Seek and Find: Influenza and other Creatures

That the fatal cluster of respiratory illnesses in Texas is due to influenza doesn't come as a surprise. What is surprising is how such a cluster is headline grabbing. 

The poor ability to diagnose influenza is what causes clusters like this to fuel speculation regarding novel pathogens that might be responsible. However, perusing any tertiary care center's ICU one will undoubtedly be able to find some sort of cluster of unexplained severe pneumonia patients. 

Why are definitive microbiologic diagnoses elusive?

An ordinary pneumonia patient  admitted to the ICU might have the following two microbiologic tests performed:

• Blood cultures: only positive in 5-14% of cases
• Sputum gram stain and culture: only 40% of patients are able to produce sputum

Other tests that are variably performed include pneumococcal and legionella urinary antigen testing. Rapid influenza and RSV antigen testing, notably unreliable but helpful if positive, may also be done. PCR testing for multiple respiratory viruses, including influenza, is unfortunately the most rarely done, often relegated exclusively to tertiary care centers.

In sum, the majority of pneumonia patients undergo a minimal amount of testing leaving the great majority of patients without an identified pathogen--a great number of which are likely viral in nature. To minimize unexplained clusters of illness, diminish the amount of unnecessary antibiotic use, improve infection control (as respiratory viral infections merit contact and droplet precautions), and identify influenza cases that will benefit from antiviral therapy, it is our diagnostic capacity that must improve.

The Only Legit "Chickenpox Party"

Parents in the developed world no longer worry about their children contracting chickenpox (varicella) thanks to the chickenpox vaccine, available in the US since 1995 (20 years after it was introduced in other countries).

The man responsible for this life saving vaccine, Dr. Michiaki Takahashi, died on Monday (the same day as Monto Ho, who I wrote about it yesterday).

Prior to the introduction of this vaccine in the US, 4 million cases, up to 18,000 hospitalizations, and 150 deaths from chickenpox occurred annually. Now that the vaccine is in widespread use, these numbers have declined drastically.

However, the gains achieved by Dr. Takahasi's vaccine are currently under threat by those who, instead of availing themselves of the protection afforded by the vaccine, engage in "chickenpox parties" to knowingly expose their children to this pathogen.

I first heard of these "parties" while on a medical student rotation in England in 1999, before the vaccine was available in the UK. As a medical student I was completely baffled by this ritual then and, now, as an infectious disease physician my incredulity has exponentially increased. 

As someone who grew up prior to the vaccine's US introduction and contracted chickenpox in the 8th grade (much later than many of my classmates), I have a special affection for this vaccine.

The only party we should be having with respect to chickenpox is one in honor of Dr. Takahasi, celebrating his achievement and the benefit we all derive from it. 

Monto Ho, Brilliant Infectious Disease Physician and Pitt Leader Dies

Yesterday, I wrote about the pioneering work Dr. Thomas Starzl has done in Pittsburgh to build it into a world reknown transplant center. Another individual who was instrumental in that development, was Dr. Monto Ho. Dr. Ho was the chief of the infectious diseases and chief of microbiology (among other titles) at Pitt and a contemporary of Dr. Starzl. Dr. Starzl's request of Dr. Ho for infectious disease physicians dedicated to transplant patients led to the birth of the field of transplantation infectious diseases. 

On December 16, 2013, Dr. Ho died.

The import this brilliant physician-scientist had on the field of infectious disease is hard to fathom. Dr. Ho's work spanned decades and involved the early identification of interferon, delineating the role of CMV in organ transplantation, as well as early work on HIV (among many other things).

After retirement, Dr. Ho took on the beast of antimicrobial resistance in Taiwan with great success. He also found time to investigate a dangerous new epidemic of EV71. The span of his career and the infectious disease problems he tackled was the subject of an entire day symposium in 2006 which I attended as a resident.  At that symposium, it was announced that Pittsburgh City Councilman (and now Mayor-elect) Peduto proclaimed it "Dr. Monto Ho Day" in Pittsburgh. 

Several years ago I met Dr. Ho at a reception for another living legend--Dr. DA Henderson, the man who eradicated smallpox from the planet--and told Dr. Ho that I was then a fellow in the department he led.  He was gracious and I was honored to meet him.

His autobiography is a great overview of his brilliant career and is, in many ways, inspirational and emblematic of Pittsburgh.

Puzzles: My Favorite Part of the Job

Today I was consulted on a complicated patient with an unexplained elevation of the WBC count. In most cases, there is a standard approach to figuring out what is triggering this immune response. It involves searching for sources of infection such as a pneumonia, urinary tract infection, skin infection, or abscess as well as non-infectious causes too.

However, in some cases it is not an easy task.

Today's patient had received a kidney transplant 10 years ago. Transplantation of an organ necessitates severely suppressing the immune system in order to allow the foreign organ to avoid rejection by the immune system. However, immunosuppression renders the patient vulnerable to infections--ordinary and unusual--and often presents particularly challenging puzzles to the infectious disease physician, something we all relish.

My patient was not only immunosuppressed with an elevated WBC count, he also had a cancerous mass on his wrist, likely another consequence of his immunosuppression. The disabled immune system of a transplant patient is not only impaired in its ability to fight infections, but also in its ability conduct tumor surveillance. As such, cancers are not infrequent in transplant patients. 

To add to the complexity, the patient was found to have a nodule in his lung. In an ordinary patient, a nodule is usually an incidental finding. But, in a transplant patient a nodule can be the result of myriad big and bad things including unusual bacterial, viral,  mycobacterial, or fungal infections as well as cancer. In a transplant patient, the cause of nodules must always be run down lest it cause severe illness (see this excellent review written by my colleagues whom I once trained under).

Pittsburgh, led by the father of transplantation Dr. Thomas Starzl (for whom our transplant center and a street is named), became a city renown for its pioneering work in organ transplantation. Dr. Starzl's memoirs are aptly entitled The Puzzle People. The title refers to the notion of transplant patients as being amalgamations of various puzzle pieces (i.e. transplanted organs) but I also like to think of transplant patients as presenting vexing and intellectually stimulating puzzles to physicians who are forced to think and think again before a solution becomes apparent--an intellectual exercise like no other.

Cerberus visits Pittsburgh: A CRE Like No Other

In most discussions of antimicrobial resistance, the menace of carbapenemase-producing Enterobacteriaceae (CRE) is mentioned. This family of bacteria,  which includes E.coli and Klebsiella species, often cause hospital-acquired infections and are extremely difficult--if not impossible to treat.

The carbapenem class of drugs are, in many ways, the last line of resort and include the drugs: imipenem-cilastatin, meropenem, ertapenem, and doripenem. CRE employ one of 3 enzymes to inactivate this class of drugs:

1. KPC: the most common mechanism in the US
2. NDM-1: reported multiple times in the US and also linked to medical tourism in India
3. OXA-48: only reported twice in the US

A team from the University of Pittsburgh led by Yohei Doi--who I am honored to have been a co-fellow with--recently reported Klebsiella pneumoniae isolated from a patient in Pittsburgh that produces both OXA-48 and NDM-1. The isolate also possessed mutations that conferred high level aminoglycoside resistance.

The patient was a woman initially hospitalized in India for a neurologic condition who was subsequently transferred to Pittsburgh for further care. Once in Pittsburgh, she bounced between the hospital and long term acute care facilities-- a common theme amongst patients who harbor pathogens such as this one. Fortunately, this pathogen was merely colonizing the patient's urinary system and not causing an overt infection meriting treatment.

This case highlights the fact that bacteria, who have dominated the earth for billions of years, are genetically very plastic and can possess several modes of resistance due to selection pressure from antibiotics, uptake of plasmids from other bacteria, or other reasons. Also, the fact that this patient had been hospitalized in India should serve to remind clinicians of the high prevalence of these resistant isolates in other countries (see this excellent review on medical tourism for more information).