The aim of our study was to determine the distribution of hepatitis B virus (HBV) genotypes and subgenotypes in ethnic minorities in Yunnan province to provide evidence supporting the theoretical basis for hepatitis B prevention and control. We obtained serum samples and demographic data from 765 individuals reported by Yunnan province who had either acute or chronic HBV infection and were from one of 20 ethnic minority populations: Achang, Bai, Brown, Tibetan, Dai, Deang, Dulong, Hani, Hui, Jingpo, Lahu, Yi, Lisu Miao, Naxi, Nu, Pumi, Wa, Yao, or Zhuang people. We sequenced the HBV DNA and determined the genotypes and subgenotypes of the isolated HBVs. We mapped the genotype and subgenotype distribution by ethnic minority population and conducted descriptive analyses. There were four genotypes among the 20 ethnic groups: genotype B (21.3% of samples), C (76.6%), D (1.8%) and I (0.3%). The most common subgenotype was C1. There were no genotype differences by gender (P = 0.954) or age (P = 0.274), but there were differences by region (P < 0.001). There were differences in genotype distribution (P < 0.001) and subgenotype distribution (P = 0.011) by ethnic group. Genotype D was most prominent in Tibet and most HBV isolates were C/D recombinant viruses. The only two genotype I virus isolates were in Zhuang people. Susceptibility and geographic patterns may influence HBV prevalence in different ethnic populations, but additional research is needed for such a determination.

With increasing demand for large numbers of testing during the coronavirus disease 2019 pandemic, alternative protocols were developed with shortened turn-around time. We evaluated the performance of such a protocol wherein 1138 consecutive clinic attendees were enrolled; 584 and 554 respectively from two independent study sites in the cities of Pune and Kolkata. Paired nasopharyngeal and oropharyngeal swabs were tested by using both reference and index methods in a blinded fashion. Prior to conducting real-time polymerase chain reaction, swabs collected in viral transport medium (VTM) were processed for RNA extraction (reference method) and swabs collected in a dry tube without VTM were incubated in Tris–EDTA–proteinase K buffer for 30 min and heat-inactivated at 98 °C for 6 min (index method). Overall sensitivity and specificity of the index method were 78.9% (95% confidence interval (CI) 71–86) and 99% (95% CI 98–99.6), respectively. Agreement between the index and reference method was 96.8% (k = 0.83, s.e. = 0.03). The reference method exhibited an enhanced detection of viral genes (E, N and RNA-dependent RNA polymerase) with lower Ct values compared to the index method. The index method can be used for detecting severe acute respiratory syndrome corona virus-2 infection with an appropriately chosen primer–probe set and heat treatment approach in pressing time; low sensitivity constrains its potential wider use.

This observational study aims to investigate the microbiological quality of commercially prepared lightly cooked foods with a major component of food of animal origin and collected as would be served to a consumer. A total of 356 samples were collected from catering (92%), retail (7%) or producers (1%) and all were independent of known incidents of foodborne illness. Using standard methods, all samples were tested for: the presence of Campylobacter spp. and Salmonella spp. and enumerated for levels of, Bacillus spp. including B. cereus, Clostridium perfringens, Listeria spp. including L. monocytogenes, Staphylococcus aureus, Escherichia coli, Enterobacteriacea and aerobic colony count (ACC). Results were interpreted as unsatisfactory, borderline or satisfactory according to the Health Protection Agency guidelines for assessing the microbiological safety of ready-to-eat foods placed on the market. Amongst all samples, 70% were classified as satisfactory, 18% were borderline and 12% were of unsatisfactory microbiological quality. Amongst the unsatisfactory samples, six (2%) were potentially injurious to health due to the presence of: Salmonella spp. (one duck breast); Campylobacter spp. (two duck breast and one chicken liver pâté); L. monocytogenes at 4·3 × 103 cfu (colony-forming units)/g (one duck confit with foie gras ballotin) and C. perfringens at 2·5 × 105 cfu/g (one chicken liver pâté). The remaining unsatisfactory samples were due to high levels of indicator E. coli, Enterobacteriaceae or ACC.

Accurate methods for determining the duration of HIV infection at the individual level are valuable in many settings, including many critical research studies and in clinical practice (especially for acute infection). Since first published in 2003, the ‘Fiebig staging system’ has been used as the primary way of classifying early HIV infection into five sequential stages based on HIV test result patterns in newly diagnosed individuals. However, Fiebig stages can only be assigned to individuals who produce both a negative and a positive test result on the same day, on specific pairs of tests of varying ‘sensitivity’. Further, in the past 16 years HIV-testing technology has evolved substantially, and three of the five key assays used to define Fiebig stages are no longer widely used. To address these limitations, we developed an improved and more general framework for estimating the duration of HIV infection by interpreting any combination of diagnostic test results, whether obtained on single or multiple days, into an estimated date of detectable infection, or EDDI. A key advantage of the EDDI method over Fiebig staging is that it allows for the generation of a point estimate, as well as an associated credibility interval for the date of first detectable infection, for any person who has at least one positive and one negative HIV test of any kind. The tests do not have to be run on the same day; they do not have to be run during the acute phase of infection and the method does not rely on any special pairing of tests to define ‘stages’ of infection. The size of the interval surrounding the EDDI (and therefore the precision of the estimate itself) depends largely on the length of time between negative and positive tests. The EDDI approach is also flexible, seamlessly incorporating any assay for which there is a reasonable diagnostic delay estimate. An open-source, free online tool includes a user-updatable curated database of published diagnostic delays. HIV diagnostics have evolved tremendously since that original publication more than 15 years ago, and it is time to similarly evolve the methods used to estimate timing of infection. The EDDI method is a flexible and rigorous way to estimate the timing of HIV infection in a continuously evolving diagnostic landscape.

We reviewed key attributes (flexibility, data quality and timeliness) of Australia's National Notifiable Diseases Surveillance System (NNDSS) over its first 21 years. Cases notified to NNDSS from 1991 to 2011 were examined by jurisdiction (six states and two territories) and sub-period to describe changes in the number of notifiable diseases, proportion of cases diagnosed using PCR tests, data quality (focusing on data completeness), and notification delays. The number of notifiable diseases increased from 37 to 65. The proportion of cases diagnosed by PCR increased from 1% (1991–1997) to 49% (2005–2011). Indigenous status was complete for only 44% notifications (jurisdictional range 19–87%). Vaccination status was complete for 62% (jurisdictional range 32–100%) and country of acquisition for 24% of relevant cases. Data completeness improved over the study period with the exception of onset date. Median time to notification was 8 days (interquartile range 4–17 days, jurisdictional range 5–15 days); this decreased from 11 days (1991–1997) to 5 days (2005–2011). NNDSS expanded during the study period. Data completeness and timeliness improved, likely related to mandatory laboratory reporting and electronic data transfer. A nationally integrated electronic surveillance system, including electronic laboratory reporting, would further improve infectious disease surveillance in Australia.

A retrospective space–time permutation model with non-Euclidean distance criteria was applied within a high-complexity hospital setting to quantitatively explore cluster patterns of 273 patients infected with or colonized by carbapenemase-producing Klebsiella pneumoniae during 4 years. Results were compared to standard nosocomial active-surveillance methods. Two clusters were identified in the period, suggesting that space–time strategies for cluster quantification within confined environments may be useful.

1. A new colicine type (type 15) of Shigella sonnei is described.

2. The epidemiological circumstances associated with its appearance in Edinburgh and Glasgow are summarized.

3. Our indices of reliability as an epidemiological marker are fulfilled by this new type.

The prevalence of anti-retroviral therapy (ART) use over time and the incidence of AIDS in a cohort of HIV-seroconverting injecting drug users (IDUs) were assessed by means of a hospital-based study of IDUs with a well documented date of HIV infection. Use of ART and clinical endpoints were assessed by hospital records. Three calendar periods (before 1992, 1992–6 and 1997–2000) were defined as corresponding to modalities of ART available. Prevalence of ART usage in each calendar period, changes in medication and, hazard of AIDS in patients reaching the same duration of HIV infection at different calendar periods were analysed. In total, 132 IDUs with a median age of 23 years at seroconversion were followed up for 6.8 years (median) (range 0.2–15.7). At the end of the study, 58 patients (44%) had developed AIDS. Before the introduction of highly active anti-retroviral therapy (HAART) 12% of patients were on ART. Starting in 1997, an increasing proportion were receiving HAART with a prevalence of 39.5% by January 2000. Taking 1992–6 as the reference category the relative hazard of AIDS during 1997–2000 was 0.42 (95% CI, 0.1–1.1) (P = 0.09). A 40% penetration of HAART in a cohort of IDUs with known dates of seroconversion resulted in a 58% reduction of the hazard of AIDS.

Cases of paratyphoid fever are often not diagnosed until the second, third or subsequent weeks of illness. When calculating clearance rates of a series of cases the calculations must be based only on the numbers known to be positive at the week under consideration. If based throughout on the total number of cases the rates of clearance in the early weeks are greatly reduced.

Cases for which laboratory records are incomplete must not be entirely rejected when calculating clearance rates but must be retained in the population for as long as they were known to be positive.

Analyses designed to show the duration of infection in paratyphoid fever can only be made with accuracy under the most favourable conditions.

A large number of cases of paratyphoid fever were repeatedly examined bacteriologically to establish the duration of the infection as distinct from the clinical illness. After an initial lag the proportion of cases remaining infected fell logarithmically until the carriers revealed themselves.

We are grateful to many medical officers for information about their cases, and to Dr Lewis Fanning and Dr Ian Sutherland for much helpful criticism.

In our investigation of our subject we have perused the literature, analysed the data of other workers, conducted a number of animal experiments, considered the bearings clinical and pathological of a case of presumed toluene poisoning, and conducted an investigation into the blood state and symptoms of co-workers with this case and yet are unable to give a categorical answer to the question. What are the relative toxicities of toluene and benzene? We would almost feel inclined to echo the words of another worker in the experimental field with regard to benzene, Neumann (1915), who concludes: “The fact that my results so often do not correspond either with one another or with those of Selling, so often indeed do not correspond to expectation, justifies the conclusion that, although benzene is to be regarded as a powerful leucotoxin, it manifests great individual differences in its mode of action and it is very difficult to lay down exactly what action is to be expected.”

We should be inclined to put the case somewhat differently however and put forward the following view as our tentative finding.

The actions of benzene and toluene are very similar. That of benzene is the more powerful because it is a more volatile substance and can therefore reach higher concentration than toluene. This greater volatility at the same time is a reason why it is eliminated more quickly and its effects are less lasting than those produced by toluene. The action of both these substances is on young body cells, probably whatever they are and wherever they may be found, but is most easily discoverable because of its action on the young bone marrow cell and the consequent effect on the cells of the peripheral blood. It is not a specific action but operates, according to circumstances, on the stem cells of the myeloid leucocyte or the erythrocyte. This does not mean that the substances have little or no effect on the lymphocyte, for the lymphoid tissue in the body is so very abundant that it would only be in extreme cases that the effect on that cell would be manifest peripherally. Like many poisons, indeed like many of the drugs which are used in Medicine, the first effects of these substances are stimulating. Leucocytosis, erythrocytosis and possibly thrombocytosis are early manifestations or the manifestation of slighter action, with histological evidence of hyperplasia. This is succeeded by the truly toxic or destructive action and the production of leucopenia, anaemia, thrombopenia and the effects due to action on other organs. The ultimate result in clinical terms is an agranulocytic anaemia accompanied by purpura haemorrhagica and, as the pathological manifestation an aplastic bone marrow. The fatal termination is commonly an infection to which there is no resistance possible in an individual deprived of defence cells and possibly also of defensive substances in the body fluids. Powerful solvents of fat as both these chemical substances are, they produce an action through this means also, on nerve cells, capillary endothelium and parenchyma of organs with consequences represented in nervous symptoms and in haemorrhages. This then is our reading of the results of our investigation and explanation of the variability which may be found, a variability which is regarded mainly as one of phase, although we do not exclude idiosyncrasy altogether as explanation.

In the UK the increasing use of pre-admission parenteral antibiotic therapy in meningococcal disease has lessened the value of routine cultures as a tool to confirm diagnosis, and laboratory confirmation of invasive meningococcal infection is achieved increasingly by non-culture, nucleic acid amplification methods. The purpose of this study was to evaluate a DNA extraction and meningococcal-specific DNA amplification methodology for detection of meningococci from oropharyngeal swabs.

One hundred and six swabs from suspected or confirmed cases of meningococcal disease, and 94 swabs from contacts of meningococcal disease cases were examined. Of laboratory-confirmed cases, 38/65 (58·5%) yielded a positive oropharyngeal swab PCR result and 5/24 (20·8%) swabs from suspected but laboratory-unconfirmed cases were PCR positive. No significant differences in PCR positivity rates were found between the types of swab transport systems utilized, but transport time to the testing laboratory was found to affect PCR positivity (P < 0·05).

Application of meningococcus-specific PCR to oropharyngeal swabs, in addition to routine culture of swabs, can provide valuable epidemiological information as well as case confirmation for contact management. PCR amplification of meningococcal PCR from oropharyngeal swabs will also increase the ascertainment in swabbing surveys carried out as part of meningococcal disease outbreak investigation and management.

In the rapidly developing city of Almaty, Kazakhstan, rates of hepatitis A have fallen, but no data on prevalence of antibody to hepatitis A virus (anti-HAV) exist with which to interpret incidence data. In the autumn of 2001, we determined the anti-HAV prevalence among household and school contacts of hepatitis A cases. For contacts aged 0–4 years, 5–9 years, 10–14 years, 15–19 years, or 20–30 years, immune prevalences were 9, 12, 33, 33 and 77% respectively, among immediate-family household contacts and 15, 28, 49, 52 and 77% respectively, among community contacts. Child community contacts were more likely to be immune than their immediate-family household counterparts (odds ratio 2·0, 95% confidence interval 1·3–3·2). Almaty is experiencing an epidemiological shift in hepatitis A incidence. Feasible and effective prevention strategies using hepatitis A vaccine should be explored.

Campylobacteriosis, the most frequent bacterial enteric disease, shows a clear yet unexplained seasonality. The study purpose was to explore the influence of seasonal fluctuation in the contamination of and in the behaviour exposures to two important sources of Campylobacter on the seasonality of campylobacteriosis. Time series analyses were applied to data collected through an integrated surveillance system in Canada in 2005–2010. Data included sporadic, domestically-acquired cases of Campylobacter jejuni infection, contamination of retail chicken meat and of surface water by C. jejuni, and exposure to each source through barbequing and swimming in natural waters. Seasonal patterns were evident for all variables with a peak in summer for human cases and for both exposures, in fall for chicken meat contamination, and in late fall for water contamination. Time series analyses showed that the observed campylobacteriosis summer peak could only be significantly linked to behaviour exposures rather than sources contamination (swimming rather than water contamination and barbequing rather than chicken meat contamination). The results indicate that the observed summer increase in human cases may be more the result of amplification through more frequent risky exposures rather than the result of an increase of the Campylobacter source contamination.

A study has been made of the properties of soluble antigen in the brains of infant mice infected intracerebrally with the Flury strain of rabies virus.

Soluble antigen is produced at the same time as infective virus, and reaches a high concentration in a period of 2–3 days.

It can be partially purified by precipitation at pH 4·3. It is partially resistant to the action of trypsin, RNAse and DNAse. It is relatively stable at pH 6–10.

Experimental results suggest that the soluble antigen remains antigenically active after heating at 56° C. and treatment with 0·5% phenol or 0·35% formal-dehyde, but that such heating markedly reduces the ability to stimulate formation of neutralizing antibody.

Rabbits and mice appear to differ in the production of neutralizing antibody following immunization against soluble antigen in which residual live virus was inactivated by heat, phenol or formaldehyde.

It is suggested that this difference may depend on the different susceptibility to traces of incompletely inactivated virus remaining in the immunizing antigens.

The authors are grateful to Miss T. Madsen for her assistance in some aspects of this work. Dr N. Sapeika kindly made available facilities for the in vitro anaphylaxis experiments.

Financial assistance was received from the Nkana-Kitwe and Chingola Poliomyelitis Research Funds.

Rabies virus (RABV) is a deadly zoonosis that circulates in wild carnivore populations in North America. Intensive management within the USA and Canada has been conducted to control the spread of the raccoon (Procyon lotor) variant of RABV and work towards elimination. We examined RABV occurrence across the northeastern USA and southeastern Québec, Canada during 2008–2018 using a multi-method, dynamic occupancy model. Using a 10 km × 10 km grid overlaid on the landscape, we examined the probability that a grid cell was occupied with RABV and relationships with management activities (oral rabies vaccination (ORV) and trap-vaccinate-release efforts), habitat, neighbour effects and temporal trends. We compared raccoon RABV detection probabilities between different surveillance samples (e.g. animals that are strange acting, road-kill, public health samples). The management of RABV through ORV was found to be the greatest driver in reducing the occurrence of rabies on the landscape. Additionally, RABV occupancy declined further with increasing duration of ORV baiting programmes. Grid cells north of ORV management were at or near elimination ($\hat{\psi }_{{\rm north}}$ = 0.00, s.e. = 0.15), managed areas had low RABV occupancy ($\hat{\psi }_{{\rm managed}}$ = 0.20, s.e. = 0.29) and enzootic areas had the highest level of RABV occupancy ($\hat{\psi }_{{\rm south}}$ = 0.83, s.e. = 0.06). These results provide evidence that past management actions have been being successful at the goals of reducing and controlling the raccoon variant of RABV. At a finer scale we also found that vaccine bait type and bait density impacted RABV occupancy. Detection probabilities varied; samples from strange acting animals and public health had the highest detection rates. Our results support the movement of the ORV zone south within the USA due to high elimination probabilities along the US border with Québec. Additional enhanced rabies surveillance is still needed to ensure elimination is maintained.

Steatorrhoea was a significant feature in an outbreak of rotavirus gastroenteritis which affected adults and infants in hospital. Fat globules or fatty acid crystals were obvious by light microscopy (LM) in faeces from 14 of 25 patients examined. Ten of the fatty stools and two of the remainder were very pale. By electron microscopy (EM) a rotavirus was seen in 11 of the 14 fatty faeces and in only two of 11 specimens without visible fat.

In a further study of pale or fatty faeces 20 such specimens sent for laboratory examination from patients not involved in the hospital outbreak were compared microbiologically with a similar number which were neither pale nor fatty. Viruses were found by EM in 11 (55%) of the pale or fatty stools; eight rotaviruses, two astroviruses and an uncultivable adenovirus were seen; one further patient had acute jaundice. In contrast, no viruses were seen by EM in the twenty specimens which were normally pigmented and without evident fat.

Steatorrhoea was significantly associated with rotavirus infection of the alimentary tract which usually presented as a fatty enteritis. We conclude that rotaviruses certainly, and other viruses possibly, can impede both the digestion of fat and the pigmentation of the faeces. Inspection and LM of faeces are easy. In acute enteritis a fatty or pale stool is an indication for virological examination.

Haemophilus ducreyi, the causal organism of chancroid, has increased in significance recently due to its association with HIV transmission. Most previous typing systems have exploited phenotypie characteristics. Detection of ribosomal RNA cistrons, ribotyping, was successfully developed to examine H. ducreyi, but required the use of 32P.

We have used digoxigenin to define ribotypes from 30 strains of H. ducreyi from diverse geographical locations. This was achieved by agarose gel electrophoresis of restriction enzyme (RE) digested DNA extracts. These extracts were vacublotted onto nylon membrane and probed using digoxigenin labelled complementary DNA probe, prepared from Escherichia coli 16S and 23S ribosomal RNA. From 19 REs tested, Ava II, Hinc II, Bgl II and BstE II gave clear ribotypes. The ribotypes of BstE II and Bgl II used together gave the highest index of discrimination (D = 0·95), 16 types, and showed good reproducibility. This nonradioactive method demonstrates the three important features of a typing system: discrimination, typability and reproducibility.

The following experiments constitute an attempt to follow out in detail the stages by which immunity is established, in the course of a generalised bacterial infection (Pseudotuberculosis of rabbits). Two aspects of immunity are considered, firstly the presence, in the circulating fluids, of specific antibacterial substances, and secondly the power of rapidly producing such substances in answer to the specific stimulus. That is to say, attention is directed, not only to the quantity of specific antibodies present on any day of the disease, but also to the response which the animal can make to various doses of bacterial vaccine. For the immune animal is both more vigorous and more sensitive than the normal, in its reaction to a renewed dose of poison (Wassermann and Citron, 1905). Naturally the facts established with regard to one disease only, cannot be predicated at once of other diseases, in other animals. Still it is hoped that the systematic study of one disease may give some help in coordinating the large but somewhat disjointed mass of clinical observation which is already available.

A total of 21 rubella seronegative children vaccinated subcutaneously with Wistar RA 27/3 strain live attenuated rubella vaccine in a family study of vaccine virus transmissibility were reviewed after 6 years. Haemagglutinating inhibiting (HAI) antibody titres of sera collected 46 days, 2 years and 6 years after vaccination were compared. Antibody titres in the vaccinated subjects were not significantly influenced by time, infection in susceptible siblings or revaccination.

Kittens with maternal antibodies to myxoma virus, the offspring of rabbits which had recovered from myxomatosis, were exposed to fleas contaminated with myxoma virus and/or contact with infected rabbits from birth. All kittens died or became infected before 8 weeks of age. When compared with adult animals similarly infected the kittens showed no advantage in terms of survival time or recovery rate attributable to maternal antibodies. Flea transmission of virus was found more effective than contact transmissions.