Phanorsri Attanath

Persistence of antibodies in children after intradermal or intramuscular administration of preexposure primary and booster immunizations with purified Vero cell rabies vaccine

BACKGROUND The use of intradermal (i.d.) injections of purified Vero cell rabies vaccine (PVRV) for preexposure prophylaxis has not been well-established. We studied the safety and immunogenicity of i.d. and intramuscular (i.m.) PVRV injections for primary and booster preexposure immunizations. METHODS One of two rabies preexposure PVRV regimens comprising three doses of either 0.1 ml i.d. or 0.5 ml i.m. administered during 28 days was assigned at random to 190 school children. One booster dose was given 1 year later either i.d. or i.m., according to their initial randomization group. Serologic results were available from 155 (82%) children at 1 year after primary immunization and 118 (62%) children at 2 years after booster. RESULTS Although children vaccinated i.d. had significantly lower rabies-neutralizing antibody titers after primary immunization as well as after booster than children vaccinated i.m. (P< 0.001 for all time points), there were no significant differences in the percentages of children with adequate titers (> or =0.15 IU/ml) between the i.d. and i.m. groups after both primary and booster immunizations. Mild local reactions were more frequent after i.d. vaccination. Mild or moderate systemic reactions were infrequent and similar after i.d. and i.m. vaccinations. Fever and headache were reported by < or =6%. The reactions after booster were not different from those of post-primary immunization. CONCLUSIONS Purified Vero cell rabies vaccine appears to be safe and immunogenic for primary and booster preexposure immunizations. An i.d. PVRV preexposure regimen should be useful especially for rabies-endemic countries with low per capita income.

In vivo and in vitro sensitivity of Falciparum malaria to quinine in Thai children.

The study was carried out to assess the efficacy of quinine in children with Falciparum malaria in relation to in vitro sensitivity (measured in terms of minimum inhibitory concentration: MIC) and to trough serum levels of quinine during the course of treatment. Fifty children aged ten months to 12 years with Falciparum malaria were randomly divided into two groups. Group I: 24 children were treated with quinine 10 mg base per body weight every eight hours for 14 days. Group II: 26 children were treated with quinine at the dosage adjusted to the body surface area based on an adult dose of 500 mg base eight hourly for 14 days. There were three treatment failures, one RI and one RII in group I, and one RI in group II. The serum concentrations of quinine reached a peak level on day two and levelled off by the end of the first week. Concentrations in group II were higher than in group I. The mean minimal inhibitory concentration (MIC) of quinine in the two groups was 14.89 nmol per ml ranging from 8-26 nmol per ml. In cases with treatment failure, the trough serum quinine levels became lower than the corresponding MIC after day six (RI) and after day two (RII). The rise of MIC suggests that sensitivity of Falciparum malaria parasites to quinine may be decreasing in Thailand. Failures of treatment in standard dosage may occur in cases infected by parasites with high MIC, in which trough serum quinine levels cannot be maintained above the MIC longer than six days during the course of treatment. However in one cured case, the trough serum quinine levels were below the MIC throughout treatment. More research is needed on the real relationship between serum quinine concentrations, the MIC, and clinical and parasitological response to quinine.

A New Vero Cell Rabies Vaccine: Results of a Comparative Trial with Human Diploid Cell Rabies Vaccine in Children

We evaluated the immunogenicity and safety of a chromatographically purified rabies vaccine (CPRV) compared with human diploid cell rabies vaccine (HDCV) after pre-exposure immunizations (both primary and booster). Intramuscular doses of either 0.5 mL of CPRV or 1.0 mL of HDCV were given to 400 schoolchildren on days 0, 7, 28, and 365 (booster). Adequate titers of antibody (> or = 0.15 IU/mL, as defined by the Centers for Disease Control and Prevention) were observed in serum samples from all children 14 days after primary immunization with CPRV and HDCV; the antibodies persisted in all but one child up until 1 year. Fourteen days after the primary immunization series (day 42) and 7 days after booster immunization (day 372), all children had antibody titers of > or = 0.5 IU/mL. Local and systemic reactions after primary and booster immunizations occurred significantly less frequently in the CPRV group. A severe allergic reaction (angioedema) was reported in only one child after booster immunization with HDCV. CPRV has adequate immunogenicity for primary and booster pre-exposure immunizations in children and has a better safety profile than does HDCV.

Red cell and plasma concentrations of combined quinine-quinidine and quinine in falciparum malaria.

Red cell and plasma quinine-quinidine, and quinine concentrations in children with uncomplicated falciparum malaria who were treated with a combination of quinine/quinidine/cinchonine (combined drug) and quinine alone, respectively, were measured, using the extraction fluorescence method. The cure rates obtained with the high dose regimen of the combined drug (100%) were significantly higher than in the low dose regimen group (37.5%) (p less than 0.05), and the quinine regimen produced a 50% cure rate. Similar mild and transient ECG effects were noted in both the combined drug group and the quinine group. In patients treated with the combined drug, quinine-quinidine concentrations in both red cell and plasma of the high dose regimen group were significantly higher than those in the low dose regimen group (p less than 0.001, p less than 0.001). In quinine-treated patients, red cell quinine concentration in those with RII failure was significantly lower than that in patients with cure or RI failure (p less than 0.05). Both red cell and plasma levels of quinine-quinidine were higher than quinine levels. The red cell:plasma quinine-quinidine concentration ratios rose steadily to the high level from day 3 to day 6, while the ratio of quinine alone fluctuated around the low level and then gradually fell. The evidence suggests that red cell drug concentrations are more closely related to the outcome of treatment than to plasma concentrations and that the combined drug may be very useful for treatment of multi-drug-resistant P. falciparum infections. Further study is needed.