Response to measles revaccination among toddlers in Saudi Arabia by the use of two different trivalent measles-mumps-rubella vaccines.

This trial confirmed the immunogenicity of a standard dose of measles vaccine Edmonston-Zagreb strain administered at the age of 6 months as evaluated serologically at 12 months of age in 94 healthy children in Saudi Arabia. The residual seropositivity rate for measles was 53.4 and 80.

Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria.

To examine the effect of iron chelation on mortality in cerebral malaria, we enrolled 352 children in a trial of deferoxamine in addition to standard quinine therapy at 2 centres in Zambia, one rural and one urban. Entrance criteria included age < 6 years, Plasmodium falciparum parasitaemia, normal cerebral spinal fluid, and unrousable coma. Deferoxamine (100 mg/kg/d infused for a total of 72 h) or placebo was added to a 7 d regimen of quinine that included a loading dose.

Effect of food on the bioavailability of triclabendazole in patients with fascioliasis.

Aims: Preliminary results indicate higher absorption of triclabendazole (TCBZ) administered postprandially. Therefore, the influence of food on the pharmacokinetics of TCBZ and its active sulphoxide (TCBZ-SO) and sulphone (TCBZ-SO2) metabolites was investigated.

Methods: Two single doses (10 mg kg(-1)) of TCBZ were administered to 20 patients with fascioliasis.

Transferrin saturation and recovery from coma in cerebral malaria.

To determine if the elevated transferrin saturations found in some patients with severe malaria are associated with an adverse outcome in cerebral malaria, we retrospectively measured baseline saturations in stored serum samples from 81 Zambian children with strictly defined cerebral malaria. The children had been treated with quinine, sulfadox-ine-pyrimethamine, and intravenous infusions of either placebo (n = 39) or the iron chelator, desferrioxamine B (n = 42), in a previously reported trial (Gordeuk et al, N Engl J Med 327:1473, 1992). More than one-third of children in both the placebo- and iron chelator-treated groups had transferrin saturations exceeding 43%, which is 3 standard deviations above the expected mean for age.

Iron chelation as a chemotherapeutic strategy for falciparum malaria.

To examine the effect of iron chelation against human malaria, 37 Zambians with asymptomatic Plasmodium falciparum infections were randomly assigned to 72-hr infusions of desferrioxamine B or placebo. Mean concentrations of ring forms decreased significantly with desferrioxamine B (P < 0.001) but not with a placebo.

Plasmodicidal effect of desferrioxamine B in human vivax or falciparum malaria from Thailand.

Desferrioxamine B (DFO, Desferal), an iron chelator, was earlier shown to be active against Plasmodium falciparum in vitro and in vivo. The present open pilot study served to assess its clinical tolerability and efficacy in human malaria under hospital conditions. Continuous intravenous DFO was administered to 28 Thai males at a dose of 100 mg/kg over 24 h for 3 consecutive days.

[Distomatosis of the bile ducts. Value of retrograde cholangiography. Efficacy of triclabendazole].

A case of chronic biliary fascioliasis is reported, which was confirmed by endoscopic retrograde cholangiography. After unsuccessful attempts of treatment with classic antiparasitic drugs, cure was obtained with triclabendazole the absorption of which was studied.

Fine structure of microfilariae in the skin of onchocerciasis patients after exposure to amocarzine.

Transmission electron microscopy was used to demonstrate the effects of amocarzine (CGP 6140) on the fine structure of Onchocerca volvulus microfilariae (mf) in skin biopsies from patients treated orally in Guatemala or transepidermally exposed in Liberia. After 6-10 hours exposure to the drug most mf did not show any alterations and only a few mf contained increased numbers of vacuoles in the cytoplasm and clefts between cuticle and hypodermis. At 20-48 hours after treatment most of the mf showed distinct signs of damage.

Longterm follow-up of onchocerciasis patients in Latin America after treatment and retreatment with amocarzine. Preliminary results.

Amocarzine has been reported to have onchocercacidal effects. Four months posttherapy the majority of adult worms were dead or moribund. The effect of skin microfilariae lasted up to one year as reflected by markedly reduced microfilaridermia.

Use of an ophthalmologic ultrasoundscanner in human onchocercal skin nodules for non-invasive sequential assessment during a macrofilaricidal trial with amocarzine in Guatemala. The first experiences.

Ultrasonography of onchocercal skin nodules was performed with an ophthalmologic real time linear scanner with a B probe of 10 MHz. A clinical trial in Guatemala with amocarzine (CGP 6140)--a new oral macrofilaricidal compound--investigated three repeat dose regimens and one placebo control group, each group consisting of six patients. Onchocercal nodules were scanned before treatment and on day 10, 30 and 60 after start of amocarzine.

Microfilaricidal effect of amocarzine in skin punch biopsies of patients with onchocerciasis from Latin America.

Skin punch biopsies were performed in 54 selected patients with onchocerciasis participating in a clinical trial with amocarzine (CGP 6140) in Ecuador and Guatemala. Skin snipping for counting microfilariae of Onchocerca volvulus was done before treatment (day 0) and day 4 and 8 following start of the therapy which consisted of 3 mg/kg amocarzine postprandially twice daily for three consecutive days. The mean microfilarial skin density has been reduced by 45% on day 4 and 95% on day 8.

Concentrations of amocarzine in plasma of 71 Ecuadorian patients of two different races receiving 3 mg/kg b.i.d. and 5 mg/kg o.d. oral postprandial doses for 3 days.

The possible influence of sex, race and of postprandial administration conditions (either immediately after the end of meal or one hour later) on the plasma concentrations of amocarzine and its N-oxide metabolite, CGP 13 231, was investigated. 71 Ecuadorian patients (48 males and 23 females) of two different races (Indio and Negro) infected with Onchocerca volvulus participated in the study. The concentrations were measured on day 3 at times 3 and 6 h after postprandial administration in the morning of a treatment with either a dose of 5 mg/kg of amocarzine once daily (12 patients) or 3 mg/kg twice daily (59 patients) for 3 days.

Influence of food related to dose on the pharmacokinetics of amocarzine and of its N-oxide metabolite, CGP 13 231, after oral administration to 20 onchocerciasis male patients from Guatemala.

Twenty male patients from Guatemala infected with Onchocerca volvulus received a 3 mg/kg oral dose of amocarzine twice daily for three days. The patients were randomly assigned to the sequence fasting/non-fasting and non-fasting/fasting for the morning administration on days 1 and 3. All other doses were given after food intake.

Onchocercacidal effect of three drug regimens of amocarzine in 148 patients of two races and both sexes from Esmeraldas, Ecuador.

The objective of this multidisciplinary clinical investigation was to test whether amocarzine was absorbed effectively and safely in patients of two races and either sex infected with Onchocerca volvulus while living in the holoendemic area of Esmeraldas Province, Ecuador. The prerequisite for a systemic onchocercacidal effect is the regular absorption of orally administered amocarzine. Single dosing after overnight fasting proved to produce irregular absorption of amocarzine, although some microfilaricidal effect was achieved.

Amocarzine investigated as oral onchocercacidal drug in 272 adult male patients from Guatemala. Results from three dose regimens spread over three days.

The clinical investigations with three types of a three days regimen of amocarzine permitted to adjust the fixed dosing to the body weight related dosing and subsequently the administration of amocarzine from fasting state to drug intake after food. The main objective to reach a dose with predictable and sustained absorption was achieved, and this in turn proved to be onchocercacidal and safe. A combined clinicopharmacokinetic study showed enhancement and consistency of amocarzine absorption after food.

Onchocercacidal effects of amocarzine (CGP 6140) in Latin America.

An open clinical trial of amocarzine was carried out in onchocerciasis patients in Ecuador and Guatemala. Administration after food was more effective than that during fasting. The most effective and best tolerated regimen, 3 mg/kg twice daily after food for 3 days (in 312 patients), killed 73% of 1477 female worms at nodulectomy 4 months after treatment.

The influence of food on the pharmacokinetics of CGP 6140 (amocarzine) after oral administration of a 1200 mg single dose to patients with onchocerciasis.

Eleven male patients from Mali with Onchocerca volvulus infections received in random order a 1200 mg single oral dose of CGP 6140 after an overnight fast and after food intake. The concentrations of CGP 6140 and of its N-oxide metabolite, CGP 13231, were measured in plasma and urine. Mean (+/- s.

Pharmacokinetics of CGP 6140 (amocarzine) after oral administration of single 100-1600 mg doses to patients with onchocerciasis.

The concentrations of CGP 6140 [4-nitro-4'-(N-methyl-piperazinylthiocarbonylamido)-diphenylamine] and of its N-oxide metabolite, CGP 13,231, were measured in plasma and urine after single oral dose of 100-1600 mg of CGP 6140 to 41 fasted Ghanaian patients with Onchocerca volvulus infections. The absorption of CGP 6140 was rapid and its terminal elimination half-life was about 3 h. The plasma concentrations of CGP 6140 were essentially proportional to the dose.

The in vitro determination of the visual resolution in onchocercal nodules of bovine and human origin by a portable ophthalmologic ultrasound scanner.

A portable ophthalmologic real-time ultrasound linear scanner (Ophthascan) was used to determine the optic resolution of excised onchocercal nodules of Onchocerca volvulus and O. gibsoni origin. Fresh, thawed and fixed nodules were used.