Association between type-specific influenza circulation and incidence of severe laboratory-confirmed cases; which subtype is the most virulent?

OBJECTIVES: Excess population mortality during winter is most often associated with influenza A(H3N2), though susceptibility differs by age. We examined differences between influenza types/subtypes in their association with severe laboratory-confirmed cases, overall and by age group, to determine which type is the most virulent. METHODS: We used nine seasons of comprehensive nationwide surveillance data from Greece (2010-2011 to 2018-2019) to examine the association, separately for influenza A(H1N1)pdm09, A(H3N2) and B, between the number of laboratory-confirmed severe cases (intensive care hospitalizations or deaths) per type/subtype and the overall type-specific circulation during the season (expressed as a cumulative incidence proxy). Quasi-Poisson models with identity link were used, and multiple imputation to handle missing influenza A subtype. RESULTS: For the same level of viral circulation and across all ages, influenza A(H1N1)pdm09 was associated with twice as many intensive care hospitalizations as A(H3N2) (rate ratio (RR) 1.89, 95% CI 1.38-2.74) and three times more than influenza B (RR 3.27, 95%CI 2.54-4.20). Similar associations were observed for laboratory-confirmed deaths. A(H1N1)pdm09 affected adults over 40 years at similar rates, whereas A(H3N2) affected elderly people at a much higher rate than younger persons (≥65 vs. 40-64 years, RR for intensive care 5.42, 95% CI 3.45-8.65, and RR for death 6.19, 95%CI 4.05-9.38). Within the 40-64 years age group, A(H1N1)pdm09 was associated with an approximately five times higher rate of severe disease than both A(H3N2) and B. DISCUSSION: Influenza A(H1N1)pdm09 is associated with many more severe laboratory-confirmed cases, likely due to a more typical clinical presentation and younger patient age, leading to more testing. A(H3N2) affects older people more, with cases less often recognized and confirmed.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Ongoing measles outbreak in Greece related to the recent European-wide epidemic.

We report an ongoing measles outbreak in Greece. The first cases were notified through the mandatory notification system on May 2017 in Northern Greece and concerned a cluster of three imported cases in unvaccinated Roma siblings. So far, 3150 cases have been reported in all 13 Regions. Initially, the outbreak mainly affected Greek Roma but as it progressed it spread to non-minority Greek nationals. The outbreak reached its ultimate peak on week 10/2018 but from week 15/2018 has been gradually declining. Most cases (60.6%) were Roma (especially children <10 year-old) followed by non-minority Greek nationals (29.3%; mostly young adults). The majority (80.4%) were unvaccinated. Interestingly, 129 (4.1%) cases were healthcare workers (HCWs). Genotype B3 was identified by molecular methods in all 87 cases tested. Overall, 61.3% of the cases were hospitalised. Complications were reported in 17.1% of the cases among which four deaths. The outbreak occurred after 3 years without local endemic measles transmission. Extensive vaccination implemented as the major public health measure managed to prevent the emergence of a large number of cases in refugee/migrant hosting sites. Mitigation efforts currently focus on raising awareness among HCWs and closing the immunisation gap in populations with suboptimal vaccination coverage.

Ιnfluenza A(H3N2) genetic variants in vaccinated patients in northern Greece.

BACKGROUND: Influenza A(H3N2) viruses predominated during the influenza 2016/2017 season and showed extensive genetic diversification. A high vaccination failure rate was noticed during the 2016/17 season in Greece, especially among the elderly. OBJECTIVES: The scope of the study was to investigate the genetic characteristics of A(H3N2) circulating viruses and viruses detected in vaccinated patients. STUDY DESIGN: Virus samples originated from vaccinated and unvaccinated patients, obtained at the National Influenza Centre for northern Greece. Phylogenetic analysis and comparison of the haemagglutinin gene of the viruses to the vaccine virus A/Hong Kong/4801/2014 was performed. RESULTS: The majority of analysed viruses are clustering in the genetic clade 3C.2a, and in a newly emerged subclade, designated as 3C.2a1. The highest proportion of viruses detected in vaccinated patients fell into a distinct subcluster within the 3C.2a1 subclade, which is characterised by the amino acid substitutions N122D and T135K in haemagglutinin. CONCLUSIONS: Viruses that belong to the 3C.2a clade are generally considered to resemble antigenically to the northern hemisphere vaccine component A/Hong Kong/4801/2014 that was recommended by WHO to be included also into the 2017/18 vaccine. However, viruses belonging to a specific 3C.2a1 subcluster was extensively circulating in northern Greece and among vaccinated individuals. Both substitutions carried by this strain were located on antigenic sites and caused losses of N-linked glycosylation sites of the virus, which could potentially affect viral antigenicity. Further studies are needed to determine the antigenicity of this variant strain and its possible implication in vaccine effectiveness.

Excess mortality among the elderly in European countries, December 2014 to February 2015.

Since December 2014 and up to February 2015, the weekly number of excess deaths from all-causes among individuals ≥ 65 years of age in 14 European countries have been significantly higher than in the four previous winter seasons. The rise in unspecified excess mortality coincides with increased proportion of influenza detection in the European influenza surveillance schemes with a main predominance of influenza A (H3N2) viruses seen throughout Europe in the current season, though cold snaps and other respiratory infections may also have had an effect.

Epidemiology of human leishmaniasis in Greece, 1981-2011.

Leishmaniasis is endemic and mandatorily notifiable in Greece. Epidemiological surveillance data for leishmaniasis in Greece between 1981 and 2011 are presented. In 1998, the notification system began distinguishing between visceral and cutaneous leishmaniasis. The mean annual incidence of reported leishmaniasis cases between 1998 and 2011 was 0.36 per 100,000 population. Of a total 563 leishmaniasis cases reported after 1998, 523 (93%) were visceral leishmaniasis cases. Incidence of reported visceral leishmaniasis cases fluctuated during this period, generally decreasing after 2007, with a small re-increase in 2011. The mean annual incidence rate of reported visceral leishmaniasis cases was significantly higher in less than four year-olds (p <0.001). Leishmaniasis cases occurred both in the country mainland and islands. Between 1998 and 2011, Attica concentrated almost half of the reported visceral leishmaniasis cases, with incidence rates in western Attica and western Athens above 12.00 per 100,000 population. Compared to visceral leishmaniasis, cutaneous leishmaniasis had a rather sporadic distribution, with many prefectures appearing free of cases. From 2004, the notification also included risk factors and of 287 cases with known immune status, 44 (15%) were immunocompromised. Moreover having a dog at home was reported by 209 of 312 leishmaniasis cases (67%), whereas 229 of 307 cases (75%) reported the presence of stray dogs near their residence. Linking clinical surveillance data with laboratory data and improving collaboration with the veterinary public health sector are some of the future challenges for leishmaniasis surveillance in Greece.

Outbreak investigation of brucellosis in Thassos, Greece, 2008.

In spring 2008, the Hellenic Center for Disease Control and Prevention was notified about human brucellosis cases in Thassos, a Greek island that had been up to that point under a brucellosis eradication programme. Following the verification of the outbreak a 1:1 case­ control study was conducted in the island. The study revealed that consumption of locally produced raw cheese was a risk factor for Brucella melitensis infection (odds ratio (OR): 15.1, 95% confidence interval (CI): 6.56­34.7). Brucella melitensis biotype 3 was identified in two clinical samples. As a result of the outbreak, the island is no longer officially considered as an area with farms free of brucellosis and is currently under a brucellosis control programme. The investigation of this outbreak demonstrated that control and eradication of brucellosis is not only a question of designing a strategy, but rather of ensuring its continuous, strict implementation. Furthermore, it revealed the lack of appropriate education of the public regarding the risks associated with raw, non heat-treated cheese consumption.

A waterborne Campylobacter jejuni outbreak on a Greek island.

A case-control and a case-crossover study were performed to investigate a Campylobacter jejuni outbreak in Crete in 2009. Most cases originated from rural areas, served by a different water-supply system from that of the adjacent town. Thirty-seven cases and 79 controls were interviewed; cases were interviewed for two different time periods for the case-crossover study. Stool cultures, PFGE and MLST subtyping were run in human samples. Univariately, consumption of tap water was associated with C. jejuni infection. Stratified analysis revealed that water-supply system was an effect modifier of this association. In the multivariable analysis, the rural areas' water supplier and drinking tap water were risk factors. No risk factors were revealed in the case-crossover study. No Campylobacter were isolated in the tested water samples. There is strong epidemiological evidence that tap water was the vehicle of the outbreak.

Algorithm for statistical detection of peaks--syndromic surveillance system for the Athens 2004 Olympic Games.

INTRODUCTION: No generally accepted procedure exists for detecting outbreaks in syndromic time series used in the surveillance of natural epidemics or biologic attacks. OBJECTIVES: This report evaluates the usefulness for syndromic surveillance of the Pulsar approach, which is based on removing long-term trends from an observed series and identifying peaks in the residual series of surveillance data with cutoffs determined by using a combination of peak height and width. METHODS: Simulations were performed to evaluate the Pulsar method and compare it with other approaches. The daily syndromic counts in emergency departments of four major hospitals in the Athens area during August 2002-August 2003 were analyzed for two common syndromes. A standardized residual series was generated by omitting trends and noise in the original data series; this series was examined for the presence of peaks (i.e., points having magnitude higher than at least one of three probabilistically determined cutoffs). The whole process was iterated, and the baseline was recalculated by assigning reduced weight to the identified peaks. RESULTS: For the specific simulation schema used, the Pulsar method fared well when compared with other approaches in meeting the performance criteria of sensitivity, specificity, and timeliness. CONCLUSIONS: Although the suggested algorithm needs further validation regarding the correspondence between detected peaks and true biologic alerts, the Pulsar technique appears effective for observing peaks in time series of syndromic events. The simplicity of the algorithm, its ability to detect peaks based not only on height but also on width, and its performance in the simulated data sets make it a promising candidate for further use in syndromic surveillance.