Congenital cytomegalovirus, parvovirus and enterovirus infection in Mozambican newborns at birth: A cross-sectional survey.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is the most prevalent congenital infection acquired worldwide, with higher incidence in developing countries and among HIV-exposed children. Less is known regarding vertical transmission of parvovirus B19 (B19V) and enterovirus (EV). We aimed to assess the prevalence of CMV, B19V and EV vertical transmission and compare results of screening of congenital CMV obtained from two different specimens in a semirural Mozambican maternity. METHODS: A cross sectional study was conducted among pregnant mothers attending Manhiça District Hospital upon delivery. Information on maternal risk factors was ascertained. Dried umbilical cord (DUC) samples were collected in filter paper for CMV, B19V and EV detection by real-time polymerase chain reaction (RT-PCR), and nasopharyngeal aspirates (NPA) to test for CMV by RT-PCR. Maternal blood samples and placental biopsy samples were also obtained to investigate CMV maternal serology, HIV status and immunopathology. RESULTS: From September 2014 to January 2015, 118 mothers/newborn pairs were recruited. Prevalence of maternal HIV infection was 31.4% (37/118). CMV RT-PCR was positive in 3/115 (2.6%) of DUC samples and in 3/96 (6.3%) of NPA samples obtained from neonates. The concordance of the RT-PCR assay through DUC with their correspondent NPA sample was moderate (Kappa = 0.42 and p<0.001. No differences on cCMV prevalence were found among HIV-exposed and unexposed. All (100%) mothers were seropositive for CMV IgG. RT-PCR of EV and B19V in DUC were both negative in all screened cases. No histological specific findings were found in placental tissues. No risk factors associated to vertical transmission of these viral infections were found. CONCLUSIONS: This study indicates the significant occurrence of vertical transmission of CMV in southern Mozambique. Larger studies are needed to evaluate the true burden, clinical relevance and consequences of congenital infections with such pathogens in resource-constrained settings.

[Diagnosis of congenital infection]. / Diagnóstico de infección congénita.

In general, congenital diagnosis is based on: a) maternal serologic assays; b) microbiologic study of amniotic fluid or fetal blood sampling; and c) serology in children and microorganism detection by polymerase chain reaction (PCR) or culture. Congenital infections due to cytomegalovirus, herpes simplex, varicella, B19 erythrovirus and toxoplasmosis are usually the result of primary infection in the mother. Therefore, when IgG antibodies are detected before pregnancy, these infections are ruled out. Definitive serologic diagnosis of acute infection in pregnant women requires the demonstration of seroconversion (i.e., from seronegative to seropositive). In these cases, amniotic fluid or fetal blood sampling should be performed to determine the presence of intrauterine congenital infection. Cytomegalovirus, rubella and toxoplasmosis can be diagnosed by detection of specific IgM antibodies in fetal blood. However, PCR in amniotic fluid has replaced conventional prenatal diagnostic techniques, including fetal blood sampling, in the diagnosis of these infections. In the newborn, these infections may be confirmed by measuring IgM specific antibodies. B19 erythrovirus can be detected by PCR in amniotic fluid or fetal blood. Congenital varicella-zoster infection may be diagnosed on the basis of persistence of IgG antibodies after birth. Definitive diagnosis of herpes simplex virus infection requires viral isolation. Swabs or scraping from clinical specimens can be inoculated into susceptible cell lines for isolation.

Fetal stroke and congenital parvovirus B19 infection complicated by activated protein C resistance.

UNLABELLED: Parvovirus B19 infection in gestation has been associated with severe fetal complications such as anaemia, hydrops and fetal demise. Fetal infection in the first trimester poses the greatest risk for these complications, but infection during the third trimester is more common than previously appreciated and can be associated with severe complications, i.e. fetal death, in the absence of hydrops or classical clinical symptoms. Parvovirus B19 infection has been associated with vasculitis and pathological changes in the central nervous system, which may cause stroke. We report a newborn infant with a rare combination of a recent central nervous system infection with parvovirus B19 and a factor V Leiden mutation, who developed fetal stroke. CONCLUSION: Factor V Leiden mutation leads to activated protein C resistance and increases the risk of thromboembolism. Thromboembolism occurs rarely in newborns with activated protein C resistance, but can be precipitated by dehydration, asphyxia and infection. Although parvovirus B19 infection of the central nervous system may be a precipitant in neonatal and/or fetal stroke, it can also cause stroke independent of a thrombophilic mutation. In this case, both causative factors may have coincided.

Intrauterine therapy for parvovirus B19 infected symptomatic fetus using B19 IgG-rich high titer gammaglobulin.

Parvovirus B19-infected hydrops fetalis was treated using gammaglobulin injection into the peritoneal cavity (GIFPeC) with B19-IgG-rich immunoglobulin. Fetal anemia and hydrops resolved, and B19-DNA in fetal ascites decreased despite no change in maternal B19-IgG or B19-DNA. Gammaglobulin injection into the peritoneal cavity is thus useful for treating hydrops fetalis while avoiding intrauterine blood-transfusion risks.

Serologic and virologic evidence for frequent intrauterine transmission of human parvovirus B19 with a primary maternal infection during pregnancy.

OBJECTIVE: To define the intrauterine viral transmission rate during primary maternal parvovirus B19 infection and identify factors that may influence this rate. METHODS: Forty-three pregnant women at two medical centers were identified with a primary B19 infection and followed to delivery. At delivery maternal and infant (umbilical cord) blood was obtained for B19 serologic and virologic PCR testing. RESULTS: All of the women delivered healthy infants at term and none was hydropic. Overall 22 (51%) of the 43 infants had some evidence of a congenital B19 infection. B19-specific IgM was detected in 11 infants at delivery, B19 IgA was detected in 10 and B19 DNA was detectable by PCR in 11 infants. One infant was negative at birth but became positive for IgM, IgA and PCR at 6 weeks of age. No association was found between the likelihood of intrauterine infection and: maternal age; symptomatic maternal infection; method of delivery; maternal IgG titer at delivery; maternal IgG avidity at delivery; or maternal viremia at delivery. Intrauterine infection was associated with maternal IgM positivity at delivery; this association may have been a result of maternal infection occurring later in gestation. CONCLUSION: Although the incidence of intrauterine hydrops and fetal demise after maternal infection is low, there is a high rate of intrauterine viral infection that occurs throughout gestation and yields newborns who, although infected in utero, are asymptomatic at birth.

Neonatal erythema infectiosum.

A report is presented of a patient with neonatal erythema infectiosum who developed petechiae, transient thrombocytopenia and transient cardiac failure due to transplacental transmission of human parvovirus B19 (HPV B19) infection. It is suggested that the thrombocytopenia was caused by platelet-associated IgG produced by the patient, and that the cardiac failure may have been caused by direct entry of HPV B19 into the cardiac tissue.

Human parvovirus B19 infection within a family and risk for pregnant women.

During an outbreak of parvovirus B19 infection among four related families at least 70% of the household contacts, including a woman at the 33rd week of pregnancy, became infected. Twins were born at the 39th week of pregnancy, both with B19 infection. B19 DNA was detected in their sera by a nested PCR, anti-B19 IgM was detectable only by an immunofluorescence assay, and low levels of maternal anti-B19 IgG were demonstrable by an immunoenzymatic test in the serum of both children. All the haematological parameters were normal at birth and 6 months later, when B19 DNA and anti-B19 antibody were no longer detectable in serum samples. This observation emphasizes the high risk of B19 infection among household contacts and the possibility of a favourable outcome of the foetal infection, possibly related to infection late in the pregnancy.

B19 parvovirus.

B19 parvovirus is pathogenic in man and causes a variety of clinical illnesses, among them several haematological diseases. Acute infection of a host with underlying haemolysis produces transient aplastic crisis; of the midtrimester fetus, hydrops fetalis; and of an immunocompromised patient, pure red cell aplasia. The target of B19 parvovirus infection is the human erythroid progenitor cell. Infection is cytotoxic due to expression of the viral nonstructural protein. The virus can be propagated in cultures of human bone marrow, blood, and fetal liver. Humoral immunity normally terminates infection, and commercially available immunoglobulin can be used to treat persistent infection. Recombinant capsids, produced in a baculovirus system, are suitable as a vaccine reagent.

Management strategies for congenital infections.

Information on congenital infection is continuously expanding. New diagnostic techniques are making significant contributions to the prenatal diagnosis of several fetal infections. In this review we highlight some of the most recent advances in the diagnosis and management of the most common fetal infections, those caused by cytomegalovirus, human immunodeficiency virus 1, Toxoplasma, varicella-zoster virus, and parvovirus B19.

Congenital anaemia after transplacental B19 parvovirus infection.

We report three children with congenital anaemia after intrauterine infection with B19 parvovirus. All the fetuses developed hydrops fetalis that was treated by blood transfusion. After delivery the infants had hypogammaglobulinaemia. In all three, sera lacked B19 but viral DNA was found in bone marrow. All were treated with immunoglobulin. One child died and B19 was found in various tissues. In the other two cases, virus could no longer be detected after therapy but the patients remain persistently anaemic. Persistent B19 infection should be suspected in infants with congenital red-cell aplasia.

Has percutaneous umbilical blood sampling improved the outcome of high-risk pregnancies?

PUBS offers distinct advantages to the perinatologist in the management of the high-risk pregnancy. Improvement in outcome has clearly been attained in the severely anemic fetus, for example, whereas fetal blood sampling has also led to great advances in both diagnosis and treatment of many other perinatal abnormalities. The exact role for PUBS in the management of problems such as intrauterine growth retardation and the fetus at risk for thrombocytopenia in ITP remains controversial. It is quite evident, however, that overall PUBS offers tremendous aid to the perinatologist in management of the high-risk pregnancy, with future promise for even greater application.

Fetal medicine.

Fetal therapy continues to be an exciting yet controversial field. In utero treatment of a variety of fetal conditions is discussed: parvovirus B19 infection, fetal thyroid dysfunction, fetal ovarian cysts, twin-twin transfusion syndrome, and fetal hemolytic disease. Fetal surgery continues to be controversial. Despite considerable publicity, fetal surgery appears to be rarely, if ever, truly indicated. A new area of fetal therapy, ie, antenatal transplantation of fetal liver stem cells, is discussed.