The recent decline in cardiovascular disease mortality in Western countries has been linked with changes in life style and treatment. This study considers periods of decline before effective medical interventions or knowledge about risk factors. Trends in annual age-standardized death rates from cerebrovascular disease, heart disease and circulatory disease, and all cardiovascular disease are reviewed for three phases, 1881–1916, 1920–1939, and 1940–2000. There was a consistent decline in the cerebrovascular disease death rate between 1891 and 2000, apart from brief increases after the two world wars. The heart disease and circulatory disease death rate was declining between 1891 and 1910 before cigarette smoking became prevalent. The early peak in cardiovascular mortality in 1891 coincided with an influenza pandemic and a peak in the death rate from bronchitis, pneumonia and influenza. There is also correspondence between short-term fluctuations in the death rates from these respiratory diseases and cardiovascular disease. This evidence of ecological association is consistent with the findings of many studies that seasonal influenza can trigger acute myocardial infarction and episodes of respiratory infection are followed by increased risk of cardiovascular events. Vaccination studies could provide more definitive evidence of the role in cardiovascular disease and mortality of influenza, other viruses, and common bacterial agents of respiratory infection.

For studies examining risk factors of sexually transmitted infections (STIs), confounding can stem from characteristics of partners of study subjects, and persist after adjustment for the subjects’ individual-level characteristics. Two conditions that can result in confounding by the subjects’ partners are: (C1) partner choice is assortative by the risk factor examined and, (C2) sexual activity is associated with the risk factor. The objective of this paper is to illustrate the potential impact of the assortativity bias in studies examining STI risk factors, using smoking and human papillomavirus (HPV) as an example. We developed an HPV transmission-dynamic mathematical model in which we nested a cross-sectional study assessing the smoking–HPV association. In our base case, we assumed (1) no effect of smoking on HPV, and (2) conditions C1–C2 hold for smoking (based on empirical data). The assortativity bias caused an overestimation of the odds ratio (OR) in the simulated study after perfect adjustment for the subjects’ individual-level characteristics (adjusted OR 1·51 instead of 1·00). The bias was amplified by a lower basic reproductive number (R0), greater mixing assortativity and stronger association of smoking with sexual activity. Adjustment for characteristics of partners is needed to mitigate assortativity bias.

West Nile virus (WNV) is an emerging vector-borne arbovirus with a zoonotic life-cycle whose main reservoir hosts are birds. In humans and horses, WNV infections rarely result in clinical disease but on occasions – depending on factors such as climatic conditions, insect communities and background immunity levels in local populations – they can lead to outbreaks that threaten public and animal health. We tested for the presence of WNV antibodies in 149 birds belonging to 32 different species. Samples were first tested using a bird-specific ELISA kit and then both positive and doubtful results were confirmed by neutralization tests using WNV and Usutu virus. WNV antibodies were confirmed in a resident Sylvia melanocephala juvenile, supporting the idea of local transmission of WNV in southern Spain in 2013. In addition, the serum from an adult blackbird (Turdus merula) showed neutralization of both WNV and Usutu virus. We discuss our results in light of the occurrence of WNV on horse farms in southern Spain in 2013.

In Germany tularemia is a re-emerging zoonotic disease. Therefore, we investigated wild animals and environmental water samples for the presence and phylogenetic diversity of Francisella tularensis in the poorly studied Berlin/Brandenburg region. The phylogenomic analysis of three isolates from wild animals revealed three new subclades within the phylogenetic tree of F. tularensis [B.71 from a raccoon dog (Nyctereutes procyonoides); B.74 from a red fox (Vulpes vulpes), and B.75 from a Eurasian beaver (Castor fiber albicus)]. The results from histological, PCR, and genomic investigations on the dead beaver showed that the animal suffered from a systemic infection. Indications were found that the bacteria were released from the beaver carcass into the surrounding environment. We demonstrated unexpectedly high and novel phylogenetic diversity of F. tularensis in Germany and the fact that the bacteria persist in the environment for at least one climatic season. These findings support a broader host species diversity than previously known regarding Germany. Our data further support the assumption derived from previous serological studies of an underestimated frequency of occurrence of the pathogen in the environment and in wild animals. F. tularensis was isolated from animal species not previously reported as natural hosts in Germany.

In July 2013, a Belgian couple were admitted to hospital because of pneumonia. Medical history revealed contact with birds. Eleven days earlier, they had purchased a lovebird in a pet shop in The Netherlands. The bird became ill, with respiratory symptoms. The couple's daughter who accompanied them to the pet shop, reported similar symptoms, but was travelling abroad. On the suspicion of psittacosis, pharyngeal swabs from the couple were taken and sent to the Belgian reference laboratory for psittacosis. Culture and nested polymerase chain reaction (PCR) tests were positive for the presence of Chlamydia psittaci, and ompA genotyping indicated genotype A in both patients. The patients were treated with doxycycline and the daughter started quinolone therapy; all three recovered promptly. Psittacosis is a notifiable disease in Belgium and therefore local healthcare authorities were informed. They contacted their Dutch colleagues, who visited the pet shop. Seven pooled faecal samples were taken and analysed using PCR by the Dutch national reference laboratory for notifiable animal diseases for the presence of Chlamydia psittaci. Four (57%) samples tested positive, genotyping revealed genotype A. Enquiring about exposure to pet birds is essential when patients present with pneumonia. Reporting to health authorities, even across borders, is warranted to prevent further spread.

Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a serious hospital and community-acquired infection and some strains are associated with greater severity. We investigated the clinical variability and molecular characteristics of MRSA infections in Shenzhen, China through a study at nine sentinel hospitals from January to December 2014. MRSA infections were classified as community-associated (CA-MRSA), healthcare-associated (HA-MRSA), and healthcare-associated community-onset (HACO-MRSA). In total, 812 MRSA isolates were collected and 183 of these were selected for further study. Patients with HA-MRSA infections were generally of greater age compared to other groups. Distinct body site and clinical presentations were evident in infected patients, e.g. CA-MRSA (skin and soft tissue, 53%), HA-MRSA (respiratory tract, 22%; surgical site, 20%; trauma wounds, 20%) and HACO-MRSA (mastitis, 47%). In contrast to HA-MRSA, other categories of strains were significantly more susceptible to gentamicin, sulfamethoxazole/trimethoprim, and tetracycline. No resistance to vancomycin or linezolid was recorded. The predominant clonal lineage within each strain category was CC59-t437-SCCmec IV/V-agr I (CA, 51·4%; HA, 28·9%; HACO, 52·9%) which exhibited characteristics of a traditional CA clone together with agr I which is more often associated with HA clones. In conclusion, for the three categories of MRSA infections, there were significant differences in clinical characteristics of patients, but the predominant clone in each category shared a similar genetic background which suggests that transmission of MRSA strains has occurred between the community and hospitals in Shenzhen.

Indoor transmission of respiratory droplets bearing influenza within humans poses high risks to respiratory function deterioration and death. Therefore, we aimed to develop a framework for quantifying the influenza infection risk based on the relationships between inhaled/exhaled respiratory droplets and airborne transmission dynamics in a ventilated airspace. An experiment was conducted to measure the size distribution of influenza-containing droplets produced by coughing for a better understanding of potential influenza spread. Here we integrated influenza population transmission dynamics, a human respiratory tract model, and a control measure approach to examine the indoor environment–virus–host interactions. A probabilistic risk model was implemented to assess size-specific infection risk for potentially transmissible influenza droplets indoors. Our results found that there was a 50% probability of the basic reproduction number (R0) exceeding 1 for small-size influenza droplets of 0·3–0·4 µm, implicating a potentially high indoor infection risk to humans. However, a combination of public health interventions with enhanced ventilation could substantially contain indoor influenza infection. Moreover, the present dynamic simulation and control measure assessment provide insights into why indoor transmissible influenza droplet-induced infection is occurring not only in upper lung regions but also in the lower respiratory tract, not normally considered at infection risk.

We conducted a longitudinal assessment in 466 underweight and 446 normal-weight children aged 6–24 months living in the urban slum of Dhaka, Bangladesh to determine the association between vitamin D and other micronutrient status with upper respiratory tract infection (URI) and acute lower respiratory infection (ALRI). Incidence rate ratios of URI and ALRI were estimated using multivariable generalized estimating equations. Our results indicate that underweight children with insufficient and deficient vitamin D status were associated with 20% and 23–25% reduced risk of URI, respectively, compared to children with sufficient status. Underweight children, those with serum retinol deficiency were at 1·8 [95% confidence interval (CI) 1·4–2·4] times higher risk of ALRI than those with retinol sufficiency. In normal-weight children there were no significant differences between different vitamin D status and the incidence of URI and ALRI. However, normal-weight children with zinc insufficiency and those that were serum retinol deficient had 1·2 (95% CI 1·0–1·5) times higher risk of URI and 1·9 (95% CI 1·4–2·6) times higher risk of ALRI, respectively. Thus, our results should encourage efforts to increase the intake of retinol-enriched food or supplementation in this population. However, the mechanisms through which vitamin D exerts beneficial effects on the incidence of childhood respiratory tract infection still needs further research.

Differences by ethnic group in STI diagnosis rates have long been recognized in England. We investigated whether these may be explained by ethnic disparities in socioeconomic deprivation (SED). Data on all diagnoses made in sexual health clinics in England in 2013 were obtained from the mandatory STI surveillance system. Poisson regression was used to calculate incidence rate ratios (IRRs) of STIs, by ethnicity, with and without adjustment for index of multiple deprivation (IMD) a measure of area-level deprivation. Unadjusted IRRs (95% confidence intervals) were highest for gonorrhoea [8·18 (7·77–8·61) and 5·76 (5·28–6·29)] and genital herpes [4·24 (3·99–4·51) and 3·58 (3·23–3·98)] for people of black Caribbean and non-Caribbean/non-African black ethnicity and IRRs were highest for syphilis [8·76 (7·97–9·63)] and genital warts [2·23 (2·17–2·29)] for people of non-British/non-Irish white ethnicity compared to white British ethnicity. After adjustment for IMD, IRRs for gonorrhoea [5·76 (5·47–6·07)] and genital herpes [3·73 (3·50–3·97)] declined but remained highest for black Caribbeans and IRRs for syphilis [7·35 (6·68–8·09)] and genital warts [2·10 (2·04–2·16)] declined but remained highest for non-British/non-Irish white compared to white British. In England, ethnic disparities in STI diagnosis rates are partially explained by SED, but behavioural and contextual factors likely contribute. Clinic and community-based interventions should involve social peer networks to ensure they are targeted and culturally sensitive.

On 30 May 2012, Surrey and Sussex Health Protection Unit was called by five nurseries reporting children and staff with sudden onset vomiting approximately an hour after finishing their lunch that day. Over the following 24 h 50 further nurseries supplied by the same company reported cases of vomiting (182 children, 18 staff affected). Epidemiological investigations were undertaken in order to identify the cause of the outbreak and prevent further cases. Investigations demonstrated a nursery-level attack rate of 55 out of 87 nurseries (63·2%, 95% confidence interval 52·2–73·3). Microbiological tests confirmed the presence of Bacillus cereus in food and environmental samples from the catering company and one nursery. This was considered microbiologically and epidemiologically consistent with toxin from this bacterium causing the outbreak. Laboratory investigations showed that the conditions used by the caterer for soaking of pearl haricot beans (known as navy bean in the USA) used in one of the foods supplied to the nurseries prior to cooking, was likely to have provided sufficient growth and toxin production of B. cereus to cause illness. This large outbreak demonstrates the need for careful temperature control in food preparation.

In this study, we evaluated the association between high-risk human papillomavirus (hrHPV) and the vaginal microbiome. Participants were recruited in Nigeria between April and August 2012. Vaginal bacterial composition was characterized by deep sequencing of barcoded 16S rRNA gene fragments (V4) on Illumina MiSeq and HPV was identified using the Roche Linear Array® HPV genotyping test. We used exact logistic regression models to evaluate the association between community state types (CSTs) of vaginal microbiota and hrHPV infection, weighted UniFrac distances to compare the vaginal microbiota of individuals with prevalent hrHPV to those without prevalent hrHPV infection, and the Linear Discriminant Analysis effect size (LEfSe) algorithm to characterize bacteria associated with prevalent hrHPV infection. We observed four CSTs: CST IV-B with a low relative abundance of Lactobacillus spp. in 50% of participants; CST III (dominated by L. iners) in 39·2%; CST I (dominated by L. crispatus) in 7·9%; and CST VI (dominated by proteobacteria) in 2·9% of participants. LEfSe analysis suggested an association between prevalent hrHPV infection and a decreased abundance of Lactobacillus sp. with increased abundance of anaerobes particularly of the genera Prevotella and Leptotrichia in HIV-negative women (P < 0·05). These results are hypothesis generating and further studies are required.

To describe the consequences of medical care interruptions (MCIs) we selected patients with at least two medical encounters between January 2006 and June 2013 in the Dat'AIDS cohort. Patients with any time interval >15 months between two visits were defined as having a MCI, as opposed to uninterrupted follow-up (UFU). Patients’ characteristics at the time of HIV diagnosis and at the censoring date were compared between groups. Cox proportional hazards models were built to assess the role of interruptions on survival (total and AIDS-free). Of 11 116 patients, 824 had at least one MCI. These patients were younger at the time of HIV diagnosis (30 vs. 33 years, P < 0·0001). MCI was less frequent in men having sex with men vs. heterosexual patients [odds ratio (OR) 0·81, 95% confidence interval (CI) 0·69–0·96)], and a centre effect was described. MCI was independently associated with AIDS (OR 2·54, 95% CI 2·10–3·09) and death (OR 2·65, 95% CI 1·94–3·61). At the censoring date, 52·2% of patients with at least one MCI had viral load below detection vs. 85·3% of the UFU group (P < 0·0001). In conclusion, MCIs were associated with patients’ survival and with the proportion of viral loads below detection in our cohort, compromising individual and collective treatment benefits.

This report describes an increased number of cases of Chikungunya virus (CHIKV) infection imported in northern Italy (Emilia-Romagna region) during the period May–September 2014, indicating that the recent spread of CHIKV and its establishment in the Caribbean and in central America, resulted in a high number of imported cases in Europe, thus representing a threat to public health. From May to September 2014, 14 imported cases of CHIKV infection were diagnosed; the patients were returning to Italy from Dominican Republic (n = 6), Haiti (n = 3), Guadeloupe (n = 2), Martinique (n = 1), Puerto Rico (n = 1) and Venezuela (n = 1). Phylogenetic analysis performed on the envelope protein (E1) gene sequences, obtained from plasma samples from two patients, indicated that the virus strain belongs to the Caribbean clade of the Asian genotype currently circulating in the Caribbean and Americas. The rise in the number of imported cases of CHIKV infection should increase healthcare professionals' awareness of the epidemiological situation and clinical presentation of CHIKV infection in order to enhance surveillance and early diagnosis in the forthcoming season of vector activity in Europe and North America.

To examine evidence of positive antibodies against immunogenic proteins of Anaplasma phagocytophilum in patients with other tick-borne infections and to diagnose possible co-infections, 412 serum specimens were tested by immunoblotting using three specific Anaplasma antigens: surface proteins p44 and Asp62 and outer membrane protein A (OmpA). In total, 284 serum samples from children with Lyme borreliosis and 12 serum samples from children with tick-borne encephalitis were tested. Sera from patients with viral aseptic meningitis (n = 47) and from blood donors (n = 69) were used as controls. Among all serum specimens from patients with tick-borne infections submitted for this study, six samples (2·0%) showed positive IgM reactions and seven samples (2·4%) were IgG positive for A. phagocytophilum by immunoblot. Borderline reactivity was found in 30 samples (10·14%) for IgM and 36 samples (12·2%) for IgG. The difference between patients and blood donors was statistically significant for IgM (P = 0·006) and for IgG (P = 0·0007) antibodies. A statistically significant result was obtained for IgG (P = 0·02) but not for IgM between patients and children with aseptic meningitis. Immunoblot using three specific antigens provides novel information about the positivity of antibodies to A. phagocytophilum in children with other tick-borne infections. Taking into account clinical and laboratory findings of children despite antibody positivity, no case of human granulocytic anaplasmosis was demonstrated.

Coxsackievirus A6 (CV-A6), coxsackievirus A16 (CV-A16) and enterovirus 71 (EV-A71) were the major enteroviruses causing nationwide hand, foot and mouth disease (HFMD) epidemics in Singapore in the last decade. We estimated the basic reproduction number (R0) of these enteroviruses to obtain a better understanding of their transmission dynamics. We merged records of cases from HFMD outbreaks reported between 2007 and 2012 with laboratory results from virological surveillance. R0 was estimated based on the cumulative number of reported cases in the initial growth phase of each outbreak associated with the particular enterovirus type. A total of 33 HFMD outbreaks were selected based on the inclusion criteria specified for our study, of which five were associated with CV-A6, 13 with CV-A16, and 15 with EV-A71. The median R0 was estimated to be 5·04 [interquartile range (IQR) 3·57–5·16] for CV-A6, 2·42 (IQR 1·85–3·36) for CV-A16, and 3·50 (IQR 2·36–4·53) for EV-A71. R0 was not significantly associated with number of infected children (P = 0·86), number of exposed children (P = 0·94), and duration of the outbreak (P = 0·05). These enterovirus-specific R0 estimates will be helpful in providing insights into the potential growth of future HFMD epidemics and outbreaks for timely implementation of disease control measures, together with disease dynamics such as severity of the cases.

Although outbreaks of acute respiratory infection (ARI) at shelters are hypothesized to be associated with shelter crowding, no studies have examined this relationship. We conducted a retrospective study by reviewing medical records of evacuees presenting to one of the 37 clinics at the shelters in Ishinomaki city, Japan, during the 3-week period after the Great Eastern Japan Earthquake and tsunami in 2011. On the basis of a locally weighted scatter-plot smoothing technique, we categorized 37 shelters into crowded (mean space <5·5 m2/per person) and non-crowded (⩾5·5 m2) shelters. Outcomes of interest were the cumulative and daily incidence rate of ARI/10 000 evacuees at each shelter. We found that the crowded shelters had a higher median cumulative incidence rate of ARI [5·4/10 000 person-days, interquartile range (IQR) 0–24·6, P = 0·04] compared to the non-crowded shelters (3·5/10 000 person-days, IQR 0–8·7) using Mann–Whitney U test. Similarly, the crowded shelters had an increased daily incidence rate of ARI of 19·1/10 000 person-days (95% confidence interval 5·9–32·4, P < 0·01) compared to the non-crowded shelters using quasi-least squares method. In sum, shelter crowding was associated with an increased incidence rate of ARI after the natural disaster.

Injecting drug use is often associated with deep-seated infection. In Lothian in Scotland there has been a recent increase in the use of injected new psychoactive substances (NPS). Patients who have injected NPS have presented with Staphylococcus aureus bacteraemia (SAB) with life-threatening complications. We describe a unique case-series of 14 episodes of SAB in ten patients. Users of injected NPS had a significantly higher incidence of endocarditis and cavitating pulmonary lesions (P < 0·05) compared to those who inject only opiates. Cases of SAB in people who inject NPS have contributed to a significant rise in the overall incidence of SAB in people who inject drugs (P < 0·05) which has in turn impacted on the ability of Lothian to meet national targets for reducing the incidence of SAB.

Pathogens utilize type III secretion systems to deliver effector proteins, which facilitate bacterial infections. The Escherichia coli type III secretion system 2 (ETT2) which plays a crucial role in bacterial virulence, is present in the majority of E. coli strains, although ETT2 has undergone widespread mutational attrition. We investigated the distribution and characteristics of ETT2 in avian pathogenic E. coli (APEC) isolates and identified five different ETT2 isoforms, including intact ETT2, in 57·6% (141/245) of the isolates. The ETT2 locus was present in the predominant APEC serotypes O78, O2 and O1. All of the ETT2 loci in the serotype O78 isolates were degenerate, whereas an intact ETT2 locus was mostly present in O1 and O2 serotype strains, which belong to phylogenetic groups B2 and D, respectively. Interestingly, a putative second type III secretion-associated locus (eip locus) was present only in the isolates with an intact ETT2. Moreover, ETT2 was more widely distributed in APEC isolates and exhibited more isoforms compared to ETT2 in human extraintestinal pathogenic E. coli, suggesting that APEC might be a potential risk to human health. However, there was no distinct correlation between ETT2 and other virulence factors in APEC.

The first large outbreak of hand, foot, and mouth disease (HFMD) with severe complications primarily caused by enterovirus 71 was reported in Taiwan in 1998. Surveillance of HFMD to evaluate the spread of HFMD with and without infection control policy is needed. We developed a new dynamic epidemic Susceptible-Infected-Recovered (SIR) model to fit the surveillance data on containing valuable information on the severity of HFMD in order to accurately estimate the basic reproductive number (R0) of HFMD. After fitting the empirical data, in conjunction with other relevant parameters extracted from the literature, the estimated transmission coefficients were close to 5 × 10−7 (per day) and the proportion of severe HFMD cases ranged between 0 and 0·0036 (per day). Taking into account the distribution of all parameters considered in our dynamic epidemic model, the R0 computed was 1·37 (95% confidence interval 0·24–5·84), suggesting a higher likelihood of the spread of HFMD if no infection control policy is provided. The isolation strategy against the spread of HFMD not only delayed the epidemic peak with the delayed time ranging from 4 weeks for only 20% isolation to 47 weeks for 100% isolation but also reduced total number of HFMD cases with the percentage of reduction ranging from 1·3% for only 20% isolation to 13·3% for 100% isolation. The proposed model can also be flexible for evaluating the effectiveness of two other possible policies for containing HFMD, quarantine and vaccination (if the vaccine can be developed).

In late 2011 the New Zealand Ministry for Primary Industries reported an increase in confirmed laboratory diagnoses of salmonellosis in dairy herds. To identify risk factors for herd-level outbreaks of salmonellosis we conducted a case-control study of New Zealand dairy herds in 2011–2012. In a multivariable analysis, use of continuous feed troughs [adjusted odds ratio (aOR) 6·2, 95% confidence interval (CI) 2·0–20], use of pelletized magnesium supplements (aOR 10, 95% CI 3·3–33) and use of palm kernel meal as a supplementary feed (aOR 8·7, 95% CI 2·5–30) were positively associated with a herd-level outbreak of salmonellosis between 1 July 2011 and 31 January 2012. We conclude that supplementary feeds used on dairy farms (regardless of type) need to be stored and handled appropriately to reduce the likelihood of bacterial contamination, particularly from birds and rodents. Magnesium supplementation in the pelletized form played a role in triggering outbreaks of acute salmonellosis in New Zealand dairy herds in 2011–2012.