Comparison of a fifth dose of a five-component acellular or a whole cell pertussis vaccine in children four to six years of age.

BACKGROUND AND OBJECTIVES: Acellular pertussis vaccines are now preferred for all five childhood immunization doses; however, there are few data on the safety and immunogenicity of five consecutive doses. This study compared a fifth dose of an acellular and a whole cell pertussis vaccine in 4- to 6-year-old children previously immunized with four doses of acellular or whole cell pertussis vaccine. STUDY DESIGN: In a double blind, multicenter study, 366 healthy children were randomly allocated to receive a single injection of a 5-component acellular or a whole cell pertussis vaccine, each combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine. RESULTS: Although injection site redness > or =50 mm and swelling > or =50 mm were common in children who had received five doses of acellular (50% and 48.1%, respectively) or whole cell (66.2% and 59.7%) pertussis vaccine, limb soreness and limitation of motion were less frequently reported after acellular (1.9% and 0%) than after whole cell (49.2% and 36.3%; P < 0.0001) pertussis vaccine. Pre-fifth dose antipertussis antibody titers were higher in children who previously had received four doses of acellular pertussis vaccine. Postimmunization antibody titers against pertussis toxin, filamentous hemagglutinin, pertactin and tetanus toxin were higher in recipients of five doses of acellular pertussis vaccine, whereas antibody titers to diphtheria toxin, pertussis fimbriae and poliovirus serotypes were higher in recipients of five doses of the whole cell pertussis vaccine (P < 0.05 for all comparisons). CONCLUSIONS: A regimen consisting of five doses of a five-component acellular pertussis combination vaccine is safe and immunogenic in pre-school children. Local adverse reactions are common but are less painful and activity-limiting than a regimen of five doses of a whole cell pertussis vaccine.

Epidemic and endemic seroprevalence of antibodies to Cryptosporidium and Giardia in residents of three communities with different drinking water supplies.

This study was carried out to compare cryptosporidiosis and giardiasis seroprevalence rates in residents of three communities. Community (Com 1) uses drinking water from deep wells, community 2 (Com 2) uses surface water from a protected watershed, and community 3 (Com 3) uses surface water frequently containing Cryptosporidium oocysts and Giardia cysts. Unfiltered drinking water from each community was collected at the tap and tested for Cryptosporidium oocysts and Giardia cysts during the 12 months in which sera were collected for testing. No oocysts or cysts were detected in the water from the Com 1 deep wells; oocysts and cysts were detected intermittently in the drinking water from the other two communities. A waterborne outbreak of cryptosporidiosis occurred in a municipality adjacent to Com 3 six months into this 12-month study. Sera from residents of each of the communities were collected proportionately by month and by population size. Coded sera were tested for IgG to Cryptosporidium using a previously developed Western blotting method. The presence or absence of bands at 15-17 kD and/or 27 kD was recorded for the 1,944 sera tested. Definite bands at 15-17 kD and/or 27 kD were detected in 981 (50.5%) of the sera. A total of 33.2% of sera from Com 1 (community using deep wells) were positive using the same criteria compared with 53.5% (Com 2) and 52.5% (Com 3) of sera from the two communities using surface drinking water. Both bands (15-17 kD plus 27 kD) were detected in 582 sera (29.9%) from the three communities: 14.1% of sera from Com 1 compared with 32.7% from Com 2 and 31.5% from Com 3. These findings are consistent with a lower risk of exposure to Cryptosporidium from drinking water obtained from deep well sources. However, analysis of results by calendar quarter showed a significant (P < 0.001) increase in the number of Com 3 positive sera (compared with Com 1) following the waterborne outbreak. Without this outbreak-related observation, a significant overall difference in seropositivity would not have been seen. We also observed that in sera from the community affected by the outbreak, the presence on immunoblots of both Cryptosporidium bands appeared to be the best indicator of recent infection. Seroprevalence rates using an ELISA to detect IgG to Giardia were estimated using the same sera. Overall 30.3% (590 of 1,944) of sera were positive by the ELISA. A total of 19.1% of sera from Com 1, 34.7% from Com 2 and 16.0% from Com 3 were seropositive. Rates for both Com 3 and Com 1 did not change significantly over time. In Com 2, rates decreased significantly (P < 0.001) during the last half of the study period (third and fourth calendar quarters). The reasons for the decrease in seroprevalence in Com 2 sera are presently not known. These studies show intriguing associations between seroprevalence, outbreak-related laboratory serologic data, and patterns of parasite contamination of drinking water. Further studies are required to validate the serologic approach to risk assessment of waterborne parasitic infections at a community level.

Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine.

To determine if an acellular pertussis-diphtheria-tetanus vaccine could be combined with a Haemophilus influenzae b conjugate vaccine as a single injection, we randomized 468 children between 17 and 21 months of age previously immunized with three doses of each vaccine to receive a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae b-tetanus toxoid conjugate vaccine either as separate injections on separate days, separate injections on the same day, or as a single combined injection. Rates of adverse reactions were similar amongst the groups except for increased injection site tenderness (29.2% vs 17%, RR 1.76, 95% CI 1.09-2.85) and fussiness (36.4% vs 23.3%, RR 1.59, 95% CI 1.05-2.41) in the group given the combined injection rather than separate injections on separate days. Antibody levels against the capsular polysaccharide of H. influenzae b after the single combined injection (47.1 micrograms ml-1) were lower than after separate injections on the same day (66.0 micrograms ml-1; P < 0.05) but higher than when the injections were administered on separate days (28.4 micrograms ml-1; P < 0.001). We conclude that the five-component acellular pertussis vaccine is safe and immunogenic when combined with diphtheria and tetanus toxoids and H. influenzae b-tetanus toxoid conjugate vaccine in children receiving the fourth dose of the immunization series.

Adverse reactions and antibody response to four doses of acellular or whole cell pertussis vaccine combined with diphtheria and tetanus toxoids in the first 19 months of life.

To assess the safety, immunogenicity, and lot consistency of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoid (Connaught Laboratories Limited), we randomly allocated 432 infants to receive one of three lots of an acellular pertussis vaccine or a single lot of whole cell pertussis vaccine. Infants were immunized at 2, 4 and 6 months of age and between 17 and 19 months of age. Local and systemic adverse reactions were reported significantly more frequently by recipients of the whole cell than acellular vaccine after each dose. The antibody response against pertussis toxin, filamentous hemagglutinin, and 69 kDa protein was of greater magnitude in acellular pertussis vaccine recipients than whole cell pertussis vaccine recipients. Small differences were detected amongst the vaccine lots tested. We conclude that the acellular pertussis vaccine is safe and immunogenic for the first four doses in children under 2 years of age.

Safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate) administered concurrently or combined with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine to healthy infants at two, four and six months of age.

The safety and immunogenicity of Haemophilus influenzae vaccine (tetanus toxoid conjugate (PRP-T) administered concurrently in separate sites or mixed in the same syringe with diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine were assessed in 439 infants at 2, 4 and 6 months of age. The proportions with local redness, tenderness and swelling in the separate and combined groups were 18% vs. 11% (P < 0.001), 27% vs. 24% and 15% vs. 13%, respectively. Systemic reactions occurred at similar rates in both groups. The combined vaccine induced tetanus and diphtheria antitoxin titers > or = 0.01 IU/ml in 99.5 and 99.1% of infants, pertussis agglutinin titers > or = 64 in 92.4%, anti-polyribosylribitol phosphate titers > or = 0.15 microgram/ml in 93.8% and > or = 1.0 microgram/ml in 75% and polio-neutralizing titers > or = 8 in > 98% of infants. However, antibody concentrations to PRP-T, some pertussis antigens and tetanus toxoid were significantly lower after combined than after separate injections of DPT/diphtheria and tetanus toxoids, pertussis vaccine and inactivated poliomyelitis vaccine and PRP-T. The clinical significance of these differences is not known, but the interactions observed among the components of the pentavalent vaccine may be of concern because they might influence antibody persistence until the fourth dose is administered.

The changing pattern of neoplastic disease in Canadian Eskimos.

The records of the two main referral centres for the western and central Arctic were reviewed for Eskimo patients with cancer diagnosed between 1949 and 1974 inclusive. To these were added the records for the past 6 years of patients from the eastern Arctic, giving the toatal of 180 histologically proved cases of malignant disease. Athe data were analysed for prevalence, relative frequency, geographic distribution and changes with time of the various neoplasms. Salivary gland and renal neoplasms have in recent years been displaced by cancer of the lung and uterine cervix as the most common malignant tumours in Canadian Eskimos. The prevalence of lung cancer in Eskimo women, particularly of the central Artic, is striking. Cancer of the nasopharynx kept the same relative position during early and late years of the survey period. Breast cancer is still uncommon in Eskimos. Lactation rather than gestation history appeared to be an important protective factor. Cases of cervical cancer outnumbered those of breast cancer by 18 to 4, in sharp contrast to the relative proportions of these tumours in all Canadian women.