#14,600
With news reports and fresh studies often in short supply during the holidays, each year at this time I review some of the infectious disease papers we looked at during the past year. Too often these studies are published, and then quickly lost in the never-ending deluge of new data.
During the month of April, while we were watching a mystery outbreak in a mining town in Guyana, increasing MERS cases in Saudi Arabia, China's one and only H7N9 case of the year, multiple outbreaks of Equine Influenza around the globe, and another (failed) attempt to have Ebola in the DRC declared a PHEIC (Public Health Emergency of International Concern), we also looked at:
EID Journal: Equine Influenza - A Neglected, Reemergent Disease Threat
While Equine (H3N8) influenza is not currently regarded as a zoonotic threat, it jumped species (to dogs) roughly 16 years ago and has since been show capable of infecting cats (see Equine influenza A(H3N8) virus infection in cats). A review of the history of (H3 & H7) equine influenza suggests it has jumped species - including to humans - in the past, and could do so again.
From the Abstract:
Equine influenza virus (EIV) is a common, highly contagious equid respiratory disease. Historically, EIV outbreaks have caused high levels of equine illness and economic damage. Outbreaks have occurred worldwide in the past decade. The risk for EIV infection is not limited to equids; dogs, cats, and humans are susceptible.
This is a scenario we looked at previously in 2018 in Equine H3N8: Looking At A long-shot In The Pandemic Sweepstakes. Canine and equine flu are of particular interest because the H3N8 and H3N2 subtypes they carry are similar to pandemic strains of the past .
OFID: Avian H5, H7 & H9 Contamination Before & After China's Massive Poultry Vaccination Campaign
During the summer of 2017 China implemented an emergency experimental poultry vaccination program using a new H5+H7 vaccine, in hopes of stemming the rising tide of H7N9 (and to a lesser extent) H5N6 human infections that threatened a pandemic.
While successful beyond anyone's expectations, vaccines don't always halt disease transmission -sometimes they only suppress it - and that can allow `vaccine escape' variants to evolve and spread (see last week's EID Journal: Antigenic Variant of Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2019).
Surveillance in Zhejiang Province (China) showed a 90% reduction in H7 virus activity following the vaccination program, but detection of H5 viruses remains pretty much unchanged, while the prevalence of H9N2 viruses had increased significantly.
The authors concluded:
Despite the sharp decrease in H7 subtype prevalence, reduction measures for avian influenza virus circulation are still imperative, given the high type A prevalence and the increase in H9 subtype contamination across different sampling places and types.
Emer. Microb. & Inf.: Avian Flu Co-Infection in Poultry - Cambodia, 2017–2018
Credit CDC
Cambodia has a long history of HPAI H5N1 outbreaks in poultry, and human infections, going back to early in the last decade. In March and early April of this year, both HPAI H5N6 and a new H7N4 virus - similar to one that infected a woman in China in 2018 - were reported to be circulating in Cambodia as well.
This research letter, published in Emerging Microbes & Infections, describes recent AI surveillance results, and quantifies the level and types of co-infections, found in Cambodian poultry.
From the Abstract:
Cambodian LBMs have high levels of AIV circulation, with 30–50% of ducks and 20–40% of chickens testing positive. Intense circulation of A/H5N1 and other avian influenza viruses in Cambodian live-bird markets with serological evidence of sub-clinical human infections.
Concerningly, a multitude of high and low pathogenic AIVs circulate concurrently. Previous studies suggest peak AIV circulation corresponds to the dry season (November to May) especially around Lunar New Year (LNY) celebrations when poultry consumption is highest.
Not unexpectedly, more than 90% of the co-infections reported involved the highly promiscuous H9N2 virus, which - while it has some pandemic potential on its own (see CDC IRAT Score) - is more infamous for lending its internal genes to many of the HPAI viruses of greatest concern today (see The Lancet's Poultry carrying H9N2 act as incubators for novel human avian influenza viruses).
J. Inf. Pub. Health: Diagnostic Delays in MERS Coronavirus Patients & Health Systems
MERS - like most viral illnesses - can present with a wide spectrum of symptoms - ranging from mild to severe - and are often clinically indistinguishable from other, more common and routine respiratory infections.
This, along with Intermittent Positive Testing For MERS-CoV and the Saudi's heavy reliance on a reportedly flawed Visual Triage System for the Screening of MERS-CoV Patients, has led to multiple instances where patients not diagnosed early, which can delay treatment and increase the chances of nosocomial transmission.
From the Abstract:
The health-system delay in identifying a MERS-CoV case may be attributed to the delay in the virus recognition in medical institutions [6] and to the limited awareness among healthcare-workers [11], as a survey conducted on 1216 healthcare-workers revealed that only 47.6% of the physicians and 30.4% of the nurses were aware that some infected patients had no symptoms [11].
Also diagnosis of MERS-CoV [3] and medical care for patients with MERS-CoV [12] remain major challenges in healthcare facilities. Further understanding on the causes of patient and health-system delay is needed, as it can be used as a modifiable factor to reduce diagnostic delay and to improve the diagnostic process.
Access Microbiology: Inter-Species Transmission of Avian Influenza Virus to Dogs
Over the years we've followed the work of Dr. Daesub Song - and many others - on potential for seeing a novel flu spread by companion animals such as dogs and cats. In 2011 we looked at a study (by Dr. Song, et al.) on the Interspecies Transmission of Canine H3N2 to domestic cats in Korea.
A year later (2012) Dr. Song and company were back with another study (see Interspecies Transmission Of Canine H3N2 In The Laboratory) that looked at laboratory transmission of the canine H3N2 virus to cats, and to (a far lesser degree), ferrets.
In November of 2018, in EID Journal: Canine Influenza Virus A(H3N2) Clade with Antigenic Variation, China, 2016–2017, we learned of the emergence and rapid spread of an antigenically distinct canine H3N2 virus with signs of additional mammalian adaptation in China.
This paper, again by Dr. Song, et al. , is a review of what we've learned over the past decade on the interspecies transmission of canine influenza. Very much worth reading.
JVI: Aerosol Transmission of Gull-Origin Iceland Subtype H10N7 Influenza A Virus in Ferrets
In 2004 the first known human H10 infections (see Avian Influenza Virus A (H10N7) Circulating among Humans in Egypt) were reported, followed in 2012 by a limited outbreak among workers at a chicken farm in Australia (see in EID Journal: Human Infection With H10N7 Avian Influenza).
Most of these avian flu infections were mild or asymptomatic, but in late 2013 a new H10N8 virus emerged in Mainland China (see Lancet: Clinical & Epidemiological Characteristics Of A Fatal H10N8 Case) infecting three people, killing at least two.
While human cases of H10 infection haven't been reported since early 2014, these avian viruses continue to turn up in aquatic mammals, often producing significant mortality (see PLoS One: Pathology Of A/H10N7 In Harbor Seals).
Which brings us to the following abstract, published in the Journal of Virology (full article behind paywall), that reports that a `. . . . gull-origin H10N7 virus can be transmitted between ferrets through the direct contact and aerosol routes, without prior adaptation.'
The Air That We Breathe (Out)
Not the only way to spread the Flu - Photo Credit PHIL
Evidence continues to mount that pre-symptomatic (and presumably asymptomatic) flu carriers are able to share their viruses with others simply via their normal exhaled breath.
No sneezing, coughing or fever required.
Over a year ago in PNAS: Infectious Virus Exhaled In Breath Of Symptomatic Seasonal Flu Cases, we looked at study that showed coughing and sneezing are not required to spread the flu virus.
A new paper - presented to the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam last April - documents the apparent stealth transmission of influenza by pre-symptomatic carriers in a hospital setting.
Hospital study finds substantial proportion of patients and healthcare workers shed flu virus before symptoms appear
New research examining influenza transmission in a tertiary hospital finds that a substantial proportion of patients and healthcare works shed the flu virus before the appearance of clinical symptoms. The findings, being presented at this year's European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) in Amsterdam, Netherlands (13-16 April), raise the possibility that current influenza infection control measures may not be enough to protect healthcare workers and patients during routine care in hospitals.
C.I.D.: Influenza A Reinfection in Sequential Human Challenge
Although we know that the effectiveness of influenza vaccines can wane over time, it has been widely believed that once you are naturally infected with a specific influenza virus, you will carry lifelong - or at least long-lasting - immunity to that specific virus.
This `acquired immunity' is also expected to extend to antigenically similar viruses, although things get much murkier once even minor changes to the virus begin to accrue.
In a nutshell, in this study researchers exposed a small group of healthy volunteers to a specific H1N1 virus, and recorded their subsequent infections and immune responses.
A year later, they repeated this virus challenge on the same group (n=7) with the exact same virus, expecting their residual immunity would protect them, but found instead that at least 3 - and possibly 5 - of the 7 were reinfected with the exact same virus.The authors wrote:
Conclusion
The data presented in this report demonstrate that sequential infection with the identical influenza A virus can occur and suggest it may not be rare. These data raise questions about immune memory responses in an acute superficial respiratory mucosal infection and their implications in development of broadly protective influenza vaccines. Further investigation of these observations is warranted.
While many studies simply add to or build upon what was known before, in the case of the last one in this series, we saw a completely unexpected result. One that could have major implications for the eventual development of a `Universal Flu Vaccine' (see J.I.D.: NIAID's Strategic Plan To Develop A Universal Flu Vaccine).
While I can't predict what the next decade will bring, I'm confident there will be more than a few surprises along the way.
