Evaluation of a prescreening blood donor program for prevention of perinatal transfusion-acquired cytomegalovirus (CMV) infection.

The purpose of this study was to evaluate the efficacy of a prescreened CMV seronegative blood donor group in preventing transfusion-acquired CMV infection in premature infants in the perinatal period. Group 0 donors with known CMV seronegative status were recruited to supply blood to the neonatal intensive care nurseries. One hundred and twenty-seven low birth weight infants born of CMV seronegative mothers remained seronegative when blood for transfusion was screened for CMV antibody. Twenty two infants shared six units of CMV seropositive blood due to technical errors or poor sensitivity of the test kit in the initial phase of the study. Fifteen of these patients were in the study group. One infant died of immaturity at four weeks of age and two of the remaining 14 showed asymptomatic CMV infection. Another infant who received granulocyte concentrates from CMV seropositive donors had symptomatic CMV infection. Throughout the 24 month study period, blood supply to the ICN was adequate and timely. The donor seroconversion rate was 0.7% per annum. Only one infant was exposed to the risk of CMV infection due to donor seroconversion. We conclude that the prescreening donor program is a sensible and efficient approach for providing CMV seronegative blood in neonatal transfusion therapy.

Evaluation of cytomegalovirus (CMV) antibody screening tests for blood donors.

Four technics were compared to find the most suitable screening test for the cytomegalovirus (CMV) antibody status in blood donors. One hundred thirty-five donor samples were tested by two enzyme immunoassays, EIA(Litton) and EIA(Abbott), and by latex agglutination (LA) and complement fixation (CF). The seroreactivity of the tests were judged by concordance of three or more methods. The authors found that the test performance of the EIA(Litton) could be improved with adjustment of sample color variation, which increased the test sensitivity and specificity from 48.8% and 87.2% to 83.8% and 96.4%, respectively. Both the EIA(Abbott) and LA technics proved to be ideal screening tests with 100% sensitivity and negative predictive values. However, the rapid turnaround time and the simplicity in technics and equipment used with the LA test make it the test of choice for blood donor screening.

Antiviral chemotherapy.

The above discussion is not intended to be exhaustive but rather to discuss several compounds which are particularly promising at this time. There is no question that great strides have been made in the development of antiviral compounds over the past couple of decades. Many questions remain unanswered such as long-term effects on the host, possible emergence of resistant viruses, optimal routes of administration, and the proper regimens for particular viruses and diseases. In addition, current studies are evaluating combinations of antiviral agents as well as combination therapy involving interferon or antibody or immunity stimulants along with an antiviral agent. Surprising progress has been made to date resulting not only in new therapeutic modalities but promising a new era of progress.

Cytomegalovirus infections of the neonate and infant.

Cytomegalovirus is ubiquitous. While most infections are asymptomatic, infants and children acquiring CMV may excrete the virus for years in spite of significant antibody responses. CMV may be transmitted vertically or horizontally. Transplacental passage of CMV leads to congenital infection of the neonate. The most severely affected infants are born to mothers who develop a primary infection early in pregnancy and have a suboptimal cell-mediated response. During the perinatal period, the virus may be acquired by the infant from infected breast milk, passage through an infected birth canal, or by blood transfusion. Full-term infants infected during the perinatal period, though usually asymptomatic, may present with rash, hepatomegaly, lymphadenopathy, and/or pneumonia. Perinatally acquired infections in sick preterm infants may cause significant morbidity and mortality. Although specific therapy for infected individuals is currently unavailable, the outlook for an effective vaccine is promising.

Primary cytomegalovirus infection in adolescent pregnancy.

In a prospective study of 3,253 pregnant adolescents, 1,404 were seronegative for cytomegalovirus (CMV). Specimen collection at each antenatal visit, including urine for viral culture and serum for complement-fixing antibody, allowed definition of primary CMV infection in 14 subjects (1%). Seven of 14 subjects delivered congenitally infected infants, including 5/7 subjects with third trimester infections, and 2/5 subjects with second trimester infections. The single mother with a first trimester infection delivered an uninfected infant, despite recurrent maternal viremia. The mean birth weight of congenitally infected infants did not differ significantly from the mean birth weight of uninfected infants. None of the infants had stigmata of cytomegalic inclusion disease. One infected infant died suddenly at 6 weeks of age from pneumonia. Follow-up examinations of the six living children failed to detect cognitive, behavioral, or audiologic sequelae. These data demonstrate that primary maternal CMV infection occurs in 1% of susceptible women and is associated with a 50% risk of intrauterine infection. Fetal infection, particularly if it occurs late in pregnancy, is not invariably accompanied by fetal damage.

A prospective study of maternal cytomegalovirus infection and its effect on the fetus.

In order to define the effects of maternal cytomegalovirus infection in pregnancy and to identify risk factors associated with delivery of a cytomegalovirus-infected infant, a cohort of 1089 adolescents were prospectively evaluated during pregnancy. One hundred twenty-four subjects (11.4%) manifested cytomegaloviruria during pregnancy. Primary cytomegalovirus infection, defined virologically and serologically, occurred in three subjects. Infants of 119 cytomegalovirus-excreting mothers were cultured at birth, with detection of 12 congenital infections (10%), including one infant delivered of a mother with a third-trimester primary infection. A high titer of urinary virus or a fourfold or greater increase in antibody during the third trimester was significantly associated with delivery of a congenitally infected infant. All maternal and infant infections were asymptomatic. None of the congenitally infected infants manifested adverse effects during the first year of life. Our data demonstrate that pregnant women with cytomegaloviruria are at increased risk of being delivered of congenitally infected infants, particularly if active infection occurs late in pregnancy. If the maternal infection represents reactivation, overall probability of a poor fetal outcome is low.

Postnatally acquired cytomegalovirus infections in infants of CMV-excreting mothers.

A prospective study of cytomegalovirus-excreting pregnant women allowed us to identify a group of infants at high risk of acquiring CMV infection. Eighty-one infants free of CMV infection at birth were observed during the first year of life. Twenty-one became infected with CMV; 16 (76%) of these were detected within the first 14 weeks of life. Placental cultures from two of the 21 infants were CMV positive. The geometric mean cord blood antibody titers of postnatally infected and uninfected infants did not differ significantly. Clinical symptoms, including hepatosplenomegaly, lymphadenopathy, or pneumonia, occurred in association with CMV infection in seven infants. Postnatally acquired CMV infections can be symptomatic, and by virtue of their prevalence, constitute an important health problem.

Congenital and postnatally acquired cytomegalovirus infections: long-term follow-up.

To determine long-term outcome of children with inapparent congenital cytomegalovirus infection, an assessment of congenitally infected children observed since birth was undertaken. Children with early postnatal acquisition of CMV infection were also evaluated. Cognitive, behavioral, neurologic, audiometric, and speech and language evaluations were performed in 48 patients, including 17 congenitally infected children, 10 children with postnatal infection, and 21 uninfected control subjects. Mean IQ of the three groups of children did not differ significantly. Behavioral, neurologic, speech and language examinations similarly failed to distinguish differences among the three groups. Audiologic abnormalities were present in four congenitally infected children, including one child with a severe unilateral sensorineural loss; in none of the children was hearing loss functionally significant. No hearing abnormalities were detected in postnatally infected children. Although inapparent CMV infection can result in audiologic sequelae, the continued lack of cognitive, behavioral, and neurologic sequelae in these school-age children reemphasizes the need to focus attention on prevention of primary maternal CMV infection to avoid the potentially devastating effects of intrauterine CMV infection.

Humoral and cell-mediated immune responses to herpesvirus antigens during pregnancy--a longitudinal study.

Humoral and cellular immune responses were studied during the second trimester, third trimester, and postpartum periods in 11 pregnant women and in nonpregnant control women. Complement fixing (CF) and indirect hemagglutinating antibody (IHA) titers for herpes simplex type 1 (HSV-1), herpes simplex type 2 (HSV-2), and cytomegalovirus (CMV) were determined. Cellular response was measured by [3H]thymidine uptake by stimulated lymphocytes. Phytohemagglutinin (PHA), HSV-1, HSV-2, and CMV antigens were used as stimulants. No differences in the mean titers of CF and IHA antibodies were found. The cellular response to PHA had a transient decrease (P less than 0.02) during the third trimester. The cellular response to CMV was significantly lower during the second and third trimesters. A diminished response to HSV-1 antigen was observed during the second and third trimesters; the cellular response to HSV-2, though reduced, was not significantly altered during pregnancy. These data indicate a suppression of cellular responses to various herpesviruses and PHA during pregnancy.

Cytomegalovirus infection. Overview and new developments.

Cytomegalovirus (CMV) is a ubiquitous agent that causes infection in all age-groups. Fortunately, the infection is usually asymptomatic, and thus it goes unnoticed. It can, however, have serious sequelae in affected neonates. One of the most significant new developments in our understanding of CMV is its possible role in acquired immune deficiency syndrome, a syndrome that has an extremely high mortality rate. CMV is also closely related to Epstein-Barr and herpes simplex viruses, both of which have known oncogenic potential. Drs Bhumbra and Nankervis discuss the disease potential of CMV and research being done on prevention of CMV infection.

Latex agglutination test for rapid detection of bacterial antigens in body fluids.

A modified latex agglutination (LA) test performed on glass slides was evaluated for the detection of Streptococcus pneumoniae (Pn), Hemophilus influenzae type b (Hib), and K1 antigens in serum, cerebrospinal fluid (CSF), nasopharyngeal secretions, and other body fluids in patients suspected of having infection. Forty-eight, 61, and 31 specimens were tested for the presence of Pn, Hib, and K1 antigens, respectively, by countercurrent immunoelectrophoresis (CIE) and LA. Of the specimens positive by CIE or LA, 16 of 28 specimens (57 percent) were positive for Pn antigen by CIE while all 16 (100 percent) were positive by LA. LA was unique in detecting type 7 and 14 Pn antigens which are not detected by CIE. Twenty-seven of 37 specimens (73 percent) were positive for Hib by CIE, while all (100 percent) were positive by LA. LA test (11 of 11) was superior (p < 0.002) to CIE (4 of 11) in detecting Hib antigens on patients with nonmeningitic Hib diseases (cellulitis, epiglottitis and pneumonia). Sensitivity of CIE and LA were identical in detecting K1 (5 of 5) antigen. LA is a simple, sensitive and specific test for the detection of Pn, Hib, and K1 antigens in various body fluids.

Acquisition of cytomegalovirus infection in infants following exchange transfusion: a prospective study.

A prospective study of newborn infants who required exchange transfusion was undertaken to evaluate the risk of transmission of cytomegalovirus (CMV). Buffy coat-, urine- and saliva-saturated throat swabs for viral cultures and serum specimens for CMV complement-fixing (CF) antibody were obtained from 45 infant-mother pairs. Buffy coat from the donor blood was cultured and CMV CF titers measured. Viral studies were repeated on infants and mothers at six and 12 weeks after exchange transfusion. Fifteen infants received CMV seropositive blood and 14 infants received CMV seronegative blood. Sixteen infants who did not receive blood or blood products served as controls. Three of 12 antibody-positive newborns developed infection after getting seropositive blood. One of three antibody-negative newborns developed infection after getting seropositive blood. The presence of transplacental antibody does not appear to protect the infants. None of the control infants developed CMV infection. None of the infected infants were symptomatic. Although CMV infection in infancy can be acquired by routes other than blood, exchange transfusion with seropositive blood enhances the likelihood of acquiring infection.

Cytomegalovirus infections.

Cytomegalovirus infections are common throughout the world. Certain populations, including pregnant women and their fetuses, immunosuppressed patients, and recipients of large amounts of transfused blood, are at increased risk. Although the majority of infections in all groups of patients are clinically inapparent, variable symptoms, including fever, rash, pneumonitis, and hepatitis, can occur. The infected host develops antibodies against CMF, but frequently, despite this appropriate immune response, infection becomes chronic with prolonged excretion of virus. In some instances, a latent infection, with disappearance of virus, develops and under a variety of circumstances, including immunosuppression, infection can later be reactivated with reappearance of viral excretion. The human consequences of latent infection with CMV are not yet fully appreciated, and future research on this virus with multifaceted potential will need to focus on this issue.

Patient compliance to antibiotic regimens. A simple method of evaluation.

Clinicians are often perplexed by patients with bacterial infection who are not responding to oral antibiotic therapy. Since most of the commonly used antibiotics are excreted in the urine, inhibitory activity of urine against susceptible organisms can be used as a measure of patient compliance. To assess the reliability of this technique, we studied 42 hospitalized patients documented to be receiving oral antibiotics. All urine samples from patients receiving oral antibiotics inhibited bacterial growth at a dilution of greater than or equal to 1:32, while none of the specimens from control patients inhibited growth. Subsequent experience in the outpatient clinic has corroborated the reliability and simplicity of this test as a measure of compliance in patients who are receiving antibiotics either for prophylaxis or for therapy of acute infection.

Experimental congenital infection with cytomegalovirus: a guinea pig model.

An animal model permitting study of congenital infections with cytomegalovirus (CMV) has been developed in guinea pigs. Fifteen Hartley strain guinea pigs in the latter half of pregnancy were inoculated intraperitoneally with 10(5.5) 50% tissue culture infective doses of guinea pig CMV. Forty percent of infected mothers delivered litters containing at least one infected newborn, as defined by a positive culture of lung, spleen, or brain. All tissues were cultured by an explant technique. The three mothers who had no detectable complement-fixing antibody to CMV prior to experimental infection delivered infected litters, whereas three of 12 immune mothers delivered infected litters (P less than 0.01). A low-passage, tissue culture-adapted virus produced neonatal infection as frequently as did salivary gland-passaged virus. No congenital abnormalities were found in any of the seven infected newborns. CMV was isolated from lung, spleen, or brain in the four newborns of nonimmune mothers; CMV was isolated from lung only in the three newborns of immune mothers. These preliminary experiments demonstrate that the guinea pig is a suitable animal for further study of maternal-fetal CMV infections.

Diagnosis of pneumonia by counterimmunoelectrophoresis of respiratory secretions.

Several recent studies in adults have indicated that counterimmunoelectrophoresis (CIE) of sputum can distinguish persons with pneumococcal pneumonia vs those in whom merely colonization of pneumococcus occurs--CIE being positive in the former and negative in the latter. Counterimmunoelectrophoretic determinations were done on nasopharyngeal (NP) secretions in 20 children with bacterial pneumonia as evidenced by physical and radiological findings, leukocytosis, response to a penicillin, and in some cases, evidence of bloodstream invasion. Thirty-five children with other types of respiratory illness served as controls. Ten of 16 children from the pneumonia group had pneumococcal antigen in their NP secretions. Four of the six patients without pneumonia had evidence of disease associated with type 14 pneumococcus, which is not generally detected by CIE. The four additional patients with pneumonia had Haemophilus influenzae type b, and H influenzae type b antigen was present in the NP secretions. In the control group, one patient had pneumococcal antigen, and one patient had H influenzae type b antigen in the NP secretions, although 17/35 were positive for pneumococcus by culture. Counterimmunoelectrophoretic determinations of NP secretins are reliable in distinguishing patients with pneumococcal pneumonia vs those who are merely carriers (P less than .001).