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

Updated Recommendations for Tdap in Adults

ACIP Recommendations, March 2, 2006; www.cdc.gov/nip/vaccine/Tdap

In October 2005, the American Committee on Immunization Practices provided provisional recommendations for the acellular pertussis vaccine (Tdap) (ADACELTM, Sanofi Pasteur) as a single booster dose for persons 11-64 years of age. Additional provisional recommendations were drafted in February, which include:

  • Health Care Personnel with direct patient contact, especially those with direct contact with infants < 12 months of age, should receive a single booster dose of Tdap as soon as possible. Immediate vaccination should be encouraged by clinics and hospitals if the last dose of Td was at least 2 years previous; otherwise, HCWs should wait 2 years following their last dose of Td to receive a booster dose of Tdap.
  • Adults who have or anticipate having contact with an infant < 12 months of age should receive a single booster dose of Tdap. This includes parents, uncles, aunts, grandparents, childcare providers, and tweener and teen sibs. Ideally, Tdap should be administered one month before contact with the infant. An interval of at least 2 years since the last dose of Td was administered is recommended, although a "shorter interval can be used."
  • Pregnant and parturient women who received their last dose of Td < 10 years ago should receive Tdap after delivery.
  • Pregnant women who received their last dose of Td > 10 years previous who require Td during pregnancy should receive Td in preference to Tdap.
  • Pregnancy is not a contraindication to Tdap, but no formal recommendations for its use during pregnancy have been made.
  • Adults who have an incomplete or unknown tetanus vaccination history should receive the series of 3 vaccinations: The preferred schedule is an initial dose of Tdap, followed by a dose of Td 4 weeks later, and a second dose of Td 6 to 12 months later; however, the dose of Tdap can be substituted for any one of the doses in the series.

These recommendations will become official following review and publication in the MMWR, although physicians, clinics, and hospitals should be prepared to implement them as soon as they are formalized.

Avian Influenza—Its Not the Birds

ProMED-mail post; www.promedmail.org; June 6, 2006.

This interesting tidbit, first published in the Hindustan Times, contradicts the presumption that recent outbreaks of Avian Influenza around the globe are due to migratory birds heading across western Asia and Europe. Recent molecular studies completed on virus strains from recent outbreaks occurring in India in February and March of this year identified 2 different viruses (with 3.5% divergence). Sequencing of the HA1 and HA2 genes showed that the viruses had likely originated in central and southern China—and not in regional migratory birds. Outbreaks occurred in 2 communities, Navapur and Jalgaon, which are located about 140 km apart in Maharashtra. The outbreak in Navapur was milder, predominately struck backyard poultry, and was relatively easier to control. The outbreak in Jalgaon occurred 12 days later, was more serious, struck larger poultry farms, and took longer to control. The 2 viruses subsequently spread to other areas, but have been controlled, and no new cases have been reported in 2 months.

Everyone assumed that given the regional proximity and time-frame, the outbreaks were due to the same virus from a common source. Recent data from Africa also suggest that migratory birds are not the source of infection in that country. Smuggled birds, poultry parts, and contaminated feed are hot suspects.

Plumes of Bacteria Surround Animal Facilities

Green CF, et al. J Occup Environ Hyg. 2006;3:9-15.

Bioaerosols have been found surrounding large animal facilities where bacteria routinely slough from the skin and cavities of pigs or cattle, and animals root around in feces and waste. Generally such facilities are open to the outdoors or have large ventilation systems venting exhaust to the outdoors.

Levels of bacteria were evaluated in the air upwind at 25 meters and downwind 25 m, 50 m, 100 m, and 150 m from a large, confined animal feeding operation housing hogs. The buildings were only 4 years old. Samplers designed to detect colony forming units of bacteria were spaced at various locations from the facility, at various times of the day, on 4 separate dates in the summer of 2003 (somewhere in the Midwest). The samplers were designed with a cascade impactor containing 200 orifices, which allowed for the separation of non-respirable particles or respirable particles (< 8 micrometers in diameter). Wind direction, wind speed, and humidity were recorded. Interestingly, the more humid the environment, the bacteria absorb more water, become denser, and are less susceptible to the bactericidal effects of UV radiation. This being the Midwest in the summer, it was quite humid at 87-93%. (Thus, there are more bacteria floating around in hot, humid summer months.)

Upwind of the facility, the samplers detected an average of 82 CFU/m3, of which 62% was respirable. Inside the facility, the culturable level of bacteria averaged 18,185 CFU/m3, of which ~8500 CFU/m3 was respirable. Downwind, there was an approximate 1-log drop in culturable bacteria at 25 m, and about a 2-log drop by 100 m. However, even at 150 m downwind, there were still 2.5 times more culturable bacteria organisms as found upwind of the facility. Surprisingly, Staphylococcus aureus represented about 76% of the bacteria cultured inside the facility, and was the dominant organism found downwind. Total coliforms represented ~7% of the culturable organisms. Not all of the bacteria cultured were identified.

The bacterial plumes downwind of large animal facilities may be a source of infection for humans, and may lead to spread of antibacterial resistance. Since the greatest exposure occurs inside the facility, Green and colleagues recommend the use of particle respirators when entering and working within the facility, and removing all clothing and showering prior to heading home at the end of the day. Ideally, ventilation systems should filter air released to the outdoors.

I am curious what the real risk to workers and populations living downwind of these facilities might be. It is notable that these experiments were conducted at least 5 months after the last application of manure to surrounding farmland, suggesting Green et al were concerned about a sufficient risk of contamination of these results from routine farm work. Outbreaks of infection have rarely occurred in barn dances and at county fairs, other venues for kicking up your heels and throwing shit around. Perhaps the concentration of animals in these larger facilities warrants additional precautions, but for someone who grew up around animals and who still routinely spreads manure around the garden, it's hard to get too worked up. After all, as one of my Infectious Disease attendings was fond of pointing out, you just have to imagine the world as covered by a thin layer of feces.

Risk of PML with Natalizumab

Yousry TA, et al. Evaluation of Patients Treated with Natalizumab for Progressive Multifocal Leukoencephalopathy. N Engl J Med. 2006;354:924-933.

Following reports of 3 cases of progressive multifocal leukoencephalopathy (PML) associated with the administration of natalizumab (Tysabri, Biogen Idec and Elan Pharmaceuticals), the FDA suspended the use of this agent in February 2005, much to the disappointment of many people with multiple sclerosis. Natalizumab is a recombinant humanized antibody directed tot he alpha-4 integrins, and had been approved for use in relapsing MS. These authors conducted a detailed review of patients receiving natalizumab in clinical trials for multiple sclerosis, Crohn's disease, or rheumatoid arthritis. Of 3417 patients enrolled in clinical trials, 3116 (91%) had more recently received the drug for a mean of 17.9 months, and were included in the evaluation. Of those patients with MS, 97% were evaluated within 3 months after discontinuing drug.

Forty-four patients developed a suspicious triad of progressive neurologic disease, abnormal MRI scan, and high levels of plasma JC DNA, and were examined by an expert panel. JC virus was not detected in the cerebrospinal fluid of 43 of these patients; the final patient developed progressive MS and was classified as indeterminate because follow-up data could not be obtained. After intensive review, only the original 3 cases of PML were confirmed, and no new cases of PML were identified. Based on these data, the risk of PML associated with the administration of natalizumab is estimated to be ~1/1000 (95% confidence interval, 0.2 to 2.8 per 1000).