Hitoshi Ochiai

Single genotype of measles virus is dominant whereas several genotypes of mumps virus are co-circulating.

We have reported that in Japan measles virus strains have been classified into three distinct different genotypes (C1, D3 and D5) under the new international genotype classification since 1984. Similarly, mumps virus strains have been divided into two genotypes with three subtypes (B1, B2, B3, and D) under the proposed international classification since 1976. To differentiate these genotypes we developed a restriction fragment length polymorphism assay in the hemagglutinin (H) region for measles virus and in the hemagglutinin‐neuraminidase (HN) region for mumps virus to facilitate the expanded molecular epidemiology. In the Sapporo 1995/1996 measles outbreak, all 26 strains were classified as D5. Among 32 samples from patients with measles from 1994 to 1997 in Tokyo, 28 were identified as D5 and four were D3; these D3 strains were ascertained as a same hospital acquired infection. Among 45 strains obtained in the Tokyo 1999 outbreak, 38 were D3 and the remaining seven were D5. The dominant genotype of measles in Tokyo has replaced from D5 to D3 similar to the Chicago1/89 strain. We obtained 220 samples from patients with mumps from 1993 to 1997 and they were classified into one strain of B1, 14 strains of B2, 151 strains of B3, and 54 strains of D. Therefore, we suggest that two or three subtypes of mumps virus are co‐circulating with a different geographic pattern in genotype distribution, whereas a single measles virus genotype is dominantly observed, showing different epidemiological patterns. J. Med. Virol. 62:278–285, 2000.

Markedly elevated levels of β2-microglobulin in urine with measles viruria in patients with measles

BACKGROUND Measles is a highly contagious infectious disease in children. However, the pathogenesis has not yet been fully defined since susceptible cells to measles virus (MV) had not been developed. Recently, B95a cells, which are very susceptible to MV, have been reported. OBJECTIVES To evaluate measles viruria in patients with measles, isolation of MV from urine was performed using B95a cells. STUDY DESIGN Isolation of MV from supernates or sediments of urine in patients with measles was performed using B95a cells. The levels of beta2-microglobulin (MG) in urine and serum were also measured. RESULTS MV was isolated from either supernates or sediments of urine. MV was isolated from 10 of 11 samples (91%) within 2 days of the appearance of a rash. MV was isolated from supernates of urine for up to 4 days after the appearance of a rash, and from sediments for up to 5 days. The levels of urinary beta2-MG were elevated within 2 days of the appearance of a rash. The levels of urinary beta2-MG with measles viruria were significantly higher compared to those without measles viruria. CONCLUSIONS Measles viruria may occur early in all patients with measles and elevated levels of urinary beta2-MG in patients with measles may be the consequence of tubular injury.

Laboratory Diagnosis of Breakthrough Varicella in Children.

Background: Breakthrough varicella (BV) develops in vaccinated persons as a result of infection by wild-type varicella-zoster virus more than 42 days after varicella vaccination. The clinical symptoms are atypical, and clinical diagnosis can be difficult. We investigated laboratory-based diagnostic methods that are relatively simple and highly precise to conduct accurate surveillance. Subjects and Methods: We enrolled 42 patients with suspected BV at 2 pediatric hospitals and performed a real-time polymerase chain reaction (PCR) on the skin lesions to confirm the BV diagnosis. We performed PCR on saliva and blood collected during the acute phase, as well as direct fluorescent antibody (DFA) imaging on lesions, and measured varicella-zoster virus immunoglobulin (Ig) G and IgM during the acute and convalescent phases. Results: We confirmed the BV diagnosis in 31 of 42 enrolled patients. The sensitivity of DFA imaging of the lesion, and PCR of saliva and blood were 93.5%, 87.1% and 61.3%, respectively. IgM was detected in 12.9% of patients during the acute phase and in 65.5% during the convalescent phase. IgG increased more than 4-fold in 86.2% of patients between the acute and convalescent phases. The sensitivity and specificity of the assay were 83.9% and 81.8%, respectively, when the diagnostic criteria for IgG were set to greater than 20 during the acute phase. Conclusions: The gold standard of laboratory-based diagnosis of BV has been the PCR of samples taken from lesions. However, DFA of the lesion showed equivalent sensitivity when compared with PCR. PCR using saliva samples is an effective, noninvasive method of diagnosis. We found that high values of IgG during the acute phase can aid in the diagnosis of BV.

Species differences in circulation and inflammatory responses in children with common respiratory adenovirus infections

Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but previous epidemiological studies lacked analysis of the characteristics of the inflammation. Consecutive patients <13 years old with acute febrile illness during a 2‐year period were tested. HAdV strains were isolated from nasopharyngeal swabs, and molecular identification was performed by hexon, fiber, and species‐specific PCR methods. Blood inflammatory markers, including the white blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187 patients were enrolled, and HAdV types were identified from 175 patients (93.5%). Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%, followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected predominantly in 1‐year‐old, whereas B and E were in older ages. Species C and B had seasonal circulation patterns, but E was found in only one season during the 2‐year study period. The WBC count was highest in patients with species C. Eleven of the 29 tested serum cytokines were detected. Seven kinds, including G‐CSF, IL‐6, and TNF‐α, were elevated in species C infections, whereas IL‐10 was lowest in species C. Species differences in inflammatory responses, especially regarding serum cytokines were described in common pediatric HAdV infections. Species C causes the strongest inflammatory responses in young children.