Madoka Hashido

Genome Type Analysis of Adenovirus Types 3 and 7 Isolated during Successive Outbreaks of Lower Respiratory Tract Infections in Children

ABSTRACT Adenovirus is an important cause of respiratory infections in infants and children. Fifty-one serotypes have been identified, and adenovirus type 3 (Ad3) and Ad7 have often been associated with outbreaks of severe respiratory tract infections. Each serotype can be further divided into genome types based on the patterns of digestion of their DNAs with restriction enzymes. DNA restriction analysis was performed with 56 strains of Ad3 and 98 strains of Ad7 by using 12 restriction enzymes recognizing 6 bp (BamHI, BclI, BglI, BglII, BstEII, EcoRI, HindIII, HpaI, SalI, SmaI, XbaI, and XhoI). The virus strains were isolated during outbreaks of lower respiratory tract infections in children during an 11-year period from 1990 to 2000 in Seoul, Korea. Among the Ad3 strains, seven genome types were identified; Ad3a and six novel types (Ad3a13, Ad3a14, Ad3a15, Ad3a16, Ad3a17, and Ad3a18). Multiple genome types cocirculated during outbreaks, and some of these were isolated during the 11-year observation period, while others were restricted to particular outbreaks. For Ad7, two genome types, Ad7d and Ad7l, the latter of which is a novel genome type, were identified. A shift in genome types occurred from Ad7d to Ad7l during successive outbreaks. Mortality was 3.6% among children with Ad3 infections and 18% among children infected with either of the Ad7 genome types. In conclusion, the data confirm that Ad3 genome types are more diverse than those of Ad7 and suggest that shifts of genome types may occur during successive outbreaks of Ad3 and Ad7.

An epidemiologic study of herpes simplex virus type 1 and 2 infection in Japan based on type-specific serological assays

A seroepidemiologic study of herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) was performed on Japanese adults. Serum samples collected between 1985-9 from a total of 536 healthy adults, female prostitutes, males with sexually transmitted diseases (STD), homosexual men, and pregnant women were studied by immunodot assays using HSV type-specific antigens, glycoproteins G (gG1 and gG2). HSV-1 infections correlated mostly with age and was widely prevalent among subjects < 40 years. HSV-2 prevalence varied greatly among subgroups defined by sexual activity and was associated with risk behaviours for prostitution, infection with STD, and homosexual activity. HSV-2 seroprevalence was highest among prostitutes (80%), lowest among pregnant women (7%), and intermediate in STD patients (23%) and homosexuals (24%). Because HSV-1 infection during childhood has been decreasing, primary genital HSV-2 infection, with its higher frequency of clinical manifestations, will become a greater burden to the public health in Japan.

Changes in Prevalence of Herpes Simplex Virus Type 1 and 2 Antibodies from 1973 to 1993 in the Rural Districts of Japan

Using the gG‐capture ELISA, changes in the seroprevalence of HSV‐1 and HSV‐2 from 1973 to 1993 were studied for 614 sera collected from general adults living in rural Japan. The HSV‐1 seroprevalence for men and women decreased from 75.3 and 80.6% in 1973 to 54.4 and 59.6%, respectively, in 1993. The HSV‐2 seroprevalence also decreased from 10.2 and 9.9% in 1973 to 1.8 and 1.2%, respectively, in 1993. Although the decrease in HSV‐2 prevalence seemed to be correlated with the general decrease of sexually transmitted diseases in Japan since the 1950s, these findings should not be interpreted as typical, as HSV‐2 infections are particularly known to distribute unevenly among populations, according to sexual activity and cohorts.

Molecular and serological characterization of adenovirus genome type 7h isolated in Japan

In 1996, three adenovirus type 7 (Ad7) strains were isolated from children with fever and upper respiratory diseases in Japan. Restriction endonucleases (REs) analysis and PCR amplification of the E3 7.7 kDa ORF revealed that these strains were genotype Ad7h and closely related to an Argentine Ad7h strain, which has been reported to be highly virulent and so far predominant only in South America. These strains showed weak cross-neutralizing activity and specific haemagglutination-inhibition activity to Ad3 antiserum. The present findings suggest that Ad7h in South America has spread to other parts of the world. Since the seroprevalence to Ad7 in the current Japanese population is very low due to the absence of Ad7 circulation in Japan for decades, Ad7 outbreak as a typical case of re-emerging infectious diseases is a cause for serious concern.

Detection of herpes simplex virus type-specific antibodies by an enzyme-linked immunosorbent assay based on glycoprotein G

In order to develop a simple and quantitative method to detect herpes simplex virus (HSV) type‐specific antibodies, the usefulness of an enzyme‐linked immunosorbent assay (ELISA) using HSV glycoprotein G (gG) captured on a plate by monoclonal antibodies as antigen was studied. The gG1‐ and gG2‐specific IgG antibody activities were measured by the ELISA for 54 sera which had been collected from culture‐proven genital herpes patients and pre‐characterized by an immunodot assay using purified gG antigens. Thirty control sera without antibodies against the HSV whole antigens were also included. In comparison with the immunodot assay as standard, the sensitivities of the ELISA were 88.9% (32/36) for HSV‐1 antibody and 89.2% (33/37) for HSV‐2 antibody and the specificities were both 100%. Sera taken within a few months after primary infection tended to give false negative results. The HSV type‐specific ELISA based on easy‐to‐prepare gG antigens might be useful to help improve the serological assessment of HSV infections. J. Med. Virol. 53:319–323, 1997.

Herpes Simplex Virus‐Specific IgM, IgA and IgG Subclass Antibody Responses in Primary and Nonprimary Genital Herpes Patients

To clarify the humoral immunity in herpes simplex virus (HSV) infection, HSV‐specific IgM, IgA and IgG subclass antibody responses were studied in patients with genital herpes: 17 primary, 13 recurrent and 6 nonprimary first episode. A total of 181 serum samples serially collected from the patients, 5 per patient until 213 days after the onset of disease (on average), were analyzed by an enzyme‐linked immunosorbent assay. IgGl, IgG3 and IgA were detected in all patients with primary and nonprimary infections, whereas IgG4 was detected in 74% of only those with nonprimary infections and IgG2 was detected in none. IgM was detected in 100% of the patients with primary infections, but also in 68% of those with nonprimary infections. IgA showed a peak similar to that of IgM in patients with primary infections. No significant difference was observed in the detection rate or pattern of antibody responses between the recurrent and nonprimary first episode infections, nor between the HSV‐1 and HSV‐2 infections. These findings may be useful to improve the diagnostic potential of HSV serology.

EPIDEMICS OF ASEPTIC MENINGITIS DUE TO ECHOVIRUS 30 IN JAPAN

Two rages of epidemic of aseptic meningitis (AM) due to echovirus 30 (E30) in Japan were analyzed with respect to two sources of information, AM incidence and E30 isolation, both gathered through the National Epidemiological Surveillance of Infectious Diseases. The first E30 epidemic spread throughout Japan in 1983 and ceased within the year. The second epidemic, starting in 1989, continued for the three successive years, and in the last year, 1991, the total E30 reports numbered 4,061, the largest number of a single virus type ever reported. Although the epidemic showed temporal and geographical shift and lasted for one or two years in some areas, most laboratories reported the largest number of E30 isolation in 1991. Among E30-yielding cases with clinical information during 1982-1992, the associating frequency with AM was as high as 82.5%. Other central nervous system involvements such as encephalitis, myelitis, encephalomyelitis and/or paralysis were reported in 36 E30-yielding cases and their monthly and age distributions were different from those of AM cases. The proportion of such disease among E30-yielding cases (0.60%) was close to that of other enteroviruses (0.56%). During the epidemics, E30 was isolated more frequently from cerebrospinal fluid than was E4 or E9 which prevailed coincidentally. E30 was most frequently isolated from cases of 4-7 years of age, sharing the common characteristic pattern of age distribution with other enteroviral meningitis. E30-yielding cases, however, involved a large number of older age groups than those of other enterovirus infections, and this tendency was the most pronounced in the first epidemic year, 1983. The contribution of these E30 epidemics on the yearly trend of clinically reported AM incidence and on the shift of its age distribution was also analyzed.

Evaluation of an enzyme-linked immunosorbent assay based on binding inhibition for type-specific quantification of poliovirus neutralization-relevant antibodies.

To detect neutralization‐relevant antibodies against 3 types of poliovirus (PV) without using tissue cultures and live viruses, an enzyme‐linked immunosorbent assay (ELISA) based on monoclonal antibody‐binding inhibition was evaluated using sera from 80 vaccinated Japanese children and 60 Pakistani poliomyelitis patients. Compared with the neutralization test, the sensitivity of the inhibition ELISA was 100% (111/111) for detection of anti‐PV1 antibody, 98.3% (118/120) for anti‐PV2, and 96.5% (82/85) for anti‐PV3, and the specificity was 93.1% (27/29), 100% (20/20), and 92.7% (51/55), respectively. Thus, the inhibition ELISA showed excellent potential as a seroepidemiologic tool in both vaccinated and naturally‐infected populations.

Prevalence of Herpes Simplex Virus Type 1- and 2- Specific Antibodies among the Acute, Recurrent, and Provoked Types of Female Genital Herpes

Sixty‐eight sera from the acute, recurrent, and provoked types of female genital herpes were compared for the seroprevalence of herpes simplex virus (HSV) types 1 and 2 by immunodot assay using HSV glycoprotein G. In the HSV‐1‐isolated patients, no HSV‐2 antibodies were detected, whereas in the HSV‐2‐isolated patients, HSV‐1 seroprevalence was 9% for the acute type, 89% for the provoked type (P< 0.005), and 55% for the recurrent type (P<0.05). The natural history of female genital herpes and the possible protective role of pre‐existing antibodies in preventing the acquisition or clinical manifestation of a subsequent HSV infection are discussed.

Class-Specific Antibody Response in Acyclovir-Treated and Adenine Arabinoside-Treated Patients with Primary Genital Herpes Simplex Virus Infection

Herpes simplex virus (HSV) class‐specific antibody responses after primary genital herpes infection were evaluated with an enzyme‐linked immunosorbent assay (ELISA) in 16 patients treated with acyclovir (ACV), given orally, and 17 patients treated with adenine arabinoside (Ara‐A), given topically. ACV significantly suppressed the levels of IgM, IgA, and IgG. In the ACV‐treated patients, IgM and IgG were not detected in 4 of the 16 and in 1 of the 16 patients, respectively. We must take into account this suppressive effect of ACV on antibody responses, especially on the IgM response, when serodiagnosis of HSV infection is made.