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.

How the Black Death Shaped Modern Public Health Emergency Preparedness: A Review of Expelling the Plague

One of the core functions of government is to keep those whose individual rights it was constituted to protect free from contagion from other humans (through both accidental non-deliberate transmission as well as deliberate transmission in acts of biological warfare or bioterrorism) . This function  manifested through infectious disease surveillance programs, quarantine and isolation laws, and various biodefense programs. These programs are largely managed through public health agencies that have existed for quite some time and their place of origin is not a all obvious as these organized activities really began several centuries ago in the time of the Black Death (1377) on the Dalmatian Coast in a now-defunct republic called Ragusa (Dubrovnik) -- now part of Croatia. 

The operations of this nascent public health office and its battle with the plague are the subject of the 2015 book Expelling the Plague: The Health Office and the Implementation of Quarantine in Dubrovnik, 1377– 1533 by Zlata Blažina Tomić and Vesna Blažina. In this scholarly book, the literal day-to-day operations of this agency are recounted in meticulous detail drawn from extensive records from the city-state that still exist. 

I think it was prescient of the Ragusans to realize, as the authors note, that "more threatening than the mortality itself was, and still is, the challenge of the epidemic disease to the ideological structures that sustain all societies. The sense of origin, identity, purpose, and future of a society are all badly shaken and seriously disrupted by epidemics." This recognition underlies the creation of the health office, its prominence, and the delegated powers it possessed. 

The authors emphasize how important scientific knowledge underlied the use of quarantine as it is preventive isolation and presupposes the ideas of contagion (before the articulation of the germ theory of disease, health carriers, and the limitations of physical examination. 

The book also details the sentences -- many of which were extremely severe -- for those who broke the laws. These sentences were matched to the severity of the consequences of the accused action (e.g. did it lead to the death of someone) and could range from fines to branding to execution. 

To me, the chief value of this academic work is the illustration of a pioneering proactive approach to infectious disease outbreak management that forms the basis of how many nations respond to these threats over 600 years later. While the penalties imposed are revolting to the modern reader (or should be), it is important to not drop historical context and fail to realize that the Ragusans were reacting to what would be, in modern terms, a global catastrophic biological risk.