By Carol A. Kemper, MD, FACP, Section Editor: Updates, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor for Infectious Disease Alert.

Recall of Typhoid Vaccine

FDA. Recall of Typhim Vi, Typhoid Vi Polysaccharide Vaccine, September 24, 2012. http://www.fda.gov/BiologicsBloodVaccines/SafetyAvailability/Recalls/ucm321705.htm.

Sanofi Pasteur announced September 28, 2012 a recall of 6 lots of Typhim Vi polysaccharide vaccine, the injectable "killed" vaccine. A significant portion of the stock has been shown to be insufficiently immunogenic and at risk for "low antigen content." As a result, individuals who received this vaccine after January 2011 may not be protected against Typhoid fever. The 6 lots are posted on the FDA website, one of which includes a batch of pre-filled syringes.

Typhoid fever vaccine is routinely recommended for travelers to developing countries, especially those heading to India and Southeast Asia. It is generally considered to be a modestly effective vaccine, providing approximately 50%-80% effectiveness. Even when vaccinated, travelers are nonetheless advised to observe good food and water precautions. Preliminary observations do not suggest there has been an increase in typhoid cases since January 2011.

The company wished to stress that, other than the lack of potency, there are no safety concerns. Vaccines from other companies, such as Typherix or the live oral Ty21a vaccine (Vivotif® Oral) are not affected by this recall.

Flu Vaccine: Does Egg Allergy Matter?

Kelso JM,e t al. Adverse Reactions to vaccines practice parameter update 2012. J Allergy Clin Immunol 130 (1); 25-43. http://www.mayoclinic.com/health/flu-vaccine-egg-allergy/ANO233.

Data continues to lend support for the administration of influenza vaccine to individuals with serious egg allergy. Serious egg allergy occurs in about 1.5% of people, most of whom, as a result, choose not to get influenza vaccination. Influenza vaccine is developed in chicken egg, and does include minute amounts of egg protein.

Researchers at the Mayo Clinic evaluated 367 individuals, mostly children, with a history of serious egg allergy, who received annual influenza vaccine for 5 years. One-third of participants reported a history of anaphylaxis to egg. During the 5-year project, only 13 (3.5%) developed "allergy-type" side effects from vaccination, none of which were severe, and most of which consisted of mild rash or urticaria within a day of vaccination.

The investigators also examined 26 additional influenza vaccine studies involving a total of more than 4000 egg-allergic people, and found that none of the participants had developed serious reaction to the injectable vaccine. The investigators stressed that the benefits of influenza vaccination outweigh the potential risks, especially in small children under the age of 5.

How to keep the Moon and Mars disease-free?

Garber M. Swabbing and hoping: how NASA keeps germs from colonizing Mars. September 11, 2102; http://www.theatlantic.com/technology/archive/2012/09

This fascinating article delves into a previously unrecognized area of Infectious Disease for me - Space ID! The 1967 "Outer Space" treaty between the United States, England, and the Soviet Union that governs space travel stipulates that countries should avoid contamination of other worlds and planets with microbial life from Earth. Not quite the "Prime Directive" Gene Roddenberry had in mind, which governed Star Fleet interstellar travel — (remember, "the right of each sentient species to live in accordance with its normal cultural evolution is considered sacred"?) — but something close.

Similar to the Prime Directive, this treaty provision is variably applied by NASA depending on where the mission is going, and which vehicle is employed to get there. The space agency actually classifies missions according to the estimated risk of bacterial cross-contamination, although budget concerns help to frame the guidelines. While travel to the space station is considered lower risk, travel to Mars is higher risk. Therefore, when the space rover Curiosity was being developed, she spent her life in a "clean room" at the Jet Propulsion Laboratory, tended to by engineers and technicians wearing protective gear. The shell of the Rover and all external equipment was specifically designed to diminish the risk of bacterial and fomite carriage, with a goal of total surface bacterial colonization less than 300,000 colonies (a wee amount when compared with the human body). Alcohol is routinely used to decontaminate hands equipment and surfaces. The implementation of a second drill bit on Curiosity, which had not been stored in the same manner as another, reportedly created a serious disagreement between engineers and microbiologists supervising the project.

Ms. Garber reminds us that several Earth species have a phenomenal ability to survive in extreme conditions, such as the recently recognized thermophiles and halophiles found in lava shafts, which use iron in basalt rock as an energy source. Tardigrades, which are those bizarre pod like creatures that hang out in lichens and moss, have been found to withstand heating to 150 degrees for a few minutes, extreme cold to as low as -200 C for days, and have been found under layers of ice in the Himalyas. They can even withstand lethal amounts of gamma rays. Tardigrades can actually suspend their metabolism and go into a state of cryptobiosis for nearly 10 years. So you can understand why microbiologists are concerned about the risk of colonizing another planet. I just worry about what kind of terrifically durable species they might bring back.

Transmission of HSV – Despite Antivirals

Johnston C, et al. Standard-dose and high-dose daily antiviral therapy for short episodes of genital HSV-2 reactivation: three randomized open-label, cross-over trials. The Lancet 2012; 379: 641-647.

Van DePerre P and Nagot N. Herpes Simplex virus: A new era ? Lancet 2012;379:598-599.

I just had a patient present for consultation, concerned he'd transmitted HSV to two new sexual partners, despite a lack of symptoms or obvious lesions, and expressing concern about the adequacy of suppressive acyclovir therapy. He had tried to convince both new partners is was not him! I had to disappoint him.

These investigators conducted three open-label, cross-over treatment trials of suppressive antiviral therapy in 113 participants with known active HSV, examining genital swabs collected 4 times daily during treatment for quantitative HSV DNA by PCR. Patients were given no treatment vs oral acyclovir standard dose 400 mg twice daily; or standard dose acyclovir 400 mg twice daily vs 800 mg three times daily; or standard dose valcyclovir 500 mg daily vs 1 gram three times daily. Treatment duration ranged from 4 to 7 weeks, with a one-week wash-out. While the treatment was provided in an open-label manner for the patients, the study monitors were blinded to the treatment group.

A total of 23,603 swabs were collected, 1272 (5.4%) of which were positive for HSV DNA. Eighty percent of all episodes detected were sub-clinical. Not unexpectedly, 18.1% of the swabs collected from patients on no treatment were HSV positive compared with 1.2% of the swabs from patients receiving standard-dose acyclovir. But an even more important finding was the frequency of HSV detection in patients receiving high dose treatment. The frequency of HSV detection was 4.5% vs 4.2% in persons receiving standard dose ACV vs high dose valcyclovir; and, 5.8% vs 3.3 % in persons receiving standard dose valcyclovir vs high dose valcyclovir.

While no statistically significant difference in the number of episodes of shedding per person-years was observed for any of the treatment groups, there was an observed difference in the duration of viral shedding during episodes. The median duration of an episode was longer for patients on no treatment vs standard ACV treatment (13 hrs vs 7 hrs, p = .01); and, similarly, for standard vs high dose valcyclovir treatment (10 hrs vs 7 hrs,, p= .03). A small but statistically significant difference was also observed in the maximum copy number of HSV particles detected in persons receiving no treatment vs standard ACV; and standard ACV vs higher dose valcyclovir.

Overall, HSV was detected on 3% of the days during standard dose ACV treatment, 7% of the days on high dose valcyclovir, and 9% of the days during treatment with either standard dose valcyclovir or high dose acyclovir. While on no treatment, genital swabs were positive for HSV DNA 24% of the days. That's one–fourth of the time!

The accompanying editorial suggests that we are functioning under a mistaken impression of genital HSV as a latent infection, punctuated by short but self-limited "bursts" of viral replication, some of which is symptomatic. A more accurate model may (unfortunately) be one of constant low-grade viral replication, with ongoing production of small numbers of viral particles (40-90 virions) from infected neurons every day. Propagation of HSV than occurs, with more rapid spread of virions to the skin surface — which is only controlled in situ by CD8 cells. Data suggests that low-level replication may actually be harder to suppress with antiviral therapies, and therefore increases the risk of transmission. In other words, people with recognized outbreaks of symptomatic infection may be easier to suppress and at lower risk than those with low-level replication and subclinical infection.

Patients are often under the mistaken impression that viral shedding is a rare event if they take long-term suppressive therapy. Clearly this data speaks otherwise. Patients should be counseled that, while suppressive antiviral therapy may reduce viral shedding, it may still occur — and with surprising frequency. Use of condoms may further reduce the risk of viral shedding, but also does not prevent sexual transmission.