In 2014, the Food and Drug Administration approved a new human papillomavirus 9-valent vaccine (9vHPV), targeting nine HPV types: HPV types 6, 11, 16, and 18, which are also targeted by the quadrivalent HPV vaccine (qHPV), plus five additional high cancer risk HPV types (HPV types 31, 33, 45, 52, and 58). The aim of the current study was to systematically retrieve, qualitatively and quantitatively pool, as well as critically appraise all available evidence on 9vHPV from randomized controlled trials (RCTs). We conducted a systematic review of the literature on 9vHPV efficacy, immunogenicity and safety, as well as a systematic search of registered, completed, and ongoing RCTs. We retrieved and screened 227 records for eligibility. A total of 10 publications reported on RCTs’ results on 9vHPV and were included in the review. Sixteen RCTs on 9vHPV have been registered on RCT registries. There is evidence that 9vHPV generated a response to HPV types 6, 11, 16 and 18 that was non-inferior to qHPV. Vaccine efficacy against five additional HPV type-related diseases was directly assessed on females aged 16–26 years (risk reduction against high-grade cervical, vulvar or vaginal disease = 96·7%, 95% CI 80·9%–99·8%). Bridging efficacy was demonstrated for males and females aged 9–15 years and males aged 16–26 years (the lower bound of the 95% CIs of both the geometric mean titer ratio and difference in seroconversion rates meeting the criteria for non-inferiority for all HPV types). Overall, 9vHPV has been proved to be safe and well tolerated. Other RCTs addressed: 9vHPV co-administration with other vaccines, 9vHPV administration in subjects that previously received qHPV and 9vHPV efficacy in regimens containing fewer than three doses. The inclusion of additional HPV types in 9vHPV offers great potential to expand protection against HPV infection. However, the impact of 9vHPV on reducing the global burden of HPV-related disease will greatly depend on vaccine uptake, coverage, availability, and affordability.

Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20 % of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.

Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968–9.

The Poisson model can be applied to the count of events occurring within a specific time period. The main feature of the Poisson model is the assumption that the mean and variance of the count data are equal. However, this equal mean-variance relationship rarely occurs in observational data. In most cases, the observed variance is larger than the assumed variance, which is called overdispersion. Further, when the observed data involve excessive zero counts, the problem of overdispersion results in underestimating the variance of the estimated parameter, and thus produces a misleading conclusion. We illustrated the use of four models for overdispersed count data that may be attributed to excessive zeros. These are Poisson, negative binomial, zero-inflated Poisson and zero-inflated negative binomial models. The example data in this article deal with the number of incidents involving human papillomavirus infection. The four models resulted in differing statistical inferences. The Poisson model, which is widely used in epidemiology research, underestimated the standard errors and overstated the significance of some covariates.

1. Second attacks of typhoid fever are uncommon. In the literature this has been taken to imply that an attack of typhoid fever confers a high degree of immunity which, nevertheless, may be overcome by such factors as re-infection by a large dose, an organism of a different strain, or one of high virulence.

2. Two large outbreaks of typhoid fever in the same community within 5 months produced eleven examples of second attacks. Clinical descriptions of four of these are given.

3. Details are given of the population at risk and the attack rates in various groups.

4. The evidence of these facts and figures, though inconclusive, suggests that an attack of typhoid fever does not confer more than a moderate degree of specific immunity. The influence of chloramphenicol upon immunity remains sub judice.

A total of 89760 human and 22551 non-human isolates of salmonella were serotyped in Canada during the period 1983–92. There were 2180 reported outbreaks associated with 10065 cases during the 10-year period. The most common salmonella serovars isolated from human and non-human sources were S. typhimurium and S. hadar. The third and fourth most common serovars from human sources were S. enteritidis and S. heidelberg, respectively, and from non-human sources they were S. heidelberg and S. infantis. The number of S. typhimurium isolations from human and non-human sources showed a downward trend over the 10-year period. A total of 222 outbreaks of S. typhimurium associated with 1622 cases occurred. The S. hadar isolations from human and non-human sources reached a peak during the years 1987–90 and declined thereafter. The number of human isolates of S. enteritidis increased until 1985 and fluctuated at a level of 8·3–12·8% of all human isolates thereafter. Seventy-three outbreaks of S. enteritidis infection associated with 568 cases occurred. More than 50% of the S. enteritidis infections in humans were caused by phage type (PT) 8. During the review period, infections caused by PT4 were less common and were almost exclusively found in people who had travelled abroad. The annual isolation rates of S. heidelberg from human and non-human sources increased steadily during the period. Bacteriophage typing of serovars from outbreaks showed that contaminated food products of poultry and bovine origin were common sources of human infection. Salmonella typhi was identified as the cause of 43 small outbreaks affecting 116 persons.

Enterotoxigenic Escherichia coli (ETEC) is a common cause of profuse watery diarrhoea in the developing world, often leading to severe dehydration or death. We found only 15 population-based studies in low and medium human development index (HDI) countries from 1984 to 2005 that evaluate disease incidence. Reported incidence ranged from 39 to 4460 infections/1000 persons per year. The peak incidence of ETEC appeared to occur between ages 6 and 18 months. A median of 14% (range 2–36%) of diarrhoeal specimens were positive for ETEC in 19 facility- and population-based studies conducted in all age groups and 13% (range 3–39%) in 51 studies conducted in children only. Heat-labile toxin (LT)-ETEC is thought to be less likely to cause disease than heat-stable toxin (ST)-ETEC or LT/ST-ETEC. Because population-based studies involve enhanced clinical management of patients and facility-based studies include only the most severe illnesses, reliable data on complications and mortality from ETEC infections was unavailable. To reduce gaps in the current understanding of ETEC incidence, complications and mortality, large population-based studies combined with facility-based studies covering a majority of the corresponding population are needed, especially in low-HDI countries. Moreover, a standard molecular definition of ETEC infection is needed to be able to compare results across study sites.

Methods are described for the isolation and identification of aerobic bacteria occurring naturally in the hind-gut of the cockroach Blatta orientalis captured from a number of wild sources, to establish whether or not human pathogens occurred naturally within the gut. During the investigation an organism was frequently found which could not be classified in any described species, and for which we propose the name Escherichia blattae.

Over the past decade, frozen fruits have been a major vehicle of foodborne illnesses mainly attributed to norovirus (NoV) and hepatitis A virus (HAV) infections. Fresh produce may acquire viral contamination by direct contact with contaminated surface, water or hands, and is then frozen without undergoing proper decontamination. Due to their structural integrity, foodborne viruses are able to withstand hostile conditions such as desiccation and freezing, and endure for a long period of time without losing their infectivity. Additionally, these foods are often consumed raw or undercooked, which increases the risk of infection. Herein, we searched published literature and databases of reported outbreaks as well as the databases of news articles for the viral outbreaks associated with the consumption of frozen produce between January 2008 and December 2018; recorded the worldwide distribution of these outbreaks; and analysed the implication of consumption of different types of contaminated frozen food. In addition, we have briefly discussed the factors that contribute to an increased risk of foodborne viral infection following the consumption of frozen produce. Our results revealed that frozen fruits, especially berries and pomegranate arils, contributed to the majority of the outbreaks, and that most outbreaks were reported in industrialised countries.

A survey of the species composition and distribution of the Culicoides midge populations at a range of sites where bluetongue is enzootic isolated a group of dominant species: C. cornutus, C. grahamii, C. magnus, C. milnei, C. pallidipennis and C. 23.† Monthly light-trap sampling of Culicoides showed that the population densities of the dominant species greatly increased after the rain seasons and that these species concentrated around flocks of sheep and cattle. The larval habitats of C. cornutus and C. pallidipennis were found associated with stock pens. Precipitin tests on blood-fed Culicoides showed that most of the dominant species regularly feed on sheep and cattle. Bluetongue virus was isolated from C. milnei, C. pallidipennis and C. 23. Serological surveys of wild and domestic bovids from the enzootic area showed a high proportion with antibody to bluetongue virus. The colonization of C. cornutus, a potential vector, is described briefly. A causal relationship between peak rainfall in April-May, peak numbers of Culicoides in May-June and peak bluetongue incidence in June-July is postulated. The vector status of the above species and C. austeni was evaluated.

The spatial epidemiology of intestinal nematodes in Uganda was investigated using generalized additive models and geostatistical methods. The prevalence of Ascaris lumbricoides and Trichuris trichiura was unevenly distributed in the country with prevalence greatest in southwest Uganda whereas hookworm was more homogeneously distributed. A. lumbricoides and T. Trichiura prevalence were nonlinearly related to satellite sensor-based estimates of land surface temperature; hookworm was nonlinearly associated with rainfall. Semivariogram analysis indicated that T. trichiura prevalence exhibited no spatial structure and that A. lumbricoides exhibited some spatial dependency at small spatial distances, once large-scale, mainly environmental, trends had been removed. In contrast, there was much more spatial structure in hookworm prevalence although the underlying factors are at present unclear. The implications of the results are discussed in relation to parasite spatial epidemiology and the prediction of infection distributions.

Maternal malaria and under-nutrition are established risk factors for small-for-gestational-age (SGA) births; however, whether malaria is associated with intrauterine growth restriction (IUGR) is unknown. We investigated IUGR risk among 177 HIV-negative pregnant women enrolled in a longitudinal ultrasound study conducted in Democratic Republic of Congo from May 2005 to May 2006. Malaria infection, maternal anthropometrics, and ultrasound estimated fetal weight were measured monthly. All positive malaria cases were treated and intermittent presumptive therapy (IPTp) provided. Log-binomial regression models for IUGR were fitted using generalized estimating equations to account for statistical clustering of repeat IUGR measurements. Twenty-nine percent of fetuses experienced an episode of IUGR with the majority occurring in the third trimester. The risk of IUGR associated with malaria was greatest after three or more cumulative infections (RR 3·3, 95% CI 1·3–8·2) and was two- to eight-fold higher among women with evidence of under-nutrition. Receiving antimalarial treatment in the previous month (for IPTp or treatment) was significantly protective against IUGR (RR 0·5, 95% CI 0·3–0·7). The interaction observed between malaria and under-nutrition suggests that antenatal programmes in malaria endemic areas should incorporate nutritional screening and supplementation in addition to IPTp.

An examination of salmonella isolates collected by the Scottish Agricultural College Veterinary Services Division from April 1994 to May 1995 was conducted to determine the extent to which Salmonella enterica serotype Typhimurium phage type 104 (DT104) occurred and to investigate the antimicrobial resistance patterns of isolates. Typhimurium DT104 was the predominant salmonella and was isolated from nine species of animal. All isolates of this phage type possessed resistance to at least one antimicrobial and 98% of the isolates were resistant to multiple antimicrobials with R-type ACTSp the predominant resistance pattern. Various other resistance patterns were identified and transferable resistance to the veterinary aminoglycoside antimicrobial apramycin was demonstrated in three strains. A retrospective study for gentamicin resistance in isolates from the Scottish Salmonella Reference Laboratory collection revealed a human isolate of Typhimurium DT104 resistant to gentamicin but sensitive to apramycin and a bovine isolate with apramycin and gentamicin resistance.

Newly developed interferon-gamma release assays have become commercially available to detect tuberculosis (TB) infection in adults. However, little is known about their performance in children. We compared test results between the QuantiFERON-TB® Gold test (QFT) and tuberculin skin test (TST) in young children living with pulmonary TB patients in Cambodia. Of 195 children tested with both QFT and TST, the TST-positive rate of 24% was significantly higher than the QFT-positive rate of 17%. The agreement between the test results was considerable (κ-coefficient 0·63). Positive rates increased from 6% to 32% for QFT and from 15% to 43% for TST, according to the sputum smear grades of the index cases. The presence of Bacille Calmette-Guérin (BCG) scars did not significantly affect the results of TST or QFT in a logistic regression analysis. In conclusion, QFT can be a substitute for TST in detecting latent TB infection in childhood contacts aged ⩽5 years, especially in those who may have a false-positive TST due to BCG vaccination or non-tuberculous mycobacterial infection.

The indirect immunofluorescent technique has been used to detect and titrate the specific immunoglobulins in serum specimens from 154 infants with confirmed or suspected congenital rubella. IgM antibody was stained more efficiently in sucrose density gradient fractions than in whole serum and was detected in this way in 27 out of 40 patients with confirmed congenital rubella at ages ranging from birth to 2 years. It was present in 48 out of 50 serum specimens during the first 6 months of life and in 11 out of 38 specimens obtained at ages between 6½ months and 2 years. IgM antibody was therefore estimated to persist for about 6 months in the majority of cases and up to 2 years in a few individuals. IgM antibody was also detected by this method in 11 out of 114 infants with suspected but unconfirmed congenital rubella at ages up to 5 months. The total concentrations of IgM were above the normal range in nearly all sera taken from confirmed cases during the first 3 months of life and in half the specimens obtained between the ages of 3 and 6 months.

IgG antibody was detected by fluorescent staining of whole serum in all patients with congenital rubella. Geometric mean titres increased during the first 3 months of life and then declined slowly. IgA antibody was not detected, except in two patients in whom traces were present at the age of 6 months, and the total concentrations of IgA were usually within normal limits.

Fluorescent staining of fractions showed that the sedimentation characteristics of rubella IgG and IgM antibodies were the same in infants as in adults. The peak IgM fractions never contained IgG antibody, and the presence of specific IgM in these fractions could usually have been safely inferred from their HAI titres. Fluorescent staining, however, was more sensitive and frequently detected IgM antibody in fractions which had no definite HAI activity.

Fluorescent staining of whole serum for IgM antibody was less distinct, and often unsuccessful, even in specimens in which specific IgM was detected in the fractions. The addition of IgG- to IgM-containing fractions caused depression of IgM staining and suggested that failure to detect IgM antibody in whole serum was partly due to competitive inhibition by specific IgG.

The first case of 2019-nCoV pneumonia infection occurred in Wuhan, Hubei Province, South China Seafood Market in December 2019. As a group with a high probability of infection, health workers are faced with a certain degree of psychological challenges in the process of facing the epidemic. This study attempts to evaluate the impact of 2019-nCoV outbreak on the psychological state of Chinese health workers and to explore the influencing factors. During the period from 31 January 2020 to 4 February 2020, the ‘Questionnaire Star’ electronic questionnaire system was used to collect data. The 2019-nCoV impact questionnaire and The Impact of Event Scale (IES) were used to check the psychological status of health workers in China. A total of 442 valid data were collected in this study. Seventy-four (16.7%) male and 368 (83.3%) female individuals participated in this study. The average score of high arousal dimension was 5.15 (s.d. = 4.71), and the median score was 4.0 (IQR 2.0, 7.0). The average score of IES was 15.26 (s.d. = 11.23), and the median score was 13.5 (IQR 7.0, 21.0). Multiple regression analysis showed that there were critical statistical differences in high arousal scores among different gender groups (male 3.0 vs. female 5.0, P = 0.075). Whether being quarantined had significant statistical differences of IES scores (being quarantined 16.0 vs. not being quarantined 13.0, P = 0.021). The overall impact of the 2019-nCoV outbreak on health workers is at a mild level. Chinese health workers have good psychological coping ability in the face of public health emergencies.

Giardiasis is a common waterborne gastrointestinal illness. In 2007, a community giardiasis outbreak occurred in New Hampshire, USA. We conducted a cohort study to identify risk factors for giardiasis, and stool and environmental samples were analysed. Consuming tap water was significantly associated with illness (risk ratio 4·7, 95% confidence interval 1·5–14·4). Drinking-water samples were coliform-contaminated and a suspect Giardia cyst was identified in a home water filter. One well was coliform-contaminated, and testing indicated that it was potentially under the influence of surface water. The well was located 12·5 m from a Giardia-contaminated brook, although the genotype differed from clinical specimens. Local water regulations require well placement at least 15 m from surface water. This outbreak, which caused illness in 31 persons, represents the largest community drinking-water-associated giardiasis outbreak in the USA in 10 years. Adherence to well placement regulations might have prevented this outbreak.

Childhood rubella infection in early pregnancy can lead to fetal death or congenital rubella syndrome (CRS) with multiple disabilities. Reduction of transmission via universal vaccination can prevent CRS, but inadequate coverage may increase CRS numbers by increasing the average age at infection. Consequently, many countries do not vaccinate against rubella. The World Health Organization recommends that for safe rubella vaccination, at least 80% coverage of each birth cohort should be sustained. The nonlinear relationship between CRS burden and infection dynamics has been much studied; however, how the complex interaction between epidemic and demographic dynamics affects minimum safe levels of coverage has not been quantitatively evaluated across scales necessary for a global assessment. We modelled 30-year CRS burdens across epidemiological and demographic settings, including the effect of local interruption of transmission via stochastic fadeout. Necessary minimum vaccination coverage increases markedly with birth and transmission rates, independent of amplitude of seasonal fluctuations in transmission. Susceptible build-up in older age groups following local stochastic extinction of rubella increased CRS burden, indicating that spatial context is important. In low birth-rate settings, 80% routine coverage is a conservative guideline, particularly if supplemented with campaigns and vaccination of women of childbearing age. Where birth and transmission rates are high, immunization coverage must be well above 80% and campaigns may be needed. Policy-makers should be aware of the potential negative effect of local extinction of rubella, since heterogeneity in vaccination coverage will shape extinction patterns, potentially increasing CRS burdens.

1. Of 1552 strains of Staph. pyogenes tested by the slide-agglutination technique, using the absorbed and unabsorbed sera suggested by Cowan, 74% of strains were identified while 26% remained untyped. Of untyped strains, half were inagglutinable while the remainder gave ‘indefinite’ results and remained unclassified. The introduction of two new sera, used diluted but unabsorbed, considerably reduced the number of untyped organisms but made little difference to the proportion of ‘indefinite’ strains. The method was simple and quick, but the variety of cross-reactions often prevented a clearcut differentiation of strains and the number of types identifiable was limited.

2. Of three methods of agglutination, titrations on glass slides were preferred because by this technique end-points were clearer than those obtained in a water-bath or by the method for determination of Vi antibody.

3. Agglutination of seventeen strains of Staph. pyogenes with homologous and heterologous sera showed that the use of unabsorbed sera was of limited value for typing because of the marked cross-reactions.

4. Christie & Keogh's division of Staph. pyogenes into nine types was promising but their absorbing methods allowed much antigenic overlap.

5. Experiments with absorbed sera showed that no single strain of Staph. pyogenes could be used successfully to absorb all sera. There appeared to be groups or pairs of types in which serologically the individual members resembled each other very closely and yet were not identical. In these instances the absorption of a serum by a heterologous strain nearly related to the homologous strain proved of most value in the preparation of specific sera.

6. A set of seventeen absorbed sera was prepared from Cowan's three types of Staph. pyogenes, from six of Christie & Keogh's type strains and from eight additional strains freshly isolated from staphylococcal lesions. With some absorbed sera there was specific agglutination with the homologous strain and no heterologous reactions, other sera reacted with several strains and could not be made specific.

7. Seven specific serological types were recognized while a further eight types showed less specific reactions and were identifiable by a pattern of reactions. A number of strains differed slightly one from another in their agglutination reactions, and it was not possible to decide whether these were additional types or variants within types.

8. In a small series of experiments the precipitin reaction, using unabsorbed sera, seemed of little value in the differentiation of strains of Staph. pyogenes.

9. Of 259 coagulase-positive strains examined during 1946 and 1947, all were identified by agglutination reactions, although they varied in their specificity; 67.5% of these strains were identified by staphylococcal bacteriophage reactions.

10. A preliminary comparison of serological and bacteriophage types showed a fairly regular but not complete correlation between the results obtained by the two methods. A number of serological types were regularly lysed by the same bacteriophage filtrates; a few were consistently untypable by phage indicating that filtrates had not as yet been found for them or that the strains were phage resistant.

Others which were not clear-cut in their reactions and which were recognized by patterns of reactions with both sera and phage filtrates did not always show a close correlation in the typing results.

11. The application of both serological and bacteriophage typing to the investigation of outbreaks of staphylococcal infection has proved to be of value in tracing sources and paths of spread of infection. In several instances the use of both methods of typing has led to conclusions which would not have been warranted if one method alone had been used.

Between July 1976 and February 1989, 50 incidents of suspected red kidney bean poisoning were reported in the UK. Nine incidents in which nausea, vomiting and diarrhoea developed within 1–7 h of ingestion, were confirmed by the detection of haemagglutinin in the beans. The diagnosis was made on a further 23 incidents on the basis of symptoms, incubation time and the description of preparation of beans prior to consumption. The haemagglutinin (lectin), which occurs naturally in the red kidney bean, is inactivated by thorough cooking of well soaked beans. In many of the outbreaks reported the implicated beans were consumed raw or following an inadequate heat process.

From January 1997 to December 2003, all patients with non-tuberculous mycobacteria (NTM) isolation who were treated at a university hospital in Taiwan were evaluated. Among the 2650 NTM isolates, 1225 (46·2%) were from 412 patients with clinically significant diseases. The annual incidence (per 100000 patients) of disease caused by NTM was 8·96 in 1997, 21·53 in 2002, and 16·55 in 2003. The major types of infections caused by NTM included isolated pulmonary infection and pleurisy (59·5%), skin/soft-tissue infections and osteomyelitis (13·8%), and disseminated diseases (13·3%). The two most common groups of organisms involved were rapidly growing mycobacteria (RGM) (41·4%) and Mycobacteriumavium complex (MAC) (39%). The most common organism involved in isolated pulmonary infection and pleurisy was MAC (44·1%). RGM predominated in keratitis (94%), skin/soft-tissue infections and osteomyelitis (43·9%), and lymphadenitis (66·7%). This retrospective 7-year study demonstrated an increase in the incidence of NTM disease in a university hospital.