Enteroviral meningitis in infants.
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Enterovirus Infections↗
Biomedical subjects
J F Modlin
Publications and source records attributed to J F Modlin.
Localization of human immunodeficiency virus core antigen in term human placentas.
Evidence of human immunodeficiency virus (HIV) replication was sought in human placentas obtained at term from pregnancies complicated by maternal HIV infection. Placentas were obtained from the pregnancies of 19 HIV-seropositive women, 4 women who were seronegative, and 4 untested women with no risk factors for HIV infection. These placentas were each examined by immunoperoxidase immunocytochemistry using monoclonal anti-p24/55 antibodies. In addition, minced placental tissue from 11 of the seropositive pregnancies and the 3 seronegative pregnancies were co-cultivated with stimulated human peripheral blood mononuclear cells. The clinical status of the infants born to the HIV-seropositive women was assessed when the infants were 8 to 28 months of age. P24/55 antigen was detected in 5 of the 19 placentas of the HIV-seropositive pregnancies and in none of the 8 placentas of seronegative or low-risk pregnancies. This HIV core viral antigen was located exclusively in the cytoplasm of villous cells with morphological characteristics of macrophages. The HIV antigen-containing cells were very sparsely distributed. Staining of the trophoblast was not observed in any placental specimen. Human immunodeficiency virus was isolated in culture from 3 of the 11 placentas from seropositive pregnancies. Clinical follow-up has not revealed a relationship between infection of the infant and either p24/55 antigen identification or isolation of virus from the placenta. Virological and histological evidence of HIV replication is found in approximately one fourth of placentas obtained at term from pregnancies complicated by maternal HIV infection. Replicating virus appears localized to sparse macrophages located within the chorionic villi, but specifically not within the trophoblastic layer.(ABSTRACT TRUNCATED AT 250 WORDS)
Acquired Immunodeficiency Syndrome↗
Early diagnosis of perinatal HIV infection by detection of viral-specific IgA antibodies.
OBJECTIVES: To evaluate the clinical utility of a human immunodeficiency virus (HIV)-IgA serological assay for diagnosis of perinatally acquired HIV infection. DESIGN: Coded serum samples prospectively collected from children born to HIV-infected mothers and uninfected mothers were analyzed by HIV-IgA immunoblot. SETTING: A university hospital in Baltimore, Md, and an outpatient clinic in Port-au-Prince, Haiti. POPULATION: Five hundred thirty-nine serum samples were obtained sequentially from 278 children born to HIV-infected women (116 from The Johns Hopkins Hospital and 62 from Port-au-Prince) and from 42 control children born to HIV-seronegative children in Port-au-Prince. OUTCOME MEASURES: Results from the HIV-IgA serological assays were compared with the known infection status of the child at 15 months of age as determined by the standard IgG Western blot and the clinical classification of the Centers for Disease Control. Sensitivity, specificity, and predictive values were calculated at different ages and collectively for children 3 months of age or older. RESULTS: The HIV-IgA assay was positive in one of six specimens from HIV-infected children under 1 month of age, six of nine specimens from infected children at 3 months of age, and 160 of 161 specimens from 47 HIV-infected children 6 months of age or older. Of 334 specimens from 243 uninfected children, 333 were negative by the HIV-IgA assay. The overall sensitivity and the specificity of the IgA assay for children older than 3 months of age were 97.6% and 99.7%, and the positive and negative predictive values were 99.4% and 98.7%, respectively. CONCLUSION: Although the HIV-IgA assay had a low sensitivity within the first months of life, the high sensitivity, specificity, and predictive values of this assay demonstrate its utility for the diagnosis of perinatally acquired HIV infection after the third month of age. Early diagnosis with this relatively simple and inexpensive serological assay should aid in the implementation of antiviral therapy and provide useful information for the care of children born to HIV-infected mothers in both developing and developed countries.
Blotting, Western↗
A multicenter trial of oral zidovudine in children with advanced human immunodeficiency virus disease. The Protocol 043 Study Group.
BACKGROUND AND METHODS: Zidovudine has been shown to be an effective antiretroviral treatment in adults with human immunodeficiency virus (HIV) infection. We examined the safety of zidovudine and the tolerance of and therapeutic response to the drug in 88 children with advanced HIV disease. During a 24-week outpatient trial, zidovudine (180 mg per square meter of body-surface area per dose) was given by mouth every six hours and serial measurements were made of clinical, immunologic, and virologic indexes. Children who completed 24 weeks of treatment were permitted to continue receiving zidovudine. RESULTS: Of the 88 children (mean age, 3.9 years; range, 4 months to 11 years), 61 completed the initial 24-week trial, and 49 continued to receive zidovudine for up to 90 weeks (median follow-up, 56 weeks). The patients generally tolerated zidovudine well. One or more episodes of hematologic toxicity occurred in 54 children (61 percent)--anemia (hemoglobin level, less than 75 g per liter) in 23 children (26 percent) and neutropenia (neutrophil count, less than 0.75 x 10(9) per liter) in 42 (48 percent). Many of these abnormalities resolved spontaneously, but 30 children required transfusions or a modification of the dose of zidovudine. Only three children had to stop receiving the drug because of hematologic toxicity. Kaplan-Meier analysis demonstrated that the probability of survival was 0.89 after 24 weeks and 0.79 after 52 weeks. There was marked improvement in weight gain, cognitive function (mainly in children less than 3 years old), serum and cerebrospinal fluid concentrations of p24 antigen, and the proportion of cerebrospinal fluid cultures negative for HIV. CD4+ lymphocyte counts (mean at base line, 0.263 x 10(9) per liter) improved during the first 12 weeks, although the improvement was not sustained through the 24th week. CONCLUSIONS: Zidovudine in a dose of 180 mg per square meter every six hours can be safely administered to children with advanced HIV disease. The resultant clinical, immunologic, and virologic improvements in children are similar to those reported with zidovudine in adults.
Acquired Immunodeficiency Syndrome↗
Microbiology of chronic sinusitis in children.
To better understand the factors involved in chronic sinusitis in childhood, we cultured the sinuses, middle meatus, and nasopharynx in 39 children requiring surgical intervention. Sixty-nine percent of these patients had other medical problems, including asthma (49%) and immunologic compromise (18%). We cultured coagulase-negative staphylococcus in 18 patients, Streptococcus viridans in 14 patients, normal flora in 10 patients, Staphylococcus aureus in nine patients, group D streptococcus in five patients, Corynebacterium in five patients, Haemophilus influenzae in three patients, Neisseria in three patients, and Streptococcus pneumoniae, group A streptococcus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella oxytoca, Propionibacterium acnes, Actinomyces, and an anaerobic gram-negative bacillus in one patient each. Cultures yielded no growth in nine patients. A strong association between cultures of the middle meatus obtained ipsilaterally and cultures of the maxillary (83%) and ethmoid sinuses (80%) occurred. A poor correlation was found between cultures of the nasopharynx and maxillary (45%) and ethmoid sinuses (49%). All seven patients who had both maxillary and ethmoid sinus cultures showed the same organisms in both sinuses. Only 41% of organisms were found on both sides when procedures were performed bilaterally. Cultures of the middle meatus appear to be sensitive and specific for organisms within sinuses. The presence of predominantly nonvirulent organisms in low titers suggests that additional factors other than bacterial overgrowth contribute to the pathogenesis of chronic sinusitis in children.
Adolescent↗
Mucosal immunity induced by enhance-potency inactivated and oral polio vaccines.
Oral polio vaccine (OPV) is recommended for routine immunization in the United States in part because of its ability to induce intestinal and pharyngeal immunity to reinfection. Mucosal immunity produced by OPV and enhanced-potency inactivated polio vaccine (E-IPV) was compared by challenging vaccines with type 1 OPV. Fewer OPV (25%) than E-IPV (63%) vaccinees excreted OPV virus in stool after challenge. The mean stool virus titer was higher and the duration of shedding longer among E-IPV excreters. Only one E-IPV and three OPV vaccinees shed virus in the pharynx after challenge. Prechallenge serum neutralizing antibody levels were not statistically different among E-IPV vaccinees who did and did not shed virus; these levels were much higher than those of OPV vaccinees. Poliovirus-specific IgA levels in stool did not correlate with viral excretion. E-IPV was less effective than OPV in preventing and limiting intestinal infection, even though it induced higher postvaccination serum antibody levels.
Antibodies, Viral↗
Mucosal immunity following oral poliovirus vaccine and enhanced potency inactivated poliovirus vaccine immunization.
Mucosal immunity is considered to be an important barrier for inhibiting person-to-person transmission of naturally occurring (wild type) poliovirus infection. This review briefly summarizes the results of a previously published study in which 79 oral poliovirus vaccine (OPV) vaccinated children and 93 enhanced-potency inactivated poliovirus vaccine (IPV) children were challenged with one of two doses of type 1 OPV virus to test the oropharyngeal and gastrointestinal mucosal immunity conferred by each type of poliovirus vaccine. Although both OPV and IPV produced excellent oropharyngeal immunity, OPV was clearly superior in decreasing fecal shedding of the challenge virus.
Child, Preschool↗
Focal encephalitis with enterovirus infections.
We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.
Adolescent↗
The humoral immune response to type 1 oral poliovirus vaccine in children previously immunized with enhanced potency inactivated poliovirus vaccine or live oral poliovirus vaccine.
Sixty-one children who had previously received three doses of enhanced potency inactivated poliovirus vaccine (epIPV) at 2, 4, and 18 months of age and 56 children who had previously received oral poliovirus vaccine (OPV) according to the same schedule were challenged with a single dose of monovalent, type 1 oral poliovirus vaccine (OPV1) between 19 and 52 months of age. Before the OPV1 challenge, the previously epIPV-immunized recipients had a geometric mean poliovirus type 1 microneutralization antibody titer (geometric mean titer [GMT]) of 11.1 IU, which was significantly higher than the prechallenge GMT of 2.2 IU among the children who had previously received OPV. Three weeks after the OPV1 challenge, the GMTs for the epIPV-immunized recipients and the OPV-immunized recipients were 35.3 IU and 5.1 IU, respectively. For the epIPV-immunized recipients, both the prechallenge GMT and the postchallenge GMT were dependent on the D antigen content of the vaccine that they had previously received. A fourfold or greater rise in poliovirus type 1 antibody occurred after the OPV1 challenge in 50.9% of the epIPV-immunized children and in 28.6% of the OPV-immunized children; this difference was statistically significant. For both groups, antibody boosts were inversely correlated with the pre-challenge serum antibody titer. However, the epIPV-immunized children consistently were more likely to boost than the OPV-immunized children at equivalent levels of prechallenge antibody. This experience indicated that OPV1 administration effectively raises the level of serum antibody in children previously immunized with three doses of epIPV, especially in children with lower levels of preexisting antibody. This booster response was superior to the booster response of children who received three doses of OPV.
Antibodies, Viral↗
Comparative evaluation of immunization with live attenuated and enhanced-potency inactivated trivalent poliovirus vaccines in childhood: systemic and local immune responses.
Serum neutralizing, nasopharyngeal neutralizing, and IgA antibodies were determined in 123 infants immunized with one of four schedules containing live oral vaccine (OPV), inactivated vaccine (IPV), or combinations of the two trivalent poliovirus vaccines: OPV-OPV-OPV, IPV-IPV-IPV, IPV-OPV-OPV, or IPV-IPV-OPV. Nearly 100% of individuals formed serum neutralizing antibodies. The highest geometric mean titer (GMT) of antibody to polioviruses 1, 2, and 3 occurred in groups IPV-IPV-OPV, IPV-OPV-OPV, and IPV-IPV-IPV, respectively. Local neutralizing and IgA antibody responses were detected in 41%-88% and 75%-100%, respectively. Peak GMT of nasopharyngeal antibodies differed minimally between immunization groups. The data suggest that incorporation of at least one dose of IPV at the start of the immunization schedule tends to increase systemic as well as local antibody production.
Antibodies, Viral↗
Zidovudine treatment of an infant with congenital human immunodeficiency virus infection.
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Female↗
Prevalence of enteric pathogens in homosexual men with and without acquired immunodeficiency syndrome.
We studied 388 homosexual or bisexual men from the Baltimore-Washington area to define the spectrum of enteric pathogen carriage in a population at high risk for "gay bowel syndrome" in association with human immunodeficiency virus infection. Seventy-seven patients with acquired immunodeficiency syndrome, 68 gay men with symptoms of acute diarrhea or proctitis, and 243 gay men without gastrointestinal symptoms and participating in a natural history study of human immunodeficiency virus infection were selected for study. Approximately 12% of the asymptomatic men harbored at least one enteric pathogen; the most frequently recovered were Chlamydia trachomatis, herpes simplex virus, and Giardia lamblia. Men carrying a pathogen were more likely to be human immunodeficiency virus seropositive (48%) than men without a pathogen (25%) (p = 0.018), more likely to have fewer T helper cells (p = 0.015), and more likely to have a mucopurulent exudate (p = 0.014). We recovered an agent of enteric disease from 68% of gay men presenting with diarrhea or proctitis. Campylobacter species, herpes simplex virus, Neisseria gonorrhoeae, C. trachomatis, G. lamblia, and Shigella species were identified most frequently. The most common pathogen associated with diarrhea in acquired immunodeficiency syndrome was Cryptosporidium (16% of 49 cases). Other agents identified were Clostridium difficile, Vibrio parahemolyticus, Campylobacter species, G. lamblia, Isospora, and cytomegalovirus. Approximately half of the identifiable etiologic agents of diarrhea in acquired immunodeficiency syndrome patients were treatable with antibiotics, but these agents required special culture procedures for detection.
Acquired Immunodeficiency Syndrome↗
Chronic group A coxsackievirus infection in agammaglobulinemia: demonstration of genomic variation of serotypically identical isolates persistently excreted by the same patient.
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Agammaglobulinemia↗
Echovirus infections of newborn infants.
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Cross Infection↗
Perinatal echovirus and group B coxsackievirus infections.
Enteroviral infections late in pregnancy are common, especially during periods of high prevalence of community infection. Most of these infections, however, are not associated with significant maternal or neonatal disease. Conversely, as many as 65 per cent of women who give birth to infants with proven enteroviral infection have symptomatic disease during the perinatal period. Maternal echovirus or coxsackievirus B infections are not associated with an increased risk of spontaneous abortions, but stillbirths late in pregnancy have been described. Although a slightly increased risk for congenital heart defects and urogenital anomalies has been reported for the offspring of women who seroconverted to the group B coxsackievirus during pregnancy, these data are highly tentative. Transmission of enteroviruses from mother to infant is relatively common (30-50 per cent) and may occur through contact with maternal secretions during vaginal delivery, blood, or upper respiratory tract secretions. Intrauterine transmission has been documented, but its frequency is unknown. Postnatal transmission from maternal or nonmaternal sources also occurs regularly. Neonatal disease may range from inapparent infection to overwhelming systemic illness and death. Common clinical syndromes associated with neonatal enteroviral infections are meningoencephalitis, pneumonia, myocarditis, and hepatitis. The severity and outcome of perinatally acquired enteroviral infection is influenced by several factors, including the virus strain involved, mode of transmission, and presence of passively acquired serotype-specific maternal antibody. Newborn nursery outbreaks of nonpolio enteroviral infections usually coincide with seasonal peaks of enteroviral disease in the community. These outbreaks have been due mostly to echovirus 11 or group B coxsackievirus serotypes 1 to 5 and are associated with attack rates of up to 50 per cent.
Animals↗
Perinatal transmission of coxsackievirus B3 in mice.
Oral infection of pregnant mice with coxsackievirus B3 (CB3) late in gestation produced maternal viremia, which peaked three to four days after challenge, then rapidly diminished. Ninety percent of mice developed IgG antibody to CB3 by ten days after challenge. CB3 titers from placental tissue peaked at two to four days after maternal infection, but moderate titers persisted for at least eight days. Though virus could be recovered (less than 1.0-1.5 log10 pfu/g) from fetal tissue in only a small percentage (3%-13%) of pregnancies, virus could be found in some fetuses eight days after maternal infection. Despite the low rate of fetal infection, many pups born to dams infected one to eight days before delivery were either stillborn (4%-41%) or died from infection shortly after birth (14%-68%). The actual percentages depended on the time interval from infection of the dams to delivery. Maternal IgG antibody to CB3, which appeared at six to eight days after infection, protected against postnatal mortality, but did not protect against stillbirth.
Animals↗
Rationale for the sequential use of inactivated poliovirus vaccine and live attenuated poliovirus vaccine for routine poliomyelitis immunization in the United States.
Despite the concerns mentioned in the last section, there are many reasons to believe that a polio immunization schedule that incorporates sequential doses of inactivated poliovirus vaccine and live attenuated poliovirus vaccine would provide both humoral and intestinal immunity to the fully immunized person that is at least as good, if not better, than the immunity achieved by the use of IPV or OPV alone. A substantial degree of protection should also extend to partially immunized and unimmunized preschool aged children in the community. Furthermore most of the cases of OPV-associated paralytic poliomyelitis could be prevented. Because the reasons for these beliefs are based on data from small studies and on inferences from related research, specific recommendations for a change from current polio immunization policy must depend on additional clinical research. Well-designed trials comparing several different options for sequencing both inactivated and live vaccines are needed, and these studies should focus carefully on both humoral and intestinal immunity conferred by the various vaccine schedules.
Drug Administration Schedule↗
Perinatal enterovirus infections.
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Animals↗