Cutaneous Leishmaniasis In Colombia Research Articles

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments.

Eficacia y tolerancia de la pentamidina en el tratamiento de la leishmaniasis cutánea producida por Leishmania (V.) panamensis en Colombia

Current treatment for human cutaneous leishmaniasis (CL) relies on pentavalent antimonials. Although efficacy of these drugs is high (around 85%), their widely documented toxicity and increasing resistance makes the search for therapeutic alternatives a priority for endemic countries. To evaluate the efficacy and tolerability of the pentamidine isethionate for the treatment of cutaneous leishmaniasis caused by L. (V) panamensis in a pilot clinical trial. Sixty three individuals suffering CL were enrolled. Patients received four intramuscular injections of pentamidine (4 mg/Kg/injection) administered every other day, and both clinical efficacy and side effects were documented during the following 6 months. Of the 63 patients enrolled, 43 could be followed for 6 months. 86% (37/43) of treated patients healed all their lesions by 1.5 months after therapy. Treatment failure was observed in only five patients (11.6%; 5/43). One patient showed relapse. Overall tolerance of treatment was good, with adverse events such as local pain and swelling at the site of injection, dizziness and fever, varying from mild to moderate. Hypoglycemia, hypotension or diabetes were not observed. These results confirm the previously reported efficacy of pentamidine for the treatment of CL in Colombia and Brazil, and, additionally, highlight the low intensity and frequency of side effects in a civilian population. No serious adverse events were recorded.

Lutzomyia longiflocosa, posible vector en un foco de leishmaniasis cutánea en la región subandina del departamento del Tolima, Colombia, y el conocimiento que tiene la población sobre este insecto

Between 2003 and 2004 the largest epidemic of cutaneous leishmaniasis in Colombia (2,810 cases, with the highest incidence of 6,202 x 100,000 in 2004) occurred in the sub-Andean rural area of the municipalities of Chaparral and San Antonio in the department of Tolima. The present study was carried out to identify suspected vectors and to establish the knowledge that the inhabitants have about sand flies in order to use this information for vector control. 46 houses were sampled with CDC light traps set up indoors to establish the sand fly species composition, abundance and the percentage of infestation. Houses were examined during daylight to identify endophagy. A questionnaire was applied in order to estimate the knowledge about sand flies, their role in transmission and the sites and seasons of highest abundance. Three anthropophilic sand fly species of possible epidemiological importance were found. L. longiflocosa was the dominant sand fly species accounting for 81.7% (192 / 235) of all catches and infested the highest number of houses (41.7%). The other two species were L. columbiana and L. nuneztovari, with relative abundances of 3.4% and 2.1%, respectively, and house infestations of 13.0% and 6.5%, respectively. There was no evidence of endophilic behavior. Inhabitants recognized sand flies and their role in transmission. They identified the houses and the dry season as the site and time period of highest sand fly abundance. Based on its high anthropophily, predominance and apparent endophagic behavior, L. longiflocosa is the most probable vector of leishmaniasis indoors. L. columbiana and L. nuneztovari could be involved as secondary vectors outdoors. The importance of these findings on sand fly control is discussed.

Environmental factors associated with American cutaneous leishmaniasis in a new Andean focus in Colombia

To evaluate the environmental and ecological factors associated with Leishmania transmission and vector abundance in Chaparral, Tolima-Colombia. First, we compared the ecological characteristics, abundance of phlebotomies and potential reservoir hosts in the peridomestic environment (100 m radius) of randomly selected houses, between two townships with high and low cutaneous leishmaniasis incidence. Second, we examined peridomestic correlates of phlebotomine abundance in all 43 houses in the higher risk township. The high transmission township had higher coverage of forest (23%vs. 8.4%) and shade coffee (30.7%vs. 11%), and less coffee monoculture (16.8%vs. 26.2%) and pasture (6.3%vs. 12.3%), compared to the low transmission township. Lutzomyia were more abundant in the high transmission township 2.5 vs. 0.2/trap/night. Lutzomyia longiflocosa was the most common species in both townships: 1021/1450 (70%) and 39/80 (49%). Numbers of potential wild mammal reservoirs were small, although four species were found to be infected with Leishmania (Viannia) spp. In the high transmission township, the overall peridomiciliary capture rate of L. longiflocosa was 1.5/trap/night, and the abundance was higher in houses located nearer to forest (ρ = -0.30, P = 0.05). The findings are consistent with a domestic transmission cycle with the phlebotomies dependent on dense vegetation near the house.

An Epidemic Outbreak of Canine Cutaneous Leishmaniasis in Colombia Caused by Leishmania braziliensis and Leishmania panamensis

The largest recorded outbreak of cutaneous leishmaniasis in Colombia's history occurred during 2005-2009 in soldiers of the Colombian Army, with ~40,000 cases. This outbreak was caused by the influx of military personnel into the jungle with the mission of combat illicit crops and the guerrilla. The soldiers remain for long periods within the rainforest and are exposed to the bite of infected sand flies. During the military activities, soldiers work with dogs specially trained to detect landmines, and therefore, dogs are also exposed to the infected sand flies and show high incidence of cutaneous leishmaniasis (CL). This work describes an epidemic outbreak of canine CL caused by Leishmania braziliensis and Leishmania panamensis in Colombia, South America. The clinical features of the disease and the response to treatment with pentavalent antimonials observed in 72 guard dogs from the Colombian Army are described. A program for prevention and control of canine CL is also discussed.

Phlebotomine Vector Ecology in the Domestic Transmission of American Cutaneous Leishmaniasis in Chaparral, Colombia

Phlebotomine vector ecology was studied in the largest recorded outbreak of American cutaneous leishmaniasis in Colombia in 2004. In two rural townships that had experienced contrasting patterns of case incidence, this study evaluated phlebotomine species composition, seasonal abundance, nocturnal activity, blood source, prevalence of Leishmania infection, and species identification. CDC miniature light traps were used to trap the phlebotomines. Traps were set indoors, peridomestically, and in woodlands. Natural infection was determined in pools by polymerase chain reaction-Southern blot, and blood sources and species identification were determined by sequencing. Large differences were observed in population abundance between the two townships evaluated. Lutzomyia longiflocosa was the most abundant species (83.1%). Abundance was higher during months with lower precipitation. Nocturnal activity was associated with human domestic activity. Blood sources identified were mainly human (85%). A high prevalence of infection was found in L. longiflocosa indoors (2.7%) and the peridomestic setting (2.5%). L. longiflocosa was responsible for domestic transmission in Chaparral.

Relationship between coffee cultivation practices in Colombia and exposure to infection with Leishmania

The inhabitants of coffee-growing municipalities consistently report the highest annual rates of cutaneous leishmaniasis in Colombia. During the last two decades most Colombian coffee growers have changed from the traditional system of cultivation, where the crop is grown under different species of shade trees, to an intensified system where it is grown at high densities in full sunlight. This change may affect transmission of Leishmania spp. to humans in several ways, probably resulting from reduced human-vector contact. The responses of residents of traditional and intensified coffee plantations to the leishmanin skin test were compared to ascertain whether intensification has indeed affected Leishmania transmission. Although prevalence of infection was significantly higher (P< or =0.01) among residents of traditional plantations (26.8%) than among those of intensified ones (13.2%), no significant difference could be demonstrated with respect to incidence of infection at the time of the study. Similar rates of infection were found for men and women, although the incidence of infection was significantly higher among the latter in intensified plantations. Changes to the type of data collected and the data collection process will facilitate the evaluation of the long-term effects of intensification of coffee plantations on Leishmania transmission.

The efficacy of thermotherapy to treat cutaneous leishmaniasis in Colombia: a comparative observational study in an operational setting

An open label, comparative study to compare the efficacy of thermotherapy to meglumine antimoniate in treating cutaneous leishmaniasis patients in an operational context was carried out in Chaparral, Colombia. After enrollment patients were followed-up for up to 100 days. Per protocol and intention-to-treat cure rates for 47 patients treated using thermotherapy (one-time 50 degrees C applications for 30s) were 100 and 19%, respectively. Per protocol and intention-to-treat cure rates for meglumine antimoniate (20 mg/kg body weight administered intramuscularly for 21 d) were 78 and 23%, respectively.

Treatment of New World cutaneous leishmaniasis with miltefosine

Miltefosine (2.5 mg/kg/day for 28 days) was investigated for treatment of New World cutaneous leishmaniasis in Colombia and Guatemala. The data from a controlled study was remarkably similar to the data of a prior uncontrolled pilot study. In the controlled study, the per-protocol 6-month cure rate for Leishmania panamensis disease was 91% compared with a concomitant placebo cure rate of 38%. In Guatemala, the cure rate for L. braziliensis and L. mexicana disease was approximately 50% compared with approximately 20% for placebo. In both countries, nausea but not 'motion sickness' and vomiting but not diarrhoea were experienced by approximately 30% more miltefosine patients than placebo patients. Mild elevation of creatinine, but not of aspartate aminotransferase or alanine aminotransferase, was also more frequently seen in the miltefosine group than in the placebo group. Miltefosine was well tolerated, and as effective as historic values of antimony for treatment of L. panamensis disease.

Failure of a killed Leishmania amazonensis vaccine against American cutaneous leishmaniasis in Colombia

We report the results of a double-blind, randomized, placebo-controlled clinical trial of a killed whole-cell Leishmania amazonensis candidate vaccine against American cutaneous leishmaniasis (CL) in Colombia. The trial subjects were 2597 healthy volunteers with negative leishmanin skin test (LST) selected from rural Colombian soldiers who were going to patrol endemic areas. They were randomized to receive either three doses of vaccine (n=1295) or placebo (n=1302) given at 20-day intervals. An active and passive case detection system was established to follow-up volunteers for 1 year after vaccination. Safety and efficacy of the vaccine were determined by comparing local and systemic adverse reactions after each dose and the incidence of parasitologically confirmed CL. In the vaccine and placebo groups 101 (7.7%) and 88 (6.8%) volunteers developed CL respectively. The vaccine was shown to be safe but offered no protection against CL caused by L. panamensis in the proposed vaccination schedule.

SHORT REPORT: EFFICACY OF PENTAVALENT ANTIMONY FOR TREATMENT OF COLOMBIAN CUTANEOUS LEISHMANIASIS

Two hundred twenty-six consecutive adult patients with cutaneous leishmaniasis in Colombia were treated with Glucantime and 81% were cured. The 19% who failed treatment had received a statistically significant lower total amount of antimony (354 mg/kg) than those who were cured (405 mg/kg) (P = 0.002). Thirty-nine of the failures were re-treated with Glucantime and 59% were cured. This large experience on initial and re-treatment cure rates probably represents the values found in clinical practice. In this series, parasite resistance may have been induced by the relatively low initial dose of antimony administered to some patients.

Safety and immunogenicity of a killed Leishmania (L.) amazonensis vaccine against cutaneous leishmaniasis in Colombia: a randomized controlled trial

The safety and immunogenicity of an intramuscular (IM) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebocontrolled, double-blind trial in Colombia. There were 4 vaccination groups: IM vaccine, IM placebo, ID vaccine, and ID placebo. The ID formulations were mixed with BCG as adjuvant at the time of injection. For each group, 3 vaccinations were given with a 20-day interval between injections, and adverse events were monitored at 20 min, and at 2, 7 and 21 days after each injection. BCG-induced adverse reactions resulted in cancellation of the third vaccine administration in the ID groups. Antibody titres did not differ significantly between the groups. Montenegro skin-test conversion was achieved by 86·4% and 90% of the IM vaccine group and by 25% and 5% of the IM placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigzn lymphocyte proliferation indexes was observed after IM vaccine immunization, but not after IM placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFNγ but not IL-10 were observed 1 year after vaccination in the IM vaccine group compared to the IM placebo group. The good safety profile and evidence of Th1 immune reactions due to IM vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the IM vaccine should be initiated.

Treatment of cutaneous leishmaniasis in Colombia with dapsone

Treatment of cutaneous leishmaniasis in Colombia with dapsone

Lack of association between 5-HT 2A gene promoter polymorphism and susceptibility to anorexia nervosa

and response to treatment at 2, 4, 6, and 13 weeks. Clinical response was defined as complete re-epithelialisation of all lesions at the end of treatment and no reactivation or mucosal involvement during 52 weeks of follow-up. Anaemia was considered as a haematocrit of less than 36% (men) or less than 32% (women) and methaemoglobinaemia was defined clinically by the presence of cyanosis with no evidence of heart or lung disease. Most patients were adults (range 17–39 years), men (10/11), and had one to three cutaneous lesions. Mean duration of lesions at the time of enrolment was 2·1 months. Two of the six patients who completed the course of treatment had a favourable clinical response. Four patients were clinical failures: lesions of three failed to reepithelialise and a fourth responded initially but developed parasitologically confirmed mucosal involvement at 30 weeks. Of the remaining five patients: one was withdrawn because of adverse effects (anaemia, methaemoglobinaemia, and headache), one dropped out because of headache, and three were lost to follow-up after 2, 5, and 6 weeks of treatment. Anaemia (8/11) and methaemoglobinaemia (5/11) were the most frequent adverse effects, probably due to the high dosage used. Nausea (4/11) and vomiting (2/11) also occurred. Leishmania (V) panamensis was identified from each of the six cases where parasite isolation was successful. Although the results of treatment of a small number of patients in an uncontrolled trial do not provide conclusive results, dapsone does not appear to be a promising alternative in the treatment of cutaneous leishmaniasis in Colombia.

Limited efficacy of injectable aminosidine as single-agent therapy for Colombian cutaneous leishmaniasis

Ninety military patients with cutaneous leishmaniasis in Colombia were randomly allocated to 3 treatment regimens of parenteral aminosidine sulphate: (i) 12 mg aminosidine base/kg/d for 7 d, (ii) 12 mg/kg/d for 14 d, and (iii) 18 mg/kg/d for 14 d. With the 89 evaluable patients, the cure rates 12 months after the end of treatment were 10%, 45%, and 50%, respectively. Fifty-eight of the 66 patients who were not cured had lesions that enlarged or were unchanged by 1.5 months after treatment follow up. The other 8 patients had lesions that relapsed between 3 and 12 months after therapy. Even in group (iii) the cure rate was inferior to that (>90%) with antimony or pentamidine previously reported in this patient population. This study indicates that parenteral aminosidine alone is less likely to be successful in the treatment of cutaneous leishmaniasis than visceral leishmaniasis, for which a 74% cure rate has been reported. Further trials might consider the combination of aminosidine with other antileishmanial drugs.

Epidemiology of Cutaneous Leishmaniasis in Colombia: A Longitudinal Study of the Natural History, Prevalence, and Incidence of Infection and Clinical Manifestations

This prospective study measured the incidence of Leishmania infection, by Leishmanin skin test (LST) conversion, and leishmaniasis, by new acquisition of lesions, in a Leishmania braziliensis endemic area of Colombia, during 7243 person-years. The incidence rate of infection and leishmaniasis varied greatly by village, ranging from 2.8 to 23.0/100 person-years and 0.0 to 20.4/1000 person-years, respectively. Adult males experienced greater rates of both infection and leishmaniasis. Most primary infections (91%) were subclinical initially. Typical scars were predictive of subsequent leishmaniases both for persons initially LST-reactive (risk ratio = 11.3, P = .003) and for those initially nonreactive (risk ratio = 3.2, P = .02). Only one-third of the diagnosed leishmaniasis cases (24/77) were due to newly acquired infections in naive hosts. The relative contribution of existing lesions, recurrences, and new infections to the burden of disease should be considered in the planning of leishmaniasis control programs.

Epidemiology of Cutaneous Leishmaniasis in Colombia: Environmental and Behavioral Risk Factors for Infection, Clinical Manifestations, and Pathogenicity

Through a longitudinal, active surveillance for Leishmania (Viannia) braziliensis and Leishmania (Viannia) panamensis infection and lesions on the Pacific Coast of Colombia, risk factors for infection (leishmanin skin test conversion), leishmanial lesions, and pathogenicity were examined. Risk factor information was obtained prior to and independently of case ascertainment. Similar factors were associated with acquisition of infection and of leishmaniasis, including male sex, age > 10 years, and farming occupation. The behaviors of entering the forest after sunset, hunting, and lumbering were most strongly associated with Leishmania infection independently of age, sex, and farming occupation. Environmental conditions associated with infection, including tall trees near the home, home located > 15 m from the nearest neighbor, and floor and roof made of open material, were less strong predictors of risk. Pathogenicity, the risk of lesion given a new infection, was reduced in those > 30 years of age and those entering the forest frequently.

Colombian strains of Leishmania from man: growth characteristics in culture media and hamsters

Growth characteristics in culture media and hamsters were studied for 14 isolates obtained from patients with cutaneous leishmaniasis in Colombia. All isolates were identifiable with the Leishmania braziliensis complex having poor to moderate in vitro growth, and producing slow-growing, non-metastasizing lesions in hamsters. Eleven of the isolates originated from coastal areas and had characteristics of L. b. braziliensis; three isolates came from inland sites and had characteristics similar to L. b. panamensis.