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The oral agent miltefosine has demonstrated a >95% cure rate in Indian visceral leishmaniasis. We performed a large, placebo-controlled study of miltefosine therapy (2.5 mg/kg per day orally for 28 days) against cutaneous leishmaniasis in Colombia and Guatemala. In regions in Colombia where Leishmania vianna panamensis is common, the per-protocol cure rates for miltefosine and placebo were 91% (40 of 44 patients) and 38% (9 of 24). These values are similar to historic values for the antimony standard of care and placebo. In regions in Guatemala where L. v'. braziliensis and L. mexicana mexicana are common, the per-protocol cure rates were 53% (20 of 38) for miltefosine and 21% (4 of 19) for placebo. The miltefosine rate was lower than historic antimony cure rates of >90%. Miltefosine was well tolerated. Miltefosine is a useful oral agent against cutaneous leishmaniasis due to L. v. panamensis in Colombia but not against leishmaniasis due to L. v'. braziliensis in Guatemala. [ABSTRACT FROM AUTHOR]

Background: Primaquine had a prophylactic efficacy of 90% to 95% against infection with Plasmodium falciparum and P. vivax in Indonesian settlers.Objective: To evaluate the efficacy of primaquine prophylaxis for protecting nonimmune persons from malaria.Design: Randomized, double-blind, placebo-controlled field study.Setting: A malaria-endemic area in Colombia.Patients: 176 healthy, young, nonimmune adult male soldiers.Intervention: Primaquine, 30 mg/d, or matching placebo during 15 weeks of patrol in the endemic area and 1 week afterward.Measurements: Symptomatic parasitemia was determined over the 16-week intervention period and for 3 weeks in base camp.Results: Protective efficacy in the primaquine group (122 participants) was 89% (95% CI, 75% to 96%) against all types of malaria, 94% (CI, 78% to 99%) against P. falciparum malaria, and 85% (CI, 57% to 95%) against P. vivax malaria. Six primaquine recipients had mild to moderate gastrointestinal distress, and three had severe distress.Conclusions: For prophylaxis against P. falciparum malaria, primaquine has an efficacy and toxicity competitive with those of standard agents. A potential advantage of primaquine is that prophylaxis may be discontinued 1 week after the recipient has left the endemic area. [ABSTRACT FROM AUTHOR]

Malarone was compared with placebo in a double-blind, randomized, placebo-controlled trial of prophylaxis of malaria in predominately Plasmodium vivax areas of Colombia. The study population consisted of 180 completely non-immune Colombian soldiers, male, average age 19 years, and average weight 63 kg. Twenty-four subjects were considered unevaluable because of compliance issues, including one Malarone subject (with no detectable drug levels) who became infected with P. vivax. Of the 97 evaluable subjects who received Malarone (250 mg atovaquone plus 100 mg proguanil hydrochloride) daily from 1 day before entering the endemic area to 7 days after leaving the endemic area, none became parasitemic. Of the 46 evaluable placebo subjects, 11 became infected with P. vivax and 2 became infected with Plasmodium falciparum. The protective efficacy of Malarone for all malaria and for P. vivax malaria was 100% (LL 95% CI = 63%) and 100% (LL 95% CI = 58%), respectively, and was 96% if the one case with undetectable blood levels was included. Malarone has high protective efficacy for P. vivax in Colombia.

The cost of generic pentavalent antimony (generic stibogluconate) is approximately one-sixth that of branded pentavalent antimony (stibogluconate in the form of Pentostam or meglumine antimoniate in the form of Glucantime. We compared generic stibogluconate to Pentostam and Glucantime for the treatment of cutaneous leishmaniasis patients in Bolivia and Colombia. For all 114 patients, the per-protocol cure rates were 83-91% and the intent-to-treat cure rates were 75-83%. The highest values were in the generic stibogluconate group. The incidence of pancreatic enzyme abnormalities was 48-88% and the incidence of liver enzyme abnormalities was 48-87%. The lowest incidences were in the generic stibogluconate group. The efficacy and tolerance of inexpensive generic stibogluconate appears comparable to branded formulations for the treatment of cutaneous leishmaniasis in these endemic regions.

There is no recognized oral treatment for American cutaneous leishmaniasis. A rising-dose, open-label phase I/II trial of the oral agent miltefosine against Colombian cutaneous leishmaniasis was conducted. Seventy-two male Colombian soldiers (mean weight, 67 kg) received miltefosine at 50-100 mg/day for 3 weeks (for 32 evaluable patients) or at 133-150 mg/day for 3-4 weeks (for 32 evaluable patients). The per-protocol cure rate for 50-100 mg/day was 21 (66%) of 32 patients. The per-protocol cure rate for 133-150 mg/day was 30 (94%) of 32 patients (P =.01, by use of Fisher's exact test). The historic per-protocol cure rate for standard injections of antimony is 93%. "Motion sickness" that did not interfere with normal duties was experienced by 40% of patients and was dose related. Vomiting and diarrhea were reported on approximately 2% of treatment days. In this uncontrolled study of oral miltefosine for treatment of patients with American cutaneous leishmaniasis, a dosage of approximately 2.25 mg/kg/day for 3-4 weeks was effective and tolerated.

Chloroquine-resistant Plasmodium vivax has been the subject of numerous case reports and prospective studies from Oceania and Asia. In contrast, only case reports exist from the Americas. We performed a prospective study with 28-day follow-up of clinical responses to chloroquine in 2 P. vivax-endemic regions of Colombia. Three (11%) of 27 patients failed to respond to treatment with the standard regimen of chloroquine (1,500 mg of base over 3 days). One patient demonstrated RI resistance on Day 26; one patient demonstrated RI resistance due to recrudescence of blood stages on Day 11; and one patient demonstrated RII resistance of blood stages by never displaying clearing of peripheral parasitemia. All patients were successfully treated with primaquine, which has some blood stage efficacy against P. vivax, combined with a second course of chloroquine. Clinical resistance of P. vivax to chloroquine is present in Colombia and should be monitored in the Americas.

To improve upon the efficacy of primaquine prophylaxis for malaria (94%, Plasmodium falciparum malaria; 85%, Plasmodium vivax malaria), we administered chloroquine (300 mg weekly) in combination with primaquine (30 mg daily) to nonimmune Colombian soldiers during 16 weeks of patrol in a region of endemicity and for a further 1 week in base camp. The occurrence of symptomatic parasitemia was determined during those 17 weeks and during a further 3 weeks in base camp. The protective efficacy for the chloroquine/primaquine treatment group of 100 subjects, compared with that for the placebo treatment group of 51 subjects, was 88% (95% confidence interval [CI], 76-94) against all types of malaria, 89% (95% CI, 61-97) against P. falciparum malaria, and 88% (95% CI, 58-93) against P. vivax malaria. Two chloroquine/primaquine recipients had severe gastrointestinal distress. Comparison of these data with data from a previous study indicates that the addition of chloroquine did not increase the prophylactic efficacy of primaquine.

The most extensive investigations of treatment of New World cutaneous leishmaniasis have been performed against L. panamensis disease in Colombia, and the relative value of regimens shown there may be instructive for disease from other areas. In Colombia, a 90-95% cure rate was achieved with three different drug regimens: The standard regimen of pentavalent antimony (20 mg/ kg/day for 20 days parenterally) A short course of pentamidine (3 mg/kg every other day for four injections intramuscularly The marketed combination of topical paromomycin (15%)-MBCl (12%) for 10 days, plus antimony (20 mg/kg/day parenterally) for 7 days. My view is that all these regimens could be chosen as first-line therapy for cutaneous disease in Colombia. The antimony regimen has the advantage of established use; the disadvantages are cost, requirement for injections each day for 20 days, and considerable morbidity in the last two weeks of therapy. The pentamidine regimen has the advantage of a short time course; the disadvantages are lack of experience with this new regimen and frequent, although moderate, morbidity. The combined topical-parenteral regimen has the advantage of requiring few and nontoxic injections; the primary disadvantage is that the regimen is novel and its efficacy has not been confirmed. It would be expected that cases of lesions in other areas caused by L. braziliensis complex would respond in a similar manner to these regimens. To date, however, only the efficacy of the standard antimonial regimen has been confirmed. In certain regions of Central America, other regimens may be effective. Thus, ketoconazole appears to be effective for the more rapidly self-curing forms of disease (cutaneous disease caused by L. mexicana and L. panamensis from Central America), and a short course of antimony may be effective against L. braziliensis in Guatemala.

We determined the efficacy of the use of permethrin-impregnated uniforms for prevention of malaria and leishmaniasis in a double-blind, randomized study of Colombian soldiers on patrol. In the study of malaria, soldiers were issued impregnated uniforms (i.e., a shirt, an undershirt, pants, socks, and a hat) or uniforms washed in water; the soldiers wore the uniforms day and night for a mean of 4.2 weeks and were observed for an additional 4 weeks. Three (3%) of 86 soldiers wearing impregnated uniforms contracted malaria, whereas 12 (14%) of 86 soldiers wearing control uniforms contracted malaria (P = .015). In the study of leishmaniasis (soldiers were in the area of endemicity for 6.6 weeks and were observed for 12 weeks thereafter), 4 (3%) of 143 soldiers wearing impregnated uniforms and 18 (12%) of 143 soldiers wearing control uniforms acquired disease (P = .002). In the leishmaniasis study, and presumably in the malaria study, breakthrough infections in the treated group were primarily due to bites in unclothed regions of the body (face and hands). Permethrin-treated uniforms were virtually nontoxic (there were only two cases of mild skin irritation among 229 subjects), and impregnation is quick and inexpensive. Impregnation of clothing with permethrin is suggested for nonimmune populations who are likely to be exposed to malaria or leishmaniasis over a period of 1-2 months.

We previously found that 2 mg of pentamidine isethionate/kg, administered every other day in seven injections, was 95% curative for Colombian cutaneous leishmaniasis. However, 17% of the patients had to prematurely terminate therapy due to drug toxicity and another 30% had mild-to-moderate toxic clinical reactions. In this report, we show that the same daily dose of drug, 2 mg/kg, but administered in only four every-other-day injections, resulted in an 84% cure rate in 38 patients. Twenty-one patients (55%) experienced side effects, three of which were moderate to severe. A higher daily dose of drug, 3 mg/kg, administered in four every-other-day injections, resulted in a 96% cure rate in 51 evaluable patients. Thirty-six of the treated patients (64%) experienced side effects, five of which were moderate to severe. Although hypotension and hypoglycemia were looked for in all patients, only one patient experienced hypoglycemia and it had normalized by follow-up. We propose that the regimen of 3 mg of pentamidine/kg every other day in four injections is optimal for Colombian cutaneous leishmaniasis and competitive with standard Glucantime therapy, in terms of cure rate, toxicity, length of time the patient has to be under medical supervision, and cost of drug plus medical attention. We suggest that such a short course of injectable agent be studied for the treatment of patients with cutaneous leishmaniasis from other endemic areas.

Ninety-two patients in Colombia with cutaneous leishmaniasis were randomly assigned to groups to be treated with meglumine antimonate (infected control subjects; 10 mg of antimony/kg intramuscularly, twice a day for 20 days), pentamidine (2 mg/kg every other day intramuscularly, for a total of seven injections), or itraconazole (200 mg orally, twice a day for 28 days) or to receive no treatment (negative control subjects). In the group treated with meglumine antimonate, 21 of 23 patients healed by the first follow-up visit, 1.5 months after the end of therapy, and did not relapse (91% cure rate). In the pentamidine-treated group, 23 of 24 patients healed and did not relapse (96%). Four of the 23 pentamidine-treated patients who ultimately were cured had terminated therapy prematurely (after receiving 4-6 injections) because of hypotension (2 patients), hypoglycemia (1 patient), or headache and myalgias (1 patient). In a subsequent group of 19 patients who were administered 2 mg of pentamidine/kg every other day for a total of only four injections, 14 healed without relapse (74% cure rate). The itraconazole-treated group was similar to the no-treatment control group in terms of the number of patients for whom therapy failed (75% and 64%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)