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.

Case identification is an ongoing issue for the COVID-19 epidemic, in particular for outpatient care where physicians must decide which patients to prioritise for further testing. This paper reports tools to classify patients based on symptom profiles based on 236 severe acute respiratory syndrome coronavirus 2 positive cases and 564 controls, accounting for the time course of illness using generalised multivariate logistic regression. Significant symptoms included abdominal pain, cough, diarrhoea, fever, headache, muscle ache, runny nose, sore throat, temperature between 37.5 and 37.9 °C and temperature above 38 °C, but their importance varied by day of illness at assessment. With a high percentile threshold for specificity at 0.95, the baseline model had reasonable sensitivity at 0.67. To further evaluate accuracy of model predictions, leave-one-out cross-validation confirmed high classification accuracy with an area under the receiver operating characteristic curve of 0.92. For the baseline model, sensitivity decreased to 0.56. External validation datasets reported similar result. Our study provides a tool to discern COVID-19 patients from controls using symptoms and day from illness onset with good predictive performance. It could be considered as a framework to complement laboratory testing in order to differentiate COVID-19 from other patients presenting with acute symptoms in outpatient care.

Following the end of universal testing in the UK, hospital admissions are a key measure of COVID-19 pandemic pressure. Understanding leading indicators of admissions at the National Health Service (NHS) Trust, regional and national geographies help health services plan for ongoing pressures. We explored the spatio-temporal relationships of leading indicators of hospitalisations across SARS-CoV-2 waves in England. This analysis includes an evaluation of internet search volumes from Google Trends, NHS triage calls and online queries, the NHS COVID-19 app, lateral flow devices (LFDs), and the ZOE app. Data sources were analysed for their feasibility as leading indicators using Granger causality, cross-correlation, and dynamic time warping at fine spatial scales. Google Trends and NHS triages consistently temporally led admissions in most locations, with lead times ranging from 5 to 20 days, whereas an inconsistent relationship was found for the ZOE app, NHS COVID-19 app, and LFD testing, which diminished with spatial resolution, showing cross-correlation of leads between –7 and 7 days. The results indicate that novel surveillance sources can be used effectively to understand the expected healthcare burden within hospital administrative areas though the temporal and spatial heterogeneity of these relationships is a key determinant of their operational public health utility.

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.

Records of absenteeism from primary schools are valuable data for infectious diseases surveillance. However, the analysis of the absenteeism is complicated by the data features of clustering at zero, non-independence and overdispersion. This study aimed to generate an appropriate model to handle the absenteeism data collected in a European Commission granted project for infectious disease surveillance in rural China and to evaluate the validity and timeliness of the resulting model for early warnings of infectious disease outbreak. Four steps were taken: (1) building a ‘well-fitting’ model by the zero-inflated Poisson model with random effects (ZIP-RE) using the absenteeism data from the first implementation year; (2) applying the resulting model to predict the ‘expected’ number of absenteeism events in the second implementation year; (3) computing the differences between the observations and the expected values (O–E values) to generate an alternative series of data; (4) evaluating the early warning validity and timeliness of the observational data and model-based O–E values via the EARS-3C algorithms with regard to the detection of real cluster events. The results indicate that ZIP-RE and its corresponding O–E values could improve the detection of aberrations, reduce the false-positive signals and are applicable to the zero-inflated data.

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.

The increasing number of diversified small-scale farms (DSSF) that raise outdoor-based livestock in the USA reflects growing consumer demand for sustainably produced food. Diversified farms are small scale and raise a combination of multiple livestock species and numerous produce varieties. This 2015–2016 cross-sectional study aimed to describe the unique characteristics of DSSF in California, estimate the prevalence of Shiga toxin-producing Escherichia coli (STEC) in livestock and evaluate the association between risk factors and the presence of STEC in livestock, using generalised linear mixed models. STEC prevalence was 13.62% (76/558). Significant variables in the mixed-effect logistic regression model included daily maximum temperature (OR 0.95; CI95% 0.91–0.98), livestock sample source (cattle (OR 4.61; CI95% 1.64–12.96) and sheep (OR 5.29; CI95% 1.80–15.51)), multiple species sharing the same barn (OR 6.23; CI95% 1.84–21.15) and livestock having contact with wild areas (OR 3.63; CI95% 1.37–9.62). Identification of STEC serogroups of public health concern (e.g. O157:H7, O26, O103) in this study indicated the need for mitigation strategies to ensure food safety by evaluating risk factors and management practices that contribute to the spread and prevalence of foodborne pathogens in a pre-harvest environment on DSSF.

Applying a method of selective separation of the specific high polymers the intracellular site of the specific substance in the Copenhagen strain of Pneumococcus Type II was demonstrated, by electron microscopy; the specific polymeric material assumed to form the capsule is situated within the bacterial cell and the electron density of this material is sufficiently high to permit its detection.

The possibility of obtaining electron micrographs of the polymeric substances as contained in the cells or after their diffusion into the medium or when secreted as slime, suggests that the current concept of the capsules as the site of the specific substances may have to be reviewed.

The electron micrographs were made by Dr A. Petrovici to whom I express my thanks.

Transmission of varicella occurs frequently in schools and households. We investigated the characteristics of varicella cases derived from within-household transmission and the modes of varicella transmission between school and household settings in Shanghai, China, from 2009 to 2018. Within-household transmission occurred in 278 households, of which 134 transmission events were between children. Sixty-one household varicella transmission events may be attributed to isolation procedures for infected students during school outbreaks, and 7.6% of school outbreaks were caused by schoolchildren cases derived from within-household transmission. The frequency of ‘school-household-school’ transmission adds an additional layer of complexity to the control of school varicella outbreaks. Administration of varicella vaccine as post-exposure prophylaxis after exposure is considered to be an effective measure to control varicella spread within households and schools.

The conclusions I seek to draw from this part of my investigations are:—

1. That a malarial form of horse-sickness probably occurs naturally.

2. That when animals which are either naturally relatively susceptible, such as the donkey, ox, and goat, or animals which have acquired protection, e.g. “salted” horses, are inoculated with virulent horse-sickness blood, their blood conveys a modified infection of horse-sickness which is malarial in type.

3. That this malarial from is associated with the presence of parasites within the red corpuscles of the blood of the infected animal.

4. That the blood of “salted” horse which have been previously regularly inoculated during several months is of a dangerous order of virulence. Vide former experiments.

5. That the blood of “salted” horses which have only been once inoculated after several months' rest conveys a fairly severe fever.

6. That the blood of “salted” horses, which have not been inoculated for even a year, can still convey infection.

7. That “unsalted” horses which have been inoculated a year previously with “salted” blood convey only a week infection.

8. That a severe attack of malarial horse-sickness gives a considerable degree of protection against subsequent inoculation with “salted” blood.

9. That when regularly inoculated “salted” horses are used to produce blood giving severe fever, such fever may become so severe as to cause death with symptoms of horse-sickness.

10. That the blood of the latter animals which die can produce virulent horse-sickness in clean horses, if used in a considerable dose, i.e. 20 c.c.

As the on-going severe acute respiratory syndrome coronavirus 2 pandemic, we aimed to understand whether economic reopening (EROP) significantly influenced coronavirus disease 2019 (COVID-19) incidence. COVID-19 data from Texas Health and Human Services between March and August 2020 were analysed. COVID-19 incidence rate (cases per 100 000 population) was compared to statewide for selected urban and rural counties. We used joinpoint regression analysis to identify changes in trends of COVID-19 incidence and interrupted time-series analyses for potential impact of state EROP orders on COVID-19 incidence. We found that the incidence rate increased to 145.1% (95% CI 8.4–454.5%) through 4th April, decreased by 15.5% (95% CI −24.4 −5.9%) between 5th April and 30th May, increased by 93.1% (95% CI 60.9–131.8%) between 31st May and 11th July and decreased by 13.2% (95% CI −22.2 −3.2%) after 12 July 2020. The study demonstrates the EROP policies significantly impacted trends in COVID-19 incidence rates and accounted for increases of 129.9 and 164.6 cases per 100 000 populations for the 24- or 17-week model, respectively, along with other county and state reopening ordinances. The incidence rate decreased sharply after 12th July considering the emphasis on a facemask or covering requirement in business and social settings.

To assess areas at risk for poliovirus circulation in Ecuador, we first selected provinces at highest risk based on low immunization coverage with three doses of oral poliovirus vaccine, and a low number of reported cases of acute flaccid paralysis (AFP). Subsequently, we reviewed discharge data for the period 1996–2000 for diagnoses compatible with AFP in the only two national referral hospitals in Quito, and at least two main hospitals in each of the six selected provinces. Environmental samples from one or two cities/towns in each selected province were tested for poliovirus. Of the 14 identified AFP-compatible cases, 8 (57%) had been previously reported and investigated. We visited four out of the six unreported cases; none of those four had sequelae compatible with poliomyelitis. From the 14 environmental samples taken, we identified Sabin viruses in six of the samples; no vaccine-derived polioviruses were isolated. Using this methodology, we found no evidence of undetected poliovirus circulation in Ecuador.

In recent years, human leptospirosis has been reported in Jinping and Liping counties, Guizhou province, but the leptospires have never been isolated. To track the source of infection and understand the aetiological characteristics, we performed surveillance for field mice carriage of leptospirosis in 2011. Four strains of leptospire were isolated from Apodemus agrarius. PCR confirmed the four isolates as pathogenic. Multiple-locus variable-number tandem repeat analysis (MLVA) showed that the four strains were closely related to serovar Lai strain 56601 belonging to serogroup Icterohaemorrhagiae, which is consistent with the antibody detection results from local patients. Furthermore, the diversity of leptospiral isolates from different hosts and regions was demonstrated with MLVA. Our results suggest that A. agrarius may be the main carrier of Leptospira in Jinping and Liping counties, and the serogroup Icterohaemorrhagiae serovar may be the epidemic serogroup of Leptospira. This will contribute to the control and prevention of leptospirosis in these localities.

All respiratory illnesses which were reported to the medical officers between September 1966 and December 1967 on a Royal Air Force station of 350 men were studied virologically.

Three periods of increased respiratory infections were observed: two occurred in the autumn, one in each year, and the third in the winter during January and February. The autumnal outbreaks were associated mainly with rhinovirus infections, and high isolation rates (82·1, 65·9%) were achieved at these times. Few of the illnesses during the winter outbreak could be diagnosed in the laboratory, and no evidence was found of infection with ‘coronaviruses’.

Despite the entrance of 30 fresh recruits direct from civilian life every 5 weeks, the respiratory infections encountered on the station were very similar to those in the local population and were not predominantly infections with adenoviruses, Coevirus, and Mycoplasma pneumoniae, as previously reported from larger military recruit centres.

On February 10th, 1911, the attention of the Medical Officer of Health was called by the practitioner in charge to an outbreak of diarrhoea in a family named R. residing in Paddington. The note made at the interview was to the effect that cases had occurred on the 8th, 9th, and 10th (2 cases) of the month, the four patients having violent diarrhoea and passing much blood. The onset was quite sudden in every case. It was thought that “food poisoning” could be excluded, and the main object in directing attention to the outbreak was to ascertain if any defective drainage existed at the house. Incidentally it may be remarked that the house drainage, etc. had been completely overhauled in 1907 and that no defects existed in February last except one leaky joint on a waste pipe.

The blood of plague-infected rats may contain an enormous number of plague bacilli, even as many as 100,000,000 per c.c. having been found before death. On the other hand rats occasionally die from plague with little or no septicaemia. An insect sucking the blood of most rats shortly before death would imbibe a large number of bacilli.

While the blood of a rat may have as many as 100,000,000 organisms in a c.c. the urine may have none at all, or at least less than 10 per c.c. Plague bacilli were discovered in the urine in 29 per cent. of the cases. When the urine does contain plague bacilli they are always present in much fewer numbers than in the blood.

The faeces of rats dead of plague and the blood of which contained abundant bacteria are not highly infective and would appear to play little part in the spreading of the epizootic.

1. The principle cause of post-scarlatinal diptheria is the admission into the scarlet fever wards of patients who, whether suffering from clinical diphtheria or not, are carriers of virulent diphtheria bacilli.

2. In large centres of population, where diphtheria always exists, diphtheria bacilli are to be found in a not inconsiderable proportion of school-children. In the absence both of evidence of clinical diphtheria and of a history of exposure to that affection, the bacilli are, in the majority of cases, of the non-virulent or saprophytic type and of little hygienic importance; in cases, on the other hand, where the clinical supports the bacteriological examination the bacilli are almost certainly virulent, and therefore dangerous; while in cases where the patient is known to have been exposed to infection the chances are great that the organisms are of the pathogenic variety, and such cases should always be regarded with grave suspicion.

3. On account of the prevalence of the non-virulent bacillus and the fallacies of single cultures, it may be doubted whether a routine bacteriological examination of throat and nose of all patients on admission would prove of sufficient value to repay the labour involved. Chief reliance must be placed on a careful inspection on admission, not only of the throat, but also of the nasal cavities, bacteriological examination being resorted to in cases of doubt.

4. In eradicating infection from an invaded ward bacteriological methods are, on the other hand, of prime importance, since children with apparently healthy throats and noses are often found to have acquired the virulent bacillus. An attempt to stamp out any outbreak of diphtheria by bacteriological examination of the throat alone is, however, futile, owing to the frequent infection of the nasal cavities.

5. Fibrinous rhinitis, which appears to be a not infrequent, though often unrecognised, affection of children is a common form of postscarlatinal diphtheria.

6. Although the treatment of diphtheria in the same hospital has no appreciable influence on the incidence of this complication of scarlet fever, it is advisable that precautions should be taken lest nurses harbouring diphtheria bacilli carry infection from the diphtheria to the scarlet fever wards.

7. To limit the risk of exposure to infection many-bedded wards should be avoided, and the mixing of patients from different wards prevented.

The sensitivity of in vitro- and in vivo-grown strains of S. typhi was determined not only by their antigenic structure, but also by their growth phase. An increased vulnerability to the antibody-complement system has been found in cells during the lag and the early exponential phase, while non-multiplying cells devoid of any nutrient were almost invulnerable to the antibody-complement system. Extracts of organs from normal and infected animals may promote the growth of S. typhi, and, therefore, increase its vulnerability to the antibody-complement system. The majority of extracts from organs of mice infected with strain Ty 2 inhibited markedly the bactericidal action of serum on this strain and, to a lower extent, on strain O 901.