The COVID-19 epidemic showed inter-regional differences in Italy. We used an ecological study design and publicly available data to compare the basic reproduction number (R0), the doubling time of the infection (DT) and the COVID-19 cumulative incidence (CI), death rate, case fatality rate (CFR) and time lag to slow down up to a 50-days doubling time in the first and the second 2020 epidemic waves (δDT50) by region. We also explored socio-economic, environmental and lifestyle variables with multiple regression analysis. COVID-19 CI and CFR changed in opposite directions in the second vs. the first wave: the CI increased sixfold with no evidence of a relationship with the testing rate; the CFR decreased in the regions where it was initially higher but increased where it was lower. The R0 did not change; the initially mildly affected regions, but not those where the first wave had most severely hit, showed a greater δDT50 amplitude. Vehicular traffic, average temperature, population density, average income, education and household size showed a correlation with COVID-19 outcomes. The deadly experience in the first epidemic wave and the varying preparedness of the local health systems might have contributed to the inter-regional differences in the second COVID-19 epidemic wave.

1. In 19 out of 100 experiments guinea-pigs allowed to run free in houses which were presumably plague infected developed the disease and died.

2. On three occasions, namely, on every occasion on which the experiment was made, fleas transferred from plague-infected rats found in houses infected fresh guinea-pigs in the laboratory.

3. Rat fleas, caught on guinea-pigs in plague houses and transferred to fresh guinea-pigs, transmitted the disease in 35% of the cases.

4. A census of rat fleas in houses in Bombay, which were proved plague infected, indicated that rat fleas were 12 times as numerous as in control houses; and that in presumably infected houses rat fleas were four times as numerous as in control houses.

5. In 41 out of 130 fleas taken on guinea-pigs in plague-infected houses, bacilli microscopically indistinguishable from plague were found in the stomach.

6. In the case of 24 of the 27 houses definitely proved to be plague infected, dead rats had been found shortly before the experiments were made.

Rubella is a highly contagious mild viral illness. It is a leading cause of congenital rubella syndrome (CRS). Routine data of rubella do not exist in Ethiopia. However, laboratory-based conformation of rubella cases from measles negative samples were collected from a measles surveillance system. The current study was to analyse the epidemiological distribution of rubella cases from measles-suspected cases in Ethiopia from 2011 to 2015. National-based secondary data analysis of rubella through measles-based surveillances was carried out. Measles-suspected cases were investigated using the case investigation form, and a serum sample collected and sent to the Ethiopian laboratory for conformation. Samples tested for measles immunoglobulin M (IgM) were tested for rubella. The investigation results were entered into an electronic database using SPSS version 25 for analysis. Out of 11749 samples tested for rubella IgM from 2011 to 2015, 2295 (19.5%) were positive for rubella IgM and 51% of rubella-positive cases were female. Five per cent of all cases were female aged between 15 and 49. Cases were confirmed from all regions, two administrative towns and seasonal variations were observed with peaks in the first and fourth seasonal periods of the years. As fear of congenital abnormality (CRS), the Ethiopian government should focus on rubella syndrome surveillance with the aim of starting a rubella vaccine.

Typhoid fever is one of the prevailing endemic diseases of Palestine. In 1925 and 1926 epidemic outbreaks of considerable magnitude occurred in various parts of the country (Kligler, 1927). As a part of a general programme of the study of the epidemiology of this disease, we have attempted to ascertain the incidence of typhoid carriers in a general population group. Owing to the large number of typhoid cases which occurred there in 1925 and 1926, Afule, a village of some 1200 inhabitants, was chosen as a desirable spot for such an investigation.

Nosocomial outbreak of varicella zoster virus (VZV) has been reported when susceptible individuals encounter a case of chicken pox or shingles. A suspected VZV outbreak was investigated in a 50-bedded in-patient facility of Physical Medicine and Rehabilitation in a tertiary care multispecialty hospital. A 30-year-old female patient admitted with Pott’s spine was clinically diagnosed with chicken pox on 31 December 2022. The following week, four more cases were identified in the same ward. All cases were diagnosed as laboratory-confirmed varicella zoster infection by PCR. Primary case was a housekeeping staff who was clinically diagnosed with chicken pox 3 weeks prior (9 December 2022). He returned to work on eighth day of infection (17 December 2022) after apparent clinical recovery but before the lesions had crusted over. Thirty-one HCWs were identified as contacts a and three had no evidence of immunity. Two of these susceptible HCWs had onset of chickenpox shortly after first dose of VZV vaccination was inoculated. All cases recovered after treatment with no reported complications. VZV infection is highly contagious in healthcare settings with susceptible populations. Prompt identification of cases and implementation of infection prevention and control measures like patient isolation and vaccination are essential for the containment of outbreaks.

A series of spontaneous epidemics of a paratyphoid infection among guinea-pigs is described. It is shown that an epidemic may result from the introduction of a fresh susceptible population into an infected area and vice versa. Such epidemics developed only when the new population was exposed during certain months. The bringing in of a fresh population at the end of November was not followed at the time by an epidemic outbreak; the epidemic did not occur until the following July.

The observed seasonal occurrence was not due to a change in virulence. The strains isolated at the end of the 1926 epidemic did not differ in virulence from those cultivated at the height of the 1927 epidemic.

The guinea-pig may remain a carrier for a long time whilst eliminating bacteria in the faecal discharges only intermittently and in small numbers. In general, even in the case of infected animals, the discharge of pathogenic bacteria is relatively small, except a few days before death.

Attention is called to the parallelism between the seasonal prevalence of human typhoid epidemics in this country and the epidemics of paratyphoid observed in our guinea-pig stock.

It is pointed out that a sound theory of the epidemiology of certain diseases must take into account the seasonal variation in host susceptibility.

Vaccination has reduced the disease burden of vaccine-preventable diseases. However, the extent to which seasonal cycles of immunity could influence vaccine-induced immunity is not well understood. A national cross-sectional serosurveillance study performed in the Netherlands (Pienter-2) yielded data to investigate whether season of vaccination was associated with antibody responses induced by DT-IPV (diphtheria, tetanus and poliomyelitis), MMR (measles, mumps and rubella) and meningococcus C (MenC) vaccines in children. In total, 434 children met the inclusion criteria to study DT-IPV immunity, 811 for MMR and 311 for MenC. Differences in log(antibody levels) by season of vaccination were investigated with linear multivariable regression analyses. Seroconversion rates varied according to season of vaccination for rubella (90% of autumn-vaccinated children vs. 99% of winter-vaccinated had concentrations above cut-off levels). Summer-vaccinated boys showed a slower decline of tetanus antibodies (6% per month), in comparison with winter-vaccinated boys. In conclusion, season of vaccination showed little association with immunological protection. However, a number of associations were seen with a P-value of about 0.03; and adding data from a just-completed nationwide serological study might add more power to the current study. Further immunological and longitudinal investigations could help understand the mechanisms of seasonal influence in vaccine-induced responses.

While tetanus toxoid vaccination has reduced the incidence of tetanus in the developed world, this disease remains a substantial health problem in developing nations. Tetanus immune globulin (TIG) is used along with vaccination for prevention of infection after major or contaminated wounds if vaccination status cannot be verified or for active tetanus infection. These studies describe the characterisation of a TIG produced by a caprylate/chromatography process. The TIG potency and presence of plasma protein impurities were analysed at early/late steps in the manufacturing process by chromatography, immunoassay, coagulation and potency tests. The caprylate/chromatography process has been previously shown to effectively eliminate or inactivate potentially transmissible agents from plasma-derived products. In this study, the caprylate/chromatography process was shown to effectively concentrate TIG activity and efficiently remove pro-coagulation factors, naturally present in plasma. This TIG drug product builds on the long-term evidence of the safety and efficacy of TIG by providing a product with higher purity and low pro-coagulant protein impurities.

To mitigate the known high transmission risk in day-care facilities for children aged 0–6 years, day-care staff were given priority for SARS-CoV-2 vaccination in Rhineland-Palatinate, Germany, in March 2021. This study assessed direct and indirect effects of early vaccination of day-care staff on SARS-CoV-2 transmission in daycares with the aim to provide a basis for the prioritisation of scarce vaccines in the future. Data came from statutory infectious disease notifications in educational institutions and from in-depth investigations by the district public health authorities. Using interrupted time series analyses, we measured the effect of mRNA-based vaccination of day-care staff on SARS-CoV-2 infections and transmission. Among 566 index cases from day-care centres, the mean number of secondary SARS-CoV-2 infections per index case dropped by −0.60 case per month after March 2021. The proportion of staff among all cases reported from daycares was around 60% in the pre-interruption phase and significantly decreased by 27 percentage points immediately in March 2021 and by further 6 percentage points each month in the post-interruption phase. Early vaccination of day-care staff reduced SARS-CoV-2 cases in the overall day-care setting and thus also protected unvaccinated children. This should inform future decisions on vaccination prioritisation.

The SARS-CoV-2 pandemic persists with global repercussions. Initial COVID-19 symptoms encompass pneumonia, fever, myalgia, and fatigue. The human immune system produces IgM and IgG antibodies in response to SARS-CoV-2. Despite previous research, a comprehensive understanding of the interplay between clinical manifestations and humoral immune responses remains elusive. This study aims to scrutinize this association. 134 COVID-19 patients were enrolled, and stratified into mild, moderate, and severe symptom groups. Serum IgM and IgG levels were assessed thrice at one-month intervals using ELISA. The findings reveal significant elevation in serum IgG levels in moderate compared to mild cases (P < 0.001). Additionally, IgG production was significantly heightened in severe cases compared to both mild (P < 0.0001) and moderate (P < 0.05) groups. IgM and IgG levels peaked initially and diminished over time. While anti-SARS-CoV-2 antibodies are expected to confer protection, the direct correlation between IgG levels and symptom severity may arise from delayed immune activation, resulting in an intense antibody response in severe cases. Given evidence linking delayed immune function with a dysregulated innate immune response, comprehensive data collection should encompass not only serum IgG and IgM, but also early measurement of type I interferons at symptom onset. This could provide a more thorough understanding of COVID-19 progression.

Concentrations of the rodenticide ergocalciferol (vitamin D2) in samples of rodent baits laid in foodstores and in the laboratory were monitored over several months. Bait samples were solvent extracted and ergocalciferol concentration determined by high pressure liquid chromatography (HPLC). Ergocalciferol levels were constant for more than 21 days in dry samples and did not fall by more than 30% in 100 days. When water (10% w/w) was added to the baits in the laboratory the ergocalciferol concentration fell by approximately 30 % in 30 days. In these wet laboratory samples there was a rapid visible growth of fungus and in normal rodent control use baits should have been replaced when such deterioration became evident.

The association between time to positivity (TTP) of blood culture and the clinical prognosis of patients with Klebsiella pneumoniae bloodstream infection (BSI) remains unclear. A retrospective study of 148 inpatients with BSI caused by K. pneumoniae was performed at Shanghai Tongji Hospital, China, from October 2016–2020. The total in-hospital fatality rate was 32%. The median TTP was 11.0 (7.7–16.1) h and the optimal cutoff for prediction of in-hospital mortality was 9.4 h according to the ROC curve. Early TTP (<9.4 h) was a risk factor for in-hospital mortality by univariate analysis (OR = 2.5, 95% CI 1.2–5.0, P = 0.01), but not by multivariate analysis (OR = 2.7, 95% CI 1.0–7.4, P = 0.06). Old age, serum creatinine, white blood cells, and C-reactive protein values were risk factors for in-hospital mortality by multivariate analysis. Early TTP was not a risk factor for septic shock (OR = 1.8, 95% CI 0.6–5.1, P = 0.27) or ICU admission (OR = 1.0, 95% CI 1.0–1.0, P = 0.32). In conclusion, the in-hospital fatality rate of patients with K. pneumoniae BSI was relatively high and associated with an early TTP of blood cultures. However, no increased risk of mortality, septic shock or ICU admission was evident in early TTP patients.

Bile is often referred to as if its chemical composition was constant and that by treating samples of bile with extractives similar results would be obtained, whereas samples of human bile differ to such an extent that the term bile in itself signifies little. Two samples of human bile may differ to such an extent that while one sample has the qualities of true bile as regards its bile salt content the other may be entirely devoid of lytic action on red blood cells. Numerous experiments made with human bile obtained during life and from the post mortem room have shown this to be correct. The actual bile salt content of bile can be judged by boiling the bile to remove much of the protein, and also to destroy bacterial activity and then contrast the haemolytic activity of the treated sample with a 1 per cent, solution of bile salt in normal saline.

1. The chain of evidence incriminating the house fly as a disseminator of typhoid fever is at present fairly complete, but many of the links are weak and not thoroughly strengthened by experimentation.

2. The bulk of experimental work has hitherto been done under highly unnatural and artificial circumstances and the results so obtained cannot be accepted unreservedly as giving a correct view of conditions in nature.

3. The experiments described in the present paper show that flies can ingest typhoid bacilli from natural matter, i.e. human faeces and urine, and carry them for a certain period of time.

4. There is no evidence to show that the typhoid bacilli multiply in the house fly. On the contrary the evidence goes to show that they are not adapted for prolonged life on or in the fly.

5. It thus follows that the house fly is a purely mechanical carrier of the typhoid bacillus and is not a natural “host” in the strict sense of the term.

6. Many bacilli closely resembling B. typhosus in cultural characteristics appear to be natural or, at least, common inhabitants of the intestine of the house fly. These are extremely likely to be mistaken for B. typhosus unless the most stringent tests are employed.

7. As might be expected there is evidence to show that a process of bacterial selection occurs in the fly's intestine. Some bacteria appear to flourish but others are rapidly eliminated. Among the latter must be numbered B. typhosus.

I have to thank my colleagues at the Lister Institute, particularly Dr Ledingham, Dr Henderson Smith and Dr Petrie, for much valuable help and advice during the course of these investigations. To Prof. Bainbridge, Dr Arkwright, Dr Penfold and Dr Macalister my thanks are also due, inasmuch as they helped to smooth over many difficulties both theoretical and practical.

The investigation deals with the bacteriological examination of 386 samples of water from Manchester swimming baths where the method of purification could be studied.

There were 339 samples from chlorinated pools of which 160 gave acid and gas in MacConkey broth at 37° C. and 2130 strains were isolated. The remaining forty-seven samples were from untreated open-air pools. Thirty of these samples were positive and 270 strains were isolated. The strains were classified according to Wilson's method into the coli, intermediate, aerogenes and irregular groups, and only 1·78% of the total were found to be irregular. Both series of samples included more than 72% which contained coli, and among the chlorinated samples no less than 70% yielded aerogenes and nearly 49% intermediate type, while among the non-chlorinated baths there were 43% with aerogenes and 40% with intermediate type. There was a similar difference in the proportions of coli, aerogenes and intermediate type in chlorinated and in non-chlorinated baths when the results were considered on the basis of strains (Table II).

Since these differences in proportion were considered significant, and since the chief variation in conditions between outdoor and indoor baths consists of chlorination, a series of experiments was devised to test the effect of chlorine on pure cultures of coli, aerogenes, and intermediate type. There was very little change after adding 0·1 part of chlorine per million, but the addition of 0·3 and 0·5 part was followed by very rapid reduction in numbers with diminution in free chlorine. This reduction was on the whole least with aerogenes. The numbers continued to fall for about 48 hr. until all trace of chlorine had disappeared and then regrowth occurred. This regrowth was most vigorous and most rapid with aerogenes (see figures) but was very slow in all cases.

For the measles-mumps-rubella (MMR) vaccine, the World Health Organization-recommended coverage for herd protection is 95% for measles and 80% for rubella and mumps. However, a national vaccine coverage does not reflect social clustering of unvaccinated children, e.g. in schools of Orthodox Protestant or Anthroposophic identity in The Netherlands. To fully characterise this clustering, we estimated one-dose MMR vaccination coverages at all schools in the Netherlands. By combining postcode catchment areas of schools and school feeder data, each child in the Netherlands was characterised by residential postcode, primary and secondary school (referred to as school career). Postcode-level vaccination data were used to estimate vaccination coverages per school career. These were translated to coverages per school, stratified by school identity. Most schools had vaccine coverages over 99%, but major exceptions were Orthodox Protestant schools (63% in primary and 58% in secondary schools) and Anthroposophic schools (67% and 78%). School-level vaccine coverage estimates reveal strong clustering of unvaccinated children. The school feeder data reveal strongly connected Orthodox Protestant and Anthroposophic communities, but separated from one another. This suggests that even at a national one-dose MMR coverage of 97.5%, thousands of children per cohort are not protected by herd immunity.

Lockdowns have been a core infection control measure in many countries during the coronavirus disease 2019 (COVID-19) pandemic. In England's first lockdown, children of single parent households (SPHs) were permitted to move between parental homes. By the second lockdown, SPH support bubbles between households were also permitted, enabling larger within-household networks. We investigated the combined impact of these approaches on household transmission dynamics, to inform policymaking for control and support mechanisms in a respiratory pandemic context. This network modelling study applied percolation theory to a base model of SPHs constructed using population survey estimates of SPH family size. To explore putative impact, varying estimates were applied regarding extent of bubbling and proportion of different-parentage within SPHs (DSPHs) (in which children do not share both the same parents). Results indicate that the formation of giant components (in which COVID-19 household transmission accelerates) are more contingent on DSPHs than on formation of bubbles between SPHs, and that bubbling with another SPH will accelerate giant component formation where one or both are DSPHs. Public health guidance should include supportive measures that mitigate the increased transmission risk afforded by support bubbling among DSPHs. Future network, mathematical and epidemiological studies should examine both independent and combined impact of policies.

The results of experiments designed to determine the threshold values for various thermal stimuli have been reported. The threshold increments in the intensity of radiation in ‘still’ air were determined first for several areas of exposure. In further experiments the effects of simultaneous changes in both the speed and temperature of the air, and the air speed and radiation intensity, were examined.

The data from these experiments were then used to estimate the relation between the temperature and speed of the air on the rate of heat loss by convection. The findings were shown to be in good accord with previously published data.