Miltefosine for new world cutaneous leishmaniasis.

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.

Randomized, controlled, double-blind trial of topical treatment of cutaneous leishmaniasis with paromomycin plus methylbenzethonium chloride ointment in Guatemala.

A double-blind, randomized trial was undertaken in Guatemala to determine the therapeutic efficacy of an ointment for the treatment of cutaneous leishmaniasis that contained 15% paromomycin and 12% methylbenzethonium chloride and that was applied twice a day for 20 days. The treatment group included 35 patients, and the placebo group included 33 patients. The initial clinical response rate (13 weeks after completing the treatment) was 91.4% in the treatment group and 39.4% in the placebo group. The final clinical response rate at the 12-month follow-up examination was 85.7% (31 of 35) in the treatment group and 39.4% (13 of 33) in the placebo group (P < or = 0.001). In general, the treatment was well tolerated and was never interrupted because of adverse effects. The number of adverse effects reported in the placebo group was lower than in the treatment group (16 events versus 30 events). All adverse effects reported by patients disappeared within 1 week of completing the treatment. Our findings show that the combination of paromomycin with methylbenzethonium chloride for 20 days is a good alternative for antimonial treatments of cutaneous leishmaniasis in Guatemala.

Cutaneous leishmaniasis in Guatemala: people's knowledge, concepts and practices.

Ten rural communities in the northern area of Guatemala where cutaneous leishmaniasis (CL) is endemic were investigated to determine the residents' knowledge of the disease, their related concepts and practices, and their treatment preferences, and to identify the communication channels they use to acquire information. Of 425 heads of household interviewed, 96.7% could accurately describe a typical CL lesion. CL was found to be the fourth most frequently mentioned disease (in studies based on a free list format) and to be considered the sixth most serious (in studies based on paired comparisons). A series of three-way comparisons, used to analyse the subjects' concepts about the similarities of various discases, indicated that CL was considered to be most closely related to skin problems and to be different from any other group of diseases. All interviewees believed that it was necessary to receive treatment for CL, because without treatment the disease would progress, reach the bone, and take years to heal. More than half (55%) of the respondents knew about meglumine antimonate (Glucantime), the most commonly prescribed drug for treating CL in Guatemala. Only a few communication channels that were used by respondents to receive information were identified; the use of radio broadcasts and direct communication via the community leaders appeared to be the most effective.

Evaluation of a standardized leishmanin skin test in Guatemala.

Before recommending the skin-test use at national level in Guatemala of an antigen prepared from Leishmania major (a Leishmania species not found in the New World), we conducted a study in 100 Guatemalans to determine its sensitivity and specificity. The antigen consisted of 0.1 mL of a solution that contained 5 x 10(6) promastigotes of L. major (MRHO/IR/75/VAX). Positive leishmanin skin test (LST) reactions at 48 h were observed in 16 (80%) of 20 patients with proven active cutaneous leishmaniasis (CL), 18 (90%) of 20 with previously treated proven CL, and in 18 (90%) of 20 with a history and compatible scan of previously suspected but unconfirmed CL. None of 20 healthy controls or 20 patients with skin lesions due to causes other than CL had positive reactions to the LST, giving a sensitivity of 85% and specificity of 100%. There were no statistically significant differences in ethnic group, age, duration of the lesion, lesion size or Leishmania species between the 34 persons with true positive reactions. Even though it will be necessary to test this antigen on a larger number of patients, these preliminary results show that this antigen is specific and reasonably sensitive in identifying current or past CL and that it is a reasonable choice for epidemiological studies on CL in Guatemala.

First reported outbreak of abdominal angiostrongyliasis.

Human abdominal angiostrongyliasis is a potentially fatal disease caused by Angiostrongylus costaricensis, a nematode found in the Americas. During the period of December 1994 through August 1995, an outbreak of this disease occurred in Guatemala. We identified 22 cases of abdominal angiostrongyliasis and conducted a matched case-control study to identify risk factors for illness. The median age of the 18 cases enrolled in the study was 37 years (range, 9-68 years), and 11 (61.1%) were male. Consumption of the following six raw food items was associated with angiostrongyliasis: mint (odds ratio [OR], 6.9; 95% confidence interval [CI], 1.5-66.0), shrimp (OR, infinite; 95% CI, 1.4 to infinite), and four kinds of ceviche that reportedly contained raw mint (OR for consumption of mint or ceviche that contained mint, 7.0; 95% CI, 1.0-315). We conclude that raw mint was the likely vehicle of infection for this outbreak. To our knowledge, this is the first reported outbreak of abdominal angiostrongyliasis and the first time that a specific food item has been epidemiologically linked to the disease.

The Leishmania hertigi (Kinetoplastida; Trypanosomatidae) complex and the lizard Leishmania: their classification and evidence for a neotropical origin of the Leishmania-Endotrypanum clade.

The relationships of the Leishmania hertigi complex and the lizard Leishmania species to the main groups of mammalian Leishmania and Endotrypanum parasites were examined. Restriction fragment length polymorphisms and sequences of small subunit ribosomal RNA genes and hybridization studies of kinetoplast DNA indicated that the L. hertigi complex was more closely related to the genus Endotrypanum than to the genus Leishmania. The lizard Leishmania species were found to be at the crown of the Leishmania tree. The data provides strong evidence for a Neotropical origin of the Endotrypanum/Leishmania clade since the parasites closest to the root of the tree are all found exclusively in the Neotropics. The evolution of the Leishmania/Endotrypanum clade in relation to the evolution of the known hosts of these parasites is discussed.

Efficacy of a short course (10 days) of high-dose meglumine antimonate with or without interferon-gamma in treating cutaneous leishmaniasis in Guatemala.

Sixty-six Guatemalan men with parasitologically confirmed cutaneous leishmaniasis, due most commonly to Leishmania braziliensis, were randomly assigned to receive one of three treatment regimens: meglumine antimonate (meglumine) for 20 days; meglumine for 10 days; and meglumine for 10 days plus alternate-day injections of interferon-gamma. In each group, meglumine was given intravenously as 20 mg of antimony/(kg of body weight.d). All treatment regimens were associated with similar response rates: the lesions of 19 (90%) of 21 patients who received meglumine for 20 days, 18 (90%) of 20 patients who received meglumine for 10 days, and all 22 patients who received meglumine plus interferon-gamma were completely reepithelialized by 13 weeks. In addition, for patients receiving all treatment regimens, test-of-cure cultures for Leishmania were negative and reactivation of lesions did not occur during 12 months of follow-up. The high efficacy of our 10-day course of meglumine indicates that the currently recommended duration of 20 days may be unnecessary for infections caused by L. braziliensis and suggests that a 10-day course of high-dose antimony should be tested as therapy for cutaneous leishmaniasis in other geographic areas.

The natural history of cutaneous leishmaniasis in Guatemala.

The natural history of American cutaneous leishmaniasis was studied in Guatemala by analyzing the characteristics of 355 untreated leishmanial lesions, observing the evolution of 57 lesions on persons who received a placebo in treatment trials, and analyzing data from a population-based survey concerning the duration of 82 untreated lesions. Of 25 lesions caused by Leishmania mexicana that were followed prospectively, 22 (88%) completely reepithelialized by a median lesion age of 14 weeks, and 17 (68%) were classified as cured (no residual wound inflammation or reactivation during at least 6 months of follow-up). In contrast, 7 (22%) of 32 lesions caused by Leishmania braziliensis reepithelialized by a median lesion age of 13 weeks, and only 2 (6%) cured. These data demonstrate that the species of Leishmania is the primary determinant of the clinical course and outcome of untreated lesions and underscore the need for field-applicable diagnostic techniques that provide rapid species identification.

Placebo-controlled clinical trial of sodium stibogluconate (Pentostam) versus ketoconazole for treating cutaneous leishmaniasis in Guatemala.

To determine the relative efficacy and toxicity of stibogluconate and ketoconazole for the treatment of cutaneous leishmaniasis, a comparative trial was conducted in which 120 Guatemalan men with parasitologically proven cutaneous leishmaniasis were randomly divided into three treatment groups: sodium stibogluconate (20 mg of antimony per kilogram per day intravenously for 20 days), ketoconazole (600 mg per day orally for 28 days), and placebo. Treatment outcome was influenced by species. Among patients infected with Leishmania braziliensis, 24 (96%) of 25 in the stibogluconate group but only 7 (30%) of 23 in the ketoconazole group responded. Among Leishmania mexicana-infected patients, only 4 (57%) of 7 in the stibogluconate group but 8 (89%) of 9 in the ketoconazole group responded. These differences emphasize the importance of speciation in the treatment of leishmaniasis.

Comparison of active and passive case detection of cutaneous leishmaniasis in Guatemala.

To estimate the degree to which passive case detection underestimates the true incidence of cutaneous leishmaniasis in Guatemala, we compared data from the passive surveillance system of the Guatemalan Ministry of Health with a cross-sectional population-based survey of cutaneous leishmaniasis in Guatemala. Of the 2,938 persons interviewed, 143 (5%) reported having had cutaneous leishmaniasis at some time in the past, 37 (1.3%) reported the onset of infection in the 12 months before the survey, 31 (1.1%) had active infections, and 16 (0.5%) had parasitologically confirmed infections. Calculated on the basis of these reports and the estimated population of the endemic area, the total number of new cases in the leishmaniasis-endemic area in the 12 months before the survey was approximately 2,574; during the same 12 month period, Ministry of Health data based on passive surveillance listed 64 cases of cutaneous leishmaniasis. In Guatemala, incidence estimates based on passive surveillance may underestimate the occurrence of cutaneous leishmaniasis by as much as a factor of 40.

Cutaneous leishmaniasis in Guatemala: comparison of diagnostic methods.

A comparison was made of methods used to diagnose suspected cutaneous leishmaniasis in Guatemala. The most sensitive method was a combination of thin smears made from superficial scrapings of the ulcers and inoculation of culture medium with either aspirates or scrapings. The diagnosis was confirmed in 252 (70%) of 362 patients. Ability to cultivate Leishmania was correlated with the concentration of amastigotes seen on thin smears. Leishmania were cultured in 42 (27%) of 153 patients with no amastigotes found in 400 oil-immersion fields and in 174 (83%) of 209 patients with at least 1 amastigote. No difference in diagnostic outcome was found when we compared smears or cultures taken from the center or the border of the ulcer or from an incision made tangential from the ulcer. We found no difference when we compared smears obtained with scalpels, capillary tubes, or dental broaches. The use of scrub brushes soaked in iodine neither decreased the rate of culturing parasites nor decreased contamination rates.

Placebo-controlled clinical trial of meglumine antimonate (glucantime) vs. localized controlled heat in the treatment of cutaneous leishmaniasis in Guatemala.

Sixty-six Guatemalans with parasitologically proven cutaneous leishmaniasis were randomly and equally divided into 3 treatment groups: those receiving meglumine antimonate (Glucantime), 850 mg antimony/day im for 15 days; those receiving localized controlled heat from a radio-frequency generator, 50 degrees C for 30 sec, 3 treatments at 7 day intervals; and those receiving treatment with a placebo. Of 53 isolates identified, 40 were Leishmania braziliensis braziliensis and 13 were L. mexicana mexicana. Thirteen weeks after beginning treatment, the number of patients from each group with completely healed and parasitologically negative lesions were as follows: meglumine antimonate, 16 (73%); localized heat, 16 (73%); and placebo, 6 (27%). The cure rate for those with infections due to L. b. braziliensis in each group was as follows: meglumine antimonate, 11 out of 14 (79%); controlled heat, 9 out of 14 (64%); and placebo, 0 out of 11.