Ken Tokugawa

Exanthema subitum and human herpesvirus 6 infection : clinical observations in fifty-seven cases

Exanthema subitum had been speculated to be a viral disease although its pathogen is unknown. Human herpesvirus 6 (HHV-6), first isolated in 1986, was proved by Yamanishi et al. to be the causal agent of exanthema subitum. To evaluate the role of HHV-6 as the causal agent in clinically diagnosed exanthema subitum, we tested for HHV-6 antibody in 57 infants with clinical exanthema subitum and exanthema subitum-like rash without fever. Of the 53 patients with clinical exanthema subitum 43 showed seroconversion or a significant rise in antibody titer to HHV-6, 7 were seropositive without significant rise and 3 remained seronegative. The clinical manifestations of these 43 infants with serologically confirmed HHV-6 infection were consistent with the classical characteristics of exanthema subitum. The 4 patients with atypical exanthema subitum showed significant rises in antibody titer. Our results therefore show that the majority of cases with typical clinical manifestations of exanthema subitum had HHV-6 infection. Most cases with HHV-6 infection had the typical clinical course of exanthema subitum, and a few cases might show an afebrile exanthema subitum-like rash.

Trivalent cold recombinant influenza live vaccine in institutionalized children with bronchial asthma and patients with psychomotor retardation.

Twenty asthematic children and 48 patients with severe psychomotor retardation were inoculated intranasally with trivalent cold-adapted recombinant (CR) influenza vaccine containing CR-125 (H1N1), CR-159 (H3N2) and CRB-117 (B). The vaccinees were mostly seropositive. Severe adverse reactions or asthmatic attacks were not observed, but 7 (15%) of 48 vaccinees with severe psychomotor retardation developed mild to moderate fever. Significant antibody responses in hemagglutination-inhibition tests were demonstrated in 33 (49%) vaccinees to CR-125, 20 (29%) to CR-159 and 8 (12%) to CRB-117. Two nosocomial outbreaks of influenza were observed in the subsequent winter. During an outbreak with H3N2 in one ward of severe psychomotor retardation patients. 2 (11%) of 18 vaccinees became infected compared with 10 (48%) of 21 placebo controls in the same ward (P < 0.05). In the other outbreak, with influenza B virus, 2 (14%) of 14 vaccinees and 13 (52%) of 25 controls in the ward for asthmatic children were infected (P < 0.05). The results indicate that trivalent CR vaccine is safe and effective against nosocomial outbreaks of influenza.

Immunization of institutionalized asthmatic children and patients with psychomotor retardation using live attenuated cold-adapted reassortment influenza A H1N1, H3N2 and B vaccines

Live attenuated cold-adapted reassortant (CR) influenza virus vaccines were evaluated in institutionalized asthmatic children and severe psychomotor-retarded (SPR) patients. Almost all the vaccinees were seropositive to the vaccine strains before immunization. Trivalent CR vaccine (containing A H1N1 (CR-125), A H3N2 (CR-149) and B (CRB-117)), bivalent CR vaccine (CR-125 and CR-149) and monovalent CRB-117 were inoculated to 19 asthmatic children and 36 and 16 SPR patients, respectively. Overall 49, 22, and 11% of vaccinees were infected by A H1N1, A H3N2 or B vaccine viruses, respectively, as indicated by significant haemagglutination-inhibition (HI) antibody titre rises 4 weeks after inoculation. No severe adverse reactions associated with CR vaccination were observed in the handicapped patients. A nosocomial outbreak of influenza A H1N1 occurred in the ward with asthmatic children, but none of the 19 CR-trivalent vaccinees became infected. However, five of 20 non-vaccinees in the same ward, and ten of 30 vaccinees in another ward that received inactivated split vaccine became infected. The CR vaccines demonstrated significant protective effects against natural exposure to the A H1N1 virus, and were well tolerated and safe when given to patients with bronchial asthma and severe psychomotor retardation.

Pharyngoconjunctival fever caused by adenovirus type 11.

Among a group of hospitalized children in Fukuoka, southern Japan, an epidemic of pharyngoconjunctival fever-like disease caused by adenovirus type 11 was observed in the autumn of 1988. Of the 47 children studied 38 were seronegative in neutralizing antibody for adenovirus type 11 before the epidemic, and sero-conversion occurred in 16 (42%) including 5 subclinical cases. Of the 11 symptomatic patients the incidences of conjunctivitis, pharyngitis and fever were 91, 64 and 46%, respectively. Four patients (36%) had all three symptoms. Fifteen patients (94%) were boys. The sex predominance and high incidence of conjunctivitis suggested that infection may have been transmitted in the large bathroom where boys took baths together.

Hemolytic Anemia Following Postnatally Acquired Rubella During the 1975-1977 Rubella Epidemic in Japan

Hemolytic anemia following postnatally acquired rubella first was reported by Sato et al. in 1977. Thirteen cases of hemolytic anemia (including two cases of hemolytic uremic syndrome) following postnatally acquired rubella infection reported in a nationwide epidemic of rubella in Japan in 1975-1977 are reviewed in this article, and another case is added. Clinical symptoms of hemolytic anemia occurred 2 to 6 days from the onset of rubella rash. Direct Coombs test was positive in three of the 11 cases tested, and the indirect test was positive in two of the 13 cases. Hemolytic anemia should be considered as a complication of postnatally acquired rubella, though to date, it has only been reported in Japan.

Perinatal viral infections

Among the TORCH agents, the occurrence of rubella and human T-lymphotropic virus type 1 (HTLV-1) in Japan were studied. Rubella epidemics occurred throughout Japan from 1964 to 1969 and from 1975 to 1979. Low prevalences of CRS were observed in northeastern Japan, and high prevalences in southwestern Japan, with the highest in Okinawa. These conditions could be explained by the lower rate of rubella H1 antibody in the female population of southwestern Japan. Time of maternal rubella was in the gestational age interval from 26 to 57 days for cataract, from 25 to 62 days for heart disease and from 16 to 131 days for deafness. HTLV-1 is the causative agent of adult T-cell leukemia. Main route of transmission of this virus is mother-to-child transmission, through breast milk. Among the 311 mother-child pairs in Okinawa, 65 mothers (20.9%) and 10 children (3.2%) were seropositive for HTLV-1. Ten (15.4%) of the 65 seropositive mothers had seropositive children. These children had acquired their HTLV-1 antibodies by the age of 3 years. A significant difference existed between the prevalence rate of HTLV-1 antibodies in mothers and children.

Growth Hormone in Children With Congenital Rubella Syndrome

Six 10‐year‐old boys with congenital rubella syndrome (CRS) were studied for their growth hormone levels as well as other endocrinological functions. All cases were observed to show normal responses after the insulin, arginine, or the propranolol‐glucagon tolerance tests. The other hormonal values were also observed to be normal. These results suggested that the postnatal growth retardation observed in CRS is not due to an endocrinological abnormality.

Long-term sequential changes of antibody to p40tax in HTLV-I carrier mothers and children

Antibody to p40tax (anti‐p40tax) in serum specimens obtained sequentially from a human T cell lymphotropic virus type I carrier population of mothers and children were assayed. The prevalences of anti‐p40tax at the initial sampling were 88% (7/8) in children and 55% (16/29) in mothers. Two of the seven positive children lost their anti‐p40tax during the investigation period, resulting in a final prevalence of 63% (5/8) in children. However, anti‐p40tax status was constant in all the 22 mothers with multiple serum samples (15 remained positive and seven remained negative). A decline in the absorbance value of EIA for anti‐p40tax was observed in seven of the 15 anti‐p40tax positive mothers. This decline may result in the disappearance of anti‐p40tax in some of them.

A case of congenital herpes zoster.

A 5 day old girl was transferred to the pediatric ward of Kyushu University Hospital because of papules noted since birth. The papules were distributed on her skin corresponding to the dermatomes innervated by the left Th1‐Th3 and the left L1‐L3. Varicella‐zoster virus antigens were detected in scrapings of incised papules. The diagnosis of herpes zoster was made and acyclovir (ACV) was administered. She responded to ACV well, but she experienced a recurrence twice after discontinuation of ACV. This is the first report of ‘congenital herpes zoster’, which supports the hypothesis that varicella embryopathy is the sequelae of herpes zoster in utero.

Prevention of horizontal transmission of hepatitis B: efficacy of hepatitis B immunoglobulin and vaccine in an institution for the handicapped

In a Japanese institution for the handicapped with confirmed continuous outbreaks of hepatitis B virus (HBV) infection by horizontal nosocomial transmission, 29 susceptible subjects (8 institutionalized children and 21 medical staff) were injected intramuscularly with anti-human HBs immunoglobulin (HB Ig) and subcutaneously with HB vaccine. All cases acquired HBs antibody after injection of HB Ig and seropositivity for HB after the third inoculation of HB vaccine was 78.6%. No new case of HB occurred among the study population throughout the period investigated. This suggested the effectiveness of HB Ig and HB vaccine in the prevention of horizontal nosocomial transmission of HBV.