Credit CDC NESS
#17,478
While `big-ticket' viruses like Influenza A and (now) a handful of Coronaviruses (SARS, SARS-CoV-2, MERS-CoV) get the bulk of our attention, the world is filled with literally hundreds of `lesser' seasonal virus threats that can have significant public health impacts.
Over the past year we've looked at a number of outbreaks of RSV (see here, here, here), Adenoviruses (see here, and here), Parechoviruses (see here), and enteroviruses (see here).
These viruses are of particular concern because they tend to impact young children the hardest, and while they don't tend to mutate as rapidly as influenza or COVID, they can and do evolve over time.
Prior to 2014, EV-D68 was considered both rare and mild, but over the past decade it has evolved into a more pathogenic (and neurotropic) virus (see mBio: Contemporary EV-D68 Strains Have Acquired The Ability To Infect Human Neuronal Cells).
Although they are generally not reportable diseases, the CDC's The National Respiratory and Enteric Virus Surveillance System (NREVSS) and the National Enterovirus Surveillance System (NESS) monitor reports that are voluntarily submitted by laboratories across the nation, as do other countries.
Yesterday the WHO published a DON (Disease Outbreak News) report on an increase in an Enterovirus (Echovirus-11) in France over the past year, resulting in at least 9 severe infections in neonatal patients including 7 deaths.
Of note, France is reporting two new recombinant lineages of E-11, and all of the identified samples since the first of the year belong to the lineage linked to these severe cases. That said, only about 4% of known infections have proved severe.
First some excerpts from yesterday's report, then I'll return with a postscript.
Enterovirus Infection - France
31 May 2023
Situation at a glance
On 5 May 2023, France reported an increase in cases of severe neonatal sepsis associated with Enterovirus (Echovirus-11 (E-11)). A total of nine cases of neonatal sepsis with hepatic impairment and multi-organ failure were reported between July 2022 and April 2023 from four hospitals in three regions of France. As of 5 May 2023, seven cases have died and two were still hospitalized in neonatal unit.
The current increase in incidence and severity in neonates, associated with a recombinant lineage of E-11 that previously was not detected in France, and is considered unusual due to the extremely rapid deterioration and associated case fatality rate amongst the affected babies.
Based on the limited information available, WHO assesses the public health risk for the general population to be low, despite the concerning nature of the increase.
(SNIP)
Epidemiology of disease
Enteroviruses are a group of viruses that can cause various infectious illnesses and are responsible for annual epidemics. Illness is usually mild but has been found to affect neonates differently and sometimes more severely than older children and adults. There are multiple transmission routes, particularly in the neonatal period, including intrapartum by exposure to maternal blood, secretions, and/or stool, or postnatally from close contacts with infected caregivers. Echovirus 11 (E-11) is a positive-strand RNA virus belonging to the genus Enterovirus of the family Picornaviridae.
The infections can cause severe inflammatory illnesses in neonates, including severe acute hepatitis with coagulopathy.
WHO risk assessment
A review of the epidemiological data collected from 2016 to 2022 in France through routine surveillance of enterovirus infections among hospitalized patients showed a significant increase in incidence and mortality for all severe neonatal infections associated with E-11, defined as infections with at least one organ failure and/or requiring admission to intensive care.
A total of 443 enterovirus neonatal infections (severe and non-severe types) including seven deaths (case fatality rate, (CFR) 1.6%) were reported in France in 2022. Of these, 72% (n=317) had a known enterovirus type. E-11 was the predominant circulating enterovirus type (all ages included) and was identified in 30.3% (96 of 317) of neonatal infections (severe and non-severe) with known enterovirus type. It has been continuously detected since June 2022.
Of the reported neonatal infections in 2022, 4.5% (22 of 443) were classified as severe. Of these 20 had known enterovirus types. E-11 represented 55% (11 of 20) of these cases as compared to 6.2% (3 of 48) of cases with known enterovirus type out of the total reported severe neonatal infections (n=62) between 2016 to 2021.
In 2022, there were seven deaths (case fatality rate, (CFR) 1.6%) out of the cumulative 443 enterovirus neonatal infections recorded in 2022 (six associated with E-11), compared to seven deaths (CFR 0.4%), out of 1774 neonatal infections from 2016 to 2021(none associated with E-11). As mentioned above, there have also been seven deaths so far in 2023.
Sequence analyses showed the circulation of at least two lineages of recombinant origin, of which the predominant one included all the sequences associated with the nine severe cases together with sequences associated with non-neonatal or non-severe neonatal infections. This new variant of E-11 had not been observed in France before July 2022, nor elsewhere based on available sequences on Genbank, as of 28 April 2023. As of 5 May 2023, E-11 sequences retrieved from samples collected in 2023 all belong to this predominant lineage.
Although higher pathogenicity of this new lineage cannot be excluded, the severity of infections may also be explained by the young age, prematurity, and the absence of maternal immunity. Further analyses are warranted to delineate the characteristics of this recombinant virus.
Based on the limited information available, WHO assesses the public health risk for the general population to be low. However, asymptomatic carriage and shedding of infectious viruses are a feature of enterovirus infection. Echovirus infection was confirmed in four out of five mothers by analyzing blood samples three days before or at delivery. There have been previous reports of severe E-11 infection in twin neonates, however, the observation of four sets of twins amongst nine cases is more than expected. As non-polio enterovirus infection is often not a notifiable disease in Member States, additional cases of severe neonatal enterovirus infection may have gone undiagnosed and/or unreported.
Detection of recombinant breakpoint in the genome of human enterovirus E11 strain associated with a fatal nosocomial outbreakMartina Rueca, Simone Lanini, Emanuela Giombini, Francesco Messina, Concetta Castilletti, Giuseppe Ippolito, Maria Rosaria Capobianchi & Maria Beatrice Valli
Echovirus 11 infection induces pyroptotic cell death by facilitating NLRP3 inflammasome activation
Chong Wang ,Ruyi Yang ,Fengxia Yang,Yang Han,Yujie Ren,Xiaobei Xiong,Xingyun Wang,Yidan Bi,Lijun Li,Yang Qiu ,Yi Xu ,Xi Zhou
Risk factors and early markers for echovirus type 11 associated haemorrhage-hepatitis syndrome in neonates, a retrospective cohort study
Ping Wang, 1 , † Yi Xu, 2 , † Ming Liu, 3 , † Huixian Li, 4 Hui Wang, 5 Yumei Liu, 6 Bin Wang, 7 Shiwen Xia, 5 Heng Su, 1 Mou Wei, 1 Li Tao, 1 Xiaowen Chen, 1 Bingtai Lu, 8 Xiaoqiong Gu, 9 Hui Lyu, 3 Wei Zhou, 1 ,* Huayan Zhang, 1 , 10 ,* and Sitang Gong 11 ,*
Last year, after the UK reported an unusual increase in acute pediatric hepatitis with unknown etiology it led to dozens of other countries looking at their epidemiological data, and finding similar patterns of infection (see CDC HAN Advisory On Adenovirus Testing and Reporting Of Children With Acute Hepatitis).
Hopefully, if today's report is more than a transient, localized, outbreak we'll hear from other countries in the days and weeks ahead.
