Got a spare $6.3-billion? Experts could use it to discover the missing 320,000+ mammalian viruses we don't yet know about

...or just $1.4-billion for 85% of those. And that's not including the non-mammalian ones. This is according to a new paper in mBio today by Andrew and colleagues from a collaborative team including Prof Ian Lipkin, from Columbia University's Mailman School of Public Health. 

The study advocates for a much more structured, systematic approach to discovery and notes that existing studies, such as the U.S. Agency for International Development's (USAID) Emerging Pandemic Threats (EPT) program including the PREDICT project (more detail in Lancet article here), have made headway into the list already. Each adding valuable assets to our virology intelligence archive.

Finding these viruses, and the animals they reside in, is key to limiting zoonoses. Sure, discovery does not equal simultaneous cure, but ignorance does equal surprise outbreak and death. Most emerging human infectious are caused by animal viruses infecting us. This is well defined by the One Health concept which promotes investigation of all aspects of the network of links between humans and their hairier, more leggy or winged co-habitants.

If we ever want to get ahead of the curve, investing in this sort of research is essential to allow us to know our enemy. It let's us be ready to meet them at the door instead of scrambling to action when they kick our door in! And it is a scramble; just look through the literature and media surrounding any virus that has spilt over from animals to humans in recent decades....a degree of controlled panic over the many things we don't yet know in the early stages of an unexpected emergence. For example: 

• We'd have no laboratory testing methods (culture, PCR or serology) nor the procedures to confirm weird results.
• Which country would "own" the virus, what would we call it (mock you may, but a lot of electrons and ink have been wasted on that story for the MERS-CoV for instance) and how long would it take before commercial detection kits were available (for MERS-CoV - its been nearly 15-months since the first cases in Jordan and still nothing well validated and widely available for use by non-reference laboratories)?
• When would we have enough of the virus to make positive controls for those tests or to kick off research into how the virus does what it does?
• We don't yet know what it does! What is the clinical spectrum of disease, how big is the iceberg let alone it's tip; what are the signs and symptoms; what does it do in different patient groups - those with and without comorbidities, different ages and sex?
• What is the proportion of fatal cases?
• Where did the invader came from?
• How best to handle the pathogen in hospital settings
• How fast and to how many does each case transmit (it will be a while until we can calculate the R₀)?
• What drugs do we already have that can moderate disease?
• How long will it take for an antiviral or vaccine, if they can be prepared, to be available and how long thereafter will antiviral resistance become an issue?
• How many that the virus infects will die?
• Does the virus interact with other viruses, bacteria, fungi or parasites?
• Does it have a peak season and is that affected by the environment?

Pretty much ALL of these things can be addressed if we invest in finding the culprits, their host and begin to unravel how they tick sooner rather than (too) later. Sure, they may never spillover, but when just 1 does, the impact is felt around the world, be it from loss of life, financial instability, healthcare burden, travel and tourism decline, animal culling or just a global feeling of insecurity. Any 1 virus outbreak can wield a lot of power in today's highly interconnected world. 

Count VDU in the cheer squad for this sort of proactive research. Money well invested.

Healthcare workers may stay on the job when ill and can be shedding viral RNA...

In a prospective study in the journal Infection Control and Hospital Epidemiology, Esbenshade and colleagues described their analysis of 319 samples from a cohort of ill (119) and asymptomatic (200) healthcare workers (HCW) serving inpatients at Monroe Carell Jr. Children’s Hospital at Vanderbilt (MCJCHV) in Nashville, Tennessee, during Nov 16 2009 - April 16 2012. 

This was a 20-week period when influenza was expected to be circulating. Most HCWs had been vaccinated against influenza A(H1N1)pdm09 virus

Nasal (not nasopharyngeal) swabs were collected by a trained staff member every 2-weeks, with extra swabs taken if a period of illness arose in the meantime. Nasopharyngeal swabs (NPS) do yield higher proportions of viral detections but are not pleasant and may have caused study drop-outs among the volunteers so they were not used. 

Influenza viruses, respiratory syncytial virus, rhinovirus (RV), human metapneumovirus (HMPV), parainfluenzavirus (PIV), endemic coronavirus (HCoV), adenovirus, bocavirus and enterovirus shedding was represented by the presence of viral RNA detected using a commercial PCR assay (MultiCode-PLx-RVP). An internal control target, β-actin, was included to monitor the integrity of the extracted nucleic acids. 

A PCR positive is assumed to represent shedding of an infectious virus.

The findings are relevant to my recent rant on prospective testing (seek and you shall find). Some key findings were:

• HCWs often worked despite being ill
• The strongest and most statistically significant risk of finding a virus in a subject was associated with that subject being symptomatic (I'm going to be writing about asymptomatic infections in the coming weeks)
• Only 42 specimens were positive for a virus - mostly RV (33) followed by PIV (4), CoV (4) and HMPV (1) - lower than expected
• Younger age was positively associated with viral shedding while the subject's role as a nurse or a physician was not
• 15% of RV detections were made from asymptomatic subjects - 25% of PIV or HCoV (OC43 and NL63) detections were from this group.
• 85% of RV detections were from symptomatic (ill) subjects

The authors conclude that HCWs should consider avoiding patient care duties while ill and that institutional policies should be updated to reflect this need to limit hospital-acquired infections.

When you test for things, its amazing what gets found and how this can impact on policy, understanding of infectious disease transmission and improved patient management. 

This is also a timely reminder that issues around infection prevention and control (IPC) are in no way limited to the management of newly emerged viruses like H7N9 or MERS-CoV. IPC is a problem the world over and it requires constant vigilance to stay ahead of. I commend the authors for this study.