Updates

By Carol A. Kemper, MD, FACP

Not Your Ordinary Dog Bite

Ngauy V, et al. J Clin Micro. 2005;970-972.

This unusual case report describes an 82-year old diabetic man who presented with an ulcerated nodule over his first metacarpophalangeal joint. He had been bitten by a dog about 3 months earlier, with initially a small scratch that gradually enlarged and ulcerated with purulent drainage. He failed to respond to separate courses of Augmentin and Keflex, although he did have some response to a 7-day course of levofloxacin. X-rays showed no bone involvement, and a chest radiograph showed only mild bibasilar interstitial disease.

Wound culture grew. . . (you’ll never guess! A clue: the patient was a WWII POW in the South Seas). See the end of this column for the answer. . .

Wash That Malassezia furfur Out of My. . .

Dolk E, et al. Applied Environ Microbiol. 2005;71:442-450.

Many scientists now believe that an overgrowth or imbalance of Malassezia furfur on the scalp may contribute to dandruff. Usually part of the normal skin flora, greater numbers of M. furfur can be found on the scalps of people with dandruff than those without, although whether this is a primary phenomena or a secondary event, remains a matter of some debate. However, treatment with agents active against M. furfur, such as ketoconazole, selenium sulfides, and zinc, can decrease the severity of dandruff.

Searching for ways to improve upon existing dandruff shampoos, Dolk and colleagues created a library of single variable domain (VHH) antibodies with a high specificity for cell surface proteins of M. furfur (Malf1) that would remain active in various shampoo products. VHHs were investigated because of their physical properties, their antigen specificity, and their ability to inhibit the growth and, perhaps, even neutralize antigens of M. furfur. Antibody production was induced by repeated inoculation of a llama with extracts of Malf1. A series of heavy-chain antibodies with a single variable domain (VHH) for antigen binding were subsequently identified from the blood of the llama by polyclonal rabbit anti-llama and swine anti-rabbit immunoglobulins. A library of 107 VHH clones was constructed.

Only those VHHs that highly bound to Malf1 in the presence of various shampoos were deemed acceptable candidates for further investigation. Not surprisingly, most VHHs did not bind to Malf1 well under the harsh conditions of most ordinary shampoos, but a few did. Interestingly, those VHHs that were especially stable in the presence of shampoo were also stable in the presence of denaturants, urea, and guanidine HCL. Stability proved to be related to specific amino acids present at certain positions within the chain. VHHs identified as being particular specific for Malf1 could be further engineered for increased stability, even in the harsh climate of ordinary shampoo.

Whether these llama-derived antibodies will prove useful in reducing numbers of M. furfur on the scalp and improving dandruff, remains to be seen. (Do we get to ask if the llama’s dandruff improved?)

Really Hot Cash

ProMED-mail post January 28, 2005; www.promedmail.org.

Federal authorities have issued an alert, and are seeking additional information, in a bizarre criminal case in Philadelphia involving the Russian mob and purported drug money possibly contaminated with Staphylococcal exotoxin. Details are sketchy (and no one is talkin’), but during a routine traffic stop, police stumbled upon $250,000 in cash.

After the funds were counted, several of the agents became ill and one required hospitalization with severe flu-like symptoms. For unstated reasons, authorities suspect the cash was laced with Staphylococcal exotoxin.

One of a group of agents now believed to function as superantigens, Staphylococal exotoxin B (SEB) has been investigated as a possible agent of bioterrorism for many years. Various superantigens, including staphylococcal exotoxin A, B, and C, toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin can be detected in up to 42% of patients in septic shock, 31% of septic patients without shock, and 6% of patients with systemic inflammatory response without infection. Streptococcal pyrogenic toxin has been implicated in Kawasaki’s syndrome. Similar to toxic shock, patients with low or undetectable levels of antibodies to these superantigens may be at greater risk for more severe inflammatory response. Patients in the ICU with low levels of antibody to staphylococcal exotoxins and/or TSST-1 have been found to have higher levels of TNF-alpha than those with higher antibody titers.

In contrast, cutaneous and inhalational exposures to staphylococcal exotoxins may produce a different constellation of symptoms. Following laboratory exposure to aerosolized SEB, flu-like symptoms with fever and respiratory symptoms have been reported. In a laboratory accident that occurred in 1964, the US Army reported that 9 laboratory workers exposed to aerosolized SEB variously developed fever, rigors, shortness of breath, cough chest pain, vomiting, loss of appetite, and muscle aches.

Fever developed within 12 hours of exposure and lasted an average of 2 days, although chest discomfort and exertional dyspnea was more prolonged. In another incident, ocular exposure resulted in severe conjunctivitis and periorbital swelling, followed by gastrointestinal symptoms. While further information is lacking, authorities have suggested that police agencies handling suspected drug money use appropriate protective gear.

Preventing Traveler’s Diarrhea

ISTM Travel Medicine List, January 18, 2005.

Despite extensive experience in travel medicine and treating traveler’s diarrhea, many physicians express frustration at the inability to diminish the frequency of diarrheal illness in travelers. In an upcoming article in Infectious Disease Clinics of North America, Dr. David Shlim nicely summarizes the problems in preventing traveler’s diarrhea (TD):

1) Travelers make frequent mistakes while eating; >95% of travelers fail to follow current food guidelines while traveling.
2) To some degree, this may not be a problem, as studies suggest no relationship between the type of food eaten and illness; thus, current food precautions and recommendations may not be as effective as hoped.
3) Studies repeatedly demonstrate that eating in hotels and restaurants is not a guarantee against TD. In fact, one investigator observed that eating in restaurants in Mexico is a risk factor for TD.
4) Most restaurants in developing countries lack basic facilities and hygiene, such as sinks in employee bathrooms, adequate storage and refrigeration for food, and clean water and soap.
5) Produce and meat in developing countries is often contaminated with bacteria (even in the United States, meat is contaminated with bacteria). Flies are numerous and efficient vectors of transmission of bacteria. Cross-contamination of foods during preparation and undercooking of meat is common.
6) Since most travelers eat 21 meals per week in restaurants (unless they are fortunate to be staying in someone’s home), eating in restaurants is largely unavoidable, and is generally viewed as part of the fun of travelling.

Perhaps the only way to effectively prevent traveler’s diarrhea is not to travel! For those willing to risk it, common sense should be the rule of the day. Avoid the most risky types of food and drink, make sure your meat is well cooked, and have ready access to medications for TD. But for all practical purposes, travelers should think of the world as covered by a thin layer of feces.

Dog Bite (Answer)

. . .continued from beginning of column.

Wound culture grew a gram-negative bipolar rod, with creamy colonies on both blood and MacConkey agar. The organism was sensitive to levofloxacin, piperacillin-tazobactam, cefipime, and imipenem, but not aminoglycosides. It was subsequently identified, and later confirmed by PCR, as Burkholderia pseudomallei.

The man had been taken as POW in March 1942 by the Japanese and did hard labor building railways in Java, Singapore, Malaysia, and Burma, finally ending up in a labor camp in Thailand for 2 years. After returning to the United States, he lived in Texas and never traveled again.

Meliodosis most often presents with skin and soft tissue infection and pneumonia; acute sepsis occurs in about 20% of patients. Current theory holds that most human infections are acquired through cutaneous inoculation, not inhalation or ingestion. Late presentations are not uncommon, but generally fall into the category of chronic pulmonary disease. Notoriously difficult to treat (meta-analysis suggests that prolonged treatment with cefipime or imipenem is most effective), relapses following treatment are common. Late reactivation is unusual, but has been reported. Two other cases similar to this one have been reported in a Vietnam veteran and a WWII veteran, 18 and 28 years post-exposure. If Ngauy and colleagues are correct, this man’s latent infection was acquired about 62 years earlier!

Tsunami-related B pseudomallei infections are just beginning to be reported, mostly involving persons with soft tissue injury. Preliminary reports from physicians in Finland have identified 2 patients, returning from tsunami areas, who have been diagnosed with pneumonia, and a third who grew the organism following surgical repair of an Achilles tendon injury. Tsunami-related infections may help to expand our understanding of the distribution of this organism in southeast Asia.

Dr. Kemper, Clinical Associate Professor of Medicine, Stanford University, Division of Infectious Diseases; Santa Clara Valley Medical Center, is Associate Editor of Infectious Disease Alert.