Ermias D. Belay

Reye's Syndrome in the United States from 1981 through 1997

BACKGROUND Reyes syndrome is characterized by encephalopathy and fatty degeneration of the liver, usually after influenza or varicella. Beginning in 1980, warnings were issued about the use of salicylates in children with those viral infections because of the risk of Reyes syndrome. METHODS To describe the pattern of Reyes syndrome in the United States, characteristics of the patients, and risk factors for poor outcomes, we analyzed national surveillance data collected from December 1980 through November 1997. The surveillance system is based on voluntary reporting with the use of a standard case-report form. RESULTS From December 1980 through November 1997 (surveillance years 1981 through 1997), 1207 cases of Reyes syndrome were reported in patients less than 18 years of age. Among those for whom data on race and sex were available, 93 percent were white and 52 percent were girls. The number of reported cases of Reyes syndrome declined sharply after the association of Reyes syndrome with aspirin was reported. After a peak of 555 cases in children reported in 1980, there have been no more than 36 cases per year since 1987. Antecedent illnesses were reported in 93 percent of the children, and detectable blood salicylate levels in 82 percent. The overall case fatality rate was 31 percent. The case fatality rate was highest in children under five years of age (relative risk, 1.8; 95 percent confidence interval, 1.5 to 2.1) and in those with a serum ammonia level above 45 microg per deciliter (26 micromol per liter) (relative risk, 3.4; 95 percent confidence interval, 1.9 to 6.2). CONCLUSIONS Since 1980, when the association between Reyes syndrome and the use of aspirin during varicella or influenza-like illness was first reported, there has been a sharp decline in the number of infants and children reported to have Reyes syndrome. Because Reyes syndrome is now very rare, any infant or child suspected of having this disorder should undergo extensive investigation to rule out the treatable inborn metabolic disorders that can mimic Reyes syndrome.

Chronic wasting disease and potential transmission to humans.

Chronic wasting disease (CWD) of deer and elk is endemic in a tri-corner area of Colorado, Wyoming, and Nebraska, and new foci of CWD have been detected in other parts of the United States. Although detection in some areas may be related to increased surveillance, introduction of CWD due to translocation or natural migration of animals may account for some new foci of infection. Increasing spread of CWD has raised concerns about the potential for increasing human exposure to the CWD agent. The foodborne transmission of bovine spongiform encephalopathy to humans indicates that the species barrier may not completely protect humans from animal prion diseases. Conversion of human prion protein by CWD-associated prions has been demonstrated in an in vitro cell-free experiment, but limited investigations have not identified strong evidence for CWD transmission to humans. More epidemiologic and laboratory studies are needed to monitor the possibility of such transmissions.

A Novel Human Disease with Abnormal Prion Protein Sensitive to Protease

To report a novel prion disease characterized by distinct histopathological and immunostaining features, and associated with an abnormal isoform of the prion protein (PrP) that, contrary to the common prion diseases, is predominantly sensitive to protease digestion.

Chronic Wasting Disease of Elk: Transmissibility to Humans Examined by Transgenic Mouse Models

Chronic wasting disease (CWD), a prion disease affecting free-ranging and captive cervids (deer and elk), is widespread in the United States and parts of Canada. The large cervid population, the popularity of venison consumption, and the apparent spread of the CWD epidemic are likely resulting in increased human exposure to CWD in the United States. Whether CWD is transmissible to humans, as has been shown for bovine spongiform encephalopathy (the prion disease of cattle), is unknown. We generated transgenic mice expressing the elk or human prion protein (PrP) in a PrP-null background. After intracerebral inoculation with elk CWD prion, two lines of “humanized” transgenic mice that are susceptible to human prions failed to develop the hallmarks of prion diseases after >657 and >756 d, respectively, whereas the “cervidized” transgenic mice became infected after 118–142 d. These data indicate that there is a substantial species barrier for transmission of elk CWD to humans.

Epidemiology of Kawasaki Disease in Asia, Europe, and the United States

Kawasaki disease (KD) is a systemic vasculitis that mainly affects children younger than 5 years. Although Dr. Tomisaku Kawasaki first reported KD over 40 years ago, the cause of the disease remains unknown. Currently, KD has been diagnosed in more than 60 countries, including those in Asia, the Middle East, Latin America, and Africa, as well as in North America and Europe. The purpose of this review is to describe the epidemiologic features of KD—particularly its incidence, seasonality, and the occurrence of coronary artery abnormalities—primarily in Japan and the United States, but also in Europe and other Asian countries.

Variably protease-sensitive prionopathy: a new sporadic disease of the prion protein

The objective of the study is to report 2 new genotypic forms of protease‐sensitive prionopathy (PSPr), a novel prion disease described in 2008, in 11 subjects all homozygous for valine at codon 129 of the prion protein (PrP) gene (129VV). The 2 new PSPr forms affect individuals who are either homozygous for methionine (129MM) or heterozygous for methionine/valine (129MV).

Serologic Evidence of H1 Swine Influenza Virus Infection in Swine Farm Residents and Employees

We evaluated seropositivity to swine and human H1 influenza viruses in 74 swine farm owners, employees, their family members, and veterinarians in rural south-central Wisconsin, compared with 114 urban Milwaukee, Wisconsin, residents. The number of swine farm participants with positive serum hemagglutination-inhibition (HI) antibody titers >40 to swine influenza viruses (17/74) was significantly higher (p<0.001) than the number of seropositive urban control samples (1/114). The geometric mean serum HI antibody titers to swine influenza viruses were also significantly higher (p<0.001) among the farm participants. Swine virus seropositivity was significantly (p<0.05) associated with being a farm owner or a farm family member, living on a farm, or entering the swine barn >4 days/week. Because pigs can play a role in generating genetically novel influenza viruses, swine farmers may represent an important sentinel population to evaluate the emergence of new pandemic influenza viruses.

Kawasaki syndrome and risk factors for coronary artery abnormalities: United States, 1994-2003.

Background: Kawasaki syndrome (KS) causes significant morbidity among children in the United States and other countries and can result in a range of cardiac and noncardiac complications. Methods: To describe the occurrence of KS in the United States and risk factors for the development of coronary artery abnormalities (CAA), national KS surveillance data were analyzed for patients with KS onset during 1994–2003. The surveillance is a passive system, and information is collected on a standardized case report form. Results: During 1994 through 2003, 3115 patients who met the KS case definition were reported to the national KS surveillance system. The median age of KS patients was 32 months; the male-female ratio was 1.5:1. Nearly one-third (31.8%) of the cumulative number of KS cases occurred during January through March. During the study period, 362 (12.9%) of 2798 KS patients had CAA. The proportion of patients with CAA increased from 10.0% in 1994 to 17.8% in 2003. Age younger than 1 year and 9–17 years, male sex, Asian and Pacific Islander race and Hispanic ethnicity (a previously unidentified risk factor) were significantly associated with the development of CAA. Conclusions: The increase in CAA was attributed to widespread use of the criteria of de Zorzi et al, resulting in increased recognition of coronary artery dilatations. The factors contributing to a higher risk of CAA, such as delayed treatment, particularly among Hispanics, need to be investigated.

Progressive Multifocal Leukoencephalopathy in the United States, 1979–1994: Increased Mortality Associated with HIV Infection

To examine trends in progressive multifocal leukoencephalopathy (PML) mortality in the United States, we analyzed PML death rates and deaths for 1979 through 1994, using US multiple cause-of-death data. During the 16-year study period 3,894 PML deaths were reported. The age-adjusted death rate increased more than 20-fold, from less than 0.2 per million persons before 1984 to 3.3 per million persons in 1994. The increase was attributable to infection with human immunodeficiency virus (HIV) which was recorded on 2,267 (89.0%) of 2.546 death records from 1991 through 1994. PML age-adjusted death rates increased abruptly for all males beginning in 1984 and for black females in 1990. Only a small increase was observed for white females. In 1994, PML was reported in 2.1% of white males who died with HIV-associated disease compared with 1.2% of white females and 1.0% of black males and females who died of similar causes. The epidemic of PML deaths is increasing in parallel with the AIDS epidemic. The increase in HIV-associated PML deaths, first noted among males, has also become apparent among females and probably reflects the increasing importance of drug use and heterosexual transmission of HIV. The reason for the higher prevalence of PML among white males with HIV infection is unknown.

Kawasaki Syndrome in Hawaii

Objective: To describe the incidence and epidemiology of Kawasaki syndrome (KS) in Hawaii. Methods: Retrospective analysis of the State Inpatient Database for Hawaii residents hospitalized with KS during 1996 through 2001. Results: During 1996 through 2001, 267 persons younger than 18 years of age living in Hawaii were hospitalized with KS; 226 (84.6%) were younger than 5 years of age. The average annual incidence for KS was 45.2 per 100,000 children younger than 5 years of age. The incidence was higher for children younger than 1 year of age than for those 1–4 years of age (74.3 and 37.5 per 100,000). The KS incidence for Asian and Pacific Islander children and for White children was 70.9 and 35.3 per 100,000, respectively. Incidence was highest among Japanese American children living in Hawaii (197.7 per 100,000). Honolulu County had the most KS patients (85.0%) and the highest incidence (53.1 per 100,000) among Hawaii counties. For children younger than 5 years of age hospitalized with KS, the median length of stay was 2 days, and the median hospital charge was