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Background. Respiratory syncytial virus (RSV) and influenza virus are common causes of infantile lower respiratory tract infection (LRTI). It is widely believed that both viral replication and inappropriately enhanced immune responses contribute to disease severity. In infants, RSV LRTI is known to be more severe than influenza virus LRTI. Methods. We compared cytokines and chemokines in secretions of infants surviving various forms of respiratory illness caused by RSV or influenza viruses, to determine which mediators were associated with more-severe illness. We analyzed lung tissue from infants with fatal cases of RSV and influenza virus LRTI to determine the types of inflammatory cells present. Autopsy tissues were studied for the lymphotoxin granzyme and the apoptosis marker caspase 3. Results. Quantities of lymphocyte-derived cytokines were minimal in secretions from infants with RSV infection. Concentrations of most cytokines were greater in influenza virus, rather than RSV, infection. Lung tissues from infants with fatal RSV and influenza virus LRTI demonstrated an extensive presence of viral antigen and a near absence of CD8-positive lymphocytes and natural killer cells, with marked expression of markers of apoptosis. Conclusions. Severe infantile RSV and influenza virus LRTI is characterized by inadequate (rather than excessive) adaptive immune responses, robust viral replication, and apoptotic crisis. [ABSTRACT FROM AUTHOR]

The presence of respiratory syncytial virus (RSV) and several cytokines and cell adhesion molecules in middle ear effusions and mucosal tissues was evaluated using polymerase chain reaction. RSV genomic sequences were detected in 23 (52.7%) of 44 middle ear effusions tested. The sequences were detectable at an even higher rate (82.4%) in effusions of children in whom infectious virus was detected in the nasopharynx. All samples with the RSV genome contained the mRNA for interleukin-1β and -6 and tumor necrosis factor-α. The messages for these cytokines, together with intercellular adhesion molecule-1, endothelial leukocyte adhesion molecule-1, and vascular cell adhesion molecule-1, were detected in human middle ear mucosal organ cultures infected in vitro with RSV. Our results suggest that the enhanced synthesis of proinflammatory cytokines and cell adhesion molecules in the middle ear infected with RSV may contribute to the inflammatory processes in otitis media. [ABSTRACT FROM PUBLISHER]

Fecal shedding of virulent revertant polioviruses was examined in isolates from infants previously immunized with ⩾ 1 dose of orally administered live attenuated polio vaccine (OPV) alone, enhanced-potency inactivated polio vaccine (EIPV) alone, or a combination of both. After administration of OPV alone, vaccine poliovirus serotypes were recovered in feces within 1 week and for as long as 31–60 days in 30%–80% of subjects after 1 or 2 doses and in 30%–50% after immunization with ⩾3 doses. No revertant poliovirus shedding was observed after OPV challenge in subjects immunized previously with ⩾3 doses of OPV. However, fecal shedding of revertant poliovirus after OPY challenge was observed in 50%–100% of subjects previously immunized with ⩾3 doses of the EIPV. These findings suggest that prior immunization with EIPV does not prevent fecal shedding of revertant polioviruses after subsequent reexposure to OPV. [ABSTRACT FROM PUBLISHER]

Groups of infants were immunized with one or two doses of orally inoculated live attenuated Sabin poliovirus vaccine (OPV group) or with one or two doses of enhanced-potency inactivated poliovirus vaccine (EIPV) administered parenterally followed by one or two doses of OPV (EIPV-OPV group). The fecal specimens from both groups were tested for poliovirus shedding 1–2 months after OPV. The virus isolates were examined for nucleic acid sequences in the 5′ noncoding regions (bases 480, 481, and 472 for serotypes 1,2, and 3, respectively) to determine whether the viruses shed represented nonattenuated revertants, attenuated parent vaccine strains (nonrevertants), or both. In the OPV group, 4 of the 6 virus isolates recovered 30–60 days after the first immunization dose and 1 of the 3 isolates obtained after the second dose were found to be nonrevertants (parent vaccine strain). In contrast, 11 of the 12 isolates in the EIPV-OPV group were of the nonvaccine revertant virus types. The frequency for reversion appeared to differ for different poliovirus serotypes. However, all revertant type 3 isolates were recovered from subjects previously immunized with EIPV [ABSTRACT FROM PUBLISHER]

Serum neutralizing, nasopharyngeal neutralizing, and 19A 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 19A 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 ofthe immunization schedule tends to increase systemic as well as local antibody production. [ABSTRACT FROM PUBLISHER]

Twenty-oneinfants experienced 29 episodes of otitis media with effusion caused by nontypable Hemophilus influenzae (NTHI) during 2 y of observation. Bactericidal antibody was detected in acute serum of 26% of the subjects at a mean titer of 0.8 ± 0.3 (log2) and was observed in convalescent serum of all of the individuals at a mean titer of 4.0 ± 0.3 (log2, P < .001). The serum bactericidal antibody response was not age-dependent (r = .08, P > .05). Serum concentrations of bactericidal antibody remained stable for the entire observation period in 90% of the children. The presence of serum bactericidal antibody correlated significantly with a reduction in the number of bacteria present in the middle ear fluid (P < .025). Eight children experienced a second episode of otitis media with effusion caused by a different serotype of NTHI. All those who lacked bactericidal antibody against the organism causing the second episode possessed bactericidal antibody against the first strain at the time of the second episode. These data suggest that the immune response to NTHI in otitis media with effusion is type-specific. The occurrence of second episodes of otitis media with effusion due to different strains of NTHI in the face of preexisting heterologous bactericidal antibody suggests a lack of cross-protection. [ABSTRACT FROM PUBLISHER]

By using immunoblotting, neutralization, and ELISA, the development of secretory antibody responses to poliovirus type 3 virion proteins (VP1, VP2, VP3) and to intact or trypsin-treated poliovirus type 3 was studied in the nasopharyngeal secretions in groups of infants after immunization with live attenuated poliovirus vaccine (OPV), enhanced potency inactivated poliovirus vaccine (IPV-EP), or after combined vaccination with IPV-EP followed by OPV. After three doses of vaccine, infants in all vaccine groups developed similar secretory IgA response to VP1 and VP2. The antibody response to VP3 was observed in 76.5% of subjects immunized with OPV alone and in ∼60% of those immunized with IPV-EP followed by OPV. However, only 13% of those immunized with IPV-EP alone exhibited VP3-specific antibody response. Significant differences in poliovirus type 3 specific antibody activity were observed between OPV and IPV-EP immunized subjects when trypsin-treated poliovirus was used as the antigen for neutralization or for ELISA in vitro. The neutralizing antibody activity against cleaved virus was significantly higher than against whole virus in the OPV vaccinated subjects. Both neutralizing and ELISA antibody activity against cleaved virus was significantly lower than against the whole virus in IPV-EP immunized subjects. [ABSTRACT FROM PUBLISHER]

Groups of infants were immunized with high-potency, inactivated polio vaccine (IPV) or live, attenuated oral polio vaccine (OPV)and studied for antibody responses to whole virus and polypeptides VP1, VP2,and VP3. Both vaccines induced neutralizing and enzyme linked immunosorbent assay (ELISA) IgG to the whole virus, IgG antibody to VP1 and VP3, and similar secretory IgA to VP1 and VP2 in the nasopharyngeal secretions (NPS) without any VP3 response. Virus-specific neutralizing activity in NPS was observed in 70% of subjects receiving OPV and in only 26.7% of subjects receiving IPV. ELISA antibody also appeared to be lower in IPV than in OPV subjects. These observations suggest that specific ELISA antibody to poliovirus virion proteins can be frequently induced in the secretory sites, by DPV as well as by IPV. Neutralizing antibody response in the NPS appeared, however, to be more effectively induced by DPV than by the high-potency IPV. [ABSTRACT FROM PUBLISHER]

The effect of respiratory syncytial virus (RSV) antibody complexes on the metabolism of human neutrophils was determined by examining the generation of luminol-dependent chemiluminescence, superoxide, and thromboxane B2. Incubation of neutrophils with RSV antibody complexes resulted in a significant increase in the production of chemiluminescence. The increase in chemiluminescence appeared to be due to (1) active phagocytosis of RSV antibody complexes as evidenced by 70% inhibition with cytochalasin B (P < 0.001) or (2) increased superoxide production as evidenced by 40% inhibition with superoxide dismutase (P < 0.001). The generation of superoxide was confirmed by specific analysis in a superoxide dismutase-inhibitable ferricytochrome c reduction assay. Of particular importance was the observation that RSV antibody complexes induced the release of significant quantities of thromboxane B2 from neutrophils as determined by radioimmunoassay. Oxygen radicals and/or products of arachidonic acid metabolism may, in part, mediate the pathogenesis of RSV infection through direct tissue damage and bronchoconstriction. [ABSTRACT FROM PUBLISHER]

The effects of middle ear effusions from patients with serous, seromucoid, mucoid, and purulent forms of otitis media with effusion on lymphoproliferative responses and polyclonal immunoglobulin synthesis were determined in peripheral blood and adenoidal lymphocytes. The responses were studied after stimulation of lymphocytes by phytohemagglutinin, pokeweed mitogen, purified protein derivative, herpes simplex virus, sheep red blood cells, or ovalbumin. Serous and seromucoid middle ear effusions resulted in significant suppression of proliferative responses to phytohemagglutinin, purified protein derivative, and herpes simplex virus and of polyclonal immunoglobulin synthesis in response to pokeweed mitogen, sheep red blood cells, and ovalbumin. The suppressive activity appeared to be associated with low-molecular-weight soluble products liberated by esterase-positive adherent population of cells in middle ear fluid. [ABSTRACT FROM PUBLISHER]

The characteristics of cellular elements in the middle ear effusions, peripheral blood, and adenoidal tissue and the effects of middle ear macrophages on the functional activity of lymphocytes were examined in 50 subjects with chronic otitis media. Macrophages were the predominant cell type in middle ear effusions, and they constituted up to 63% of the total number of cells. T cells were 11%–66% of the total number of cells. The proliferative responses induced by phytohemagglutinin or pokeweed mitogen in middle ear lymphocytes were generally low compared with the responses observed in peripheral blood and adenoidal lymphocytes. Cocultures of middle ear macrophages with adenoidal lymphocytes resulted in a significant depression of proliferative response and immunoglobulin synthesis in the lymphocytes. These observations suggest that macrophages in the middle ear may have a profound influence on the regulation of the immune response in the middle ear in patients who have otitis media with effusion. [ABSTRACT FROM PUBLISHER]

The transmission of rubella virus to newborn infants via the process of breast-feeding was studied after immunization of 16 breast-feeding and 10 non-breast-feeding mothers with HPV-77 DE5 live, attenuated rubella virus vaccine administered subcutaneously or RA 27/3 live, attenuated rubella virus vaccine administered intranasally or subcutaneously in the immediate postpartum period. Infectious rubella virus or virus antigen was observed in the breast milk of 11 (68%) of the 16 vaccinated, breast-feeding women studied. After maternal immunization, infectious rubella virus or virus antigen was recovered from the nasopharynx and throat of 56% of the breast-fed infants and from none of the non-breast-fed infants. Of the breast-fed infants, 25% showed transient seroconversion to rubella virus but without any clinical disease. No rubella virus-specific seroconversion was observed in the non-breast-fed infants. These observations provide strong support for the communicability of rubella virus to neonates via the process of breast-feeding. [ABSTRACT FROM PUBLISHER]

The development of an immune response to rubella virus in milk, serum, and nasopharyngeal secretions was studied in lactating postpartum women after immunization with HPV -77 DES or RA 27/3 live, attenuated rubella virus vaccine administered subcutaneously or intranasally. Over 69% of the women shed virus in milk after immunization. A predictable nasopharyngeal IgA and serum JgG antibody response to rubella virus was observed after subcutaneous or intranasal immunization with RA 27/3 vaccine. Little or no nasopharyngeal antibody response was seen after subcutaneous immunization with HPV -77 DES vaccine. A virus-specific IgA antibody response in milk was seen in all women. The presence of rubella virus in breast milk seemed to potentiate the peak levels of virus-specific antibody in the milk. Cellular immune reactivity to rubella virus in milk was observed in all vaccine groups. Thus, the virus-specific immune response induced in human milk after immunization with rubella virus vaccine may be intimately linked with the reactivity in bronchial lymphoid tissue. [ABSTRACT FROM PUBLISHER]

The in vitro correlates of cell-mediated immunity to liver tissue antigens and hepatitis B surface antigen (HBsAg) were studied in groups of subjects with acute and chronic hepatitis B virus (HBV) infection and in a population of HBV-seronegative controls. The technique of in vitro lymphocyte transformation (LTF) was employed in these studies. No LTF response to liver-specific antigen and HBsAg was observed in the control population. LTF activity in response to HBsAg was present in II of the 14 subjects with acute type B viral hepatitis during the early phase of the disease, and eight of these subjects also had LTF reactivity to liver antigen. During the convalescent phase the LTF reactivity to these antigens usually disappeared. More than 70% of patients with chronic carriage of HBsAg who had elevated levels of liver enzymes showed LTF responses to HBsAg, and a significant number of these subjects also exhibited LTF response to liver-specific antigen. On the other hand, chronic HBsAg carriers who persistently showed normal liver enzyme values (asymptomatic carriers) failed to show significant responses to liver antigen or HBsAg. It is suggested that the persistence of cellular reactivity to liver antigens may lead to the establishment of chronic liver disease. [ABSTRACT FROM PUBLISHER]

Groups of infants and children with infections due to respiratory syncytial virus (RSV) were tested at the onset of illness and one, two, and five months later for the presence of RSV-specific cell-mediated immunity, as determined by in vitro lymphocyte transformation (LTF) activity, and for complement-fixing (CF) antibody. An LTF response specific for RSV was observed in 65% of patients, and the response was largely associated with E-rosette-forming thymus-derived (T) lymphocytes. A significant cell-mediated immune response was observed in 78% of patients six months of age or younger, whereas only 46% of patients older than six months exhibited such responses. The difference between the mean stimulation index of the maximal LTF response in the two age groups was statistically significant (P < 0.05). On the other hand, a fourfold or greater rise in titers of CF antibody was observed in only 22% of patients six months of age or younger, whereas significant rises in antibody activity were observed in 50% of subjects older than six months. In view of the fact that RSV infection is most severe in the young infant, these observations raise the possibility that cell-mediated hypersensitivity reactions may be related to the pathogenesis of RSV infection of infants. [ABSTRACT FROM PUBLISHER]

Groups of schoolchildren were immunized with an inactivated recombinant influenza virus vaccine specific for the neuraminidase antigen of Port Chalmers influenza A virus (HeqIN2ch), a conventional biphasic Port Chalmers strain of influenza virus vaccine (H3chN2ch), or a placebo. Immunization with either virus vaccine was found to be safe and had no major adverse effects. Immunization with the Heq1N2ch vaccine resulted in no specific hemagglutination-inhibiting antibody response to H3ch antigen, although a specific neuraminidase antibody response to N2ch antigen was observed in >90% of the vaccinees. A subsequent natural outbreak of influenza virus resulted in serologically proven infection with H3ch virus in 26% of vaccinees receiving H3chN2ch virus vaccine, 47% of those receiving HeqIN2ch virus vaccine, and 44% of those receiving a placebo. However, the protective efficacy against illness was 74.3% for the H3chN2ch vaccine and only 51.4% for the HeqIN2ch vaccine. Regardless of the type of vaccine employed, vaccinees with serologic evidence of infection and clinical illness were found to have very low titers of hemagglutination-inhibiting and neuraminidase antibody. However, vaccinees with serologically proved infection but without clinical illness were found to have titers of antibody to neuraminidase before infection that were four- to eightfold higher than titers in vaccinees who were infected and who had clinical illness. [ABSTRACT FROM PUBLISHER]

Specimens of blood, feces, urine, and nasopharyngeal washings collected at regular intervals from subjects in an institutionalized population were tested for the presence of hepatitis B surface antigen (HBs Ag) and antibody by passive hemagglutination, radioimmunoassay, and immune electron microscopy. HBs Ag, confirmed by radioimmunoassay and immune electron microscopy, was frequently detected in nasal washings, urine, and feces of chronic carriers of HBs Ag and occasionally in subjects with recent seroconversion for HBs Ag. In addition, some subjects who had recently become positive for antibody to HBs Ag in serum had HBs Ag transiently present in urine and occasionally in the feces, without demonstrable antigenemia. [ABSTRACT FROM PUBLISHER]

The techniques of hemagglutination inhibition and in vitro lymphocyte transformation and the assay of migration inhibitory factor were used for study of the development of rubella antibody activity in serum and tonsillar tissue washings and of the appearance of rubella-specific, cell-mediated immunity in circulating and tonsillar lymphocytes in groups of children who underwent tonsillectomy at various intervals after natural rubella infection, subcutaneous immunization with HPV-77 DE/5 vaccine. or intranasal inoculation with RA27/3 live. attenuated rubella virus vaccine. Antibody response in serum and tonsillar tissue washings was detected regularly after natural infection or immunization. Development of specific cell-mediated immunity in circulating lymphocytes was regularly observed after natural infection and frequently after immunization. Natural infection or intranasal immunization with rubella vaccine resulted in the appearance of cell-mediated immunity in the tonsillar lymphoid tissue, and the response was detectable up to several years after natural infection in several cases. It is significant, however, that the level of cell-mediated immunity in tonsils was conspicuously low after subcutaneous immunization. These data suggest the induction of local cell-mediated immunity in tonsillar lymphoid tissue after local mucosal application of rubella virus. [ABSTRACT FROM PUBLISHER]

Neutrophil functions were evaluated in 13 normal subjects who had received 300 mg of clindamycin orally four times each day for two days. The mean serum concentration of clindamycin was 1.6 mg/l. Intracellular killing of a clindamycin-resistant strain of Staphylococcus aureus increased from 38% to 45%, P less than 0.005, during clindamycin therapy. In contrast, clindamycin therapy did not significantly alter chemotaxis, phagocytosis, chemiluminescence of neutrophils, or the ability of serum to generate chemotactic factor and opsonize particles of yeast. The potentially synergistic relationship between clindamycin and neutrophils may prove to be valuable for the treatment of staphylococcal infections in patients with defects in oxygen-dependent mechanism of neutrophil-mediated bacterial killing such as in chronic granulomatous disease. [ABSTRACT FROM AUTHOR]

The presence of histamine and eosinophil cationic protein in nasopharyngeal secretions of infants with respiratory syncytial virus (RSV)-induced bronchiolitis implies the activation of basophil and eosinophil leukocytes, but the specific mechanism of their recruitment has not been elucidated. Chemokines are potent and selective leukocyte chemotactic molecules that are also expressed by airway epithelial cells. Therefore, the pattern of chemokines produced in response to RSV infection was investigated in primary cultures of human nose- and adenoid-derived epithelial cells. Interleukin-8, growth-related peptide-α, and monocyte chemotactic protein-I were constitutively released by uninfected epithelial cells and were not further enhanced by infection with RSV. RANTES (regulated upon activation, normal T cell-expressed and -secreted), which was present in negligible concentrations in uninfected cultures, was strongly induced by RSV infection, in a dose- and timedependent manner. Through the release of RANTES, epithelial cells may control the selective concentration and activation of basophils and eosinophils in RSV-infected airway mucosa. [ABSTRACT FROM PUBLISHER]