Sunday, December 29, 2019

ICYMI: The Passing Parade - Pt. 5










Note: During the last half of December, and the first week of January, news and new journal articles are often in short supply. During this time I like to do a review of research papers we've looked at over the past year.  
You'll find the first 4 entries in this year's series here, here, here, and here
#14,602

Last May - while we were following the 2nd unusual detection of H1N2 in Europe in a year, the first (and only) admission of African Swine Fever in North Korea,  the spread of an unusually virulent LPAI H3N1 among Belgian poultry, an imported case of Monkeypox in Singapore, and Nepal's 1st H5N1 human infection -  we also looked at a number of research articles, including:


Emerg. Microbes & Inf.: Bactrian Camels Shed Large Quantities of MERS-CoV After Experimental Infection
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Bactrian Camel – Credit Wikipedia
Dromedaries and Bactrian camels share some limited geographic regions, so the potential of MERS-CoV spreading to Bactrian camels - and thereby extending its threat to other human populations - is obviously a concern.
A 2015 Research letter in the EID Journal  reassuringly found an Absence of MERS-Coronavirus in Bactrian Camels, Southern Mongolia, November 2014.
In this new study, published in Emerging Microbes & Infections, researchers from NIAID and the Department of Biomedical Sciences at Colorado State University, inoculated two Bactrian camels and monitored them for nasal shedding and seroconversion.
Despite the current lack of field evidence of MERS-CoV infection in Bactrian camels, this study demonstrates that Bactrian camels can be readily infected and shed large quantities of virus in nasal secretions. If MERS-CoV were to be introduced into populations of Bactrian camels, we would expect that a potential endemic and sustained pattern of infection may result and they could act as a reservoir, similar to dromedaries, potentially exposing associated human communities to infection.


Hong Kong CDW: A Review of Psittacosis in 2018-2019
Psittacosis - often called parrot fever - is a rarely reported, atypical bacterial pneumonia caused by Chlamydia psittaci. The CDC cites an average of 10 cases of Psittacosis reported each year in the US, although many others may go undiagnosed. 
Hong Kong, with a population of roughly 7 million, reported psittacosis infections last year (n=17) at a per capita rate roughly 70 times greater than the United States, and has already reported 7 cases in the first 4 months of 2019.
Human infection, at least until recently, has been solely attributed to direct or indirect contact with infected birds. But in 2012, the journal Eurosurveillance carried a report called Psittacosis outbreak in Tayside, Scotland, December 2011 to February 2012, involving four family members and a health-care worker, which suggested human-to-human transmission.
The following year, in Sweden Reports Rare Outbreak Of Parrot Fever, we saw a credible report of human transmission of parrot fever, where a 75 year old man who died in Kronoberg appeared to have spread the infection to at least 8 close contacts, including healthcare personnel.
This blog covers not only the Hong Kong review, but several other pertinent scientific reports.  


Eurosurveillance: The re-emergence of HPAI H7N9 Human Infection in Mainland China, 2019
Following China's massive H5+H7 poultry vaccination campaign of 2017, we saw the incidence of human infection with H7N9 plummet. In April of 2017, China reported their first confirmed case in a year, and in this Eurosurveillance report we learn that re-emergent virus has accrued a number of worrisome mutations during this lull.       
The H7N9 viruses isolated from the patient, and poultry from around his home, carried changes in the HA that may reduce the effectiveness of current vaccines, and a number of mutations that may increase adaptation to mammalian hosts.
From the report:
No H7N9 human cases was reported since February 2018. However, in late March 2019, we identified one HPAI H7N9 human case with fatal outcome, and HPAI H7N9 viruses with high genome identity to those of the case were detected from environmental samples. Together, these HPAI H7N9 viruses formed a subclade which exhibited a long genetic distance to the previously reported HPAI H7N9 viruses (Figure 1). 
This report suggests that H7N9 viruses might still circulate in poultry at a low level in limited locations. In addition, several immune escape mutations, which had not been detected in previously reported HPAI H7N9 viruses, occurred in the HA1 proteins of these viruses (Table 1). The antigenic features of these HPAI H7N9 viruses may differ from the current HPAI H7N9 candidate vaccine strain.
We saw additional evidence of worrisome changes to the H7N9 virus a week ago in  EID Journal: Antigenic Variant of Highly Pathogenic Avian Influenza A(H7N9) Virus, China, 2019


CDC: Guidance for Human Infections with Swine Flu Viruses
While 2019 proved to be a relatively quiet year, over the past 15 years we've seen more than 460 confirmed human infections with these swine-origin viruses, mostly associated with pig exposure at county and state animal exhibits.

The CDC's general risk assessment of these swine variant (H1N1v, H1N2v, H3N2v) viruses reads:
CDC Assessment
Sporadic infections and even localized outbreaks among people with variant influenza viruses may occur. All influenza viruses have the capacity to change and it’s possible that variant viruses may change such that they infect people easily and spread easily from person-to-person. The Centers for Disease Control and Prevention (CDC) continues to monitor closely for variant influenza virus infections and will report cases of H3N2v and other variant influenza viruses weekly in FluView and on the case count tables on this website.
In May, the CDC released updated interim guidance for clinicians who may see suspected swine-variant influenza cases and a CDC Expert commentary was published by Medscape (link).


PNAS: Low Ambient Humidity Impairs Barrier Function & Innate Resistance Against Influenza Infection
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Photo Credit PHIL (Public Health Image Library)
   
Although largely anecdotal, there is growing evidence suggesting that raising the humidity inside homes, offices, and health care facilities might be a reasonably effective NPI (Non-pharmaceutical Intervention) during times of heightened flu activity (see PLoS One Humidity as a non-pharmaceutical intervention for influenza A).
Most of the research on this topic has centered on the viability of the flu virus at lower humidity levels, but the impact of lower ambient humidity on the host's ability to fight off infection may also play a role.
With the caveat that the following study was done using mice - which may or may not fairly represent a human response - researchers have found that lower ambient humidity can impair `. . . mucociliary clearance, innate antiviral defense, and tissue repair function'. 
Earlier this year, the World Health Organization declined to recommend modifying humidity as an effective environmental NPI during a pandemic



J. Gen. Virology: Mutations in PB2 and HA Enhanced Pathogenicity of H4N6 Avian Influenza Virus in Mice


LPAI H4N6 - which while common in wild and migratory birds - has also been found in Chinese, Canadian (1999) and American swine (see Virology: Detection & Characterization Of Avian H4N6 In Midwestern Swine (2015)), and has been increasingly on our radar. 
In August of 2017, in Cell: Avian-to-Human Receptor-Binding Adaptation by Influenza A Virus Hemagglutinin H4, researchers presented evidence that avian H4N6 viruses can adapt to human receptor cells while in a swine host (using the 1999 Canadian isolate).
This study, published in the Journal of General Virology, takes the H4N6 virus and runs it through a classic serial passage study. After just 12 passages a virulent mouse-adapted virus emerged, with four significant mutations appearing in PB2 (E158K and E627K) and HA (L331I and G453R, H3 numbering).
The E627K substitution in the PB2 protein (swapping out Glutamic acid (E) for Lysine (K)) makes avian influenza viruses better able to replicate at the lower temperatures (roughly 33C) found in the upper respiratory tract of mammals. 
Although the two HA mutations did not individually raise the pathogenicity of the virus, they did so in concert . . . at least in mice.

CDC: The 8 Zoonotic Diseases Of Most Concern In The United States
The list of zoonotic diseases is long and continues to expand, and includes such well known infections as SARS, MERS, Babesiosis, Borrelia (Lyme), Nipah, Hendra, Malaria, Dengue, Zika, Hantavirus, Ebola, Bartonella, Leptospirosis, Q-Fever, several flavors of avian flu and many, many others.
Emerging infectious diseases are considered such an important threat that the CDC maintains as special division – NCEZID (National Center for Emerging and Zoonotic Infectious Diseases) – to deal with them.
The zoonotic diseases of most concern in the U.S. are:
Although the CDC targeted just 8 zoonotic diseases of greatest concern in their press release, the full One Health Zoonotic Disease Prioritization report, characterizes 57 zoonotic threats to the United States.