In May 2016 a Norovirus (NoV) gastroenteritis outbreak involved a high school class visiting a seaside resort near Taormina (Mascali, Sicily). Twenty-four students and a teacher were affected and 17 of them showed symptoms on the second day of the journey, while the others got ill within the following 2 days. Symptoms included vomiting, diarrhoea and fever, and 12 students required hospitalisation. Stool samples tested positive for NoV genome by Real-Time polymerase chain reaction assay in all 25 symptomatic subjects. The GII.P2/GII.2 NoV genotype was linked to the outbreak by ORF1/ORF2 sequence analysis. The epidemiological features of the outbreak were consistent with food/waterborne followed by person-to-person and/or vomit transmission. Food consumed at a shared lunch on the first day of the trip was associated to illness and drinking un-bottled tap water was also considered as a risk factor. The analysis of water samples revealed the presence of bacterial indicators of faecal contamination in the water used in the resort as well as in other areas of the municipal water network, linking the NoV gastroenteritis outbreak to tap water pollution from sewage leakage. From a single water sample, an amplicon whose sequence corresponded to the capsid genotype recovered from patients could be obtained.

Commercial point-of-care (POC) diagnostic tests for Group A Streptococcus, Streptococcus pneumoniae, and influenza virus have large potential diagnostic and financial impact. Many published reports on test performance, often funded by diagnostics companies, are prone to bias. The Standards for Reporting of Diagnostic Accuracy (STARD 2015) are a protocol to encourage accurate, transparent reporting. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool evaluates risk of bias and transportability of results. We used these tools to evaluate diagnostic test accuracy studies of POC studies for three respiratory pathogens. For the 96 studies analysed, compliance was <25% for 14/34 STARD 2015 standards, and 3/7 QUADAS-2 domains showed a high risk of bias. All reports lacked reporting of at least one criterion. These biases should be considered in the interpretation of study results.

We determined the molecular epidemiology of Bordetella pertussis isolates to evaluate its potential impact on pertussis reemergence in a population of Mexico. Symptomatic and asymptomatic cases were included. Pertussis infection was confirmed by culture and real-time polymerase chain reaction (PCR). Selected B. pertussis isolates were further analysed; i.e. clonality was analysed by pulsed-field gel electrophoresis (PFGE) and ptxP-ptxA, prn, fim2 and fim3 typing was performed by PCR and sequencing. Out of 11 864 analysed samples, 687 (5.8%) were positive for pertussis, with 244 (36%) confirmed by both culture and PCR whereas 115 (17%) were positive only by culture and 328 (48%) were positive only by PCR. One predominant clone (clone A, n = 62/113; 55%) and three major subtypes (A1, A2 and A3) were identified by PFGE. All 113 selected isolates had the allelic combination ptxP3-ptxA1. The predominant clone A and the three major subtypes (A1, A2 and A3) corresponded to the emerging genotypes ptxP3-ptxA1-prn2-fim2-1-fim3-2 and ptxP3-ptxA1-prn2-fim2-1-fim3-1. In conclusion, the presence of an endemic clone and three predominant subtypes belonging to the genotypes ptxP3-ptxA1-prn2-fim2-1-fim3-2 and ptxP3-ptxA1-prn2-fim2-1-fim3-1 were detected. This finding supports the global spread/expansion reported for these outbreaks associated genotypes.

Xpert MTB/RIF (Xpert) is the preferred first-line test for all persons with tuberculosis (TB) symptoms in South Africa in line with a diagnostic algorithm. This study evaluates pre- and post-implementation trends in diagnostic practices for drug-sensitive, pulmonary TB in adults in an operational setting, following the introduction of the Xpert-based algorithm. We retrospectively analysed data from the national TB database for Greater Tzaneen sub-district, Limpopo Province. Trends in a number of cases, diagnosis and outcome and characteristics associated with death are reported. A total of 8407 cases were treated from 2008 until 2015, with annual cases registered decreasing by 31·7% over that time period (from 1251 to 855 per year). After implementation of Xpert, 69·9% of cases were diagnosed by Xpert, 29·4% clinically, 0·6% by smear microscopy and 0·1% by culture. Cases with a recorded microbiological test increased from 76·2% to 96·4%. Cases started on treatment without confirmation, but with a negative microbiological test increased from 7·1% to 25·7%. Case fatality decreased from 15·0% to 9·8%, remaining consistently higher in empirically treated groups, regardless of HIV status. Implementation of the algorithm coincided with a reduced number of TB cases treated and improved coverage of microbiological testing; however, a substantial proportion of cases continued to start treatment empirically.

This study evaluated the impact of maternal vaccination against rubella on the levels of specific rubella IgG (rIgG) in 198 newborn cord sera samples. Detailed maternal vaccination data were available. Specific rIgG was measured using a commercial enzyme immunoassay. Most mothers (78.8%) had been vaccinated against rubella at least once in their lives. In 15 (7.6%) cord sera samples, the concentration of specific rIgG was below 11 IU/ml, which was classified as seronegative. Statistical analysis using multiple logistic regression (n = 198) showed that newborns of mothers born between 1986 and 1995, and those born to unvaccinated mothers, were more likely to be seronegative (odds ratio (ORs) 5.2 and 4.9, respectively, adjusted for sex and gestational age). For vaccinated mothers (n = 156), those born between 1986 and 1995 were more likely to have seronegative newborns (OR 11.5 adjusting for sex, gestational age and time since last vaccination). Mothers of the 15 (7.6%) seronegative newborns might have been susceptible to rubella during pregnancy. Checking the vaccination status therefore recommended.

Risk populations for HIV infections tend to neglect condom use, making alternative preventive approaches necessary. Accordingly, we modelled the risk of sexual HIV transmission for condom use vs. use of rapid diagnostic test (RDT) systems with subsequent exclusion of potential sexual partners with a correctly or falsely positive test from unprotected sex with and without the use of HIV pre-exposure prophylaxis (PrEP) in a bio-statistical approach. We combined a previously described model of transmission risk for HIV-exposed individuals with a newly suggested model of risk of HIV exposure for sexually active HIV-negative individuals. The model was adapted for several stages of infection and different strategies of HIV infection prevention.

HIV prevention with RDTs can reduce the transmission risk by up to 97% compared with having sex without any prevention and up to 80% compared with condom use. Nevertheless, RDT-based prevention strategies demonstrate a lack of protection in several stages of infection; in particular, RNA-based RDT systems may fail under treatment. RDT-based pre-screening of potential sex partners prior to unprotected sexual contacts substantially reduces HIV transmission risk. Combination of different prevention strategies is advisable for high-risk groups.

In this study, we describe a contained measles outbreak in a London prison, the second such outbreak in a custodial setting. Once vaccination commenced, just under a third of eligible prisoners were immunised due to a low uptake of the vaccine. We conducted a root-cause analysis in order to identify factors which may have prevented or altered the course of the outbreak. Our analysis revealed that many of the factors identified are those that cannot be easily changed. It is unlikely that mass vaccination at the time, even in the absence of some of the more easily rectifiable issues, could have fully avoided further cases in the event of a mass outbreak. Both measles outbreaks in a custodial setting started with a member of staff and immunisation status of the staff were largely unknown. We argue that mass vaccination following an outbreak in a prison is unlikely to fully prevent a mass outbreak, and that implementing opt-out testing, empirical vaccination and insisting on full immunisation of staff are most likely to both prevent and contain outbreaks in the future.

Capsular type K54 of Klebsiella pneumoniae is associated with hypervirulence and we sought to discover the basis for this among isolates submitted to the UK reference laboratory between 2012 and 2017. Isolates were typed by variable number tandem repeat analysis, and capsular type and virulence elements sought by PCR. The most prevalent type found (15/31 isolates) corresponded to clonal group (CG) 29 and included five representatives carrying rmpA, rmpA2 (regulators of mucoid phenotype), iutA and iroD (from the aerobactin and salmochelin siderophore clusters) associated with virulence plasmids. These included isolate KpvK54, recovered from pus. The remaining isolates did not carry a virulence plasmid. We also noted 11 further related isolates, including NCTC 9159, not of capsular type K54, but nevertheless sometimes associated with sepsis and abscesses. Whole-genome sequencing showed that KpvK54 carried a large virulence plasmid and an ICEKp3-like structure carrying the yersiniabactin cluster, absent in NCTC 9159. Comparative chromosomal analysis with an additional four genomes showed that KpvK54 shared further genes with K1-ST23 hypervirulent isolates, and with LS358, a K54-ST29 isolate from liver abscess puncture fluid. While CG29 isolates displayed varying degrees of virulence, some, especially those with the virulence plasmid (all K54), were clearly associated with hypervirulence.

As campylobacteriosis is one of the most important foodborne infections, a European Union (EU)-27 level cost-effectiveness model has been developed on the socio-economic costs and benefits of applying certain control measures for the reduction of Campylobacter in broiler meat. This is expected to be a gold standard for food safety policymakers in the EU; hence, the validity of its modelling assumptions is essential. The authors of the present paper conducted an independent review of model input parameters on health and economic burden and found that the model most probably overestimated the burden of human campylobacteriosis. A discounted, quality-adjusted life year (QALY)-based European estimate has been developed for human campylobacteriosis and resulted in 15.23 QALY loss per 1000 human gastroenteritis cases. Country-specific cost of illness estimates have been developed for various countries in the EU-27. Based on these model adaptations, a selected Campylobacter control strategy was re-assessed and its high cost-effectiveness was confirmed at the EU level, and also in all but three Member States. Bacteriocin treatment or vaccination of the animals, two alternative control measures were also re-evaluated, and these strategies seemed to be far less cost-effective than the investigated strategy. Putative barriers to the rapid implementation of the investigated Campylobacter control strategy are discussed, and potential solutions are proposed. Further research is required on stakeholder perspectives pertaining to the realistic barriers and implementation opportunities.

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.

Disease surveillance can be made more effective by either improving disease detection, providing cost savings, or doing both. Currently, cattle herds in low-risk areas (LRAs) for bovine tuberculosis (bTB) in England are tested once every 4 years. In Scotland, the default herd testing frequency is also 4 years, but a risk-based system exempts some herds from testing altogether. To extend this approach to other areas, a bespoke understanding of at-risk herds and how risk-based surveillance can affect bTB detection is required. Here, we use a generalized linear mixed model to inform a Bayesian probabilistic model of freedom from infection and explore risk-based surveillance strategies in LRAs and Scotland. Our analyses show that in both areas the primary herd-level risk factors for bTB infection are the size of the herd and purchasing cattle from high-risk areas of Great Britain and/or Ireland. A risk-based approach can improve the current surveillance system by both increasing detection (9% and 7% fewer latent infections), and reducing testing burden (6% and 26% fewer animal tests) in LRAs and Scotland, respectively. Testing at-risk herds more frequently can also improve the level of detection by identifying more infected cases and reducing the hidden burden of the disease, and reduce surveillance effort by exempting low-risk herds from testing.

Although Middle East respiratory syndrome coronavirus (MERS-CoV) has a recorded 5 years of circulation in 27 countries worldwide, there is no international study to assess whether there is variation in mortality by region. Neither has there been a comprehensive study detailing how the disease characteristics of MERS-CoV influence mortality in patients presenting symptoms. This study aimed to assess how region, patient and disease characteristics influence 14- and 45-day mortality in MERS patients. The author utilised publically available data on MERS-CoV. The study included 883 MERS patients reported between 5 January 2015 and 10 March 2017. Data on patient and disease characteristics were collected. The mean age at MERS-CoV diagnosis was 54.3 years: 69.1% were male, and 86.7% of the cases were reported from Saudi Arabia. About 40% of MERS patients studied were over the age of 60. The study estimated 14- and 45-day survival rates after initial onset of symptoms: 83.67% and 65.9%, respectively. Saudi Arabian MERS patients exhibited 4.1 and 5.0 times higher 14-day (adjusted hazard risk (aHR) = 4.1; 95% confidence interval (CI) 1.012–16.921) and 45-day (aHR = 5.0; 95% CI 1.856–13.581) mortality risk compared with MERS patients in the Republic of Korea or other countries. Similarly, Middle Eastern MERS patients showed 5.3 and 4.1 times higher 14-day (aHR = 5.3; 95% CI 1.070–25.902) and 45-day (aHR = 4.1; 95% CI 1.288–113.076) mortality risk compared with MERS patients in the Republic of Korea or other countries. The results demonstrated a link between mortality and geography, disease and patient factors such as regions, symptoms, source of infections, underlying medical conditions, modes of transmission, non-healthcare workers and those of older age. Educational programmes, access to healthcare and early diagnosis could be implemented as modifiable factors to reduce the higher mortality rates in MERS patients.

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) – dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients’ quality of life. Integrating PK/PD–EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

In 2007–2008, the city of Rio de Janeiro underwent an epidemiological change, with increases in the incidence in children and in severe forms of dengue. To describe the clinical profile and spatial distribution of dengue we performed an ecological study based on dengue surveillance data using the Brazilian classification (2005): dengue fever, dengue haemorrhagic fever (DHF) and dengue with complications. χ2 test was used to describe the clinical and socio-demographic variables (P < 0.05). Spatial distribution of incidence and case-fatality was explored with thematic maps, Moran and Geary indices (P < 0.05). Of the total of 151 527 dengue cases, 38 808 met the inclusion criteria; 42.4% <18 years; 22.9% dengue with complications and 2.7% DHF. Case-fatality was higher in infants (1.4%) and in DHF (7.7%). Bleeding was more frequent in adolescents and adults while plasma leakage was more common in preschoolers and schoolchildren. The highest incidence was found in the West Zone of the city, in a different area from that of the worst case-fatality (P < 0.05). Although the incidence of DHF was higher in schoolchildren, infants showed higher case-fatality. The area with the highest case-fatality did not present the highest incidence, which suggests problems in the organization of health services.

Healthcare-associated infections in veterinary hospitals are commonly attributed to Salmonella enterica, particularly in large animal facilities, and are characteristically associated with widespread environmental contamination. The objective of this study was to investigate factors influencing the likelihood of identifying environmental contamination of a veterinary hospital with S. enterica, while exploring different analytic methods to model complex factors that may influence this ecology. Environmental surveillance samples were collected in a large veterinary hospital as part of a long-term infection control programme. Data were collected retrospectively from the electronic medical records database. Many easily measured variables were complex in nature (i.e., they represented variance that is unmeasured or unidentified as a specific factor) necessitating the use of alternative analytic methods (variable cluster and principal components analyses) to provide perspective regarding the complex data structure and latent factors that may be contributing to this ecology. Subsequently, multivariable logistic regression was performed using generalised estimating equations. Results suggest the probability of detecting Salmonella in the environment increased as demand on personnel increased (e.g., in a busy hospital). Veterinary personnel need to remain vigilant in implementing practices that we believe empirically will mitigate risk for widespread environmental contamination and sustained transmission among patients (i.e., rigorous hygiene for personnel and the environment).

A link between infection, inflammation, neurodevelopment and adult illnesses has been proposed. The objective of this study was to examine the association between infection burden during childhood – a critical period of development for the immune and nervous systems – and subsequent systemic inflammatory markers and general intelligence. In the Avon Longitudinal Study of Parents and Children, a prospective birth cohort in England, we examined the association of exposure to infections during childhood, assessed at seven follow-ups between age 1·5 and 7·5 years, with subsequent: (1) serum interleukin 6 and C-reactive protein (CRP) levels at age 9; (2) intelligence quotient (IQ) at age 8. We also examined the relationship between inflammatory markers and IQ. Very high infection burden (90+ percentile) was associated with higher CRP levels, but this relationship was explained by body mass index (adjusted odds ratio (OR) 1·19; 95% confidence interval (CI) 0·95–1·50), maternal occupation (adjusted OR 1·23; 95% CI 0·98–1·55) and atopic disorders (adjusted OR 1·24; 95% CI 0·98–1·55). Higher CRP levels were associated with lower IQ; adjusted β = −0·79 (95% CI −1·31 to −0·27); P = 0·003. There was no strong evidence for an association between infection and IQ. The findings indicate that childhood infections do not have an independent, lasting effect on circulating inflammatory marker levels subsequently in childhood; however, elevated inflammatory markers may be harmful for intellectual development/function.

Giardia duodenalis and Cryptosporidium spp. are common intestinal protozoa that can cause diarrhoeal disease. Although cases of infection with Giardia and Cryptosporidium have been reported in Alaska, the seroprevalence and correlates of exposure to these parasites have not been characterised. We conducted a seroprevalence survey among 887 residents of Alaska, including sport hunters, wildlife biologists, subsistence bird hunters and their families and non-exposed persons. We tested serum using a multiplex bead assay to evaluate antibodies to the Giardia duodenalis variant-specific surface protein conserved structural regions and to the Cryptosporidium parvum 17- and 27-kDa antigens. Approximately one third of participants in each group had evidence of exposure to Cryptosporidium. Prevalence of Giardia antibody was highest among subsistence hunters and their families (30%), among whom positivity was associated with lack of community access to in-home running water (adjusted prevalence ratio [aPR] 1.15, 95% confidence interval (CI) 1.02–1.28) or collecting rain, ice, or snow to use as drinking water (aPR 1.09, 95% CI 1.01–1.18). Improving in-home water access for entire communities could decrease the risk of exposure to Giardia.

Common childhood infectious diseases have been associated with a reduced risk of following haematopoietic malignancies, but investigations on multiple myeloma (MM) are scarce. Information about 213 MM cases and 1128 healthy controls were obtained from a multicentre population-based Italian case-control study. The association between chickenpox, measles, mumps, pertussis and rubella and the MM risk was estimated by unconditional logistic regression, adjusting for age, gender and residence area. No association was found between MM risk and any considered infectious disease. The number of infections was slightly inversely associated with the risk of MM, but statistical significance was not reached (OR 0.87, 95% CI 0.55–1.4 for 1-2 diseases vs. none and OR 0.68, 95% CI 0.41–1.1 for 3-5 diseases, respectively, P = 0.131). We did not find a clear evidence that common infections during childhood are associated with the subsequent risk of developing MM.

Following an extensive contact tracing exercise at a school in a London borough with one of highest tuberculosis (TB) rates in England, we estimated the background prevalence of latent TB infection to be significantly less than the widely accepted 10%. We screened 271 pupils aged 14–15 years in two groups: 96 pupils in group 1 had significant exposure (>8 h/week in the same room) to a case of infectious TB and 175 in group 2 who had minimal exposure. In group 1, 26% were diagnosed with latent or active TB, compared to 6.3% in group 2. Risk factors for TB infection (e.g. previous exposure or link to high-prevalence communities) were analysed using a cohort study design. In the univariable analysis only being in contact group 1 was statistically significantly associated with being a case (OR 5.25, 95%, P < 0.001). In the multivariable model contact group 1 remained significantly associated with being a case (adjusted OR 4.40, P = 0.001). We concluded that the 6.3% yield of TB infection in contact group 2 is either similar to or higher than the background prevalence rate of latent TB infection (LTBI) in this high TB prevalence London borough. Other parts of England with lower TB prevalence are likely to have even lower LTBI rates.

Following a cluster of serious pseudomonas skin infections linked to a body piercing and tattooing premises, a look-back exercise was carried out to offer clients a screen for blood-borne viruses. Of those attending for screening 72% (581/809) had a piercing procedure in the premises of interest: 94 (16%) were under 16 years of age at the time of screening. The most common site of piercing was ear (34%), followed by nose (27%), nipple (21%) and navel (21%). A small number (<5) tested positive for hepatitis B and C, with no evidence this was linked to the premises. However, 36% (211/581) of clients reported a skin infection associated with their piercing. Using data from client forms, 36% provided a false age. Those aged under 16 years (OR 4.5, 95% CI 2.7–7.7) and those receiving a piercing at an intimate site (OR 2.1, 95% CI 1.3–3.6) were more likely to provide a false age. The findings from this exercise were used to support the drafting of the Public Health (Wales) Bill which proposed better regulation of piercing premises and the need to provide proof of being 18 years of age or over before having a piercing of an intimate site.