Placental evidence of cytomegalovirus infection of the fetus and neonate.

Nine cases of congenital cytomegalovirus infection were diagnosed at Brigham and Women's Hospital in Boston from September 1977 through July 1982. The majority of infected fetuses and newborn infants had intrauterine growth retardation, congenital malformations, microcephaly, or hydrops fetalis. In four cases, cytomegalovirus was recovered from placentas. Eight placentas were examined morphologically. Varying degrees of chronic villitis were noted in all. The most frequent lesion, found in six cases, was focal villous inflammation with mononuclear cell infiltrates. Lymphocytes predominated in this reaction. In three cases, however, the villi were also intensely infiltrated by plasma cells. Typical cytomegalic inclusion bodies were noted in these three placentas. The fetus and infants in whose placentas the plasmacytic villitis and inclusion bodies were discovered displayed the most severe manifestations of cytomegalovirus infection.

Antibody reactivity to human and vervet cytomegalovirus early antigen(s) in sera from patients with active cytomegalovirus infections and from asymptomatic donors.

Human fibroblasts were infected with vervet cytomegalovirus (VCMV) and cultured in medium containing 50 micrograms of cytosine arabinoside per ml for 72 h. Early antigens (EAg) were detected in the nuclei of infected cells by an indirect fluorescent antibody test with human sera having antibody to EAg of human cytomegalovirus (HCMV). Sera from patients with serological and/or virological evidence of active HCMV infection and from asymptomatic blood donors were examined for antibody activity with the HCMV and VCMV EAg's. The HCMV and VCMV EAg's were comparable in detecting levels of antibody activity and fluctuations in antibody titer of paired sera from patients. A total of 81% of patient sera reactive with HCMV EAg were also reactive with VCMV EAg. In contrast, only 14% of the asymptomatic donor sera reactive with HCMV EAg were also reactive with VCMV EAg. The VCMV EAg, therefore, appeared to differentiate latent from active infections in humans more effectively than did HCMV EAg.

Epidemiology of congenital rubella syndrome. The role of maternal parity.

Rubella vaccination policies are primarily directed at control of congenital rubella syndrome. In the United States, vaccination of children of both sexes, ages 1 theough 12 years, has been recommended. This policy depends on the hypothesis that children are the major source of infection for pregnant women. If true, then as maternal parity increases one would expect an increasing prevalence of rubella antibody or an increase in the frequence of rubella syndrome in babies. A serologic survey of 3,081 pregnant women has failed to show an increase in prevalence of rubella antibody with increasing parity. Case-control studies comparing groups of children with rubella syndrome to birth certificate and hospital control groups also have failed to show an excess of multiparae among the mothers of babies with rubella syndrome. Thus, these results do not support the hypothesis that children are the major source of infection for pregnant women.

Blastogenic response of human lymphocytes to early antigen(s) of human cytomegalovirus.

The lymphocytes of asymptomatic, seropositive donors demonstrated blastogenic responses to early antigens of human cytomegalovirus whether or not antibodies to early antigens were detectable. The lymphocytes of six of nine patients with active cytomegalovirus infections gave stimulation indexes of greater than or equal to 2.00 with antigens of productively infected cells, whereas only two patients demonstrated comparable stimulation indexes with early antigens. Four patients with stimulation indexes of greater than or equal to 2.00 to productively infected antigens had stimulation indexes of less than or equal to 2.00 to early antigens. Viral polypeptides with molecular weights of 83,000, 72,000, 62,000, 56,000, and 40,000 were identified in early antigen preparations.

Evaluation of a new latex agglutination method for detection of antibody to herpes simplex virus.

A new latex agglutination (LA) test (Wampole Laboratories, Cranbury, N.J.) for detection of antibody to herpes simplex virus was compared with a reference complement fixation (CF) method in a premarket evaluation. Of 102 serum samples tested, 19 were LA negative and CF negative, 79 were LA positive and CF positive, and 4 were LA positive and CF negative. An enzyme immunoassay (M. A. Bioproducts, Walkersville, Md.) performed on the four LA-positive and CF-negative serum samples agreed with LA in all cases. Most LA titers were two to four doubling dilutions higher than CF titers. We conclude that this new LA test is a rapid, sensitive, and simple method for documentation of past infection with herpes simplex virus.

Rubella hemagglutination inhibition: removal of nonspecific agglutination due to manganous chloride.

Nonspecific inhibitors of rubella hemagglutination can be removed by treatment of sera with heparin-manganous chloride for use in the hemagglutination-inhibition test. After removal of nonspecific inhibitors by this procedure, an excess of manganous chloride may remain. This may cause the cells to agglutinate, thus obscuring the reading at low serum dilutions. This disadvantage can be overcome by the addition of sodium carbonate, which forms an insoluble compound with manganous chloride and does not interfere with antibody determination. The procedure presents a further refinement of the hemagglutination inhibition test for rubella by increasing specificity and sensitivity; it permits detection of antibody levels as low as 1:4 in sera.

Rubella reinfection during pregnancy. A case of mistaken diagnosis of congenital rubella.

A case of subclinical rubella reinfection during pregnancy with serologic findings in the offspring initially led to an erroneous diagnosis of fetal infection. Laboratory diagnosis of congenital rubella infection, based on finding hemagglutination-inhibition (HI) activity in immunoglobulin M (IgM) fractions of newborn's serum after sucrose gradient fractionation, was questioned when apparent IgM-HI activity was to be probably due to nonspecific inhibitors, which resulted from bacterial action on the beta-lipoprotein in the serum. These findings emphasize some pitfalls encountered in arriving at a diagnosis based soley on serologic data. This case also illustrates the importance of keeping serum samples sterile when performing serologic tests.

Association of Ureaplasma urealyticum in the placenta with perinatal morbidity and mortality.

We investigated the presence of ureaplasmas, mycoplasmas, chlamydiae, fungi, aerobic and anaerobic bacteria, and cytomegalovirus in fetal membranes and evaluated their association with perinatal morbidity and mortality. We cultured 801 placentas from three groups of subjects (144 who died in the perinatal period, 452 neonates admitted to the intensive-care unit, and 205 controls). Ureaplasma urealyticum, Mycoplasma hominis, or both were isolated from 21 per cent of placentas of premature and term infants who died in the perinatal period, 25 per cent of those admitted to intensive care, and 11 per cent of controls. Gestational age and birth weight were inversely related to isolation of ureaplasma, and chorioamnionitis was positively related to isolation. The presence of ureaplasmas in the placenta suggests the transcervical migration of these microorganisms from the lower genitourinary tract. These data show a strong association between ureaplasma infection of the placenta and low birth weight of the neonate and suggest that the association is causal.