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Biomedical subjects

D Ambrosino

Publications and source records attributed to D Ambrosino.

8 recordsLinked to original sources
PubMed2001

Effects of alum adjuvant or a booster dose on immunogenicity during clinical trials of group B streptococcal type III conjugate vaccines.

Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular polysaccharide (CPS)-protein conjugate vaccines in healthy adults have demonstrated their safety and improved immunogenicity compared with uncoupled CPSs. Two recent trials sought to determine (i) whether adsorption of conjugate vaccine to aluminum hydroxide would improve immunogenicity and (ii) whether the CPS-specific immunoglobulin G (IgG) response could be boosted by administration of a second dose. Adsorption of GBS type III CPS-tetanus toxoid (III-TT) conjugate vaccine to alum did not improve the immune response to a 12.5-microg dose in healthy adult recipients. Four weeks after vaccination, the geometric mean antibody concentrations (GMCs) for the 15 recipients of III-TT with or without alum were 3.3 and 3.6 microg/ml, respectively. In the second trial, 36 healthy adults vaccinated previously with GBS III-TT conjugate were given a second 12.5-microg dose 21 months later. At 4 weeks after the second dose, the GMCs of type III CPS-specific IgG were similar to those measured 4 weeks after the primary vaccination, suggesting a lack of a booster response. However, 8 (22%) of the 36 participants who had undetectable III CPS-specific IgG (<0.05 microg/ml) before the first dose of III-TT conjugate exhibited a booster response to the second dose, with a fourfold-greater GMC of type III CPS-specific IgG than after the initial immunization. These results suggest that prior natural exposure to type III GBS or a related antigen may be responsible for the brisk IgG response to CPS noted in most adults after vaccination. However, a second dose of GBS III-TT conjugate vaccine may be required for adults whose initial CPS-specific IgG concentrations are very low and would also restore the initial peak-specific III CPS-IgG in responders to previous vaccination.

Adjuvants, Immunologic↗
PubMed1990

Effect of intravenous gammaglobulin therapy in IgG2 deficient and IgG2 sufficient children with recurrent infections and poor response to immunization with Hemophilus influenzae type b capsular polysaccharide antigen.

Nine children with recurrent sinopulmonary infections and normal IgG levels failed to improve after a 12-month period of prophylactic antibiotic therapy with trimethoprim-sulfamethoxazole. Five of these children had selective deficiency of IgG2 subclass, while the other four did not, but all nine children had a poor response to immunization with Hemophilus influenzae type b (Hib) capsular polysaccharide. Following the institution of intravenous immunoglobulin (IVIG) therapy, there was a significant decrease in the episodes of sinusitis and otitis media in all patients. Intravenous immunoglobulin therapy resulted in a significant increase in total serum IgG, IgG2, and IgG anti-Hib antibody levels. Discontinuation of IVIG therapy was followed by the return of recurrent infections. This preliminary study demonstrates that IVIG replacement therapy in children with recurrent infections and selective antibody deficiency is associated with a significant reduction in the frequency of sinopulmonary infections.

Antigens, Bacterial↗
PubMed1988

Prevention of pneumococcal otitis media in chinchillas with human bacterial polysaccharide immune globulin.

Clinical and experimental observations suggest that immune globulin may prevent otitis media (OM) in children. We performed experiments in chinchillas to test the hypothesis that human bacterial polysaccharide immune globulin (BPIG) might prevent OM caused by Streptococcus pneumoniae. Animals were given BPIG or saline intraperitoneally on day 0. On day 3 the epitympanic bulla was inoculated with S. pneumoniae type 7F. All 12 saline-treated and none of 12 BPIG-treated animals developed pneumococcal OM by day 7 (P less than 0.0001). Bacteremia developed in 6 of 12 saline- and 0 of 12 BPIG-treated animals (P = 0.007). Death with pneumococcal OM occurred within 28 days in 5 of 12 saline- and 0 of 12 BPIG-injected animals (P = 0.02). A chinchilla-specific immunoassay was used to show that surviving saline-injected animals developed serum anticapsular antibody; BPIG-treated animals had no detectable response. At levels of anticapsular immunoglobulin G similar to those of human adults, BPIG given systemically prevented pneumococcal OM and disseminated infection in chinchillas. BPIG may be of value in preventing human bacterial infection and may also inhibit development of antibody if it affects local infection or colonization. Specific immunoglobulin G antibody may provide an important antibacterial defense of mucosal surfaces of the respiratory tract.

Animals↗
PubMed1983

Trimethoprim and rifampin in combination for chemoprophylaxis of household contacts of patients with invasive infections due to Haemophilus influenzae type b.

We compared the effectiveness of rifampin-trimethoprim in fixed combination (3.75:1) to rifampin alone in the eradication of Haemophilus influenzae type b carriage among contacts of patients with invasive infection caused by this organism. The study population was composed of 127 index patients and 620 contacts. Twenty-six percent of contacts were colonized. Rifampin-trimethoprim eradicated carriage in 77.6% of contacts (71.1% in contacts less than 5 years, 84.2% in contacts greater than or equal to 5 years) whereas rifampin eradicated carriage in 69.9% of contacts (56.4% in contacts less than 5 years, 81.8% in contacts greater than or equal to 5 years). A single isolate resistant to rifampin and rifampin-trimethoprim was encountered. The eradication rate achieved with this regimen of rifampin-trimethoprim was too low to recommend its routine use. However, a higher dose or longer course might merit clinical trial.

Carrier State↗
PubMed1983

Efficacy of human hyperimmune globulin in prevention of Haemophilus influenzae type b disease in infant rats.

To determine the protective efficacy of human hyperimmune globulin to Haemophilus influenzae type b disease in an infant rat model, we compared hyperimmune globulin containing 600 mug of anti-polyribophosphate (PRP) antibody per ml to conventional immune globulin containing 66 mug of anti-PRP antibody per ml. The hyperimmune globulin was fractionated from the pooled plasma of 55 adult donors immunized with PRP, the capsular polysaccharide of H. influenzae type b. The disappearance of passively administered antibody was biphasic, with a linear first-order disappearance curve during the first 7 days. The initial half-life for anti-PRP antibody was 2.38 days in rats nasally colonized but not detectably bacteremic with H. influenzae type b and significantly longer (half-life, 10.3 days; P < 0.01) in noncolonized animals. Hyperimmune globulin afforded 10 times the protection of conventional globulin against bacteremia and meningitis. Globulin depleted of anti-PRP antibody offered no protection. The initial serum antibody levels and the levels during the 8-day observation period predicted protection. Rats maintaining serum antibody levels greater or equal to 50 ng/ml to day 8 had a 10% bacteremia and 5% meningitis incidence in contrast with 95% bacteremia (P < 0.001) and 55% meningitis (P < 0.001) in rats with less than 50 ng of anti-PRP antibody per ml. We conclude that studies of the pharmacology and efficacy of hyperimmune globulin are warranted in high-risk children unable to respond to active immunization.

Animals↗
PubMed1981

Rifampin chemoprophylaxis for household contacts of patients with invasive infections due to Haemophilus influenzae type b.

To determine the efficacy of rifampin chemoprophylaxis in eradication of oropharyngeal carriage of Haemophilus influenzae type b, we conducted a multicenter, double-blind, placebo-controlled trial among household contacts of patients hospitalized for invasive HIB infection. Seventy-nine index patients and 400 close contacts were studied; 26.5% of contacts were colonized. The efficacy of rifampin (10 mg/kg/dose, 600 mg/dose maximum, twice daily for two days) in eradicating carriage was 52% and varied with age (75.6% in persons greater than or equal to 5 and 27% in those less than 5 years). Eradication rates in those less than 5 years were not significantly better than for placebo. No resistant isolates were encountered in sensitivity testing. The low efficacy of this rifampin regimen in young children precludes its routine use as a chemoprophylactic agent for family contacts. The occurrence of three cases of invasive HIB infection in individuals outside the defined contact group raises concern regarding the efficacy of any chemoprophylactic regimen.

Clinical Trials as Topic↗
PubMedDate not supplied

Rifampin alone and in combination with trimethoprim in chemoprophylaxis for infections due to Haemophilus influenzae type b.

The efficacy of rifampin in eradicating Haemophilus influenzae type b from the pharynx of colonized individuals was assessed for 1,467 close contacts of 291 children hospitalized with invasive infections due to H. influenzae type b. Twenty-six percent of all contacts were carrying H. influenzae type b in the pharynx, and 52% of contacts younger than age five had throat cultures positive for this organism. Four different regimens of rifampin were studied and compared with placebo for efficacy in eradication of carriage of H. influenzae type b. The most effective dosage was 20 mg of rifampin/kg given once daily for four days. This schedule was associated with eradication of carriage in 96.2% of 52 colonized, compliant contacts. Carriage of H. influenzae type b was eradicated in 90.9% of the 22 colonized contacts who were younger than age five. Significantly lower rates of carriage eradication were seen with other regimens of rifampin. Potential problems associated with widespread rifampin usage are reviewed.

Carrier State↗