There were multiple waves of influenza-like illness in 1918, the last of which resulted in a highly lethal pandemic killing 50 million people. It is difficult to study the initial waves of influenza-like illness in early 1918 because few deaths resulted and few morbidity records exist. Using extant military mortality records, we constructed mortality maps based on location of burial in France and Belgium in the British Army, and on home town in Vermont and New York in the USA Army. Differences between early and more lethal later waves in late 1918 were consistent with historical descriptions in France. The maps of Vermont and New York support the hypothesis that previous exposure may have conferred a degree of protection against subsequent infections; soldiers from rural areas, which were likely to have experienced less mixing than soldiers from urban areas, were at higher risk of mortality. Differences between combat and disease mortality in 1918 were consistent with limited influenza virus circulation during the early 1918 wave. We suggest that it is likely that more than one influenza virus was circulating in 1918, which might help explain the higher mortality rates in those unlikely to have been infected in early 1918.

Clostridioides (Clostridium) difficile infection (CDI) is the leading cause of infectious diarrhoea in hospitalised patients, representing a substantial economic burden driven mainly by increased length of hospital stay (LoS). Currently in Japan, limited evidence on CDI-associated excess LoS is available. We conducted a retrospective, matched-cohort study using a large, Japanese, hospital-based administrative database. CDI was defined as CDI treatment plus either CDI diagnosis or positive enzyme immunoassay result. Propensity score matching at the time of CDI or recurrent CDI (rCDI) onset was applied to adjust baseline confounding and immortal time bias. The analysis included 5 994 054 hospitalisation records during 2008–2017, of which 11 823 were identified as CDI and 1359 as rCDI. The median excess LoS attributable to CDI and rCDI was 3 days and 6.5 days, respectively. The excess mortality attributable to CDI was 6.9%; there was no excess mortality attributable to rCDI (−1.9%). The median difference in costs attributable to CDI and rCDI during the residual stay was JPY 130 296 (USD 1185) and JPY 81 054 (USD 737) per hospitalisation, respectively. By adjusting the biases, the burden of CDI in Japan was evaluated. The findings could support decision making and resource allocation for CDI management in Japanese hospitals.

This longitudinal field study investigated the hypothesis that persistently high antibody levels indicate a high risk of Salmonella Dublin shedding in animals in 14 endemically infected dairy herds. A hierarchical multivariable logistic regression was used to analyse 6614 paired faecal cultures and four types of temporal antibody profiles from cattle aged ≥180 days. Age and repeated measurements on animals nested within herds were taken into account. Overall, the prevalence of faecal shedders was low (0·3% and 2·8% in the lowest and highest risk groups, respectively). An important predictor of faecal shedding was young age. There was a significant, but modest increase in risk in cattle with persistently high or recently increased antibody levels, but no difference between these two groups. Contrary to previous recommendations, the detection of carriers by the use of repeated antibody testing is not likely to be a plausible control option in most Salmonella Dublin-infected dairy herds.

This review aimed to compare the clinical features and CT imaging features between patients with pulmonary tuberculosis (PTB) and lung cancer and patients with PTB alone. That would help to analyse the differences between the two and consequently providing a theoretical basis for the clinical diagnosis and treatment for the patients. Relevant case-control studies focusing on the clinical and CT imaging characteristics between PTB with lung cancer and PTB alone were systematically searched from five electronic databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for comparison. As of 2021-07-06, a total of 1735 articles were retrieved. But only 15 articles were finally included for meta-analysis. The results showed a higher proportion of irritable cough, haemorrhagic pleural effusion and lower proportion of night sweating in PTB patients with lung cancer than in PTB patients, and the differences were statistically significant (irritable cough: OR 2.43, 95% CI 1.43–4.11; haemorrhagic pleural effusion: OR 5.73, 95% CI 1.63–20.12; night sweating: OR 0.56, 95% CI 0.36–0.87). In addition, there are many differences in the imaging characteristics of the two types of patients. In conclusion, this review summarises the similarities and differences in clinical symptoms and imaging features between patients with PTB and lung cancer and patients with PTB alone, suggesting that we should be alert to the occurrence of lung cancer in patients with obsolete PTB relapse.

This study assessed the incidence rate of all-cause pneumonia (ACP) and invasive pneumococcal disease (IPD) and associated medical costs among individuals aged ≥16 in the German InGef database from 2016 to 2019. Incidence rate was expressed as the number of episodes per 100 000 person-years (PY). Healthcare resource utilisation was investigated by age group and by risk group (healthy, at-risk, high-risk). Direct medical costs per ACP/IPD episode were estimated as the total costs of all inpatient and outpatient visits. The overall incidence rate of ACP was 1345 (95% CI 1339–1352) and 8.25 (95% CI 7.76–8.77) per 100 000 PY for IPD. For both ACP and IPD, incidence rates increased with age and were higher in the high-risk and at-risk groups, in comparison to the healthy group. ACP inpatient admission rate increased with age but remained steady across age-groups for IPD. The mean direct medical costs per episode were €8075 (95% CI 7121–9028) for IPD and €1454 (95% CI 1426–1482) for ACP. The aggregate direct medical costs for IPD and ACP episodes were estimated to be €8.5 million and €248.9 million respectively. The clinical and economic burden of IPD and ACP among German adults is substantial regardless of age.

On 16–17 January 2020, four suspected mumps cases were reported to the local Public Health Authorities with an epidemiological link to a local school and football club. Of 18 suspected cases identified, 14 were included in this study. Laboratory results confirmed mumps virus as the cause and further sequencing identified genotype G. Our findings highlight that even with a high MMR vaccine coverage, mumps outbreaks in children and young adults can occur. Since most of the cases had documented immunity for mumps, we hypothesise that waning immunity or discordant mumps virus strains are likely explanations for this outbreak.

Attempts to demonstrate reversed passive anaphylaxis in the guinea-pig with crystalline egg albumin as sensitizing antigen have been uniformly negative.

When purified anti-pneumococcal antibody globulin was used as sensitizing antigen, reversed anaphylactic shock could be elicited in guinea-pigs by the intravenous injection of precipitins for the antibody globulin.

The mild reactions which could be elicited when the total globulins from the serum of normal rabbits were used as sensitizing antigen are probably dependent on the presence of small amounts of y globulin.

Reversed passive anaphylaxis, like direct anaphylaxis, is dependent on a cellular mechanism, and the success of experiments in which rabbit antibody globulin was used as sensitizing antigen depends on the acceptability of the antibody to the cells of the guinea-pig's tissues.

Antigenic differences between antibody globulins and total normal globulins from rabbit serum are noted.

Measles surveillance data in Blantyre, Malawi were reviewed for 1996–8 to describe the epidemiology of infection and to estimate vaccine efficacy (VE) by the screening method. A total of 674 measles cases were reported to the Blantyre District Health Office during this period. Age distribution showed that 108 (16.1%) of the cases were aged less than 1 year. The median age was 5 years. Eighty percent of the cases between 1 and 19 years had been previously vaccinated. VE was 68.6% (95% CI, 52.7–79.2) for children 12–23 months of age and 67.3% (95% CI, 48.3–79.3) for infants 9–11 months of age. Reasons for this low vaccine efficacy are discussed. Previous vaccination history was negatively associated with the risk for developing cough during measles infection (odds ratio (OR), 0.30; 95% CI, 0.09–0.91), diarrhoea (OR, 0.64; CI, 0.44–0.95) and pneumonia (OR, 0.40; CI, 0.25–0.62). Logistic regression analysis showed that pneumonia in adults was negatively associated with vaccination history. The passive surveillance system for measles in Malawi was useful to describe the epidemiology of measles.

To provide comprehensive information on the epidemiology and burden of respiratory syncytial virus hospitalisation (RSVH) in preterm infants, a pooled analysis was undertaken of seven multicentre, prospective, observational studies from across the Northern Hemisphere (2000–2014). Data from all 320–356 weeks' gestational age (wGA) infants without comorbidity were analysed. RSVH occurred in 534/14 504 (3.7%) infants; equating to a rate of 5.65 per 100 patient-seasons, with the rate in individual wGA groups dependent upon exposure time (P = 0.032). Most RSVHs (60.1%) occurred in December–January. Median age at RSVH was 88 days (interquartile range (IQR): 54–159). Respiratory support was required by 82.0% of infants: oxygen in 70.4% (median 4 (IQR: 2–6) days); non-invasive ventilation in 19.3% (median 3 (IQR: 2–5) days); and mechanical ventilation in 10.2% (median 5 (IQR: 3–7) days). Intensive care unit admission was required by 17.9% of infants (median 6 days (IQR: 2–8) days). Median overall hospital length of stay (LOS) was 5 (IQR: 3–8) days. Hospital resource use was similar across wGA groups except for overall LOS, which was shortest in those born 35 wGA (median 3 vs. 4–6 days for 32–34 wGA; P < 0.001). Strategies to reduce the burden of RSVH in otherwise healthy 32–35 wGA infants are indicated.

A ‘black box’ paradigm has prevailed in which researchers have focused on the association between the total number of pathogens for which individuals are seropositive (i.e. total pathogen burden) and various chronic diseases, while largely ignoring the role that seropositivity for specific combinations of pathogens may play in the aetiology of such outcomes and consequently mortality. We examined the association between total pathogen burden as well as specific pathogen combinations and all-cause mortality in the United States. Data were from individuals aged ⩾25 years tested for cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2 and Helicobacter pylori, with mortality follow-up to 31 December 2006 in the National Health and Nutrition Examination Survey (NHANES) III (N = 6522). We did not observe a statistically significant graded relationship between total pathogen burden level and all-cause mortality. Furthermore, compared to those seronegative for all four pathogens, the greatest statistically significant rate of all-cause mortality was for those CMV+/HSV-2+ (hazard ratio 1·95, 95% confidence interval 1·13–3·35) adjusting for age, gender, race/ethnicity, education level, body mass index (kg/m2) and smoking status. Interventions targeting prevention or treatment of particular pathogens may be more effective for reducing mortality than those focused solely on reducing overall pathogen burden.

A cohort study on a barbecue-associated Salmonella outbreak was conducted to describe the burden of disease and to identify the outbreak vehicle. Dose–response relationships were tested with Fisher's exact and Wilcoxon rank sum tests (alpha = 0·05). S. Enteritidis isolates were cultured and phage-typed. Information was available for 11 out of 14 individuals attending the barbecue; all were healthy young adults (median age 27 years). The attack rate was 100%. Three cases were hospitalized and two developed acute pancreatitis. The exposure common to all cases was a vegetable pasta salad that had been stored unrefrigerated for 23 h. Consuming higher doses was associated with longer median symptom duration (7 days vs. 4 days, P = 0·11). S. Enteritidis was found in the stools of nine barbecue guests. Phage type 8/7 was identified in the stools of the salad preparer and one barbecue guest. This outbreak shows that S. Enteritidis can cause serious infection in young healthy individuals without well-known risk factors.

Persistent infection with one or more highly oncogenic human papillomaviruses (HPVs) or high-risk-HPV (HR-HPV) is necessary but not a sufficient aetiological agent for the development of cervical neoplasia. A number of viral, host, environmental and behavioural factors are suggested to be associated with the progression of cervical disorder. This study aimed to evaluate the impact of environmental and behavioural cofactors on the development of cervical disorders in HR-HPV-infected women in Serbia. A total of 541 women have been tested by PCR for the presence of HPV on the cervix. HPV genotypes were determined by direct DNA sequencing. Women identified as HR-HPV-positive were further classified into four subgroups according to their cytological status. All relevant information about demographical and behavioural factors was obtained by interviewer-based questionnaire. A number of analytical and descriptive statistical methods were used for processing the data. The cofactors found to be of significance for the progression of cervical disease were older age, body mass index >25, lower educational level, long-term smoking, previous genital infections and cervical interventions. On the other hand, condom use was found to have a protective role. Information about these cofactors might be very important for the development of more efficient cancer prevention programmes and promotion of anti-HPV vaccination.

In a 2-year longitudinal study of adult animals on 15 dairy farms and four sheep farms in Lancashire, UK, Arcobacter spp. were isolated from all farms although not at every sampling occasion. Faecal samples were collected and cultured using standard techniques for isolation of campylobacters. Assignment to species was via PCR assays. Apparent prevalence of Arcobacter spp. was higher in dairy cattle compared to sheep (40·1% vs. 8%, P < 0·001) and in housed cattle compared to cattle at pasture (50·1% vs. 20·9%, P < 0·001). This was reflected in the higher prevalence observed in herds that were housed (n = 4) all year compared to herds that grazed cattle on pasture in the summer and housed cattle in the winter (n = 11) (55·5% vs. 36%, P < 0·001). In the case of sheep, peak prevalence was observed in autumn with increased prevalence also being associated with improving pasture quality. There was an apparent inverse association between the faecal pat prevalence of Arcobacter spp. and Campylobacter jejuni although this may in part be an artefact of laboratory test method sensitivity, whereby a relative increase in the frequency of one bacterial species would reduce the sensitivity of detecting the other.

During a 5-year (2007–2011) surveillance period a total of 435 (15·34%) of 2834 stool specimens from children aged <14 years with acute gastroenteritis tested positive for norovirus and 217 strains were characterized upon partial sequence analysis of the polymerase gene as either genogroup (G)I or GII. Of the noroviruses, 99·2% were GII with the GII.P4 genotype being predominant (80%). GII.P4 variants (Yerseke 2006a, Den Haag 2006b, Apeldoorn 2008, New Orleans 2009) emerged sequentially during the study period. Sequence analysis of the capsid gene of 57 noroviruses revealed that 7·8% were recombinant (ORF1/ORF2) viruses including GII.P7_GII.6, GII.P16_GII.3, GII.P16_GII.13, GII.Pe_GII.2, and GII.Pe_GII.4, never identified before in Italy. GII.P1_GII.1, GII.P2_GII.1, GII.P3_GII.3 and GII.P6_GII.6 strains were also detected. Starting in 2011 a novel GII.4 norovirus with 3–4% nucleotide difference in the polymerase and capsid genes from variant GII.4 New Orleans 2009 was monitored in the local population. Since the epidemiology of norovirus changes rapidly, continuous surveillance is necessary to promptly identify the onset of novel types/variants.

An enzyme-linked immunosorbent assay (ELISA) for the rapid diagnosis of antibiotic-associated colitis (AAC) is presented. Commercially available antisera to Clostridium difficile toxins contain antibodies to other antigens found in non-toxigenic C. difficile and other bacteria. Removal of these unwanted antibodies by absorption increased the specificity of ELISA for detection of C. difficile toxins. Specimens tested included 40 faecal extracts positive for cytotoxicity from cases of AAC, 30 diarrhoeic and 30 well-formed stools negative for cytotoxicity and 50 culture filtrates of toxigenic and non-toxigenic C. difficile and other clostridial species. Use of absorbed sera reduced false-positive reactions observed with faecal specimens frqm 23 to 8 %. About 90 % of specimens that were positive by the tissue culture cytotoxicity test were positive by ELISA using the absorbed sera. The relative merits of ELISA and other methods for the rapid diagnosis of AAC are discussed.

The objectives of this work were (i) geographical analysis of the 2012–2014 outbreak of rabies in Greece using GIS and (ii) comparative analysis of animal cases with data of potential human exposure to rabies together with environmental data, in order to provide information for risk assessment, effective monitoring and control. Most animal cases (40/48) involved red foxes, while domestic animals were also diagnosed with rabies. Overall, 80% of the cases were diagnosed in central northern Greece; 75% of the cases were diagnosed in low altitudes (<343·5 m), within a distance of 1 km from human settlements. Median distance from livestock farms was 201·25 m. Most people potentially exposed to rabies (889/1060) presented with dog bite injuries. Maximum entropy analysis revealed that distance from farms contributed the highest percentage in defining environmental niche profiles for rabid foxes. Oral vaccination programmes were implemented in 24 administrative units of the country during 2013 and 2014, covering a total surface area of ~60 000 km2. Rabies re-occurrence in Greece emphasizes the need for ongoing surveillance in cross-border areas and in areas with intense human activity.

Wells (1937) discovered that field voles in this country are subject to an epizootic disease due to an acid-fast bacillus. The natural disease in the vole is characterized by the deposition of a cheesy substance in the areolar tissue spaces and the formation in the organs, the lungs particularly, of lesions which have a close resemblance to those of tuberculosis.

Good antibody responses usually follow infection with Campylobacter jejuni. A comparison of agglutination, complement fixation and immunofluorescence tests was done on 55 sera from 40 sporadic patients with diarrhoeal disease and positive cultures for C. jejuni. Results showed 82 % positive with immunofluorescence, 62 % by complement fixation but only 38 % by agglutination, using two reference strains COP and MEL as antigens. Overall 90 % of the 40 patients were positive by one or more serological tests. Paired sera from 15 patients showed a fourfold or greater rise in only five, confirming previous observations that antibody formation occurs early in the course of infection. Results also suggest that different test systems may be detecting antibodies of different specificities. Results confirm the value of serological tests, but further information on serotypes is required for selection of suitable reference strains.

It is shown that the assay for infectivity in bits of allantois-on-shell, which has been standardized on the BEL strain, is optimal also for nine representative strains of influenza virus tested.

On the average, the sensitivity of the technique is the same as of orthodox allantoic infectivity tests; its precision is always higher. The relative sensitivity of the two tests varies from strain to strain, the log tray/egg differences being SW (+0.88), MEL (+0.51), CAM (+0.31), PR8 (0.28), WSE (+0.25), HUT (−0.02), BEL (−0.22), FMI (−0.35), LEE (−0.47), BON (−1.02). This gradient is the same for fully infective and incomplete forms of influenza virus.

The tray/egg gradient of susceptibility is negatively correlated with the variation in host resistance.

The differences in susceptibility are not due to any effect of the plastic trays, to thermal inactivation of the virus, to differences in adsorption or viropexis in the two test systems or to the effect of allantoic fluid on the virus particle. The critical step has been shown to occur during the intracellular stage of multiplication.

Twenty-two reference isolates and 30 local isolates of group A Streptococci were classified into 36 electrophoretic types (ET) on the basis of allozyme variation at 27 enzyme loci. Local isolates were characterized by a high frequency of M-non typable strains. M-type and ET were more closely associated in local isolates from an endemically-infected population; nevertheless, amongst the local isolates there were also strains of the same ET type with different M-types. A possible explanation is that genetic exchange between strains may introduce different M-types into strains of defined ET when these are exposed to strong selection in the presence of heavy loads of infection.

In contrast to the reported clustering of strains associated with toxic shock-like syndrome into two closely related ET clones, we found no relationship of ET phenotype to acute poststreptococcal glomerulonephritis or rheumatic fever.