Confronting Our Deadliest Enemy

The world of infectious disease changes almost daily and with the well-overdue newstream-like enhanced focus on emerging infectious diseases the field has basically transformed. Emerging infectious diseases did not, however, supplant other concerns such as bioterrorism, dual use research, endemic infections, and antimicrobial resistance. All of these topics are now the bread-and-butter of infectious disease. A new book by Professor Michael Osterholm, a renowned leader in the field, is a must read for those with an interest (advanced or novice) in the field.

Deadliest Enemy: Our War Against Killer Germs is a comprehensive expertly-guided tour that spans all the major issues, outbreaks, and controversies in the field that have occurred over the past several decades. While many of these incidents are familiar, the value of the book is getting Professor Osterholm's analysis and opinion which provide deep insights and platforms for further thinking on the issues

Chapters topics span toxic shock syndrome to gain-of-function research and everything in between. Some particular standouts, to me, where Professor Osterholm's very personal battle with Lacrosse encephalitis, his discussion of MERS, his treatment of the economics of vaccine, his four-tiered threat matrix analysis (pathogens of pandemic potential, pathogens of critical regional importance, bioterrorism, and endemic infections), his "Crisis Agenda", and his unrivalled analysis and solution to influenza vaccine shortcomings.

In his decades long career, Professor Osterholm has been at the forefront of the field and led myriad investigations and influenced policy at the highest level and his book is an important distillation that I highly recommend.

Ebola Back in the DRC: An Opportunity for New Tools to be Tried

The latest appearance of the Ebola virus, which has caused approximately 30 identified outbreaks in humans since it was first recognized in 1976, will provide an opportunity to gauge how outbreak response has improved over the past 3 years. That this outbreak is occurring in the DRC, a nation relatively adept at managing the virus, will likely lead to its rapid extinguishment. Thus far, there are 11 suspected cases and 3 deaths in the remote area of the DRC where the disease has reappeared. The index case has secondarily (and fatally) infected one of his caregivers and his taxi driver. Contacts are under surveillance and thus far one has tested positive (and there is some concern that all suspect cases are not truly Ebola).

In recent years, in the wake of the horrific 2014 West African Ebola outbreak, new tools and strategies have been formulated and refined including a vaccine, a concept-of-operations for vaccination, and enhanced supportive care (not to mention the rapid involvement of WHO for technical assistance). 

In the coming days, as the outbreak unfolds and case numbers change it will be important to see if, in addition to the tried-and-true measures of case finding, isolation, and body fluid protection, the Merck vaccine (or others) is used to accelerate the control of this outbreak. Currently, a GAVI stockpile of 300,000 doses of the Merck vaccine stands at the ready.

Emerging infectious diseases, exemplified by Ebola, will continue to plague the human race and it is only by continually improving our response efforts through science and preparedness that they can be beaten back.

Rat Lungworm Backwash: Why Slugs are Not the Best Drinking Partners

One of the latest obscure and tantalizing infectious diseases to garner sensationalistic headlines is "rat lungworm disease" in Hawaii.

This infection, caused by the roundworm Angiostrongylus cantonesis, is not a very common entity in the US though outbreaks and sporadic infections occur worldwide. In its natural infective cycle, this worm is ingested by rats via mollusk intermediaries such as snails, prawns, and slugs. The larvae migrate through the vasculature to the lungs and to the brain. Adult parasites live in the lung and lay eggs which, after hatching, are coughed up, swallowed, and passed into the feces to find a mollusk host and the cycle repeats. 

When humans get caught up in the cycle after, for example, ingesting an uncooked snail or a salad contaminated by larvae the result is eosinophilic meningitis arising from larval migration to the brain. This condition is usually just a mild illness but can lead to coma and death with massive infections. Fever, nausea, vomiting, and neck stiffness are common symptoms. It is diagnosed clinically and through spinal tap where a larvae may be spotted in the cerebrospinal fluid. Treatment is usually with steroids. 

This year 11 cases have been reported on two of Hawaii's islands and represents an increase over the expected number of cases which usually number about this many for the entire year. Speculation is that an influx of semislugs on Maui may be responsible for this increase as at least 2 cases arose from a homemade kava elixir which they shared with slugs. 

I suspect that this outbreak will be contained once public awareness rises and people are more careful of their exposure to foods that might harbor the parasite and take appropriate action like cooking it, washing it, and discarding it if slugs have decided to have a bite or drink too. 

A general rule of thumb, however, is not to share straws with a slug.

Kiss A Frog, Fight the Flu

There is always speculation about particular compounds that exist naturally in the wild that may have benefits for human health. Indeed, history is full of stories like this from quinine to aspirin. New research from Emory shows that frog mucus contains a potentially flu-fighting antimicrobial peptide. 

For the study peptides contained in the mucus from Hydrophylax bahuvistara frogs were screening for both anti-influenza activity and non-toxicity to human cells. Of these screens, one peptide, named urumin, emerged as the leading candidate. Urumin was noted to interact directly with the influenza virus at an important site: the conserved stalk area of the H1 hemagglutinin. Because it is a "conserved" region (i.e. one not highly mutable) the frog peptide retained activity against drug-resistant variants. This region is one of the targets of the long sought after universal flu vaccine. In the study, urumin worked not only in vitro but also in a mouse model.  The peptide was specific for just H1 variant influenza A viruses.

I found the paper to be very interesting and the discoveries may have wide-ranging implications not only for novel antivirals but for understanding influenza. As the authors note, innate defense mechanisms are less likely to be prone to resistance because they presumably were selected  via natural selection for their durability against their target. It is unclear what role amphibians have with influenza A epidemiology but it appears they can be infected and perhaps urumin is one of its natural defenses against the virus. Future studies with ferrets will be important to perform as they are important surrogates for humans.

Clinical Care Gaps in US Zika Cases

Today, the CDC released important new information on the Zika outbreak and its impact on pregnant women. The report, which details approximately 1300 US pregnancies, contains several important points:

  • The risk for fetal malformation is the highest in the 1st trimester with 15% of confirmed 1st trimester infections having this horrific result
  • Overall, the risk of fetal malformation appears to be 10% with confirmed maternal infection
  • The vast majority of babies with possible Zika infection or brain malformation did not get further testing (either for diagnosis or brain imaging)

This last point is the most ominous as it shows just how hard it is for crucial public health and medical messaging to find its way to the front line clinicians. Diffusion of knowledge in ordinary care is a difficult decade long process -- clearly not something that can be tolerated in the midst of an infectious disease emergency like Zika.