Pursuing Diagnoses to the End of the Earth


One of my general principles when treating and diagnosing infectious diseases is to try and pursue a cause as far as I can. With a specific cause, one can discontinue treatments that were being used to cover all possibilities and provide as specific targeted therapy as is available. In addition to immediate treatment related implications there are others that, while not changing treatment (a mantra I hear all too often), are vitally important: infection control and epidemiologic intelligence. 

When a hospitalized person with pneumonia is diagnosed with a specific virus such as, for example, parainfluenza virus for which there is not a specific antiviral treatment several things happen which include discontinuation of antibiotics (hopefully) and placement of the patient in droplet isolation to prevent contagion. However, if the specific diagnosis is not made the patient will languish on the floor marinating in antibiotics while coughing the virus onto his roommate and others. 

A recent news story from a suburban Pittsburgh newspaper highlights the other important aspect of specific diagnoses: epidemiologic intelligence. The piece details a 74% uptick in the number of pneumonia cases in young adults diagnosed in a chain of urgent care centers in the area. This cluster of illnesses is important and interesting as influenza season really hasn't fully commenced in the region. However, what strikes me about this episode is that there seems to be no effort to understand which microbe is behind the cases: is it parainfluenza, an adenovirus, mycoplasma, RSV, a rhinovirus, a coronaviruses, legionella, pneumococci or some combination of different viruses and bacteria? Unfortunately, that is something that urgent care centers not associated with hospitals tend never to pursue because "it doesn't change patient care" despite the fact that it could have crucial epidemiologic importance. In many ways urgent care centers are places where symptomatic treatment without regard to causation is the norm and expected treatment paradigm.

What if these undiagnosed cases contain new microbes making their first forays into humans? What if there are important changes in viral prevalence occurring? We probably won't know because no diagnostic tests were likely done. Also, a good proportion of those cases are likely viral in nature but invariably were given a "Z-pack" nonetheless or potentially harmful steroids.

To me exploring these syndromes to identify the cause is what the specialty of infectious diseases is about. To me, in 2017, when there are multiple diagnostic tools in relatively easy reach in the US ranging from point-of-care influenza molecular diagnostic tests to multiple pathogen assays (also point of care) that there really should be no barrier to ordering these tests, especially at urgent care centers where patients are insured. 

The diagnostic black hole in infectious disease in developed countries really baffling to me and makes no sense given that microbes have no borders. Recall that the 2009 H1N1 influenza virus emerged in Mexico and was first recognized in San Diego in a patient with mild symptoms who happened to have a diagnostic test that "doesn't change treatment" ordered. 

The diagnostic test you order or fail to order may be more consequential than you think. 

A Humorous (and informative) Look at Plagues: A Review of Get Well Soon


It's hard to write a humorous but yet historically and scientifically sound account of plagues that have thrown our species into calamity time and time again. Yet, Jennifer Wright does just that in Get Well Soon: History's Worst Plagues and the Heroes that Fought Them

In this easily digestible book, Wright covers topics very familiar to connoisseurs of death and destruction due to infectious diseases such as syphilis, typhoid, plague, cholera, smallpox, and tuberculosis but also ones that received comparatively less attention but are nevertheless endlessly fascinating such as Von Economo's encephalitis, the dancing plague, and a human-induced plague of lobotomies for psychiatric illness. 

Some of the most humorous aspects of the book include discussion of the exploding frog cure for plague, the pigeon cure for plague, and her unrepentant challenge of the anti-vaccine movement. One of my favorite lines, explaining herd immunity, is:

“So if enough people decide that their yoga teacher is really onto something and they are not going to immunize their kids, because they are going to feed them a whole bunch of grapes instead, then the number of immunized people drops beneath the percentage necessary for herd immunity to be effective.”

Integrated into the narratives of these episodes is not just humor but many important recommendations for how to deal with infectious disease emergencies. For example, in her account of the 1918 influenza pandemic Wright highlights the constraining effects of WWI laws in the US  prohibiting journalists from writing about anything that could diminish morale. Wright explodes the sheer insanity and backwardness of such an approach, in what I believe to be the most valuable chapter of her book. These lessons need learning as evidenced by the 2003 experience of SARS in China and the ongoing campaign to call cholera just "acute watery diarrhea" in parts of Africa.

For a great overview and uncanny insights into history's plague's I highly recommend Get Well Soon and hope that Ms. Wright continues to apply her considerable talent to these topics in the future.


Giving the Plague no Quarter in Madagascar


Plague, for very good reasons, is something that will always capture headlines and panic individuals. It is an infectious disease that entirely disrupted civilization on multiple occasions and has become the stuff of legends involving everyone from Roman emperors to Nostradamus. Indeed for most of human history plague, caused by a bacteria that spreads from rodents via the bite of flea, was an existential threat, until it was tamed by scientific discoveries that discovered its origin and its susceptibility to antibiotic therapy. In many parts of the world, this taming of plague has made it a non-issue but a new outbreak on the African island nation of Madagascar has some worrying characteristics that merit swift action to extinguish what could become a larger problem. 

In Madagascar, close to 700 individuals have been infected with 57 succumbing to the infection. What makes this outbreak particularly notable, despite occurring in a country that has hundreds of annual plague cases, is that many of the cases are of the pneumonic form. This form of plague, which involves infection of the lungs, is the form that can be transmitted between humans through coughs and sneezes in little droplets that travel about 3 feet. Also, cases are occurring in urban areas giving the bacteria more opportunity to find new hosts. 

These factors have prompted public health agencies to take prompt actions including the creation of a treatment center and the delivery of antibiotics. So far, the risk of international spread is low -- despite an importation to the Seychelles. However, in the wake of Ebola it is crucial, even in low international risk situations and with effective antibiotic therapies, to not allow infectious diseases to any breathing room 

The Mystery of Malaria in Italy


It's said that half of all humans have died from one infection -- malaria. But today in many parts of the developed world malaria is just a travel or global health concern. However, it must be remembered that relegating malaria to such a status was a great human achievement as malaria had a much bigger planetary profile in the past -- indeed Washington DC was literally, at one time, a malarious swamp. 

A new case of fatal cerebral malaria in northern Italy is a stark reminder that this disease can have a much bigger impact if it is allowed to. Italy was freed of malaria in only 1970 the result of strong eradication campaigns that beat the mosquito back. However, there have been reports of recent possible local transmission in the southcentral part of the country. It is unclear, at this time, how the disease was contracted as the patient had not traveled abroad. An unknown pool of possibly Italian Anopheles mosquitoes is infected with the parasite and just found the right opportunity to transmit to the now deceased four year old child. There is some question whether a contaminated needle may have played a role as well as travel related malaria cases were treated around the same time at the same hospital.

Malaria is a complex infectious disease that has marked the human race and provided a tremendous evolutionary pressure on our species. Alarming rates of drug resistance to artemesinin, if they spread to Africa, could be catastrophic.

The disease, however, can be defeated --but only if humans put all the resources of their mind into the fight. Bed nets, insecticides, vaccines, antimalarials, and genetically modified mosquitoes should all have major roles in this fight for the best chance at success. 

A Little Blue in the Face over Yellow Fever Vaccination

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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.