The results of this investigation may be summarised as follows:

1. The qx or cage-age mortality curve of a herd increases rapidly to a maximum and thereafter descends to an approximately constant level which is much above the level of the qx for normal mice of ages within the range of real, physiological, age of animals living in the herds.

2. At the latest ages under observation the principal factor of mortality is still the specific factor, so that the advantage produced by selective mortality and active immunisation is brought to a standstill far above the zero line. Exposure in a herd under the conditions of these experiments will not produce an ultimate population fully resistant to the specific factor of infection.

3. It is probable that a large proportion, perhaps a majority, of the members of a herd become infected early in herd life, and gradually increase their degree of immunity because variations of environmental conditions, so far as these are measured by the general herd mortality, become less and less influential on the ultimate mortality of the exposed to risk the later the point in time chosen for measurement.

4. Study of the form of the age-mortality curve is still proceeding; at present we cannot offer an adequate mathematical description of it which takes due account of the biological factors requiring attention.

5. Quite provisionally, we attribute the difference in time of the maxima of the qx curves of Pasteurella and aertrycke epidemics to a difference of average interval between infection and death.

Since the introduction of toxoid-antitoxin floccules by Glenny & Pope (1927) little has been done to improve their value as an antigen. Watson, Taggart & Shaw (1941) and Barr (1949) confirmed the work of these investigators in showing that heating at 80° C. increased their antigenic value.

It has been shown in this article that about 80% of the toxoid contained in floccules may be recovered if they are dissolved in n/20-NaOH, the alkali being allowed to act for 1 hr. before being neutralized with acid. A purity of between 0·002 and 0·0025 mg. N/Lf is obtained regularly. Such a dissolved floccule solution is a relatively poor antigen when tested in guinea-pigs, but may be rendered highly antigenic when precipitated with alum or adsorbed on AIPO4.

The method has the advantage of simplicity. It would appear that any medium capable of yielding a toxin convertible into flucculable toxoid may be used, thus doing away with cumbersome media-making methods. However, for the best results in terms of both recovery and purity, a high-value, quickly flocculating, toxoid should be used. Further, the choice of antitoxin appears to be important where recovery is concerned. With most of the antitoxins used, recoveries of between 70 and 90 % were got, although with that used, for most of the work recorded here, the recoveries were much lower.

It is not yet established which is the antigen of choice—alum-precipitated (P.D.F.) or AIPO4-adsorbed (A.D.F.) dissolved floccules. A.D.F. has the advantage of ease of preparation and of constant mineral carrier content, but further work is necessary to establish the optimum amount of carrier before a definite answer can be given. A paper on immunity responses in man will be published shortly in the Lancet.

Acute poststreptococcal glomerulonephritis (APSGN) is an inflammatory kidney condition that can complicate Group A streptococcal infections. Two clusters of APSGN occurred recently in New South Wales (NSW), Australia; one in a rural town in December 1999 and the other in a Sydney suburb in January 2000. We interviewed carers of the affected children but found no common exposures except three of the Sydney cases were cousins in frequent contact. To assess the probability of these clusters occurring, we analysed hospital admissions for acute glomerulonephritis, as a proxy for APSGN in younger patients. The incidence of acute glomerulonephritis in NSW during 1989/90–1997/8 in residents aged under 20 years was 2·2/100000/year (95% CI 2·0–2·5). Incidence was highest in children aged 5–9 years, boys and Aboriginal children. We found no evidence for other clusters during that period. The recent clusters highlight the continued potential for unexpected future outbreaks of APSGN.

Although Finland has not experienced a classical swine fever (CSF) epidemic since 1917, the concern about early detection is relevant. The time until detection of CSF on a pig-breeding farm was predicted by simulation, and earlier detection of CSF-infected farms was assessed. Eight to 12 weeks will pass before CSF is detected on a Finnish pig-breeding farm, which resembles detection of the index farm for actual CSF epidemics in Europe. Although notification of suspected CSF on the infected farm accelerates detection the most, interventions aimed at promoting investigations of the general health problem noticed on the farm, or a more comprehensive testing of samples currently arriving from pig farms to the investigating laboratory could shorten detection time by 3 weeks. Results are applicable for further simulation of an event of a CSF epidemic in Finland, and for studying contingency options to promote more rapid detection of infectious diseases of swine not found at present in the country.

The purpose of this study was to examine whether certain salmonella serovars, other than Typhi and Paratyphi, may have an increased ability to enter the human body fluids. The data are based on over 20000 salmonella isolated from humans during 1984–9, among them 436 from extra-intestinal (EI) sources. The mean percentage of EI salmonella isolated in Israel (excluding Typhi and Paratyphi), was 2·1 %. In three serovars: S. 9, 12:1, v:-, Virchow and Saintpaul, the percentage of blood isolations and of EI isolations in general, was high. Among the frequent serovars, ser. Infantis and Hadar had a much lower percentage of EI isolations.

The notification rate of Legionnaires' disease (LD) in France was 2·4/100 000 population in 2010, varying across regions with an increasing rate from west to east. Two sources [mandatory notifications (MN) and a survey of hospital laboratories] were used in a capture–recapture study to estimate the number of LD cases and the sensitivity of the MN system at national and regional levels in 2010. The number of missed cases was estimated using Chapman's method. The estimated sensitivity of MN was 88·5% (95% CI 88·0–89·0) and ranged from 70% to 100% by region. The estimated incidence was 2·7/100 000 population. Sensitivity of the MN system improved since the previous capture–recapture estimates (10% in 1995, 33% in 1998). This study confirmed that the observed west–east gradient is not related to regional notification disparities. Ecological studies should be conducted to better understand the observed spatial variations in LD incidence.

Injecting drug use is often associated with deep-seated infection. In Lothian in Scotland there has been a recent increase in the use of injected new psychoactive substances (NPS). Patients who have injected NPS have presented with Staphylococcus aureus bacteraemia (SAB) with life-threatening complications. We describe a unique case-series of 14 episodes of SAB in ten patients. Users of injected NPS had a significantly higher incidence of endocarditis and cavitating pulmonary lesions (P < 0·05) compared to those who inject only opiates. Cases of SAB in people who inject NPS have contributed to a significant rise in the overall incidence of SAB in people who inject drugs (P < 0·05) which has in turn impacted on the ability of Lothian to meet national targets for reducing the incidence of SAB.

When applicable, case-crossover studies may be quicker and cheaper to complete than case-control studies. Because time is a major issue in outbreak investigations, we evaluated the interest of this design during a continuous common source food-borne outbreak of salmonellosis for which the vehicle (hamburgers) was also implicated by environmental and laboratory investigations. Seventeen of the 35 cases identified in the outbreak were included in the study according to the availability of menu records with detailed information on food consumed at each meal. Food exposures during a 3-day risk period before onset of illness were compared to those of a control time-interval of the same duration that preceded the risk period by two days. Seventy-seven per cent of the cases (13/17) had consumed hamburgers in the three days preceding onset of illness compared with 29% (5/17) during the control period (P=0·04, odds ratio=5, 95% CI: 1·1–46·9). In this investigation the case-crossover design proved to be a useful and efficient alternative to the case-control approach. However, further evaluation of this design in outbreak investigation is needed.

Multilocus enzyme electrophoretic analysis was employed to assess the genetic relatedness of Neisseria gonorrhoeae. Based on the diversity of electromorphs at 9 enzyme loci, 16 electrophoretic types (ETs) were estabilished amongst the 65 isolates. The average number of alleles per enzyme locus was 1·7 and the mean genetic diversity per locus was 0·212. The majority of isolates belonged to either ET1 (32·3%) or ET2 (16·9%). No specific correlation of ETs was seen with serovars as the major types, ETs 1 and 2, were found distributed amongst the various serovars. Major serovars such as Bacjk (IB-1/2) and Bajk (IB-3/6) were each represented by 6 or 8 ETs respectively. Analysis of the genetic relationships of ETs to each other showed some clustering of subgroups that were more closely related than others.

Asymptomatic colonisation of the gastrointestinal tract by carbapenemase-producing Enterobacteriaceae is an important reservoir for transmission, which may precede infection. This retrospective observational case–control study was designed to identify risk factors for developing clinical infection with OXA-48-producing Klebsiella pneumoniae in rectal carriers during hospitalisation. Case patients (n = 76) had carbapenemase-producing K. pneumoniae (CPKP) infection and positive rectal culture for CPKP. Control patients (n = 174) were those with rectal colonisation with CPKP but without CPKP infection. Multivariate analysis identified the presence of a central venous catheter (OR 4·38; 95% CI 2·27–8·42; P = 0·008), the number of transfers between hospital units (OR 1·27; 95% CI (1·06–1·52); P < 0·001) and time at risk (OR 1·02 95% CI 1·01–1·03; P = 0·01) as independent risk factors for CPKP infection in rectal carriers. Awareness of these risk factors may help to identify patients at higher risk of developing CPKP infection.

A dispersal chamber (body box) technique has been used to compare bacterial dispersal from the skin of subjects carrying out a stepping test under controlled conditions while wearing four differing garment systems namely:

(a) basic underwear, cotton ‘blues’ (standard pyjama style jacket and trousers for men or dress for women), ankle socks, boots for men and shoes for women, mask and theatre hat; (b) the basic set covered with a cotton gown; (c) the basic set covered by a gown with a front made from GORE-TEX fabric in which an expanded polytetrafluoroethylene membrane is sandwiched between layers of woven or knitted polyester; (d) the basic set covered with a fully enclosed suit of the same fabric.

A slit sampler was used to measure the number of bacteria liberated in a downward current of air. Six subjects (three female and three male) were studied. Males liberated more bacteria. Covering the ‘blues’ with a cotton gown increased the bacterial count; a gown of the new material reduced the increase by 50%, and the suit cut the dispersal to virtually zero.

Preliminary work suggests that GORE-TEX garments survive laundering better than cotton, and may be cost-effective, but are not yet as comfortable. Research is presently in progress to improve this aspect.

Samonella johannesburg has been prevalent in Hong Kong since 1973 and most strains were resistant to a multiplicity of antibiotics. The susceptibility of S. johannesburg strains isolated in a 5-year period from 1973 to 1977 to eight antimicrobial drugs including ampicillin (A), streptomycin (S), tetracycline (T), chloramphenicol (C), Kanamycin (K), sulphadiazine (Su), trimethoprim (Tm) and gentamicin (G) was tested by the agar dilution method. The proportion of strains resistant to chloramphenicol and ampicillin increased steadily during the 5-year period while those resistant to tetracycline decreased dramatically. This change was associated with an alteration of predominant patterns of antibiotic resistance: strains with the resistance pattern A.S.T.C.K.Su predominated in years 1973, 1974 and 1975 while those with the resistance pattern A.S.C.K.Su predominated in years 1976 and 1977. Analysis of the resistance patterns of S. johannesburg strains isolated from the same cases showed that the resistance pattern A.S.C.K.Su was more stable, and changed less frequently to other patterns of resistance than strains with the resistance pattern A.S.T.C.K.Su. In donor salmonella strains with the A.S.T.C.K.Su resistance pattern, transmissible factorscarrying resistance to A.S.T.C.K.Su in to to, to A.S.T.C.Su, A.T.C.K.Su and to A or T alone were demonstrated. In donor salmonella strains with the A.S.C.K.Su resistance pattern, transmissible factors carrying resistance to A.S.C.K.Su in toto and to A.S.K.Su were detected. The significance of the carriage of such transmissible resistance factors by this Salmonella is briefly discussed.

The haemagglutinin of influenza virus A 2/Hong Kong/1/68 was shown to be markedly different from that of previously isolated A 2 virus strains. No haemagglutination-inhibiting (HI) antibody to A 2/Hong Kong/1/68 virus was detected in serum specimens collected in 1966 from persons aged 60 years or less. In contrast, HI antibody tests with 270 sera collected in 1968 indicated that 9·6% had demonstrable HI antibody at low titres, and 35·2% of 454 postepidemic (1969) sera had demonstrable HI antibody at relatively high titres. Most sera from persons aged 80 years and more collected in 1968 and 1969 had demonstrable HI anti-body to influenza virus A 2/Hong Kong/1/68. No HI antibody to the Hong Kong virus was detected in pre-epidemic sera from children aged 6 months to 3 years, whereas 32 % of postepidemic sera had HI antibody. The acquisition of HI antibody to A 2/Hong Kong/1/68 was not accompanied by an increase hi the incidence or titres of HI antibody to heterotypic A 2 influenza viruses. For sera from children aged 4–11 years, an increase of HI titre to heterotypic A 2 influenza was found.

1. Coramine increases the sensitivity of the central nervous system, particularly the centres situated in the medulla.

2. In large doses, Coramine increases the activity of the spinal cord, producing muscular twitchings of the limbs and body which, when severe, take on the character of convulsive movements.

3. There is a wide margin of safety between the therapeutic and lethal doses.

4. Lethal doses produce convulsions and respiratory failure owing to the involvement of the muscles of respiration.

5. Coramine acts as a powerful respiratory stimulant and is able to over-come the depressant effects of morphine on the respiratory centre in the medulla.

6. Small doses of Coramine raise the blood pressure which is due to a peripheral vasoconstriction. This is partly due to a stimulating effect of the drug on the medulla and to some extent to a peripheral action on either the vasoconstrictor nerves or the arterial muscle. Slightly larger but moderate doses sometimes cause a primary relaxation of the arterioles lasting a few seconds, which may cause a small short-lived fall in blood pressure which is never serious in the normal animal. The rise in blood pressure may last ¼–2 hr., according to the dosage employed.

7. Small amounts of Coramine may increase the amplitude and stroke volume of the heart. This effect was never constant. Larger but moderate doses always produced a diminution in cardiac stroke volume with a decrease in cardiac output. The same effect is seen when large doses are employed. This appears to be the cause of the prolonged lowering of the blood pressure following the administration of large doses of Coramine.

8. Coramine dilates the coronary vessels of the myocardium producing an increase in coronary flow.

9. Coramine lowers the pressure in the right auricle of the heart and the pulmonary artery.

10. Coramine has no effect upon intestinal movements except, when large doses are employed, it causes a slight diminution in the amplitude of the movements with a small increase in muscular tone.

Infant mice were used for the evaluation of the efficacy of bismuth subaslicylate (BSS) in the prevention the growth of Campylobacter jejuni in the intestine. The MIC90 of ten C. jejuni strains was 900 μg/ml. Of three dosage regimens tested, continuous treatment before and after the bacterial challenge, mimicking the way BSS is used in the prevention of traveller's diarrhoea, was the most effective. Growth inhibition was dose dependent; the high dose of 2000 μg per day was more effective than 300 μg per day. After cessation of treatment, campylobacter counts increased to the same level as in the control animals.

Klebsiella vaccine was prepared from strains of Klebsiella aerogenes with capsular types Kl, K36, K44 and K Cross (a type which cross-reacts in vitro with sera from many klebsiella capsular types). The vaccine was extracted by dialysis and ultrafiltration from capsular material released during growth of the bacteria in a five-day batch culture.

Mice given one dose of vaccine from K1a (l·0 μg/mouse) survived lethal intraperitoneal challenge of 11/11 homologous klebsiella strains four days after vaccination; 14 days after vaccination protection against the same challenge strains had declined to 5/11 strains. Vaccines from Kla, b, c, K3G, K44 and K Cross induced homologous protection and protected mice against different ranges of heterologous klebsiella capsular types.

The protective response of the mice was greatly enhanced by administering three doses of the vaccines. Vaccines from Kl, K36, K44 and K Cross protected mice against 14/20, 11/20, 10/20 and 9/20 homologous and heterologous klebsiella challenge strains respectively.

None of the klebsiella vaccines was toxic for mice at the immunizing dose (l·0 μg/mouse). Vaccine from K36 was the most lethal, killing mice at 103 immunizing doses. The least toxic vaccine was from K44, which killed mice at 104 immunizing doses.

One-hundred and twenty-one isolates of Salmonella enterica serotype Montevideo, representing different biotypes and incidents of infection detected in the UK between 1977 and 1995, were analysed by EcoRI ribotyping, PvuII ribotyping and IS200 fingerprinting. Among the isolates examined, 7 EcoRI ribotypes, 5 PvuII ribotypes and 55 IS200 profile types were recognized and 4 arbitrary groups defined. All 33 isolates of biotype 2d belonged to EcoRI/PvuII ribotype 1/1 and IS200 lineage A and comprised Group I. The other 88 isolates of biotype 10di and its variants were assigned to Groups II–IV. All 27 isolates in Group II were of EcoRI/PvuII ribotype 2/2 and IS200 lineage B. Among the 43 isolates in Group III, 42 of which were of EcoRI/PvuII ribotype 3/3, IS200 analysis identified 38 profiles in lineages C–I. Six EcoRI/PvuII ribotypes and 8 IS200 profiles, mostly in lineages C–E, were recognized among the 18 isolates in Group IV. The combined use of biotyping and ribotyping, and to some extent IS200 profiling, has enhanced our understanding of the clonal structure of serotype Montevideo and provides a basis for further study.

Blastocystis is a protist of controversial pathogenicity inhabiting the gut of humans and other animals. Despite a century of intense study, understanding of the epidemiology of Blastocystis remains fragmentary. Here, we aimed to explore its prevalence, stability of colonisation and association with various factors in a rural elementary school in northern Thailand. One hundred and forty faecal samples were collected from 104 children at two time points (tp) 105 days apart. For tp2, samples were also obtained from 15 animals residing on campus and seven water locations. Prevalence in children was 67% at tp1 and 89% at tp2, 63% in chickens, 86% in pigs, and 57% in water. Ten STs were identified, two of which were shared between humans and animals, one between animals and water, and three between humans and water. Eighteen children (out of 36) carried the same ST over both time points, indicating stable colonisation. Presence of Blastocystis (or ST) was not associated with body mass index, ethnicity, birth delivery mode, or milk source as an infant. This study advances understanding of Blastocystis prevalence in an understudied age group, the role of the environment in transmission, and the ability of specific STs to stably colonise children.

Pathogen burden is a construct developed to assess the cumulative effects of multiple, persistent pathogens on morbidity and mortality. Despite the likely biological wear and tear on multiple body systems caused by persistent infections, few studies have examined the impact of total pathogen burden on such outcomes and specifically on preclinical markers of dysfunction. Using data from two waves of the National Health and Nutrition Examination Survey, we compared three alternative methods for measuring pathogen burden, composed of mainly persistent viral infections, using a cumulative deficits index (CDI) as an outcome: single pathogen associations, a pathogen burden summary score and latent class analyses. We found significant heterogeneity in the distribution of the CDI by age, sex, race/ethnicity and education. There was an association between pathogen burden and the CDI by all three metrics. The latent class classification of pathogen burden showed particularly strong associations with the CDI; these associations remained after controlling for age, sex, body mass index, smoking, race/ethnicity and education. Our results suggest that pathogen burden may influence early clinical indicators of poor health as measured by the CDI. Our results are salient since we were able to detect these associations in a relatively young population. These findings suggest that reducing pathogen burden and the specific pathogens that drive the CDI may provide a target for preventing the early development of age-related physiological changes.

Our purpose was to determine the effectiveness and harms of vaccination in patients with any sexual history to prevent the prevalence of papillomavirus infection. A search strategy was conducted in the MEDLINE, CENTRAL, EMBASE and LILACS databases. Searches were also conducted in other databases and unpublished literature. The risk of bias was evaluated with the Cochrane Collaboration's tool. Analysis of fixed effects was conducted. The primary outcome was the infection by any and each human papillomavirus (HPV) genotype, serious adverse effects and short-term adverse effects. The measure of the effect was the risk difference (RD) with a 95% confidence interval (CI). The planned interventions were bivalent vaccine/tetravalent/nonavalent vs. placebo/no intervention/other vaccines. We included 29 studies described in 35 publications. Bivalent HPV vaccine offers protection against HPV16 (RD −0.05, 95% CI −0.098 to −0.0032), HPV18 (RD −0.03, 95% CI −0.062 to −0.0004) and HPV16/18 genotypes (RD of −0.1, 95% CI −0.16 to −0.04). On the other side, tetravalent HPV vaccine offered protection against HPV6 (RD of −0.0500, 95% CI −0.0963 to −0.0230), HPV11 (RD −0.0198, 95% CI −0.0310 to −0.0085). Also, against HPV16 (RD of −0.0608, 95% CI −0.1126 to −0.0091) and HPV18 (RD of −0.0200, 95% CI −0.0408 to −0.0123). There was a reduction in the prevalence of HPV16, 18 and 16/18 genotypes when applying the bivalent vaccine, with no increase in adverse effects. Regarding the tetravalent vaccine, we found a reduction in the prevalence of HPV6, 11, 16 and 18 genotypes, with no increase in adverse effects.