Viral Cataloging ≠ Pandemic Preparedness

When my Johns Hopkins Center for Health Security colleagues and I were working on our pandemic pathogens project, the report of which has been released, one of the more contentious issues we had to face was separating the task of pandemic preparedness from viral discovery and cataloging. One of the participants in our round table meeting on the topic colorfully referred to viral cataloging as "stamp collecting"! 

On its face, it might seem very reasonable to believe that knowing all the viruses "out there" will by design lead us to new pathogens that have the capacity to cause pandemics, but that is not a foregone conclusion for two main reasons:

1. Most viruses on the planet are innocuous to humans and do not have the capacity to cause damage 
2. While it is most likely that pandemics in the modern age are exclusively the province of viruses, it is possible a non-viral agent could, under certain circumstances and in certain contexts, be the cause of a pandemic

For pandemic preparedness purposes, we proposed focusing on ensuring specific diagnosis and enhanced surveillance of infectious syndromes such as respiratory infections, sepsis, and central nervous system infections in all parts of the world. By focusing on what has unequivocally demonstrated the ability to infect humans -- what would be level 2 and 3 pathogens according to an insightful paper by Woolhouse, the yield of uncovering a potential pandemic pathogen will be much higher. Such activities will have salutary effects on other activities such as antibiotic and antiviral stewardship as well as improving the epidemiology around well-characterized pathogens.

It is undeniable that viral discovery will enormously advance our understanding of virology and is very valuable but it is not synonymous with pandemic preparedness -- it is distinct. 

A new commentary published in Nature by three eminent researchers in the field, Eddie Holmes, Andrew Rambaut, and Kristian Anderson, provides some additional validation for the above conclusion we drew. The piece, entitled "Pandemics: spend on surveillance, not prediction," makes the point that:

“Broad genomic surveys of animal viruses will almost certainly advance our understanding of virus diversity and evolution. In our view, they will be of little practical value when it comes to understanding and mitigating the emergence of disease.”

Pandemic preparedness is a daunting task with many facets and varied approaches. It is only in the modern era with the sharp tools of biology coupled to advances in information and communication technology that we are even able to truly prepare for pandemics. It is essential that these powerful tools be directed at the right task.

Nipah: A Dangerous Virus That Deserves A Lot of Respect

While infectious disease headlines are rightly focusing attention on the current Ebola outbreak in the DRC, those with an eye to how pandemics unfold are watching a less prominent one unfold in India. A Nipah virus outbreak, centered in the Indian state of Kerala, was first reported last month and has killed 17 of the 18 people it has infected -- a horrific fatality rate that hovers around 75%.

Nipah is not an unknown virus as it has been responsible for sporadic deadly outbreaks since the 1990s in countries such as Singapore, Malaysia and Bangladesh. It has also appeared in India before. It is actually a priority virus when it comes to vaccine development. The virus is zoonotic and spills from fruit bats (the natural host) to pigs and humans. Humans can be infected by direct contact with bats, by consuming date palm sap contaminated with bat urine, by pigs, and by other humans. The virus causes flu like symptoms that can progress to a fulminant infection of the brain (encephalitis). There are no standard treatments for it though the antiviral ribavirin may have some positive impact.

When it comes to pandemic pathogens, as my colleagues and I argued in our recently released report, RNA viruses (because of their mutability) and respiratory-borne microbes rise to the top of the list. Nipah is a paramyxovirus and, as such, has an RNA genome. Though early outbreaks of the disease did not revolve around respiratory transmission between humans, subsequent outbreaks have been augmented by human-to-human transmission, especially to those caring for patients who were likely exposed to oral and respiratory secretions known to harbor the virus. It appears that the current Indian outbreak has been enhanced by human-to-human transmission after originating from exposure to bats. 

The major fear is that Nipah might become more efficient at transmitting from human-to-human and cause a large outbreak that spreads to multiple countries (the fictional virus in the movie Contagion was a Nipah-like agent). Such a scenario would rapidly become difficult to contain as there is no vaccine and no standard antiviral regimen. Currently, Nipah transmits only inefficiently between humans (about 1 in 12 pass it on to another human). 

While the not-so-contagious Ebola may grab headlines like no other infectious disease, and this NIpah outbreak has not been deemed a global threat, ultimately, it is viruses with the potential for respiratory spread that merit the most attention. While this outbreak will likely be contained, it underscores the danger of this class of microorganisms, the need to understand their evolution, track their transmission, and to be prepared for their appearance with robust countermeasures.

Condoms as a Instrument of Crime ?!? Law Enforcement Becomes an Instrument of Disease Transmission

When a condom is labeled an "instrument of crime" by law enforcement, law enforcement becomes an instrument of disease transmission. The recent news that police in Allegheny County, in which the city of Pittsburgh is located, are adding charges to the arrests of commercial sex workers if they are found to possess condoms is almost incredible. It illustrates just how backward and misguided the Puritanical war on prostitution is. Such actions compound the injustice that occurs each time consenting adults are arrested for a crime in which there are no victims and no violations of individual rights -- except for the ones violated by the arresting officers. 

To penalize a commercial sex worker for possessing condoms -- a sign of mindfulness regarding risks inherent in the profession -- does nothing except discourage the use of condoms and facilitate the spread of sexually transmitted infections -- an incontrovertible fact. When sexually transmitted infections increase further in the area it will be important to see how much such insane policies as this one contributed. 

The Power of a Cell Line: A Review of The Vaccine Race

When most people think of the challenges of vaccine development, the first thing that enter their mind is the serial passaging of a microbe to weaken it, the search for a microbial protein to prime the immune system, or the large clinical trials needed to show efficacy. What is almost taken for granted, in the modern era, is the ability to find suitable cells to grow the microbe in (for viral vaccines) and produce the vaccine in. The Vaccine Race: Science, Politics, and the Human Costs of Defeating Disease, a new book by Dr. Meredith Wadman, provides an exciting narrative that describes the intricacies of the development of one such cell line that has been employed to vaccinate millions upon millions of humans and contribute to their flourishing.

The chief subject of Wadman's book is Leonard Hayflick, a scientist whose name is familiar to any student of biology as it was his work that demonstrated the limits of cell division -- their "Hayflick Limit" -- as their chromosomal telomeres shortened. However, that is just one thing Hayflick discovered. He is also responsible for identifying Mycoplasma as the cause of "walking pneumonia." However, the main thrust of this book is focused on understanding Hayflick's cell line WI-38, derived from an aborted Swedish fetus, that became the standard research cell line used in vaccines that range from measles to polio to rubella. Such a cell-line, because it was human derived, removed concerned with contamination with viruses such as the infamous tumor-virus SV-40 which was harbored by rhesus and cynomolgus monkey kidney cells. 

In telling this story, which if full of giants such as Hayflick, Stanley Plotkin, Joseph Smadel, and Hilliary Koprowski, the founding and development of the Wistar Institute is also explored in great detail as is the business of scientific research, interactions with pharmaceutical companies, controversial clinical trial design, the intellectual property rights of scientists, and controversies over using vaccines grown in fetal cells.

It is hard to encapsulate all the information contained in this notable book (and there is some controversy -- see Hayflick's list of inaccuracies he identified) but it is required reading for anyone who wants to understand the fight against infectious disease, the history of medicine, and the life-saving role of vaccines. 

The Characteristics of Pandemic Pathogens Report Released

One of the perennial questions I am asked is "What's next?" in regard to infectious disease threats. Well, yesterday my colleagues and I released the report of a project I led for over a year whose aim was to understand the traits and characteristics of pandemic pathogens. We approached this project with active minds trying to jettison reliance on list-based approaches that are incomplete and almost guarantee surprise outbreaks. 

We did not limit ourselves to viruses as we embraced microorganisms of all classes. We also sought to integrate knowledge of astrobiology, plant infections, amphibian infections, prions, and even the bacteria at the limits of the earth's atmosphere into our thinking.

In the final analysis, we deemed a respiratory spread RNA virus to be the most likely pandemic pathogen for several reasons that include the fact that simple public health measures are likely to control a respiratory pathogen and an RNA genome allows a lot of mutability. While everyone may jump to influenza with this type of answer, there is a whole host of other viruses in this category that are often neglected as pandemic pathogens and for which no antivirals or vaccines are available.

One of my personal strongest recommendations is to end the satisfaction many doctors have with just calling something a "viral illness" and leaving the diagnosis as non-specific as that. This wastebasket diagnosis might contain potential pandemic pathogens making their first forays into humans and it is incumbent upon physicians -- in an era when a plethora of diagnostic tools are available -- to try to come to a specific diagnosis. This is true whether one practices in a major developed world city or in a rural clinic in Africa. Specific diagnosis leads to situational awareness and underlies preparedness.

This project was the most enjoyable and fun endeavors I engaged in as it allowed me to immerse myself in infectious disease and think deeply and widely. I hope that others find the report of value and it serves to generate deeper analysis of this field. 

Here's a link to a quick video I did explaining the report.