A Little Blue in the Face over Yellow Fever Vaccination

To many people, yellow fever is a disease from a bygone era in which giants like Benjamin Rush and Walter Reed roamed. Indeed, since yellow fever was beaten back from the United States and many other areas of the world and an effective vaccine was developed (and resulted in a Nobel Prize) yellow fever is largely thought of as a travel-related disease. However, new and recent outbreaks of the disease in various countries -- including its first ever Asian appearance in China  -- and poor vaccine supply chains and logistics have increased the threat level posed by this virus. As the virus is spread by the Aedes aegypti mosquito (aka the yellow fever mosquito) to which half the human population is exposed to yellow fever has the capacity to roar back. With a penchant for severe disease and death, such an event would be majorly disruptive. 

Yellow fever outbreaks are managed by effective vector control and vaccination campaigns. However as the frequency of these outbreaks occurs and the population sizes involved increase, it is increasingly likely that vaccine supply issues will constrain the ability to respond. Coupled to that supply issue -- which is even impacting the US -- is the logistical issues that constrain vaccine administration. 

Yellow fever was one of the original infectious disease covered by the International Health Regulations (IHR) given its high consequence nature. As part of the IHR framework, yellow fever vaccines have to be administered by certified vaccine centers in every country, including the United States. In the US, certification is done on a state level.

While all this may just seem like a minor hurdle to overcome, my experience last week procuring vaccine for myself and a couple of others left me wondering if this regulatory framework could hamper response efforts in an emergency situation that is already compromised by vaccine supply issues. Suffice it to say arranging a vaccination for a pediatric patient in Pennsylvania -- even when you are an infectious disease physician -- was daunting and really frustrating. The amount of paperwork the vaccinator has to fill out and the consequent amount of time one must wait for vaccination was almost prohibitive to someone as pathologically impatient as me.

In emergency infectious disease situations, bureaucratic inertia can rapidly make a tenuous situation worse and delays only benefit pathogen spread. If a yellow fever outbreak took hold in the US vaccination would be increasingly demanded and, just like during a flu pandemic, easily accessible vaccination points employing physicians, nurses, pharmacists, and other health care workers would be ideal in order to maximize vaccination coverage.

Relying exclusively on certified yellow fever vaccinators, to comply with IHR stipulations, could prove difficult in such a situation. In addition, state laws -- such as exist in Pennsylvania -- artificially restricting the age limits a pharmacist can vaccinate (because 17 year olds are somehow magically different than 18 year olds) will also pose problems as it does in every outbreak situation in which pharmacist-administered pediatric vaccination stipulations have to be waived.

I understand the real problem posed by fake yellow fever vaccinators and the black market in counterfeit yellow fever vaccination certificates, but a one-size-fits-all approach that could hamper the US ability to fortify itself against yellow fever is not optimal.

Old Viruses Never Die: A Spate of Hepatitis A

A virus has been grabbing headlines in the west coast the past several weeks and it one that is usually not on anyone's lists anymore: hepatitis A. Hepatitis A outbreaks in San Diego, Santa Cruz, and Los Angeles have garnered a lot of attention and public health authorities are stepping up measures to contain the fecal-oral spreading virus with emergencies declared in Los Angeles and San Diego. There is also concern of another outbreak in Utah.

Like I discuss in this video and this podcast, hepatitis A was a near ubiquitous virus that everyone contracted during childhood, sometimes with no to minimal symptoms. Others might experience nausea, vomiting, abdominal pain, and jaundice. However, unlike other viral hepatitis viruses (hepatitis B, hepatitis C), this virus does not have a chronic phase of infection that confers risks of cirrhosis and liver cancer. The introduction of the vaccine in 1995 and its adoption as a universal childhood vaccine in the US has dramatically reduced its incidence. However, there are segments of the population that are not vaccinated and were not naturally infected who remain susceptible. Of those susceptible, those with preexisting liver disease because of alcohol, hepatitis C (20% of those tested in the San Diego outbreak), and/or hepatitis B are particularly at risk for having a fulminant infection with hepatitis A. At least 16 people have died during the San Diego outbreak. 

Because hepatitis A  spreads through the fecal-oral route and has a 28 day incubation period it can cause large outbreaks -- the largest one occurred in 2003 in the Pittsburgh area and was linked to the now defunct Chi Chi's restaurant chain.

I would suspect that it is no accident that the San Diego outbreak has its epicenters within homeless populations. Homeless populations will, by definition, have less access to sanitary facilities for bodily functions as well as for handwashing. They also are likely of an age that did not have the ability to be vaccinated against the virus as children. Additionally, they often cluster together in shelters, encampments, or in enclaves within a city, allowing more opportunity for viral exchange. Medical interventions are also much more difficult to implement with populations that are transitory, mobile, and otherwise hard to reach.

Vaccination, immunoglobulin and sanitation are the two most important tools to end these outbreaks. The US had just 1234 cases of hepatitis A in 2014 -- a 95% decline from the pre-vaccine era -- so it is clear that humans have the capacity to put this virus down. Aggressive case finding coupled with vaccination, immunoglobulin use, and infection control -- all of which are occurring now -- to prevent further spread are what will ultimately prevail. 

Pasteurization is Still a Thing

I always say that Louis Pasteur invented pasteurization for a reason -- his reason was to prevent the hijacking and ruining of the fermentation process necessary to make alcohol. Of course, pasteurization has had a much broader application and impact than that. 

By making products safe for consumption, pasteurization is a cornerstone of food safety and a great example of how the human mind could solve a problem that was historically regarded as a mysterious fact of life. Pasteurization involves heating a substance to a degree to kill potentially harmful bacteria that may be present (either intrinsically or from later contamination). 

In recent years, there has been a (misguided, in my estimation) demand for unpasteurized products and hand-in-hand with this return to the primitive, almost as if pasteurization was designed for this very reason, have been reports of infections linked to consumption of these products. 

Once, as a fellow, I took care of a person who bought and consumed unpasteurized milk voluntarily, contracted a bacterial diarrheal illness (Campylobacter), developed Guillain-Barre Syndrome, and ended up on a mechanical ventilator with a tracheostomy. I thought the events were totally predictable and must've been something he thought about when he bought the milk but obviously the patient and his lawyer thought differently, filing a lawsuit accusing those involve with selling a "defective product" -- to me unpasteurized milk is, by definition, a "defective product."

Fast forward to last week and there were an important two items related to unpasteurized products consumption that illustrate the value of pasteurization: The first is the report of a Texas woman contracting the somewhat rare (because of pasteurization) brucellosis after drinking unpasteurized milk. In this case the strain of Brucella contracted was drug resistant making treatment more difficult. Brucellosis is a serious infection and it will be important to determine how many other preventable infections could have occurred.

The second is a Rhode Island warning about Listeria infections tied to consumption of queso fresco cheese. This type of soft cheese can be found in an unpasteurized, unsafe form and the risk of Listeria is real and can be devastating to pregnant women.

I can't fathom why people would knowingly expose themselves to unpasteurized products when other safer alternatives are readily available. I do, however, believe it is an adult's right to knowingly eat dangerous substances and face the consequences that Louis Pasteur has spared most of us from. 

Plague, Magnet Cities, and the Ottoman Empire: A Review of Plague and Empire in the Early Modern Mediterranean World

One of the most fascinating and impactful infectious disease outbreaks in history is the Black Death. This globally catastrophic event swept over much of the inhabited world in the medieval period when humans entered a cycle of infection between rodents, fleas, and the Yersinia pestis bacterium. There have been many many books written about this topic, some of which I have read. The latest to pop up on my list is very different than many of the others I have read because it is a truly scholarly effort. Plague and Empire in the Early Modern Mediterranean World: The Ottoman Experience 1347-1600 by Rutgers history professor Nukhet Varlik is an exhaustively researched, yet easily readable, treatment of not only how plague impacted the Ottoman Empire but, interestingly, how the Ottoman Empire impacted plague.

The book is divided into three parts and it covers three distinct phases of the plague expertly interweaving the narrative of disease with the workings of the bureaucratic regime that increasingly began to characterize the Ottoman Empire. Varlik shows how the trajectories of a bacterium and an Empire became intertwined. Starting with the nascent empire, Varlik shows how the increasing "constellation of connections" this empire developed -- east/west, north/south -- fostered new vehicles for plague to entire the Empire and to spread throughout and outside of it.

As she writes, "Consolidating the intersecting trade networks connecting the Balkans, Caucasus and Central Asia, Asia Minor, the Arabian Peninsula, Persia, North Africa, and the eastern Mediterranean provided a new set of connections over which plague could spread extensively both within the Ottoman domains and beyond."

A few interesting aspects of the book include:

• An explanation of the "capital effect" of migration to a major city such as Istanbul, which she labels a "magnet"
• The fact that not having enough fleas or lice on one's body was considered abnormal during this time period (having none could mistake one for being a leper)
• The first plague outbreaks spread from Europe to the Empire
• Once Cairo was incorporated into the empire both a east-west and north-south axis of plague spread became entrenched and plague became more endemic in the Empire
• Murders could go unnoticed if thought to be from plague

The book's value also lies in how it captures the medicalization of plague and how it moved from being the "decree of heaven" to something that, though the cause was not known, was natural and how reliance shifted from religious to secular authorities. The rise of public health measures in the Empire also developed in response to the plague.

Today plague is largely a forgotten disease in most of the Western World -- indeed people have forgotten that the Western US is home to plague and each time an animal or human case is reported, the media takes notice.

Plague is not the threat it was in the 1300s because humans tamed it through the use of their minds.By discovering its flea vector, describing its various forms (bubonic, septicemic, and pneumonic), and developing effective antibiotic therapies plague was defanged and naturally occurring plague can really never threaten the human race (a bioterrorist attack is whole different matter). However, it is important to be able to recognize what an infectious disease could do under the right circumstances and how networks of trade and commerce facilitate the passage of good and microbes and for this, Plague and Modern Empire is an excellent resource. 

Apres Le Deluge: Infectious Disease Risks and Hurricane Harvey

While the pressing issues regarding Hurricane Harvey's onslaught are responding to the acute needs of those in need of rescue from the peril of flood waters, the coming days and the recovery period will increasingly be characterized by new health-related problems. Among those will be threat of infectious diseases exacerbated by infrastructure failures.

Infrastructure provides clean water for the activities of daily living such as drinking, cooking, and bathing. Infrastructure also separates sewage from living spaces. When infrastructure fails, the chances of contamination by high levels of infectious agents increases tremendously.

Infrastructure has withstood Harvey so far. In the coming days, though, it should be anticipated that more cases of gastrointestinal infections from bacterial, viral, and parasitic causes will increase as people are increasingly exposed to these agents via water. Disruption in the water system need not be complete for exposure to occur as people wade in and are immersed in the water. It will be important that when these cases of GI infection accrue, patients receive appropriate treatment (e.g., hydration) and are prevented from further spreading the illness -- a difficult prospect in a flood-ravaged locale with alternate housing facilities. Leptospirosis from exposure to rat urine and severe Vibrio vulnificus infections are also rare -- but serious -- infections that might occur.

Huddling of people in alternate housing may also facilitate the spread of respiratory viruses and pathogens as people increasingly are kept in close quarters. Hand hygiene will be essential.

Tetanus is also a minor risk as people who are insufficiently immunized may sustain puncture wounds that become infected with the tetanus bacterium -- which is ubiquitous in the environment. Other bacterial infections can occur in this way, as lacerations and abrasions become portals of entry.

Standing water will also be a major concern given the threat of mosquito-borne illnesses in Texas. Standing water serves as breeding sites for mosquitoes and after what has happened in Texas, standing water will likely persist for some time in debris. Zika, chikungunya, dengue, and West Nile all have been locally spread in Texas and would be expected to have enhanced transmission in the weeks after this event.

Much of the decrement in infectious disease in the world today is due to modern civil infrastructure. Infrastructure failures (and absences) leave humans in the position of contending with nature in the raw. However, with foresight, planning, and preparation hopefully the infectious disease consequences can be minimized.