It is now twelve years since it first became possible to study plague by modern methods, and yet no conclusion on its aetiology has been reached which has met with general acceptance. Two causes, as it seems to me, have chiefly contributed to this disappoinment. One consists in the appeal which has been persistently made to bacteriology for the lights which in fact are not in its power to shed; the other is neglect of the epidemiological method, or at least failure to apply it effectively. In consequence, a field has been occupied by the bacteriologist which could not be profitably laboured by him. The epidemiologist has not seriously disputed this usurpation of his domain, and for his apparent apathy he has not been without excuses of some weight.

Histoplasma capsulatum was sampled in lungs from 87 migratory Tadarida brasiliensis bats captured in Mexico (n=66) and Argentina (n=21). The fungus was screened by nested-PCR using a sensitive and specific Hcp100 gene fragment. This molecular marker was detected in 81·6% [95% confidence interval (CI) 73·4–89·7] of all bats, representing 71 amplified bat lung DNA samples. Data showed a T. brasiliensis infection rate of 78·8% (95% CI 68·9–88·7) in bats captured in Mexico and of 90·4% (95% CI 75·2–100) in those captured in Argentina. Similarity with the H. capsulatum sequence of a reference strain (G-217B) was observed in 71 Hcp100 sequences, which supports the fungal findings. Based on the neighbour-joining and maximum parsimony Hcp100 sequence analyses, a high level of similarity was found in most Mexican and all Argentinean bat lung samples. Despite the fact that 81·6% of the infections were molecularly evidenced, only three H. capsulatum isolates were cultured from all samples tested, suggesting a low fungal burden in lung tissues that did not favour fungal isolation. This study also highlighted the importance of using different tools for the understanding of histoplasmosis epidemiology, since it supports the presence of H. capsulatum in T. brasiliensis migratory bats from Mexico and Argentina, thus contributing new evidence to the knowledge of the environmental distribution of this fungus in the Americas.

In this paper we propose a debate on the role of mathematical models in evaluating control strategies for vector-borne infections. Mathematical models must have their complexity adjusted to their goals, and we have basically two classes of models. At one extreme we have models that are intended to check if our intuition about why a certain phenomenon occurs is correct. At the other extreme, we have models whose goals are to predict future outcomes. These models are necessarily very complex. There are models in between these classes. Here we examine two models, one of each class and study the possible pitfalls that may be incurred. We begin by showing how to simplify the description of a complicated model for a vector-borne infection. Next, we examine one example found in a recent paper that illustrates the dangers of basing control strategies on models without considering their limitations. The model in this paper is of the second class. Following this, we review an interesting paper (a model of the first class) that contains some biological assumptions that are inappropriate for dengue but may apply to other vector-borne infections. In conclusion, we list some misgivings about modelling presented in this paper for debate.

Data were collected on 6578 patients diagnosed with AIDS at 52 clinical centres in 17 European countries during an 11-year period from 1979 to 1989. The centres were divided into four regions, North, Central, Southeast, and Southwest. Differences in the incidence of most AIDS-defining opportunistic infections and malignancies were found. After adjusting for known possible confounders, statistically significant differences between regions remained. Pneumocystis carinii pneumonia (PCP) was more common in Northern Europe, Kaposi's sarcoma and toxoplasmosis in Central Europe, cytomegalovirus retinitis in South-eastern Europe, and extrapulmonary tuberculosis in South-western Europe. These differences we attribute primarily to different degrees of exposure to the respective underlying pathogens. The prevalence of these and other micro-organisms will determine the clinical course of HIV infections in parts of Eastern Europe and elsewhere where the virus now is spreading.

West Nile virus (WNV) infection is an emerging zoonosis that threatens global public health. In this study, a total of 95 bird serum samples from 14 species and 341 horse serum samples were collected from 2008 to 2010 in Shanghai, China. All serum samples were screened initially for WNV-reactive antibodies using a competitive ELISA. The positive samples detected by ELISA were further confirmed using a plaque-reduction neutralization test (PRNT) for WNV and its most closely related flaviviruses in the area to avoid false positives due to cross-reactivity. Five (5·3%) of the bird serum samples and none (0·0%) of the horse serum samples tested positive for WNV antibodies. The findings strongly suggest that some of the birds, specifically the resident birds in China, had been exposed to WNV.

Serological investigations were carried out on 147 patients with Paul—Bunnell positive infectious mononucleosis (IM) from the general population. All possessed antibody to the Epstein—Barr virus (EBV) and 63% showed serological evidence of recent infection. Contacts of 132 patients, 306 in all, were followed serologically; within 6 months of the index cases' illness twenty one contacts developed evidence of EBV infection or re-infection and of these five developed overt IM. The secondary attack rate of EBV infection among susceptible contacts was at least 19%; the corresponding figure for clinically apparent IM was 6%. EBY antibody prevalence among patients' siblings was significantly lower than among age-matched controls, suggesting that cases of IM come from families with a lower than normal previous experience of the virus. Of thirteen patients with persistently Paul—Bunnell negative ‘glandular fever’ four had serological evidence of recent EBV infection and two had probable cytomegalovirus mononucleosis. Recent EBV infection may have been associated with the illnesses of five of the remaining patients.

Echovirus type 11 (echo 11) has been isolated at the virus laboratory of Fairfield Hospital, Melbourne, Australia, in 20 of the 28 years since the laboratory was established. During this time two major epidemics have occurred; the first, in 1971–2 involved 90 patients with aseptic meningitis or respiratory illness. The second began in June 1979 and lasted for 11 months, during which echo 11 was isolated from 174 patients admitted to Fairfield Hospital, other Victorian and Tasmanian hospitals and a children's reception centre. The patients' illnesses included viral meningitis (66%), fever (10%), respiratory infections (7%) and gastroenteritis (2%). One baby died.

Echo 11 was recovered from nasopharyngeal swabs or aspirates, cerebrospinal fluid and faecal specimens and was isolated most frequently in the Borrie cell line. Isolates were readily identified by immune electron microscopy and/or neutralization tests.

1. The total reproductive performance of two groups each of twenty-four mice over a period of one year under two different systems of mating has been recorded.

2. In the first system (monogamous pairs) the male was kept continuously with the female; in 78% of cases the females became pregnant again at post-partum oestrus and were thus subjected for the most part to unbroken intensive breeding.

3. In the second system (polygynous groups) several females were kept with one male and were removed to individual cages for the birth and rearing of the litters and were returned to the male again only after the litter had been weaned.

4. Under the first system 1149 young were successfully reared to weaning in one year by the twenty-four females; under the second system 559 young were weaned during the same period.

5. Mortality of breeding females, litter size, weight of young at weaning, the effect of parity, loss of litters and of young between birth and weaning and the sex-ratio of the young weaned were alike for both methods of mating.

6. The interaction of concurrent gestation and lactation upon the length of the gestation period is discussed, and regression lines showing the relation between the number of young suckled, the number of young in the uterus and the length of the gestation period are given.

My best thanks are due to Dr A. S. Parkes, F.R.S., for advice during the course of the work and for help in the preparation of the manuscript. I should also like to thank Dr C. W. Emmens for the statistical analyses and the calculation of the regression lines.

The action of univalent and bivalent salts on bacteria in affeting the conductivity of thick emulsions of the meningococcus and B. coli demonstrates the important fact, that they alter the conductivity of these germs in the living condition, in a very definite manner. In this alteration, the predominant part is played by the cat-ion.

All monovalent cat-ions, with the exception of the H-ion, such as those of Na, K, Li, Rb, produce a rapid increase in conductivity or a fall in resistance. In its early stages this increase in conductivity is readily reversible in these solutions. If allowed to follow its due course, however, it leads finally to death in about two hours, when the bacterial cells no longer offer any resistance to the passage of the ions. The conductivity of the emulsion then becomes that of the fluid in which the emulsion has been suspended.

Bivalent cat-ions and the H-ion, on the other hand, at first produce a slight fall in conductivity or an increase in resistance, followed, swecondly, by an irreversible increase in conductivity which is slow and gradual resulting finally in death after 48 or more hours. This is shown by the car-ions of Ca, Sr, Ba, and Cd.

In a balanced solution such as sea-water, blood plasma, Ringer's solution, van't Hoff's solution, where a certain quantity of CaCl2 antagonises a larger amount of NaCl and KCl, the conductivity of bacterial emulsions undergoes no change, but remains constant.

Dead in distinction to living bacteria offer little resistance to the passage of ions of a solution. It would seem the relativity high resistance of the bacterial cell is due to some condition present in the living and absent in the dead state.

It has been shown by experiments on animals that the condition of increased conductivity of the cell is coupled with a loss of virulence in the case of some pathogenic bacteria. It is not clear from these experiments if this is due to the actual death of the germs in a monovalent salt solution, or to a detoxicating action of these solutions on the germs. It would seem there is some evidence for believing that the latter takes place, as the lost lethal power returns in the presence of a small trace of Ca. In bivalent salt solutions no loss of toxicity takes place. It has been pointed out that the action of monovalent and bivalent salts on bacteria offers a new explanation of certain experiments with gas gangrene organisms, where it is at present considered that the action of the salts are on the tissues of the animal and not on the bacteria.

Ninety-five patients with recurrent pyogenic cholangitis had a range of specimens taken at laparotomy for bacterial culture. Bacteria were isolated from 68 % of cases. Escherichia coli was the predominant pathogen. Other aerobic and anaerobic intestinal bacteria were also isolated. Liver biopsy, bile and gallstones were the most rewarding specimens for culture. Infection was usually localized, but systemic infection occurred occasionally. The site of infection is probably in the liver parenchyma; however, the route by which intestinal bacteria invade the liver is not known. Sixty per cent of the cases of recurrent pyogenic cholangitis had gallstones and 20% were infected with Clonorchis sinensis.

In a previous communication (1921) experiments have been described showing the effect produced by continuously adding normal mice to a cage, the population of which is infected with bacilli of the group which includes B. gaertner and B. suipestifer. It was seen that under these circumstances the spread of infection progresses in a series of epidemic waves, and that the survival-time of any batch of mice varies according to the period at which they are introduced to the cage. It was further shown that, if such regular and continuous addition of susceptible animals be persisted in over long periods of time, all the micewill eventually succumb, while, if the addition of new individuals be discontinued, the epidemic will eventually subside, leaving a proportion of survivors who may remain in apparently good health over a considerable period.

England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.

Genomic profiles were obtained for 76 strains of Campylobacter jejuni isolated from bacteraemic patients in England and Wales over the period 1981–94. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis using a random cloned DNA probe, and by ribotyping with a PCR-generated C. jejuni 16S ribosomal DNA probe. Phenotypic characterization was achieved by heat-stable (HS) and heat-labile (HL) serogrouping, and Preston phagetyping and biotyping. The blood isolates were genomically heterogenous, with 24 RFLP/16S profiles occurring within the 76 strains. Forty-four percent of isolates belonged to one of three RFLP/16S genotypes, reflecting the patterns seen in faecal isolates, except that genotypes usually associated with the HS 1 antigen were uncommon. The two most prevalent genotypes, characteristic of HS 2 and HS 4 strains, showed similarity by cluster analysis. Further evidence was seen of associations between phenotypic and genotypic characters within some HS serogroups. Chromosomal profiling by RFLP analysis does not indicate that particular genotypes have a predisposition to invade the bloodstream.

This study aimed to explore the spatio-temporal patterns, geographical co-distribution, and socio-ecological drivers of childhood pneumonia and diarrhoea in Queensland. A Bayesian conditional autoregressive model was used to quantify the impacts of socio-ecological factors on both childhood pneumonia and diarrhoea at a postal area level. A distinct seasonality of childhood pneumonia and diarrhoea was found. Childhood pneumonia and diarrhoea were mainly distributed in the northwest of Queensland. Mount Isa city was the high-risk cluster where childhood pneumonia and diarrhoea co-distributed. Emergency department visits (EDVs) for pneumonia increased by 3% per 10-mm increase in monthly average rainfall in wet seasons. By comparison, a 10-mm increase in monthly average rainfall may cause an increase of 4% in EDVs for diarrhoea. Monthly average temperature was negatively associated with EDVs for childhood diarrhoea in wet seasons. Low socioeconomic index for areas (SEIFA) was associated with high EDVs for childhood pneumonia. Future pneumonia and diarrhoea prevention and control measures in Queensland should focus more on Mount Isa.

Viral haemorrhagic disease of rabbits (VHD), a potential biological control for wild rabbits in Australia and New Zealand, escaped from quarantined field trials on Wardang Island and spread to the mainland of Australia in October 1995. This study looked for any evidence of infection or illness in people occupationally exposed to the virus. Two hundred and sixty-nine people were interviewed and 259 blood samples were collected. Exposures to VHD-infected rabbits ranged from nil to very high. No VHD antibodies were detected in any of the 259 sera when tested by VHD competitive enzyme immunoassay, which had been validated with 1013 VHDV-specific antibody negative sera. A questionnaire designed to elicit symptoms of disease in a range of organ systems found no significant differences between illness in those exposed and those not exposed to VHD, nor could an association be found between exposure and subsequent episodes of illness. The findings are consistent with the view that exposure to VHD is not associated with infection or disease in humans.

1. A series of cases of repeated accidental vaccinal infections of vaccinia and vaccinoid types in subjects possessing strong or complete vaccinal immunity, is presented.

2. It is suggested that there is a similarity between such cases and the repeated infections on the hands of farm workers and milkers handling cows naturally infected with cowpox.

3. It is difficult to fit satisfactorily such facts into the framework of the modern theory of vaccinal immunity, but no explanation of the apparent discrepancy can be suggested.

The objectives of this work were (i) geographical analysis of the 2012–2014 outbreak of rabies in Greece using GIS and (ii) comparative analysis of animal cases with data of potential human exposure to rabies together with environmental data, in order to provide information for risk assessment, effective monitoring and control. Most animal cases (40/48) involved red foxes, while domestic animals were also diagnosed with rabies. Overall, 80% of the cases were diagnosed in central northern Greece; 75% of the cases were diagnosed in low altitudes (<343·5 m), within a distance of 1 km from human settlements. Median distance from livestock farms was 201·25 m. Most people potentially exposed to rabies (889/1060) presented with dog bite injuries. Maximum entropy analysis revealed that distance from farms contributed the highest percentage in defining environmental niche profiles for rabid foxes. Oral vaccination programmes were implemented in 24 administrative units of the country during 2013 and 2014, covering a total surface area of ~60 000 km2. Rabies re-occurrence in Greece emphasizes the need for ongoing surveillance in cross-border areas and in areas with intense human activity.

Cryptosporidium and Giardia are intestinal parasites of humans and of many other species of animals. Water constitutes an important route of transmission for human infections in both developed and developing countries. In Poland, contamination of water sources with oocysts/cysts is not routinely monitored and scientific research in this field is scarce. Our aim was to compare the contamination of surface and treated water and thus the success of water treatment processes. Water samples (n=94) of between 30 l (surface water) to over 1000 l for tap water, were taken in the period of 2008–2009 using specially constructed equipment with cartridge filtration (Filta-Max; IDEXX, USA). Immunofluorescent assay, and nested polymerase chain reaction were used for the detection of parasites. Cryptosporidium oocysts were found in 85% of surface water and in 59% of raw (intake) water samples. Oocysts were also detected in treated water (16%) but were absent in samples of swimming pool water. The highest mean number of Cryptosporidium oocysts [geometric mean (GM)=61/10 l] was found in samples of rinsing water. Giardia cysts were observed in 61% of surface water samples, in 6% of raw water and in 19% of treated water, with the highest number of cysts noted in rinsing water samples (GM=70 cysts/10 l). Our study highlights the frequent occurrence of parasites in surface waters in Poland and the effectiveness of water treatment for the removal of parasites from drinking water.

Dengue fever is a disease with increasing incidence, now occurring in some regions which were not previously affected. Ribeirão Preto and São Paulo, municipalities in São Paulo state, Brazil, have been highlighted due to the high dengue incidences especially after 2009 and 2013. Therefore, the current study aims to analyse the temporal behaviour of dengue cases in the both municipalities and forecast the number of disease cases in the out-of-sample period, using time series models, especially SARIMA model. We fitted SARIMA models, which satisfactorily meet the dengue incidence data collected in the municipalities of Ribeirão Preto and São Paulo. However, the out-of-sample forecast confidence intervals are very wide and this fact is usually omitted in several papers. Despite the high variability, health services can use these models in order to anticipate disease scenarios, however, one should interpret with prudence since the magnitude of the epidemic may be underestimated.

A ‘black box’ paradigm has prevailed in which researchers have focused on the association between the total number of pathogens for which individuals are seropositive (i.e. total pathogen burden) and various chronic diseases, while largely ignoring the role that seropositivity for specific combinations of pathogens may play in the aetiology of such outcomes and consequently mortality. We examined the association between total pathogen burden as well as specific pathogen combinations and all-cause mortality in the United States. Data were from individuals aged ⩾25 years tested for cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2 and Helicobacter pylori, with mortality follow-up to 31 December 2006 in the National Health and Nutrition Examination Survey (NHANES) III (N = 6522). We did not observe a statistically significant graded relationship between total pathogen burden level and all-cause mortality. Furthermore, compared to those seronegative for all four pathogens, the greatest statistically significant rate of all-cause mortality was for those CMV+/HSV-2+ (hazard ratio 1·95, 95% confidence interval 1·13–3·35) adjusting for age, gender, race/ethnicity, education level, body mass index (kg/m2) and smoking status. Interventions targeting prevention or treatment of particular pathogens may be more effective for reducing mortality than those focused solely on reducing overall pathogen burden.