Cervical Cancer: Hopefully a Relic of the Past

Last night on an episode of Showtime's Masters of Sex, a drama focused on the research of Dr. William Masters and Virginia Johnson, the early work to encourage uptake of the now ubiquitous pap smear was portrayed. This test, developed by Dr. Georgios Papanikolaou, has proved to be essential in early detection of cervical cancer, whose cause is chiefly the human papilloma virus (HPV). 

In the episode a physician--played by Julianne Nicholson--is an early promoter of the procedure who is, herself, dying from cervical cancer. 

It is largely due to the early detection of cervical cancer via routine pap smears that such deaths are almost a relic of the past in the US. However, approximately 4000 deaths per year in the US are attributed to cervical cancer. 

Vaccines against HPV, as a supplement to routine pap screening, offer the promise of further decreasing the burden of cervical cancer. Currently, two vaccines are available: Merck's Gardasil and GSK's Cervarix. Both vaccines protect against the most common cancer causing strains of HPV while Gardasil offers additional protection against strains of HPV that cause genital warts. The vaccines likely offer protection against other HPV-caused cancers (vulva, vagina, anus, oropharyngeal) and are now part of routine childhood immunization schedules after much political wrangling (see Three Shots at Prevention: The HPV Vaccine and the Politics of Medicine's Simple Solution). 

Chikungunya Virus in St. Martin

The Caribbean island of St. Martin is reporting two cases of the mosquito-borne viral illness Chikungunya with 34 additional probable or suspect cases. This is an important story because, to date, this virus had not been found in the Caribbean. Chikungunya is infamous for causing a large outbreak on the Reunion Islands in 2006 (after importation from Kenya) that went on to spread to various nations of Asia and Europe.

This virus is transmitted by the Aedes mosquito which is widely distributed in both the Caribbean and the US. It is also the vector for dengue and yellow fever. While 2 cases of chikungunya might represent recognition of travelers infected elsewhere--as has been reported in the US--34 cases are likely the result of autochthonous (local) transmission. 

As such, these cases in St. Martin may represent the tip of the iceberg. It would not be surprising to find more cases in other Caribbean islands or even on the US mainland were Aedes mosquitoes abound and are readily available to bite viremic travelers.

Antibiotic Resistance: Back to the Future

In today's Pittsburgh Tribune Review is an article by Mike Wereschagin detailing the public health emergency posed by antimicrobial resistance. I was interviewed (alongside the leading voice on this topic, Dr. Brad Spellberg of UCLA!) for this important article and made a few points that included:

• Alexander Fleming prophetically warned of this trend in the 1940s
• In my own career, I have had to "treat" totally drug resistant infections and have seen patients succumb to their infections
• The need to move from non-specific therapies such as broad spectrum antibiotics to targeted therapies such as bacteriophages and antibodies (which were the mainstay of treatment prior to the discovery of antimicrobials, see Arrowsmith)
• Brian Potoski, a stellar infectious disease pharmacist and my colleague, makes the point about the danger of using antimicrobials for common viral infections (which is incorrectly done the majority of the time)

Adding to the information contained in this article, is a small piece I wrote detailing the Lancet Infectious Diseases report on the issue and their recommendations, which include exploring the "age-old" phage therapy."

Severe ARDS Centers

An important research study focused on the geographic characteristics of severe ARDS centers undertaken by UPMC's David Wallace (who was one of my CCM co-fellows) and colleagues is to be presented at the annual SCCM meeting in abstract form.

Wallace's study looks at the locations of hospitals equipped to care for individuals with severe ARDS based on variables such as their annual mechanical ventilation volume and capacity for ECMO. What Wallace found was that between 88 and 99.7% of the US population has access (via ground or helicopter) to a severe ARDS center within 2 hours.

This study provides essential underpinning to construct a national system of severe ARDS centers--similar to trauma, cardiac, stroke, transplant, and burn centers--which could prove crucial during an outbreak of a severe respiratory infection such as influenza, SARS, MERS, or an as yet emerged pathogen.

A few years ago, my colleagues and I developed a conceptual model to construct such a system. It is with research such as conducted by Dr. Wallace that such a system may, one day, become reality.

Interferon Free Therapy for Hepatitis C!

In the last few weeks the FDA approved two new antiviral agents for hepatitis C--a scourge that infects over 3 million Americans and is the leading cause for the need for liver transplantation. 

For years the standard treatment for hepatitis C virus had been a combination of two drugs, interferon via injection and ribavirin, taken for up 24- 48 weeks (depending on which genotype of hepatitis C virus is present). These medications had serious side effects including depression, anemia, and flu-like symptoms causing many individuals to stop treatment early. 

A few years ago, the landscape of hepatitis C changed with the approval of two new drugs to be used in combination with interferon and ribavirin in the treatment of the most common type (genotype 1) of hepatitis C. These protease inhibitors, boceprevir and telaprivir, have improved treatment response rates and can, in some instances, decrease the duration of treatment. Last month, the FDA approved simeprevir a once-daily protease inhibitor that can also be used in combination with interferon and ribavirin.

The 2nd drug the FDA  approved is sofosbuvir, a potential pathbreaking nucleotide analog.  The excitement over this drug stems from the fact that it can be administered in an interferon-free regimen, sparing patients months of dreadful side effects. Interferon-free regimens are restricted to genotype 2 and 3 infections. For genotype 1 infections, triple therapy with an interferon backbone remains the preferred treatment  because clinical trial data does not support the use of interferon-free regimens.