Kawasaki disease (KD) is an acute multisystem vasculitis of unknown etiology that primarily affects young children and predominantly involve the coronary arteries.

We previously suggested that gut bacteria may be involved in the onset of KD. In this study we have evaluated the production of heat-shock proteins (HSP) and superantigens (sAgs) by microorganisms isolated from the jejunal mucosa of 19 children with KD children in the acute phase and 15 age-matched control children. We found 13 strains of Gram-negative microbes from patients with KD which produced large amounts of HSP 60 and induced proinflammatory cytokine production by peripheral blood mononuclear cells. The Gram-negative microbes also elicited endogenous HSP 60 production, leading to anti-inflammatory IL-10 secretion. We also identified 18 strains of Gram-positive cocci which had suparantigenic properties and which induced the expansion of Vb2 T-cells in vitro. All of the bacteria were antibiotic-resistant. These data strongly suggest that sAg and HSP productions by gut bacteria might be involved in KD.

The pandemic influenza A H1N1 (pdm H1N1) emerged in California and Mexico in April 2009. There was initial fear that the case fatality rate (CFR) could be 2% as reported in Mexico, but now it is clear that the pdm H1N1 causes a disease no more severe than seasonal influenza with a CFR between 0.1 to 0.2%. However it could cause serious morbidities and deaths in pregnant women, obese persons and patients with chronic underlying disease.

Early animal studies using ferrets, mice and macaques of pdm H1N1 infection suggest more severe illness compared with seasonal influenza, although much less virulent than H5N1 or the 1918 pdm Spanish flu virus. However later studies using human immune cells and respiratory epithelial tissues ex vivo suggest similar capacity of pdm H1N1 for cytokine induction as seasonal influenza virus, but differs in its ability to replicate in human conjunctiva. Post-mortem studies of patients died from pdm H1N1 revealed tracheitis, bronchiolitis and diffuse alveolar damage. Viral antigen was seen most commonly in the epithelium of tracheobronchial tree. Marked expression of TLR-3 and IFN-g, with CD8+T cells and granzme B+ cells were noted in the lung, with no evidence of viral dissemination outside the lung. Evidence of secondary bacterial superinfection with Streptococcus pneumoniae and Staphylococcus aureus was common.

Susceptibility to pdm H1N1 is less in elderlies over 65 years old than the younger population because of their higher prevalence of cross-reacting antibodies. The overall mild disease severity of pdm H1N1 influenza may be related to pre-existing T-cell memory due to the conservation of a large fraction of T-cell epitopes between seasonal influenza and pdm H1N1. There is also some evidence to suggest people deficient in IgG2 may be more susceptible to pdm H1N1.We are interested in defining cross-reacting T cell responses as well as the role of mannose binding lectin in pdm H1N1.

From July 24, 2009 to Dec 4, 2009, we collected cases infected with 2009 novel H1N1. Their demographics, underlying medical conditions, clinical data, receipt of antiviral therapy, need for intensive care and outcome were analyzed to find clinical features and risk factors of hositalization and severe infections.

The risk factors associated with hospitalization were age less than 1 year old and underlying disease including cardiovascular disease, hematological and oncological disease, and immunosuppression host. Of the inpatients, obesity, dyspnea, C-reactive protein (CRP) >3 mg/dL, having pleural effusion, and delayed antiviral therapy were significantly associated with the need of intensive care and/or death. Cautious monitoring of these parameters and early treatment may improve the outcome. 

We also enrolled novel H1N1 patients and their household members to undergo clinical evaluations, virological studies and questionnaire-based interviews between August 2009 and November 2009. Novel H1N1 virus infection was defined as either positive H1N1 RT-PCR or serum hemagglutinin inhibition (HAI) titer ≥1:40. Clinical manifestations and outcomes were analyzed and household transmission rate was calculated. Eighty seven families including 87 index cases and 223 household members were enrolled. The mean (SD) age of index cases was 10.6 (7.2) years and that of household contacts 33.8 (17.9) years. The overall novel H1N1 virus transmission rate to household contacts was 27% (60/223): 61% (35/57) to household children and 15% (25/166) to household adults. The transmission rates were 63% (35/56) for siblings, 14% (20/138) for parents, 22% (4/18) for grandparents, and 20% (1/5) for uncles and aunts, respectively (p<0.001). Of 115 infected children, 4 (3%) were asymptomatic, 101 (88%) patients received outpatient medical care, and 10 (9%) patients were hospitalized: 2 of them had pneumonia, 3 had bronchopneumonia, 2 suffered from asthma exacerbation, and 1 had complication of aseptic meningitis. Of 32 infected adults, 25 (78%) were symptomatic but no adults needed hospitalization.

In conclusion, the overall household transmission rate of novel H1N1 virus was 27% and the rate to household children was 4 folds high as that to household adults (61% v.s.15%). Infected children significantly tended to be symptomatic and hospitalized than infected adults.