Enterovirus 71 infection with CNS involvement and cardiopulmonary failure may be associated with neurologic sequelae, delayed neurodevelopment, and reduced cognitive functioning. Children with CNS involvement without cardiopulmonary failure did well on neurodevelopment tests. (ClinicalTrials.gov number, NCT00172393 [ClinicalTrials.gov].).

Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

ABSTRACT:We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p ϭ 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (␥-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular ␥-interferon reported from the United States, Europe, Australia, Japan, Brazil and Malaysia (1-10), since it was originally characterized from a 1969 California outbreak (1). Before 1998, there were three large outbreaks with dozens of fatal cases occurring in Bulgaria, Hungary, and Malaysia (l975, l978, and 1997, respectively) (3,5,10). The largest and most severe EV71 epidemic to date occurred in Taiwan in 1998 (11-16). A total of 129,106 cases of hand-foot-and-mouth disease and herpangina (HFMD/HA) were reported (15). Severe neurologic complications and/or pulmonary edema were reported in 405 cases, and 78 children died (15).Most EV71 fatalities were cases of fulminant pulmonary edema (15). However, EV71 infection causes very diverse symptoms, ranging from none (about 71%) to fatality (about 0.05%) (17,18). It remains unknown why different hosts of the same EV71 infection have such a range of clinical outcomes (17,18). Perhaps this range is related to virulence or load of the virus, or particular host factors. To date no relationship has been found between EV71 genotypes and clinical outcome (19,20), and EV71 virulence factors have not been clarified. It is possible that host factors, especially host immune response, may be of ultimate importance to clinical outcome.To clarify severe EV71 infection pathogenesis, we investigated factors of cellular versus humoral immune response and correlated this with clinical outcome. SUBJECTS AND METHODS Subjects. After National Taiwan University Hospital Research EthicsCommittee approved this study and informed parental consent was obtained, 30 EV71 cases of different severity were enrolled. EV71 infection was confirmed by positive EV71 isolation and/or positive EV71 specific IgM at the onset of their disease.The CNS involvement was indicated in four types of cases. Those with aseptic meningitis had headache and irritability along with cerebrospinal fluid (CSF) pleocytosis (Ͼ5 leukocytes/L) and without an altered level of consciousness. The second type of cases involved encephalitis had altered level of consciousness plus cerebrospinal fluid (CSF) pleocytosis. Poliomyelitislike syndrome was ...

A large outbreak of Legionnaires' disease caused by a cooling tower occurred in a medically vulnerable community. The outbreak prompted enactment of a new city law on the operation and maintenance of cooling towers. Ongoing surveillance and evaluation of cooling tower process controls will determine if the new law reduces the incidence of Legionnaires' disease in New York City.

Kawasaki disease (KD) is an acute systemic vasculitis syndrome that primarily affects infants and young children. Its etiology is unknown; however, epidemiological findings suggest that genetic predisposition underlies disease susceptibility. Taiwan has the third-highest incidence of KD in the world, after Japan and Korea. To investigate novel mechanisms that might predispose individuals to KD, we conducted a genome-wide association study (GWAS) in 250 KD patients and 446 controls in a Han Chinese population residing in Taiwan, and further validated our findings in an independent Han Chinese cohort of 208 cases and 366 controls. The most strongly associated single-nucleotide polymorphisms (SNPs) detected in the joint analysis corresponded to three novel loci. Among these KD-associated SNPs three were close to the COPB2 (coatomer protein complex beta-2 subunit) gene: rs1873668 (p = 9.52×10−5), rs4243399 (p = 9.93×10−5), and rs16849083 (p = 9.93×10−5). We also identified a SNP in the intronic region of the ERAP1 (endoplasmic reticulum amino peptidase 1) gene (rs149481, pbest = 4.61×10−5). Six SNPs (rs17113284, rs8005468, rs10129255, rs2007467, rs10150241, and rs12590667) clustered in an area containing immunoglobulin heavy chain variable regions genes, with pbest-values between 2.08×10−5 and 8.93×10−6, were also identified. This is the first KD GWAS performed in a Han Chinese population. The novel KD candidates we identified have been implicated in T cell receptor signaling, regulation of proinflammatory cytokines, as well as antibody-mediated immune responses. These findings may lead to a better understanding of the underlying molecular pathogenesis of KD.