Transmission of acute infectious illness among cases of Kawasaki disease and their household members.

BACKGROUND/PURPOSE: Kawasaki disease (KD) is a disease of unknown cause and the causative agent is most likely to be infectious in nature. To investigate the household transmission pattern of infectious illness and etiology, we thus initiated a prospective case and household study. METHODS: We enrolled KD cases and their household members from February 2004 to September 2008. The KD cases and their household members accepted questionnaire-based interviews of the contact history, signs of infection, and symptoms to check whether clusters of infectious illness occurred. RESULTS: A total of 142 KD cases and 561 household members were enrolled. Among the 142 KD cases, 136 cases (96%) were typical KD, and six (4%) were atypical KD. Of the 561 household members, 17% were siblings, 46% were parents, 18% were grandparents, and the others were cousins or babysitters. Prior to the onset of their KD illness, 66% (94/142) KD cases had contact with ill household members. On the same day of the onset of KD cases' illness, 4% (6/142) KD cases had household members with illness. After KD cases' disease onset, 70% (100/142) KD cases had at least one other family member with illness. Overall, 61% (343/561) of all the household members had acute infectious illness during KD cases' acute stage, and 92% (130/142) of the families had clusters of infectious illness. CONCLUSION: A total of 66% KD cases had positive contact with ill household members prior to their disease onset and 92% of families had clusters of infectious illness, so KD is strongly associated with infections.

Neurodevelopment and cognition in children after enterovirus 71 infection.

BACKGROUND: Enterovirus 71 is a common cause of hand, foot, and mouth disease and encephalitis in Asia and elsewhere. The long-term neurologic and psychiatric effects of this viral infection on the central nervous system (CNS) are not well understood. METHODS: We conducted long-term follow-up of 142 children after enterovirus 71 infection with CNS involvement - 61 who had aseptic meningitis, 53 who had severe CNS involvement, and 28 who had cardiopulmonary failure after CNS involvement. At a median follow-up of 2.9 years (range, 1.0 to 7.4) after infection, the children received physical and neurologic examinations. We administered the Denver Developmental Screening Test (DDST II) to children 6 years of age or younger and the Wechsler intelligence test to children 4 years of age or older. RESULTS: Nine of the 16 patients with a poliomyelitis-like syndrome (56%) and 1 of the 5 patients with encephalomyelitis (20%) had sequelae involving limb weakness and atrophy. Eighteen of the 28 patients with cardiopulmonary failure after CNS involvement (64%) had limb weakness and atrophy, 17 (61%) required tube feeding, and 16 (57%) required ventilator support. Among patients who underwent DDST II assessment, delayed neurodevelopment was found in only 1 of 20 patients (5%) with severe CNS involvement and in 21 of 28 patients (75%) with cardiopulmonary failure (P<0.001 for the overall comparison). Children with cardiopulmonary failure after CNS involvement scored lower on intelligence tests than did children with CNS involvement alone (P=0.003). CONCLUSIONS: 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].).

An outbreak of coxsackievirus A16 infection: comparison with other enteroviruses in a preschool in Taipei.

BACKGROUND/PURPOSE: The transmission rate of enteroviruses in young children remains unclear. Therefore, we carried out active surveillance in preschool children to investigate the transmission rate and clinical manifestation of enteroviruses. METHODS: From September 2006 to December 2008, we monitored infectious diseases in children 2(-3 years of age) in a preschool in Taipei. If any child had a febrile illness or symptoms/signs of enteroviral infection [e.g. herpangina or hand-foot-and-mouth disease (HFMD)], we performed viral isolation and enterovirus polymerase chain reaction. VP1 sequencing was performed to define their serotypes. We also collected clinical data and analyzed transmission rates. RESULTS: There were eight episodes of enterovirus infection during the study period. The serotypes included coxsackievirus A4 (CA4), CA2 and CA16. The transmission rates of CA4 and CA2 among children in same class were 26% and 35%, respectively. Between November 28 and December 12, 2008, 13/21 (61.9%) children contracted herpangina and/or HFMD. The average age was 2.82 (range, 2.43-3.39) years. CA16 was detected in 10/13 (76.9%) of the throat swabs by polymerase chain reaction VP1 genotyping. Compared with previous CA2 and CA4 outbreaks, CA16 had a significantly higher transmission rate (p = 0.035) and resulted in more cases of HFMD (p < 0.001). The transmission duration of coxsackie A viruses within the same class ranged from 12 to 40 days. CONCLUSION: Compared with CA2 and CA4, CA16 infections resulted in more cases of HFMD and had significantly higher transmission rates in preschoolers.

Attention-deficit/hyperactivity-related symptoms among children with enterovirus 71 infection of the central nervous system.

BACKGROUND: No study has investigated the association between enterovirus 71 central nervous system infection and symptoms related to attention-deficit/hyperactivity disorder. In this study we evaluated attention-deficit/hyperactivity disorder-related symptoms and internalizing problems as long-term sequelae resulting from enterovirus 71 central nervous system infection in children. METHODS: We enrolled 86 children 4 to 16 years old with virus-culture-confirmed enterovirus 71 infection and central nervous system involvement diagnosed 3 to 7 years before the study and 172 control subjects, matched for age, gender, and parents' education levels. Their mothers and teachers were asked to report on possible attention-deficit/hyperactivity disorder-related symptoms, and their mothers were asked to report on possible internalizing problems. All of the children previously infected with enterovirus 71 received intelligence tests. RESULTS: Forty-two (49%) of the children previously infected with enterovirus 71 had had viral meningitis; 35 (41%) had severe central nervous system involvement, such as encephalitis, poliomyelitis-like syndrome, or encephalomyelitis; and 9 (10%) had cardiopulmonary failure and central nervous system involvement. The children previously infected with enterovirus 71 had higher scores than matched control subjects on teacher- and mother-rated scales of inattention, hyperactivity-impulsivity, oppositional symptoms, and attention-deficit/hyperactivity disorder index. The rate of elevated attention-deficit/hyperactivity disorder-related symptoms among children with enterovirus 71 central nervous system infection was 20%, whereas that rate among matched control subjects was only 3%. They also had more internalizing problems. Their verbal and performance IQs, as well as verbal comprehension indices, were significantly inversely correlated with symptoms of inattention, hyperactivity-impulsivity, and attention-deficit/hyperactivity disorder index scores. CONCLUSIONS: Enterovirus 71 central nervous system infection may affect long-term regulation of attention and emotion and cause hyperactivity-impulsivity in children.