Molecular analysis of Streptococcus pyogenes strains isolated from patients with recurrent pharyngitis after oral amoxicillin treatment.

PURPOSE: The most common illness caused by Streptococcus pyogenes (Group A streptococcus; GAS) is acute pharyngitis. It has been reported that a small percentage of patients experience recurrent GAS pharyngitis after 10 days of treatment with oral amoxicillin. The aim of this study was to clarify whether recurrent GAS pharyngitis is reactivation caused by the primary strain remaining at the infection site, or if the reinfection is caused by newly acquired strains. METHODOLOGY: A total of 135 GAS clinical strains were isolated from the tonsils of 116 pediatric patients with acute GAS pharyngitis between November, 2012 and April, 2014 in Saga, Japan. These strains were analysed by pulsed-field gel electrophoresis (PFGE)-typing methods. RESULTS: The isolates were grouped into 16 PFGE-types. The epidemic PFGE types that caused pharyngitis were found to change dynamically during 18 months. Eleven strains caused recurrent pharyngitis within 40 days after the last treatment, all of them showing the same PFGE-type as the primary strains. Eight of the strains caused recurrence more than 40 days after the treatment. Among them, six showed different PFGE-types from the primary strains. CONCLUSION: When recurrent pharyngitis emerges more than 40 days after the last treatment, penicillin can be prescribed again because reinfection is suspected. However, when recurrent pharyngitis takes place within 40 days after completing the treatment, alternative drugs should be considered for retreatment because the pharyngitis is likely to be due to reactivation.

Phase III clinical trials comparing the immunogenicity and safety of the vero cell-derived Japanese encephalitis vaccine Encevac with those of mouse brain-derived vaccine by using the Beijing-1 strain.

The immunogenicity and safety of an inactivated cell culture Japanese encephalitis vaccine (CC-JEV) were compared with those of an inactivated mouse brain-derived Japanese encephalitis vaccine (MB-JEV) in phase III clinical multicenter trials conducted in children. The vaccines contain the same Japanese encephalitis virus strain, the Beijing-1 strain. Two independent clinical trials (trials 1 and 2) were conducted. Trial 1 was conducted in 468 healthy children. Each subject was injected with 17 µg per dose of either CC-JEV or MB-JEV, and the immunogenicity and safety of the vaccines were investigated. Trial 1 showed that CC-JEV was more immunogenic and reactive than MB-JEV at the same dose. Therefore, to adjust the immunogenicity of CC-JEV to that of MB-JEV, a vaccine that has had a good track record regarding its efficacy for a long time, trial 2 was conducted in 484 healthy children. To improve the stability, CC-JEV was converted from a liquid type to a freeze-dried type of vaccine. Each subject was injected subcutaneously with either 4 µg per dose of CC-JEV, 8 µg per dose of CC-JEV, or 17 µg per dose of MB-JEV twice, at an interval of 2 to 4 weeks, followed by an additional booster immunization 1 to 15 months after the primary immunization. Based on the results of trial 2, 4 µg per dose of the freeze-dried CC-JEV (under the label Encevac) was selected as a substitute for the MB-JEV. Encevac was approved and launched in 2011 and has since been in use as a 2nd-generation Japanese encephalitis vaccine in Japan. (These studies have been registered at the JapicCTI under registration no. JapicCTI-132063 and JapicCTI-080586 for trials 1 and 2, respectively).

Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

BACKGROUND: Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). METHODS: A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. RESULTS: Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. CONCLUSIONS: DTaP-sIPV was shown to be a safe and immunogenic vaccine. CLINICAL TRIALS REGISTRATION: JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).