A systematic review and meta-analysis of patient data from the West Africa (2013-16) Ebola virus disease epidemic.

BACKGROUND: Over 28 000 individuals were infected with Ebola virus during the West Africa (2013-2016) epidemic, yet there has been criticism of the lack of robust clinical descriptions of Ebola virus disease (EVD) illness from that outbreak. OBJECTIVES: To perform a meta-analysis of published data from the epidemic to describe the clinical presentation, evolution of disease, and predictors of mortality in individuals with EVD. To assess the quality and utility of published data for clinical and public health decision-making. DATA SOURCES: Primary articles available in PubMed and published between January 2014 and May 2017. ELIGIBILITY: Studies that sequentially enrolled individuals hospitalized for EVD and that reported acute clinical outcomes. METHODS: We performed meta-analyses using random-effect models and assessed heterogeneity using the I2 method. We assessed data representativeness by comparing meta-analysis estimates with WHO aggregate data. We examined data utility by examining the availability and compatibility of data sets. RESULTS: In all, 3653 articles were screened and 34 articles were included, representing 16 independent cohorts of patients (18 overlapping cohorts) and at least 6168 individuals. The pooled estimate for case fatality rate was 51% (95% CI 46%-56%). However, pooling of estimates for clinical presentation, progression, and predictors of mortality in individuals with EVD were hampered by significant heterogeneity, and inadequate data on clinical progression. Our assessment of data quality found that heterogeneity was largely unexplained, and data availability and compatibility were poor. CONCLUSIONS: We have quantified a missed opportunity to generate reliable estimates of the clinical manifestations of EVD during the West Africa epidemic. Clinical data standards and data capture platforms are urgently needed.

Temporal relationship between occurrences of hand, foot and mouth disease, respiratory virus detection and febrile seizures in children in tropical Singapore: a time-series analysis.

Febrile seizure (FS) in children is a common complication of infections with respiratory viruses and hand, foot and mouth disease (HFMD). We conducted a retrospective ecological time-series analysis to determine the temporal relationship between hospital attendances for FS and HFMD or respiratory virus infections. Epilepsy attendance was used as a control. Data from 2004 to 2012 FS and epilepsy hospital attendance, HFMD notifications to the Ministry of Health and from laboratory-confirmed viral respiratory infections among KK Women's and Children's Hospital inpatients were used. A multivariate linear regression analysis was conducted to evaluate the relationship between FS and the virus time series. Relative risks of FS by age were calculated using Bayesian statistical methods. Paediatric accident and emergency (A&E) attendances for FS were found to be associated with influenza A (extra 0.47 FS per influenza A case), B (extra 0.32 per influenza B case) and parainfluenza 3 (extra 0.35 per parainfluenza type 3 case). However, other viruses were not significantly associated with FS. None of the viruses were associated with epileptic seizure attendance. Influenza A, B and parainfluenza 3 viruses contributed to the burden of FS resulting in A&E attendance. Children at risk of FS should be advised to receive seasonal influenza vaccination.

Preparing clinicians for (re-)emerging arbovirus infectious diseases in Europe.

BACKGROUND: Arthropod-borne virus (Arbovirus) infections are considered an emerging threat for Europe, with an increase in cases in recent decades. The increase in global travel and trade has contributed to the introduction of vectors and viruses into new geographical areas. Tropical arboviruses such as dengue and chikungunya have re-emerged causing local, sporadic outbreaks ignited by travel-imported cases. The recent Zika virus outbreak in the Americas highlighted a need to strengthen preparedness for (re-)emerging arbovirus infections globally. AIMS: To strengthen preparedness for the early identification of (re-)emerging arbovirus outbreaks in Europe and highlight areas for research. SOURCES: An evidence review of published and grey literature together with consultations with European arbovirus experts. CONTENT: This paper presents an overview of endemic and travel-imported arboviruses of clinical significance in Europe. The overview includes syndromic presentation, risk factors for infection and risk of transmission as well as an update on treatments and vaccinations and surveillance notifications and reporting. The paper also presents predictive modelled risks of further geographical expansion of vectors and viruses. IMPLICATIONS: There are a range of arboviruses of clinical significance to Europe. There has been an increase in notifications of endemic and travel-imported arbovirus cases in recent years and an increased geographical range of vectors and viruses. The heterogeneity in surveillance reporting indicates a risk for the early identification of (re-)emerging outbreaks. The data presented show a need to strengthen preparedness for (re-)emerging arbovirus infections and a need for research into neglected arboviruses, risks of non-vector transmission and effective therapeutics and vaccinations.

Temporal and spatial association of Streptococcus suis infection in humans and porcine reproductive and respiratory syndrome outbreaks in pigs in northern Vietnam.

Porcine reproductive and respiratory syndrome (PRRS) outbreaks in pigs are associated with increased susceptibility of pigs to secondary bacterial infections, including Streptococcus suis - an important zoonotic pathogen causing bacterial meningitis in humans. This case-control study examined the association between human S. suis infection and PRRS outbreaks in pigs in northern Vietnam. We included 90 S. suis case-patients and 183 non-S. suis sepsis controls from a referral hospital in Hanoi in 2010, a period of major PRRS epizootics in Vietnam. PRRS exposure was determined using data from the National Centre of Veterinary Diagnosis. By univariate analysis, significantly more S. suis patients were reported residing in or adjacent to a PRRS district compared to controls [odds ratio (OR) 2·82, 95% confidence interval (CI) 1·35-5·89 and OR 3·15, 95% CI 1·62-6·15, respectively]. Only residency in adjacent districts remained significantly associated with risk of S. suis infection after adjusting for sex, occupation, and eating practices. SaTScan analysis showed a possible cluster of S. suis infection in humans around PRRS confirmed locations during the March-August period. The findings indicate an epidemiological association between PRRS in pigs and S. suis infections in humans. Effective strategies to strengthen control of PRRS in pigs may help reduce transmission of S. suis infection to humans.

Population susceptibility to a variant swine-origin influenza virus A(H3N2) in Vietnam, 2011-2012.

A reassortant swine-origin A(H3N2) virus (A/swine/BinhDuong/03-9/2010) was detected through swine surveillance programmes in southern Vietnam in 2010. This virus contains haemagglutinin and neuraminidase genes from a human A(H3N2) virus circulating around 2004-2006, and the internal genes from triple-reassortant swine influenza A viruses (IAVs). To assess population susceptibility to this virus we measured haemagglutination inhibiting (HI) titres to A/swine/BinhDuong/03-9/2010 and to seasonal A/Perth/16/2009 for 947 sera collected from urban and rural Vietnamese people during 2011-2012. Seroprevalence (HI ⩾ 40) was high and similar for both viruses, with 62·6% [95% confidence interval (CI) 59·4-65·7] against A/Perth/16/2009 and 54·6% (95% CI 51·4-57·8%) against A/swine/BinhDuong/03-9/2010, and no significant differences between urban and rural participants. Children aged <5 years lacked antibodies to the swine origin H3 virus despite high seroprevalence for A/Perth/16/2009. These results reveal vulnerability to infection to this contemporary swine IAV in children aged <5 years; however, cross-reactive immunity in adults would likely limit epidemic emergence potential.

Preparedness for admission of patients with suspected Ebola virus disease in European hospitals: a survey, August-September 2014.

In response to the Ebola virus disease (EVD) outbreak in West Africa, the World Health Organization has advised all nations to prepare for the detection, investigation and management of confirmed and suspected EVD cases in order to prevent further spread through international travel. To gain insights into the state of preparedness of European hospitals, an electronic survey was circulated in August­September 2014 to 984 medical professionals representing 736 hospitals in 40 countries. The survey addressed the willingness and capacity to admit patients with suspected EVD as well as specific preparedness activities in response to the current Ebola crisis. Evaluable responses were received from representatives of 254 (32%) hospitals in 38 countries, mostly tertiary care centres, of which 46% indicated that they would admit patients with suspected EVD. Patient transfer agreements were in place for the majority of hospitals that would not admit patients. Compared with non-admitting hospitals, admitting hospitals were more frequently engaged in various preparedness activities and more often contained basic infrastructural characteristics such as admission rooms and laboratories considered important for infection control, but some gaps and concerns were also identified. The results of this survey help to provide direction towards further preparedness activities and prioritisation thereof.

Antibody landscapes after influenza virus infection or vaccination.

We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.

Avian influenza--a review for doctors in travel medicine.

First identified in humans in Hong Kong, influenza A/H5N1, known commonly as avian influenza, has caused human disease in 15 countries around the world. Although the current number of confirmed patients is tiny compared to seasonal and the recently emerged H1N1 'swine' influenza, H5N1 remains a candidate for the next highly pathogenic influenza pandemic. Currently, H5N1 has very limited ability to spread from person-to-person but this may change because of mutation or reassortment with other influenza viruses leading to an influenza pandemic with high mortality. If this occurs travellers are likely to be affected and travel medicine doctors will need to consider avian influenza in returning febrile travellers. The early clinical features may be dismissed easily as 'the flu' resulting in delayed treatment. Treatment options are limited. Oral oseltamivir alone has been the most commonly used drug but mortality remains substantial, up to 80% in Indonesia. Intravenous peramivir has been filed for registration and IV zanamivir is being developed. This review will focus on the epidemiological and clinical features of influenza A/H5N1 avian influenza and will highlight aspects relevant to travel medicine doctors.

What is the evidence of a role for host genetics in susceptibility to influenza A/H5N1?

The apparent family clustering of avian influenza A/H5N1 has led several groups to postulate the existence of a host genetic influence on susceptibility to A/H5N1, yet the role of host factors on the risk of A/H5N1 disease has received remarkably little attention compared to the efforts focused on viral factors. We examined the epidemiological patterns of human A/H5N1 cases, their possible explanations, and the plausibility of a host genetic effect on susceptibility to A/H5N1 infection. The preponderance of familial clustering of cases and the relative lack of non-familial clusters, the occurrence of related cases separated by time and place, and the paucity of cases in some highly exposed groups such as poultry cullers, are consistent with a host genetic effect. Animal models support the biological plausibility of genetic susceptibility to A/H5N1. Although the evidence is circumstantial, host genetic factors are a parsimonious explanation for the unusual epidemiology of human A/H5N1 cases and warrant further investigation.

SARS transmission in Vietnam outside of the health-care setting.

To evaluate the risk of transmission of SARS coronavirus outside of the health-care setting, close household and community contacts of laboratory-confirmed SARS cases were identified and followed up for clinical and laboratory evidence of SARS infection. Individual- and household-level risk factors for transmission were investigated. Nine persons with serological evidence of SARS infection were identified amongst 212 close contacts of 45 laboratory-confirmed SARS cases (secondary attack rate 4.2%, 95% CI 1.5-7). In this cohort, the average number of secondary infections caused by a single infectious case was 0.2. Two community contacts with laboratory evidence of SARS coronavirus infection had mild or sub-clinical infection, representing 3% (2/65) of Vietnamese SARS cases. There was no evidence of transmission of infection before symptom onset. Physically caring for a symptomatic laboratory-confirmed SARS case was the only independent risk factor for SARS transmission (OR 5.78, 95% CI 1.23-24.24).

Avian influenza H5N1 in viverrids: implications for wildlife health and conservation.

The Asian countries chronically infected with avian influenza A H5N1 are 'global hotspots' for biodiversity conservation in terms of species diversity, endemism and levels of threat. Since 2003, avian influenza A H5N1 viruses have naturally infected and killed a range of wild bird species, four felid species and a mustelid. Here, we report fatal disseminated H5N1 infection in a globally threatened viverrid, the Owston's civet, in Vietnam, highlighting the risk that avian influenza H5N1 poses to mammalian and avian biodiversity across its expanding geographic range.

A boarding school outbreak of pertussis in adolescents: value of laboratory diagnostic methods.

Culture for Bordetella pertussis (B. pertussis) is the traditional gold standard for laboratory diagnosis of pertussis but is insensitive, especially later in the course of illness and in vaccinated persons. Interpretation of serology is limited by the lack of an appropriate reference standard. An outbreak of pertussis in a crowded boarding-school dormitory allowed evaluation of laboratory correlates of infection. Questionnaires, serum samples and throat swabs were collected from members of the exposed group. Serum samples from unexposed controls of a similar age group were used for comparison. B. pertussis PCR was performed on throat swabs, and sera were tested for IgA antibodies against whole-cell (WC) B. pertussis antigen and IgG antibodies to pertussis toxin (PT). The Centers for Disease Control and Prevention definition for pertussis was used to define clinical cases. We evaluated the use of a previously published cut-off for PT IgG of 125 EIA units (EU)/ml. Completed questionnaires were obtained from 115 students, of whom 85 (74%) reported coughing symptoms, including 32 (28%) who met the clinical case definition for pertussis. B. pertussis was detected by PCR in 17 (15%) and WC IgA in 22 (19%) students; neither correlated with symptoms, but dormitory of residence strongly predicted PCR status. The mean PT IgG geometric mean concentration, in this situation of high pertussis exposure, correlated with severity of symptoms and was significantly higher in both symptomatic and asymptomatic children exposed during the outbreak (P < 0.001) than in control children. A cut-off for PT IgG of 125 EU/ml was too high in an outbreak situation to be sensitive enough to identify pertussis cases. A case of pertussis in a crowded boarding-school dormitory resulted rapidly in an outbreak. Serology and PCR were useful in identifying the outbreak and commencing disease control measures. The use of serology has mostly been evaluated in community serosurveys, where it is not possible to determine if immunity reflects vaccination, asymptomatic disease or symptomatic disease. This outbreak gave us the opportunity to evaluate the value of serology and PCR in the presence of confirmed exposure to pertussis.

A national outbreak of multi-resistant Salmonella enterica serovar Typhimurium definitive phage type (DT) 104 associated with consumption of lettuce.

Between 1 August and 15 September 2000, 361 cases of Salmonella enterica serotype Typhimurium definitive phage type (DT) 104, resistant to ampicillin, chloramphenicol, streptomycin, sulphonamides, spectinomycin and tetracycline (R-type ACSSuSpT), were identified in England and Wales residents. Molecular typing of 258 isolates of S. Typhimurium DT104 R-type ACSSuSpT showed that, although isolates were indistinguishable by pulsed-field gel electrophoresis, 67% (174/258) were characterized by a particular plasmid profile. A statistically significant association between illness and consumption of lettuce away from home was demonstrated (OR = 7.28; 95% CI=2.25-23.57; P=0.0006) in an unmatched case-control study. Environmental investigations revealed that a number of food outlets implicated in the outbreak had common suppliers of salad vegetables. No implicated foods were available for microbiological testing. An environmental audit of three farms that might have supplied salad vegetables to the implicated outlets did not reveal any unsafe agricultural practices. The complexity of the food supply chain and the lack of identifying markers on salad stuffs made tracking salad vegetables back to their origin extremely difficult in most instances. This has implications for public health since food hazard warnings and product withdrawal are contingent on accurate identification of the suspect product.

SARS: UK public health response--past, present and future.

The emergence of severe acute respiratory syndrome (SARS) in China, the occurrence of epidemics of SARS in China and a number of Southeast Asian countries, and its spread to countries elsewhere, have presented major challenges to public health systems throughout the world. Although very few true cases of SARS were detected in the United Kingdom, the public health response to the threat of SARS was considerable. The main components of this response were the early detection, isolation and reporting of cases, and the provision of comprehensive information to health professionals, cases, their contacts and the public. The development of the response to SARS raised a number of more general issues relevant to future infectious epidemic threats. Although the World Health Organisation has now declared SARS 'contained', the possibility of re-emergence is ever present. All countries will need to be vigilant and plan their response to the possibility of a renewed SARS epidemic.

Variant Creutzfeldt-Jakob disease: an unfolding epidemic of misfolded proteins.

Variant Creutzfeldt-Jakob disease (vCJD) is an emerging infectious disease believed to be the human manifestation of bovine spongiform encephalopathy (BSE). Variant CJD belongs to a family of human and animal diseases called transmissible spongiform encephalopathies (TSE). The pathogenesis of TSE is not fully understood, but a modified form of a normal cellular protein plays a central role. Current measures to control vCJD aim to prevent transmission of the infectious agent from animals to humans through food or pharmaceutical products and to prevent transmission from person to person via medical interventions. The anticipated development of preclinical diagnostic tests and treatments for vCJD will create new control options and difficult choices.

PHLS overview of communicable diseases 1999.

Every other year since 1995 the Public Health Laboratory Service has undertaken a consultation exercise to identify communicable diseases of high public health priority. The purpose of identifying disease priorities is to guide rational and transparent service planning and resource allocation. Also, the process aims to ensure a customer sensitive service. This paper presents the results of the priority setting exercise undertaken in 1999. A postal questionnaire was sent to 1130 key professionals involved in communicable disease control in the United Kingdom. Respondents were asked to assess the relative priority of 61 communicable diseases and to identify priority areas of work associated with these diseases. Five criteria were used to assess relative priority. The five criteria were; present burden of ill-health, social and economic impact, potential threat to health, health gain opportunity and public concern and confidence. For each disease, respondents were asked to score the importance of each criterion. Forty six percent of participants (518/1130) returned completed questionnaires. There was no significant difference in response rate by professional group. Based on the scores assigned to each of the five criteria, the relative priority of 61 communicable diseases has been established. The top ten diseases in descending order of priority are, HIV/AIDS, meningococcal diseases, Chlamydia trachomatis, influenza, tuberculosis, E. coli O157, Methicillin resistant Staphylococcus aureus, salmonellosis, transmissible spongiform encephalopathies and Helicobacter pylori. The opinion of a large number of health care professionals has been used to establish a priority rank for a wide range of communicable diseases. This work provides planners and policy makers with a synthesis of current professional opinion that can be used as a foundation for making decisions on service developments.

The capability of accident and emergency departments to safely decontaminate victims of chemical incidents.

OBJECTIVES: To evaluate the capability of accident and emergency (A&E) departments in six health regions of England to safely decontaminate casualties exposed to hazardous chemicals. METHODS: In January 1999 a postal questionnaire was sent to the clinical director of all A&E departments in Trent, North and South Thames, South and West, North West and, Anglia and Oxford Health Regions. The questionnaire inquired about characteristics of the department, decontamination facilities and equipment, and staff training. Nonresponders were sent a second questionnaire and contacted by telephone if they failed to respond to the second mailing. RESULTS: 308 of 326 departments identified (94%) returned a questionnaire. There was no significant difference in response rate by region (p = 0.99). Analysis was restricted to 154 major departments seeing more than 20000 new attendances per year. Of these 154 departments, 109 (71%) had a written chemical incident plan but only 55 (36%) maintained a list of nearby industrial chemical sites. Fifty nine departments (38%) stated that members of staff had received training in the management of chemically contaminated casualties in the preceding year. Eighteen departments (12%) possessed the level of personal protective equipment (PPE) recommended for decontamination by the Ambulance Services Association. Ninety six departments (62%) had a designated decontamination room but only seven (7%) of them incorporated all the features generally considered necessary for safe decontamination. Forty one units (27%) had the capability to decontaminate casualties outside of the department either with warm water from a shower attachment or with a mobile decontamination unit. Thirty six departments (23%) had neither a decontamination room nor the ability to decontaminate casualties outside the department. Only 16 units (10%) had both adequate PPE and either a decontamination room or the capability to decontaminate outside the department. CONCLUSIONS: This study has identified deficiencies in the current NHS capability to respond to chemical incidents. To resolve this, nationally recognised standards for decontamination facilities, equipment and training should be formulated, agreed and implemented.

Haemophilia A in the highlands: the investigation and management of two families in Tari.

A 12-year-old boy from Tari in the Southern Highlands of Papua New Guinea presented with prolonged bleeding from a minor injury to the lip. He had a history of profuse bleeding and joint swelling following minor trauma. He has two younger brothers with a similar history. It was demonstrated that they had a coagulation profile compatible with factor VIII deficiency and a family tree suggestive of haemophilia A. A further case was investigated some months later. Despite the neighbouring places of residence of the two families no familial connection could be established by involved discussions between family members. This was confirmed by reviewing the data held on the demographic surveillance system of the Tari Unit of the Papua New Guinea Institute of Medical Research. These families are considered against a background of the diagnosis and management of this condition in a rural part of Papua New Guinea. The long-term support of these patients and other similarly affected individuals presents difficult clinical and ethical problems for rural health services.