1. Antisera prepared by immunizing rabbits with C. diphtheriae gravis, mitis, and intermedius and C. hofmannii contain antibodies which will give complement-fixation reactions with alcoholic extracts of the organisms.

2. By means of cross-absorption experiments three different lipoid antigens can be demonstrated: (a) a specific antigen h present only in C. hofmannii; (b) a specific antigen d characteristic of C. diphtheriae mitis but probably present also in small amount in C. diphtheriae gravis and intermedius; and (c) a non-specific or group antigen G present in large amount in C. diphtheriae gravis and intermedius and C. hofmannii, and in small amount in C. diphtheriae mitis; this G antigen is probably made up of a number of components.

3. Sera of human diphtheria convalescents may contain antibodies reacting with alcoholic extracts of C. diphtheriae. Sera from mitis cases usually react only with extracts of G. diphtheriae mitis, i.e. they contain only d antibody, while sera from gravis or intermedius cases usually contain only G antibody and react with extracts of C. diphtheriae gravis, intermedius and C. hofmannii, but not with extracts of G. diphtheriae mitis.

Complement-fixation tests with psittacosis-trachoma group antigens, if set up with complement prepared from guinea-pigs cross-infected with any of the Bedsonia agents, may give completely false positive results. The use of C.F. positive or C.F. inhibition positive samples of guinea-pig sera as a source of complement can induce also a significant increase or decrease, respectively, of the actual C.F. titres in Bedsonia-positive serum samples tested. Observations made both in routine serology and in experimental studies show the necessity of testing carefully, for possible presence of Bedsonia titres, individual sera of guinea-pigs intended for use as source of complement in C.F. tests performed with Bedsonia group antigens.

I have pleasure in thanking Dr F. B. Gordon and Dr E. Weiss for the valuable suggestions made and HM3 C.O. Wiese for the technical assistance.

It has been already shown by Darwin and others that reproduction is a function of environment and that unfavourable conditions of life are likely to increase the number of seeds formed or offspring produced; hence so many are reproduced that the chance of the species being perpetuated is maintained, despite the unfavourable conditions for survival. To extend this idea, and say that a dying species tends to reproduce faster than one actively evolving, is a suggestion worthy of enquiry. It has been argued that the varying birth rates in man may to some extent reflect the future biological possibilities of his race. In so far as all environments are really functions of time, or, to put it another way, we measure the nature of an environment by the length of time it takes to produce a certain result, it is quite a natural sequence to consider the effect of time, that is, age on fertility. Dr Matthews Duncan and others have dealt with the immediate effect of time, that is personal age, and the question of the transmitted effect, if any, remains to be considered. If the idea that a species which is dying out tends to reproduce more rapidly, holds good for man, then our previous finding, that the later born do not on the average live so long as the earlier born, would suggest that they might possess as compensation an enhanced fertility. To solve this problem we must correlate the number of offspring produced by each unit with the age of the parents when he or she was born, the reproductive period being made constant.

1. Many horses immunised against other bacteria or bacterial products will give a large local reaction to mallein, but this is usually not associated with a rise in temperature. In the case of horses injected with diphtheria toxin, the size of the swelling appears to related to the degree of immunity attained. This point has not yet been established in the case of horses immunised against other bacterial products.

2. This local reaction disappears rapidly and can thus be distinguished from the reaction in the case of glandered horses.

3. In the few cases when a rise in temperature took place (3 cases out of 56) the curve was markedly different from that obtained in the case of glandered animals.

4. Other bacterial products react similarly to mallein upon immune horses.

We present a mathematical model for the simulation of the development of an outbreak of coronavirus disease 2019 (COVID-19) in a slum area under different interventions. Instead of representing interventions as modulations of the parameters of a free-running epidemic, we introduce a model structure that accounts for the actions but does not assume the results. The disease is modelled in terms of the progression of viraemia reported in scientific studies. The emergence of symptoms in the model reflects the statistics of a nation-wide highly detailed database consisting of more than 62 000 cases (about a half of them confirmed by reverse transcription-polymerase chain reaction tests) with recorded symptoms in Argentina. The stochastic model displays several of the characteristics of COVID-19 such as a high variability in the evolution of the outbreaks, including long periods in which they run undetected, spontaneous extinction followed by a late outbreak and unimodal as well as bimodal progressions of daily counts of cases (second waves without ad-hoc hypothesis). We show how the relation between undetected cases (including the ‘asymptomatic’ cases) and detected cases changes as a function of the public policies, the efficiency of the implementation and the timing with respect to the development of the outbreak. We show also that the relation between detected cases and total cases strongly depends on the implemented policies and that detected cases cannot be regarded as a measure of the outbreak, being the dependency between total cases and detected cases in general not monotonic as a function of the efficiency in the intervention method. According to the model, it is possible to control an outbreak with interventions based on the detection of symptoms only in the case when the presence of just one symptom prompts isolation and the detection efficiency reaches about 80% of the cases. Requesting two symptoms to trigger intervention can be enough to fail in the goals.

Since 1985. nosocomial infections have been frequently treated with a new fluoroquinolone, pefloxacin, at the Cardiological and Neurological Hospital in Lyon. From 1986 to 1988. the incidence of resistance of clinical Staphylococcus epidermidis strains to pefloxacin increased from 31 to 57%. Dispersion of these resistant strains in the hospital environment was recognized when they were detected on 22% of staff members' fingers (139 samples were investigated) and in 28% of the environmental samples (180 were investigated). There was an association between carriage rate and work place. Most of the pefloxacin-resistant S. epidermidis were resistant to oxacillin, gentamicin. erythromycin, cotrimoxazole and fosfomycin. Intensive use of pefloxacin selected multiresistant S. epidermidis which became ubiquitous in the hospital environment.

The community burden of enterovirus is often monitored through syndromic monitoring systems based on reported cases of enterovirus-related infection (EVI) diagnoses. The extent to which this is affected by under- and over-diagnosis has not been reported. In Taiwan, children often make more than one healthcare visit during an episode of infection. We used change of diagnosis within an episode of infection as a guide of diagnostic uncertainty in a nationally representative cohort of Taiwanese children (n = 13 284) followed from birth to the 9th birthday through electronic health records. We conducted a nested case-control analysis and estimated cross-diagnosis ratios (CDRs) as the observed proportion of acute respiratory infection (ARI) diagnoses following an EVI diagnosis in excess of background ARI burdens. With 19 357 EVI diagnoses in this cohort, the CDR within 7 days was 1·51 (95% confidence interval 1·45–1·57), confirming a significant excess of ARI diagnoses within the week following an EVI diagnosis. We used age-specific CDRs to calibrate the weekly EVI burden in children aged 3–5 years in 2008, and the difference between observed and calibrated weekly EVI burdens was small. Therefore, there was evidence suggesting a small uncertainty in EVI diagnosis, but the observed EVI burdens through syndromic monitoring were not substantially affected by the small uncertainty.

I Know that you have finished your study in tropical medicine and hygiene at this school. And so, surely, I am not wide of the mark if I suppose there is very little in the way of facts and views you have not, at least, heard of. I think it rather useless to try to add one more small fact, or one more insignificant view, to the hoard of knowledge stored in your brains, or in your notebooks.

The discovery of cobalt tetra-carbonyl by Dr Hirtz and Mr Cowapp in Dr Ludwig Mond's laboratories offered a further opportunity of studying the toxic action of volatile compounds of the heavy metals. Through the kindness of Dr Mond, a sufficient quantity of cobalt carbonyl was placed at my disposal for physiological experimentation.

The clinical characteristics of male patients with pulmonary Mycobacterium avium complex disease have not been clearly defined. We aimed to clarify the clinical characteristics of male patients with pulmonary Mycobacterium avium complex disease compared with female patients.

We retrospectively reviewed the medical records of patients with pulmonary Mycobacterium avium complex disease who visited the outpatient clinic of the Shinshu University Hospital between 2003 and 2016 and compared the clinical characteristics of male and female patients.

A total of 234 patients with pulmonary Mycobacterium avium complex disease were identified (68 men and 166 women). Male patients were significantly older than female patients. Blood examination results showed that the lymphocyte count, total protein level and albumin level were significantly lower in men than in women. Chest imaging findings were broadly categorised into the fibrocavitary and nodular bronchiectasis types. There were no significant differences in chest imaging findings and the time from diagnosis to disease exacerbation between men and women.

During the study period, the incidence of the nodular bronchiectasis type of pulmonary Mycobacterium avium complex disease in male patients increased compared with previous reports. Men had no difference in time to exacerbation compared with women.

Kansas City, Missouri, became one of the major United States hotspots for COVID-19 due to an increase in the rate of positive COVID-19 test results. Despite the large numbers of positive cases in Kansas City, MO, the spatial-temporal analysis of data has been less investigated. However, it is critical to detect emerging clusters of COVID-19 and enforce control and preventive policies within those clusters. We conducted a prospective Poisson spatial-temporal analysis of Kansas City, MO data to detect significant space-time clusters of COVID-19 positive cases at the zip code level in Kansas City, MO. The analysis focused on daily infected cases in four equal periods of 3 months. We detected temporal patterns of emerging and re-emerging space-time clusters between March 2020 and February 2021. Three statistically significant clusters emerged in the first period, mainly concentrated in downtown. It increased to seven clusters in the second period, spreading across a broader region in downtown and north of Kansas City. In the third period, nine clusters covered large areas of north and downtown Kansas City, MO. Ten clusters were present in the last period, further extending the infection along the State Line Road. The statistical results were communicated with local health officials and provided the necessary guidance for decision-making and allocating resources (e.g., vaccines and testing sites). As more data become available, statistical clustering can be used as a COVID-19 surveillance tool to measure the effects of vaccination.

Clostridium botulinum causes infant botulism by colonising the intestines and producing botulinum neurotoxin in situ. Previous reports have linked infant botulism cases to C. botulinum spores in household dust, yet the baseline incidence of C. botulinum spores in residential households is currently unknown. Vacuum cleaner dust from 963 households in 13 major Canadian cities was tested for C. botulinum using a novel real-time PCR assay directed against all known subtypes of the botulinum neurotoxin gene. None of the samples tested positive for C. botulinum. Analysis of a random subset of samples by MALDI Biotyper revealed that the most common anaerobic bacterial isolates were of the genus Clostridium and the most common species recovered overall was Clostridium perfringens. Dust that was spiked with C. botulinum spores of each toxin type successfully produced positive real-time PCR reactions. These control experiments indicate that this is a viable method for the detection of C. botulinum spores in household dust. We make several recommendations for future work that may help discover a common environmental source of C. botulinum spores that could lead to effective preventative measures for this rare but deadly childhood disease.

The second patient with Arizona gastroenteritis to be diagnosed in Britain had just returned from the United States, where his illness began.

Two unidentified mycoplasmas, N3 and N11, isolated from the respiratory tract of horses, were found to cross-react with strains of M. mycoides subsp. mycoides in indirect immunofluorescence tests, growth-inhibition tests carried out by the running drop/agar-well method, and in complement-fixation and double immunodiffusion tests. Serologically, the equine mycoplasmas were not completely identical with any of the reference strains of M. mycoides with which they were compared. Their cultural characteristics, ability to digest coagulated serum and casein, and survival at 45 °C, however, suggested that they were more closely related to strains of M. mycoides subsp. mycoides, such as Y-goat, which are found in goats, than to strains of that subspecies which are pathogenic for cattle.

This paper proposes and analyses a stochastic model for the spread of an infectious disease transmitted between clients and care workers in the UK domiciliary (home) care setting. Interactions between clients and care workers are modelled using specially generated networks, with network parameters reflecting realistic patterns of care needs and visit allocation. These networks are then used to simulate a susceptible-exposed-infected-recovered/dead (SEIR/D)-type epidemic dynamics with different numbers of infectious and recovery stages. The results indicate that with the same overall capacity provided by care workers, the minimum peak proportion of infection and the smallest overall size of infection are achieved for the highest proportion of overlap between visit allocation, i.e. when care workers have the highest chances of being allocated a visit to the same client they have visited before. An intuitive explanation of this is that while providing the required care coverage, maximising overlap in visit allocation reduces the possibility of an infectious care worker inadvertently spreading the infection to other clients. The model is generic and can be adapted to any directly transmitted infectious disease, such as, more recently, corona virus disease 2019, provided accurate estimates of disease parameters can be obtained from real data.

Dengue is a mosquito-borne disease caused by four closely related dengue virus (genus Flavivirus) serotypes (DENV-1–4). The clinical outcomes vary from mild febrile illness to life-threatening haemorrhagic manifestations. DENVs are endemic in the tropics and subtropics globally and currently no specific treatment or vaccines are available. In Venezuela, the American-Asian genotype of DENV-2 is the most prevalent and has been associated with severe disease outcomes. We aimed to follow-up the molecular epidemiology of DENV-2 in Venezuela to investigate if the evolution of the virus has remained the same throughout time or if the same dynamics documented in Brazil (hyperendemic co-circulation) also occurred. The results show that whereas the epidemiology of DENV in several endemic areas is characterized by serotype replacements through time, in Venezuela the American-Asian genotype DENV-2 has evolved into several genetic lineages and has remained in hyperendemic co-circulation with the other serotypes.

Streptococcus pneumoniae (S. pneumoniae) is one of the most common community-associated pathogens responsible for pneumonia in children. This retrospective study aimed to investigate the molecular characteristics of S. pneumoniae isolated from children with community-acquired pneumonia (CAP) under 5 years in Chengdu, China. Molecular characteristics of S. pneumoniae included serotype and virulence factor performed by using PCR method and sequence types (STs) determined by sequencing seven housekeeping genes. In addition, the potential relationships between molecular characteristics were depicted by minimum spanning tree and correspondence analysis. The prevailing serotypes were 19F (18.52%), 6B (17.59%), 19A (13.89%), 6A (6.48%) and 23F (5.56%) among 108 isolates. The overall coverage rates of 7-valent, 10-valent, 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccines (PCVs) were 47.32, 48.1, 75, 75 and 78.7%, respectively. Meanwhile, the coverage rates of PCV13 among the isolates from CAP patients aged <1 year were high up to 84.2%. MLST analysis results showed that there were 56 different STs identified, of which the dominant STs were ST271 (22.22%) and ST320 (12.04%). Five international clones among STs were observed, including Spain23F‐1, Spain6B‐2, Taiwan19F‐14, Netherlands3‐31 and Denmark14‐32. Additionally, most of the isolates carried ply, psaA, nanA, pavA, piaA and CC271 isolates expressed more of nanA than non-CC271 isolates. Moreover, there were strong relevant relationships among STs, serotypes and virulence factors. Considering serotypes and virulence factors together can be used as the foundation for the formulation of vaccine strategy.

Graded doses of live and heat-killed cells of Campylobacter jejuni were injected into the yolk-sac of 5-day-old chick embryos, and the 50% lethal dose (LD50) was determined 7 days later. A strain dependent virulence was seen. In the diluted series of cultures the LD50 values for live campylobacter ranged from 106 c.f.u. beyond the last dilution showing growth, that is to less than one organism per embryo. When the 22 strains were tested as heat-killed cells, the chick embryo LD50 values retained the same relative order of toxicity obtained with viable cells, but the LD50 values were increased by + 1 to + 4 log units. Heat-killed cells from strains known to be invasive, but non-toxigenic, were still lethal for the embryos, suggesting that viability was not solely necessary for virulence. Semi-pure lipopolysaccharide from a non-virulent strain of C. jejuni was not toxic to the embryos, but semi-pure and ultracentrifuge-purified lipopolysaccharide from the most lethal campylobacter strains gave LD50 values in the order of 3·0 μg lipopolysaccharide per ml (0·6 µg per embryo) in the yolk-sac assay. No relationship between serotype and lethality was seen. Injection into the yolk-sac appears to be an easy, rapid and reproducible in vivo assay of the virulence of C. jejuni.

The possibility that the prevalence of diseases in which there is no specific causal organism may be affected by the prevalence of other diseasses of a contagious nature is well recognised. Even in the early days of bactriology interrelationships between infectious diseases and puerperal septicaemia were suspected on purely statistical grounds. Longstaff (1891), for example, pointed out the remarkably close correlation between the seasonal variations and the secular trends of the mortalities of erysipelas and childbed fever—a relationship so close that he “found it difficult to avoid the conclusion that they were both due to the one poison.” A somewhat similar but less striking association was shown with other inflammatory diseases, such as pyaemia, scarlet fever, “rheumatism of the heart or pericardium” and diphtheria. Even more emphatic were the views of Minor (quoted by Longstaff) who, with reference to the association between erysipelas and puerperal fever, gave reasons for the belief that there existed an intimate connection between them, and that “in any place where erysipelas is found, there will be found puerperal fever.”

In Portugal, the recommended age for the second dose of MMR (MMR2) was changed from 10–13 years to 5–6 years for those born in 1994 and afterwards. This study aimed to assess if MMR schedule and time elapsed from the last dose are associated with the concentration of rubella and mumps IgG antibodies. Three Portuguese birth cohorts (convenience samples) were selected for this study (66, 59 and 41 participants born respectively in 1990–1993, 1994–1995 and 2001–2003). Geometric mean concentrations (GMC) for mumps IgG were respectively 36, 30 and 38 RU/ml (P = 0·236) and for rubella IgG were 18, 20 and 17 IU/ml (P = 0·641). For both specific antibodies, no differences were observed with time since MMR2. Receiving MMR2 at 5–6 or 10–13 years was not associated with concentration of both antibodies. The GMC of rubella IgG was lower in males (P = 0·029). Taking into account previous evidence and the logistics needed to change vaccination schedules, it seems reasonable that sustaining very high coverage with two doses of MMR is currently the most pragmatic way to control mumps and rubella rather than any changes to the schedule.