Terminal complement component deficiency predisposes to meningococcal infection and is inherited in an autosomal co-dominant manner. An Irish family is described, in which 2 of 3 brothers had recurrent meningococcal infection. A novel screening assay was used to investigate for terminal complement deficiency and the 2 affected brothers were found to be completely deficient in the seventh component of complement (C7). Enzyme-linked immunosorbent assay for C7 revealed lower than normal levels in the remaining brother and parents. C7 M/N protein polymorphism allotyping, used to investigate the segregation of the C7 deficiency genes, showed that the apparently complement sufficient brother was heterozygous C7 deficient and a carrier of one of the deficiency genes. Complement screening should be carried out in any individual suffering recurrent meningococcal infection or infection with an uncommon meningococcal serogroup. Identification of complement deficient patients allows the implementation of strategies to prevent recurrent infection.

During a 7½ year period pneumococci were isolated from body fluids of 124 patients at the Radcliffe Infirmary, Oxford – 72 with pneumonia, 26 with meningitis and 26 with other serious infections. Eighty-one (65%) of the patients were over 50, and 33 (27%) were over 70 years old. Of the 124 pneumococcal strains 104 (84%), including 23 (79%) of those from patients who died, belonged to types included in the vaccines successfully used in South Africa and in Papua New Guinea. The relative frequencies of types in the Oxford series and in a larger British series agreed closely with those found in a recent survey of 3644 bacteraemic pneumococcal infections in 10 American cities. Any polyvalent pneumococcal vaccine licensed for use in the United States is thus likely to be relevant to the situation in Britain.

We investigated two sequential outbreaks of severe diarrhoea in two neighbouring villages of Orissa, in 2005. We conducted descriptive and matched case-control studies. The attack rates were 5·6% (n=62) and 5·2% (n=51), respectively, in the first and second villages. One death was reported in the second village (case fatality 2%). We identified that consumption of milk products prepared in the household of the index case [matched odds ratio (mOR) 5·7, 95% confidence interval (CI) 1·7–30] in the first village, and drinking well water in the second village were associated with the illness (mOR 4·7, 95% CI 1·6–19). We isolated Vibrio cholerae El Tor O1 Ogawa from stool samples from both the villages. Mishandling of milk products led to a cholera outbreak in the first village, which led to sewerage contamination of a well and another outbreak in the second village. Environmental contamination should be expected and prevented during cholera outbreaks.

1. A series of experiments is described in whichthe efficacy of vaccination with the vole acid-fast bacillus against tuberculosis in cattle has been studied. Various methods of vaccination have been tried and intravenous inoculation has proved to be the most satisfactory.

2. A single intravenous inoculation of 5 mg. of vole bacilli can raise the resistance of cattle to infection with the bovine bacillus to a high degree, this resistance being evidenced by a complete absence of infection or by a marked diminution in the severity of lesions following exposure to artificial or natural infection.

3. The resistance takes time to develop, reaches its maximum between 6 and 18 months after vaccination and then slowly wanes. The resistance induced by a single inoculation is of insufficient duration in many animals to warrant the practice of single vaccination being used in the field except in special circumstances.

4. Revaccination can intensify resistance provided that it is delayed until the end of the fourth week. A long-term experiment is being carried out to determine if revaccination, in addition to intensifying the initial resistance, can also lengthen its duration.

5. The degree of resistance set up in cattle is correlated with the virulence of the vaccinating strain of vole bacillus for its natural host. This fact will necessitate that any strain used for vaccine purposes will have to be maintained at a high level of virulence by repeated passage through its native host.

6. Care is necessary in the selection of a strain of the vole bacillus for vaccine purposes, for we have encountered one strain, G564, which can set up a fatal infection in calves. Nothing has been noted which would contra-indicate the use of strain LV 285.

7. The histopathological changes pathognomic of tuberculous infection which follow the intravenous inoculation of vole bacilli are mainly confined to the lungs and thoracic glands. They reach their maximum about the 28th day and have undergone resolution by the 84th day.

8. The changes which occur in the cells of the reticulo-endothelial system following vaccination have been described. These changes must be taken into consideration in deciding the optimal time and dosage for revaccination and a further study of them is advisable.

Our thanks are due to Prof. T. Dalling for his unfailing interest in our work and for much helpful advice, and also io Dr A. Q. Wells for suppfyihg cultures of vole bacilli and for the loan of his multiple-puncture instrument. We are indebted to Dr V. D. Davies for painstaking examination of the joint lesions and to Dr J. R. M. Innes, who examined many histological sections of vole-inoculated animals and drew up a short report of which we have made much use. Mr V. L. Mastin was associated with us during part of the work and we gratefully acknowledge the help he gave. We also owe a deep debt of gratitude to our technical assistants, particularly Mr W. Nicholson and Mr C. Spurgeon, much of the routine bacteriological work being done by the former whilst the latter prepared the bulk of the histological sections. The local slaughterhouse officials of the Ministry of Food, particuiarfy Mr Bacchus, the slaughterhouse manager, and Mr C. Rose, the foreman slaughterman, have been most co-operative over the arrangements for the slaughter of many animals. Our thanks are also due to the farmers who allowed us to expose experimental animals to natural infection on their farms, and to these and other farmers who have placed their herds at our disposal for the purpose of field trials.

The cost of these investigations was met mainly by grants from the Agricultural Research Council, but partly from the funds of the Institute of Animal Pathology.

Hendra virus (HeV) was first described in 1994 in an outbreak of acute and highly lethal disease in horses and humans in Australia. Equine cases continue to be diagnosed periodically, yet the predisposing factors for infection remain unclear. We undertook an analysis of equine submissions tested for HeV by the Queensland government veterinary reference laboratory over a 20-year period to identify and investigate any patterns. We found a marked increase in testing from July 2008, primarily reflecting a broadening of the HeV clinical case definition. Peaks in submissions for testing, and visitations to the Government HeV website, were associated with reported equine incidents. Significantly differing between-year HeV detection rates in north and south Queensland suggest a fundamental difference in risk exposure between the two regions. The statistical association between HeV detection and stockhorse type may suggest that husbandry is a more important risk determinant than breed per se. The detection of HeV in horses with neither neurological nor respiratory signs poses a risk management challenge for attending veterinarians and laboratory staff, reinforcing animal health authority recommendations that appropriate risk management strategies be employed for all sick horses, and by anyone handling sick horses or associated biological samples.

Between April and September 2000, 60 injecting drug users in Scotland died or were hospitalized with severe illness. Laboratory investigations suggested that Clostridium novyi and other bacteria were important aetiological agents. To determine associated environmental/behavioural factors a case-control study was undertaken with 19 ‘definite’ and 32 ‘probable’ cases in Glasgow, Scotland. For every deceased case (n=19), up to three proxy individuals were interviewed. Three controls were identified for each case. Multivariate logistic regression analyses compared (i) all cases and controls; (ii) definite cases and matched controls; (iii) probable cases and matched controls. In all three analyses injecting into muscle or skin and injecting most of the time with a filter used by someone else were the variables most strongly associated with illness. Comparing only muscle-injecting cases and controls, cases were significantly more likely to have injected larger amounts of heroin per average injection than were controls. The findings make an important epidemiological contribution to the understanding of the public health and clinical implications of the contamination of illicit drugs by histotoxic clostridia.

There are limited data examining whether outcomes of methicillin-resistant Staphylococcus aureus (MRSA) healthcare-associated infections (HAIs) are worse when caused by community-associated (CA) strains compared to HA strains. We reviewed all patients’ charts at our institution from 1999 to 2009 that had MRSA first isolated only after 72 h of hospitalization (n = 724). Of these, 384 patients had a MRSA-HAI according to CDC criteria. Treatment failure was similar in those infected with a phenotypically CA-MRSA strain compared to a phenotypically HA-MRSA strain (23% vs. 15%, P = 0·10) as was 30-day mortality (16% vs. 19%, P = 0·57). Independent risk factors associated with (P < 0·05) treatment failure were higher Charlson Comorbidity Index, higher APACHE II score, and no anti-MRSA treatment. These factors were also associated with 30-day mortality, as were female gender, older age, MRSA bloodstream infection, MRSA pneumonia, and HIV. Our findings suggest that clinical and host factors, not MRSA strain type, predict treatment failure and death in hospitalized patients with MRSA-HAIs.

We describe the largest outbreak of hepatitis B virus infection reported to date in the UK. Between July 2001 and December 2005, 237 cases were identified in Avon, South West England. The likely route of transmission was injecting drug use in 44% (104/237) and heterosexual intercourse in 30% (71/237) of cases. A case-control study in injectors showed that injecting crack cocaine [adjusted odds ratio (aOR) 23·8, 95% confidence interval (CI) 3·04–186, P<0·001] and sharing injecting paraphernalia in the year before diagnosis (aOR 16·67, 95% CI 1·78–100, P=0·010) were strongly associated with acute hepatitis B. In non-IDUs number of sexual partners and lack of consistent condom use were high compared to a national sample. We describe the control measures implemented in response to the outbreak. This outbreak has highlighted the problems associated with the low uptake from the national hepatitis B vaccination policy which targets high-risk groups, the difficulties of identifying those at risk of acquiring hepatitis B infection through heterosexual sex, and injecting crack cocaine as a risk factor for hepatitis B.

Botulism has rarely been reported in Africa. In October 2008, botulism was reported in three Ugandan boarding-school students. All were hospitalized and one died. A cohort study was performed to assess food exposures among students, and clinical specimens and available food samples were tested for botulinum toxin. Three case-patients were identified; a homemade, oil-based condiment was eaten by all three. In the cohort study, no foods were significantly associated with illness. Botulinum toxin type A was confirmed in clinical samples. This is the first confirmed outbreak of foodborne botulism in Uganda. A homemade, oil-based condiment was the probable source. Consumption of homemade oil-based condiments is widespread in Ugandan schools, putting children at risk. Clinicians and public health authorities in Uganda should consider botulism when clusters of acute flaccid paralysis are seen. Additionally, schools should be warned of the hazard of homemade oil-based condiments, and take steps to prevent their use.

Human papillomavirus (HPV) types 6 and 11 are the aetiological agent of recurrent respiratory papillomatosis (RRP). The complete genome of an HPV6 isolate with a 170 base pair (bp) duplication identified within the long control region (LCR) from a patient with aggressive recurrent respiratory papillomatosis was determined. The promoter sequence from the HPV LCR including the 170 bp duplication was placed upstream of a heterologous reporter gene and the activity of the reporter gene product determined using transfected cells. In total, mutations were observed at 157 nucleotide positions of the complete genome and included nucleotide substitutions, deletions and insertions, resulting in amino acid changes at 43 residue positions. Reporter gene activity using an HPV-derived LCR region with a 170 bp duplication was significantly higher than that using an HPV-derived LCR region with no duplication within this region. The results suggest that novel HPV variants warrant further investigation for potential biomarkers of aggressive disease.

A detailed investigation of the possible role of wild mammals, other than badgers, in the maintenance of Mycobacterium bovis in an area on the South Downs of East Sussex was carried out over 3 years. Estimates of population sizes were made where possible and minimum sample sizes were selected to be 95 % certain of including at least one infected animal if the prevalence was at least 5 %. Samples of wild mammals were taken from populations which had the highest potential direct or indirect contact rate with known infected badgers. M. bovis was not isolated from any of the 15 species of wild mammals.

It was concluded that badgers are able to maintain M. bovis in an area independently of other species, and that in the area studied other species were not a source of infection for the cattle herds.

Systematic, national surveillance of outbreaks of intestinal infectious disease has been undertaken by Public Health England (PHE) since 1992. Between 1992 and 2002, there were 19 outbreaks linked to raw drinking milk (RDM) or products made using raw milk, involving 229 people; 36 of these were hospitalised. There followed an eleven-year period (2003–2013) where no outbreaks linked to RDM were reported. However, since 2014 seven outbreaks of Escherichia coli O157:H7 (n = 3) or Campylobacter jejuni (n = 4) caused by contaminated RDM were investigated and reported. Between 2014 and 2017, there were 114 cases, five reported hospitalisations and one death. The data presented within this review indicated that the risk of RDM has increased since 2014. Despite the labelling requirements and recommendations that children should not consume RDM, almost a third of outbreak cases were children. In addition, there has been an increase in consumer popularity and in registered RDM producers in the UK. The Food Standards Agency (FSA) continue to provide advice on RDM to consumers and have recently made additional recommendations to enhance existing controls around registration and hygiene of RDM producers.

Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) led to a significant disease burden and disruptions in health systems. We describe the epidemiology and transmission characteristics of early coronavirus disease 2019 (COVID-19) cases in Bavaria, Germany. Cases were reverse transcription polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infections, reported from 20 January−19 March 2020. The incubation period was estimated using travel history and date of symptom onset. To estimate the serial interval, we identified pairs of index and secondary cases. By 19 March, 3546 cases were reported. A large proportion was exposed abroad (38%), causing further local transmission. Median incubation period of 256 cases with exposure abroad was 3.8 days (95%CI: 3.5–4.2). For 95% of infected individuals, symptom onset occurred within 10.3 days (95%CI: 9.1–11.8) after exposure. The median serial interval, using 53 pairs, was 3.5 days (95%CI: 3.0–4.2; mean: 3.9, s.d.: 2.2). Travellers returning to Germany had an important influence on the spread of SARS-CoV-2 infections in Bavaria in early 2020. Especially in times of low incidence, public health agencies should identify holiday destinations, and areas with ongoing local transmission, to monitor potential importation of SARS-CoV-2 infections. Travellers returning from areas with ongoing community transmission should be advised to quarantine to prevent re-introductions of COVID-19.

Experiments performed on spore formation in B. anthracis, in a wide range of closed atmospheres of chemically controlled humidity, showed that the sporing time of B. anthracis is prolonged considerably as the humidity decreases, both at 26 and 37° C. The effect is less noticeable at the lower temperature.

Experiments performed on spore germination in the same organism showed that a temperature range of 20–44° C. permitted germination of the five strains tested. Above a temperature of 39° C. and below 30° C. germination time lengthened considerably.

Experiments performed on the influence of humidity on spore germination, both at 26 and 37° C. showed that no germination could take place at a relative humidity of 80% or below. Germination time was considerably prolonged when the humidity value fell below 100%.

This work formed part of a thesis for the degree of M.D. in Bristol University. I wish to thank Dr G. S. Wilson for his advice in preparing this paper.

The efficacy of seven rodenticides for use against Sigmodon hispidus was investigated in the laboratory. The poisons (warfarin, coumatetralyl, difenacoum, brodifacoum, bromadiolone, calciferol and zinc phosphide) were all toxic at the concentrations normally used against Rattus rattus and R. norvegicus and all were palatable.

Trials are now needed to confirm the efficacy of these poisons in the field, but it seems likely that, if used in suitable bait formulations, they would all be useful for the practical control of S. hispidus.

It is important to assess the suitability of sentinel sites for human disease; however, there have been few publications documenting the process of formal evaluation. We describe an approach to examining the representativeness of a single sentinel site employed for campylobacteriosis surveillance and source attribution, utilizing a selection of data sources and statistical comparisons of demographic, epidemiological and pathogen genotyping data across selected regions of New Zealand. Our findings showed that while this region captured the national variability in many variables, for example by containing sizable urban and rural populations, the relative frequency of these features did vary from other regions of New Zealand. We discuss the value of choosing a sentinel site that represents the national distribution of key variables, compared to a site that captures the broad features of the wider population, but provides greater power for the monitoring of sub-populations.

Summary Surface waters in 14 selected sites were examined for the presence of salmonella using modified Moore's swabs. The sites included an upland impounding reservoir, 3 rivers and 10 streams within Lancashire and Cheshire, selected because of their accessibility to farm livestock. Salmonellas were isolated from 22 out of the 57 swabs examined representing 10 sites. The probable source of pollution was shown to be sewage or farm effluent and an examination of sites over a wider area may be expected to produce similar results.

The significance of these findings is discussed in relation to the epidemiology of salmonella infections and the possible disinfection of effluent discharges.

1. Altogether 117 strains of Brucella, belonging to different types and isolated from different parts of the world, have been examined by the thermoagglutination, salt agglutination, acid agglutination, and specific serum agglutination tests.

2. The results obtained by the thermo-agglutination and the serum agglutination tests are in close agreement; there is a fairly high degree of correlation between these tests and the acid agglutination test, and a rather lower correlation with the salt agglutination test.

3. Generally speaking, a strain which is highly thermo-agglutinable is frequently agglutinated by salt, is usually agglutinated strongly by acid, and reacts to a paramelitensis, but not to an abortus serum.

4. A strain which is moderately thermo-agglutinable is seldom agglutinated by salt, is frequently agglutinated by acid, and reacts either with an abortus or a paramelitensis serum, or with both sera.

5. A strain which is not thermo-agglutinable is not agglutinated by salt, seldom reacts markedly to acid agglutination, and is generally agglutinated by an abortus, but not by a paramelitensis serum.

6. There remain, however, a certain number of strains, particularly of the porcine and bovine abortus types which, though non-thermo-agglutinable, inagglutinable by salt, and reacting only with an abortus serum, yet show some degree of acid agglutination.

7. Of the twelve porcine strains examined only one strain was strongly thermo-agglutinable; of the forty-seven bovine strains only two were strongly thermo-agglutinable, a further two showing a milder degree of thermoagglutinability; of the forty-seven melitensis strains eight were strongly, and thirteen were moderately thermo-agglutinable; while of the eleven paramelitensis strains ten were strongly thermo-agglutinable.

8. These results are taken to indicate, in accordance with the suggestion made by certain previous workers, that those strains which are non-thermoagglutinable, are not agglutinated by salt, and are agglutinated by an abortus but not by a paramelitensis serum, represent the smooth form, while those strains which are strongly thermo-agglutinable, are frequently agglutinated by salt, and are agglutinated by a paramelitensis but not by an abortus serum, represent the rough form.

9. If this interpretation is correct it will be noticed that the great majority of the porcine and bovine strains examined were of the smooth type, that nearly half the melitensis strains were partially or completely rough, while all but one of the paramelitensis strains were rough.

10. Whether melitensis strains have a greater tendency than abortus strains to undergo the smooth to rough transformation it is difficult to say with certainty, but the reports in the literature and the observations in the present paper render this probable.

11. By serial passage through broth at 5-day intervals, it is possible to transform smooth strains of all three types into the rough form. This transformation appears to occur more readily and to proceed further in a given time with melitensis than with abortus strains; but since only three strains of each type were examined, the results may have been determined as much by chance selection of strains as by any greater inherent tendency of the strains of the melitensis type to undergo variation.

12. It is clear that none of the tests employed suffices to differentiate individual strains of abortus and melitensis. The thermo-agglutination test and the agglutination test with specific smooth and rough sera do, however, enable a differentiation to be made between smooth and rough strains of all types.

13. In the present paper no attempt has been made to distinguish abortus and melitensis strains by specific agglutination and absorption tests. The general failure of workers hitherto to obtain any clear-cut serological distinction between these types may possibly be due to the fact that many of the strains with which they worked were either partially or completely rough. Since the rough antigen seems to be more or less alike in strains of all types, it is clear that its presence would tend to obscure any difference that might exist between the smooth antigens of the different types. If such a difference does exist it is probable that it will be elicited only by a comparison of absolutely smooth strains.

Escherichia coli O157 is a human pathogen carried asymptomatically by cattle and shed in their faeces. Infection can occur from the consumption of contaminated beef or by direct contact. Large variations of E. coli O157 shedding in cattle exist and vary in the number of cattle positive for E. coli O157 and the amount of bacteria (c.f.u./g faeces) shed by positive animals. To investigate E. coli O157 shedding and super-shedding (>104 c.f.u./g) we used daily sampling over two 8-day periods; in January 2013 (n = 12) and February 2013 (n = 21). Samples were tested by direct faecal culture for enumeration and by immunomagnetic separation to detect lower levels of shedding. We identified three patterns of shedding, similar to previously observed descriptions: intermittent, transient and consistent. The most commonly observed pattern was intermittent shedding and variation in the level of shedding could be large. This extreme variation is demonstrated by a heifer from which E. coli O157 could be not detected one day, was super-shedding E. coli O157 the next and was detected as shedding >100 c.f.u./g the following day. Recto-anal mucosal swab testing did not predict super-shedding in this cohort of heifers. The variable individual patterns of shedding suggest that a common mechanism of infection may not operate within such a herd when considering previously described patterns and the inferred mechanisms. The sporadic and intermittent nature of shedding is a challenge to identifying risk factors and potential intervention strategies.

Schistosoma japonicum infection associated with a rectal carcinoid in an asymptomatic 44-year-old female from the Philippines is described. A systematic review of the literature could not identify similar reports, suggesting a rare coincidence. However, epidemiological data on the frequency of both conditions as well as published results of a colorectal screening programme from China indicate that underreporting of this concurrence is likely. Moreover, several studies suggest a causal link between schistosomiasis caused by S. japonicum and more common gastrointestinal malignancies such as colorectal carcinoma. Hence the presented case and the apparent neglect of this observation in the current literature allow speculation on a role of S. japonicum in the pathogenesis of rare gastrointestinal neoplasms such as carcinoid tumours as well. Future reports on similar observations could help to determine the need for systematic investigations and are strongly encouraged.