The antigenic variation of influenza A 2 virus and the antibody present in the population to different variants are described and related to the occurrence of epidemics of influenza in England since 1957.

The phage types and antimicrobial susceptibilities of 226 isolates of Salmonella enterica serovar Typhi from imported cases in Japan between 2001 and 2006 were investigated. Most (93·8%) had travelled to Asian countries, particularly South East Asia. Twenty-one phage types were identified with E1 (30·5%), UVS (15·9%) and B1 (9·3%) being the most common. The frequency of multidrug-resistant strains reached 37·0% in 2006 with phage types E1 and E9 predominating. Almost half (48·2%) of the isolates were resistant to nalidixic acid and two isolates displayed high-level fluoroquinolone resistance. Three mutations, two in gyrA and one in parC, were identified in both isolates.

In several lately published studies, the association between single-nucleotide polymorphism (SNP, rs12252) of IFITM3 and the risk of influenza is inconsistent. To further understand the association between the SNP of IFITM3 and the risk of influenza, we searched related studies in five databases including PubMed published earlier than 9 November 2017. Ten sets of data from nine studies were included and data were analysed by Revman 5.0 and Stata 12.0 in our updated meta-analysis, which represented 1365 patients and 5425 no-influenza controls from four different ethnicities. Here strong association between rs12252 and influenza was found in all four genetic models. The significant differences in the allelic model (C vs. T: odds ratio (OR) = 1.35, 95% confidence interval (CI) (1.03–1.79), P = 0.03) and homozygote model (CC vs. TT: OR = 10.63, 95% CI (3.39–33.33), P < 0.00001) in the Caucasian subgroup were discovered, which is very novel and striking. Also novel discoveries were found in the allelic model (C vs. T: OR = 1.37, 95% CI (1.08–1.73), P = 0.009), dominant model (CC + CT vs. TT: OR = 1.48, 95% CI (1.08–2.02), P = 0.01) and homozygote model (CC vs. TT: OR = 2.84, 95% CI (1.36–5.92), P = 0.005) when we compared patients with mild influenza with healthy individuals. Our meta-analysis suggests that single-nucleotide T to C polymorphism of IFITM3 associated with increasingly risk of severe and mild influenza in both Asian and Caucasian populations.

Isolations of subgenus III salmonellas (arizonas) made in the regional Public Health Laboratory, Cardiff, between 1959 and 1971 are reviewed. The techniques of isolation are listed for the various materials examined. The necessity of using bismuth sulphite agar as a plating medium is stressed, as some strains might appear on brilliant green MacConkey agar as rapid lactose fermenters and be missed. The serotypes isolated in Cardiff are discussed with reference to isolations by other authors. The culture of a subgenus III salmonella from pig faeces is described. It is thought that this is the first record of such an isolation from a pig in the United Kingdom.

The Salmonella Reference Centre in Johannesburg received 14059 strains of human origin between 1979 and 1984. A significant proportion (6·3%) proved to belong to subspecies II. The majority were cultured from faecal material, usually associated with symptoms related to the gastrointestinal tract. They comprised 884 isolates, represented by 203 serotypes, of which 45 were new serotypes.

The poor hygienic conditions found in many rural areas, together with possible contamination of food and water by wild animals, may contribute to the greater frequency of human S.II infections and the widespread occurrence of unusual serotypes in man in this geographic region.

The prevalence and genotype distribution of human papillomavirus (HPV) infection in women with normal cervical cytology varies widely according to the population studied. Two non-overlapping population-based cohort studies of women aged ⩾30 years for the periods 2008–2009 (n=5026) and 2004–2005 (n=10 014) were analysed. The prevalence rate of HPV was 11·0% (95% CI 10·5–11·6). HPV infection was significantly associated with age, menopausal status, and inversely associated with hormone replacement therapy. There was an increasing trend of α3/α15, α5/α6, and multiple HPV infections with increasing age. The five most common types were HPV52, 18, 53, 58 and 70, while HPV16, 31, 33 ranked 21st, 25th, and 16th, respectively, in the merged cohort with normal cytology (n=14 724). HPV16, 31, and 33 were significantly associated with abnormal cytology, which could have resulted in their rarity in the total merged cohort (n=15 040).

We examined the association between water exposures and acute diarrhoeal illness (ADI) in children under non-outbreak conditions in a major US metropolitan area. We used a nested case-control study of children seen in an urban/suburban emergency department. Cases were those seen for a complaint of diarrhoea, while controls were age-matched children with a non-gastrointestinal complaint. Parents of subjects completed a validated water-use survey. Stratum-specific adjusted odds ratios (aOR) were calculated for the three main water effects: water source [surface vs. ground (well)], drinking-water type (tap vs. bottled), and use of water filters. Of 2472 subjects, 45% drank mostly or only bottled water. Well-water use was associated with increased odds of ADI compared to surface water [aOR 1·38, 95% confidence interval (CI) 1·01–1·87]. Use of bottled water did not affect the odds of ADI in well-water users, but increased the odds of ADI for surface-water users (aOR 1·27, 95% CI 1·02–1·57). We conclude that well-water use and bottled-water use are associated with increased odds of ADI in children.

It will be accepted that milk containing large numbers of bacteria, as well as the products of their growth, is less suitable for food than unpolluted milk. A bacteriological examination of the milk in great cities generally will show that much of it in hot weather, and some of it at all seasons of the year, abounds in bacteria. Clinical experience also teaches that much of the milk in hot weather is unsuitable for food, especially for infants; because in them, owing to the rapidity with which the milk passes through the stomach, gastric digestion is almost no safeguard against the entrance of disturbing microorganisms into the intestines. Even pasteurization of milk charged with bacteria and their products does not restore it to its original condition, for the dead bodies of the bacteria and their toxins still remain. The changes in milk which are most deleterious being now known to be due to bacteria, it is theoretically conceded by all, that commercial cow's milk, the substitute for maternal milk, should be as nearly free as practicable from bacteria.

Herpesviruses can remain dormant in once-infected hosts and, upon reactivation, cause such hosts to become infectious. This phenomenon of latency and reactivation may enable herpesviruses to persist for a long time in small host populations. To quantify the effect of reactivation on persistence, the time to extinction of bovine herpesvirus type 1 (BHV-1) in small cattle populations was calculated. For realistic parameter values the mean time to extinction is already more than 100 years in a population of 10 animals. In a population of 20 animals the time to extinction is approximately 2000 years. The effects of vaccination on persistence were also studied, revealing that continued vaccination of the whole population could result in much faster eradication. For instance, in an isolated herd of 20 animals BHV-1 could be eradicated in 44 years.

Mycobacterium bovis infects the wildlife species badgers Meles meles who are linked with the spread of the associated disease tuberculosis (TB) in cattle. Control of livestock infections depends in part on the spatial and social structure of the wildlife host. Here we describe spatial association of M. bovis infection in a badger population using data from the first year of the Four Area Project in Ireland. Using second-order intensity functions, we show there is strong evidence of clustering of TB cases in each the four areas, i.e. a global tendency for infected cases to occur near other infected cases. Using estimated intensity functions, we identify locations where particular strains of TB cluster. Generalized linear geostatistical models are used to assess the practical range at which spatial correlation occurs and is found to exceed 6 in all areas. The study is of relevance concerning the scale of localized badger culling in the control of the disease in cattle.

The spread of the Zika virus (ZIKV) in the Americas led to large outbreaks across the region and most of the Southern hemisphere. Of greatest concern were complications following acute infection during pregnancy. At the beginning of the outbreak, the risk to unborn babies and their clinical presentation was unclear. This report describes the methods and results of the UK surveillance response to assess the risk of ZIKV to children born to returning travellers. Established surveillance systems operating within the UK – the paediatric and obstetric surveillance units for rare diseases, and national laboratory monitoring – enabled rapid assessment of this emerging public health threat. A combined total of 11 women experiencing adverse pregnancy outcomes after possible ZIKV exposure were reported by the three surveillance systems; five miscarriages, two intrauterine deaths and four children with clinical presentations potentially associated with ZIKV infection. Sixteen women were diagnosed with ZIKV during pregnancy in the UK. Amongst the offspring of these women, there was unequivocal laboratory evidence of infection in only one child. In the UK, the number and risk of congenital ZIKV infection for travellers returning from ZIKV-affected countries is very small.

Previous workers (Stuart-Harris, Pownall, Scothorne & Franks, 1953; May, 1953)have reported studies on the bacterial flora of the sputum in cases of chronic bronchitis. Both pneumococci and Haemophilus influenzae have been reported frequently in the sputum but the source of these organisms, which might be either the patient's own upper respiratory tract or the environment, has not been traced.A long-term study of individuals with and without chronic bronchitis and of their families was therefore begun in an attempt to discern the role of exogenous infection in this disease. Observations were limited to the pneumococcus because serological identification of individual strains was readily possible in this species.

In the present study an attempt has been made to determine the relative importance of several factors on the mortality rates of infancy. In view of the differences in the rates at the several ages under one year and of the differential decline in these rates within recent years, it has been suggested that for any complete consideration of the death rates in infancy, some subdivision of the rate, either of a biological or temporal character, must be effected, and each of these subdivisions examined separately. The infant mortality rate has been treated in three broad categories, namely, the antenatal, neo-natal and post-natal death rates; and it has been shown that each of these depends on different factors.

Considered as death rates per unit of time the neo-natal rate is much higher than at any other period of life. The ante-natal death rate is much lower than this, and the post-natal rate lowest of all.

In relation to these rates, the influence of three, presumably important, factors have been measured. These are:

1. The provision of skilled attendance to mothers in childbed.

2. The health of the mothers.

3. Environmental and social conditions.

The indices used as measures of these three variables and their limitations have been pointed out. The author feels only too conscious of these limitations and, with such vital statistical data as the only indices available of the factors the influence of which on the mortalities of infancy it is desired to measure, it is probable that any conclusions drawn from such an analysis should be accepted with some degree of caution and reserve. Nevertheless. I am firmly convinced that even these (to the clinician and administrator) rather crude results are immeasurably superior to expressions of opinion, unsupported by facts, so frequently found forming the basis of much of the medical literature on the subject. That we have so relatively little exact quantitative knowledge of the influential factors concerned in the growth, nutrition and mortality of infants is surely not for lack of opportunity of collecting the requisite data. An admirable machinery for such a purpose—the various maternity and child welfare centres—is in extensive operation throughout this country; and if the medical officers in charge of these centres could only be persuaded to collect and analyse (or have analysed) periodically the data contained in suitably framed and completed questionnaires, many questions of scientific importance as well as of the efficacy of administrative efforts would soon cease to be subjects of controversy.

Our results show that, of these factors, only the provision of skilled medical assistance to mothers in childbed is of importance in connection with antenatal mortality. The general health of the mother and external environmental conditions have no direct influence on the death rate at this period of life. The magnitude of the correlation leads to the further conclusion that a great part of the still-birth rate is not to be controlled by improvements in even all of these factors.

The neo-natal death rate is related both to variations in external environment and in the obstetrical assistance available for mothers in childbed. At this state of life, again, the health of the mother has no substantial influence on the death rate. External surroundings and the quality of the obstetrical assistance afforded to the mother are of approximately equal importance in determining these rates; but here again the conclusion is advanced that the greater part of the death rate at this stage of life is beyond human efforts of control.

The post-natal death rate seems to offer the greatest scope for administrative measures. In this case the health of the mother would appear to come first in order of importance, environment also is of some importance, whereas the effects of variations in obstetrical services have now ceased to be reflected on the mortality of infancy.

In isolated rural communities there is a part of the post-natal death rate which could be eliminated by the speedy arrival of skilled medical assistance.

Foreign statistics have been collected and analysed to enquire into the causation of still-births. An obvious defect in these was pointed out, namely, the large proportion of deaths due to unknown causes. A comparison of these figures with those collected from several maternity hospitals has shown that hospital figures give a biassed view of the problem. The proportion of deaths due to causes in which the life of the mother as well as that of the foetus is endangered is greatly magnified, and consequently will produce a too optimistic estimate of the amount of amelioration which will result from increased attention to pregnant and parturient women. The statistics which have been given in this section show that in a really random sample of the population only a small proportion of still-births is the result of causes which can be controlled by this method, and that the chief causes of ante-natal death are developmental defects of the foetus and prematurity.

A short study has been made of certain statistico-anatomical features of the foetus and infant. From this it has been inferred that the foetus is physically in a state of extreme instability, that the conditions which kill in utero are rapidly fatal to the foetus, and that this instability is a somewhat more prominent feature in the male than in the female. As infancy advances, visceral variability decreases steadily, so that it would seem probable that some time is necessary for the foetus to adapt itself to its new mode of existence after birth. This state of unstable equilibrium in early life may provide some reason for the higher mortalities at these ages.

A study of the kinetics of inactivation of foot-and-mouth disease virus type SAT 2 strains revealed that in most cases the rate of neutralization was not rectilinear. Deviations from first-order kinetics observed represented biphasic or parabolic and stepwise reactions. The initial rate was rapid and showed no lag phase or shoulder. The effects of deviations from linearity could be minimized by dilution of antiserum to a suitable extent. Treatment of virus–antibody mixtures with anti-species globulin resulted in enhancement of the rate of neutralization of homologous and heterologous reactions without significantly altering the relation between the two. This treatment also considerably reduced the amount of the persistent fraction. In attempt to disaggregate virus it was observed that sodium dodecyl sulphate inhibited neutralization of virus by specific antiserum.

Shigellosis is endemic in Central Australia and the infections are predominantly due to Shigella flexneri 6, Shigella flexneri 2a and Shigella sonnei. Plasmid profiles of isolates collected from 1985–9, suggested that infections caused by Shigella flexneri 6 were predominantly due to a single clone, whereas those caused by Shigella flexneri 2a and Shigella sonnei were due to several genetically diverse strains, although strains with identical plasmid profiles were found in widely separated geographical areas and in different years.

A case-controlled study of the incidence of heat-labile enterotoxin-producing Escherichia coli (LT+ETEC) and other enteric pathogens in travellers returning to the Sheffield area was conducted from May 1984 to April 1986. LT+ETEC were found in 35 (5.8%) of 600 travellers to developed countries (mainly popular Mediterranean holiday resorts), 36 (11.3%) of 320 travellers to less-developed countries, and 11 (0.9%) of 1282 control patients whose illness was not associated with recent travel abroad. A seasonal peak of LT+ETEC infection was observed only in travellers to developed countries, with infections being significantly commoner in August to October. There was no significant deviation from expected age/sex distribution of LT+ETEC infection. Strains of LT+ETEC from travellers produced more toxin than strains from control patients, strains from travellers to less-developed countries producing most of all.

1. A quantitative theory has been developed for the reactions between antigens and antibodies, applicable in particular to the precipitin reaction. The theory is equally applicable to unspecific precipitations, for instance the reaction between proteins and protein precipitating agents such as nucleic acids, etc.

2. The theory is based on the concept that the antigen-antibody interaction is governed by the same principles as the dissociation of a polybasic acid, HNT, where the antibody corresponds to the hydrogen ion H, and the antigen to the anion T. In their mutual reactions the antigen G is supposed to be polyvalent and the antibody A monovalent: hence the result of the interaction is a mixture of compounds ANG, AN-1G, …, AG.

3. A mathematical deduction is performed starting from the law of mass action, which leads to expressions for the amounts of total precipitate and its constituents in terms of the quantities of antigen and antibody which were mixed and the known equilibria constants.

4. A numerical example is given for a tetravalent antigen. Three cases are represented in graphical forms: the ‘X case’ without inhibition zones, the ‘Y case’ with one and the ‘Z case’ with two inhibition zones. Certain characteristics are described and the significance of the ‘equivalence point’ is analysed.

5. A discussion deals with the irreversibility in relation to the Danysz phenomenon and the dilution effect, and finally the parameters of the theory are more closely considered.

In August 2015 a gastroenteritis outbreak occurred following a wedding. An outbreak investigation was undertaken and a cohort study was conducted using an online survey. Of 140 guests, 134 received the survey and 113 responded (84·3% response rate). Seventy respondents met the case definition of vomiting and/or diarrhoea within 72 h of the wedding (61·9% attack rate). Fifteen exposures were associated with illness; on stratification, all were confounded by the ham hock starter. Multivariable analysis showed a significant association with exposure to ham hock (risk ratio 6·62, 95% confidence interval 2·19–20·03). Eight guests and two catering staff submitted stool samples. All tested positive for norovirus GI-6 infection, including a food handler who had vomiting less than 48 h before the wedding. A single genotype was detected among all samples, suggesting a single source of contamination. The transmission pattern suggested point-source exposure. The most plausible cause of the outbreak was transmission from an infected food handler via contaminated food. This highlights the importance of appropriate exclusions for symptomatic food handlers. Additionally, the food handler's stool sample was submitted 7 days after symptom resolution. The potential for extended viral excretion, and the extremely low infective dose of norovirus, may mean that current exclusion guidelines are not of sufficient duration.

We report key learning from the public health management of the first two confirmed cases of COVID-19 identified in the UK. The first case imported, and the second associated with probable person-to-person transmission within the UK. Contact tracing was complex and fast-moving. Potential exposures for both cases were reviewed, and 52 contacts were identified. No further confirmed COVID-19 cases have been linked epidemiologically to these two cases. As steps are made to enhance contact tracing across the UK, the lessons learned from earlier contact tracing during the country's containment phase are particularly important and timely.

1. Pneumonic Plague epidemics arise as a secondary manifestation of Bubonic Plague.

2. The prevalence of purely septicaemic cases towards the end of the epidemic is significant as a probable explanation of its decline and termination.

3. Subacute or chronic plague may exist among tarabagans (Arctomys bobac) in Mongolia and Siberia, giving rise to periodical outbreaks of bubonic plague in man, as a result of direct infection from injury due to skinning by trappers or marmot eaters.

4. The tarabagan is easily susceptible to pneumonic plague produced by inhalation of B. pestis in spray form.

5. The existence of Pneumonic Plague carriers has been proved in the 1921 Manchurian epidemic.

6. Rooms where patients have died of pneumonic Plague are not particularly dangerous. In all four instances recorded, sick patients travelling in railway carriages have not infected their fellow passengers.

7. Disinfectants and antiseptics, even in strengths above those usually employed, have very little effect upon plague sputum. Alcohol is the surest means of sterilising the hands and gloves in plague work.

8. We have cultivated B. pestis from seemingly dry sputum of partients.

9. The mask is the principal means of personal protection against Pneumonic Plague.

10. The problem of successful vaccination against Pneumonic Plague still awaits solution.