The theories of Ehrlich on the Substances and Mechanisms concerned in the production of Immunity have opened up a very wide field for speculation and research. His view on the formation of the Antitoxins forms the most satisfactory and useful hypothesis which has been produced upon this subject, and is constantly receiving fresh support from the accumulating evidence of numerous observers. But of the more recent developments of his theories as applied to antimicrobic agencies some of the details appear to be at present insufficiently established. With certain of these details it is here proposed to deal.

Cylinder-model vacuum cleaners cause no bacterial contamination of the air, whereas even on oiled floors domestic brooms caused statistically significant contamination of the air when compared with a vacuum cleaner.

The Hoover model 402 was the only machine tested whose bag is never removed, a theoretical as well as a practical advantage. Domestic brooms can destroy an otherwise efficient barrier nursing system and should bo avoided in hospital wards.

This study describes the development of a pilot sentinel school absence syndromic surveillance system. Using data from a sample of schools in England the capability of this system to monitor the impact of disease on school absences in school-aged children is shown, using the coronavirus disease 2019 (COVID-19) pandemic period as an example. Data were obtained from an online app service used by schools and parents to report their children absent, including reasons/symptoms relating to absence. For 2019 and 2020, data were aggregated into daily counts of ‘total’ and ‘cough’ absence reports. There was a large increase in the number of absence reports in March 2020 compared to March 2019, corresponding to the first wave of the COVID-19 pandemic in England. Absence numbers then fell rapidly and remained low from late March 2020 until August 2020, while lockdown was in place in England. Compared to 2019, there was a large increase in the number of absence reports in September 2020 when schools re-opened in England, although the peak number of absences was smaller than in March 2020. This information can help provide context around the absence levels in schools associated with COVID-19. Also, the system has the potential for further development to monitor the impact of other conditions on school absence, e.g. gastrointestinal infections.

A total of 270 serum samples collected in Chiang Mai province were examined for antibodies against leptospira using the microscopic agglutination test (MAT). Four of 40 serum specimens from patients who visited the hospital with the common cold, were positive with a titre of 20. Twelve (10·4%) of the 115 samples in the Doi Saket district showed a positive reaction. Only 2 of 115 sera of school children in Chiang Mai city had antibodies.

Specific serovars detected were Leptospira hebdomadis (5), L. australis (3), L. icterohaemorrhagiae (2), L. bataviae (2), and one each of L. canicola, L. javanica and L. pyrogenes. One case of mixed infection with L. hebdomadis and L. javanica, and L. auhnnnalis and L. australis were observed.

Pseudomonas aeruginosa is one of the leading nosocomial pathogens. The question of the respective contribution of endogenous and exogenous sources remains controversial. In this study, we shed new light on this issue by means of a multilevel logistic regression analysis which allowed a simultaneous investigation of factors associated with prevalence of patients infected with P. aeruginosa at two levels: patient and healthcare facility (HCF) in the eastern regions of France. A total of 25 533 in-patients from 51 HCFs were included in the analysis. The overall prevalence was 0·37% (range 0–1·65%). Multilevel modelling estimated that <14% of total variability of the outcome variable was explained by differences between HCFs and that after adjusting for patient-level variables, which explained 52% of HCF-level variance, the latter became non-significantly different from zero. A compositional effect (patient factors), rather than a contextual effect (ecological factors), explains heterogeneity of the prevalence of patients infected with P. aeruginosa in the eastern HCFs of France.

A cluster of 10 cases of tuberculosis disease (one of them extrapulmonary) occurred from July 2001 until November 2003 in a health district in Southern Austria. Eight patients were culture confirmed and shared an identical strain. One of these eight cases was identified as outbreak-related by molecular strain typing only. Due to public pressure, a further 600 persons received chest X-ray and clinical examinations. Apart from one case which could be excluded from the outbreak because of a different strain pattern, no outbreak-related case of active tuberculosis was detected by this non-targeted procedure. Tuberculin skin testing, not part of the Austrian routine protocol of contact investigation in adults, was initiated after diagnosis of case 8. Forty-nine latently infected contacts were detected. Population-based genotyping of all isolates, prioritization of contact investigations and early use of targeted tuberculin skin testing are critical for effective tuberculosis control in low-incidence countries.

1. Mice infected intracerebrally with M. tuberculosis H 37 Rv in doses of 400,000–1,300,000 bacillary units gave a graduated series of responses whose regression provided an arbitrary 100% standard of mouse virulence for human tubercle bacilli.

2. Under certain experimental conditions this standard remained stable and its confidence limits could be defined.

3. The relative virulence of other strains of tubercle bacilli could be assessed quantitatively in relation to this standard, and expressed as a (percentage) virulence ratio.

4. 100% virulence was defined as that of a strain showing a threshold of response of 600,000–1,300,000 bacillary units, lethal cerebral lesions at 8–20 days or necrotic pulmonary lesions at 20–30 days, and a mean 50% mortality time of less than 36 days.

5. Qualitative and quantitative responses characteristic of intermediate and very low virulence were also defined.

6. Higher proportions of virulent cells were obtained from 3 to 7 days than from older cultures in Tween-albumin liquid media, but inocula were more suitably standardized by obtaining cells from 11 to 12-day cultures.

7. Passage in the mouse and guinea-pig failed to alter the virulence of H 37 Rv. A slight increase was effected by passage in the lung of the rabbit.

8. The technique employed was a measure essentially of the ability of the organism to multiply in, and damage, resistant tissues.

There is a paucity of information on the risk from potable water in non-passenger merchant vessels (NPMVs) particularly with regard to Legionella and other bacteria. This retrospective study examined water samples from 550 NPMVs docked in eight UK ports. A total of 1027 samples from 412 NPMVs were examined for total aerobic colony counts (ACC), coliforms, Escherichia coli and enterococci; 41% of samples yielded ACC above the action level (>1 × 103 c.f.u./ml) and 4·5% contained actionable levels (>1 c.f.u./100 ml) of faecal indicator bacteria. Eight hundred and three samples from 360 NPMVs were cultured specifically for Legionella and 58% of vessels proved positive for these organisms with 27% of samples showing levels greater than the UK upper action limit of 1 × 103 c.f.u./l. Cabin showers (49%) and hospital shower (45%) were frequently positive. A subset of 106 samples was analysed by quantitative polymerase chain reaction for Legionella and identified a further 11 Legionella-positive NPMVs, returning a negative predictive value of 100%. There was no correlation between NPMV age or size and any microbial parameters (P > 0·05). Legionella pneumophila serogroup 1 was isolated from 46% of NPMVs and sequence-based typing of 17 isolates revealed four sequence types (STs) previously associated with human disease. These data raise significant concerns regarding the management of microbial and Legionella risks on board NPMVs and suggest that better guidance and compliance are required to improve control.

During the 2009 influenza pandemic, a rapid assessment of disease severity was a challenge as a significant proportion of cases did not seek medical care; care-seeking behaviour changed and the proportion asymptomatic was unknown. A random-digit-dialling telephone survey was undertaken during the 2011/12 winter season in England and Wales to address the feasibility of answering these questions. A proportional quota sampling strategy was employed based on gender, age group, geographical location, employment status and level of education. Households were recruited pre-season and re-contacted immediately following peak seasonal influenza activity. The pre-peak survey was undertaken in October 2011 with 1061 individuals recruited and the post-peak telephone survey in March 2012. Eight hundred and thirty-four of the 1061 (78.6%) participants were successfully re-contacted. Their demographic characteristics compared well to national census data. In total, 8.4% of participants self-reported an influenza-like illness (ILI) in the previous 2 weeks, with 3.2% conforming to the World Health Organization (WHO) ILI case definition. In total, 29.6% of the cases reported consulting their general practitioner. 54.1% of the 1061 participants agreed to be re-contacted about providing biological samples. A population-based cohort was successfully recruited and followed up. Longitudinal survey methodology provides a practical tool to assess disease severity during future pandemics.

Invasive group A streptococcal (GAS) disease is a condition of clinical and public health significance. We conducted epidemiological analyses to determine if the presence of gastrointestinal (GI) complaints (diarrhea and/or vomiting) early in the course of invasive GAS disease is associated with either of two severe outcomes: GAS necrotizing fasciitis, or hospital mortality. Subjects were hospitalized for invasive GAS disease throughout the state of Florida, USA, during a 4-year period. Multiple imputation using the Markov chain Monte Carlo method was used to replace missing values with plausible values. Excluding cases with missing data resulted in a sample size of 138 invasive GAS patients (the complete subject analysis) while the imputed datasets contained 257 records. GI symptomatology within 48 h of hospital admission was not associated with hospital mortality in either the complete subject analysis [adjusted odds ratio (aOR) 0·86, 95% confidence interval (CI) 0·31–2·39] or in the imputed datasets. GI symptoms were significantly associated with GAS necrotizing fasciitis in the complete subject analysis (aOR 4·64, 95% CI 1·18–18·23) and in the imputed datasets but only in patients aged <55 years. The common cause of GI symptoms and necrotizing fasciitis may be streptococcal exotoxins. Clinicians who are treating young individuals presumed to be in the early stages of invasive GAS disease should take note of GI symptoms and remain vigilant for the development of a GAS necrotizing soft-tissue infection.

A statistical analysis has been made of the figures collected during the last eight years in the Edinburgh area, relating to asthmatic patients who presented themselves for examination in certain departments of the Edinburgh Royal Infirmary. The figures for males and females are considered separately, and refer to the numbers of individuals who presented themselves at various, ages, and in whom the disease first manifested itself at various earlier ages. In all, complete records were obtained of 193 males and 167 females. For convenience the ages are grouped in five-year periods.

It has been shown that the figures in the case of females agree well with the assumption that asthmatics, no matter at what age they are first affected, gradually cease to suffer from the disease, or at least fail to report for examination, at a rate which is constant and independent of age. In the case of males the agreement between theory and observation is not as good as in the case of the females, but much of the discrepancy results from two or three obviously aberrant figures. Of every 100 asthmatics at any age it would appear that approximately 7 females, or 8 males as the case may be, are transferred to a non-complaining category every year. The absence of complaint may be due to death from asthma, or recovery, or to some other cause, as for example, that by repeated experience the individual learns how to avoid conditions which precipitate an attack.

On this assumption the relative rates of incidence (P) of the disease at various ages have been calculated for males and for females. Both curves fall during adolescence, rise to a maximum, and then gradually fall, but the male curve lags behind the female curve. From these figures the rates of attack amongst the potential asthmatics (p) have been calculated both for males and for females. The curves fall during adolescence, then rise, remaining practically constant until about 45 years of age, when a rise occurs towards unity. For the further analysis of these curves larger numbers of figures will be necessary, in order that confidence may be placed in the results.

The Veterans Health Administration (VHA) of the Department of Veterans Affairs tracks legionella disease in the system of 172 medical centres and additional outpatient clinics using an annual census for reporting. In fiscal year 1999, 3·62 million persons were served by the VHA. From fiscal year 1989–1999, multiple intense interventions were carried out to decrease the number of cases and case rates for legionella disease. From fiscal year 1992–1999, the number of community-acquired and healthcare-associated cases decreased in the VHA by 77 and 95·5% respectively (P=0·005 and 0·01). Case rates also decreased significantly for community and healthcare-associated cases (P=0·02 and 0·001, respectively), with the VHA healthcare-associated case rates decreasing at a greater rate than VHA community-acquired case rates (P=0·02). Over the time of the review, the VHA case rates demonstrated a greater decrease compared to the case rates for the United States as a whole (P=0·02). Continued surveillance, centrally defined strategies, and local implementation can have a positive outcome for prevention of disease in a large, decentralized healthcare system.

The coagulability of the plasma of blood taken from the retro-orbital sinus of untreated and warfarin-treated wild house mice (Mus musculus L.) was determined. Individual differences were observed in the resting clotting times of animals drawn from three different sources, so-called ‘normal’ (N) mice, home-bred warfarin resistant (HBR) mice and field-caught suspected warfarin resistant (FR) mice. Mice from the three sources also showed wide individual variation in response to injected doses of 1, 5 and 50 mg. of warfarin/kg, body weight. The overall response shown by HBR and FR mice, particularly females, was less than that shown by N animals. Some FR females failed to respond to a dose of 100 mg. of warfarin/kg, body weight.

Normal mice showed a similar response to two identical doses of warfarin (1, 5 or 50 mg./kg. body weight) given at an interval of 3 weeks. They developed a tolerance to repeated daily injected doses of 1 mg. of warfarin/kg, body weight but not to the higher doses (5 and 50 mg./kg.) to which some HBR animals became tolerant.

In comparative 21-day feeding tests with 0·025% warfarin in medium oatmeal, the mortality in N, HBR and FR mice was 100% (27), 64·5% (40/62) and 22·7% (10/44) respectively. Whereas the plasma of all N mice was rendered uncoagulable after 3 days and the animals died within 12 days, the clotting times of the surviving HBR and FR mice (24/59 males and 32/47 females) either were not at any stage appreciably increased or had declined to near normal values by the end of the test period.

In similar tests with 0·025% warfarin in oatmeal bait containing 5% mineral oil, it was found that the clotting ability of the plasma of N, HBR and FR mice was impaired earlier and that mortality in HBR and FR animals was significantly higher (62/67, 92·5% and 7/8, 87·5% respectively).

Three of seven HBR mice died after prolonged feeding on various warfarin baits but only after 186, 197 and 209 days respectively. The inclusion of mineral oil in bait containing 0-0·25% warfarin was more effective in decreasing the coagulability of the blood of these mice than either increasing the concentration of warfarin (to 0·1 and 0·2%) or including sulphaquinoxaline or corn oil.

Studies on mice given warfarin by injection and in feed indicated that in females the level of resistance to warfarin may be assessed on the basis of their response to a single injected dose of warfarin.

1. Cultures were obtained from 69 cases of ringworm of children in London County Council Schools.

2. Three of them were cases of favus, the parasite in each case being Achoroion Schōnleinii.

3. Microsporums are responsible for most of the ringworm, and were isolated from 54 of the 69 cases, or 78 per cent. Microsporum audouini was found in 70 per cent, of the Microsporum infections; M. lanosum and M. felineum each in one case; and 4 other cultures were obtained, comprising 3 species which have not yet been identified.

4.Endothrix Trichophytons were found in 17 per cent, of the cases and include the species Trichophyton crateriforme, T. sulfureum, T. acuminatum and T. violaceum.

5.A list of the species isolated arranged, according to the new classification of Ota and Langeron, is given.

6.The results are compared with those previously obtained in London by Fox and Blaxall, and Adamson, with which they broadly agree.

Disease cases are often clustered within herds or generally groups that share common characteristics. Sample size formulae must adjust for the within-cluster correlation of the primary sampling units. Traditionally, the intra-cluster correlation coefficient (ICC), which is an average measure of the data heterogeneity, has been used to modify formulae for individual sample size estimation. However, subgroups of animals sharing common characteristics, may exhibit excessively less or more heterogeneity. Hence, sample size estimates based on the ICC may not achieve the desired precision and power when applied to these groups. We propose the use of the variance partition coefficient (VPC), which measures the clustering of infection/disease for individuals with a common risk profile. Sample size estimates are obtained separately for those groups that exhibit markedly different heterogeneity, thus, optimizing resource allocation. A VPC-based predictive simulation method for sample size estimation to substantiate freedom from disease is presented. To illustrate the benefits of the proposed approach we give two examples with the analysis of data from a risk factor study on Mycobacterium avium subsp. paratuberculosis infection, in Danish dairy cattle and a study on critical control points for Salmonella cross-contamination of pork, in Greek slaughterhouses.

The lymphocyte profile of 521 HIV-infected subjects hospitalized at Jackson Memorial (2001–2002) was compared across main respiratory diseases. Study data included medical history and all laboratory evaluations performed during hospitalization. Community-acquired pneumonias (CAP, 52%), Pneumocystis jiroveci pneumonia (PCP, 24%), tuberculosis (TB, 9%) and non-tuberculous mycobacterial diseases (NTM, 12%) were the most frequent causes of admission. Patients hospitalized with PCP and NTM exhibited the lowest CD4 counts (P=0·003). PCP patients had the highest B-cell percentages (P=0·04). CAP patients had the highest CD8 and CD4 percentages and the lowest percentage of Natural Killer (NK) cells and viral burdens. TB patients exhibited the lowest NK-cell (11·4±6·3) and B-cell percentages (13·6±12) and the highest CD8 (59±14) percentage. NTM patients, in contrast, had the highest NK-cell percentages of the groups (19·1±11·6, P=0·01). Additionally, immune responses associated with respiratory pathogens differed in HIV-infected patients with CD4+ cells above and below 200 counts.

About one-fourth of the cases in a series of 160 patients suffering from scarlet fever appeared to be Dick-negative in the acute stage of the disease.

Throughout the illness there was a progressive decrease in the number of positives and in the intensity of the reactions, till in the second week two-thirds and in the fourth week nine-tenths of the total cases were negative. Almost 90 per cent, of the original positives showed this characteristic loss of the Dick-positive state. It would appear that this change occurs less readily in young children. Fluctuations in the reaction during the course of the illness are very uncommon, if indeed they occur at all.

Of eleven cases which failed to show the above change two relapsed. In the other 149 cases no relapses occurred.

Pseudo-reactions are uncommon. Two examples have been described. It is suggested that the use of heated filtrate may be unsatisfactory and that the mechanism of these reactions requires further study.

Some of the anomalous features of the Dick reaction have been briefly discussed. In the opinion of the writer these difficulties have been exaggerated, and they do not in themselves form sufficient grounds for concluding that the test is fallacious.

On the evidence at present available one must continue to regard scarlet fever as a specific toxaemia. The allergic conception of the disease is less convincing.

In previous studies of the bacterial flora of the upper respiratory tract and its variations during attacks of acute coryza (Hoyle, 1932), it was found that there was in many cases a striking relationship between the appearance of certain organisms with definite pathogenic properties towards the lower animals, in the upper respiratory tract, and the occurrence of acute infections. This relationship was especially marked in the case of the influenza bacillus, and it was suggested that this organism played a prominent part in the aetiology of upper respiratory infections. The significance of the influenza bacillus in acute coryza has been noted by various workers (Noble, Fisher and Brainard, 1928; Burky and Smillie, 1929; Webster and Clow, 1932; Kneeland and Dawes, 1932), but on the other hand various observers have found the incidence of influenza bacilli in the respiratory tract to be the same in normal health and in acute coryza, and Fleming (1929) and Fleming and Maclean (1930) have devised a technique by means of which they claim to have isolated influenza bacilli in 100 per cent, of normal throats. One possible explanation of these conflicting results may be found in the absence of any very exact criterion of what constitutes a typical influenza bacillus.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the novel global coronavirus disease 2019 (COVID-19) disease outbreak. Its pathogenesis is mostly located in the respiratory tract. However, other organs are also affected. Hence, realising how such a complex disturbance affects patients after recovery is crucial. Regarding the significance of control of COVID-19-related complications after recovery, the current study was designed to review the cellular and molecular mechanisms linking COVID-19 to significant long-term signs including renal and cardiac complications, cutaneous and neurological manifestations, as well as blood coagulation disorders. This virus can directly influence on the cells through Angiotensin converting enzyme 2 (ACE-2) to induce cytokine storm. Acute release of Interleukin-1 (IL1), IL6 and plasminogen activator inhibitor 1 (PAI-1) have been related to elevating risk of heart failure. Also, inflammatory cytokines like IL-8 and Tumour necrosis factor-α cause the secretion of von Willebrand factor (VWF) from human endothelial cells and then VWF binds to Neutrophil extracellular traps to induce thrombosis. On the other hand, the virus can damage the blood–brain barrier by increasing its permeability and subsequently enters into the central nervous system and the systemic circulation. Furthermore, SARS-induced ACE2-deficiency decreases [des-Arg9]-bradykinin (desArg9-BK) degradation in kidneys to induce inflammation, thrombotic problems, fibrosis and necrosis. Notably, the angiotensin II-angiotensin II type 1 receptor binding causes an increase in aldosterone and mineralocorticoid receptors on the surface of dendritic cells cells, leading to recalling macrophage and monocyte into inflammatory sites of skin. In conclusions, all the pathways play a key role in the pathogenesis of these disturbances. Nevertheless, more investigations are necessary to determine more pathogenetic mechanisms of the virus.

Verotoxigenic Escherichia coli (VTEC) serotype O157:H7 strains from a Swedish cattle prevalence study (n=32), and livestock-derived strains linked to human disease (n=13), were characterized by microarray and PCR detection of virulence genes. The overall aim of the study was to investigate the distribution of known virulence determinants and determine which genes are linked to increased pathogenicity in humans. A core set of 18 genes or gene variants were found in all strains, while seven genes were variably present. This suggests that the majority of VTEC O157:H7 found in Swedish cattle carry a broad repertoire of virulence genes and should be considered potentially harmful to humans. A single virulence gene type was significantly associated with strains linked to human disease cases (P=0·012), but no genetic trait to explain the increased virulence of this genotype could be found.