Core competencies in applied infectious disease epidemiology: a framework for countries in Europe.

In 2009, the European Centre for Disease Prevention and Control (ECDC) developed a competency framework to support European Union countries and the European Commission in ensuring a competent public health workforce for Europe. The coronavirus disease (COVID-19) pandemic emphasised the importance of harmonised public health strategies and competencies across international boundaries, specifically for infectious diseases. This perspective presents the process to update the competency framework for applied infectious disease epidemiology, highlighting ECDC's efforts to support countries with using the framework. ECDC commissioned the Association of Schools of Public Health in the European Region (ASPHER) to update the framework through publication and dissemination of a technical report and a self-assessment tool linked to training resources. A mixed methods approach to gather input from experts in relevant specialities included qualitative interviews with 42 experts, workshops with ECDC Technical Advisory Group and an online survey of 212 public health professionals across Europe and beyond. Modifications resulted in 157 core competencies in 23 domains, each mapping to one of six subject areas of importance in applied infectious disease epidemiology. The framework serves as a basis to update the curriculum of the ECDC Fellowship programme with two alternative paths: intervention epidemiology or public health microbiology.

Piloting a surveillance system for HIV drug resistance in the European Union.

BackgroundA steady increase in HIV drug resistance (HIVDR) has been demonstrated globally in individuals initiating first-line antiretroviral therapy (ART). To support effective use of ART and prevent spread of HIVDR, monitoring is essential.AimWe piloted a surveillance system for transmitted HIVDR to assess the feasibility of implementation at the European level.MethodAll 31 countries in the European Union and European Economic Area were invited to retrospectively submit data on individuals newly diagnosed with HIV in 2015 who were tested for antiviral susceptibility before ART, either as case-based or as aggregate data. We used the Stanford HIV database algorithm to translate genetic sequences into levels of drug resistance.ResultsNine countries participated, with six reporting case-based data on 1,680 individuals and four reporting aggregated data on 1,402 cases. Sequence data were available for 1,417 cases: 14.5% of individuals (n = 244) showed resistance to at least one antiretroviral drug. In case-based surveillance, the highest levels of transmitted HIVDR were observed for non-nucleoside reverse-transcriptase inhibitors (NNRTIs) with resistance detected in 8.6% (n = 145), followed by resistance to nucleoside reverse-transcriptase inhibitors (NRTI) (5.1%; n = 85) and protease inhibitors (2.0%; n = 34).ConclusionWe conclude that standard reporting of HIVDR data was feasible in the participating countries. Legal barriers for data sharing, consensus on definitions and standardisation of interpretation algorithms should be clarified in the process of enhancing European-wide HIV surveillance with drug resistance information.

Reported rates of all-cause serious adverse events following immunization with BNT-162b in 5-17-year-old children in the United States.

Vaccine development against COVID-19 has mitigated severe disease. However, reports of rare but serious adverse events following immunization (sAEFI) in the young populations are fuelling parental anxiety and vaccine hesitancy. With a very early season of viral illnesses including COVID-19, respiratory syncytial virus (RSV), influenza, metapneumovirus and several others, children are facing a winter with significant respiratory illness burdens. Yet, COVID-19 vaccine and booster uptake remain sluggish due to the mistaken beliefs that children have low rates of severe COVID-19 illness as well as rare but severe complications from COVID-19 vaccine are common. In this study we examined composite sAEFI reported in association with COVID-19 vaccines in the United States (US) amongst 5-17-year-old children, to ascertain the composite reported risk associated with vaccination. Between December 13, 2020, and April 13, 2022, a total of 467,890,599 COVID-19 vaccine doses were administered to individuals aged 5-65 years in the US, of which 180 million people received at least 2 doses. In association with these, a total of 177,679 AEFI were reported to the Vaccine Adverse Event reporting System (VAERS) of which 31,797 (17.9%) were serious. The rates of ED visits per 100,000 recipients were 2.56 (95% CI: 2.70-3.47) amongst 5-11-year-olds, 18.25 (17.57-18.95) amongst 12-17-year-olds and 33.74 (33.36-34.13) amongst 18-65-year olds; hospitalizations were 1.07 (95% CI 0.87-1.32) per 100,000 in 5-11-year-olds, 6.83 (6.42-7.26) in 12-17-year olds and 8.15 (7.96-8.35) in 18-65 years; life-threatening events were 0.14 (95% CI: 0.08-0.25) per 100,000 in 5-11-year olds, 1.22 (1.05-1.41) in 12-17-year-olds and 2.96 (2.85-3.08) in 18-65 year olds; and death 0.03 (95% CI 0.01-0.10) per 100,000 in 5-11 year olds, 0.08 (0.05-0.14) amongst 12-17-year olds and 0.76 (0.71-0.82) in 18-65 years age group. The results of our study from national population surveillance data demonstrate rates of reported serious AEFIs amongst 5-17-year-olds which appear to be significantly lower than in 18-65-year-olds. These low risks must be taken into account in overall recommendation of COVID-19 vaccination amongst children.

Analyses of reported severe adverse events after immunization with SARS-CoV-2 vaccines in the United States: One year on.

Objective: To analyze rates of reported severe adverse events after immunization (sAEFI) attributed to SARS-CoV-2 vaccines in the United States (US) using safety surveillance data. Methods: Observational study of sAEFI reported to the vaccine adverse events reporting system (VAERS) between December 13, 2020, to December 13, 2021, and attributed to SARS-CoV-2 vaccination programs across all US states and territories. All sAEFI in conjunction with mRNA (BNT-162b2 or mRNA-1273) or adenovector (Ad26.COV2.S) vaccines were included. The 28-day crude cumulative rates for reported emergency department (ED) visits and sAEFI viz. hospitalizations, life-threatening events and deaths following SARS-CoV-2 vaccination were calculated. Incidence rate ratios (IRRs) of reported sAEFI were compared between mRNA and adenovector vaccines using generalized Poisson regression models. Results: During the study period, 485 million SARS-CoV-2 vaccines doses were administered nationwide, and 88,626 sAEFI reported in VAERS. The 28-day crude cumulative reporting rates per 100,000 doses were 14.97 (95% confidence interval, 14.86-18.38) for ED visits, 5.32 (5.26-5.39) for hospitalizations, 1.72 (1.68-1.76) for life-threatening events, and 1.08 (1.05-1.11) for deaths. Females had two-fold rates for any reported AEFI compared to males, but lower adjusted IRRs for sAEFI. Cumulative rates per dose for reported sAEFI attributed to adenovector vaccine were 2-3-fold higher, and adjusted IRRs 1.5-fold higher than mRNA vaccines. Conclusions: Overall cumulative rates for reported sAEFI following SARS-CoV-2 vaccination in the US over 1 year were very low; single-dose adenovector vaccine had 1.5-fold higher adjusted rates for reported sAEFI, which may however equate with multiple-doses mRNA vaccine regimens. These data indicate absence of high risks of sAEFI following SARS-CoV-2 vaccines and support safety equipoise between mRNA and adenovector vaccines. Public health messaging of these data is critical to overcome heuristic biases. Furthermore, these data may support ongoing adenovector vaccine use, especially in low- and middle-income countries due to affordability, logistical and cold chain challenges.

High probability of avian influenza virus (H7N7) transmission from poultry to humans active in disease control on infected farms.

An epizootic of avian influenza (H7N7) caused a large number of human infections in The Netherlands in 2003. We used data from this epizootic to estimate infection probabilities for persons involved in disease control on infected farms. Analyses were based on databases containing information on the infected farms, person-visits to these farms, and exposure variables (number of birds present, housing type, poultry type, depopulation method, period during epizootic). Case definition was based on self-reported conjunctivitis and positive response to hemagglutination inhibition assay. A high infection probability was associated with clinical inspection of poultry in the area surrounding infected flocks (7.6%; 95% confidence interval [CI], 1.4%-18.9%) and active culling during depopulation (6.2%; 95% CI, 3.7%-9.6%). Low probabilities were estimated for management of biosecurity (0.0%; 95% CI, 0.0%-1.0%) and cleaning assistance during depopulation (0.0%; 95% CI, 0.0%-9.2%). No significant association was observed between the probability of infection and the exposure variables.

Non-travel related Hepatitis E virus genotype 3 infections in the Netherlands; a case series 2004 - 2006.

BACKGROUND: Human hepatitis E virus (HEV) infections are considered an emerging disease in industrialized countries. In the Netherlands, Hepatitis E virus (HEV) infections have been associated with travel to high-endemic countries. Non-travel related HEV of genotype 3 has been diagnosed occasionally since 2000. A high homology of HEV from humans and pigs suggests zoonotic transmission but direct molecular and epidemiological links have yet to be established. We conducted a descriptive case series to generate hypotheses about possible risk factors for non-travel related HEV infections and to map the genetic diversity of HEV. METHODS: A case was defined as a person with HEV infection laboratory confirmed (positive HEV RT-PCR and/or HEV IgM) after 1 January 2004, without travel to a high-endemic country three months prior to onset of illness. For virus identification 148 bp of ORF2 was sequenced and compared with HEV from humans and pigs. We interviewed cases face to face using a structured questionnaire and collected information on clinical and medical history, food preferences, animal and water contact. RESULTS: We interviewed 19 cases; 17 were male, median age 50 years (25-84 y), 12 lived in the North-East of the Netherlands and 11 had preexisting disease. Most common symptoms were dark urine (n = 16) and icterus (n = 15). Sixteen ate pork >/= once/week and six owned dogs. Two cases had received blood transfusions in the incubation period. Seventeen cases were viremic (genotype 3 HEV), two had identical HEV sequences but no identified relation. For one case, HEV with identical sequence was identified from serum and surface water nearby his home. CONCLUSION: The results show that the modes of transmission of genotype-3 HEV infections in the Netherlands remains to be resolved and that host susceptibility may play an important role in development of disease.

Measurement of antibodies to avian influenza virus A(H7N7) in humans by hemagglutination inhibition test.

During the epizootic of highly pathogenic avian influenza A(H7N7) in 2003 in The Netherlands, RT-PCR and culture confirmed infection was detected in 89 persons who were ill. A modified hemagglutination inhibition (HI) test using horse erythrocytes and 2 hemagglutinating units of virus was applied to assess retrospectively the extent of human (subclinical) infection. Validation of the HI-test with sera from 34 RT-PCR and culture confirmed A(H7) infected persons and sera from 100 persons from a human influenza vaccine trial in autumn 2002 showed that this HI-test had a sensitivity of 85% and a specificity of 100% when using a cut-off titer of > or =10. Using this cut-off value, A(H7) specific antibodies were detected in 49% of 508 persons exposed to poultry and in 64% of 63 persons exposed to A(H7) infected persons. Correlation of seropositivity with the occurrence of eye symptoms in exposed persons who had not received antiviral prophylaxis and of reduced seropositivity with taking antiviral prophylaxis provided further evidence that the A(H7) HI antibody titers were real. In conclusion, by applying an HI-test using horse erythrocytes human antibodies against the avian A(H7N7) virus were detected with high sensitivity and specificity in an unexpectedly high proportion of exposed persons.

Transmission of H7N7 avian influenza A virus to human beings during a large outbreak in commercial poultry farms in the Netherlands.

BACKGROUND: An outbreak of highly pathogenic avian influenza A virus subtype H7N7 started at the end of February, 2003, in commercial poultry farms in the Netherlands. Although the risk of transmission of these viruses to humans was initially thought to be low, an outbreak investigation was launched to assess the extent of transmission of influenza A virus subtype H7N7 from chickens to humans. METHODS: All workers in poultry farms, poultry farmers, and their families were asked to report signs of conjunctivitis or influenza-like illness. People with complaints were tested for influenza virus type A subtype H7 (A/H7) infection and completed a health questionnaire about type of symptoms, duration of illness, and possible exposures to infected poultry. FINDINGS: 453 people had health complaints--349 reported conjunctivitis, 90 had influenza-like illness, and 67 had other complaints. We detected A/H7 in conjunctival samples from 78 (26.4%) people with conjunctivitis only, in five (9.4%) with influenza-like illness and conjunctivitis, in two (5.4%) with influenza-like illness only, and in four (6%) who reported other symptoms. Most positive samples had been collected within 5 days of symptom onset. A/H7 infection was confirmed in three contacts (of 83 tested), one of whom developed influenza-like illness. Six people had influenza A/H3N2 infection. After 19 people had been diagnosed with the infection, all workers received mandatory influenza virus vaccination and prophylactic treatment with oseltamivir. More than half (56%) of A/H7 infections reported here arose before the vaccination and treatment programme. INTERPRETATION: We noted an unexpectedly high number of transmissions of avian influenza A virus subtype H7N7 to people directly involved in handling infected poultry, and we noted evidence for person-to-person transmission. Our data emphasise the importance of adequate surveillance, outbreak preparedness, and pandemic planning.

Automated, laboratory-based system using the Internet for disease outbreak detection, the Netherlands.

Rapid detection of outbreaks is recognized as crucial for effective control measures and has particular relevance with the recently increased concern about bioterrorism. Automated analysis of electronically collected laboratory data can result in rapid detection of widespread outbreaks or outbreaks of pathogens with common signs and symptoms. In the Netherlands, an automated outbreak detection system for all types of pathogens has been developed within an existing electronic laboratory-based surveillance system called ISIS. Features include the use of a flexible algorithm for daily analysis of data and presentation of signals on the Internet for interpretation by health professionals. By 2006, the outbreak detection system will analyze laboratory-reported data on all pathogens and will cover 35% of the Dutch population.

Avian influenza A virus (H7N7) associated with human conjunctivitis and a fatal case of acute respiratory distress syndrome.

Highly pathogenic avian influenza A viruses of subtypes H5 and H7 are the causative agents of fowl plague in poultry. Influenza A viruses of subtype H5N1 also caused severe respiratory disease in humans in Hong Kong in 1997 and 2003, including at least seven fatal cases, posing a serious human pandemic threat. Between the end of February and the end of May 2003, a fowl plague outbreak occurred in The Netherlands. A highly pathogenic avian influenza A virus of subtype H7N7, closely related to low pathogenic virus isolates obtained from wild ducks, was isolated from chickens. The same virus was detected subsequently in 86 humans who handled affected poultry and in three of their family members. Of these 89 patients, 78 presented with conjunctivitis, 5 presented with conjunctivitis and influenza-like illness, 2 presented with influenza-like illness, and 4 did not fit the case definitions. Influenza-like illnesses were generally mild, but a fatal case of pneumonia in combination with acute respiratory distress syndrome occurred also. Most virus isolates obtained from humans, including probable secondary cases, had not accumulated significant mutations. However, the virus isolated from the fatal case displayed 14 amino acid substitutions, some of which may be associated with enhanced disease in this case. Because H7N7 viruses have caused disease in mammals, including horses, seals, and humans, on several occasions in the past, they may be unusual in their zoonotic potential and, thus, form a pandemic threat to humans.

A large outbreak of Legionnaires' disease at a flower show, the Netherlands, 1999.

In 1999, an outbreak of Legionnaires' disease affected many visitors to a flower show in the Netherlands. To identify the source of the outbreak, we performed an environmental investigation, as well as a case-control study among visitors and a serologic cohort study among exhibitors to measure exposure to possible sources. Of 77,061 visitors, 188 became ill (133 confirmed and 55 probable cases), for an attack rate of 0.23% for visitors and 0.61% for exhibitors. Two whirlpool spas in halls 3 and 4 of the exhibition and a sprinkler in hall 8 were culture positive for Legionella pneumophila. One of three genotypes found in both whirlpool spas was identical to the isolates from 28 of 29 culture-positive patients. Persons who paused at the whirlpool spa in hall 3 were at increased risk for becoming ill. This study illustrates that whirlpool spas may be an important health hazard if disinfection fails.