Natural immunity to Haemophilus influenzae type b (Hib) invasive disease is based on antibodies arising in response to encounters with Hib or cross-reactive (CR) bacteria. The relative importance of Hib and CR contacts is unknown. We applied a statistical model to estimate the total rate of immunizing infections of Hib and CR prior to wide-scale vaccinations in Finland and the UK. The average rates of these contacts were 0.7 and 1.2 per year per child in Finland and the UK, respectively. Using a rough estimate of 0.1 Hib acquisitions per year per child in the UK based on carriage rates, the proportion of Hib among all immunizing contacts was in the order of 10%, suggesting that CR bacteria have a major role. In general, varying frequency of CR contacts may explain some differences in the pre-vaccination incidence and age-distribution of invasive disease in different countries.

In response to an alert due to epidemic gastroenteritis in children in a kindergarten, an outbreak investigation was carried out in a Portuguese municipality. The objectives were to establish an aetiological diagnosis, assess vaccine efficacy if possible, and to take corrective measures if necessary. The warden at the kindergarten was interviewed, and we visited the premises. The overall attack rate was 11·4% and most cases were mild. Stool samples from three symptomatic children were collected and screened for the presence of noroviruses, rotaviruses and adenoviruses. High vaccination coverage against rotaviruses was recorded in children aged <2 years. We initially thought that noroviruses and rotaviruses were more likely to have been the aetiological cause of the disease, but the outbreak was caused by infection with adenovirus 41. These viruses should not be overlooked in the laboratory protocol in the study of acute gastroenteritis outbreaks.

Despite a long history of dog-transmitted human rabies outbreaks in Liberia, West Africa, no reports exist of molecular characterisation of the causative lyssaviruses. This study investigated Rabies lyssavirus (RABV) strains isolated at the dog–human interface in Monrovia, Liberia 2016 and 2017, by reverse transcription polymerase chain reaction, using primers specific for the nucleoprotein (N) gene. Out of 20 specimens (19 dog brain samples and one human saliva) tested as suspected rabies cases, three (15%) were positive. Purified amplicons from all three positive specimens were sequenced in both forward and reverse directions. Phylogenetic analysis was conducted in MEGA7 and PhyML3 to determine their relationship with RABV sequences accessioned in NCBI GenBank. The first of three RABV strains detected clustered with China lineage 2 RABVs of dogs (99% homology to KU963489 and DQ666322). The second strain segregated with Africa lineage 2 RABVs also of dog origin, and the third strain segregated with Africa lineage 3 RABVs of Southern Africa viverrids. Our results show a transcontinental strain of rabies virus co-circulating with Africa lineages in post-conflict Liberia. This finding should stimulate more effective sub-regional planning and execution of one-health actions, towards stepwise surveillance and elimination of rabies in West Africa by 2030.

Cervical cancer is the second most frequent cancer in women in French Guiana. Studies have shown that populations living in the remote areas of the interior have early sexual debut and that multiple sexual partnerships are common. The objective of the present study was thus to determine the prevalence of human papillomavirus (HPV) infection in these areas. A study was conducted in women aged 20–65 years with previous sexual activity. Women were included on a voluntary basis after using local media and leaders to inform them of the visit of the team. HPV infection was defined by the detection of HPV DNA using the Greiner Bio-One kit. In addition to HPV testing cytology was performed. The overall age-standardized prevalence rate was 35%. There was a U-shaped evolution of HPV prevalence by age with women aged >50 years at highest risk for HPV, followed by the 20–29 years group. Twenty-seven percent of women with a positive HPV test had normal cytology. Given the high incidence of cervical cancer in French Guiana and the high prevalence of HPV infections the present results re-emphasize the need for screening for cervical cancer in these remote areas. Vaccination against HPV, preferably with a nonavalent vaccine, also seems an important prevention measure. However, in this region where a large portion of the population has no health insurance, this still represents a challenge.

In 2013–2014, the Public Health Agency of Sweden developed a web-based participatory surveillance system, Hӓlsorapport, based on a random sample of individuals reporting symptoms weekly online, to estimate the community incidence of self-reported acute gastrointestinal (AGI), acute respiratory (ARI) and influenza-like (ILI) illnesses and their severity. We evaluated Hӓlsorapport's acceptability, completeness, representativeness and its data correlation with other surveillance data. We calculated response proportions and Spearman correlation coefficients (r) between (i) incidence of illnesses in Hӓlsorapport and (ii) proportions of specific search terms to medical-advice website and reasons for calling a medical advice hotline. Of 34 748 invitees, 3245 (9·3%) joined the cohort. Participants answered 81% (139 013) of the weekly questionnaires and 90% (16 351) of follow-up questionnaires. AGI incidence correlated with searches on winter-vomiting disease [r = 0·81, 95% confidence interval (CI) 0·69–0·89], and ARI incidence correlated with searches on cough (r = 0·77, 95% CI 0·62–0·86). ILI incidence correlated with the web query-based estimated incidence of ILI patients consulting physicians (r = 0·63, 95% CI 0·42–0·77). The high response to different questionnaires and the correlation with other syndromic surveillance systems suggest that Hӓlsorapport offers a reasonable representation of AGI, ARI and ILI patterns in the community and can complement traditional and syndromic surveillance systems to estimate their burden in the community.

To understand the dynamics of transmission of Shiga toxin-producing Escherichia coli O157:H7 (STEC O157) in beef calves, serum samples were obtained from calves in a beef cow-calf herd approximately every 6 weeks from birth until weaning for three consecutive years. The presence of specific anti-O157 antibodies in these serum samples was detected using a blocking ELISA assay incorporating an anti-O157 monoclonal antibody. Using seroconversion data, the basic reproduction ratio (R0) was estimated for each of the three years as well as in aggregate using both deterministic and Martingale methods. R0 for STEC O157 infection in range beef calves by deterministic methods varied from 2·9–5·6, with an average of 4·3 (95% CI 2·8–5·9). Martingale estimates of R0 ranged from 3·5–7·4, or 5·3 (95% CI 3·9–6·6), for data from all three years. Given the above estimate of R0, it is predicted that 65–86% of a herd of calves must be effectively vaccinated, or must be rendered non-susceptible through other means, to eliminate STEC O157 infection from a herd.

Isolation rates in Canada of Salmonella enterica serovar Typhi increased from 0·29 to 0·55 isolations/100 000 population during 2000–2006. Although no ciprofloxacin resistance was detected, nalidixic acid resistance increased from 41% to 80%. Multidrug-resistant S. Typhi represented 18% of the strains tested. Pulsed-field gel electrophoresis (PFGE) analysis of 222 isolates resulted in 91 distinct patterns clustering into four major genetic similarity groups. The five most frequently occurring PFGE patterns accounted for 46% of the isolates. Drug-resistant isolates predominantly occurred in one PFGE similarity group. There were 39 phage types identified in 826 isolates analysed with 60% described by five phage types; 134 were untypable. The phage types associated with multidrug resistance were phage types 53, B1, D1, E1, E9, G3 and M1. Improved integration of epidemiological and laboratory case data will facilitate the protection of public health in Canada during an era of increasing travel and globalization.

Penicillin-resistant Streptococcus pneumoniae (PRSP) is widespread all over the world, including countries previously free of PRSP. This study was undertaken to determine the prevalence, the common serotypes and the clonality of PRSP isolated over a period of 1 year, from various clinical samples from three major hospitals in Kuwait. Strains were identified by standard methods and their antibiotic susceptibility was determined by the agar dilution method. The clonality of the isolates was determined by repetitive extragenic palindromic sequence–polymerase chain reaction (REP–PCR) genomic profiling and pulsed field gel electrophoresis (PFGE). Serotyping was done by Quellung reaction using specific antisera. We found that 55% of the S. pneumoniae were resistant to penicillin (46% and 9% exhibited intermediate and full resistance, respectively). Nearly 41% were resistant to sulfamethoxazole-trimethoprim, 9% to cefotaxime and ceftriaxone, 15% to amoxycillin-clavulanate, 17% to cefuroxime, 77% to cefaclor, and 14% to clindamycin. The commonest serotypes among the PRSPs were 6A, 6B, 14, 19F, 23F and nontypable. PFGE and REP–PCR patterns showed a large diversity of genetic clones of the PRSP. Serotypes 6B, 14, 19F and 23F were more clonally related than the others. Our data showed that the prevalence of PRSP was high, the serotypes were diversified and different genetic clones make up the population of circulating PRSP in Kuwait.

The aerosol survivals in air and nitrogen of radiation sensitive and resistant mutants of Escherichia coli B have been determined with logarithmic and resting phase bacteria. No consistent correlation was found between radiation sensitivity and aerosol sensitivity in the strains tested. Hence, the phenotypes Fil Her Exr, which determine sensitivity to radiation, do not influence aerosol survival, i.e. these known mechanisms which repair radiation-induced damage do not operate in aerosol stressed E. coli. In all cases the survival in air was less than that in nitrogen particularly so for E. coli Bs-1. The effect is explained in terms of a toxic action of oxygen. Comparison of survival of log and resting phase bacteria show that log phase cells are less aerosol stable than are resting phase cells. The ability to synthesize DNA in bacteria collected from the aerosol was less than in control unstressed bacteria, and this effect was independent of the presence of oxygen. Reduced ability to synthesize DNA could have been caused by reduced metabolic activity. It is shown that two different death mechanisms occur simultaneously in aerosols at low relative humidity. One mechanism is oxygen dependent and the other oxygen independent. The former was not through a decrease in metabolic activity, whereas the latter could be.

The injection of the small amount of diphtheria toxin used in the Schick test may act as a secondary stimulus.

A Schick test may therefore cause a great and rapid increase in the immunity of the animals tested.

Examples are quoted of six rabbits and twelve guinea-pigs in Tables II to VII.

2. A fraction of a Schick dose may act as a secondary stimulus. Rabbit G 23 quoted in Table IV, injected with 1/10 of a Schick dose, showed an immunity response, the antitoxic content of its blood rising from 1/50 to nearly 1/10 unit per c.c. in six days.

3. The action of a Schick dose as a secondary stimulus may cause an animal to give a negative reaction when tested seven days or more after the first positive reaction.

This is illustrated by rabbits G 7 in Table III, G 31 in Table II, G 32 and G 34 in Table V and four guinea-pigs in Table VI.

4. The antigenic value of a Schick dose of toxin as a secondary stimulus may be as high as that of a reasonable dose of a toxin-antitoxin mixture suitable for human immunisation. Examples are given comparing the results of the injection of a Schick dose of toxin and of a toxin-antitoxin mixture in the same rabbit in Table III, in different rabbits, G 20 and G 22 in Table IV and reference is made to the companion rabbits to those quoted in Table V.

5. The antigenic value of a Schick dose as a secondary stimulus can be demonstrated:

A. In animals which have not produced a detectable quantity of antitoxin (that is less than 1/2000 of a unit per c.c.) as the result of a primary stimulus.

See both rabbits in Table II, rabbit G 20 in Table IV, both rabbits in Table V, and guinea-pig FF 19. v in Table VII. The four guinea-pigs in Table VI probably come under the same heading.

B. In animals whose actively produced antitoxin has fallen below a de tectable level.

See rabbit G 7 in Table III.

(These results add further confirmation to the phenomenon reported in the paper “Active immunity to diphtheria in the absence of detectable antitoxin” (Glenny and Allen, 1922).

6. A Schick dose of toxin which gives a positive reaction may, by acting as a secondary stimulus, produce a rapid increase in the antitoxic value of animals already containing some actively produced antitoxin.

See guinea-pig LL 17. vi in Table VII.

7. A Schick dose of toxin which causes no reaction may, by acting as a secondary stimulus, produce a rapid increase in the antitoxic value of animals already containing some actively produced antitoxin.

See guinea-pigs in Table VII.

8. A Schick dose of toxin may fail as a secondary stimulus if the antitoxic content at the time of injection is comparatively high.

See rabbit G 21 in Table IV.

1. An investigation of ninety-eight cases of aseptic meningitis admitted to hospital resulted in the isolation of ECHO virus Type 6 from fifty-one patients.

2. The viruses were cultivated in both human embryonic skin-muscle tissue and human amniotic cell tissue. The latter was found to be more satisfactory.

3. Forty-eight strains were isolated from the stools of patients, six from the cerebrospinal fluid and four from throat-washings.

4. Serological examination of patients from whom the virus was isolated showed that a significant proportion of patients exhibited a specific antibody response. This included three out of six patients with the virus in their cerebrospinal fluid.

5. The clinical picture of aseptic meningitis from which cases ECHO virus was isolated cannot be distinguished from that caused by other known viruses.

6. The evidence presented supports the claim that ECHO virus Type 6 is one of the causes of aseptic meningitis.

Grateful appreciation is acknowledged to Prof. P. M. Holst (Oslo), Prof. Johs. Böe (Bergen), Dr B. Helland-Hanssen (Molde), Dr O. Römcke (Drammen), Dr R. Tingstad (Namsos), and Dr A. H. Brinchmann (Bærum), for providing specimens and case records. I am also grateful to Mrs B. Zapffe and Mrs L. Kohmann for expert technical assistance.

1. Highly milled parboiled rice was found to be rich in the antineuritic vitamin B1, while roughly milled raw rice was deficient. In estimating the content of vitamin B1 the method of Chick and Roscoe was used.

2. Exact comparison was made of the vitamin B1 potency of two samples of rice, the one raw, the other parboiled, after similar degrees of milling. The vitamin value of the unmilled samples was equal, but when each was highly milled to an equal degree, as judged by weight of polishings removed in a hand rice mill, the parboiled sample retained the vitamin while the raw sample did not.

3. Polishings from parboiled rice were found to contain less vitamin B1 than those from raw rice.

4. Parboiled rice contains more P2O5 than raw rice milled to the same degree.

5. It is probable that when rice is steamed in the process of parboiling, the vitamin B1 and some of the phosphate contained in the germ and pericarp diffuse through the endosperm.

6. The P2O5 content of raw rice is a good index of vitamin B1 value, but in parboiled rice a low percentage of phosphate is compatible with the presence of the vitamin.

Thanks are due to Miss L. M. B. Patterson who kindly made the phosphate estimations recorded in the paper. I am indebted to the Director of Agriculture, British Guiana, for a number of rice samples. The rice mill used was kindly lent by Jackson and Son, 30, Mincing Lane, E.C. 3. I am grateful to Miss Chick for her continued interest in these experiments.

One of the fundamental features of Ehrlich's method of standardising diphtheria antitoxic serum is the recognition of the so-called Lo and L+ limits, the L+ dose being the quantity of a toxin which when mixed with one unit of antitoxin and injected subcutaneously into a guinea-pig leaves sufficient excess of toxin free to cause the death of the animal about the fifth day after injection, the Lo dose being the largest quantity which when similarly mixed with one unit of antitoxin fails to produce a local reaction. In the region between the two doses, the so-called “ Differential-Region ” of Ehrlich, one can obtain a series of mixtures which, while they kill the guinea-pig later than the fifth day or not at all, cause local reactions of varying severity increasing as the L+ limit is reached.

1. When toxic filtrates derived from coagulase-positive staphylococci including twelve food-poisoning strains, thirty pyogenic strains of human and twelve of animal origin were applied to isolated rabbit gut in vitro, two characteristic responses were obtained, associated with the α- and β-lytic titres respectively, and abolished by the corresponding antisera. They were independent of the origin of the strains.

2. A non-specific response is also described which is thought to be due to the peptone in the medium.

3. No effect that could be attributed to enterotoxin, such as was reported by Anderson (1953), was observed and it is concluded that isolated rabbit gut is unlikely to prove a useful indicator of its presence.

We are indebted to Drs Mary Barber, J. M. Talbot, F. C. O. Valentine and H. Williams Smith for strains; to Dr R. E. O. Williams for strains and bacteriophage typing; to Prof. C. E. Dolman and Messrs Burroughs Wellcome for strains and antisera; to Mr F. Crisp of the Division of Experimental Biology, National Institute for Medical Research, Medical Research Council, for rabbit gut; and Dr H. O. Schild for continued interest and practical help.

Antisera prepared against vaccinia and cowpox viruses were absorbed with purified suspensions of vaccinia virus, red cowpox and white cowpox viruses. They were then tested for their ability to neutralize the viruses, and to precipitate the virus soluble antigens.

The results showed that some virus specific antigens were not virus surface components and that some components were present on the surface of all three viruses. However, certain components were detected on the surface of vaccinia virus but not on the surface of cowpox virus, and vice versa. Some evidence for the existence of a vaccinia-specific surface component was also obtained.

Comparisons between results of cross-neutralization tests and immunodiffusion tests on the absorbed sera indicated that antibody to a number of antigens, including the classical LS, and the cowpox-specific d antigen play no part in the process of poxvirus neutralization.

Cationic proteins isolated from the cells in bulk milk samples were shown to inhibit the growth of two pathogenic strains of staphylococci and also Streptococcus agalactiae S 13. Polyacrylamide gel disk electrophoresis studies on these proteins revealed the presence of at least 9 components some of which had isoelectric pH's between 7·0 and 9·0. Trace amounts of the isolated protein had isoelectric pH's greater than 9·0. Staphylococci incubated with milk-cell cationic proteins absorbed the protein, thereby allowing the organism to be stained with the anionic dye Fast Green FCF. Protein-treated staphylococci in isotonic solutions autoagglutinated. This autoagglutination was more marked in hypo- and hypertonic solutions. Lysozyme was not demonstrated in the isolated protein fractions in assays involving incubation with Micrococcus lysodeikticus for 90 min. The antimicrobial activity of the cationic proteins isolated from the bulk milk samples was not destroyed after heating to temperatures up to 70° C for 30 min., whereas at higher temperatures the activity diminished and was almost completely lost at 100° C.

The findings are described of a combined clinical, bacteriological and virological study which included all children admitted to the City Hospital, Edinburgh, with acute respiratory infection and whooping cough during the winters 1961–62 and 1962–63. During the first winter 131 cases aged 0–12 years and in the second winter 133 aged 0–6 years were examined. The respiratory illnesses were divisible into upper respiratory tract infection, bronchitis, pneumonia, and whooping cough; many of the cases of whooping cough had respiratory complications with bronchitis or pneumonia.

Paired sera, a throat swab and a faecal specimen were taken from each child and investigated vircdogically. Over both winters the highest total virus isolation rate was found in the group suffering from upper respiratory disease. Approximately two-thirds of the total number of patients from whom virus was isolated and from whom both acute and convalescent sera were available gave a serological response to the homologous virus; the highest proportion of these patients occurred in the pneumonia and URTI groups. The groups of viruses associated with a fourfold or greater rise in antibodies occurred in the following proportions of the cases: myxovirus 9 %; adeno virus 7 %; entero virus 4 %; herpes simplex 3 %.

Bacterial pathogens were isolated from 37 % of patients in 1961–62 and from 49 % in 1962–63, Staph. pyogenes being the most common pathogen. Isolation of pneumococci was facilitated during the second year by the examination of a nasal swab. Pre-admission chemotherapy did not significantly alter the bacterial isolation rates. Agglutination studies were carried out on forty clinical cases of whooping cough admitted during the two winters and thirty-two showed significant stable titres to Bordetella pertussis; only 9 (18 %) of these cases gave a history of prophylactic immunization.

A third of the patients had neither bacterial nor viral pathogens.

The findings in this survey illustrate the need for further intensive virological and bacteriological studies of acute respiratory infections in early childhood.

This study investigated the carriage of antimicrobial resistant Haemophilus influenzae in 582 healthy children attending kindergarten or elementary school at four intervals over a 9-month period in Seoul, Korea. Diverse colonization patterns and a lower level of long-term persistent carriage by H. influenzae status were evident in this study. Colonizing H. influenzae isolates showed a high rate of resistance to β-lactams including ampicillin (51·9%), cefaclor (52·1%), and amoxicillin/clavulanate (16·3%). Based on the ampicillin resistance mechanism, H. influenzae isolates were categorized as β-lactamase-negative, ampicillin-susceptible (BLNAS) (48·1%), β-lactamase-positive, ampicillin-resistant (BLPAR) (22·6%), β-lactamase-negative, ampicillin-resistant (BLNAR) (22·8%), and β-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains (6·5%). This study provides the first evidence of a high prevalence (22·8%) of BLNAR strains of H. influenzae nasal carriage in healthy children attending kindergarten or the first 2 years of elementary school in Korea. The high carriage of these resistant strains in overcrowded urban settings may create reservoirs for development of H. influenzae-resistant strains.

Truncated models are indirect methods to estimate the size of a hidden population which, in contrast to the capture–recapture method, can be used on a single information source. We estimated the coverage of a tuberculosis screening programme among illicit drug users and homeless persons with a mobile digital X-ray unit between 1 January 2003 and 31 December 2005 in Rotterdam, The Netherlands, using truncated models. The screening programme reached about two-third of the estimated target population at least once annually. The intended coverage (at least two chest X-rays per person per year) was about 23%. We conclude that simple truncated models can be used relatively easily on available single-source routine data to estimate the size of a population of illicit drug users and homeless persons. We assumed that the most likely overall bias in this study would be overestimation and therefore the coverage of the targeted mobile tuberculosis screening programme would be higher.