COVID-19 research has been produced at an unprecedented rate and managing what is currently known is in part being accomplished through synthesis research. Here we evaluated how the need to rapidly produce syntheses has impacted the quality of the synthesis research. Thus, we sought to identify, evaluate and map the synthesis research on COVID-19 published up to 10 July 2020. A COVID-19 literature database was created using pre-specified COVID-19 search algorithms carried out in eight databases. We identified 863 citations considered to be synthesis research for evaluation in this project. Four-hundred and thirty-nine reviews were fully assessed with A MeaSurement Tool to Assess systematic Reviews (AMSTAR-2) and rated as very low-quality (n = 145), low-quality (n = 80), medium-quality (n = 208) and high-quality (n = 151). The quality of these reviews fell short of what is expected for synthesis research with key domains being left out of the typical methodology. The increase in risk of bias due to non-adherence to systematic review methodology is unknown and prevents the reader from assessing the validity of the review. The responsibility to assure the quality is held by both producers and publishers of synthesis research and our findings indicate there is a need to equip readers with the expertise to evaluate the review conduct before using it for decision-making purposes.

Non-steroidal anti-inflammatory drugs (NSAIDs) may inhibit antibody production by peripheral blood mononuclear cells; one consequence of this could be decreased effectiveness of vaccines in NSAID users. Because many older adults use low-dose aspirin for primary or secondary prevention of coronary events, any inhibitory effect of aspirin on vaccine immune response could reduce the benefits of vaccination programmes in older adults. We tested whether immune response to vaccination differed between users vs. non-users of low-dose aspirin, using data from four randomized trials of monovalent 2009 pandemic influenza A(H1N1) vaccine. Geometric mean haemagglutination inhibition antibody titres were not significantly lower in low-dose aspirin users compared to non-users. Our results provide reassurance that influenza vaccination effectiveness is probably not reduced in older adults taking chronic low-dose aspirin.

Salmonella Typhimurium DT1 is endemic to Finland and has caused human outbreaks since the 1960s. Domestic DT1 isolates (n=235) from 1972 to 1999 from human cases, animals and other sources, as well as foreign DT1 isolates from human cases (n=20) were analysed by molecular methods. Pulsed-field gel electrophoresis (PFGE) yielded 38 XbaI profiles. Of these, XbaI profile 10 was seen in 49% (125/255) of the isolates. Twelve IS200 profiles were obtained; the most common IS200 profile D was seen in 64% (33/52) of the isolates. Two clusters were formed by compilation of the XbaI–, BlnI– and SpeI–PFGE and IS200 profiles and possession of the serovar-specific virulence plasmid. The major cluster contained eight IS200 profiles, including IS200 profile D and XbaI profile 10, and had no virulence plasmid, and can be regarded as typical of the endemic Typhimurium DT1 infection.

In 2011, from August to November, the Monroe County Department of Public Health (MCDPH) investigated 47 salmonellosis cases. Geographical information software (GIS) was used to map the address locations of these cases. The resulting GIS analysis and culture information indicated that there were two distinct clusters of Salmonella that were geographically different. Pulsed-field gel electrophoresis (PFGE) testing was run at the New York State Department of Health Wadsworth Laboratory and identified S. Enteritidis (23 cases) and S. Typhimurium (10 cases). The epidemiological investigation identified Turkish pine nuts as the link between ill S. Enteritidis cases. Pine nut samples sent for laboratory testing were a PFGE match to human isolates with S. Enteritidis. A national recall of Turkish pine nuts ensued. A multistate outbreak was identified as a result of the initial investigation of MCDPH, in which 43 people were infected with the outbreak strain from five states. GIS software and shopper card data provided important tools in the epidemiological investigation.

Pyocine typing was used for the characterization of 134 Pseudomonas aeruginosa strains isolated from bovine mastitis. The scheme of Gillies & Govan (1966) was adopted with some modifications, and the procedure gave 89·6% typability. Pyocine type 1 strains were most commonly encountered and were followed in frequency by types 10 and 3. The introduction of two additional indicator strains allowed for division of these types into subtypes.

In spite of some limitations, discussed in the paper, the pyocine typing scheme proved to be useful in ‘marking’ P. aeruginosa strains and in following their association with bovine mastitis in various herds.

Since the incursion of influenza A(H1N1)pdm09 virus in 2009, serosurveillance every year of the Norwegian pig population revealed the herd prevalence for influenza A(H1N1)pdm09 (HIN1pdm09) has stabilised between 40% and 50%. Between 30 September 2009 and 14 September 2017, the Norwegian Veterinary Institute and Norwegian Food Safety Authority screened 35,551 pigs for antibodies to influenza A viruses (IAVs) from 8,636 herds and found 26% or 8,819 pigs' sera ELISA positive (titre ≥40). Subtyping these IAV antibodies from 8,214 pigs in 3,629 herds, by a routine haemagglutination inhibition test (HAIT) against four standard antigens produced 13,771 positive results (HAIT titre ≥40) of binding antibodies. The four antigen subtypes eliciting positive HAIT titre in descending frequencies were immunogen H1N1pdm09 (n = 8,200 or 99.8%), swine influenza A virus (SIVs) subtypes swH1N1 (n = 5,164 or 62%), swH1N2 (n = 395 or 5%) and swH3N2 (n = 12 or 0.1%). Of these 8,214 pig pigs sera, 3,039 produced homologous HAIT subtyping, almost exclusively immunogen H1N1pdm09 (n = 3,026 or 99.6%). Using HAIT titre of pig and herd geometric mean titre (GMT) as two continuous outcome variables, and with the data already structured hierarchically, we used mixed effects linear regression analysis to investigate the impact of predictors of interests had on the outcomes. For the full data, the predictors in the regression model include categorical predictors antigen subtype (H1N1pdm09, swH1N1, swH1N2 & swH3N2), and production type (sow herd or fattening herd), ordinal predictors year (longitudinally from 2009 to 2017) and number of antigens in heterologous reactions (1, 2, 3, 4) in the same pig serum. The last predictor, the proportion of HAIT positive (antigen specific) in tested pigs within the herd, was a continuous predictor, which served as a proxy for days post-infection (dpi) or humoral response time in the pig or herd. Regression analysis on individual pig HAIT titres showed that antigen as a predictor, the coefficient for immunogen H1N1pdm09 was at least fourfold higher (P < 0.001) than the three SIVs antigen subtypes, whose much lower coefficients were statistically no different between the three SIVs antigen subtypes. Correspondingly, for herd GMT, immunogen H1N1pdm09 was 28–40-fold higher than the three SIVs antigen subtypes. Excluding the HAIT data of the three SIVs antigen subtypes, regression analysis focusing only on immunogen H1N1pdm09 increased greatly the coefficients of the predictors in the models. Homologous reactions (99.6% H1N1pdm09) have lower HAIT titres while the likelihood of the number of antigens involved in HAIT heterologous reactions in a single pig serum increased with higher HAIT titres of immunogen H1N1pdm09. For predictor ‘production’, sows and sow herds had higher HAIT titres and GMT compared to fattening pigs and fattening herds respectively. Herds with ‘higher proportion of pigs tested positive’ also had higher HAIT titre in the pig and herd GMT.

To investigate the frequencies of dendritic cells (DCs) and Toll-like receptor 3 (TLR3) in neonates of HBsAg-positive mothers with different HBV serological profiles, we conducted a study in Taiyuan, China. The study included 144 HBsAg-positive mothers and their neonates. The frequencies of DCs and TLR3 were determined using four-colour flow-cytometric analysis. DC and TLR3 frequencies were not related to HBV intrauterine transmission, maternal HBeAg positivity, maternal HBV DNA positivity and HBeAg/HBV DNA double-positivity. The plasmacytoid dendritic cell (pDC) frequencies in neonates whose maternal HBV DNA was >5 × 107 copies/ml decreased significantly compared to that in neonates whose maternal HBV DNA was ⩽5 × 107 copies/ml (Z = − 2·170, P = 0·03) or whose maternal HBV DNA was negative (Z = − 1·981 P = 0·048). This study suggests that neonatal pDC frequencies decrease when maternal HBV DNA loads are >5 × 107 copies/ml.

Twenty–four cultures comprising 20 clinical isolates of ‘Klebsiella aerogenes’ from two hospitals, a reference strain of ‘K. aerogenes’ and the type strains of three other Klebsiella species, were characterized by one–dimensional sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) of whole–cell proteins. The protein patterns were highly reproducible and were used as the basis of a numerical analysis which divided the clinical isolates into 12 protein types. Comparison with established typing methods indicated that the level of discrimination of SDS–PAGE was similar to that achieved with conventional typing methods but the strains were grouped differently. Protein typing sub–divided five serotype K3 isolates that could also be distinguished by phage typing. Conversely, three strains of protein type 11 were clearly distinguishable by both serotyping and phage typing. We conclude that high–resolution SDS–PAGE of proteins provides an effective adjunct to other methods for typing isolates of ‘K. aerogenes’.

1. The membrane piece technique for in vitro titrations of the infectivity of influenza virus is described. Rectangles of shell, about 8 × 25 mm., with the chorio-allantoic membrane still attached (membrane pieces) are cut from thirteenth-day fertile eggs. One piece in a test-tube with glucose-buffered salt solution forms an individual assay unit. Five or more tubes are inoculated with each virus dilution. After incubation at 37° C. for 72 hr., with agitation for the first 24 hr. the fluid in each tube is tested for haemagglutinins. From the results at each dilution, an estimate of the 50% membrane piece (MP50) infectivity titre is obtained.

2. Six hundred assay units, with pieces cut from twenty eggs, can be set up by two workers in 1 hr. and used for titration of between three and twenty-four individual virus preparations, depending on the reliability desired for the 50% end-point estimates.

3. With the D.S.P. and PR 8 strains of influenza A virus, the MP50 titres parallel the EID50 titres from egg titrations, but are eight times and twenty times lower, respectively. The MP50: EID50 ratio is the same for various preparations of the same strain, including standard allantoic fluid and chorio-allantoic membrane virus, incomplete virus, and inactivated (heated) allantoic fluid virus. Preliminary experiments with Lee influenza B virus show that slightly different experimental conditions are required, and the MP50 titres are about fifty times less than the EID50 titres.

4. Consistent results have been obtained on titration of samples of the same virus preparation on a number of occasions over a period of several months.

5. A large number of membrane pieces can be used to test each virus dilution, and sampling variations in the MP50 estimates thus made quite small. Statistical data on the reliability of a 50 % titration result, and on the minimum significant differences between two end-points, are given for different values of n, the number of membrane pieces used to test each virus dilution, and of d, the log dilution step.

We are grateful to Mr J. Collins for invaluable technical assistance, and also to Miss I. Allen for help with the computations.

During outbreaks of hospital-acquired influenza-like illness (HA-ILI) healthcare workers (HCWs), patients, and visitors are each a source of infection for the other. Quantifying the effects of these various exposures will help improve prevention and control of HA-ILI outbreaks. We estimated the attributability of HA-ILI to: (1) exposure to recorded or unrecorded sources; (2) exposure to contagious patient or contagious HCW; (3) exposure during observable or unobservable contagious period of the recorded sources; and, (4) the moment of exposure. Among recorded sources, 59% [95% credible interval (CrI) 34–83] of HA-ILI of patients was associated with exposure to contagious patients and 41% (95% CrI 17–66) with exposure to contagious HCWs. Exposure during the unobservable contagiousness period of source patients accounted for 49% (95% CrI 19–75) of HA-ILI, while exposure during the unobservable contagiousness period of source HCWs accounted for 82% (95% CrI 51–99) of HA-ILI. About 80% of HA-ILIs were associated with exposure 1 day earlier. Secondary cases of HA-ILI might appear as soon as the day after the detection of a primary case highlighting the explosive nature of HA-ILI spread. Unobservable transmission was the main cause of HA-ILI transmission suggesting that symptom-based control measures alone might not prevent hospital outbreaks. The results support the rapid implementation of interventions to control influenza transmission.

Nine caprine and ovine mycoplasma strains, said to be indistinguishable serologically from Mycoplasma mycoides subsp. mycoides (the causative organism of contagious bovine plouropneumonia; CBPP) were examined in mice by (1) a mycoplasmaemia test, and (2) a cross-protection test. Of the nine strains, two from goats belonged to a small colony (SC) type; four caprine and three ovine strains belonged to a large colony (LC) type.

The two SC strains – like a single SC strain examined in an earlier study – were indistinguishable from genuine M. mycoides subsp. mycoidesas isolated from CBPP. They produced mycoplasmaemia readily. In a cross-protection test, the two SC strains and a CBPP strain immunized completely against each other.

Of the seven LC strains, six – like six LC strains examined in an earlier study – were easily distinguished from genuine M. mycoides subsp. mycoides; except for one that was not tested, all were shown to lack the ability to produce mycoplasmaemia readily. In cross-protection tests all six strains immunized partially but not completely against a CBPP strain.

The soventh LC strain (Mankefár 2833) was exceptional: it produced mycoplasmaemia readily, resembling tho SC strains in this respect. Like other LC strains, in cross-protection tests it protected only partially against a CBPP strain. Strain Mankef´r 2833 was isolated in ca. 1005 by Brack from a Barbary sheep (Ammolragus lervia) in a German zoo.

The ability of Mankefár 2833 to produce mycoplasmaemia enabled it to be used as a challenge strain in cross-protection tests. For the purpose of such tests the collection of nine mycoplasma strains referred to above was augmented with six LC strains from an earlier study. Partial but not complete protection against Mankefár 2833 was produced by two caprine SC strains, one CBPP strain, and nine LC strains. Three further LC strains gave protection that may have been as strong as that produced by the homologous strain, but confirmatory experiments are needed. A strain of M. mycoides subsp. capri gave no protection against Mankefár 2833.

The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006–2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.

Thorough studies on whether point prevalence surveys of healthcare-associated infections (HAIs) can be used to reliably estimate incidence of surgical site infections (SSIs) are scarce. We examined this topic using surveillance data of 58 hospitals that participated in two Dutch national surveillances; HAI prevalence and SSI incidence surveillance, respectively. First, we simulated daily prevalences of SSIs from incidence data. Subsequently, Rhame & Sudderth's formula was used to estimate SSI incidence from prevalence. Finally, we developed random-effects models to predict SSI incidence from prevalence and other relevant variables. The prevalences simulated from incidence data indicated that daily prevalence varied greatly. Incidences calculated with Rhame & Sudderth's formula often had values below zero, due to the large number of SSIs occurring post-discharge. Excluding these SSIs, still resulted in poor correlation between calculated and observed incidence. The two models best predicting total incidence and incidence during initial hospital stay both performed poorly (proportion of explained variance of 0·25 and 0·10, respectively). In conclusion, incidence of SSIs cannot be reliably estimated from point prevalence data in Dutch hospitals by any of the applied methods. We therefore conclude that prevalence surveys are not a useful measure to give reliable insight into incidence of SSIs.

When the blood serum of one animal is injected into an animal of a different species the injected animal in many instances appears to take no hurt. If however after a certain interval the experiment is repeated, it has been noted that the injected animal may speedily show evidence of physical disturbance. Its breathing becomes rapid: its heart-beat grows feeble: its limbs move spasmodically and general convulsions may ensue. These phenomena have been taken to indicate that the injected animal has been supersensitized—or rendered abnormally sensitive—to the serum employed. They may attain such gravity that the animal dies. It has been suggested that the same untoward issue is possible in the case of man, and that the death of patients under treatment for diphtheria is to be apprehended in certain circumstances as the result of repeated injections of antidiphtherial serum, for the reason that the serum in question is derived not from the human subject but from the horse. A suggestion which assails the prestige of the antitoxin treatment of diphtheria cannot be viewed with indifference: it must either be sustained or rejected.

The mumps resurgence has frequently been reported around the world in recent years, especially in many counties mumps vaccines have been widely used. This study aimed to describe the spatial epidemiological characteristics of mumps in Jiangsu, and provide a scientific basis for the implementation and adjustment of strategies to prevent and control mumps. The epidemiological characteristics were described with ratio or proportion. Spatial autocorrelation, Tango's flexible spatial scan statistics, and Kulldorff's elliptic spatiotemporal scan statistics were applied to identify the spatial autocorrelation, detect hot and cold spots of mumps incidence, and aggregation areas. A total of 172 775 cases were reported from 2004 to 2020 in Jiangsu. The general trend of mumps incidence is declining with a bimodal seasonal distribution identified mainly in summer and winter, respectively. Children aged 5–10 years old are the main risk group. A migration trend of hot spots from southeast to northwest over time was found. Similar high-risk aggregations were detected in the northwestern parts through spatial-temporal analysis with the most likely cluster time frame around 2019. Local medical and health administrations should formulate and implement targeted health care policies and allocate health resources more appropriately corresponding to the epidemiological characteristics of mumps.

A review of 194 cases of enteric infection in Scotland during 1967–74, is reported. Diagnosis was confirmed by the laboratory isolation of Salmonella typhi (64 cases), S. paratyphi A (3) and S. paratyphi B (127), from blood or faeces; 174 persons were clinically ill and 20 were symptomless infections.

Most patients (81·0%) were under 35 years of age, with the highest incidence occurring among young adults of 15–24 years, many of whom had been travelling overseas. One-third of all cases (65) were imported infections; the remaining 129 patients had not been outside the United Kingdom. A significantly greater proportion of typhoid infection (54·7%) was contracted overseas, in contrast to paratyphoid B with only one-fifth of cases (21·2%) being imported; all three cases of paratyphoid A were imported. The geographic distribution of origin of imported infections is discussed, along with the frequency of organisms belonging to different phage types.

Two deaths occurred, one of which was the result of complications of paratyphoid fever. All other patients responded well to treatment, although two persons continued to excrete and became chronic carriers.

A few examples are given of episodes of particular epidemiological interest.

It is expected that in future years there will be a continued increase in the proportion of imported infections as more persons travel overseas, concurrent with the continuing decline in the number of chronic carriers resident in the British Isles.

The distribution of adenovirus types in faecal samples of patients with suspected viral gastroenteritis from South Australia was determined during the 12-month period, July 1991–June 1992. There were 3299 samples tested and 226 (6·9%) were positive for adenovirus by enzyme immunoassay. Of these 226 samples. 154 (68%) were typed directly using virus DNA extracted from the faecal samples according to the Sma I, Hind III and BstEII restriction patterns and Southern hybridization analysis with pooled viral genomic DNA probes. In this group, 86% of the samples were from patients who were < 3 years of age. Enteric adenovirus types 40 and 41 accounted for 20 and 40% respectively, of these samples, and types 1, 2, 3, 5, 6, 7 and 31 comprised the remainder. Type 40 was detected mainly in the winter and spring periods, and type 41 predominated in the autumn period. The majority of the non-enteric types were found during the late winter and spring periods.

Only 2 out of 71 German patients infected with rotavirus (3%) and 8 out of 147 German control patients (5%) showed serum antibody to the new serotype 8 rotavirus. Such antibody was detected in the sera of 232 of 870 Ecuadorian children (27%). Twelve Ecuadorian sera showed neutralizing activity only against serotype 8 and not to the other serotypes (1–4) tested, indicating that human serotype 8 rotavirus circulates in South America.

In a recent communication (Penfold 1911) I described experiments with three organisms, B. coli Escherich, B. enteritidis Gaertner and B. Grünthal, showing that limitation or complete abolition of certain gas-forming powers normally possessed by these organisms, could be brought about by their growth on chloracetic acid-agar, and further, that in the case of the latter organism, resistance to this medium was associated with such limitation or abolition.

This study was performed to investigate space–time patterns of Campylobacter spp. colonization in broiler flocks in Norway. Data on the Campylobacter spp. status at the time of slaughter of 16 054 broiler flocks from 580 farms between 2002 and 2006 was included in the study. Spatial relative risk maps together with maps of space–time clustering were generated, the latter by using spatial scan statistics. These maps identified the same areas almost every year where there was a higher risk for a broiler flock to test positive for Campylobacter spp. during the summer months. A modified K-function analysis showed significant clustering at distances between 2·5 and 4 km within different years. The identification of geographical areas with higher risk for Campylobacter spp. colonization in broilers indicates that there are risk factors associated with Campylobacter spp. colonization in broiler flocks varying with region and time, e.g. climate, landscape or geography. These need to be further explored. The results also showed clustering at shorter distances indicating that there are risk factors for Campylobacter spp. acting in a more narrow scale as well.