Two clusters of confirmed cryptosporidiosis infections were detected in Navarra, Spain, in the summer of 2012, in the context of an increased incidence in the region. Molecular subtyping of Cryptosporidium hominis determined that one cluster, occurring in an urban area, was due to the predominant circulating subtype IbA10G2R2 and the other cluster, with cases occurring in a rural area, was due to a rare subtype IaA18R3. No single exposure was associated with infection, although exposure to certain children's pools was reported by a majority of patients interviewed in each cluster. Genotyping tools were useful in the investigation and could aid investigation of cryptosporidiosis outbreaks in Spain in the future.

Thirty-six encoded isolates of Escherichia coli, 32 of which were of serotype O157. were examined by pyrolysis mass spectrometry (PyMS). Thirty-one of the serotype O157 isolates possessed the flagellar antigen H7 and produced Verocytotoxin (VT). the other isolate serotyped as H45 and was non-toxigenic. Eighteen of the VT-producing E. coli (VTEC) isolates were from sporadic disease in residents of the Northern Region. Standard principal component (PC) and canonical variate (CV) analysis of the data distinguished only the four non-O157 isolates from the remainder which were indistinguishable by this approach. A similarity matrix based on differences between individual CV means distinguished a further ten isolates. The matrix correctly clustered 2 pairs of isolates from siblings and 4 isolates from an affected family. A further 5 clusters of 3 or more isolates and 6 pairs of isolates were defined. These groupings proved to be homogenous for toxin phenotype but occasionally entrained isolates of dissimilar phage type. However, in general, PyMS-derived clustering of apparently sporadic isolates accorded with geographical locations as determined by postcode. PyMS, which is a quick and high volume capacity phenotypic technique. may be a useful addition to existing methods in the investigation of the epidemiology of sporadic VTEC disease.

The outer membrane proteins of 38 Yersinia pestis isolates from all known plague foci of north-east Brazil were analysed by SDS-PAGE. Approximately 20 bands were consistently found in all strains analysed and 11 were selected for comparative studies. Although qualitative differences among the electrophoretic profiles of outer membrane proteins of wild Y. pestis isolates were not observed, quantitative alterations were clearly noted for most of these proteins. No particular quantitative alteration of the electrophoretic profile of outer membrane proteins could be associated with the period of isolation and geographic origin of the isolates. The 64 kDa outer membrane protein was significantly expressed in higher amounts among Y. pestis strains isolated from a recent plague outbreak. The possible use of electrophoretic profiles of outer membrane proteins of wild Y. pestis isolates as a tool for epidemiological studies and for the analysis of virulence determinants is discussed.

An analysis is given of the serological tests performed over a period of 15 months with viral, rickettsial and leptospiral antigens. The analysed material is made up of about 9400 tests performed on 4036 samples of serum obtained from 2430 patients and 536 animals.

The incidence of the various diseases, the distribution of the positive results according to diseases, and the height of the specific titres, as well as the height of the residual titres found in the material, are discussed and analysed in detail.

The procedure for the preliminary screening of the material, as well as the methods used in performing the different serological tests, are described and discussed.

A few examples of possible double infections are quoted, namely atypical virus pneumonia with influenza, and influenza A with B.

An analysis of the results of 1723 tests performed with influenza antigens on 909 samples of sera is presented.

The results obtained from testing about 1000 sera for cold agglutinins and 482 sera for MG agglutinins are discussed in detail.

Some cases of liver affections showed a marked rise in titre both of cold agglutinins and of MG agglutinins.

The serum samples, numbering about 1050, drawn from normal persons or patients suffering from infections other than Q-fever, all gave titres lower than 1/64 when tested with Q-fever antigen, except the sera of four persons who were probably cases of recent inapparent infection.

The geometrical mean of the titres found in sera drawn from acute Q-fever patients between the 29th and 60th days of their illness was 1/355. Of the 500 sera from various animals, 100 from sheep and eight from cows had titres of 1/8 to 1/64 against the Q-fever antigen.

Thirty-four sera have been positive when tested with the soluble antigen of both the epidemic and the murine types of typhus but no serum has given a higher titre with the murine type antigen than with the epidemic type antigen. Of the thirty-four sera tested with both antigens the titres obtained with the epidemic antigen were higher than with the murine antigen in 28.

The results obtained with 417 sera tested with the mumps antigen, and with the 222 sera tested with the lymphocytic choriomeningitis antigen are reported and discussed in detail.

Great individual variation has been observed in the time of appearance and rise and fall of the Paul-Bunell titres. Consequently, it is advised that early and frequent blood samples should be obtained from patients who are suspected to be suffering from infectious mononucleosis. On the basis of the results of 316 Paul-Bunnell tests it is suggested that a titre of 1/20, if preceded or followed by a negative serum sample, should be taken as conclusive evidence of infectious mononucleosis.

3080 human and 164 animal sera have been investigated for the presence of antibodies to various types of leptospirae. In both human and animal sera antibodies have been found most frequently against L. sejroe and L. pomona.

The results of a few tests performed with toxoplasma antigen are mentioned briefly.

We wish to express our gratitude to all our colleagues in Belgrade and other parts of the country who have provided us with information and additional samples of blood when requested, in particular Prof. K. Todorowich of the Infectious Diseases Hospital, Belgrade, and Drs Lj. Vuksich, M. Morelj, B. Arsich, D. Mehl and R. Papo of the Army Medical School, Belgrade.

We wish to thank Dr R. Djorich of the Infectious Diseases Hospital, Belgrade, for the supply of material for testing for atypical virus pneumonia and aseptic meningitis, and Dr Ž. Perishich for help with our cases of infectious mononucleosis. Mrs Martha Milivojevich gave valuable assistance with the complement-fixation tests and with the compilation of material for this report.

Sixty three samples of dairy creamery effluent were examined for the presence of mycobacteria. Thirty two strains were isolated from 27 samples. These were classified as follows: M. fortuitum (13), M. peregrinum (6), M. gordonae (5), M. marianum (scrofulaceum) (4), unidentified (4).

Ten strains, representative of the groups isolated, were tested for their effect on experimental animals. None were pathogenic for guinea pigs or mice but a number produced a minimal amount of skin sensitization in guinea pigs to avian and mammalian tuberculin.

Thirty-three of 72 heroin addicts attending a recognized clinic for drug addition had a history of jaundice, but in only five was the serum positive for hepatitis-associated antigen (HAA) when examined by immunodiffusion, immunoelectro-osmophoresis and complement fixation. Two of these were repeatedly positive over an 8–12 month follow-up period and liver biopsy showed chronic persistent hepatitis. A third later developed acute hepatitis. A study of the injection habits suggested that the present low incidence of HAA and the decrease in number of cases with jaundice was probably related to the provision of free disposable syringes by the clinic since it was opened in 1968.

In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan – a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.

A study was made of the available statistical data bearing on the epidemiology of typhoid in Palestine. It apears from this analysis that:

1. The typhiod epidemicity is not due to a single source such as contaminated water or food. The seasonal prevalence of the disease corresponds with the normal seasonal incidence of typhiod, and is, therefore, in the nature of a contact infection.

2. There is no striking difference in age, sex or race susceptibility. In Tel Aviv the age group 5–14 shows a lower incidence than the corresponding age group in Jerusalem or the higher age group 15–29 in Jerusalem and Tel Aviv. There is, however, no difference in susceptibility between the age group 15–29 in Jerusalem and that in Tel Aviv.

3. From a graphic comparisos, the calculation of the coefficient of correlation of the limited experience (six years), and a comparison of the prevalence of the disease in the immigrant and indigenous population, there appears to be a significant correlation between the net population increment and epidemicity. These results, if confirmed by a longer experience, are in accord with those obtained in the remarkable mice experiments conducted by the English and American investigators.

4. Although, at the beginning, the morbidity and mortality is higher in the immigrant group, there is an evident tendency at equalisation, and in the second year the incidence in the indigenous population is the same as that among the immigrants.

5. The above results indicate the path of control: (a) every immigrant, particularly those between the ages 5–29, should be properly vaccinated against typhoid. By raising the resistance of the new population, the possibility of epidemics among them, and consequently later among the resident population, will be averted; (b) the reduction of endemic typhoid can be brought about by reducing the dosage of the infectious microbes. This can only be brought about by concentration of effort on the early detection and isolation of cases and the vaccination of all contacts. These two measures would seem to offer a prompt and relatively simple solution to the typhoid problem in Palestine.

1. In two areas in the Eastern Counties, Cambridge and Norwich, naso-pharyngeal swabs were taken from 400 individuals, who represented different conditions of health and social circumstances.

The investigation was made at Cambridge between the months of June and October, 1916, and at Norwich during August, 1916.

Owing to the low incidence of cerebro-spinal fever in the two towns during the year 1916 (see p. 249), the general population may be regarded as practically “non-contact” in respect of this disease.

2. As a result of the investigation, strains giving all the cultural and microscopical tests of the meningococcus were obtained as follows:

(a) From 200 swabs taken at Addenbrooke's Hospital during June and July, 1917, mostly from normal people, 30 strains.

(b) From 100 swabs taken at the Norfolk and Norwich Hospital during August, from individuals mostly in impaired health, 27 strains.

(c) From 100 swabs taken in Cambridge during October, from factory employees, who were all in good health and mostly in comfortable circumstances, 37 strains.

3. Such strains were found more often in males of every age group than in females, and in adults more often than in children.

In regard to the influence of health and surroundings, the results of the investigation grouped together show a larger proportion amongst town dwellers than amongst country people and amongst people with impaired health than amongst the healthy.

General conclusions cannot, however, be drawn from these figures because conditions were not always comparable. For instance, the majority of country people were examined in June and July, when positive findings were low.

In examining the employees at a factory, I obtained the strains in a higher proportion from the men working in those shops where air space was more restricted and ventilation less perfectly effected.

4. The 94 strains collected from 400 naso-pharyngeal swabs were tested as regards their agglutinability against certain monovalent sera. These sera were prepared from seven strains of meningococci of cerebrospinal orgin, and from two of the naso-pharyngeal cocci which had been isolated during the course of the investigation. The meningococcal strains used for preparing the sera included strains which had been found identical with others occurring with considerable frequency in cerebrospinal fluid and capable of being grouped in two main groups; they also included strains which differed from these and were apparently rarer; but there is no reason to assume that every variety occurring in the specific disease was represented.

The results of the tests on the above 94 strains may be classified as follows:

(a) 22 gave no agglutination above 1: 100 with any of the sera used.

(b) Two agglutinated well with certain sera, but also agglutinated with normal rabbit serum.

(c) 31 agglutinated up to 1–200 or 1–400 with the sera of a certain group (M I–M IV), and in some instances gave similar agglutination with other sera not belonging to this group.

(d) 39 agglutinated with the sera of the group M I–M IV to the full titre of the homologous strains, while with the sera belonging to other groups good agglutination was not often obtained.

This last group of 39 strains (41 per cent. of all tested) appears to be indistinguishable by simple agglutination tests from the M I–M IV group of cerebro-spinal meningococci. The previous group of 31 (33 per cent. of all tested) shows evidence of serological relationship with meningococci of cerebro-spinal origin, but it is not possible on their agglutination tests alone to give an opinion as to their identity with any meningococcal group.

Agglutination tests as a whole indicated that about 74 per cent. of strains collected on account of their resemblance to the meningococcus in culture, gave evidence of relationship to the meningococcus in virtue of their agglutination reactions with anti-meningococcal sera.

5. In order to determine if the absorption test would corroborate the relationship shown by agglutination, absorption tests were done against a serum prepared by inoculation of a cerebro-spinal strain of meningococcus, M I, with all the strains, culturally and by simple agglutination indistinguishable from pathogenic meningococci, which had been collected from the last 100 swabs (normal factory employees, Cambridge). Nine absorbed the agglutinin as well as the homologous coccus and four absorbed it partially.

Therefore, out of 100 normal people who had not been in contact with a case of cerebro-spinal fever, 9 per cent. were shown to be harbouring organisms in their naso-pharynx which were serologically identical with meningococci of pathological origin (cerebro-spinal fluid) and, in addition, 4 per cent., making 13 per cent. in all, were so closely allied as to be doubtfully distinguishable even by the test for absorption of agglutinin.

Similar results were obtained with strains obtained from Norwich.

The above results were confirmed by testing absorption by these cocci from another serum prepared with another spinal strain of meningococcus possessing properties almost identical with M I. I have not investigated absorption with sera prepared with strains which differ serologically from M I.

6. With regard to those naso-pharyngeal strains which were not identified with cerebro-spinal strains by serological tests (agglutination and absorption), I consider that in view of the great variation in the serological reactions shown by different strains of undoubted meningococci and even by different emulsions of the same strain, it is very difficult, if not impossible, to exclude any such microscopically and culturally typical organisms from the meningococcus group on the basis of serological tests.

Two trials were carried out by 9 and 47 laboratories to evaluate the reproducibility and sensitivity of a standard technique for the isolation of salmonellas from animal feeding stuffs.

The trials involved the examinations of test samples containing known numbers of salmonellas by a buffered peptone water pre-enrichment technique. Statistical analysis of the results of the trials showed that the method was capable of detecting salmonellas in most probable numbers as low as 2·3 per 100 g and that no significant differences in performance were observed between laboratories.

The standard technique described is recommended for the examination of animal feed and conforms to international recommendations.

We recently described a simple model through which we assessed what effect subjecting travellers to a single on-arrival test might have on reducing risk of importing disease cases during simulated outbreaks of coronavirus disease 2019 (COVID-19), influenza, severe acute respiratory syndrome (SARS) and Ebola. We build upon this work to allow for the additional requirement that inbound travellers also undergo a period of self-isolation upon arrival, where upon completion the traveller is again tested for signs of infection prior to admission across the border. Prior results indicated that a single on-arrival test has the potential to detect 9% of travellers infected with COVID-19, compared to 35%, 10% and 3% for travellers infected with influenza, SARS and Ebola, respectively. Our extended model shows that testing administered after a 2-day isolation period could detect up to 41%, 97%, 44% and 15% of COVID-19, influenza, SARS and Ebola infected travellers, respectively. Longer self-isolation periods increase detection rates further, with an 8-day self-isolation period suggesting detection rates of up to 94%, 100%, 98% and 62% for travellers infected with COVID-19, influenza, SARS and Ebola, respectively. These results therefore suggest that testing arrivals after an enforced period of self-isolation may present a reasonable method of protecting against case importation during international outbreaks.

The aim of the study was first, to determine the prevalence of Neisseria meningitidis among the family members living with patients suffering from meningococcal infections, and second, to ascertain the distribution among these family members of strains epidemiologically related to those isolated from patients.

Forty-two family groups were studied and 135 nasopharyngeal samples were taken from family members living with patients.

Twenty family groups were found to contain meningococcal carriers, and of these 20, 13 contained a carrier of the strain that caused the infection (65%). Among the family members who were carriers, the mother and father most frequently yielded the strain which caused the illness.

The serotypes most frequently encountered both in patients and carriers were 2 and 8, as well as nontypable strains.

The polyacrylamide gel electrophoretic patterns (PAGE) most frequently found were II and IV. A notable feature of the study is the high resistance of the strains to sulphadiazine, since more than 90% of the strains found in patients and more than 75% of those from carriers possessed a minimum inhibitory concentration greater than or equal to 10μg/ml.

1. A study of the literature of East Africa on the incidence of plague in field rodents shows that in no single instance has evidence been offered to prove they have any relation to the disease.

2. Recent epizootics in field rats in Kenya are described.

3. The health of house and field rats is discussed, with an account of the work carried out on a septicaemic condition present in field rats.

4. The results of bacteriological examination of 2750 field rats and attempted transmission experiments with 1285 field fleas, both investigations conducted during a period when there was heavy mortality among them, failed to establish the presence of B. pestis.

At the same time, mortality among the Rattus population, proved bacteriologically to have been caused by B. pestis, enabled successful transmissions to be accomplished with fleas from that species.

5. In the absence of any confirmatory bacteriological evidence to prove that epizootics among field rats are caused by B. pestis, and the failure to find natural infection among field fleas, together with the knowledge of their aversion to feed on man and lack of opportunity to develop such tastes, the theories that field rodents and their fleas “are definitely assisting in the perpetuation and spread of plague” or that they “ are possible factors in initial outbreaks of plague” (Thornton, 1930) appear to be fallacious.

6. Plague in Kenya is distinguished by its isolated and sporadic nature, even in endemic areas, and it is not dependent on types of housing or the general hygiene of inhabited areas, but on individual domestic habits. Any individual, neglectful in regard to food, particularly its storage and wastage, is the person responsible for the disease, by offering an unlimited supply of food to a dense rat population and encouraging its survival.

The carriage of Staphylococcus aureus was studied in a group of 28 men living in a totally isolated environment for a year. Initially, nasal, axillary and perineal swabs were taken at weekly intervals, but from week 24 throat swabs were taken from known nasal carriers. Several attempts were made during the study to eradicate S. aureus. Eight subjects consistently carried their own phage type throughout the study, despite the application of antibacterial agents. In three subjects strains were isolated late in the study of a phage type which had either not been isolated before in this study, or had not been found for a prolonged period. Nine of the 12 nasal carriers also yielded S. aureus from the throat. It is apparent that following attempted eradication, S. aureus may seem to disappear, only to reappear some time later; ‘eradication’ in this case would be an erroneous appellation.

1. The virulence of a given strain of B. aertrycke was tested on 54 occasions during the 3-year period, October 1926–October 1929. Each test was made by inoculating intra-peritoneally about 100 viable organisms into 20 parti-coloured mice, usually of 17–23 grm. in weight, drawn at random from the general laboratory stock. The average number of specific deaths caused by this procedure was 12·71 ± 3·39, but very marked deviations were noticeable, varying from a minimum of 5 to a maximum of 20. These deviations occurred without any observable regularity, and appeared to have no definite seasonal relationship. Evidence is brought to suggest that they were chiefly determined not by variations in the dosage or in the virulence of the strain, but by fluctuations in the resistance of the mice.

2. The meaning of the term “resistance” is discussed, and it is suggested that the term “fluctuating immunity” should be used to denote those variations in resistance which occur from time to time, and which are due to alterations in the physiological behaviour of the animal dependent on changing environmental conditions. This fluctuating immunity should be distinguished from innate, inherited, orgenetic immunity on the one hand and from acquired immunity on the other.

3. It is pointed out that the existence of fluctuations from time to time in the susceptibility of animals to infection renders fruitless any attempt to obtain an absolute measure of virulence. The most that can be done is to compare the relative virulence of two or more strains injected simultaneously.

It is suggested that bovine enteroviruses (BEV) are involved in the aetiology of enteric infections, respiratory disease, reproductive disorders and infertility. In this study, bovine faecal samples collected in different Brazilian states were subjected to RNA extraction, reverse transcription-polymerase chain reaction analysis and partial sequencing of the 5′-terminal portion of BEV. One hundred and three samples were tested with an overall positivity of 14.5%. Phylogenetic analysis clustered these BEV Brazilian samples into the Enterovirus F clade. Our results bring an important update of the virus presence in Brazil and contribute to a better understanding of the distribution and characterisation of BEV in cattle.

Prevalence of vancomycin-resistant enterococci (VRE) and use of daptomycin are increasing in Asia. To determine the prevalence of daptomycin non-susceptible enterococci (DNSE) and understand factors associated with reduced daptomycin susceptibility in VRE, we conducted a case-control study in a 1600-bed adult tertiary hospital in Singapore. All VRE isolates from inpatients in 2012 were tested for daptomycin susceptibility. Patients with VRE isolates of daptomycin minimum inhibitory concentration (MIC) ⩾3 µg/ml were classified as daptomycin-reduced susceptible VRE (DRS-VRE) and those with daptomycin MIC <3 µg/ml classified as daptomycin-susceptible VRE (DS-VRE). Medical records were reviewed for clinical and epidemiological data. None of 243 VRE isolates had MIC >4 µg/ml (DNSE). About half (135, 55%) had reduced susceptibility to daptomycin (MIC 3–4 µg/ml). None in the DS-VRE group had prior exposure to daptomycin. After adjusting for age, gender, comorbidity, hospitalization duration, surgical history, indwelling device use, and duration of antibiotic exposure in the prior 3 months, >1 movement between wards [odds ratio (OR) 0·35, 95% confidence interval (CI) 0·16–0·74, P = 0·006] and minocycline resistance (OR 0·45, 95% CI 0·25–0·84, P = 0·011) were independently associated with DRS-VRE. Our study suggests that daptomycin exposure, >1 movement between wards, and resistance to minocycline, were associated with reduced daptomycin susceptibility in VRE.

Using multivariable models, we compared whether there were significant differences between reported outbreak and sporadic cases in terms of their sex, age, and mode and site of disease transmission. We also determined the potential role of administrative, temporal, and spatial factors within these models. We compared a variety of approaches to account for clustering of cases in outbreaks including weighted logistic regression, random effects models, general estimating equations, robust variance estimates, and the random selection of one case from each outbreak. Age and mode of transmission were the only epidemiologically and statistically significant covariates in our final models using the above approaches. Weighing observations in a logistic regression model by the inverse of their outbreak size appeared to be a relatively robust and valid means for modelling these data. Some analytical techniques, designed to account for clustering, had difficulty converging or producing realistic measures of association.

1. The effect of either or both caloric and protein deficiency on the susceptibility of rats and mice to peroral infection with Salmonella typhi murium was studied.

2. Moderate restriction of food intake (80% of normal diet) for a period of 5 weeks was without influence on the infection susceptibility of rats, even when the diet fed was low in protein.

3. Long-term restriction of food intake (10 weeks) led to a marked lowering of the resistance of rats to the infection, there being a direct relation between the magnitude of the intake restriction and the extent of the resulting loss of resistance.

4. The infection resistance of rats was lowered more markedly by a given total restriction of food intake, when the latter was imposed in the form of a gradually reduced ration, than when it was imposed in a uniformly restricted ration. The effect so produced was independent of the protein content of the diet.

5. The effect of gradual food restriction was diminished by gradual supplementation of the diet with non-proteins and was augmented by gradual supplementation of the same diet with protein.

6. In mice kept on a restricted diet loss of resistance to S. typhi murium has been shown to be due to a deficiency of both calories and protein.

In my first report I showed that in the throats of persons not known to have been in contact with cases of cerebro-spinal fever organisms were frequently found which were indistinguishable from meningococci isolated from the cerebro-spinal fluid of persons suffering from that disease.