Escherichia coli O 157.H7 in the United Kingdom affected at least 24 persons living in East Anglia over a 2-week period. The illnesses were characterized by severe abdominal pain and bloody diarrhoea of short duration. Eleven patients were admitted to hospital and there was one death. Patients were mainly adult women who had not eaten out of the home in the 2 weeks before onset. Unlike previously reported outbreaks hamburgers were not the vehicle of infection, and a case-control study suggested that handling vegetables, and particularly potatoes, was the important risk factor.
Sixteen cases of verotoxin producing Escherichia coli (VTEC) O 157:H7 Phage Type 49 infection were identified in the North West of England from 1 September to 1 November 1991, eight of whom lived in or around the same large town. Eleven of the cases were aged 10 years or less, and five of the affected children developed haemolytic uraemic syndrome. A case control study demonstrated a strong association between VTEC O 157:H7 PT 49 infection and the consumption of a locally produced live yoghurt. This is the first time that an outbreak of VTEC O 157 infection has been linked to the consumption of yoghurt and this vehicle of infection should be considered when investigating such outbreaks in future.
We conducted a 4-year retrospective cohort study to better define the risk of haemolytic anaemia and haemolytic uraemic syndrome (HUS) in children following sporadic gastrointestinal infection with the O 157.H7 serotype of Escherichia coli. Of the 72 children infected with this organism, 9 (12.5%) developed haemolytic anaemia, 6 of whom had HUS. No child in a cohort of 72 age-matched controls with Campylobacter jejuni gastroenteritis developed haemolytic anaemia (P = 0.003). Females had a significantly greater risk of developing haemolytic anaemia after E. coli O 157. H7 infection than did males (8/29 females v. 1/43 males; P = 0.003). In a logistic regression model, female gender emerged as the only statistically significant risk factor for haemolytic anaemia (odds ratio 3.85; 95% confidence interval 1.24-12). These results are consistent with recent reports of a moderate increase in the risk of HUS for females.
Between 1989 and 1991 a total of 1092 Vero cytotoxin-producing Escherichia coli O 157 isolated in the United Kingdom were phage typed in the Laboratory of Enteric Pathogens (LEP). Twenty-three phage types was identified, the most frequent being types 2 (36.1%), 49 (29.6%), 1 (10.3%) and 4 (8.9%). Although isolations of O 157 VTEC have increased each year from 1 in 1982 to 532 in 1991, the predominant phage types have remained unchanged although the proportion of strains belonging to types 2 and 49 has increased. O 157 VTEC from 17 outbreaks were phage typed during this period with phage type 49 predominating (7 of 17 outbreaks).
This survey reports the results of investigations performed by the Laboratory of Enteric Pathogens (LEP), to identify evidence of human infection with Vero cytotoxin-producing Escherichia coli (VTEC) in the UK during the period 1989-91. Bacterial isolates, faecal specimens and serum samples were received from patients suffering from diarrhoea, bloody diarrhoea and haemolytic uraemic syndrome. Using serotyping, Vero cytotoxin gene probing and an ELISA for serum antibodies to E. coli O 157, evidence of infection was detected in 232, 428 and 615 individuals in 1989, 1990 and 1991 respectively. Of these individuals, 15% were reported as having HUS. Vero cytotoxin-producing E. coli O 157 was the most frequently encountered serogroup, with isolations from a total of 1092 individuals over the 3-year period. The incidence of VTEC infection increased from 0.41/100,000 in 1989 to 1.07/100,000 in 1991. The area with the highest rate of infection in each year was Scotland, increasing from 1.37/100,000 in 1989 to 3.97/100,000 in 1991.
Some European countries decided to include human papillomavirus (HPV) vaccines in national immunization schedules. In order to help decision makers choose the best vaccination policy for females, a decisional model has been developed. The study was performed from the National Health Service perspective. Several hypotheses of multi-cohort vaccination policies were compared. 'Potentially avoidable infections' were chosen as the outcome. The model envisioned a short-term scenario (2008-2011). The best policy was that of vaccinating 12-year-olds and, a year later, those aged 14-16 years; the most expensive strategy was that of vaccinating 12-year-old females and, after 1 year, vaccinating those aged 15, 18 and 25 years. The sensitivity analysis showed that coverage rate has a great effect on the cost of avoidable infections. The study offers stake-holders an important datum-point for the choice of the best HPV policy vaccination in the short term. Indeed, it could generate interesting savings for the National Health Service and a rapid HPV immunization of young girls.
A seroepidemiological survey was conducted on subjects who had received a full vaccination course with live attenuated poliovirus 2-16 years before. For strains 1 and 2 prevalence of seropositives and median values dropped gradually during the first 10 years; strain 3 showed a much earlier decline. Environmental displacement of wild poliovirus by the attenuated, less immunogenic strain might eventually induce a 'gap', should complacency hamper needed vaccination efforts.
Flowchart of the study population and sample size for the analysis of risk factor for typhoid fever in children in Karachi, Pakistan.  
Distribution and estimate of risk for cluster-level factors associated with typhoid fever in children of urban squatter settlements in Karachi, Pakistan
We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household- and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0·89, 95% confidence interval (CI) 0·83-0·95], was higher with an increase in population density (RR 1·13, 95% CI 1·05-1·21) and was lower in the households using a safe drinking-water source (RR 0·63, 95% CI 0·41-0·99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.
Mortality amongst 924 eligible cases (&) and 475 eligible controls (%).  
Survival (Cox's proportional hazards model) multivariable analysis
Kaplan–Meier survival curve for HCV cases and controls.  
Survival (Cox's proportional hazards model) multivariable sub-analyses
The aim of this study was to describe the natural history of HCV after 16 years of infection, in a cohort of individuals who acquired their infections on a known date in the United Kingdom. A total of 924 HCV-infected transfusion recipients (cases) and 475 anti-HCV negative transfusion recipients (controls) were eligible for inclusion in the study. Survival was compared between cases and controls to see if there was any excess mortality attributable to HCV. The results show that all-cause mortality was not significantly different between cases and controls (hazard ratio 1.17, 95% CI 0.92-1.49, P=0.21). However, the risk of death directly from liver disease was higher in cases than controls (hazard ratio 2.71, 95% CI 1.09-6.75, P=0.03). Nearly 30% of those HCV-infected cases who died directly from liver disease were known to have consumed excess alcohol.
It is generally accepted that Professor Ignaz Semmelweis was the first to identify the mode of transmission of puerperal sepsis. However no appropriate statistical analysis of Semmelweis's data supporting his theory has been reported. Mean annual percent maternal mortality rates for the Allgemeines Krankenhaus and Dublin Maternity Hospitals (1784-1858) were analysed. The introduction of pathological anatomy at the Allgemeines Krankenhaus in 1823 was associated with increased mortality. After 1840 maternal mortality was higher in Clinic 1 which was staffed by male obstetricians and medical students who, unlike the midwives in Clinic 2, attended autopsies. The introduction of chlorine washing of the male clinicians' hands in Clinic 1 by Semmelweis in 1847 reduced mortality, whereas the cessation of handwashing after Semmelweis left Vienna in 1850 was associated with increased mortality. This statistical analysis supports Semmelweis's hypothesis that 'the cadaveric particles adhering to the hand had ... caused the preponderant mortality in the first Clinic'.
Top-cited authors
Wilfrid Van Pelt
  • National Institute for Public Health and the Environment (RIVM)
Richard Pebody
  • Public Health England
Arie H Havelaar
  • University of Florida
Yvonne Van Duijnhoven
  • GGD Rotterdam-Rijnmond
Hester E de Melker
  • National Institute for Public Health and the Environment (RIVM)