Ryan A. Maddox

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.

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.

Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan.

Background: Some Kawasaki disease (KD) patients do not respond to initial treatment with intravenous immunoglobulin (IVIG). The purpose of this study was to determine potential risk factors associated with IVIG nonresponse among KD patients in Japan. Methods: Data were obtained from questionnaires used for the 18th nationwide KD survey of patients who visited hospitals in Japan from 2003 through 2004. Data for patients who met the case definition for KD and received 2 g/kg single infusion IVIG as the initial treatment within 10 days of illness were analyzed. IVIG nonresponders were defined as patients who needed secondary treatment after initial IVIG administration. Results: Among 15,940 KD patients in Japan during 2003–2004, 6330 patients received 2 g/kg single infusion IVIG within 10 days of illness onset. IVIG nonresponders accounted for 20.3% of them (n = 1286). Male sex [odds ratio (OR), 1.21, 95% confidence interval (CI), 1.06–1.37], receipt of the initial IVIG before the fifth day of illness (OR: 1.89, 95% CI: 1.66–2.15), and having recurrent KD (OR: 1.38, 95% CI: 1.00–1.90) were significantly associated with IVIG nonresponse. In addition, IVIG nonresponders had significantly higher risks for coronary artery aneurysms (OR: 10.38, 95% CI: 6.98–15.45) or giant coronary artery aneurysms (OR: 54.06, 95% CI: 12.84–227.65). Conclusions: Physicians should consider potential IVIG nonresponse among recurrent KD patients or KD patients diagnosed and treated before the fifth day of illness, particularly if they are boys and have laboratory values associated with nonresponse such as low platelet count, and elevated alanine aminotransferase and C-reactive protein. Some of these patients may benefit from administration of the alternative secondary treatment early during the illness along with the initial IVIG treatment.

Investigation of Kawasaki syndrome risk factors in Colorado.

Risk factors for Kawasaki syndrome (KS) were evaluated through a case-control study during an investigation of a KS cluster in Denver, CO. KS was associated with a humidifier in the childs room (odds ratio, 7.3; 95% confidence interval, 1.8 to 29.3) and possibly with an antecedent respiratory illness. The use of humidifiers should be further investigated as part of future studies of KS.

Creutzfeldt-Jakob disease in recipients of corneal transplants.

Purpose: Creutzfeldt-Jakob disease (CJD) transmission has been documented to occur from the use of corneal grafts. We report 4 cases of CJD with a history of corneal transplantation and assess the frequency of coincidental CJD among corneal transplant recipients. Methods: Medical records and eye bank documents were reviewed. Genetic and neuropathologic tests on available specimens were performed at the National Prion Disease Pathology Surveillance Center. Statistical analyses were used to determine the expected number of coincidental CJD cases among the US population with a history of corneal transplantation. Results: Four CJD decedents with histories of corneal transplantation were identified: 3 from the United States and 1 from Japan. The time from transplant to onset of CJD symptoms ranged from 2 years, 11 months to 18 years. Available eye bank records did not suggest evidence of neurologic illness in the donors. Using corneal transplantation and CJD death data from 1990 through 2006, statistical analyses suggest that a case of coincidental sporadic CJD will occur among the population of corneal transplant recipients approximately every 1.5 years. Conclusions: It is likely that these 4 recipients of transplanted corneas had sporadic CJD. Because of the many corneal transplantations performed each year in the United States, occasional cases of sporadic CJD in this population are expected.

Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob disease in the United States

Transmissible spongiform encephalopathies (TSEs) attracted increased attention in the mid-1980s because of the emergence among UK cattle of bovine spongiform encephalopathy (BSE), which has been shown to be transmitted to humans, causing a variant form of Creutzfeldt-Jakob disease (vCJD). The BSE outbreak has been reported in 19 European countries, Israel, and Japan, and human cases have so far been identified in four European countries, and more recently in a Canadian resident and a US resident who each lived in Britain during the BSE outbreak. To monitor the occurrence of emerging forms of CJD, such as vCJD, in the United States, the Centers for Disease Control and Prevention has been conducting surveillance for human TSEs through several mechanisms, including the establishment of the National Prion Disease Pathology Surveillance Center. Physicians are encouraged to maintain a high index of suspicion for vCJD and use the free services of the pathology center to assess the neuropathology of clinically diagnosed and suspected cases of CJD or other TSEs.

Kawasaki syndrome and factors associated with coronary artery abnormalities in California.

Background: Kawasaki syndrome (KS) occurs in children <18 years of age and is the leading cause of acquired heart disease among children in the United States. Understanding the epidemiology of KS and factors associated with coronary artery abnormalities (CAA) may lead to timely diagnosis and treatment of KS and could limit CAA. Methods: Epidemiologic characteristics, including risk factors for the development of CAA, among KS and incomplete KS patients <18 years of age with onset during 2000–2009 reported by the California Department of Public Health to the Centers for Disease Control and Prevention’s national KS surveillance system were analyzed. Results: A total of 2056 KS and incomplete KS patients <18 years of age were reported during 2000–2009. The median age of patients was 2 years; 60% of patients were male. Of 1818 patients with race information reported, 56% were white and 28% were Asian/Pacific Islander. Ninety-eight percent of patients received intravenous immunoglobulin. Of 1843 patients with information on cardiac complications, 89 (5%) had coronary artery aneurysms and 341 (19%) had CAA. Characteristics associated with the occurrence of CAA in KS patients were male sex, Asian/Pacific Islander race, age <1 year or 9–17 years, and not receiving intravenous immunoglobulin treatment before the fifth day of illness. Conclusions: This study suggests that intravenous immunoglobulin treatment before the fifth day of illness may reduce CAA among KS patients. Timely diagnosis and treatment of KS continue to be important in reducing the occurrence of cardiac complications.

Recent US Case of Variant Creutzfeldt-Jakob Disease—Global Implications

A recently diagnosed case highlights the need for continued global surveillance.

Variant Creutzfeldt-Jakob disease death, United States.

Reports of secondary bloodborne transmission of vCJD add to the uncertainty about the future of the vCJD outbreak.

Lower risk of Creutzfeldt-Jakob disease in pituitary growth hormone recipients initiating treatment after 1977.

CONTEXT Creutzfeldt-Jakob disease (CJD) caused by contaminated cadaveric pituitary-derived human GH (hGH) has been responsible for hundreds of deaths worldwide. Studies of U.S. National Hormone and Pituitary Program (NHPP) hGH recipients have found CJD only in patients treated before 1977, when a new purification procedure with column chromatography was implemented for hGH extraction. OBJECTIVE Our objective was to provide updated information on transmission of CJD to NHPP hGH recipients and determine whether recipients of hGH produced after 1977 had a significantly lower CJD risk than pre-1977 recipients. PATIENTS A total of 5570 NHPP hGH recipients were included in the study: 2099 in the pre-1977 cohort and 3471 in the post-1977 cohort. MAIN OUTCOME MEASURE We used probability distribution functions to determine whether the observed number of CJD cases in the post-1977 cohort was significantly fewer than expected if the CJD risk was equal to that of the pre-1977 cohort, controlling for treatment duration and follow-up time. RESULTS All 22 CJD cases (diagnosed from 1984-2009) occurred in the pre-1977 hGH recipients. Almost half (47.9%) of pre-1977 recipients had a treatment duration of at least 5 yr compared with only 13.8% for post-1977 recipients. Based on the rates present in the pre-1977 cohort, the probability of observing no cases in the post-1977 cohort by chance alone was low (P = 0.0019). CONCLUSIONS Risk of acquiring CJD was significantly lower for post-1977 NHPP hGH recipients than for pre-1977 recipients, suggesting that the new purification procedure in 1977 may have greatly reduced or eliminated CJD agent in hGH.