Orthobunyaviruses, tri-segmented, negative-sense RNA viruses, have long been associated with mild to severe human disease in Africa, but not haemorrhagic fever. However, during a Rift Valley fever outbreak in East Africa in 1997–1998, Ngari virus was isolated from two patients and antibody detected in several others with haemorrhagic fever. The isolates were used to identify Ngari virus as a natural Orthobunyavirus reassortant. Despite their potential to reassort and cause severe human disease, characterization of orthobunyaviruses is hampered by paucity of genetic sequences. Our objective was to obtain complete gene sequences of two Bunyamwera virus and three Ngari virus isolates from recent surveys in Kenya and to determine their phylogenetic positioning within the Bunyamwera serogroup. Newly sequenced Kenyan Bunyamwera virus isolates clustered closest to a Bunyamwera virus isolate from the same locality and a Central African Republic isolate indicating that similar strains may be circulating regionally. Recent Kenyan Ngari isolates were closest to the Ngari isolates associated with the 1997–1998 haemorrhagic fever outbreak. We observed a temporal/geographical relationship among Ngari isolates in all three gene segments suggesting a geographical/temporal association with genetic diversity. These sequences in addition to earlier sequences can be used for future analyses of this neglected but potentially deadly group of viruses.

Streptococcus pneumoniae is an important cause of community-acquired pneumonia and pneumococcal conjugate vaccines (PCVs) may reduce this burden. This study's goal was to analyse trends in lower respiratory tract infections (LRTI) hospitalisations before and during a routine vaccination programme targeting all newborns with PCV was started in the province of Quebec, Canada in December 2004. The study population included hospital admissions with a main diagnosis of LRTI among 6–59 month-old Quebec residents from April 2000 to December 2014. Trends in proportions and rates were analysed using Cochran-Armitage tests and Poisson regression models. We observed a general downward trend in all LTRI hospitalisations rate: from 11·55/1000 person-years in 2000–2001 to 9·59/1000 in 2013–2014, a 17·0% reduction, which started before the introduction of PCV vaccination. Downward trends in hospitalisation rates were more pronounced for all-cause of pneumonia (minus 17·8%) than for bronchiolitis (minus 15·4%). There was also a decrease in the mean duration of hospital stay. There was little evidence that all-cause pneumonia decreased over the study period due mainly to the introduction of PCVs. Trends may be related to changes in clinical practice. This study casts doubt on the interpretation of ecological analyses of the implementation of PCV vaccination programmes.

A detailed study is made of methods available for estimating the significance of difference in degree of pollution of water by conform bacteria and of obtaining practically useful estimates of such differences.

For estimating the significance of a difference in a single pair of samples it was considered preferable to employ as the variate the difference in the total number of fertile tubes, or n.f.t., rather than the difference in the so-called most probable number of bacteria per 100 ml. A table (Table 3) is included by which the significance of any difference in n.f.t. may be determined at a glance. The variate is also useful in determining whether a series of differences may be regarded as homogeneous and such as might be expected to arise by chance in a high proportion of trials if corresponding members in a series of pairs of samples had been taken from sources identical as to their degree of pollution. Table 5 is included to facilitate the application of a comprehensive test of identity, in degree of pollution, of the members of each pair of samples.

The application of the binomial distribution in testing the significance of consistency in sign of a series of differences is explained, and Table 13 is included to facilitate the application of the binomial for a series of pairs twenty or less in number. The use of the normal distribution as an approximation to the binomial for pairs over twenty in number is explained.

The distribution of differences in the logarithms of the ‘most probable number of bacteria per 100 ml.’, or m.p.n., between samples in a certain series, A, and those of another series, B, in an experiment carried out by Dr L. F. L. Clegg, was found to be approximately normal in form. Thus the normal test of the mean logarithmic difference in m.p.n. is applicable and the t-test is applicable to a small series of differences. The advantages of employing the logarithmic difference as the variate are pointed out.

All tests applied to Dr Clegg's data agree in showing that the degree of pollution estimated from the results of a certain method, B, was higher than that indicated by the results of another method, A. According to method A the tubes were inoculated and- incubated at once at 44° C, while according to method B the inoculated tubes were incubated at 37° C, those proving fertile at that temperature being used for inoculating fresh tubes which were then incubated at 44° C. The mean ratio, B : A was found to be 1·416 and the 0·025 points of the distribution were found to be B : A = 9·6, A : B = 4·8 respectively.

The choice of a level of significance is discussed.

The results of the application of some statistical tests of significance to data from a control experiment are discussed. In this experiment the members of each pair of samples were taken from the same water sample and treated by identical methods.

The methods of replacing a difference by the corresponding value of the normal abscissa and of applying the normal test of significance of a mean to the mean of such normal abscissae is explained. This method is applied in testing the significance of a mean difference in n.f.t. and in testing the significance of a mean error from zero.

The theoretical bases of tests of the significance of differences in m.p.n. and in n.f.t. are compared.

The advantage of knowledge of the exact distribution of a single difference in tests of the significance of a series of differences is explained and examples are given which demonstrate this advantage very clearly.

The combination of results taken at different times and places for testing the significance of time or locality effects is explained and a, suggestion is made as to the use of replicated observations when the value of P for each observation is known.

Daptomycin-non-susceptible enterococci (DNSE) are emerging pathogens. We have previously reported de novo DNSE isolates in patients with agricultural activities and exposure to livestock. We studied the geographical distribution of the residencies of 34 patients with DNSE infections described in a tertiary centre over a 5-year period in an effort to explore the association between patients’ residential locations and agricultural and farm lands. Nine patients had no prior exposure to daptomycin (de novo) and seven of these lived in areas with animal or crop operations. Of those living near an animal or crop operation, the mean number of operations in the proximity of the residence of patients with daptomycin-exposed DNSE was 13·8 (range 1–67) compared to 98·6 (3–529) for those patients with de novo DNSE (P = 0·0486). These data are consistent with previous reports that the transport of daptomycin resistance genes between animals and humans may be a possible mechanism for development of de novo daptomycin resistance in enterococci.

Close contacts of cases of meningococcal disease are at increased risk of disease themselves. We identified household-like contacts of index cases, to investigate whether relevant target groups are informed, receive and follow recommended chemoprophylaxis and vaccination, and to ascertain the time delay for implementation of these measures. A telephone interview of 172 households of index cases and a questionnaire survey among 634 parents of contacts of cases in institutions were carried out. Results were compared with reports from Medical Officers of Health. In 21% of the cases, Medical Officers reported fewer household-like contacts than were identified in this study. Written information was effective. However, 59% of households, and 36% of parents of contacts in institutions felt a lack of information about how the disease is acquired, the risk and signs of illness. For household-like contacts the coverage rate for chemoprophylaxis with an appropriate drug was 90% and for vaccination 59%. No secondary cases occurred among those treated with chemoprophylaxis, but among those not treated, there were two secondary cases. The study design provided a useful audit methodology to evaluate the completeness of implementation and the success of prophylactic measures for meningococcal disease.

By the negative staining technique both Bittner and influenza viruses are pleomorphic and have similar fringed surfaces. The present study revealed that Bittner virus had one characteristic form consisting of a head approximately 1000 Å. in diameter and a tail up to 3000 Å. long. On storage at −20° C. Bittner virus broke down to reveal a round internal component of 750 Å. diameter. Influenza virus did not break down on storage at −20° C. but a small number of spontaneously disrupted particles revealed that the internal component was in the form of a coil. The circular internal component of Bittner virus is presumed to be spherical and corresponds to the previously described type A particles as seen by negative staining. The complete enveloped particle corresponds to the type B particle of thin sectioning. It is suggested that the thinly sectioned mature type B particle may be a degenerate form of the so-called immature type B particle. In addition, it is suggested that certain murine RNA tumour viruses may have a morphology distinctive to them.

A Microscopical study of the skins of mice painted with definite carcinogenic agents and with agents which appear to be incapable of exciting the production of tumours has, in the main, enabled us to confirm the observations of previous workers on the different histological changes which take place. A brief description of our findings will first be given.

Bacteriostatic activity was measured in 244 specimens of milk collected during 1977 throughout lactation of up to one year from 78 mothers; the activity varied from very good to fair and only seven were inactive. There was a wider range of activity than was found previously in milk from English mothers. Activity usually fell slowly during lactation but some of the Gambian mothers produced milk of very high activity, like that of colostrum into the second week of lactation, and two mothers did so at six and nine months; other mothers produced good-activity milk throughout lactation. The bacteriostatic activity varied little with the season but slight decreases from that expectcd were found after the high incidence of infant diarrhoea towards the end of the rainy season.

The bacteriostatic activity of most of the milk tested could be prevented by iron salts but that of colostrum and some of the milks with high activity could not. Only these highly active colostra and milks were inhibitory in vitro when the inoculum was increased from 104 to 106 organisms per ml. These and less active milks were able to inhibit the smaller, standard inoculum for longer than 3 h with the addition of bicarbonate and extra iron-binding protein at the concentrations likely to be present in vivo. Both commensal and pathogenic E. coli were inhibited to a similar degree by these milks and there was no evidence of serotype specificity.

It has long been known that individuals who suffer from such chronic diseases as nephritis and cirrhosis of the liver are very liable to develop an acute infection during the last stages of their illness. These patients rarely die of their chronic ailment. Often in the very last days, or perhaps hours, of the disease pneumonia, a dysentery, an acute endocarditis, or a streptococcus infection sets in, which quickly terminates fatally and must be regarded as the immediate cause of death. So familiar is this course of events that such pneumonias or dysenteries are now known as a fairly definite group of infections, namely, terminal infections. Often they are not recognized before death, but at autopsy their frequency and varying characters have been well shown by Flexner in his statistical and experimental study upon the subject; and though in some cases of terminal septicaemia the portal of entry was not easily found, yet it is important to note how frequently such local infections as leg ulcer or tonsilitis served as a starting point for the general invasion of bacteria. Of still more importance are his observations upon the bactericidal action of the blood of patients who have chronic diseases. The serum from six out of nine such patients showed a distinct decrease in its destructive power toward the Staphylococcus aureus and two of three patients whose serum did not show a diminished bactericidal action left the hospital improved.

Methicillin-resistant Staphylococcus aureus (MRSA) infection is known to increase in-hospital mortality, but little is known about its association with long-term health. Two hundred and thirty-seven deaths occurred among 707 patients with MRSA infection at the time of hospitalization and/or nasal colonization followed for almost 4 years after discharge from the Atlanta Veterans Affairs Medical Center, USA. The crude mortality rate in patients with an infection and colonization (23·57/100 person-years) was significantly higher than the rate in patients with only colonization (15·67/100 person-years, P = 0·037). MRSA infection, hospitalization within past 6 months, and histories of cancer or haemodialysis were independent risk factors. Adjusted mortality rates in patients with infection were almost twice as high compared to patients who were only colonized: patients infected and colonized [hazard ratio (HR) 1·93, 95% confidence interval (CI) 1·31–2·84]; patients infected but not colonized (HR 1·96, 95% CI 1·22–3·17). Surviving MRSA infection adversely affects long-term mortality, underscoring the importance of infection control in healthcare settings.

Normally, only one isolate of Listeria monocytogenes from a case of listeriosis is subjected to characterization. Here we show that two isolates from different sites of the body were not the same strain. Such a phenomenon may not have any clinical relevance, although it may confuse the epidemiologist trying to match infection source with infection target.

The fact that the blood of ordinary laboratory animals exerts a very marked bactericidal effect upon the Bacillus typhosus and the Spirillum cholerae asiaticae, while it exerts little or no effect upon the Staphylococcus and Streptococcus pyogenes, has hardly received the attention which it would seem to merit in view of the circumstance that these facts involve the important problem as to whether the blood exerts its bactericidal action upon pathogenic organisms generally, or only upon certain species of such micro-organisms.

It is greatly to be desired that the causes of the decline of tuberculosis, which has been so striking a feature in the history of that disease in recent times, should be clearly ascertained; for only through an understanding of their nature and relative importance can our efforts to accelerate that decline hope to succeed.

Since measles is a highly contagious respiratory infection with significant airborne transmission risk in hospitals, effective prevention measures are crucial. After a mother accompanying her child on a paediatric ward lacking a negative pressure room was diagnosed with measles, exposed persons without evidence of immunity (documentary evidence of receiving two doses of measles-mumps-rubella vaccine) were treated with vaccination or intravenous immunoglobulin (IVIG). The interruption of transmission with these treatments was evaluated. There were 44 children and 101 adults exposed to the index patient. Twenty-five children and 88 adults were considered immune, providing evidence of immunity. Nineteen children and 13 adults were either given vaccination or IVIG for post-exposure prophylaxis (PEP). There were no additional cases of measles after 3 weeks follow-up. We conclude that measles is highly preventable by adequate PEP with vaccination or IVIG in a healthcare setting that lacks the benefit of a negative pressure room.

Preparations of influenza virus A0 PR 8/34 and A 2 Malaysia/68 have been studied in the electron microscope. They were similar in appearance to preparations made by others. Each preparation was degraded by Triton N 101. The process of degradation appeared to be different from that observed using ether and, by inference, a number of other agents.

The effect of a community intervention programme of antibiotics and meningitis vaccine on pharyngeal carriage of Neisseria meningitidis was investigated. Carriage rates were determined in pupils at both secondary schools (ages 11–18 years) included in the community intervention programme and compared with two schools outside the area matched for socio-economic status. A total of 1869 pupils were studied 6 months after the programmes, and 2457 pupils after 11 months.

Six months after the programme was completed there was a 72% reduction in pharyngeal carriage of Neisseria meningitidis in pupils attending the schools in the intervention area compared with pupils in the control schools. After 11 months this difference persisted in the 11–14 age group but not in the 15–18 age group. No resistance to the antibiotics used in the programme was found.

A community intervention programme of antibiotics and vaccine for the control of meningococcal disease led to a long-term reduction in Neisseria meningitidis carriage in some age groups.

The social networks of 49 ethnic Vietnamese injecting drug users (IDUs) and 150 IDUs of other ethnicities recruited in Melbourne, Australia, were examined for ethnic differences in distribution of hepatitis C virus infection risk using social network analysis and molecular epidemiology. Vietnamese IDUs were more highly connected than non-Vietnamese IDUs, and more likely to be members of dense injecting sub-networks. More related infections were detected in IDUs with discordant ethnicities than were captured in the social network data; nonetheless, most dyads and most IDU pairs with related infections had matching ethnicity, confirming that mixing was assortative on that criterion. Mixing was not obviously dissortative by risk; low-risk Vietnamese IDUs injected more frequently than did correspondingly low-risk non-Vietnamese IDUs, but results for other measures were reversed or equivocal. Network measurements suggest that ethnic Vietnamese IDUs are at elevated risk of blood-borne infection, a conclusion supported by their relatively high HIV prevalence.

This prospective, multicentre study was conducted during 2–30 April 2001 in the internal medicine/infectious diseases services in France and included data from 1858 hepatitis C virus (HCV)-infected patients, half of whom were HIV co-infected. The aims were to outline the type of pre-therapeutic evaluation of HCV infection performed (HCV RNA, genotype, liver biopsy); determine the proportion and characteristics of patients receiving antiviral treatment; and determine if any changes in these parameters had occurred between 1995 and 2001. Patients whom had a complete pre-therapeutic evaluation (39%, 709/1834) and received antiviral treatment (38%, 690/1830) were more likely to have abnormal liver biochemistry, cirrhosis and cryoglobulinaemia (P<0·001). Injecting drug users and HIV-co-infected patients were less likely to have a complete pre-therapeutic evaluation or receive antiviral treatment (P<0·001). A complete pre-therapeutic evaluation was more often performed in 2001 than in 1995 (39% vs. 6%, P<0·001), including qualitative HCV RNA testing (91% vs. 68%, P<0·001), genotyping (59% vs. 7%, P<0·001) and a liver biopsy (60% vs. 29%, P<0·001). The frequency of anti-HCV treatment approximately doubled between 1995 and 2001 (20% vs. 38%, P<0·001). Although adherence to consensus recommendations regarding pre-therapeutic evaluation is not ideal, a substantial improvement has occurred since 1995. Nevertheless, means of increasing the availability of antiviral therapies, particularly for patients with HIV co-infection or injecting drug use, require further study.

We identified an increase in the number of cases of Salmonella Typhimurium phage type 197 in New South Wales in February 2005. Cases were predominantly of Lebanese descent. To identify risk factors for illness, we conducted an unmatched case-control study including 12 cases and 21 controls. Eight of 12 cases (67%) and no controls reported eating lambs' liver (OR incalculable, P<0·05), and seven of nine cases (78%) and one of 21 controls (5%) reported eating fresh fish (OR 70·0, P<0·05). Among participants who did not eat liver, there was a strong association between eating fish and illness (OR 60·0, P<0·05). The fish was from divergent sources. Five cases had bought the liver from two different butcher's shops, which obtained the lambs' liver from a single abattoir. Consumption of liver is a risk for salmonellosis. Traditional dishes may place some ethnic groups at increased risk of foodborne disease.

The occurrence of epidemics of vaccine-preventable diseases, and the immunization coverage required to prevent them, is affected by the presence of households and heterogeneity in the community. We consider a community where individuals live in households and are of different types, according to infectivity and/or susceptibility to infection. We describe a method for computing the critical immunization coverage to prevent epidemics in such communities and discuss the effectiveness of immunization strategies. In a heterogeneous community where individuals live in households several immunization strategies are possible and we examine strategies targeting households, randomly selected individuals, or groups with highly intense transmission, such as school children. We compare estimates of the critical immunization coverage if we assume that disease is spread solely by random mixing with estimates which result if we assume the effects of the household structure. Estimates made under these two sets of assumptions differ. The results provide insights into the community effects of vaccination, and the household structure of the community should be taken into account when designing immunization policies.