Epidemiology of acute respiratory illness during an influenza outbreak in a nursing home. A prospective study.

We observed an influenza epidemic caused by influenza A/Arizona/82 (H3N2) in a nursing home during 1982 to 1983. A survey indicated that 59% of the residents were immunized before the outbreak. The outbreak was observed to begin in November, peak in February, and disappear in April. A significant level of herd immunity may have accounted for the slow progression through the nursing home. In addition, serologic evidence of concurrent infection with respiratory syncytial virus, parainfluenza virus, and Mycoplasma pneumoniae was present in many residents. Epidemics of influenza in a closed, partially immunized population in a nursing home may proceed at a slower rate than in an open, largely unimmunized community. By monitoring for infection with other respiratory agents, the complex nature of the outbreak in this nursing home became evident.

Association of influenza immunization with reduction in mortality in an elderly population. A prospective study.

We prospectively studied the efficacy of influenza vaccine during an influenza A/Arizona/80 (H3N2) outbreak at the Jewish Home and Hospital for the Aged in New York in the winter season of 1982 to 1983. All patients had been offered influenza vaccine before the outbreak; 181 chose to be vaccinated and 124 refused vaccination but agreed to participate in the study. Among those with serologic evidence of influenza infection, respiratory illness was significantly more common in the unvaccinated group (six of 14 vs one of 22). The overall mortality was 13 (7.2%) of 181 in the vaccinated group and 22 (17.7%) of 124 in the control group. The vaccinated and the control groups were examined for comparability. A logistic regression analysis, which controlled for differences in sex and level of nursing care, indicated that the difference in mortality was still significant, with a summary odds ratio of 2.7. The relative risk of death in the unvaccinated group was comparable at 2.18. Influenza vaccine reduced the mortality by 59% in the vaccinated group compared with the control group.

Potential for single high-dose influenza immunization in unprimed children.

High concentrations of split-product vaccine (SPV) are more immunogenic than lower concentrations. These studies were verified with another influenza strain, B/Singapore/22/79. Two ether-treated SPVs were compared in 80 children and young adults. The vaccine strains were influenza A/Bangkok/79, A/Brazil/78, and B/Singapore/79; 44 patients received a high-dose SPV containing 7, 7 and 60 micrograms each of the respective hemagglutinins (HA) and 36 received a standard dose SPV containing 7, 7, and 7 micrograms of HA, respectively. Among persons initially seronegative by hemagglutination inhibition (HAI) tests, the geometric mean titer (GMT) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one standard dose (P less than .05). Furthermore, 87% of high-dose recipients had HAI titer greater than or equal to 40 vs 44% of standard dose recipients. In initially seropositive persons, GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one standard dose (P less than .05). Immune response to the other two virus strains was comparable for the two vaccines. The reaction index for the high dose vaccine was 0.70 vs 0.45 for the standard dose (P = NS). An A/Bangkok epidemic struck the New York metropolitan area. The attack rate in unvaccinated matched sibling control subjects was 35% (15/43). There were no vaccine failures. In conclusions, in the small number of patients studied, a 60-micrograms HA dose of B/Singapore/79 was significantly more immunogenic than a standard 7-micrograms HA dose without an increase in reactogenicity.

Immunization of elderly people with high doses of influenza vaccine.

Healthy ambulatory elderly were immunized with increasing doses of the 1984-1985 influenza vaccine formulation. Two types of vaccines, split-product vaccine (SPV) and whole virus vaccine (WVV), were used. Three different doses, 0.5 mL (the standard volume, 1X), or 1.0 mL (2X), and 1.5 mL (3X) of each of the two vaccines were compared. The size of each of the six groups was between 23 and 26 subjects. The mean ages in each of the groups ranged from 71 to 74 years. No difference in local or systemic reaction was noted among the six groups. A dose-response effect was observed for the SPV recipients to the influenza A/Chile/83 (H1N1) strain. The geometric mean hemagglutination inhibition (HI)titer (GMT) was 1:76 after the 3X dose vs 1:38 after the 1X dose (P less than 0.025). To the influenza A/Philippines/82 (H3N2) strain the GMT was 1:70 after the 3X dose vs 1:43 after the 1X dose. A similar trend was noted for the influenza B/USSR/83 strain. A (HI) titer of greater than or equal to 1:40 for all the strains was seen in greater than 70% of the split product vaccine recipients only after the 3X dose. For the WVV recipients, increasing doses did not result in increasing GMT for any of the three vaccine strains. In addition, HI titers greater than or equal to 1:40 were not uniformly seen in greater than 70% of the vaccine recipients at any of the three whole virus vaccine doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Ocular findings in cystic fibrosis.

We examined 32 patients with cystic fibrosis, paying special attention to optic nerve performance and pupillary function. Decreased visual acuity occurred in nine of 64 eyes. Three of 17 patients (18%) who used chloramphenicol had bilaterally delayed P100 waves of the visual-evoked response of greater than 3 standard deviations. This was not found in patients who did not use chloramphenicol. Contrast sensitivity in patients with cystic fibrosis was decreased at every spatial frequency when compared to healthy controls. This decrease was noted in patients who did and did not use chloramphenicol, suggesting that chloramphenicol is not the only cause of decreased contrast sensitivity in cystic fibrosis. With pharmacologic pupil testing we determined that patients with cystic fibrosis display a preganglionic oculosympathetic paresis that corresponded to the disease severity, as measured by the Shwachman score.

Separation of serum ciliary dyskinesia substances from cystic fibrosis subjects.

Purified serum immunoglobulin G (IgG), derived from eight cystic fibrosis (CF) and five carrier subjects, has been shown to be responsible for the mucociliary disturbances noted in the rabbit tracheal bioassay. A small molecular substance of less than 10,000 but greater than 1,000 daltons (by Amicon filtration) was found associated with gamma-globulin fractions isolated from sera of these same cystic patients and their parents. Once separated by PM-10 ultrafiltration, this small substance was unable to promote the ciliary dyskinesia response in eight of eight CF and five of five CF carrier individuals unless pooled purified human IgG was added. In addition, the IgG-rich fraction retained by PM-10 ultrafiltration was still able to promote the ciliary dyskinesia response in the bioassay, an event noted in our earlier work with whole serum. The size of the small serum substance and its association with IgG closely corresponds to that described for the oyster test system, as well as to that produced by cultured cells derived from homozygotes and heteroxygotes for this genetic disorder. The persistence of the ability to promote mucociliary disturbances by the IgG-rich retentate PM-10 fractions may be indicative of the ineffective molecular separation by the Amicon ultransfiltration apparatus or may represent another CF-related, IgG-associated substance not influenced by ultrafiltration. Speculation The genetic disturbance of CF can be explained by the presence of a molecule(s) which has an affinity for IgG, which in turn gives rise to the various physiologic facets of this disorder. This molecule(s) is present in CF only because of a deficiency of an enzyme which normally controls its level by inactivation.

Thoracic kyphosis in cystic fibrosis.

The incidence of thoracic kyphosis in 91 older children and adolescents suffering from cystic fibrosis was 15.1%. Only 5.5% of 91 hospitalized "normal" adolescents had the deformity. Among the group of patients with cystic fibrosis we found a positive correlation between incidence of kyphosis and severe pulmonary disease. Because the kyphosis does not seem to represent a problem in itself, and owing to the various and multiple problems of these young people, braces are indicated only in exceptional cases with rapidly progressing deformity. A program of proper stretching, thoracic extension, and breathing exercises should be recommended for such patients.

The biologic activities of cystic fibrosis serum. II. Ultrastructural aspects of the effect of cystic fibrosis sera and calcium ionophore A23187 on rabbit tracheal explants.

Ultrastructural and cytochemical observations indicate that both cystic fibrosis (CF) sera and calcium ionophore A23187 induce a swelling or an increase in the size and possibly the number of secondary lysosomes and an increase in mucus secretion in epithelium of the rabbit tracheal bioassay system. Extended incubation of the rabbit tracheal explants with either CF or control sera produces a cytotoxic effect on the tracheal epithelium, but only after the termination of the normal bioassay time period. Comparative ultrastructural study of the effect of both CF sera and calcium ionophore A23187 on the rabbit tracheal bioassay system indicates that increased membrane permeability to calcium may be important in the production of the ciliary dyskinesia response by CF serum factor(s) in the rabbit tracheal bioassay system.

High-performance liquid chromatographic fractionation and partial characterization of cystic fibrosis serum ultrafiltrates.

Analytical separation of serum ultrafiltrates by high-performance liquid chromatography produces a distinctive peak with a retention time of 18.5-21 min (subfraction 18.5) from cystic fibrosis serum ultrafiltrates and obligate heterozygote serum ultrafiltrates, but not in significant concentrations from control or asthmatic serum ultrafiltrates. Semipreparative separation of control serum ultrafiltrates produced a small peak with similar retention time that was approximately 1% of the arbitrary absorbance units found in this cystic fibrosis subfraction. Subfraction 18.5 had biological activity only when separated from cystic fibrosis serum ultrafiltrate, but did not contain measurable amounts of C3a des-arginine and C4a des-arginine. Subfraction 18.5 is a low-molecular-weight material (1000-1400 daltons) that contains 14.9 micrograms orcinol positive material per 50 micrograms protein. The spectrum of subfraction 18.5 indicates that it has to be purified to homogeneity.

Biological activities of cystic fibrosis serum. IV. Stimulation of the calcium mediated K+ efflux from rat submandibular gland fragments.

Cystic fibrosis (CF) and heterozygote sera stimulate a significant K+ efflux from rat submandibular gland fragments in the presence of 1 mM ouabain. This sensitive parameter can be maximally stimulated by as little as 0.5% CF serum and is inhibited by the calcium channel blocker D600 and EGTA. Specific receptor blockers propranolol, phenoxybenzamine or atropine do not inhibit the CF serum-stimulated K+ efflux and agonists do not supramaximally stimulate K+ efflux when added with serum. CF serum-induced K+ efflux did not result in the leakage of lactic dehydrogenase into the bathing media nor did it mimic the action of the calcium ionophore A23187 when added in the presence of D600. In addition, ultrafiltrates of CF serum (less than 10,000 daltons) also stimulated K+ efflux from rat submandibular gland tissue fragments.

Composition of nasal secretion in patients with cystic fibrosis.

Quantitative examination of nasal secretion in patients with cystic fibrosis revealed a significantly greater than normal concentration of calcium, a finding in keeping with the hypothesized importance of this ion in the pathophysiology of the disease.

Immunization of elderly people with two doses of influenza vaccine.

A total of 104 elderly patients were immunized with one or two doses of the commercial 1985-1986 inactivated influenza vaccine formulation. Two types of vaccines (split virus [SV] vaccine and whole virus [WV] vaccine) and one or two doses 1 month apart were given. No difference in local or systemic reactions was noted among the four groups. The reciprocal geometric mean hemagglutination inhibition antibody titers against influenza A/Philippines/82 (H3N2) after one or two doses were: 78 for SV vaccine (one dose), 65 for SV vaccine (two doses), 55 for WV vaccine (one dose), and 51 for WV vaccine (two doses). Similar nonsignificant differences were observed for the other two antigens contained in the vaccine. The percentage with a hemagglutination inhibition titer of greater than or equal to 1:40 also did not differ after one or two doses. We then compared the postvaccination hemagglutination inhibition titers in young and old patients from previous studies in which apparent differences had appeared. We retested all sera simultaneously on the same day with the same reagents. No significant differences were apparent among age groups. In summary, the humoral immune response to inactivated influenza vaccine in healthy ambulatory elderly patients who have been previously immunized may not differ significantly from that of children and young adults. A booster dose 1 month after the first dose does not enhance immune responses in the elderly.

Comparison of live and inactivated influenza vaccine in high risk children.

Bivalent, live attenuated intranasally administered influenza A vaccines were compared to inactivated, parenterally administered influenza A vaccines in a double-blind clinical trial in 55 children and young adults with cystic fibrosis. No qualitative or quantitative difference in symptomatology between the group receiving intranasal live vaccine versus placebo was observed. Serum immune responses to live vaccines were somewhat less than those to inactivated vaccine, particularly in adults. IgA response in nasal secretions was minimal in each vaccine group. In contrast, an IgG response in nasal secretions was commonly seen with both topically applied live vaccine and parenterally administered inactivated vaccine.

Influenza vaccines in children. Comparison of new cetrimonium bromide and standard ether-treated vaccines.

We compared a new cetrimonium bromide (CTAB) subunit vaccine with a conventional polysorbate (Tween)-ether split-product vaccine in 63 children and young adults. The vaccines each contained influenza A/Bangkok/79, A/Brazil/78, B/Singapore/79; two doses were given one month apart. Among persons initially seronegative for A/Bangkok/79, the geometric mean antibody titer rose to more than 100 following one dose of vaccine, while those initially seropositive had titers of greater than 200 after one dose of either vaccine. Neither vaccine was able to induce comparable antibody titers to A/Brazil/78 or B/Singapore/79 after one dose in initially seronegative persons. After two doses the titers were greater than 100 for A/Brazil but not for B/Singapore. An A/Bangkok epidemic struck the New York City metropolitan area. The attack rate in the unvaccinated matched sibling control group was 35% (15/43). Only two of the 27 recipients of cetrimonium bromide vaccine and none of the 36 polysorbate-ether vaccines had a fourfold or greater increase in antibody titer during the epidemic.

Influenza vaccine in unprimed children: improved immunogenicity with few reactions following one high dose of split-product vaccine.

Thirty-one unprimed children and young adults received an influenza A/USSR/77 vaccine containing 43 microgram of hemagglutinin. Their HAI antibody response was compared to that in 92 age-matched individuals from the 1978 national influenza immunization trial who received 10 and 4 microgram HA vaccines. A dose-related antibody response was observed after the first vaccine doses in the 7- to 12- and 13- to 25-year-old groups. An HAI titer greater than or equal to 40 was present in 81% and 93% of 43 microgram HA recipients, in 38% and 43% of 10 microgram HA recipients, and in 24% and 12% of 4 micrograms HA recipients respectively. The antibody response to the 43 microgram HA dose was significantly higher than was the response to the 10 and 4 microgram HA doses. The local and systemic side effects were not significantly different among the three vaccine groups and the placebo group. Thus, a high dose of influenza A/USSR/77 split-product vaccine given to unprimed children and young adults stimulated presumably protective levels of antibody and was free of a significant incidence of side effects.

Treatment of pulmonary infections in patients with cystic fibrosis: a comparative study of ticarcillin and gentamicin.

The effectiveness of ticarcillin against Pseudomonas aeruginosa in acute exacerbations of pulmonary infection in patients with cystic fibrosis was evaluated. Seventy-one percent of patients treated with ticarcillin alone responded favorably. The response rate was similar in patients treated with a combination of ticarcillin plus gentamicin or with gentamicin alone. Severity of the underlying disease was the most important determinant of response to treatment. Ticarcillin-resistant organisms were recovered during treatment in 50% of patients who received this drug; recovery of them was not prevented by the inclusion of gentamicin in the therapeutic regimen nor did they interfere with clinical improvement. The ticarcillin-resistant strains persisted at follow-up, two to six months after completion of therapy, in only one of ten patients. No serious toxicity to ticarcillin was noted during the study period.

A controlled double-blind comparison of reactogenicity, immunogenicity, and protective efficacy of whole-virus and split-product influenza vaccines in children.

A double-blind randomized study with bivalent influenza virus vaccines was conducted to compare the local and systemic reactions and immunogenicity of a whole-virus vaccine and a split-product vaccine in children. Fevers of greater than 100 F were more frequent after vaccination with whole-virus than split-product vaccine especially in children one to four years old (69% vs 22%; P less than 0.01). Fevers of greater than or equal to 103 F did not occur in children who previously had been given influenza virus vaccine, even in the absence of preexisting homologous serum antibody. The immune response to the A/Port Chalmers/1/73 antigen in the vaccine was similar after administration of either whole-virus or split-product vaccine. However, split-product vaccine induced significantly less hemagglutination-inhibiting antibody to B/Hong Kong/5/72 virus in children younger than 10 years who had not been previously immunized; only 43% developed detectable antibody vs. 100% of those vaccinated with whole virus vaccine (P less than 0.01). These studies indicate that (1) in young children whole-virus vaccine causes fever more frequently than split-product vaccine; (2) young children previously vaccinated with influenza virus vaccine are unlikely to experience fever subsequent to immunization with a related antigen; and (3) split-product vaccine induces less antibody to B/Hong Kong/5/72 virus than whole-virus vaccine in immunologically unprimed young children.

Chlamydia pneumoniae infection in patients with cystic fibrosis.

The prevalence of atypical community-acquired infections as acute pulmonary exacerbations in patients with cystic fibrosis was prospectively studied. Thirty-two patients admitted to the hospital because of acute pulmonary exacerbations and 24 clinically stable patients seen for their routine visits were examined. The prevalence of infection with Chlamydia pneumoniae was assessed by culture and serology, and the presence of IgE to C. pneumoniae was studied by immunoblotting. A subgroup of patients was also examined for the presence of Mycoplasma pneumoniae infection. C. pneumoniae was isolated from four patients presenting with acute pulmonary exacerbations (12.5%) and from none of the stable patients; all patients for whom cultures were positive also had IgE to C. pneumoniae. Polymerase chain reaction analysis for M. pneumoniae was not positive for any patient, and only one patient with an acute exacerbation had an antibody titer compatible with a recent infection. We conclude that infection with C. pneumoniae is associated with acute pulmonary exacerbations in some patients with cystic fibrosis and that it may trigger the production of IgE specific to C. pneumoniae, thus leading to bronchial reactivity in these patients.

Comparison of new triton X-100- and tween-ether-treated split-treated vaccines in children.

Split-product vaccines (SPVs) combine the desirable properties of no systemic reactogenicity and adequate immunogenicity when two doses are given. We compared a new Triton X-100 SPV (Connaught Laboratories, Inc.) with the commercially available Tween-ether SPV (Parke-Davis & Co.) in 76 children and young adults 2 to 25 years old; there were 39 and 37, respectively, in each vaccine group. Both vaccines contained influenza A/Brazil/78, A/Texas/77, and B/Hong Kong/72 (7 microgram of hemagglutinin for each strain); two doses were administered 1 month apart. Among persons seronegative by the hemagglutination inhibition test, the geometric mean antibody titers rose to approximately 100 after the first vaccination for influenza A/Brazil/78 and A/Texas/77. For B/Hong Kong/72, however, seronegative recipients developed lower geometric mean titers of approximately 32 after one immunization. Against the new B/Singapore/79 strain neither SPV stimulated adequate cross-reacting hemagglutination inhibition antibody (geometric mean titers of approximately 10). In conclusion, the new Triton X-100 SPV appears to be comparable to the ether-treated SPV in primed subjects. Further studies in unprimed children should be done to confirm this impression. In addition, it would be advisable to study other dosage regimens in unprimed children with these SPVs.

Annual influenza vaccination: immune response in patients over 10 years.

OBJECTIVE: To determine the effect of repeated annual influenza immunization on the host's serum antibody. DESIGN: Ten year observational study with cohort design. SETTING: Cystic Fibrosis Center at St. Vincent's Hospital and Medical Center, New York City, NY. PATIENTS: Thirty-eight children and young adults with cystic fibrosis (CF). MEASUREMENTS: Serum hemagglutination inhibition (HI) antibody titers were determined at the time of vaccination and 4 weeks later each year in the fall before the influenza epidemic. Shwachman scores were determined each year. RESULTS: While the pre-vaccination and post-vaccination geometric mean serum HI antibody titers varied from year to year, no upward or downward trend was evident over the 10 year period. The reciprocal of the post-vaccination geometric mean HI titers ranged annually from 32 to 74 for the influenza A (H3N2) vaccine strains, from 53 to 133 for the influenza A (H1N1) strains, and from 18 to 174 for influenza B strains. In addition, the majority of vaccinees had a presumably protective post-vaccination serum HI titer > or = 1:40 each year for all three vaccine strains. The initial mean Shwachman score of the group was 77. The final score of 76 after 10 years was not significantly different. CONCLUSIONS: Annual influenza vaccination appears to regularly induce presumably protective serum antibody levels in most CF children and young adults studied over a 10 year period.