Safety and immunogenicity of a glycoprotein D genital herpes vaccine in healthy girls 10-17 years of age: results from a randomised, controlled, double-blind trial.

OBJECTIVE: The investigational AS04-adjuvanted herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) subunit prophylactic vaccine ('HSV vaccine'; GlaxoSmithKline Vaccines) has been shown to be well tolerated in adults, but limited data exist for pre-teen and adolescent girls, a likely target population. The primary objective of this study was to compare the occurrence of serious adverse events (SAEs) over 12 months between HSV vaccine recipients and saline recipients (placebo control group) in pre-teen and adolescent girls. The immunogenicity of the HSV vaccine was also assessed. METHODS: Healthy girls aged 10-17 years, stratified by age (10-15 years; 16-17 years), were randomised 2:1:1 to receive the HSV vaccine, a hepatitis A vaccine (Havrix™; HAV control) or placebo (saline) according to a 0-, 1-, 6-month schedule. Participants and study personnel not involved in the preparation or administration of vaccines were blinded to treatment. Safety and immunogenicity analyses were performed overall and by age (10-15 years; 16-17 years) and HSV serostatus. RESULTS: No statistically significant difference in the percentage of subjects with SAEs was observed between the HSV and saline group, or between the HSV and pooled control (HAV and saline) groups. The HSV vaccine was well tolerated, although a higher incidence of solicited local symptoms was observed in the HSV group than in the control group. Neither age nor HSV serostatus at the time of study entry had an impact on the safety profile of this vaccine. The HSV vaccine was immunogenic regardless of pre-vaccination HSV serostatus. Higher anti-gD geometric mean concentrations were observed in HSV-1 seropositive participants than in HSV-1 seronegative participants. CONCLUSION: The HSV vaccine had an acceptable safety profile, and was well tolerated and immunogenic when administered to girls aged 10-17 years regardless of age or HSV pre-vaccination serostatus.

Seasonality as a determinant of the efficacy of praziquantel in population-based chemotherapy: lessons from the practice.

During October-November 1991, 1356 male farmers, 18-40 years old from a village in Fayoum Governorate, Egypt, were examined for Schistosoma haematobium infection. The prevalence of infection was 22.2%. Infected farmers were treated immediately with praziquantel at the recommended dose of 40 mg/kg body weight in a single, oral dose. Twelve weeks after treatment 86/262 (32.8%) infected farmers were negative for S. haematobium eggs in urine. In another study conducted in a satellite village in the Nile Delta (Beheira Governorate) where S. mansoni infection is prevalent, all residents of both sexes between 5 and 50 years of age (n = 858) were examined for S. mansoni. The prevalence of S. mansoni was 69.0%. Infected subjects were treated with the same dose of praziquantel during January-February 94, with an overall resultant efficacy of 85.5% (471/551) and 97.2% (103/106) in 18-40 years old males 8-10 weeks post treatment. The high cure rate in the second study was probably because treatment took place 2 months after the end of the high transmission season.

The prevalence and intensity of Schistosoma mansoni infection among residents in two Egyptian villages, at two and twelve months post-treatment with 40 and 60 mg praziquantel per kg body weight at these two villages respectively.

Two different regiments of praziquantel, 40 mg/kg in a single dose and 60 mg/kg in two divided doses administered 6 hr apart for the treatment of S. mansoni infection, were compared at two villages of Beheira Governorate. All residents of both sexes between 5 and 50 yrs old from two rural communities (Farshout and Om El-Laban) participated in this study. The prevalence of S. mansoni infection was 58% at Farshout and 69% at Om El-Laban. Infected subjects received 60 mg/kg of praziquantel in two divided doses 6 hr apart at Farshout and 40 mg/kg in a single dose at Om El-Laban. Two months post-treatment, better cure rates (96% vs 85%, P < 0.001) were achieved with 60 mg/kg of praziquantel. Twelve months post-treatment the prevalence of infection (45% for both villages) increased, but remained lower than before treatment. This may indicate that transmission continued from cercariae transported by water from nearby hyperendemic areas. The prevalence and intensity of infection were higher in the younger (5-19 y) than in the older (20-50 y) age group both before treatment and one year post-treatment. The same applies to the incidence and reinfection of the treated subjects. We recommend that 60 mg/kg in two divided doses six hours apart be used for school children. For logistical reasons, the single dose, 40 mg/kg regimen, should be used for mass treatment. For better control of disease, mass chemotherapy with praziquantel as suggested above is essential for the whole endemic region rather than only for a focal area.

Praziquantel in the treatment of Schistosoma mansoni infection: comparison of 40 and 60 mg/kg bodyweight regimens.

Two different regimens of praziquantel, 40 mg/kg in a single dose and 60 mg/kg in two divided doses administered 6 hr apart, for the treatment of Schistosoma mansoni infection were compared in Abu Homos, Egypt. Participants in this study included 1,588 subjects of both sexes between five and 50 years old from two rural communities; 730 from Farshout and 858 from Om El-Laban. The prevalence of S. mansoni infection was 57.9% in Farshout and 69.0% in Om El-Laban. Infected subjects received 60 mg/kg of praziquantel in two divided doses 6 hr apart at Farshout and 40 mg/kg in a single dose at Om El-Laban. Eight to ten weeks after treatment, three stool samples were collected from each treated subject on three consecutive days and evaluated quantitatively by the modified Kato technique. The failure rate was significantly higher at Om El-Laban than at Farshout (14.5% versus 4.1% (odds ratio [OR] = 3.95, P < 0.0001). A significantly higher failure rate was consistent after adjustment for age and number of excreted S. mansoni eggs per gram of feces before treatment (OR = 3.75, P < 0.0001). In spite of differences among cure rates between the two regimens, we recommend 60 mg/kg on an individual basis but not for population treatment, since administration of a single dose of a drug is more practical than two doses given 6 hr apart.

Evaluation of a twice-a-week application of 1% niclosamide lotion in preventing Schistosoma haematobium reinfection.

A randomized double-blind trial was conducted to assess the efficacy of a twice-a-week application of 1% niclosamide lotion for prevention of Schistosoma haematobium reinfection. Six hundred farmers in Fayoum, Egypt, 18-40 years of age, were treated to cure their S. haematobium infection, then randomly assigned to self-apply niclosamide or placebo lotion to their limbs, neck, and torso. Subjects were exposed to schistosomal-infested water during routine irrigation activities from April to October 1992. Three hundred fifty subjects met the inclusion criteria and completed the trial, 169 (48.3%) in the niclosamide group and 181 (51.7%) in the placebo group. The subjects assigned to the niclosamide-treated group were comparable with those in the placebo group in age (27.2 versus 27.8 years), total water contact (101.9 versus 109.0 hr), lotion application compliance (93.5% versus 90.6%), and avoidance of whole body water contact (94.7% versus 96.7%). The reinfection rate with S. haematobium was 30.8% in the niclosamide-treated group and 28.2% in the placebo group. Niclosamide lotion applied to the limbs and trunk twice a week failed to prevent S. haematobium reinfection.

Field trial of 1% niclosamide as a topical antipenetrant to Schistosoma mansoni cercariae.

A randomized, double-blind, placebo-controlled field trial of a topical antipenetrant lotion, 1% niclosamide, applied daily to the upper and lower limbs of farmers occupationally exposed to Schistosoma mansoni cercarial-infested water, was conducted in the Nile Delta to assess its safety and efficacy in preventing reinfection. Farmers aged 18-40 years were treated to cure their S. mansoni infections three months prior to the onset of the trial. Subjects were randomly assigned to receive niclosamide or placebo lotion that was self-applied daily for five months. A total of 186 subjects met the inclusion criteria and completed the trial. The exposure to schistosomal-infested water occurred during routine irrigation activities from June to November 1991. Stool specimens were evaluated monthly during and for two months following the lotion application period. The subjects applying the niclosamide lotion were comparable to those applying placebo lotion in age (mean 30 years for both), total water contact (184.5 hr versus 173.8 hr), reported lotion application compliance (88% versus 92%), and reported water contact involving skin exposure other than upper and lower limbs (23% versus 27%). The schistosomal reinfection rate was lower in the niclosamide group (53.3%) compared with the placebo lotion group (71.3%), (P < 0.02). Increased protection might be obtained with total body application for shorter, less intense, water contact exposures.

Risk factors of gastric precancerous lesions in a high-risk Colombian population. I. Salt.

A case-control study for stomach cancer was conducted in a high-risk population in Nariño, Colombia to determine the risk of gastric precancerous lesions associated with salt intake measured by sodium-to-creatinine ratio of a single urine sample. Gastric biopsies and urine samples were collected from 263 individuals. Urinary sodium-to-creatinine ratios were studied in relation to histological data from the biopsies. Significantly high odds ratios for precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) were associated with higher sodium-to-creatinine ratios. Adjusted odds ratios (OR) of 2.50 for chronic atrophic gastritis and 7.24 for dysplasia were found. The association with intestinal metaplasia was weaker and not significant (OR = 1.57). Furthermore, an excess risk associated with adding salt to food at the table was found among patients with precancerous lesions (OR = 1.80). These findings support the two-step involvement of salt in the process of gastric precancerous lesions.

Risk factors of gastric precancerous lesions in a high-risk Colombian population. II. Nitrate and nitrite.

Gastric nitrite content was studied in relation to precancerous lesions of the stomach in a case-control study conducted in a high-risk Colombian population. The proportion of detectable nitrite in gastric juice and the mean pH were significantly higher among those with precancerous lesions (chronic atrophic gastritis, intestinal metaplasia, and dysplasia) than among the controls (normal and superficial gastritis); the proportion and mean pH increased with the progression of histological changes from normal to dysplasia. Nitrite was not detectable in gastric juice with a pH less than 5.0. A positive association was found between the proportion of detectable nitrite and the risk of gastric precancerous lesions. Odds ratios of 4.39 for intestinal metaplasia and 24.72 for dysplasia remained significant after controlling for confounders. This finding suggests that nitrite may be a precursor of a mutagen that targets gastric epithelial cells.