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.

Coxsackie B-1 Virus Infection in Neonates

MMWR Weekly, May 23, 2008; 20: 553-556.

An increase in coxsackie b-1 virus (CVB-1) infections was observed in 2007 in the United States, associated with an increase in neonatal cases and multiple deaths. Infections in neonates resulted in myocarditis and central nervous system infection, as well as coagulopathy and hepatitis, generally observed with enterovirus 11 infections. As reported in MMWR, a total of 514 enteroviral infections were reported from 36 states by February of this year. This is likely an underestimate of the true prevalence of this infection, as many infections go unrecognized.

Twenty-five percent were due to CVB-1. For those cases with sufficient demographic information, 65 of 95 CVB-1 infections (68%) occurred in children less than 1 year of age, including 50 cases in infants less than one-month-old. Five of these resulted in death, all of whom developed multisystem organ failure with the first four days of life. Four of the five mothers were reported to have developed fever or chorioamnitis, suggesting perinatal or intrauterine transmission of infection.

A majority of these infections were reported from California and Illinois. Following a report by the Los Angeles Public Health Department alerting clinicians in the area to the occurrence of 3 CVB-1 myocarditis cases in neonates (2 fatal), the PHD received a total of 30 reports of enteroviral infection in neonates from 7 hospitals. Half of the cases were < 1-15 days old (73% were less than one month old), nearly half required ICU care, and four (13%) died. Most of the patients had meningitis (n = 22) and/or myocarditis (n = 12), although coagulopathy occurred in six, sepsis-like febrile illness in five, respiratory difficulties in three, and hepatitis in two. Eleven patients had multisystem organ failure, including all nine patients who were < 7-days-old. Serotype b was available for 19 of the cases; 14 of which were CVB-1 strains (one patient had dual CVB-1 and CVB-3 infection). Two of the four deaths were due to CVB-1 strains.

All of the CVB-1 virus collected proved to be phylogenetically related, and similar to a strain reported from Colorado in 2006. Prior to 2007, the prevalence of circulating CVB-1, relative to other enteroviral strains, was always under 10%. These data indicate that an emerging strain of CVB-1 is circulating in some communities, and is more likely to result in neonatal infection, especially those born to mothers with acute infection, or perhaps those lacking antibodies to this strain. Enteroviral infections are more common in the late summer and fall months. Physicians should be on the alert for cases of myocarditis, aseptic meningitis or central nervous system infection, or sepsis-like conditions occurring in neonates and infants. Serotype identification is important for epidemiological purposes, and efforts should be made to retrieve virus. Enteroviral-RT-PCR can be performed on CSF and myocardial specimens, although stool viral cultures may provide virus for further study.

The Hottest Anti-fungal Agent?

Tewsbury JJ, et al. The evolutionary ecology of pungency in wild chilies. Proceedings of the National Academy of Sciences. 2008;105:11808-11811.

Chile peppers have evolved from the mildest green pepper to the hottest Scotch Bonnet or Habanero from the Yucatan peninsula. Varying degrees of "heat," or piquancy, are conveyed by capsaicinoids, which are especially prevalent in the seeds of the pepper. The intensity of the fiery heat is measured in Scoville units, a logarithmic scale developed by an American chemist named Wilbur Scoville. Thus, a green bell pepper measures zero on the Scoville scale and contains no capsainoides, whereas Habaneros generally rate between 200,000-300,000 Scoville units. (Standard US Grade pepper spray rates between 2,000,000-5,300,000 units.) Pungency values for peppers in Scoville units are imprecise, due to variations between peppers of the same species and the subjective nature of the rating. An alternate measure has been developed using high-performance liquid chromatography, which directly measures capsaicinoids.

Capsaicinoids stimulate chemoreceptors in nerve endings in the skin, especially in mucous membranes. Biologists have suspected that capsaicinoids act as a natural antimicrobial, which would convey some evolutionary advantage to those chilies at greater risk for fungal infection. Apparently, because of the heat and humidity, chilies in South America are especially susceptible to fungi, such as Fusarium semitectum. Fungi enter the pepper through small holes made by insects, resulting in infected seeds.

To help solve this puzzle, wild chilies were collected from seven different chili populations over a 618 square mile area of Bolivia. Examination showed that chilies with higher levels of capsaicinoids in the seeds had fewer fungal-infected seeds.

Next, newly grown pristine chilies were exposed to fungal-carrying insects. Those chilies with higher levels of capsainoides had 45% to 55% lower fungal burdens, which occurred in a dose-dependent fashion. A dose-dependent relationship was also observed when fake capsaicinoid-laced fruit was exposed to fungus in the laboratory. This may, in part, explain the benefits of using peppers in cooking and for storing foodstuffs in hotter climates — perhaps the food was also less susceptible to mold and spoilage.

Altitude Sickness and Adventure Travel

Sources: Leshem E, et al. Clinical features of patients with severe altitude illness in Nepal. J Travel Med. 2008;15:31-32; Kupper T, et al. Low-dose theophylline reduces symptoms of acute mountain sickness. J Travel Med. 2008;15:307-314.

Adventure travel and ecotourism has become a huge industry, and certain destinations are becoming ever more popular. More than 80,000 people travel annually to Nepal alone to trek. People come from all over the world, are of all ages, and some, it turns out, are not in the greatest shape and have underlying medical problems. Many of these individuals frequently ascend to > 5500 m over a period of 1-3 weeks; the highest altitude attained with the normal trekking permit is 5,600 m (18,400 feet), although a special permit may be obtained allowing climbers to attempt peaks from 5,600-8,848 m. The risk of altitude sickness in these travelers is not trivial. Current estimates suggest that up to 30%-40% of persons trekking above 4000 m develop some form of altitude sickness.

Leshman et al assessed the clinical and demographic features of patients seen and evaluated for altitude-related illness at the CIWED Clinic Travel Medicine Centre in Kathmandu, Nepal (located at 1310 m.) from 1999-2006. A total of 406 patients meeting criteria for some form of altitude-related illness were included in the study (some retrospectively), ranging in age from 15-73 years. Of these, 85% trekked with an organized group. Patients were grouped according to findings consistent with high altitude cerebral edema (21%), high altitude pulmonary edema (34%), both (27%), or acute mountain sickness (AMS) (18%). Demographic characteristics were compared with that of 39,402 trekkers without altitude-related illness (obtained from the permit registry), who served as a control group. In general, compared with controls, patients with altitude-related illness were older 38.6 vs 44 yrs (p < .0001) and more frequently male. Prophylactic acetazolamide was used less frequently in patients with high-altitude cerebral edema (28%) and patients with high-altitude pulmonary edema (29%), compared with 43% of those with AMS (p < .001). (Similar information on controls was not available.). Nearly 6% of patients with altitude-related illness had a history of significant medical problems, including hypertension, heart disease, asthma, diabetes, or stroke.

Individuals with altitude-related illness were more likely to have trekked Everest, where the ascent was nearly twice as rapid, and the maximal altitude greater than in other areas. Most evacuations and deaths were in Everest climbers. The estimate of altitude-related death in Nepal was 7.7 per 100,000 trekkers.

The authors recommend that current recommendations for altitude gain per day be adjusted downward, especially in the Everest area, although this means a climb will take longer. Although one might imagine that group trekking would be more safe, the authors contend that it is characterized by a more rigorous schedule, with peer pressure to stay with the group despite early warning signs of fatigue and illness. It is worth noting that 33% of those with altitude-related illness received prophylactic acetazolamide.

In a second, smaller, randomized, placebo-controlled study, Kupper et al examined the efficacy of low-dose, slow-release theophylline 300 mg daily in 17 healthy male volunteers in the reduction of AMS. The mean age was 35 yrs, and all of the patients were experienced recreational climbers. The study was conducted on Monte Rosa in Italy at 4,559 m. A 12-channel sleep recorder recorded sleep and breathing parameters thru the night.

Theophylline was well tolerated, and no participant developed high blood pressure during the study. AMS symptoms were significantly less frequent in individuals receiving theophylline compared with placebo, and none of the individuals receiving theophylline had an elevated mean AMS score at any time at the intermediate altitude of 3440 m. During ascent and during all five days at the highest altitude of 4,559 m, the difference in symptoms between the groups was still significant. Periodic breathing events (34 vs 74 per hr, p < .05) and oxygen desaturations (62 vs 122 per hr, p < .01) were significantly reduced in theophylline recipients compared to the placebo group. Kupper et al believe theophylline stimulates the respiratory drive, thereby reducing the risk of sleep disorder breathing, which adds to the hypoxic burden of high altitude.