131

Early Human Development, 29 (1992) 131-136 Elsevier Scientific Publishers Ireland Ltd.

EHD 01262

Perinatal viral infections K. Ueda, K. Tokugawa and K. Kusuhara Department

of Pediatrics,

Faculty

of Medicine,

Kyushu

University.

3-l-l

Maidnshi

Higashiku.

Fukuoka

812

(Japan)

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 Hl 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 13 1 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 (3.2O/) 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. Key worh: rubella; human T-lymphotropic TORCH agents

virus type-l; perinatal infection; virus;

Introduction Researches on perinatal viral infections has been started since the report on the discovery of ‘congenital cataract following German measles in mother’ by Gregg [l] in 1941. And this year, 1991, represents the 50th anniversary of this discovery. In this paper, general aspects on perinatal viral infections were reviewed and the Correspondence ro: K. Ueda, Department of Pediatrics, Faculty of Medicine, Kyushu University, 3-l-l Maidashi Higashiku, Fukuoka 812, Japan.

0378-3782/92/$05.00 0 1992 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland

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epidemiologic features of rubella and human T-lymphotropic were presented.

virus type 1 in Japan

General aspects TORCH agents Pathogens for perinatal infection have been grouped under the term TORCH agents, which is an acronym named by Nahmias [2] in 1971. ‘TORCH’, derived from the words toxoplasma, others, rubella, cytomegalovirus and herpes simplex virus. Nowadays, important viruses of the TORCH agents are rubella virus, cytomegalovirus, herpes simplex virus, hepatitis B virus, varicella-zoster virus, enteroviruses specially coxsackieviruses B, parvovirus B 19, human immunodeficiency virus (HIV) and human T-lymphotropic virus type 1 (HTLV-1). Period of infections The viral infections may occur at several different intrauterine and neonatal life periods, those are in the utero (congenital infection), at birth (natal infection) and after birth but during the neonatal period (postnatal infection). For rubella virus, cytomegalovirus, varicella zoster virus and parvovirus B19, their clinical important route of infection is intrauterine infection and for herpes simplex virus, hepatitis B virus and enteroviruses, their important route is at birth or postnatal infection. The important route of infection for HTLV-1 is through breast feeding [3-41. HIV infections occur in intrauterine, at birth and postnatal infection are all important routes. Fetal outcomes Congenital infections may result in resorption of the embryo, abortion, stillbirth, congenital malformation, prematurity, intrauterine growth retardation, acute disease apparent at birth or shortly after, asymptomatic infection in the neonatal period but a persistent postnatal infection with neurologic sequelae later in life, or normal infant without apparent sequelae. Natal or postnatal infections may cause acute systemic illness leading to death, persistent infection with late sequelae, selflimited disease with no discernible damage or asymptomatic infection [5]. Congenital Rubella Syndrome (CRS) in Japan Distribution of CRS in Japan Extensive rubella epidemics occurred in the United States in 1964 and 20 000 infants with CRS were born [6]. Rubella epidemic occurred throughout Japan from 1964 to 1969. An exceptionally high incidence of CRS *-‘as noted only in the Okinawa Islands or Ryukyu under the rule of the United States [7], but, the incidence was low in Japanese mainland [S]. However, the low incidence of CRS in Japan was due to a lack of notification system for CRS in Japan. Our nationwide survey on deaf children with history of maternal rubella in special schools for the deaf in Japan revealed that there were 365 cases with CRS. Most of the cases were born between 1965 and 1969 and between 1975 and 1979. This indicated that they were born after the 1965-1969 and the 1975-1977 rubella epidemics, respectively.

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Prevalence in CRS cases per 100 000 population in the Japanese mainland was 0.30 cases and that in Okinawa was 43.8 cases. Low prevalences were observed in northeastern Japan, high prevalences in southwestern Japan, with the highest in Okinawa. These conditions could be explained by the higher rate of rubella HI antibody in the female population of northeastern Japan [9]. Our retrospective seroepidemiologic investigation indicated that the high incidence of CRS in Okinawa was due to a low seropositivity and a resultant high attack rate of rubella among pregnant women (the estimated rate was 25-30%), rather to a hypothetical virulent teratogenic strain of rubella virus [7]. Time table of rubella embryopathy

We analyzed 55 cases of CRS born in southern Japan including Okinawa and Seattle in the United States in which the maternal last menstrual period and date of appearance of the rash were exactly recorded. Patients with cataract numbered 13 and the time of maternal rubella was estimated to be from 26 to 57 days of gestational age. Patients with heart disease numbered 18 and the time of maternal rubella was from 25 to 62 days of gestational age. Patients with deafness numbered 46; the time of maternal rubella was from 16 to 131 days of gestational age. Almost all infants born to mothers who had had rubella within six weeks after implantation had two or three manifestations of cataract, patent ductus arteriosus (PDA) and deafness. These data do not indicate that rubella virus does not act teratogenically on the human embryo before implantation, but rather, in those cases, the infected embryo usually does not survive. Cataract and PDA infrequently resulted when exposure was beyond 63 days of gestation [lo]. Rubella vaccine policy

The immunization program for rubella vaccine was started in the United States and Europe in 1969 and in Japan in 1977. The American policy, of immunizing mainly the children, succeeded to minimize greatly the outbreak of rubella as well as CRS. However, the efficacy of the British policy, of immunizing school girls performing in Britain and Japan, is so poor that CRS cases still exist. Therefore, both Britain and Japan have changed their policy to that of the American one since 1988-89, and Measles-Mumps-Rubella (MMR) vaccine is given when children are 12 months old. Human T-lymphotropic

virus type-l (HTLV-1)

in southern Japan

Takatsuki et al. [ 1l] of Japan described a malignant disease ‘adult T-cell leukemia (ATL)‘, which prevailed in southern Japan. Hinuma et al. [12] identified human Tlymphotropic virus type 1 (HTLV-1) as the causative agent of this disease. The endemic areas of HTLV-1 are southwest Japan, tropical Africa, Caribbean Islands, Papua New Guinea and some other areas. Epidemiology of HTL V-l

The infected subjects were seropositive and also were carriers throughout their lives. Seroprevalences in endemic areas are lo-20% for adults and l-3% for

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children. HTLV-I is transmitted through live infected lymphocytes [ 131. Three routes of transmission of this virus have been confirmed: blood-borne transmission (infection rate 63%) [ 131, husband-to-wife transmission (rate 60%) [ 14) and motherto-child transmission, mainly through breast milk (rate 15-25%) [3-4,151. And it is possible to reduce this rate of mother-to-child transmission to l/10 by refraining breast feeding [ 161. We have stored the serum specimens collected from CRS children and their mothers since 1968 in Okinawa, where HTLV-1 was endemic. Among the 311 mother-child pairs, 65 mothers (20.9%) and 10 children (3.2%) were seropositive for HTLV-I at the time of initial sampling. 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. No seropositive child was born to seronegative mothers. The 55 seronegative children born to seropositive mothers remained seronegative throughout the investigated period until 22-24 years old. There existed a significant difference between the prevalence rate of HTLV-I antibodies in mothers and children [ 151. Prevention of mother-to-child transmission of HTL V-l Researches on its prevention by refraining breast feeding are being performed by groups from Nagasaki University, Nara Medical University and Kagoshima University. Children who were breast-fed by seropositive mothers showed an infection rate of 25%, compared to 2.6% in the bottle-fed children, a reduction to l/10 [16]. However, route of transmission of this remaining l/10 is still unknown, probably by intrauterine infection. However, in order to stop this breast feeding, information to mothers for being carriers is necessary. References 1 Gregg,N.M. (1941): Congenitalcataractfollowing Germanmeaslesin the mother. Trans. Ophthal. Sot. Aust., 3, 35-46. 2 Nahmias, A., Wall, K.W., Stewart, J.A., Herrman, K.L. and Flynt, W.J. (1971): TORCH complex - perinatal infections associated with toxoplasma and rubella, cytomegalo- and herpes simplex viruses. Pediatr. Res., 5, 405-406. 3 Ando, Y., Nakano, S., Saito, K., Shimamoto, I. et al. (1987): Transmission of adult T-cell leukemia retrovirus (HTLV-1) from mother to child: comparison of bottle- with breast-fed babies. Jpn. J. Cancer Res., 18, 322-324. 4 Hino, S., Sugiyama, H., Doi, H., Ishimaru, T. et al. (1987): Breaking the cycle of HTLV-1 transmission via carrier mother’s milk. Lancet, ii, 158. 5 Overall, J.C. (1987): Viral infections of the fetus and neonate. In: Textbook of Pediatric Infectious Diseases, pp. 966-1007. Editors: R.D. Feigen and J.D. Cherry. Saunders, Philadelphia. 6 Rubella Symposium. (1965): Am. J. Dis. Child, 110, 345-476. I Ueda, K., Nishida, Y., Oshima, K., Yoshikawa, H. et al. (1978): An explanation for the high incidence of congenital rubella sysndrome in Ryuku. Am. J. Epidemiol., 107, 344-351. 8 Kono, R., Hirayama, M., Sugishita, C. and Miyamura, K. (1985): Epidemiology of rubella and congenital rubella infection in Japan. Rev. Infect. Dis., 7 (Suppl.), 56-63. 9 Ueda, K., Tokugawa, K., Nishida, Y. and Kimura, M. (1986): Incidence of congenital rubella syndrome in Japan (1965-1975). Am. J. Epidemiol., 124, 807-815. 10 Ueda, K., Nishida, Y., Oshima, K. and Shepard, T.H. (1979): Congenital rubella syndrome: correlation of gestational age at time of maternal rubella with type of defect. J. Pediatr., 94, 763-765. 11 Takatsuki, K., Uchiyama, T., Sagawa, K. and Jodi, J. (1977): Adult T-cell leukemia in Japan. In:

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Topics in Hematology, pp. 73-77. Editors: S. Seno, F. Takaku and S. Irino. Excerpta Medica, Amsterdam. Hinuma, Y., Nagata, K., Hanaoka, M., Nakai, M. et al. (1981): Adult T-cell leukemia: antigen in ATL cell line and detection of antibodies to the antigen in human sera. Proc. Natl. Acad. Sci. (Wash.), 78, 6476-6480. Okochi, K., Sato, H. and Hinuma, Y. (1984): A retrospective study on transmission of adult T-cell leukemia virus by blood transfusion: seroconversion in recipients. VOX Sang., 46, 245-253. Kajiyama, W., Kashiwagi, S., Ikematsu, H., Hayashi, H. et al. (1986): Intrafamilial transmission of adult T-cell leukemia virus. J. Infect. Dis., 154, 851-857. Kusuhara, K., Sonoda, S., Takahashi, K., Tokugawa, K. et al. (1987): Mother-to-child transmission of human T-cell leukemia virus type 1 (HTLV-1): a fifteen-year follow-up study in Okinawa, Japan. Int. J. Cancer, 40, 755-757. Hino, S. (1990): HTLV-1: Mother-to-child transmission. Clinical Virology, 18, S57 (in Japanese).

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 thr...
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