Oral miltefosine treatment in children with mild to moderate Indian visceral leishmaniasis.
BACKGROUND
Miltefosine is the first oral drug with demonstrable success in treating visceral leishmaniasis in adults. Because approximately one-half of the visceral leishmaniasis patients worldwide are children, we performed a Phase I/II dose ranging study in the pediatric population in India.


METHODS
Thirty-nine (39) children (defined as < 12 years of age) with visceral leishmaniasis demonstrated by parasites in splenic aspirates, were treated with oral miltefosine daily for 28 days: 21 patients received 1.5 mg/kg/day (Group A); and 18 patients received 2.5 mg/kg/day (Group B). About one-half of these children had failed prior antileishmanial treatment.


RESULTS
All patients were parasitologically negative and symptomatically improved by the end of therapy on Day 28 of therapy; the initial parasitologic cure rate was 100%. Two patients in each treatment group relapsed with fever, splenomegaly and parasite-positive splenic aspirates by the end of the 6-month follow-up. The per protocol final clinical cure rate was 19 of 21 = 90% in Group A and 15 of 17 = 88% in Group B. Miltefosine was well-tolerated. As per the adult experience, gastrointestinal adverse events were seen: 33 and 39% of children experienced vomiting and 5 and 17% experienced diarrhea in Groups A and B, respectively, but all episodes were mild to moderate in severity and commonly lasted <1 day without symptomatic treatment.


CONCLUSIONS
Oral miltefosine was safe and approximately 90% effective in this initial clinical trial of childhood visceral leishmaniasis.
Sundar
Shyam
S
Institutes of Medical Sciences, Banaras Hindu University, 6 SK Gupta Nagar, Varanasi 221005, India. Shyams@sancharnet.in
Jha
T K
TK
Sindermann
Herbert
H
Junge
Klaus
K
Bachmann
Peter
P
Berman
Jonathan
J
D000284:Administration, Oral; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001682:Biological Availability; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007194:India / Q000453:epidemiology; D007898:Leishmaniasis, Visceral / Q000175:diagnosis* / Q000188:drug therapy* / Q000453:epidemiology; D008297:Male; D020714:Maximum Tolerated Dose; D010767:Phosphorylcholine / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011336:Probability; D018570:Risk Assessment; D012720:Severity of Illness Index; D016896:Treatment Outcome
D000981:Antiprotozoal Agents; D010767:Phosphorylcholine; C039128:miltefosine