Updates

by Carol A. Kemper

Amazing Teen Survives Rabies

ProMED-mail post November 25, 2004; www.promedmail.org

A14-year-old Wisconsin girl has remarkably survived acute encephalitic rabies! Although the full details have not disclosed by her physicians (who plan to publish this remarkable case), she did not receive vaccine at presentation, but was instead put into a drug-induced coma and treated with various antiviral agents. It is not clear which of these interventions was important to her survival. The few survivors of rabies that have been described, of whom there are less than a handful, all received post-exposure prophylaxis or at least vaccine.

Her story, which was initially reported in the New York Times on the same day, is fairly typical for ~50% of the cases or rabies reported in the United States during the past 25 years. She was bitten by a bat, although she did not appreciate the fact; the bite was small and painless and she thought she had simply been scratched. She did not seek medical assistance. About 6 weeks later, she developed altered mental status, slurred speech, and other symptoms of rabies, and was admitted to hospital. Unfortunately the bat was not retrieved, and no virus was recovered from the teen, as it may have been helpful to examine this particular virus for virulence and attenuation factors.

India, Genetics, and HIV

Jayaraman K. Nat Med. 2004,10:1148.

Researchers have uncovered numerous genetic factors that may be directly contributing to the growing problem of HIV in India. According to this editorial, Dr. Narinder Mehra, an immunologist with the All India Institute of Medical Science in New Dehli, has shown that many Asian Indians carry various genetic factors which predispose them to HIV infection, and more rapid progression of HIV, onc3e infected. First among these is a paucity of the variant CCR5 chemokine receptor gene (CCR5-D32), which is present in < 1% of Indians, rendering them more susceptible to progressive HIV. Epidemiological studies have found that ~20% of those of northern European descent are heterozygous for this mutation and ~1% are homozygous. While CCR5-D32 heterozygotes are probably not protected from HIV infection, it does afford modest protection against disease progression. The frequency of this allele is exceedingly low in African and Asian populations.

Several other interesting differences were identified in Asian Indians: they have a high level of polymorphism in the major histo compatibility complex (MHC) region (which, among other things, appears to possibly modulate their response to Mycobacterium tuberculosis infection), as well as genes which appear to encode for a unique repertoire of peptides to block autoreactive antigens. Such differences will be important to identify if worldwide peptide-based vaccines for HIV are to be developed. Complicating these findings, many Indians are infected with HIV subclade C, and may not be candidates for vaccines targeting subclade B (the predominate subtype present in the United States).

References

1. Mehra NK, et al. Community Genet. 2002;5:162-166.

2. Sharma Sk, et al. Infect Genet Evol. 2003;3:183-188.

3. Balamurugan A, et al. J Infect Dis. 2004;189:805-811.

Illicit Botox Products

ProMED-mail post December 3 and December 8, 2004; www.promedmail.org

Botox, when injected directly into a muscle in small amounts (~15-50 IU of botulinum exotoxin A, depending on the size of the muscle), is extremely but transiently effective at diminishing wrinkles. The increasing use of Botox in cosmetic salons by non-medical personnel—and the potential for misuse of illicit products—puts individuals at risk for facial paralysis, deformity, and even death. Experts caution that a precise understanding of anatomy is necessary to achieve optimal results, and that only 2000 IU—a dilution away from dosages used above—can be a lethal dose.

Sadly, 4 individuals, including

a physician, a chiropractor, and their female companions did not get this message. After their purported self injection with an illicit botox-like product, all 4 were acutely hospitalized over the Thanksgiving weekend with suspected botulism, and are now on ventilatory support. Three of them had evidence of botulinum type A toxin in their bloodstreams.

True Botox (Allergen Inc. Irvine, CA) is FDA-approved for use as an anti-wrinkle treatment, is subject to rigorous manufacturing standards, and provides a fairly uniform and dependable dose of exotoxin. Although tests are still inconclusive, authorities found evidence at the scene to suggest that a product called botulinum neurotoxin type A may have been used, which is an illegal product sold by an Arizona distributor called Toxin Research

International. Apparently, this product is far less costly than Botox (which sells for $1250 per vial, enough for about 5-10 people), and may even contain live C. botulinum. Illicit botox products are being actively marketed on the web, especially in South America and Asia, and now even in the United States.

Sharing Your MRSA With Your Pet

Van Duijke ren E, et al. Emerg Infect Dis. 2004;10.

During investigation of an outbreak of MRSA in a local nursing home in the Netherlands, which involved 48 residents and 15 nurses, Van Duijkeren and colleagues identified a 31-year old nurse with recurrent colonization with MRSA, despite repeated attempts at decolonization with both topical and oral agents. She did have psoriasis, with numerous skin lesions (which obviously makes it more difficult to clear her), which appeared to initially clear with topical mupirocin to her nares. However, within weeks she developed recurrent infection with multiple positive cultures of nares, throat, perineum, and skin lesions. She received aggressive treatment with topical applications of triamcinolone and tetracycline to treat the skin lesions, plus a combination of orally administered doxycycline and rifampin. Again, she appeared to have cleared with multiple negative cultures. But within weeks, she was again culture-positive.

Further investigation showed that her husband and grandmother (who cared for their child) were culture-negative, but nares specimens from her 1-year-old child (who also had psoriasis) and her pet dog were both positive. All 3 isolates were similar by PFGE.

Clearance of the whole family was successfully accomplished, once the dog received a course of doxycycline and rifampin (Van Duijkeren et al thought that topical muperocin to the dog's nostrils was too impractical).

Shared MRSA between humans and their pet dogs has been previously reported—even a horse was suspected of being involved in an outbreak of MRSA infection in a veterinary hospital. This is the first report of successful clearance of MRSA from an entire family once their pet dog was also effectively treated.

Could Sepsis Respond to Nicotine?

Mattay MA, et al. Nat Med. 2004;10:1161-1162; Wang H, et al. Nat Med. 2004;10:1216-1221.

This fascinating article suggests that nicotinic acetylcholinergic receptors play an important part in the immune system response to sepsis—raising the intriguing notion that nicotine could reduce mortality in sepsis by down-modulating the inflammatory response. It turns out that one of the predominant negative-inhibitory pathways of the inflammatory system are nicotinic acetylcholine receptors (alpha 7nAChR) located on tissue macrophages, which modulate the efferent vagus nerve (this is termed the cholinergic anti-inflammatory pathway). Down modulation of this pathway leads to decreased NF-(kappa)B activation, decreased production of inflammatory cytokines and tumor necrosis factor, and ultimately, prevents shock. This important immunomodulatory effect was nicely demonstrated by Wang and colleagues, who administered nicotine to mice lethally challenged with intraperitoneal bacteria. Mortality in the mice was reduced from 84% to 51%, even when the nicotine was administered after the mice became ill. Treated mice had evidence of decreased activation ex vivo of a transcriptional factor for NF-(kappa)B production and reduced levels of high mobility group box 1 protein (HMGB-1) in serum. HMGB-1 is an important molecule in the cascading inflammatory response and activation of plasminogen activator inhibitor-1. These scientists theorize that either nicotine or other inhibitor of the nicotine (alpha)7nAChR receptor may reduce mortality from sepsis.

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 Contributing Editor for Infectious Disease Alert.