England has recently started a new paediatric influenza vaccine programme using a live-attenuated influenza vaccine (LAIV). There is uncertainty over how well the vaccine protects against more severe end-points. A test-negative case–control study was used to estimate vaccine effectiveness (VE) in vaccine-eligible children aged 2–16 years of age in preventing laboratory-confirmed influenza hospitalisation in England in the 2015–2016 season using a national sentinel laboratory surveillance system. Logistic regression was used to estimate the VE with adjustment for sex, risk-group, age group, region, ethnicity, deprivation and month of sample collection. A total of 977 individuals were included in the study (348 cases and 629 controls). The overall adjusted VE for all study ages and vaccine types was 33.4% (95% confidence interval (CI) 2.3–54.6) after adjusting for age group, sex, index of multiple deprivation, ethnicity, region, sample month and risk group. Risk group was shown to be an important confounder. The adjusted VE for all influenza types for the live-attenuated vaccine was 41.9% (95% CI 7.3–63.6) and 28.8% (95% CI −31.1 to 61.3) for the inactivated vaccine. The study provides evidence of the effectiveness of influenza vaccination in preventing hospitalisation due to laboratory-confirmed influenza in children in 2015–2016 and continues to support the rollout of the LAIV childhood programme.

Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI–GVII, with GII.4 being the most prevalent. However, in 2012–2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013–2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.

We studied the genetic diversity and the population structure of human isolates of Histoplasma capsulatum, the causative agent of histoplasmosis, using a randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) assay to identify associations with the geographic distribution of isolates from Mexico, Guatemala, Colombia and Argentina. The RAPD-PCR pattern analyses revealed the genetic diversity by estimating the percentage of polymorphic loci, effective number of alleles, Shannon's index and heterozygosity. Population structure was identified by the index of association (IA) test. Thirty-seven isolates were studied and clustered into three groups by the unweighted pair-group method with arithmetic mean (UPGMA). Group I contained five subgroups based on geographic origin. The consistency of the UPGMA dendrogram was estimated by the cophenetic correlation coefficient (CCCr = 0.94, P = 0.001). Isolates from Mexico and Colombia presented higher genetic diversity than isolates from Argentina. Isolates from Guatemala grouped together with the reference strains from the United States of America and Panama. The IA values suggest the presence of a clonal population structure in the Argentinian H. capsulatum isolates and also validate the presence of recombining populations in the Colombian and Mexican isolates. These data contribute to the knowledge on the molecular epidemiology of histoplasmosis in Latin America.

This study aims to investigate the human immunodeficiency virus (HIV) transmission rate in HIV serodiscordant couples, in addition to the relevant influencing factors. From January 1999 to August 2016, patients with HIV/AIDS (index cases) along with their fixed partners were registered and monitored to determine the rate of HIV transmission between couples, as well as relevant influencing factors. A total of 231 HIV-positive couples were investigated, of these, 45-negative (19.48%) partners were infected with HIV via sexual transmission prior to diagnosis of the first case detected in couples. After diagnosis, the transmission rate between spouses was 0.39 per 100 person-years (2/507.7), and the cumulative transmission rate was 1.08% (2/186), which was significantly lower than the transmission rate before diagnosis (χ2 = 35.714, P < 0.001). Among the 119 HIV/AIDS patients who received antiretroviral therapy (ART), the transmission rate was 0 (0/119), whereas the transmission rate was 2.99% (2/67) in HIV/AIDS patients who did not receive ART. In addition, HIV transmission rate in serodiscordant couples was high prior to diagnosis of the index case. However, following diagnosis, the transmission rate was reduced, and the risk of transmission in the index case with antiviral treatment was null. Therefore, a prompt intervention in HIV discordant couples with ART of index case is vital to reduce the risk of HIV transmission.

Retaining adolescents (aged 10–19 years), living with HIV (ALHIV) on antiretroviral therapy (ART) is challenging. In Myanmar, 1269 ALHIV were under an Integrated HIV Care (IHC) Programme by June 2017 and their attrition (death and lost to follow-up) rates were not assessed before. We undertook a cohort study using routinely collected data of ALHIV enrolled into HIV care from July 2005 to June 2017 and assessed their attrition rates in June 2018 by time-to-event analysis. Of 1269 enrolled, 197(16%) and of 1054 initiated ART, 224 (21%) had an attrition defining event. The pre-ART and ART attrition rates were 21.8 (95% CI 19.0–25.1) and 6.4 (95% CI 5.6–7.3) per 100 person-years follow-up, respectively. The factors ‘at enrolment’ that were associated with higher hazards of attrition were: (1) WHO stage 3 or 4; (2) haemoglobin <10 gm/dl; (3) no documented CD4 cell counts, hepatitis B and C test results; and (4) injection drug use. Baseline hazards were high during the initial 1–2 years and after 5–6 years. The pre-ART and ART attrition rates in ALHIV were lower than those in Africa but higher than the children under IHC. This warrants designing and implementing additional care tailored to the needs of ALHIV under IHC.

To compare the epidemiologic features (e.g. settings and transmission mode) and patient clinical characteristics associated with outbreaks of different norovirus (Nov) strains, we retrospectively analysed data of Nov outbreaks occurring in Guangzhou, China from 2012 to 2018. The results suggested that outbreaks of Nov GII.2, GII.17 and GII.4 Sydney exhibited different outbreak settings, transmission modes and symptoms. GII.2 outbreaks mainly occurred in kindergartens, elementary and high schools and were transmitted mainly through person-to-person contact. By contrast, GII.4 Sydney outbreaks frequently occurred in colleges and were primarily associated with foodborne transmission. Cases from GII.2 and GII.17 outbreaks reported vomiting more frequently than those from outbreaks associated with GII.4 Sydney.

A cohort study was performed from January 2014 to December 2016 in a Brazilian neonatal intensive care unit, including neonates with high risk for infection and death. We estimated bloodstream infection (BSI) incidence and conducted a survival analysis, considering the time to death and to the first episode of BSI as outcomes, comparing very low birth weight (VLBW) neonates with the remaining neonates. An extended Cox model was performed and the hazard ratio (HR) was calculated for different time periods. The study had 1560 neonates included, the incidence and the incidence density of BSI was 22% and 18.6 per 1000 central venous catheter-days, respectively. Considering VLBW neonates as the reference group, the HR for time to death was 4.06 (95% CI 2.75–6.00, P < 0.01) from day 0 to 60 and for time to the first episode of BSI was 1.76 (95% CI 1.31–2.36, P < 0.01) from day 0 to 36. Having the heavier neonates group as reference, the HR for time to the first episode of BSI was 2.94 (95% CI 1.92–4.34, P < 0.01) from day 37 to 90. Late-onset neonatal sepsis prevention measures should consider the differences in risk during time, according to neonates' birth weight.

The single intradermal comparative cervical tuberculin (SICCT) test and post-mortem examination are the main diagnostic tools for bovine tuberculosis (bTB) in cattle in the British Isles. Latent class modelling is often used to estimate the bTB test characteristics due to the absence of a gold standard. However, the reported sensitivity of especially the SICCT test has shown a lot of variation. We applied both the Hui–Walter latent class model under the Bayesian framework and the Bayesian model specified at the animal level, including various risk factors as predictors, to estimate the SICCT test and post-mortem test characteristics. Data were collected from all cattle slaughtered in abattoirs in Northern Ireland in 2015. Both models showed comparable posterior median estimation for the sensitivity of the SICCT test (88.61% and 90.56%, respectively) using standard interpretation and for post-mortem examination (53.65% and 53.79%, respectively). Both models showed almost identical posterior median estimates for the specificity (99.99% vs. 99.80% for SICCT test at standard interpretation and 99.66% vs. 99.86% for post-mortem examination). The animal-level model showed slightly narrower posterior 95% credible intervals. Notably, this study was carried out in slaughtered cattle which may not be representative for the general cattle population.

India is experiencing a substantial decrease in early childhood exposure to hepatitis A virus (HAV). Kerala has experienced several hepatitis A outbreaks in young adults/adults in the recent past. The current hepatitis outbreak occurred in Nellikuzhi, Kerala state, India in December 2016. Investigation was carried by preparing a line list of suspected hepatitis cases. The blood and stool samples collected from patients were tested for anti-HAV/anti-Hepatitis E virus (HEV) immunoglobulin (IgM) antibodies and RNA respectively. A total of 562 suspected hepatitis cases were reported during the outbreak. Along with the first case (35 years, male), 86.1% (484/562) of the cases gave history of consuming food/water/cold drinks from one restaurant. Anti-HAV IgM positivity was 74.5% (73/98) in tested samples and amongst the positives, 81% were adults/young adults and adolescents. None of the samples tested positive for anti-HEV IgM. There were three HAV associated deaths without any co-morbidity. Sequence analysis of HAV RNA positive stool samples showed the presence of genotype IIIA HAV. The suspected source of the infection was a private well situated in the premise of a restaurant. Considering increasing HAV naive population in Kerala, there is a need to introduce hepatitis A vaccine in high-risk age groups.

Strongyloides stercoralis is a neglected parasite that can cause death in immunocompromised individuals. There were no data on the epidemiology of S. stercoralis infection in San Marino Republic until two patients (one of whom died) were diagnosed with severe strongyloidiasis (hyperinfection) between September 2016 and March 2017. A serology test for Strongyloides spp. was introduced in routine practice in the laboratory of the State Hospital to test patients considered to be at risk for strongyloidiasis. Between August 2017 and August 2018, of 42 patients tested with serology, two (4.8%) were positive. An additional case was found by gastric biopsy. Two of the positive cases were presumably autochthonous infections (elderly people with no significant travel history), while the other was a probable imported case (young man born in Nigeria and settled in Europe since 2003). Epidemiology of strongyloidiasis in San Marino might be similar to Northern Italy, where a relevant proportion of cases was diagnosed in immigrants (mainly from sub-Saharan Africa) and in elderly Italians with eosinophilia. Screening for strongyloidiasis might be worthwhile in inhabitants of San Marino in the same categories of individuals, particularly those at risk of immune suppression.

Pneumonia is one of the leading causes of hospitalisations among adults in the USA. Individuals with diabetes mellitus (DM) have been associated with increased risk for pneumonia and complications including death. The objectives of this study were to (1) compare the prevalence and healthcare utilisation patterns for pneumonia in individuals with and without DM, and (2) identify risk factors for pneumonia in those with DM. We performed a retrospective, cross-sectional analysis of the US adult population using Medical Expenditure Panel Surveys (MEPS) data from 2014. Overall, the data represented 24 million individuals with DM and 218 million without DM in the USA. The population-based rate for a pneumonia event was 34 per 1000 persons for individuals with DM and 19 per 1000 persons without DM. Compared to the non-DM group, individuals with DM were treated 1.8x, 2.6x and 1.4x more in the ED, hospital and outpatient, respectively. Furthermore, the average cost per pneumonia event was significantly higher among individuals with DM compared to non-DM in the inpatient setting ($11 931 vs. $7751; P < 0.001). Among individuals with DM, female sex, DM complications, smokers and administration of pneumococcal vaccines were significant factors associated with a pneumonia event.

The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.

Although anorectal Chlamydia trachomatis (CT) infections are frequently diagnosed in men who have sex with men (MSM) and women, the reason for this infection often remains unexplained, as anal sex is not always reported. Oropharyngeal infections inoculating the gastrointestinal (GI) tract may contribute to anorectal-CT infections, as evidence in animals suggests that chlamydia bacteria undergo GI passage; however, no evidence exists in humans. Longitudinal patient clinic-registry data from MSM (n = 17 125) and women (n = 4120) from two Dutch sexually transmitted infection clinics were analysed. When adjusting for confounding socio-demographics, co-infections and risk behaviour, previous (from 3 weeks up to 24 months) oropharyngeal CT was not a risk factor for subsequent anorectal CT in women (odds ratio (OR) 0.46; 95% confidence interval (CI) 0.18–1.18; P = 0.11) and MSM (OR 1.33; 95% CI 0.86–2.07; P = 0.204). Despite the large dataset, the numbers did not allow for the estimation of risk in specific subgroups of interest. The role of the GI tract cannot be excluded with this epidemiological study, but the impact of preceding oropharyngeal CT on anorectal-CT infection is likely limited.

Shiga toxin-producing Escherichia coli (STEC) infection can cause serious illness including haemolytic uraemic syndrome. The role of socio-economic status (SES) in differential clinical presentation and exposure to potential risk factors amongst STEC cases has not previously been reported in England. We conducted an observational study using a dataset of all STEC cases identified in England, 2010–2015. Odds ratios for clinical characteristics of cases and foodborne, waterborne and environmental risk factors were estimated using logistic regression, stratified by SES, adjusting for baseline demographic factors. Incidence was higher in the highest SES group compared to the lowest (RR 1.54, 95% CI 1.19–2.00). Odds of Accident and Emergency attendance (OR 1.35, 95% CI 1.10–1.75) and hospitalisation (OR 1.71, 95% CI 1.36–2.15) because of illness were higher in the most disadvantaged compared to the least, suggesting potential lower ascertainment of milder cases or delayed care-seeking behaviour in disadvantaged groups. Advantaged individuals were significantly more likely to report salad/fruit/vegetable/herb consumption (OR 1.59, 95% CI 1.16–2.17), non-UK or UK travel (OR 1.76, 95% CI 1.40–2.27; OR 1.85, 95% CI 1.35–2.56) and environmental exposures (walking in a paddock, OR 1.82, 95% CI 1.22–2.70; soil contact, OR 1.52, 95% CI 2.13–1.09) suggesting other unmeasured risks, such as person-to-person transmission, could be more important in the most disadvantaged group.

Tuberculosis (TB) is the leading cause of death among infectious diseases worldwide. Among the estimated cases of drug-resistant TB, approximately 60% occur in the BRICS countries (Brazil, Russia, India, China and South Africa). Among Brazilian states, primary and acquired multidrug-resistant TB (MDR-TB) rates were the highest in Rio Grande do Sul (RS). This study aimed to perform molecular characterisation of MDR-TB in the State of RS, a high-burden Brazilian state. We performed molecular characterisation of MDR-TB cases in RS, defined by drug susceptibility testing, using 131 Mycobacterium tuberculosis (M.tb) DNA samples from the Central Laboratory. We carried out MIRU-VNTR 24loci, spoligotyping, sequencing of the katG, inhA and rpoB genes and RDRio sublineage identification. The most frequent families found were LAM (65.6%) and Haarlem (22.1%). RDRio deletion was observed in 42 (32%) of the M.tb isolates. Among MDR-TB cases, eight (6.1%) did not present mutations in the studied genes. In 116 (88.5%) M.tb isolates, we found mutations associated with rifampicin (RIF) resistance in rpoB gene, and in 112 isolates (85.5%), we observed mutations related to isoniazid resistance in katG and inhA genes. An insertion of 12 nucleotides (CCAGAACAACCC) at the 516 codon in the rpoB gene, possibly responsible for a decreased interaction of RIF and RNA polymerase, was found in 19/131 of the isolates, belonging mostly to LAM and Haarlem families. These results enable a better understanding of the dynamics of transmission and evolution of MDR-TB in the region.

Statistical models are commonly employed in the estimation of influenza-associated excess mortality that, due to various reasons, is often underestimated by laboratory-confirmed influenza deaths reported by healthcare facilities. However, methodology for timely and reliable estimation of that impact remains limited because of the delay in mortality data reporting. We explored real-time estimation of influenza-associated excess mortality by types/subtypes in each year between 2012 and 2018 in Hong Kong using linear regression models fitted to historical mortality and influenza surveillance data. We could predict that during the winter of 2017/2018, there were ~634 (95% confidence interval (CI): (190, 1033)) influenza-associated excess all-cause deaths in Hong Kong in population ⩾18 years, compared to 259 reported laboratory-confirmed deaths. We estimated that influenza was associated with substantial excess deaths in older adults, suggesting the implementation of control measures, such as administration of antivirals and vaccination, in that age group. The approach that we developed appears to provide robust real-time estimates of the impact of influenza circulation and complement surveillance data on laboratory-confirmed deaths. These results improve our understanding of the impact of influenza epidemics and provide a practical approach for a timely estimation of the mortality burden of influenza circulation during an ongoing epidemic.

Childhood morbidity and mortality of diarrhoeal diseases are high, particularly in low-income countries and noroviruses and sapoviruses are among the most frequent causes worldwide. Their epidemiology and diversity remain not well studied in many African countries. To assess the positivity rate and the diversity of sapoviruses and noroviruses in Northwest Ethiopia, during November 2015 and April 2016, a total of 450 faecal samples were collected from outpatient children aged <5 years who presented with diarrhoea. Samples were screened for noroviruses and sapoviruses by real-time RT-PCR. Partial VP1 genes were sequenced, genotyped and phylogenetically analysed. Norovirus and sapovirus stool positivity rate was 13.3% and 10.0%, respectively. Noroviruses included GII.4 (35%), GII.6 (20%), GII.17 (13.3%), GII.10 (10%), GII.2 (6.7%), GII.16 (5%), GII.7 (3.3%), GII.9, GII.13, GII.20 and GI.3 (1.7% each) strains. For sapoviruses, GI.1, GII.1 (20.0% each), GII.6 (13.3%), GI.2 (8.9%), GII.2 (11.1%), GV.1 (8.9%), GIV.1 (6.7%), GI.3 and GII.4 (2.2% each) genotypes were detected. This study demonstrates a high genetic diversity of noroviruses and sapoviruses in Northwest Ethiopia. The positivity rate in stool samples from young children with diarrhoea was high for both caliciviruses. Continued monitoring is recommended to identify trends in genetic diversity and seasonal variations.

In 2013, the national surveillance case definition for West Nile virus (WNV) disease was revised to remove fever as a criterion for neuroinvasive disease and require at most subjective fever for non-neuroinvasive disease. The aims of this project were to determine how often afebrile WNV disease occurs and assess differences among patients with and without fever. We included cases with laboratory evidence of WNV disease reported from four states in 2014. We compared demographics, clinical symptoms and laboratory evidence for patients with and without fever and stratified the analysis by neuroinvasive and non-neuroinvasive presentations. Among 956 included patients, 39 (4%) had no fever; this proportion was similar among patients with and without neuroinvasive disease symptoms. For neuroinvasive and non-neuroinvasive patients, there were no differences in age, sex, or laboratory evidence between febrile and afebrile patients, but hospitalisations were more common among patients with fever (P < 0.01). The only significant difference in symptoms was for ataxia, which was more common in neuroinvasive patients without fever (P = 0.04). Only 5% of non-neuroinvasive patients did not meet the WNV case definition due to lack of fever. The evidence presented here supports the changes made to the national case definition in 2013.

Seroprevalence estimation using cross-sectional serosurveys can be challenging due to inadequate or unknown biological cut-off limits of detection. In recent years, diagnostic assay cut-offs, fixed assay cut-offs and more flexible approaches as mixture modelling have been proposed to classify biological quantitative measurements into a positive or negative status. Our objective was to estimate the prevalence of anti-HCV antibodies among drug users (DU) in France in 2011 using a biological test performed on dried blood spots (DBS) collected during a cross-sectional serosurvey. However, in 2011, we did not have a cut-off value for DBS. We could not use the values for serum or plasma, knowing that the DBS value was not necessarily the same. Accordingly, we used a method which consisted of applying a two-component mixture model with age-dependent mixing proportions using penalised splines. The component densities were assumed to be log-normally distributed and were estimated in a Bayesian framework. Anti-HCV prevalence among DU was estimated at 43.3% in France and increased with age. Our method allowed us to provide estimates of age-dependent prevalence using DBS without having a specified biological cut-off value.