A prospective, randomized, comparative US trial of a combination hepatitis A and B vaccine (Twinrix) with corresponding monovalent vaccines (Havrix and Engerix-B) in adults.

In an open, randomized, multicenter, controlled clinical trial in the US, 773 adults were administered either a combination hepatitis vaccine (Twinrix: 720 EL.U inactivated hepatitis A antigen and 20 mcg recombinant hepatitis B surface antigen per milliliter) on a 0, 1, 6 month schedule or corresponding monovalent vaccines concurrently (Havrix, 1440 EL.U/ml of hepatitis A antigen at 0, 6 months and Engerix-B, 20 mcg of hepatitis B surface antigen at 0, 1, 6 months). Non-inferiority testing for the primary endpoint, severe soreness, and equivalence testing for the secondary endpoints, anti-HAV seroconversion and anti-HBs seroprotection, showed that safety and immunogenicity were comparable in the two groups.

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.

Oral oseltamivir treatment of influenza in children.

BACKGROUND: Oral oseltamivir administration is effective treatment for influenza in adults. This study was conducted to determine the efficacy, safety and tolerability of oseltamivir in children with influenza. METHODS: In this randomized, double blind, placebo-controlled study, children 1 through 12 years with fever [> or =100 degrees F (> or =38 degrees C)] and a history of cough or coryza <48 h duration received oseltamivir 2 mg/kg/dose or placebo twice daily for 5 days. The primary efficacy endpoint was the time to resolution of illness including mild/absent cough and coryza mild/absent, return to normal activity and euthermia. RESULTS: Of 695 enrolled children 452 (65%) had influenza (placebo, n = 235; oseltamivir, n = 217). Among infected children the median duration of illness was reduced by 36 h (26%) in oseltamivir compared with placebo recipients (101 h; 95% confidence interval, 89 to 118 vs. 137 h; 95% confidence interval, 125 to 150; P < 0.0001). Oseltamivir treatment also reduced cough, coryza and duration of fever. New diagnoses of otitis media were reduced by 44% (12% vs. 21%). The incidence of physician-prescribed antibiotics was significantly lower in influenza-infected oseltamivir (68 of 217, 31%) than placebo (97 of 235, 41%; P = 0.03) recipients. Oseltamivir therapy was generally well-tolerated, although associated with an excess frequency of emesis (5.8%). Discontinuation because of adverse events was low in both groups (1.8% with oseltamivir vs. 1.1% with placebo). Oseltamivir treatment did not affect the influenza-specific antibody response. CONCLUSIONS: Oral oseltamivir administration is an efficacious and well-tolerated therapy for influenza in children when given within 48 h of onset of illness.

An acellular pertussis vaccine in healthy adults: safety and immunogenicity. Pennridge Pediatric Associates.

Recent data indicate that Bordetella pertussis can be an important cause of illness in adolescents and adults. In a randomized observer- and subject-blinded study, adults (> or = 18 years of age) received an acellular pertussis (aP) vaccine containing genetically inactivated pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN), or a saline placebo, and were monitored for safety and immunogenicity. IgG antibodies to PT, FHA, and PRN were measured by enzyme-linked immunosorbent assay (ELISA) and PT neutralization by a Chinese hamster ovary (CHO) cell assay. Local reactions, more common in the aP group, were mild and transient. One month after immunization, geometric mean ELISA antibody concentrations for the aP and placebo groups, respectively, were: anti-PT, 463 and 7.6; anti-FHA, 417 and 18; and anti-PRN, 855 and 14. The anti-PT neutralization titers for the aP and placebo groups were 1:3439 and 1:58 respectively. This aP vaccine is a safe and immunogenic candidate booster vaccine against pertussis for adults.

Safety and immunogenicity of heptavalent pneumococcal vaccine conjugated to CRM197 in United States infants.

OBJECTIVE: To determine the safety and immunogenicity of heptavalent pneumococcal saccharide vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) individually conjugated to CRM197 (PNCRM7), administered at 2, 4, 6, and 12 to 15 months of age. DESIGN: Two hundred twelve healthy 2-month-old infants were equally randomized to receive four consecutive doses of PNCRM7 or an investigational meningococcal group C conjugate vaccine, which served as a control. Concomitantly administered routine vaccines were oral polio vaccine and combined diphtheria toxoid, tetanus toxoid, and whole cell pertussis vaccine/Haemophilus influenzae type b vaccine consisting of capsular oligosaccharides conjugated to CRM197 (DTP/HbOC) at 2, 4, and 6 months, and either measles-mumps-rubella vaccine or HbOC at 12 to 15 months. Active safety surveillance was conducted for 3 days after each dose. Antibody concentrations to each of the 7 pneumococcal serotypes were measured by enzyme-linked immunosorbent assay prevaccination, after doses two and three, prebooster, and postbooster. RESULTS: Significantly fewer children experienced local reactions at the PNCRM7 injection site than at the DTP/HbOC site. There was no increase in the incidence or severity of local reactions at the PNCRM7 site with increasing doses of vaccine. Mild to moderate postvaccination fever was common in both the PNCRM7 and control vaccine groups, however DTP/HbOC was administered concurrently. All 7 vaccine serotypes were immunogenic. The kinetics of the immune responses were serotype-specific. After three doses of PNCRM7, between 92% to 100% of children had >/=0.15 microg/mL of antibody, and 51% to 90% achieved a level of >/=1 microg/mL against specific serotypes. A booster dose of PNCRM7 resulted in a brisk anamnestic response to all 7 vaccine serotypes, demonstrating effective stimulation of T-cell memory by the primary series of vaccinations. CONCLUSION: Primary immunization followed by a booster dose of PNCRM7 seemed to be acceptably safe and resulted in significant rises in antibody to all 7 serotypes. Implications. Studies to assess vaccine efficacy of PNCRM7 for prevention of systemic disease, nasopharyngeal colonization, and acute otitis media are in progress. If PNCRM7 proves to be protective, there is the potential to prevent up to 85% of invasive pneumococcal disease occurring in US children.

Inactivated poliovirus vaccine alone or sequential inactivated and oral poliovirus vaccine in two-, four- and six-month-old infants with combination Haemophilus influenzae type b/hepatitis B vaccine.

BACKGROUND: Advisory committees have recommended the increased use of inactivated poliovirus vaccine (IPV) for children. OBJECTIVES: The purpose of this study was to assess the safety and immunogenicity of three schedules using IPV administered with diphtheria and tetanus toxoids and whole cell pertussis vaccines in a dual-chambered syringe. Children also received a combination of Haemophilus influenzae type b (Hib) and hepatitis B vaccines (COMVAX). METHODS: All infants (n = 295) received IPV and COMVAX at 2 and 4 months of age and IPV, oral poliovirus vaccine (OPV) or both vaccines at 6 months and OPV at 15 months of age. RESULTS: After two doses of IPV 96 to 100% of infants had antibodies to poliomyelitis viruses types 1, 2 and 3, and after a third dose of vaccine (IPV or OPV) all but one child had antibodies to all three poliovirus types. After two doses of COMVAX 89 and 96% of children had protective levels of antibody to Hib and hepatitis B, respectively. CONCLUSIONS: IPV is highly immunogenic in a two-dose schedule. Administration of a third dose of IPV or a dose of OPV at 6 months of age is highly effective. Simultaneous administration of a combination H. influenzae type b/hepatitis B vaccine did not interfere with the response to IPV.

Reactogenicity and immunogenicity of a three-component acellular pertussis vaccine administered as the primary series to 2, 4 and 6 month old infants in the United States.

Five hundred and fifty-seven infants received either an acellular pertussis (DTaP) vaccine containing pertussis toxoid (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) or one of two commercially available whole-cell pertussis (DTP) vaccines at 2, 4 and 6 months. One month after the third immunization, IgG antibody values to pertussis toxoid, filamentous hemagglutinin and PRN were significantly greater following DTaP than either DTP (P < 0.05). When reactions within 48 h after all three doses of vaccine were combined, fever 101 degrees, > or = moderate fussiness, > or = moderate pain, swelling 10 mm, and erythema 10 mm occurred less often after DTaP compared with DTP-Connaught (P < 0.001). The same adverse events were also less after DTaP compared with DTP-Lederle (P < 0.05), except for erythema 10 mm. This three-component DTaP vaccine produced fewer adverse events and greater antibody values to PT, FHA and PRN in comparison with either licensed DTP vaccine when given as the primary series.

Comparison of a three-component acellular pertussis vaccine with a whole-cell pertussis vaccine in 4- through 6-year-old children. Elmwood Pediatric Associates, Pennridge Pediatric Associates.

OBJECTIVE: To compare the safety and immunogenicity of a three-component acellular pertussis (DTaP) vaccine containing pertussis toxin (PT), filamentous hemagglutinin (FHA), and pertactin with whole-cell pertussis (DTwP) vaccine in 4- through 6-year-old children. PARTICIPANTS: One hundred seventy-two healthy 4- through 6-year-old children previously immunized with the DTwP vaccine at or near 2, 4, 6, and 18 months of age. INTERVENTIONS: Prevaccination serum samples were obtained on all study participants. One hundred twelve children received 0.5 mL of the DTaP vaccine intramuscularly. Fifty-three children received 0.5 mL of a commercially available DTwP vaccine intramuscularly. Approximately 30 days following vaccination, additional serum samples were obtained. MEASUREMENTS: Parents monitored adverse reactions for 7 days following immunization. Significantly fewer children in the DTaP group reported temperatures of greater than 38.1 degrees C and an area of redness of more than 10 mm and moderate-to-severe pain at the injection site. RESULTS: Antibody responses to PT, FHA, pertactin, and diphtheria and tetanus toxoids were measured by enzyme-linked immunosorbent assay. Among subjects who were seronegative prior to vaccination, response was defined as the detection of antibody levels following vaccination; among children with detectable antibody levels prior to vaccination, in terms of the rise in antibody titers. Data using a twofold and a fourfold rise in antibody titers as criteria to define response were evaluated. Children in the DTaP group had significantly greater increases in geometric mean titers of antibodies against PT, FHA, and pertactin. Over 90% of the DTaP group responded to PT, FHA, and pertactin according to the criteria of both the twofold and the fourfold rise in antibody titers. Significantly fewer of the DTwP group responded to PT, FHA, and pertactin with at least a fourfold rise in antibody titers. When analyzing subjects with at least a twofold increase in antibody titers, a statistically significant difference remained in regard to anti-FHA antibodies. All study subjects had protective antibody titers against diphtheria and tetanus toxoids following vaccination. The geometric mean titer of antibodies against tetanus was significantly greater in the DTwP group than in the DTaP group. CONCLUSION: The three-component DTaP vaccine administered as a booster immunization in 4-through 6-year-old children produced less fever and less redness and pain at the injection site than the DTwP vaccine and was as immunogenic as the DTaP vaccine.

Comparison of a three-component acellular pertussis vaccine with a whole-cell pertussis vaccine in 15- through 20-month-old infants.

OBJECTIVE: To compare the immunogenicity and reactogenicity of a diphtheria and tetanus toxoids and three-component acellular pertussis vaccine (DTaP) with a diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) when administered as a booster dose to infants 15 through 20 months of age. DESIGN: Randomized, double-blind, comparative study. SETTING: Three pediatric practices (two private; one hospital-based). PARTICIPANTS: One hundred and sixty-five healthy 15- through 20-month old infants. SELECTION PROCEDURES AND INTERVENTIONS: Infants were randomly assigned in a 2:1 ratio to receive vaccine from a single lot of DTaP or from commercially available DTwP. DTaP contained 25 micrograms of pertussis toxoid, 25 micrograms of filamentous hemagglutinin, 8 micrograms of pertactin (69-kilodalton outer membrane protein), 25 flocculating units of diphtheria toxoid, and 10 flocculating units of tetanus toxoid per 0.5-mL dose. DTwP contained one half the concentrations of diphtheria and tetanus toxoids compared with DTaP and a pertussis component with a potency of 4 U/0.5-mL dose. Serum samples were obtained on the day of immunization and 4 weeks later. Adverse reactions were recorded by parents for 7 days after immunization. An interval history was obtained 4 weeks after immunization. MEASUREMENTS AND RESULTS: IgG antibody to pertussis toxoid, filamentous hemagglutinin, pertactin, diphtheria toxoid, and tetanus toxoid was measured by an indirect enzyme-linked immunosorbent assay (ELISA) method. One month after immunization, the geometric mean antibody levels after DTaP compared with DTwP were: pertussis toxoid, 70.6 vs 28 ELISA U/mL (P = .003); filamentous hemagglutinin, 183.4 vs 43 ELISA U/mL (P < .001); pertactin, 216 vs 49.9 ELISA U/mL (P < .001); diphtheria, 14.1 vs 14.9 IU/mL (P = .74); and tetanus, 11.9 vs 14.8 IU/mL (P = .089). After immunization with DTaP, most local and systemic adverse experiences were significantly fewer compared with DTwP (P < .05). CONCLUSIONS: This three-component DTaP vaccine demonstrates significantly greater immune responses to pertussis toxoid, filamentous hemagglutinin, and pertactin, equivalent immune responses to diphtheria and tetanus toxoids, and significantly less reactogenicity compared with a licensed DTwP.

Safety and immunogenicity of a combined diphtheria, tetanus, pertussis and Haemophilus influenzae type b vaccine in young infants.

OBJECTIVE: To study the safety and immunogenicity of a combined diphtheria-tetanus-pertussis (DTP)-Haemophilus influenzae type b (HbOC) vaccine (TETRAMUNE) in infants as young as 2 months of age as compared to separate administration of DTP and HbOC. METHODS: Two-month-old infants were randomized to receive three doses 2 months apart of either DTP-HbOC as a single 0.5-mL injection or to receive 0.5 mL of DTP and HbOC concurrently in separate legs. Local and systemic adverse reactions were monitored within 72 hours of each immunization, and immunogenicity of each of the four vaccine components was measured. RESULTS: The incidence of both local and systemic adverse events following the tetravalent vaccine was similar to the incidence following separate vaccine administration. After three doses of vaccine, the response to each of the vaccine components was higher in the combined vaccine when compared to separate administration. In the case of the Haemophilus influenzae type b component, this enhancement was also seen after two doses. The response to the combined vaccine was consistent among the three lots tested as was the enhancement over separate administration. CONCLUSIONS: The DTP-HbOC vaccine was safe and immunogenic in young infants and was generally more immunogenic than separate vaccination with DTP and HbOC. The use of such a combined vaccine reduces the number of injections given to young infants by half and is an important step toward improving vaccine delivery.

Clinical survey of natural varicella compared with breakthrough varicella after immunization with live attenuated Oka/Merck varicella vaccine.

OBJECTIVE: To prospectively characterize varicella occurring in children previously immunized with a live attenuated varicella vaccine (breakthrough varicella) through daily observation by medical personnel and to compare it with natural varicella followed in the same manner. DESIGN: A blinded clinical survey. SETTING: Four pediatric practices (two private; two hospital-based). PARTICIPANTS: Healthy 12-month-old through 17-year-old children with chickenpox were studied; 92 had natural varicella and 58 had breakthrough varicella. SELECTION PROCEDURES AND INTERVENTIONS: Study personnel, unaware of vaccination status, documented the clinical characteristics of each patient in the office or at the patient's home each day from enrollment until the day after the total number of lesions increased less than 10%. A standard form documenting number and description of lesions, temperature, duration of illness, and associated clinical complaints was completed each day by the same study personnel. Acute and convalescent sera were obtained on breakthrough cases. MEASUREMENTS AND RESULTS: Antibody to varicella-zoster virus was measured by the glycoprotein-based enzyme-linked immunosorbent assay. Of those with sera available, 85% were serologically confirmed. Eighty-seven percent of enrollees had a known exposure to chickenpox, with at least two thirds of each group having a greater than 4-hour or a household exposure. The numbers of total and vesicular lesions were significantly higher in the natural varicella group, regardless of exposure status (P = .021 to < .001). The group with breakthrough varicella had a significantly lower incidence of fever (P < .001) and a significantly shorter duration of illness (P < .001). Other associated constitutional complaints and complications were not significantly different between groups. CONCLUSION: Varicella in vaccine recipients is clinically modified and significantly less severe than natural disease.

Immunogenicity of Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccine in infants.

OBJECTIVE: To compare the safety and immunogenicity of three investigational lots of Haemophilus influenzae type b polysaccharide-tetanus toxoid (PRP-T) conjugate vaccine in infants. DESIGN: A multicenter, randomized immunogenicity trial. Infants were vaccinated at 2, 4, and 6 months of age with one of three lots of PRP-T. A control group received H influenzae type b oligomers conjugated to CRM197 (HbOC). Serum was obtained before each injection and 1 month after the third dose, and assayed blindly for antibody in one laboratory. SUBJECTS: Four hundred eighty-four infants from private pediatric practices located in five geographic areas. MEASUREMENTS AND RESULTS: There were no significant differences in the number of adverse events reported for infants receiving PRP-T or HbOC, and the rates did not exceed those observed previously in infants given diphtheria-tetanus-pertussis vaccine alone. Total serum anti-PRP antibody responses were analyzed in 336 infants who met strict inclusion criteria. After one, two, or three doses, the respective antibody responses to each of the three lots of PRP-T and to HbOC vaccine were similar. The only exception was one lot of PRP-T, which after one or two injections elicited significantly higher geometric mean antibody responses than the other two lots or the HbOC vaccine. After a third injection, there were no significant lot differences. Combining the data from the different lots, there were no significant differences in the geometric mean antibody concentration after three doses of PRP-T or HbOC (8.3 vs 7.7 micrograms/mL), and 95% and 91%, respectively, of infants had greater than 1.0 microgram/mL of antibody. There were no significant differences in the magnitudes of the respective IgG1-, IgG2-, and IgM-specific antibody concentrations between infants given PRP-T or HbOC. CONCLUSIONS: The three investigational lots of PRP-T tested were safe and were as immunogenic as or more so than the licensed HbOC conjugate vaccine.

Comparative study of sultamicillin and amoxicillin-clavulanate: treatment of acute otitis media.

Sultamicillin is a mutual prodrug of ampicillin and sulbactam that is chemically linked by a diester bond. This investigational agent has beta-lactamase-inhibiting activity by virtue of sulbactam, a novel beta-lactamase inhibitor. A double blind randomized study was conducted to evaluate the safety, efficacy and tolerance of sultamicillin for treatment of acute otitis media compared with amoxicillin-clavulanate. A total of 144 subjects were included (96 randomly assigned to the sultamicillin and 48 to the amoxicillin-clavulanate groups). No safety concerns for sultamicillin were identified during the study. The clinical efficacy in effusion clearance between the two groups was found not to be statistically different at 10 days (P = 0.23) and 30 days (P = 0.72). Similar rates of side effects, primarily gastrointestinal, were reported in both study groups. Sultamicillin may be an alternative for the treatment of acute otitis media when persistence and recurrence of disease become an issue.

Acellular pertussis vaccination of 2-month-old infants in the United States.

This is the first study in children from the United States that evaluates the immunogenicity of and adverse reactions to the Connaught/Biken two-component acellular pertussis vaccine compared with whole-cell pertussis vaccine when given as a primary immunization series at 2, 4, and 6 months of age. Three hundred eighty infants were studied; 285 received acellular diphtheria-tetanus toxoids-pertussis (DTP (ADTP)) and 95 received whole-cell DTP (WDTP). Following the third dose, ADTP vaccination produced higher antibody responses than WDTP to lymphocytosis-promoting factor (enzyme-linked immunosorbent assay IgG geometric mean titer (GMT) = 131 vs 9 and Chinese hamster ovary cell assay GMT = 273 vs 16) and to filamentous hemagglutinin (IgG GMT = 73 vs 10) (all P less than .0001). Agglutinin responses were higher in WDTP compared with ADTP recipients (GMT = 50 vs 37; P = .02). Local reactions were fewer for all three doses following ADTP vaccination. Fever, irritability, drowsiness, anorexia, vomiting, and unusual crying all occurred less frequently in ADTP compared with WDTP recipients for one or more of the three doses. We conclude that this two-component ADTP vaccine when given as a primary series produces greater immunogenicity and fewer adverse effects than the currently licensed WDTP vaccine.

Immunogenicity of subcutaneous versus intramuscular Oka/Merck varicella vaccination in healthy children.

To compare the immunogenicity and safety of varicella vaccine by either subcutaneous or intramuscular injection, 166 healthy children aged 12 months to 10 years old who had no prior history of varicella were enrolled from two pediatric practices and randomly assigned to receive 0.5 mL of a single lot of varicella vaccine. Sera from the day of and 6 weeks postvaccination were tested for varicella antibody by gpELISA. Parents recorded clinical events occurring in the 6 weeks following vaccination. In the 132 evaluable children, the mean prevaccination titer was 0.3 gpELISA units for both groups. Sixty-three (97%) of the 65 receiving varicella vaccine by the subcutaneous route seroconverted compared with 67 (100%) of 67 immunized intramuscularly. Postvaccination geometric mean titer in the subcutaneous group was 6.9 +/- 7.0 gpELISA units and did not differ significantly from the geometric mean titer of 10.5 +/- 4.4 in the intramuscular group. Varicella vaccine was generally well tolerated by either route; 21% of both groups complained of reactions at the injection site and 7% had a varicella-like rash. Although varicella vaccine is recommended to be given subcutaneously, the results of this study indicate that inadvertent intramuscular administration of varicella vaccine is not reason for revaccination.

Amoxicillin or myringotomy or both for acute otitis media: results of a randomized clinical trial.

A total of 536 infants and children with acute otitis media were randomly assigned to one of six consistent year-long regimens involving the treatment of nonsevere episodes with either amoxicillin or placebo, and severe episodes with either amoxicillin, amoxicillin and myringotomy, or, in children aged 2 years or older, placebo and myringotomy. Nonsevere episodes had more favorable outcomes in subjects assigned to treatment with amoxicillin than with placebo, as measured by the proportions that resulted in initial treatment failure (3.9% vs 7.7%, P = .009) and the proportions in which middle-ear effusion was present at 2 and 6 weeks after onset (46.9% vs 62.5%, P less than .001; and 45.9% vs 51.5%, P = .09, respectively). In subjects whose entry episode was non-severe, those assigned to amoxicillin treatment had less average time with effusion during the succeeding year than those assigned to placebo treatment (36.0% vs 44.4%, P = .004), but recurrence rates of acute otitis media in the two groups were similar. In the 2-year-and-older age group, severe episodes resulted in more initial treatment failures in subjects assigned to receive myringotomy alone than in subjects assigned to receive amoxicillin with, or without, myringotomy (23.5% vs 3.1% vs 4.1%, P = .006). In the study population as a whole, severe episodes in subjects assigned to receive amoxicillin alone, and amoxicillin with myringotomy, had comparable outcomes. It is concluded that children with acute otitis media should routinely be treated with amoxicillin (or an equivalent antimicrobial drug). The data provide no support for the routine use of myringotomy either alone or adjunctively.

Comparison of an acellular pertussis-component diphtheria-tetanus-pertussis (DTP) vaccine with a whole-cell pertussis-component DTP vaccine in 17- to 24-month-old children, with measurement of 69-kilodalton outer membrane protein antibody.

Healthy 17- to 24-month-old children, previously immunized with three doses of whole-cell diphtheria-tetanus-pertussis (DTP) vaccine, were enrolled in a multi-center double-blind, randomized study comparing a DTP vaccine with an acellular pertussis-component (APDT) and a conventional whole-cell pertussis-component DTP vaccine. Thirty-eight children received APDT vaccine, and 37 children received DTP vaccine. APDT vaccine recipients had significantly less local pain and warmth than DTP vaccine recipients. Antibody responses to lymphocytosis-promoting factor were similar in the two groups. The APDT vaccine recipients had a higher IgG antibody response to filamentous hemagglutinin than the DTP vaccinees had. Equivalent agglutinin responses were seen in the two groups. The APDT vaccine recipients had a significantly better antibody re-enzyme-linked immunosorbent assay, than DTP vaccinees had 1 month and 1 year after immunization. This APDT vaccine was immunogenic and caused fewer local reactions than conventional DTP vaccine when administered as a fourth dose to 17- to 24-month-old children.

Comparison of acellular and whole-cell pertussis-component DTP vaccines. A multicenter double-blind study in 4- to 6-year-old children.

An acellular pertussis-component combined diphtheria and tetanus toxoids, and pertussis (APDT) vaccine adsorbed was compared with a licensed whole-cell pertussis-component combined diphtheria and tetanus toxoids, and pertussis (DTP) vaccine adsorbed for reactogenicity and immunogenicity when given as the fifth DTP immunization to eighty-two 4- to 6-year-old children. The reaction rates with both vaccines were low; APDT vaccine recipients had significantly less pain and warmth at the injection site than did DTP vaccine recipients. Antibody responses to pertussis antigens (lymphocytosis-promoting factor, filamentous hemagglutinin, and agglutinogens) and to diphtheria and tetanus toxoids were all brisk. The APDT vaccine recipients had a more marked response in antibodies to filamentous hemagglutinin and a less marked response in agglutinins than whole-cell vaccine recipients. On the day after immunization, both APDT and DTP vaccine recipients had an increase in mean leukocyte and neutrophil counts. This APDT vaccine is immunogenic and less reactogenic than a DTP vaccine with a whole-cell pertussis component when administered as a booster to 4- to 6-year-old children.

A comparative study of amoxicillin-clavulanate and amoxicillin. Treatment of otitis media with effusion.

A double-blind randomized clinical trial was conducted at two sites comparing amoxicillin-clavulanate potassium (Augmentin) and amoxicillin trihydrate for the treatment of otitis media with effusion ("secretory otitis media"). One hundred eight subjects were randomly assigned to receive a ten-day course of either drug regimen. Clinical response was assessed at ten days and four weeks after entry. For those without middle ear effusion at four weeks, recurrence rates were measured at 8, 12, and 16 weeks after entry. At ten days following entry, 29 (51.8%) of 56 subjects in the amoxicillin-clavulanate-treated group were effusion free compared with 16 (32.0%) of 50 subjects in the amoxicillin-treated group (P = .06). At four weeks following entry, 26 (50.0%) of 50 subjects in the amoxicillin-clavulanate-treated group were effusion free compared with 23 (51.1%) of 45 subjects in the group given amoxicillin. By the 16-week visit, eight (36.4%) of 22 subjects in the amoxicillin-clavulanate-treated group who were effusion free at four weeks had recurrence of effusion, compared with 12 (63.2%) of 19 subjects in the amoxicillin-treated group. This study suggests that there was a favorable clinical response immediately following treatment in the amoxicillin-clavulanate--treated subjects as compared with those treated with amoxicillin, but this benefit was not sustained at the four-week end point.