High rate of GB virus type C/HGV transmission from mother to infant: possible implications for the prevalence of infection in blood donors.

BACKGROUND: Because GB virus type C(GBV-C)/HGV (GBV-C/HGV) is blood-borne and sexually transmitted, persons at risk of infection with such viruses have a high prevalence of GBV-C/HGV markers. However, adults with no apparent risk factors, such as blood donors, frequently are positive for GBV-C/HGV markers. Mother-to-infant transmission could explain this high prevalence, but it has been studied only through small series of GBV-C/HGV-infected mothers co-infected with HCV or HIV. STUDY DESIGN AND METHODS: To determine the rate of mother-to-infant transmission of GBV-C/HGV RNA in women who are HCV- or HIV-negative, a prospective study was performed in a cohort of 288 mothers screened for viral RNA and in the infants born to GBV-C/HGV-infected mothers. RESULTS: Thirteen mothers (4.5%) were found positive for GBV-C/HGV RNA. Of the infants in whom at least one blood sample was collected between the third and the ninth months of life, 89 percent were positive for viral RNA. The majority of these newborns were negative for GBV-C/HGV RNA at birth and positive after the third month. The viral RNA titers of infants born to GBV-C/HGV-infected mothers appeared as elevated as those of their mothers. All the GBV-C/HGV-infected infants remained positive for viral RNA during the entire study period. No clinical events possibly linked to a primary GBV-C/HGV infection were reported in infants. Serum ALT level and blood count remained within normal values throughout the follow-up of all GBV-C/HGV-infected infants. CONCLUSION: The frequency of mother-to-infant GBV-C/HGV transmission is elevated and could explain the high prevalence of GBV-C/HGV markers (viral RNA and E2 antibody) in adults at low risk for blood-borne or sexually transmitted viruses, such as blood donors.

Prevalence of GB virus type C/hepatitis G virus RNA and of anti-E2 in individuals at high or low risk for blood-borne or sexually transmitted viruses: evidence of sexual and parenteral transmission.

BACKGROUND: The first epidemiologic evidence of GB virus type C (GBV-C)/hepatitis G virus (HGV) infection showed a high prevalence of asymptomatic carriers in blood donors and in populations at risk for blood-borne viruses. However, by using only viral RNA polymerase chain reaction, those studies underestimated the true spread of GBV-C/HGV infection. The combined detection of GBV-C/HGV RNA and of anti-E2 (which reflects recovery from infection) is necessary to define accurately the prevalence of GBV-C/HGV. STUDY DESIGN AND METHODS: The presence of both anti-E2 and GBV-C/HGV RNA was searched for in 1438 serum samples collected from various groups of individuals at low or high risk for blood-borne or sexually transmitted viruses (blood donors, organ donors, unselected pregnant women, immunocompetent or immunodepressed multiply transfused patients, HIV-positive or HIV-negative homosexual men, intravenous drug addicts). RESULTS: The presence of GBV-C/HGV RNA and/or anti-E2 (exposure to GBV-C/HGV) was frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV appeared also to be sexually transmitted, with transmission from male to female more efficient than vice versa. A particularly elevated level of exposure to GBV-C/HGV was observed in homosexual men. In immunocompetent individuals, the prevalence of anti-E2 was about twice that of GBV-C/HGV RNA, which suggests the frequency of recovery from GBV-C/HGV infection. Most of the GBV-C/HGV RNA-positive individuals had no biochemical evidence of liver damage. CONCLUSIONS: GBV-C/HGV is frequent in populations at risk for blood-borne or sexually transmitted viruses. GBV-C/HGV is not a hepatitis virus, and it seems appropriate to rename it.

Neutralizing antibodies and complement-mediated, antibody-dependent enhancement (C'-ADE) of human immunodeficiency virus infection in its vertical transmission.

PROBLEM: Mother-to-child transmission is a major route for the spread of human immunodeficiency virus (HIV) worldwide. Our understanding of its mechanisms and parameters is still limited. Among the factors possibly involved in virus passage determination are the level and quality of antiviral humoral response. METHOD OF STUDY: Anti-HIV-1/Lai neutralizing activity in sera from 35 mother-infant pairs (in which 13 transmission cases occurred) was investigated, as was the complement-mediated antibody-dependent enhancement capacity of the same sera. RESULTS: Neutralization titers of 640 or more were found only in four mothers of uninfected children, but this result was not significant. No significant link was obtained with the occurrence of complement-mediated, antibody-dependent enhancement. CONCLUSIONS: As suggested by a synthesis of the literature, vertical transmission of HIV is probably the result of multiple active and/or stochastic parameters in the mother, the fetal structures, and the viral population. The precise definition of cellular mechanisms involved in in utero infection would help to better define which immune activity in the mother should be more carefully considered.

Modulations of cytokine expression in pregnant women.

PROBLEM: Although the overall anti-infectious and anti-parasitic immunity of parous women appears normal, several aspects of maternal cell-mediated and humoral immunity are altered during pregnancy. This has been suggested to occur via preferential local and systemic secretion of Th-2 type cytokines, which down-regulate or prevent secretion/action of Th-1 type cytokines, in animals as well as in humans. METHOD: To evaluate the influence of gestation on the maternal immune system, we have measured, in pregnant women, the mRNAs coding for several cytokines (TNF alpha, IFN gamma, GM-CSF, IL-1 beta, IL-2, IL-4, IL-6, and IL-10) in peripheral blood mononuclear cells, by use of semi-quantitative RT-PCR. RESULTS: Our results show significant modulations of IFN gamma, IL-1 beta, IL-4, and IL-6 genes expression especially during the third trimester and near parturition. CONCLUSION: Cytokine expression is thus finely tuned in peripheral blood during pregnancy, in a previously unexpected complex pattern, related to gestational stage.

Acceptability and impact of zidovudine for prevention of mother-to-child human immunodeficiency virus-1 transmission in France.

We studied the propagation and the impact of zidovudine prevention on the human immunodeficiency virus-1 transmission rate from infected mothers to their infants in the French nationwide prospective cohort. Infection was diagnosed in the children on the basis of at least two positive human immunodeficiency virus-1 polymerase chain reaction tests, culture, or both. The transmission rate among treated women was compared with that among untreated women during the same period and with that among women enrolled in the cohort since 1986. The impact of zidovudine was analyzed according to the women's clinical and biologic characteristics, the mode of delivery, and use of zidovudine therapy before the pregnancy. Nearly 90% of women were treated as soon as the second half of 1994. In 1994 and 1995, 80% of mother-child pairs received at least one of the three phases of preventive treatment. Among the 663 mothers enrolled during these 2 years, only six refused the treatment. Zidovudine treatment was associated with a reduction in the transmission rate of nearly two-thirds, from 14% +/- 6% to 5% +/- 2% (p < 0.01). The degree of reduction was not influenced by the maternal CD4+ cell count or p24 antigenemia at delivery. Zidovudine treatment of the mother before the pregnancy considerably reduced the impact of preventive therapy; the transmission rate was significantly higher among pretreated mothers (20% versus 5%, p < 0.01) even after adjusting for maternal CD4+ cell count. Zidovudine prevention is now widely used in France and has had a major impact on the epidemiology of mother-child human immunodeficiency virus transmission. This justifies a policy of offering human immunodeficiency virus screening to all women before or shortly after the diagnosis of pregnancy.

Characterization of human immunodeficiency virus type 1 p17 matrix protein motifs associated with mother-to-child transmission.

In order to determine if viral selection occurs during mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1), we used a direct solid-phase sequencing method to sequence the p17 matrix protein-encoding regions of viral isolates from 12 HIV-1-infected mother-and-child pairs, 4 infected infants, 4 transmitting mothers, and 22 nontransmitting mothers and compared the sequences. The blood samples were collected during the delivery period for the mothers and during the first month of life for most of the children. The p17 nucleic sequences were distributed among several clades corresponding to the HIV-1 A, B, and G subtypes. At the amino acid level, no significant differences within the known p17 functional regions were observed among the subtypes. Statistical analyses could be performed with the B subtype. Within the major p17 antibody binding site, a constant KIEEEQN motif (amino acids 103 to 109) was found in all mother-and-child isolates from the B subtype. On the other hand, 9 of 17 nontransmitting mother isolates were variable in this 103 to 109 region. Thus, this motif was significantly associated with the transmitting status (chi square, P = 0.0034). A valine residue at position 104 was significantly associated with the nontransmitting phenotype (chi square, P = 0.014), suggesting that it has a protective role during vertical transmission. The C-terminal end of p17 was globally conserved among nontransmitting mother isolates (chi square, P = 0.0037). These results might improve the understanding of the pathogenesis of HIV-1 vertical transmission and might allow the screening of seropositive mothers by a rapid molecular or peptide test.

Relationships between humoral factors in HIV-1-infected mothers and the occurrence of HIV infection in their infants.

Based on what is known about the biology of HIV-1 vertical transmission, the HIV burden of the mother, maternal immune factors and the integrity of the placental barrier are likely to play major roles. We therefore sought to determine whether the presence of antibodies in sera from 47 HIV-1-infected mothers, including 30 non-transmitting and 17 transmitting mothers, affected the risk of HIV-1 transmission to infants. Our findings showed no significant correlation between the capacity of antibodies to mediate antibody-dependent cell-mediated cytotoxicity (ADCC) and their capacity to induce protection of the child from HIV-1 infection (P = 0.14). Furthermore, no correlation was found between the capacity of maternal antibodies to neutralize in vitro lymphocyte or macrophage heterologous viral infection and the occurrence of in vivo HIV-1 infection in the infant. Sera recovered from five of 12 transmitting mothers and from five of 11 non-transmitting mothers were compared in their capacity to neutralize the viruses drawn from the same individuals. Four out of five maternal isolates from transmitting mothers and all maternal isolates from non-transmitting mothers were sensitive to enhancement of infection mediated by the maternal serum.

Clearance of HIV infection in 12 perinatally infected children: clinical, virological and immunological data.

OBJECTIVE: A case of HIV infection clearance in a perinatally infected infant has been recently reported. We report here on the molecular, biological and clinical features of such virus clearance in 12 children. DESIGN AND METHODS: We performed a retrospective analysis of the diagnosis in our 6-year cohort of 188 children born to HIV-seropositive mothers. HIV-1 was detected by coculture of infant peripheral blood mononuclear cells (PBMC) with cord blood cells, direct culture of infant cells, and DNA polymerase chain reaction (PCR). The children were diagnosed three times during the first 3 months of life and then followed up over a postnatal period of 18-36 months. RESULTS: The 12 reverted children had at least two positive PCR in at least two amplified regions. Among them, six were tested positive in culture/coculture assay, and five were treated long-term with zidovudine. Thus, seven out of 12 reversions cannot be attributed to antiretroviral therapy. All the virological results became negative during the first year of life, and serology lowered to negative values between 9 and 23 months. We could not find any correlation between either neutralizing or antibody-dependent cellular cytotoxicity-mediating antibodies and HIV clearance. CONCLUSION: In our cohort, we showed that an unexpected number of children born to HIV-seropositive mothers (6.7%) cleared HIV infection during the first year of life, and subsequently became seronegative. Interestingly, most of these children exhibited unspecified clinical signs during the first months of life. Five of these children were tested positive only by PCR, which suggests a low virus load and could, at least partly, explain spontaneous clearance. However, 4 years later, among the seven remaining infants, two seronegative children presented recurrent hepatosplenomegaly, which may indicate the presence of hidden virus not detectable by peripheral blood testing.

[Treatment of a positive Rhesus D neonate born of a mother with idiopathic thrombopenic purpura with anti-D immunoglobulins (Rh O)]. / Traitement d'un nouveau-né Rhésus D positif né de mère atteinte d'un purpura thrombopénique idiopathique par immunoglobulines anti-D (Rh O).

A Rhesus D positive infant, born at 37 weeks of gestational age, admitted for neonatal passive immune thrombocytopenia was given 3 intravenous anti-Rhesus D immunoglobulin infusions at 3 weeks of age. This thrombocytopenia which had not responded to conventional therapy improved after the third of anti-Rhesus D immunoglobulin infusion, but the efficacy of this treatment could not be proven in this case report. However, the tolerance was good. No side-effects (jaundice, severe anemia) were observed.

Acute fetal distress after fetal blood sampling (case report).

The authors report a case of acute fetal distress after fetal blood sampling, performed for fetal karyotype because of a precocious and symmetrical fetal growth retardation without maternal hypertension or ultrasonographic evidence of fetal malformation. A cesarean section performed because of acute fetal distress showed the newborn to be hypotrophic, with a major acidosis and a refractory hypoxemia. The new born died despite intensive care. Acute fetal anemia was assumed to be the cause of acute fetal distress. The authors emphasize the use of FHR in fetal survey after fetal blood sampling.

[Ante-partum administration of preventive treatment of Rh-D immunization in rhesus-negative women. Parallel evaluation of transplacental passage of fetal blood cells. Results of a multicenter study carried out in the Paris region]. / Application anté-partum du traitement préventif d'immunisation rhésus D chez les femmes rhésus négatif. Evaluation parallèle des passages transplacentaires d'hématies foetales. Résultats d'une étude multicentrique menée en région parisienne.

1,969 non immunized rhesus negative primiparous women were followed up in 23 maternity units in the geographical region of Paris. 1,882 could be retained to study antepartum protection and 1,884 to study transplacental passage of fetal blood cells. Two groups were defined according to whether they were born in even or uneven years, so that: 955 were the "control" group who delivered 590 rhesus D positive infants, and 927 were the "treated" group who delivered 599 rhesus D positive infants. The "control" group were used as controls at the 28th and 34th weeks of pregnancy, while the "treated" group received two injections of anti-D immunoglobulin given on the same dates after taking the necessary tests. Immunological testing at the time of the delivery and after the delivery showed that 7 women had become Rh D immunized in the "control" group whereas only one in the "treated" group. This difference, which is statistically significant, confirms the results of other authors about the efficiency of antepartum rhesus disease prevention. The incidence of immunisation during or immediately after the first pregnancy in women who had no previous story of blood transfusions or of terminations of pregnancy is 1.11%, which is a figure relatively low as compared with studies of series carried out in North America, but close to those carried out in other European centres. When primipara of all categories are lumped together the frequency rises to 1.5%. A study of the passage of fetal red blood cells into the maternal circulation shows that at the 29th week of pregnancy out of 1,884 cases there were 5.5% positive kleihauer tests, without a large volume of blood being detected and at the 34th week of pregnancy when 957 tests were carried out, 7% were positive with one of them being of a massive transfusion of blood from the fetus to the mother, which was life-threatening for the fetus. It may be that the incidence had been under-estimated and that the positive results in the two groups, control and treated, show that there is a statistically significant difference that demonstrates that antepartum treatment in the trial has eliminated a worthwhile percentage of positive kleihauer tests which arose from the transfusion of small quantities of blood.(ABSTRACT TRUNCATED AT 400 WORDS)

[Post-transfusion cytomegalovirus infection in newborn infants]. / Les infections post-transfusionnelles à cytomégalovirus du nouveau-né.

Post-transfusional cytomegalovirus infection (P.T.C.M.V.) represents a minor part (perhaps about 0.2%) when compared with C.M.V. infections or maternal origin (congenital 0.2-0.5% - post-natal first year 20%). However P.T.C.M.V. infections are associated with higher morbidity and mortality because: These infections develop in infants born from uninfected mothers (C.M.V. sero-negative mothers). These newborns have no passively acquired antibodies from maternal origin which probably prevent or limit the spreading of P.T.C.M.V. infection in infants born from C.M.V. seropositive mothers. Transfused newborns are essentially recruited among great premature infants. The transfusional needs of these newborns are great: many of them receive more than ten micro-transfusions of red blood cells during their hospitalisation period. So the risk for developing C.M.V. infection is high (10-20%). The limited immune competence of these newborns and the fact that many already suffer from other developmental defects explain the severity of these P.T.C.M.V. infections. This contrasts with the well-supported C.M.V. infections post-natally acquired in term newborns. Prevention of P.T.C.M.V. infections is possible (A. Yeager, 1981) when using blood from C.M.V. sero-negative donors. Frozen blood appears also effective. It is highly desirable that blood Transfusion Centers permit such a prevention for red blood cells transfusion or exchange-transfusion in newborns less than 1 500 g B.W. and for intra-uterine transfusions.