Comparative study of the effectiveness and pharmacokinetics of two rectal artesunate/oral mefloquine combination regimens for the treatment of uncomplicated childhood falciparum malaria.

BACKGROUND: Rectal artesunate has been shown to be an effective treatment for falciparum malaria and is useful in patients who cannot take medicine orally or when parenteral medication is inconvenient. A combination with mefloquine can decrease the duration of treatment, increase compliance and delay development of resistance. There are no clear data on whether a higher dosage of rectal artesunate results in a better clinical response. AIM: To assess two rectal artesunate/oral mefloquine regimens for treating uncomplicated multi-drug-resistant childhood falciparum malaria. METHODS: Seventy children aged 1-14 years with uncomplicated falciparum malaria were randomly assigned to receive either 10 (range 8-12) or 20 (range 16-24) mg/kg/day rectal artesunate for 3 days followed by 25 mg/kg oral mefloquine. The study endpoints were fever clearance time, parasite clearance time and proportion of patients with recrudescence. Serum levels of artesunate and dihydro-artemisinin were measured after the first dose of rectal artesunate in 16 subjects. RESULTS: Both regimens were safe and effective. The cure rate was 100% in the 53 patients who completed 28-day follow-up. All of the study endpoints were comparable between both treatment groups. CONCLUSION: A regimen of rectal artesunate 10 mg/kg/day for 3 days followed by mefloquine 25 mg/kg is optimal for the treatment of uncomplicated falciparum malaria. There was no definite benefit from increasing the dosage of rectal artesunate from 10 to 20 mg/kg/day.

Life-saving rectal artesunate for complicated malaria in children.

We report the effectiveness of two regimens of rectal artesunate formulation in treating 13 Thai children with cerebral/complicated falciparum malaria. The drug was given at an initial dose of 40 mg/kg bodyweight, in 3 or 4 divided doses in the first 24 hours, followed by 10 mg/kg bodyweight once daily for three consecutive days. Mefloquine, at a dose of 15 mg/kg bodyweight was given orally at 72 hours after the initial dose of artesunate, followed by 10 mg/kg bodyweight 6 hours later. Three cases with cerebral malaria gained consciousness within 20 hours of artesunate administration. The median time required for reduction of parasitemia by 90% of the initial value (P90) in 13 children was 11.2 hours. No recrudescence was observed in any of the patients during the 28-day follow-up period. Plasma concentrations of artesunate and dihydroartemisinin (active plasma metabolite of artesunate) measured in two patients who received the high initial dose regimen (20 mg/ kg bodyweight) suggested rapid absorption and adequate plasma concentrations of both compounds following the administration of artesunate via the rectal route. Further studies for the optimized regimen of rectal artesunate in the treatment of cerebral/complicated childhood falciparum malaria in areas of multidrug resistance are warranted.

Safety and immunogenicity of a three dose regimen of two tetravalent live-attenuated dengue vaccines in five- to twelve-year-old Thai children.

OBJECTIVE: The safety and immunogenicity of tetravalent live-attenuated dengue vaccines after a three dose vaccination series were evaluated in Thai children. METHOD: One hundred three healthy flavivirus-seronegative schoolchildren ages 5 to 12 years were randomized to receive either dengue vaccine containing 3, 2, 1 and 2 log10 of the 50% cell culture infective dose, respectively, of the live-attenuated dengue vaccine serotypes 1, 2, 3 and 4 per dose (F3212; n = 40) or 3, 3, 1 and 3 log10 of the 50% cell culture infective dose (F3313; n = 42) or purified Vero cell rabies vaccine (control group; n = 21) given in a two dose schedule (3 to 5 months apart). A third dose was administered 8 to 12 months after the second dose to 90 subjects. Safety and immunogenicity were evaluated within 28 days after each injection. RESULTS: No serious adverse event related to the vaccines occurred. Most children experienced mild to moderate fever, rash, headache and myalgia occurring within 12 days after Dose 1 and generally lasting 3 days or less. One subject in Group F3212 had a 1-week dengue-like fever. Reactogenicity was minimal after Doses 2 and 3. Transient mild variations in liver enzymes and hematologic indices were noted mainly after Dose 1. After the third dose 89% of the subjects in Group F3212 seroconverted (neutralizing antibody response, > or =10) to all four serotypes, and all children in Group F3313 seroconverted. CONCLUSION: This study demonstrates a moderate although improvable reactogenicity and high seroconversion rates against the four serotypes of dengue after a three dose schedule of tetravalent live-attenuated dengue vaccine in children.

Prevalence of intestinal parasitic infection among Thai people with mental handicaps.

The prevalence of intestinal parasitic infection was studied by stool examination in institutionalized and non-institutionalized Thai people with mental handicaps. It was found that the prevalence of infection was much higher in institutionalized (57.6%) than in non-institutionalized people (7.5%). The common parasites found in institutionalized people were Trichuris trichiura (29.7%), Entamoeba coli (23.1%), Giardia intestinalis (8.0%), Hymenolepis nana (7.8%), and Entamoeba histolytica/dispar (7.1%). Institutionalized mentally handicapped people should be considered as a high risk group for intestinal parasitic infection and a parasitic control measure should be emphasized.

Safety and immunogenicity of tetravalent live-attenuated dengue vaccines in Thai adult volunteers: role of serotype concentration, ratio, and multiple doses.

Dengue fever, caused by four serotypes of a mosquito-borne virus, is a growing problem in tropical countries. Currently, there is no treatment or vaccine. We evaluated safety and immunogenicity of two doses, given six months apart, of seven formulations of dengue tetravalent live-attenuated vaccine (containing different concentrations of the component viruses) versus placebo in 59 flavivirus-seronegative Thai adults. The first dose was the more reactogenic. Most volunteers experienced clinically moderate fever, headache, myalgia, eye pain or rash 7-11 days after injection, generally lasting three days or less. Modest decreases in platelets and neutrophils were observed. After one dose, 58% of dengue recipients seroconverted (neutralizing antibody level > or = 1:10) against > or = 3 serotypes; 35% seroconverted against all four. After the second dose, seroconversion was 76% and 71%, respectively. All subjects seroconverted to serotype 3 after one dose. Serotype 4 elicited the lowest primary response but the highest increase in seroconversion after the second dose.

Single-dose therapy for giardiasis in school-age children.

A randomized controlled trial was carried out to study the efficacy of combined albendazole and praziquantel in the treatment of giardiasis in school-age children. Eighty-four children were randomly allocated to 3 groups: group 1 (n = 31) albendazole 400 mg combined with praziquantel 20 mg/kg; group 2 (n = 26) albendazole 800 mg as a single dose; group 3 (n = 27) tinidazole 50 mg/kg as a single dose. The treatment was considered curative when Giardia was not found in two consecutive stool samples. The parasitological cure rate was 74.2% for combined single-dose albendazole-praziquantel, 50% and 92.6% in the albendazole and tinidazole groups respectively (p = 0.0023). There was no statistically significant difference between the cure rates of the combined regimen and tinidazole (p > 0.05). This combined regimen was considered safe, with only minor side-effects being observed. Of the single-dose regimens, tinidazole still achieves the highest parasitological cure rate for giardiasis. The albendazole-praziquantel combined regimen may be an alternative single-dose therapy for giardiasis in children, especially as this combination will eradicate common intestinal protozoa and co-existing helminths. Whether the dosage of this combination treatment should be adjusted for G. intestinalis remains to be established by further study.