A compartmental, age-structured mathematical model was developed and recent US pertussis epidemiology data were used to evaluate the impact on pertussis infection rates of routine and targeted adult immunization strategies. Model simulations predict that the implementation of adolescent immunization only could reverse the current rise in pertussis infection rates but may lead to a resurgence of pertussis in subsequent decades. In contrast, inclusion of a routine adult strategy is likely to lead to sustained control of pertussis. Routine adult vaccination could control the disease even with relatively low coverage rates of 40% for routine vaccination of all adults every 10 years, or 65% for a targeted vaccination of close contacts of newborns completed by one booster dose for all adults. The model also predicts that the optimal age for this booster dose is 40 years. These results support the 2006 American Academy of Immunization Practices' recommendations for adolescent and adult vaccination against pertussis.

The aim of this study was to identify the high-risk factors associated with the development of ocular lesions in a large cohort of children with congenital toxoplasmosis (CT), irrespective of their gestational age at the time of maternal infection. Children were managed according to a standardized protocol and monitored for up to 14 years at the Croix-Rousse Hospital, Lyon, France. Cox model and a flexible regression, spline-based method were used for the analysis. During a median follow-up time of 6 years, 79 of the 327 children (24%) had at least one retinochoroidal lesion. No bilateral impairment of visual acuity was observed. The risk of a child developing ocular disease was higher not only when mothers were infected early during pregnancy, which was expected, but also when CT was diagnosed prior to or at the time of birth, when non-ocular manifestations were present at baseline and when birth was premature.

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.

Three different methods were used for estimating the basic reproductive number (R0) from data on 110 outbreaks of highly pathogenic avian influenza (HPAI) subtype H5N1 that occurred in village poultry in Romania, 12 May to 6 June 2006. We assumed a village-level infectious period of 7 days. The methods applied were GIS-based identification of nearest infectious neighbour (based on either Euclidean or road distance), the method of epidemic doubling time, and a susceptible–infectious (SI) modelling approach. In general, the estimated basic reproductive numbers were consistent: 2·14, 1·95, 2·68 and 2·21, respectively. Although the true basic reproductive number in this epidemic is unknown, results suggest that the use of a range of methods might be useful for characterizing epidemics of infectious diseases. Once the basic reproductive number has been estimated, better control strategies and targeted surveillance programmes can be designed.

The objective of this study was to investigate risk factors for norovirus-associated infectious intestinal disease (IID) and asymptomatic norovirus infection. Individuals with IID and healthy controls were recruited in a community-based study in England (1993–1996). This is the first risk-factor study to use viral load measurements, generated by real-time RT–PCR, to identify cases of norovirus-associated IID and asymptomatic infections. Using multivariable logistic regression the main risk factor identified for norovirus-associated IID was contact with a person with IID symptoms. Infectious contacts accounted for 54% of norovirus cases in young children and 39% of norovirus cases in older children and adults. For young children, contacts outside the household presented the highest risk; for older children and adults, the highest risk was associated with child contacts inside the household. Foreign travel and consumption of shellfish increased the risk of norovirus-associated IID. Lifestyle and dietary factors were associated with a decreased risk of both norovirus-associated IID and asymptomatic infection. No risk factors were identified for asymptomatic norovirus infection.

This paper originated in a project to develop a practical, generic tool for the economic evaluation of surveillance for farm animal diseases at national level by a state veterinary service. Fundamental to that process is integration of epidemiological and economic perspectives. Using a generalized example of epidemic disease, we show that an epidemic curve maps into its economic equivalent, a disease mitigation function, that traces the relationship between value losses avoided and mitigation resources expended. Crucially, elementary economic principles show that mitigation, defined as loss reduction achieved by surveillance and intervention, must be explicitly conceptualized as a three-variable process, and the relative contributions of surveillance and intervention resources investigated with regard to the substitution possibilities between them. Modelling the resultant mitigation surfaces for different diseases should become a standard approach to animal health policy analysis for economic efficiency, a contribution to the evolving agenda for animal health economics research.

The anti-haemagglutinin antibody response in adult human volunteers to inactivated whole virus or tween ether split influenza A/Victoria/75 (H3N2) and A/Scotland/74 (H3N2) virus vaccines was investigated using antibody adsorption and single-radial-haemolysis (SRH) techniques. The concentrations of haemagglutinin (HA), nucleoprotein (NP) and matrix (M) antigens measured by single radial diffusion (SRD) and rocket immunoelectrophoresis were similar for both the whole virus and split vaccines. Whole virus and split vaccines induced cross-reactive (CR) antibody in 87% of vaccinees. Strain specific (SS) antibody to A/Hong Kong/1/68 or the homologous virus was induced less frequently than CR antibody. Higher anti-haemagglutinin antibody titres were detected in persons receiving the split virus vaccines than in those receiving the whole virus vaccines. No antibody to the type-specific matrix protein was detectable, but 33% of volunteers developed an antibody rise to type-specific nucleoprotein antigen.

The specificity of the anti-haemagglutinin antibody response in human adults to natural infection with A/Port Chalmers/73 (H3N2) virus was similar to that induced by inactivated vaccines in that a high proportion of subjects developed CR anti-haemagglutinin antibody, which reacted with A/Hong Kong/68 virus and the homologous A/Port Chalmers/73 virus, and SS antibody for A/Hong Kong/68 virus but SS antibody for A/Port Chalmers/73 virus was infrequently stimulated by natural infection.

In order to determine whether hand carriage of aerobic Gram-negative rods is continuous we used the glove-handwash technique to sample the hands of two groups (four each) of health care workers with normal hands (surgical intensive care unit, medical ward) and one group (four) with hand dermatitis (HD) and a group (five) of control subjects – secretaries with no exposure to patients. Each subject was sampled repeatedly over three to six weeks. The mean number of samples for each group was 25.2, 23.2, 19.8 and 25.8 respectively. The HD group had more samples positive for aerobic Gram-negative rods than did the other two groups of health care workers while the control group had more samples positive than any of the three health care groups.

Using various typing schemes and the following definition of continuous carriage (the isolation of an organism of the same serotype, pyocin type or biotype from more than two handwash samples) we found that 4 of 11 subjects from whom Klebsiella pseumoniae was isolated carried this organism continuously; 2 of 3 carried Pseudomonas aeruginosa continuously and 4 of 5 of the control subjects carried the same biotype of Enterobacter agglomerans continuously.

We conclude that continuous hand carriage of aerobic Gram-negative rods is common and, among health care workers, those with hand dermatitis carry Gram-negative rods more frequently and in greater numbers than health care workers without hand dermatitis.

In June 2011, a cluster of suspected cases of Guillain–Barré syndrome (GBS), which can follow Campylobacter jejuni infection, was identified in San Luis Río Colorado (SLRC), Sonora, Mexico and Yuma County, Arizona, USA. An outbreak investigation identified 26 patients (18 from Sonora, eight from Arizona) with onset of GBS 4 May–21 July 2011, exceeding the expected number of cases (n = 1–2). Twenty-one (81%) patients reported antecedent diarrhoea, and 61% of 18 patients tested were seropositive for C. jejuni IgM antibodies. In a case-control study matched on age group, sex, ethnicity, and neighbourhood of residence, all Arizona GBS patients travelled to SLRC during the exposure period vs. 45% of matched controls (matched odds ratio 8·1, 95% confidence interval 1·5–∞). Exposure information and an environmental assessment suggested that GBS cases resulted from a large outbreak of C. jejuni infection from inadequately disinfected tap water in SLRC. Binational collaboration was essential in investigating this cross-border GBS outbreak, the first in mainland North America since 1976.

Measles vaccination is estimated to have averted 13·8 million deaths between 2000 and 2012. Persisting heterogeneity in coverage is a major contributor to continued measles mortality, and a barrier to measles elimination and introduction of rubella-containing vaccine. Our objective is to identify determinants of inequities in coverage, and how vaccine delivery must change to achieve elimination goals, which is a focus of the WHO Decade of Vaccines. We combined estimates of travel time to the nearest urban centre (⩾50 000 people) with vaccination data from Demographic Health Surveys to assess how remoteness affects coverage in 26 African countries. Building on a statistical mapping of coverage against age and geographical isolation, we quantified how modifying the rate and age range of vaccine delivery affects national coverage. Our scenario analysis considers increasing the rate of delivery of routine vaccination, increasing the target age range of routine vaccination, and enhanced delivery to remote areas. Geographical isolation plays a key role in defining vaccine inequity, with greater inequity in countries with lower measles vaccine coverage. Eliminating geographical inequities alone will not achieve thresholds for herd immunity, indicating that changes in delivery rate or age range of routine vaccination will be required. Measles vaccine coverage remains far below targets for herd immunity in many countries on the African continent and is likely to be inadequate for achieving rubella elimination. The impact of strategies such as increasing the upper age range eligible for routine vaccination should be considered.

The efficiency of the direct detection of Mycoplasma pneumoniae in respiratory exudates by an antigen capture, indirect enzyme immunoassay (Ag-EIA), has been compared with its detection with a cDNA probe (‘Gen-Probe assay’) directed against the specific ribosomal RNA sequences of the organism (‘Mycoplasma pneumoniae Rapid Diagnostic System’, Gen-Probe, San Diego, California).

Both assays showed excellent specificity against a range of mycoplasma species suspended in negative nasopharyngeal aspirates; only M. pneumoniae and M. genitalium reacted. In experiments with graded doses of viable M. pneumoniae cells suspended in negative nasopharyngeal aspirate, the Gen-Probe assay was more sensitive than Ag-EIA; detection limits were respectively 2 × 103 c.f.u./ml (3·2 × 105 genomes) and 2·5 × 104 c.f.u./ml (4 × 106 genomes); detection levels 10–100 times less sensitive than culture.

The two assays were also tested on nasopharyngeal aspirates or sputum specimens from 90 patients with respiratory infection; 67 of these were culture-or seronegative for M. pneumoniae and 23 were culture-or seropositive. Ag-EIA detected 21 (91%) of the latter but the Gen-Probe assay detected only 5 (22%). Both assays were negative with the 67 culture-/sero-negatives; there were no Gen-Probe assay positive/Ag-EIA negatives.

Overall, it is concluded that although Ag-EIA and the Gen-Probe assay are effective substitutes for culture as a diagnostic procedure, there is a significant problem with samples which are culture-negative and from patients who have good serological evidence of current infection. Possible reasons for the disparity between the two assays are advanced.

In animals exposed to foot-and-mouth disease virus by indirect contact, virus was recovered from the blood, milk, pharynx, vagina and rectum for variable periods of time before clinical disease was apparent. Virus instilled into the mammary gland multiplied rapidly and virus concentrations greater than 107 p.f.u./ml. were recorded within 8–32 hr., depending on the virus strain and dose inoculated. Virus multiplication was accompanied by clinical signs of mastitis but the classical signs of foot-and-mouth disease did not appear for 52–117 hr. Dissemination of virus from the mammary gland occurred within 4–24 hr. and in some animals samples taken from the pharynx, mouth, nose and vagina contained virus for periods up to 97 hr. before the appearance of vesicular lesions. Virus production in the udder declined with the appearance of virus neutralizing activity in the blood and the milk but persisted in some animals for periods of 3–7 weeks. The ability of foot-and-mouth disease virus to persist in mammary tissue was confirmed by the demonstration of virus multiplication in the udders of immune animals.

It has been suggested that the incidence of herpes zoster may increase due to lack of natural boosting under large-scale vaccination with the varicella vaccine. To study the possibility and magnitude of such negative consequences of mass vaccination, we built a mathematical model of varicella and zoster epidemiology in the Finnish population. The model was based on serological data on varicella infection, case-notification data on zoster, and new knowledge about close contacts relevant to transmission of infection. According to the analysis, a childhood programme against varicella will increase the incidence of zoster by one to more than two thirds in the next 50 years. This will be due to increase in case numbers in the ⩾35 years age groups. However, high vaccine coverage and a two-dose programme will be very effective in stopping varicella transmission in the population.

During Easter 2009, almost 200 people resident in a small Swedish village fell ill with gastrointestinal symptoms. We conducted a retrospective cohort study and a molecular investigation in order to identify the source of the outbreak. Residents living in households connected to the public water network were at an increased risk of developing disease (relative risk 4·80, 95% confidence interval 1·68–13·73) compared to those with no connection to the public network. Norovirus genotype GI.3 was identified in stool samples from six patients and in a sample from the public water network. Contamination of one of the wells supplying the public water network was thought to be the source of the outbreak. This is a description of a norovirus outbreak linked to a municipal drinking-water supply in Sweden. Information from epidemiological and molecular investigations is of utmost importance to guide outbreak control measures and to prevent future outbreaks.

The study objective was to evaluate three methods of Salmonella enterica prevalence estimation in swine herds (faecal culture, culture of abattoir-collected samples, and serum ELISA). From each of six swine herds, we necropsied approximately 100 finishing pigs (>70 kg); one-half on farm and the other half at the abattoir, after transport and approximately 2·5 h holding. We collected the same samples for S. enterica culture at both locations (1 g faecal, 10 g caecal contents, ileocaecal lymph nodes, superficial inguinal lymph nodes, 25 g of gluteal muscle for serum ELISA). On farm, the 1 g faecal sample only detected 13·3% (2/15) of all positive pigs necropsied on farm. However, with abattoir and on-farm results combined, the faecal sample detected 57·4% (74/129) of positive pigs. Abattoir-collected samples provided prevalence estimates much higher than on-farm collected samples (39·9 vs. 5·3%; P<0·001). This study shows that faecal samples have a low sensitivity for detecting infected pigs and that abattoir-collected samples overestimate the on-farm S. enterica prevalence. For most herds, serology overestimated the on-farm culture prevalence.

The subtypes of Campylobacter isolates from human infections in two Danish counties were compared to isolates from retail food samples and faecal samples from chickens, pigs and cattle. During a 1-year period, 1285 Campylobacter isolates from these sources were typed by two methods: ‘Penner’ heat-stable serotyping and automated ribotyping (RiboPrinting). C. jejuni was the dominating species, but C. coli was more prevalent among food and chicken isolates (16%) compared to human isolates (4%). In total, 356 different combined sero-ribotypes (subtypes) were found. A large subtype overlap was seen between human isolates and isolates from food (66%), chickens (59%) and cattle (83%). This was verified by PFGE typing of 212 isolates representing selected subtypes. All frequent (n>3) subtypes found in food were also present in humans. Sixty-one per cent of the isolates from domestically acquired infections had subtypes that were also found in food as opposed to 31% of travel-associated infections. The results showed differences in the various Campylobacter populations, e.g. the Danish population as reflected in the domestically acquired infections and the Danish-produced food was more uniform than the isolates originating from outside the country. The study shows that most C. jejuni subtypes found in poultry food samples, broiler chickens, and cattle were represented in the domestically acquired cases, indicating that C. jejuni from these reservoirs are likely sources of human infections in Denmark.

The effects of ingested Salmonella enteritidis (SE) dose on incubation period and on the severity and duration of illness were estimated in a cohort of 169 persons who developed gastroenteritis after eating hollandaise sauce made from grade–A shell eggs. The cohort was divided into three groups based on self–reported dose of sauce ingested. As dose increased, median incubation period decreased (37 h in the low exposure group 21 h in the medium exposure group v. 17·5 h. in the high exposure group, P = 0.006) and greater proportions reported body aches (71 v. 85 v. 94%, P = 0.0009) and vomiting (21 v. 56 v. 57%, P = 0.002). Among 118 case-persons who completed a follow–up questionnaire, increased dose was associated with increases in median weight loss in kilograms (3.2 v. 4.5 v. 5.0, P = 0.0001), maximum daily number of stools (12.5 v. 15.0 v. 20.0, P = 0.02), subjective rating of illness severity (P = 0.0007), and the number of days of confinement to bed (3.0 v. 6.5, P = 0.04). In this outbreak, ingested dose was an important determinant of the incubation period, symptoms and severity of acute salmonellosis.

We investigated the prevalence of β-lactamase genes and plasmid-mediated quinolone resistance (PMQR) determinants in 51 carbapenem-resistant Enterobacteriaceae (CRE) from five teaching hospitals in central China. The prevalence of carbapenem resistance in Enterobacteriaceae was 1·0% (51/5012). Of 51 CRE, 31 (60·8%) isolates were positive for one tested carbapenemase gene, while 10 (19·6%) were simultaneously positive for two tested carbapenemase genes. The positive rates of bla KPC-2, bla NDM-1, bla IMP-4, bla IMP-26 and bla IMP-8 were 54·9%, 17·6%, 11·8%, 11·8% and 3·9%, respectively. Of 10 CRE with two carbapenemase genes, three, five, one and one were positive for bla KPC-2 and bla IMP-4, bla KPC-2 and bla IMP-26, bla KPC-2 and bla IMP-8, and bla KPC-2 and bla NDM-1, respectively. Eight of nine bla NDM-1-positive isolates lacked carbapenemases by the modified Hodge test, while 27/28 isolates harbouring bla KPC-2 were positive for carbapenemases determined by this test; 41·2% of the CRE-positive isolates also harboured ESBL genes in various combinations (three and two positive for bla KPC-2 also carried bla DHA-1 and bla CMY-2). The positive rates of qnrS1, qnrA1, qnrB and aac-(6/)-Ib-cr in CRE were 25·5%, 9·8%, 23·5% and 15·7%, respectively. In particular, 7/9 isolates harbouring bla NDM-1 were positive for these quinolone resistance genes, of which five carried qnrS1 and two carried qnrS1 and qnrB4. All but two of 29 Klebsiella pneumoniae isolates were grouped into 20 clonal clusters by PFGE, with the predominant cluster accounting for four bla KPC-2-positive isolates distributed in the same hospital. We conclude that there is a high prevalence of bla NDM-1 and PMQR determinants in CRE isolates in central China. Multiple resistance determinants in various combinations co-exist in these strains and we report for the first time the co-existence of bla KPC-2 and bla IMP-26 in a strain of Klebsiella oxytoca.

Although most foodborne infections are undiagnosed, the incidence of these infections is usually calculated from reported cases. We present a novel population-based method to estimate the incidence of non-typhoid Salmonella infections. From 154 patients with confirmed Salmonella serotype Enteritidis infection, we determined the kinetics of the antibody response. The estimated mean responses for the three classes of serum antibodies were combined such that the time from infection could be estimated from antibody measurements. Next, serum samples collected in 1983, 1986, 1992, and 1999 from the general population were analysed for antibodies. We demonstrated how these measurements can be translated into an estimate of the general incidence. Based on serology markers there were 13 exposures leading to seroresponse of Salmonella Enteritidis/1000 person-years in 1983; the similar number in 1999 was 217. This trend confirms the increase in the number of culture-confirmed cases reported to the national surveillance system.

One hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 μg of HA or saline alone in a 0·5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response.

The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 μg HA and least for those given 5 μg HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 μg HA, 22 (96%) showed a fourfold rise in antibody titre and all volunteers had antibody titres of > 40 following immunization: for volunteers given 5 μg HA the g.m.t. increased from 16·6 to 86·1; and for those given 10 and 20 μg HA the response was intermediate. Following challenge, the lowest incidence of infection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50% protection titre of serum HI antibody was estimated as 15 to 20.