Antibody responses to bovine parainfluenza virus type 3 (PIV3) vaccination and human PIV3 infection in young infants.

A phase 2 clinical trial was conducted to evaluate the antibody responses to bovine parainfluenza virus type 3 (bPIV3) vaccination in young infants. Three groups were tested as follows: placebo (n=66) and 10(5) (n=64) or 10(6) (n=62) TCID(50) of bPIV3. The vaccine or placebo was administered intranasally at ages 2, 4, 6, and 12-15 months, and serum specimens were collected at ages 2, 6, 7, 12-15, and 13-16 months. Serum hemagglutination inhibition (HI) and IgA antibody titers against bPIV3 and human PIV3 (hPIV3) were measured. The results indicate that antibody responses to bPIV3 vaccination are more likely to be detected by the bPIV3 IgA and HI assays than by the hPIV3 IgA and HI assays, that bPIV3-induced antibody response can be differentiated from hPIV3-induced antibody response most reliably by comparing bPIV3 and hPIV3 HI titers, and that bPIV3 vaccine prevents vaccine recipients from developing antibody profiles of hPIV3 primary infection.

Cost-effectiveness analysis of an intranasal influenza vaccine for the prevention of influenza in healthy children.

OBJECTIVE: Intranasal influenza vaccine has proven clinical efficacy and may be better tolerated by young children and their families than an injectable vaccine. This study determined the potential cost-effectiveness (CE) of an intranasal influenza vaccine among healthy children. METHODS: We conducted a CE analysis of data collected between 1996 and 1998 during a prospective 2-year efficacy trial of intranasal influenza vaccine, supplemented with data from the literature. The CE analysis included both direct and indirect costs. We enrolled 1602 healthy children aged 15 to 71 months in year 1, 1358 of whom were enrolled in year 2. One or 2 doses of intranasal influenza vaccine or placebo were administered to measure the cost per febrile influenza-like illness (ILI) day avoided. RESULTS: During the 2-year study period, vaccinated children had an average of 1.2 fewer ILI fever days/child than unvaccinated children. In an individual-based vaccine delivery scenario with vaccine given twice in the first year and once each year thereafter at an assumed base case total cost of $20 for the vaccine and its administration (ie, per dose), CE was approximately $30/febrile ILI day avoided. CE ranged from $10 to $69/febrile ILI day avoided at $10 to $40/dose, respectively. In a group-based delivery scenario, vaccination was cost saving compared with placebo and remained so if vaccine cost was <$28 (the break-even price per dose). In the individual-based scenario, vaccination was cost saving if vaccine cost was <$5. In this scenario, nearly half of lost productivity in the vaccine group was attributable to vaccine visits, which overshadowed the relatively modest savings in ILI-associated costs averted. CONCLUSIONS: Routine use of intranasal influenza vaccine among healthy children may be cost-effective and may be maximized by using group-based vaccination approaches. cost-effectiveness, influenza, vaccine, children.

Safety, efficacy and effectiveness of the influenza virus vaccine, trivalent, types A and B, live, cold-adapted (CAIV-T) in healthy children and healthy adults.

Influenza is a major cause of illness. We have assessed the safety, efficacy, and effectiveness of CAIV-T vaccine. A two year, multicenter, double-blind, placebo-controlled, efficacy field trial in pre-school aged children was conducted; 1602 enrolled in Year One and 1358 (85%) returned in Year Two. In both study years combined, the overall vaccine efficacy against culture-confirmed influenza was 92% (95% CI: 88, 94). The vaccine efficacy was 95% (95% CI: 62, 99) against lower respiratory illness, 94% (95% CI: 90, 96) against febrile illness and 96% (95% CI: 88, 99) against otitis media associated with culture-confirmed influenza. A multicenter, double-blind, placebo-controlled, effectiveness field trial was conducted in 4561 working adults aged 18 to 64 years. Episodes and days of febrile illness (FI), severe febrile illness (SFI), febrile upper respiratory illness (FURI), work loss, and health care use were assessed. Vaccination significantly reduced the numbers of SFI, 18.8% reduction (95% CI: 7, 29), and FURI, 26.3% reduction (95% CI: 13, 33); and led to fewer days of illness (22.9% reduction for FI, 27.3% reduction for SFI), fewer days of work lost (17.9% reduction for SFI, 28.4% for FURI), and fewer days of health care provider visits (24.8% for SFI, 40.9% for FURI). Prescription antibiotics and over-the-counter medications were also reduced. The vaccine was generally safe and well tolerated with no vaccine related serious adverse events. LAIV represents an additional important option for the control of influenza.

Half-life of human parainfluenza virus type 3 (hPIV3) maternal antibody and cumulative proportion of hPIV3 infection in young infants.

During a phase 2 trial of parainfluenza virus type 3 (PIV3) vaccine, sequential serum samples were obtained from infants at 2, 6, 7, 12-15, and 13-16 months of age. Paired serum samples obtained at 2 and 6 months of age were used to estimate the biologic half-life of human PIV3 (hPIV3) maternal antibody in young infants. On the basis of the assumption that hPIV3 maternal antibody decays exponentially and constantly, the biologic half-life was estimated without adjusting for body weight increases. Cumulative proportions of hPIV3 infection in young infants were further estimated after adjusting for maternal antibody decline. A hemagglutination inhibition assay was used to quantify hPIV3 antibody. The mean (95% confidence interval) biologic half-life was estimated to be 51 (42-60) days, on the basis of which cumulative proportions of hPIV3 infection were estimated to be 11% at 6 months of age, 47% at 12-15 months of age, and 50% at 13-16 months of age.

A comparison of multiple regimens of pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine and pneumococcal polysaccharide vaccine in toddlers.

Children who had been randomized to receive one dose of either heptavalent pneumococcal polysaccharide-meningococcal outer membrane protein complex conjugate vaccine (PCV) or 23-valent pneumococcal polysaccharide vaccine (PN23) at 12, 15, or 18 months of age were subsequently randomized to receive a booster injection of either PCV or PN23 12 months later. For those children who received a priming dose of PCV (N=75) compared to PN23 (N=48) at 12, 15, or 18 months of age, higher serum antibody concentrations were achieved 1 month following a booster injection of either PCV or PN23 for all serotypes tested (p<0.001). Within the group of children receiving a priming dose of PCV, those children who received a booster dose of PN23 developed higher serum antibody concentrations for four of the seven serotypes tested and similar opsonic antibody titers to serotype 6B, yet more frequent erythema (p=0.030) and pain or soreness (p=0.024) at the injection site compared to those boosted with PCV. In conclusion, a single dose of PCV at 12-18 months of age primed for responses to booster doses of either PCV or PN23 12 months later. For those children who received a priming dose of PCV, boosting with PN23 resulted in more frequent injection site pain and erythema than boosting with PCV, yet higher antibody concentrations for most of the serotypes tested.

Estimation of the efficacy of live, attenuated influenza vaccine from a two-year, multi-center vaccine trial: implications for influenza epidemic control.

The authors provide an analysis of data from a two-year (1996-1998), multicenter (ten US cities), double-blinded, placebo-controlled influenza vaccine trial in children. The vaccine was the trivalent cold-adapted influenza vaccine. Estimates are made of the vaccine efficacy for susceptibility to culture-confirmed influenza (VE(S)) while taking inter-center variability in the risk of infection into account. Our overall estimate of VE(S) against influenza is 0.92 (95% confidence interval (CI) 0.89-0.94). In addition, for the second year, although the vaccine contained antigen for A/Wuhan-like (H3N2), the estimated VE(S) for epidemic variant A/Sydney-like (H3N2) was 0.89 (95% CI 0.81-0.94). Thus, the vaccine showed a high degree of protection against a variant not closely matched to the vaccine antigen. With regard to natural immunity, an influenza A infection in the first year reduces the estimated risk of an influenza A infection in the second year by a factor of 0.88 (95% CI 0.21-0.98). When comparing year 1 to year 2, there is a negative correlation of -0.50 in the center-specific attack rates in the placebo groups. This is consistent with the theory that natural immunity provides overall community protection to children. The authors argue that mass vaccination of 70% of the children with the cold-adapted influenza vaccine could provide substantial protection to the community at large.

Correlates of immune protection induced by live, attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine.

The authors conducted a 2-year, multicenter, double-blind, placebo-controlled efficacy field trial of live, attenuated, cold-adapted, trivalent influenza vaccine administered by nasal spray to children 15-71 months old. Overall, vaccine was 92% efficacious at preventing culture-confirmed infection by influenza A/H3N2 and influenza B. Because influenza A/H1N1 did not cause disease during the years in which this study was conducted, the authors sought to determine vaccine efficacy and correlates of immune protection against experimental challenge with 107 TCID50 of attenuated H1N1 (vaccine strain) by intranasal spray. Prechallenge assessments included serum hemaglutination-inhibiting (HAI) antibody and nasal wash IgA antibody to H1N1. Vaccine was 83% efficacious (95% confidence interval, 60%-93%) at preventing shedding of H1N1 virus after challenge. Any serum HAI antibody or any nasal wash IgA antibody was correlated with significant protection from H1N1 infection as indicated by vaccine-virus shedding, and high efficacy against H1N1 challenge was demonstrated.

Genotypic stability of cold-adapted influenza virus vaccine in an efficacy clinical trial.

An investigational live influenza virus vaccine, FluMist, contains three cold-adapted H1N1, H3N2, and B influenza viruses. The vaccine viruses are 6/2 reassortants, in which the hemagglutinin (HA) and neuraminidase (NA) genes are derived from the circulating wild-type viruses and the remaining six genes are derived from the cold-adapted master donor strains. The six genes from the cold-adapted master donor strains ensure the attenuation, and the HA and NA genes from the wild-type viruses confer the ability to induce protective immunity against contemporary influenza strains. The genotypic stability of this vaccine was studied by employing clinical samples collected during an efficacy trial. Viruses present in the nasal and throat swab specimens and in supernatants after culturing the specimens were detected and subtyped by multiplex reverse transcriptase (RT)-PCR. Complete genotypes of these detected viruses were determined by a combination of RT-PCR and restriction fragment length polymorphism, multiplex RT-PCR and fluorescent single-strand conformation polymorphism, and nucleic acid sequencing analysis. The FluMist vaccine appeared to be genotypically stable after replication in the human host. All viruses detected during the 2-week postvaccination period were shed vaccine viruses and had maintained the 6/2 genotype.

Efficacy of vaccination with live attenuated, cold-adapted, trivalent, intranasal influenza virus vaccine against a variant (A/Sydney) not contained in the vaccine.

OBJECTIVE: To determine the safety, immunogenicity, and efficacy of revaccination of children with live attenuated influenza vaccine. STUDY DESIGN: A 2-year multicenter, double-blind, placebo-controlled, efficacy field trial of live attenuated, cold-adapted trivalent influenza vaccine administered by nasal spray to children. This report summarizes year 2 results, a year in which the epidemic strain of influenza A/Sydney was not well matched to the vaccine strains. Each year, vaccine strains were antigenically equivalent to the contemporary inactivated influenza vaccine. In year 2, a single intranasal revaccination was administered. Active surveillance for influenza was conducted during the influenza season by means of viral cultures. Influenza cases were defined as illnesses with wild-type influenza virus isolated from respiratory secretions. RESULTS: In year 2, 1358 (85%) children, 26 to 85 months of age, returned for revaccination. The intranasal vaccine was easily accepted, well tolerated, and immunogenic. Revaccination resulted in 82% to 100% of the vaccinated children in a subset studied for immunogenicity being seropositive as compared with 26% to 65% of placebo recipients, depending on the influenza strain tested. No serious adverse events were associated with the vaccine. In addition to the strains in the vaccine, antibody was induced to the variant strain A/Sydney/H3N2. In year 2, influenza A/Sydney/H3N2, a variant not contained in the vaccine, caused 66 of 70 cases of influenza A; nonetheless, intranasal vaccine was 86% efficacious in preventing A/Sydney influenza. Eight cases of lower respiratory tract disease were associated with A/Sydney influenza; all cases were in the placebo group. CONCLUSIONS: This live attenuated, cold-adapted influenza vaccine was safe, immunogenic, and efficacious against influenza A/H3N2 (including a variant, A/Sydney, not contained in the vaccine) and influenza B. The characteristics of this vaccine make it suitable for routine use in children to prevent influenza.

Effectiveness of live, attenuated intranasal influenza virus vaccine in healthy, working adults: a randomized controlled trial.

CONTEXT: Influenza virus is a major cause of illness, disruption to daily life, and increased use of health care in all age groups. OBJECTIVE: To assess the safety and effectiveness of intranasally administered trivalent, live, attenuated influenza virus (LAIV) vaccine for reducing illness, absenteeism, and health care use among healthy, working adults. DESIGN: Randomized, double-blind, placebo-controlled trial conducted from September 1997 through March 1998. SETTING: Thirteen centers across the United States. PARTICIPANTS: A total of 4561 healthy, working adults aged 18 to 64 years recruited through health insurance plans, at work sites, and from the general population. INTERVENTION: Participants were randomized 2:1 to receive intranasally administered trivalent LAIV vaccine (n = 3041) or placebo (n = 1520) in the fall of 1997. MAIN OUTCOME MEASURES: Episodes of febrile illness, severe febrile illness, febrile upper respiratory tract illness, work loss, and health care use during the peak and total influenza outbreak periods, and adverse events. RESULTS: Recipients of LAIV vaccine were as likely to experience 1 or more febrile illnesses as placebo recipients during peak outbreak periods (13.2% for vaccine vs 14.6% for placebo; P=.19). However, vaccination significantly reduced the numbers of severe febrile illnesses (18.8% reduction; 95% confidence interval [CI], 7.4%-28.8%) and febrile upper respiratory tract illnesses (23.6% reduction; 95% CI, 12.7%-33.2%). Vaccination also led to fewer days of illness across all illness syndromes (22.9% reduction for febrile illnesses; 27.3% reduction for severe febrile illnesses), fewer days of work lost (17.9% reduction for severe febrile illnesses; 28.4% reduction for febrile upper respiratory tract illnesses), and fewer days with health care provider visits (24.8% reduction for severe febrile illnesses; 40.9% reduction for febrile upper respiratory tract illnesses). Use of prescription antibiotics and over-the-counter medications was also reduced across all illness syndromes. Vaccine recipients were more likely to experience runny nose or sore throat during the first 7 days after vaccination, but serious adverse events between the groups were not significantly different. The match between the type A(H3N2) vaccine strain and the predominant circulating virus strain (A/Sydney/05/97[H3N2]) for the 1997-1998 season was poor, suggesting that LAIV provided substantial cross-protection against this variant influenza A virus strain. CONCLUSION: Intranasal trivalent LAIV vaccine was safe and effective in healthy, working adults in a year in which a drifted influenza A virus predominated.

Safety of a trivalent live attenuated intranasal influenza vaccine, FluMist, administered in addition to parenteral trivalent inactivated influenza vaccine to seniors with chronic medical conditions.

We conducted a randomized, double-blind trial to evaluate the safety and tolerability of a live attenuated cold adapted trivalent intranasal influenza vaccine, FluMist, compared with intranasal placebo when given in addition to a licensed trivalent injected inactivated influenza vaccine (TIV). The study population consisted of persons 65 years of age and older with chronic cardiovascular or pulmonary conditions or diabetes mellitus. During the 7 days post-vaccination, sore throat was reported on at least one day by 15% (15/100) of FluMist recipients compared with 2% (2/100) of intranasal placebo recipients (p = 0.001). No other reactogenicity symptom was statistically associated with receipt of FluMist. Among this group, FluMist was safe and well tolerated when administered with TIV.

The efficacy of live attenuated, cold-adapted, trivalent, intranasal influenzavirus vaccine in children.

BACKGROUND: Influenzavirus vaccine is used infrequently in healthy children, even though the rates of influenza in this group are high. We conducted a multicenter, double-blind, placebo-controlled trial of a live attenuated, cold-adapted, trivalent influenzavirus vaccine in children 15 to 71 months old. METHODS: Two hundred eighty-eight children were assigned to receive one dose of vaccine or placebo given by intranasal spray, and 1314 were assigned to receive two doses approximately 60 days apart. The strains included in the vaccine were antigenically equivalent to those in the inactivated influenzavirus vaccine in use at the time. The subjects were monitored with viral cultures for influenza during the subsequent influenza season. A case of influenza was defined as an illness associated with the isolation of wild-type influenzavirus from respiratory secretions. RESULTS: The intranasal vaccine was accepted and well tolerated. Among children who were initially seronegative, antibody titers increased by a factor of four in 61 to 96 percent, depending on the influenza strain. Culture-positive influenza was significantly less common in the vaccine group (14 cases among 1070 subjects) than the placebo group (95 cases among 532 subjects). The vaccine efficacy was 93 percent (95 percent confidence interval, 88 to 96 percent) against culture-confirmed influenza. Both the one-dose regimen (89 percent efficacy) and the two-dose regimen (94 percent efficacy) were efficacious, and the vaccine was efficacious against both strains of influenza circulating in 1996-1997, A(H3N2) and B. The vaccinated children had significantly fewer febrile illnesses, including 30 percent fewer episodes of febrile otitis media (95 percent confidence interval, 18 to 45 percent; P<0.001). CONCLUSIONS: A live attenuated, cold-adapted influenzavirus vaccine was safe, immunogenic, and effective against influenza A(H3N2) and B in healthy children.

Safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine (PedvaxHIB) in Papua New Guinean children.

BACKGROUND: In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit. The choice of the Hib conjugate vaccine will be based on the evaluation of several Hib conjugate vaccines, after consideration of such factors as the ease of incorporation into the current vaccination schedule, cost, kinetics of antibody responses and safety. METHODS: This study evaluated the safety and immunogenicity of Hib polysaccharide-Neisseria meningitidis outer membrane protein complex conjugate vaccine (PRP-OMPC) in Papua New Guinea. 95 children were recruited at Goroka Base Hospital, Eastern Highlands Province, and enrolled in the study. PRP-OMPC was administered at ages 2, 4 and 12 to 15 months. Blood was collected before each dose, one month after the second and booster doses, and at ages 18 and 24 months. Antibody to PRP (anti-PRP) was measured by radioimmunoassay. RESULTS: PRP-OMPC was generally well tolerated. At successive sampling times from the prevaccination bleed through the 1-month post-booster bleed, geometric mean titres were 0.18, 1.45, 2.54, 1.03 and 8.05 micrograms/ml, respectively (n = 60). The proportions of subjects with anti-PRP titres > or = 1.0 microgram/ml were 2%, 62%, 73%, 47% and 93%, respectively (n = 60). Persistence of anti-PRP was ascertained in 41 subjects. The GMTs at 18 and 24 months were 3.42 and 2.0 micrograms/ml, respectively. CONCLUSIONS: PRP-OMPC was found to be immunogenic after the first dose and to elicit a robust booster response. Antibody titres persisted until age 24 months, at which time 100% of subjects had anti-PRP > or = 0.15 microgram/ml. These results are consistent with previous studies in US Native American infants and in Gambian infants.

Immunogenicity and safety of Haemophilus influenzae type b polysaccharide-Neisseria meningitidis conjugate vaccine in 7.5 micrograms liquid formulation: a comparison of three lots with the 15.0 micrograms lyophilized formulation. Study Group for 7.5 micrograms Liquid PedvaxHIB.

We conducted a multicenter, single-blind, randomized comparisons of the immunogenicity and safety of three manufacturing-scale lots of 7.5 micrograms liquid Haemophilus influenzae type b polysaccharide- Neisseria meningitidis conjugate vaccine (PRP-OMPC) and a single lot of 15.0 micrograms lyophilized PRP OMPC. A total of 908 infants were entered into the study. Each infant received two primary injections intramuscularly 2 months apart beginning at age 2-6 months and a booster injection at 12-15 months. Blood samples for serology were obtained before each injection and 1 month after the second and the booster dose. Immune responses were measured by radioimmunoassay. Approximately 80% of the infants achieved a titer > 1.0 micrograms ml-1 after the second primary dose of all four lots tested: the geometric mean titer (GMT) was ca 3 micrograms ml-1 for each vaccine group. After the booster dose, more than 90% of infants from each vaccine group had a titer > 1.0 microgram ml-1;GMTs ranged from 8 to 10 micrograms ml-1. No serious vaccine-associated adverse reactions were reported. Thus the 7.5 liquid PRP OMPC vaccine was at least as immunogenic and well tolerated as the 15.0 micrograms lyophilized vaccine.

Reduction of nasopharyngeal carriage of pneumococci during the second year of life by a heptavalent conjugate pneumococcal vaccine.

Children 12-18 months old were randomized to receive one dose of a conjugate heptavalent pneumococcal vaccine, two doses of the same vaccine, or one dose of a 23-valent native polysaccharide vaccine. Before immunization, pneumococci included in the conjugate vaccine were isolated from 24% of the children, and an antibiotic-resistant pneumococcus was isolated from 22% of the children. The vaccines had no effect on carriage of non-vaccine-type pneumococci. In contrast, there was a significant reduction in carriage of vaccine-type pneumococci 3 months after one dose and 1 month after a second dose of conjugate vaccine (from 25% to 9% and 7%, respectively; P < .001). No effect was seen after vaccination with the nonconjugate vaccine. One year after immunization, carriage of antibiotic-resistant vaccine-type pneumococci in children receiving conjugate vaccine was lower than that in children receiving the nonconjugate vaccine (4% vs. 14%, P = .042). Conjugate pneumococcal vaccines may reduce spread of pneumococci in the community.

Immunogenicity of heptavalent pneumococcal conjugate vaccine in infants.

OBJECTIVE: To evaluate the safety, immunogenicity, and immunologic memory in young infants of a seven-valent (6B, 14, 19F, 23F, 18C, 4, 9V) pneumococcal vaccine conjugated to the outer membrane protein complex of Neisseria meningitidis. VACCINEES: Healthy 2-month-old infants 12- to 15-month-old control infants were recruited from participating private practices. METHODS: Infants (n = 25) were vaccinated at 2, 4, and 6 months of age with the conjugated pneumococcal vaccine, followed by a single dose of licensed pneumococcal polysaccharide vaccine (n = 20) at 12 to 15 months of age. Thirteen infants who had not received the investigational pneumococcal conjugate vaccine served as control subjects and were given a single dose of the licensed pneumococcal polysaccharide vaccine at 12 to 15 months of age. RESULTS: The investigational pneumococcal conjugate vaccine was well tolerated by infants. The vaccine was highly immunogenic in young infants, with significant increases in antibody to all seven serotypes after either two or three injections. At 12 to 15 months of age, infants who had been primed with the investigational pneumococcal conjugate vaccine had a brisk immunologic response to the booster injection of the licensed pneumococcal polysaccharide vaccine. Control infants, who received a single primary injection of the licensed pneumococcal polysaccharide vaccine, had negligible immunologic responses to four of the seven serotypes and low responses to the other three types. CONCLUSION: The investigational seven-valent pneumococcal conjugate vaccine administered to young infants was well tolerated and highly immunogenic and provided immunologic memory to an injection of the licensed pneumococcal polysaccharide vaccine.

Cerebrospinal fluid analysis in children with seizures.

Cerebrospinal fluid (CSF) examinations of 212 children aged two to 24 months with idiopathic nonfebrile seizures, complex febrile seizures, or status epilepticus, who had a lumbar puncture within 24 hours of the convulsion, were reviewed to determine whether an idiopathic convulsion can result in CSF abnormalities. Children with complex febrile seizures had a median CSF white blood cell count of 1 cell/mm3 (range 0-19 cells/mm3) and a median CSF polymorphonuclear (PMN) cell count of 0 cells/mm3 (range 0-8 cells/mm3). The CSF white blood cell (WBC) count was elevated above the upper limit of normal of 5 cells/mm3 in 9.8% and the absolute number of polymorphonuclear cells was more than 0 cells/mm3 in 26.2% of the complex febrile seizure subjects. Values at the 95th percentile were calculated; a total of 8 WBC/mm,3 4 PMN/mm,3 protein of 73 mg/dl and glucose of 119 mg/dl determined the 95th percentile CSF values for the patients with complex febrile seizures. Patients with nonfebrile seizures or with status epilepticus had similar findings. We conclude that complex febrile, idiopathic nonfebrile convulsions or status epilepticus may affect CSF findings in children: CSF with > 20 WBC/mm3 or > 10 PMN/mm3 should not be attributed to seizures.

Comparison of cefpodoxime proxetil and cefixime in the treatment of acute otitis media in infants and children. Otitis Study Group.

OBJECTIVE: To compare the use of once-a-day cefpodoxime proxetil to once-a-day cefixime in the treatment of acute suppurative otitis media. DESIGN: Randomized, multicenter, investigator-blinded. SETTING: Outpatient. PATIENTS: A total of 368 patients (age 2 months to 17 years) were randomized to receive either cefpodoxime or cefixime in a 2:1 ratio (245 cefpodoxime, 123 cefixime); 236 patients (155 cefpodoxime, 81 cefixime) were evaluable for drug efficacy. INTERVENTIONS: Patients received either cefpodoxime proxetil oral suspension (10 mg/kg/day, once daily for 10 days) or cefixime oral suspension (8 mg/kg/day, once daily for 10 days). MAIN OUTCOME MEASURES: Clinical evaluations were performed before treatment (study day 1), at an interim visit (study day 3 through 6), at the end of therapy (study day 12 through 15), and at final follow-up (study day 25 through 38). Microbiologic evaluations were performed at enrollment and whenever appropriate thereafter. RESULTS: End-of-therapy clinical cure rates in evaluable patients were 56% for the cefpodoxime group and 54% for the cefixime group. Clinical improvement rates were 27% for both groups. Clinical response rates were not significantly different between treatment groups (P = .541; 95% confidence interval = -8.1%, 15.2%). At long-term follow-up, 17% of patients in the cefpodoxime group and 20% in the cefixime group had a recurrence of infection. Drug-related adverse events (eg, diarrhea, diaper rash, vomiting, rash) occurred in 23.3% of cefpodoxime-treated patients and 17.9% of cefixime-treated patients (P = .282). CONCLUSIONS: These findings suggest that cefpodoxime proxetil administered once daily is as effective and safe as cefixime given once daily in the treatment of acute suppurative otitis media in pediatric patients.

Risk of serious acute neurological illness after immunization with diphtheria-tetanus-pertussis vaccine. A population-based case-control study.

OBJECTIVE: To evaluate the association between serious acute neurological illness and receipt of whole-cell pertussis vaccine, given as diphtheria-tetanus-pertussis (DTP) vaccine. DESIGN: Population-based case-control study. SETTING: Outpatient and inpatient hospital settings, physician practices, and the general population in Washington and Oregon states. SUBJECTS: A total of 424 confirmed cases of neurological illness were identified prospectively during a 12-month period by statewide active surveillance from the population of 218,000 children 1 to 24 months of age living in Washington and Oregon (estimated 368,000 DTP immunizations given). Each case child was matched to two population control children by birth date (+/- 5 days), gender, and county of birth. Written immunization records were used to determine whether illness occurred within 7 days of immunization in case children, or within 7 days of the same reference date in control children, thus qualifying as exposed. MAIN OUTCOME MEASURES: Outpatient and inpatient cases of complex febrile seizures, seizures without fever, infantile spasms, and acute encephalitis/encephalopathy confirmed by an expert panel masked to immunization history. RESULTS: The estimated odds ratio (OR) for onset of serious acute neurological illness within 7 days for young children exposed to DTP vaccine was 1.1 (95% confidence interval [CI], 0.6 to 2.0). When the analysis was restricted to children with encephalopathy or complicated seizures and adjusted for factors possibly affecting vaccine administration, the OR was 3.6 (95% CI, 0.8 to 15.2). Odds ratios for specific study diagnoses varied, but all CIs included 1. No elevated risk was observed for the largest group of illnesses studied, nonfebrile seizures (OR, 0.5; 95% CI, 0.2 to 1.5). CONCLUSIONS: This study did not find any statistically significant increased risk of onset of serious acute neurological illness in the 7 days after DTP vaccine exposure for young children.