RESUMEN
Canine cutaneous leishmaniasis (CCL) is an emerging zoonotic infection endemic in several countries of the world. Due to variable response to therapy and frequency of relapses, a more effective, safer, and inexpensive treatment is needed. Recently, it was reported that the hederagenin glucoside saponins (SS) and chromane-derived hydrazone (TC2) combined in a 1:1 ratio has high potential in antileishmanial therapy since both compounds alter the survival of Leishmania and the ability to infect adjacent macrophage. Not only the skin permeation and the absorption of an ointment containing 2% TC2 and 2% SS (w/w) was determined in this work, but also the acute dermal toxicity in both in vitro and in vivo assays. Last, the effectiveness and safety of the topical therapy with 2% TC2-2% SS ointment was evaluated in an observational study in dogs with diagnosis of cutaneous leishmaniasis (CL). Both TC2 and SS diffused through pig ear skin and traces of TC2 (but not SS) were detected in the stratum corneum of mice at 6-24 h. Neither TC2 nor SS was detected in plasma. The acute dermal toxicity was negative. Treatment with 2% TC2-2% SS ointment produced a complete long-term clinical cure in 56 dogs (24 females and 32 males) from the Orinoco and Amazonas regions in southeastern Colombia without adverse effects. All dogs have remained disease-free for the last 24 months. In conclusion, these results support the use of this topical therapy as a safer and new first-line local treatment of CCL that could help limit the spread of CL from dogs to humans.
Asunto(s)
Antiprotozoarios , Leishmaniasis Cutánea , Saponinas , Animales , Antiprotozoarios/uso terapéutico , Perros , Femenino , Glucósidos/uso terapéutico , Hidrazonas/uso terapéutico , Leishmaniasis Cutánea/tratamiento farmacológico , Leishmaniasis Cutánea/veterinaria , Masculino , Ratones , Pomadas/uso terapéutico , Ácido Oleanólico/análogos & derivados , Saponinas/uso terapéutico , PorcinosRESUMEN
In Colombia, most cases of human cutaneous leishmaniasis are caused by Leishmania (Viannia) panamensis. Interestingly, up to 30% of the exposed population do not suffer from clinical leishmaniasis although it is likely that they are continuously infected with Leishmania parasites. Since it is believed that the induction of efficient Th1 immune responses protects against Leishmania infections both in humans and in animal models, we determined if endemically exposed asymptomatics showed stronger Leishmania-specific Th1 immune responses than patients with active localized cutaneous leishmaniasis (LCL). We found that Montenegro skin test responses were slightly higher among asymptomatic individuals compared to patients suffering from LCL. However, PBMC from patients with LCL showed similar Leishmania-specific proliferative responses compared to PBMC from asymptomatic individuals. Furthermore, PBMC from both groups also secreted similar amounts of IFN-gamma, IL-12p40 and IL-10 after in vitro exposure to L. panamensis. No IL-4 was detected in the supernatants. Taken together our results suggest that lack of LCL development in endemically exposed asymptomatics cannot be explained by stronger systemic anti-Leishmania Th1 immune responses or decreased Th2 responses in these individuals in comparison to individuals who develop LCL. It may be possible that other mechanisms are responsible for resistance to cutaneous leishmaniasis in Colombia in endemically exposed asymptomatics.
Asunto(s)
Leishmania guyanensis/inmunología , Leishmaniasis Cutánea/inmunología , Piel/inmunología , Células TH1/inmunología , Adolescente , Adulto , Animales , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Células Cultivadas , Citocinas/biosíntesis , Enfermedades Endémicas , Femenino , Humanos , Hipersensibilidad Tardía , Lectinas Tipo C , Leishmania guyanensis/crecimiento & desarrollo , Leishmaniasis Cutánea/parasitología , Leishmaniasis Cutánea/patología , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Piel/parasitología , Piel/patologíaRESUMEN
We present evidence that the El Niño phenomenon intensifies the annual cycle of malaria cases for Plasmodium vivax and Plasmodium falciparum in endemic areas of Colombia as a consequence of concomitant anomalies in the normal annual cycle of temperature and precipitation. We used simultaneous analyses of both variables at both timescales, as well as correlation and power spectral analyses of detailed spatial (municipal) and temporal (monthly) records. During "normal years," endemic malaria in rural Colombia exhibits a clear-cut "normal" annual cycle, which is tightly associated with prevalent climatic conditions, mainly mean temperature, precipitation, dew point, and river discharges. During historical El Niño events (interannual time scale), the timing of malaria outbreaks does not change from the annual cycle, but the number of cases intensifies. Such anomalies are associated with a consistent pattern of hydrological and climatic anomalies: increase in mean temperature, decrease in precipitation, increase in dew point, and decrease in river discharges, all of which favor malaria transmission. Such coupling explains why the effect appears stronger and more persistent during the second half of El Niño's year (0), and during the first half of the year (+1). We illustrate this finding with data for diverse localities in Buenaventura (on the Pacific coast) and Caucasia (along the Cauca river floodplain), but conclusions have been found valid for multiple localities throughout endemic regions of Colombia. The identified coupling between annual and interannual timescales in the climate-malaria system shed new light toward understanding the exact linkages between environmental, entomological, and epidemiological factors conductive to malaria outbreaks, and also imposes the coupling of those timescales in public health intervention programs.
Asunto(s)
Clima , Brotes de Enfermedades/estadística & datos numéricos , Malaria Falciparum/epidemiología , Malaria Vivax/epidemiología , Animales , Colombia/epidemiología , Ecología , Enfermedades Endémicas/estadística & datos numéricos , Ambiente , Humanos , Incidencia , Tiempo (Meteorología)RESUMEN
Leishmaniasis in Colombia has traditionally been seen as a health risk for adult males, as they become infected when they enter the vector's biotopes to tap natural resources. National health statistics seem to confirm this theory. However, during field studies, the Program for the Study and Control of Tropical Diseases (PECET) observed both equal proportions of men and women with active leishmaniasis and delayed hypersensitivity skin tests and equal proportions of males and females having had contact with the parasite from early childhood. Several factors that have not been analyzed in depth in Colombia thus far appear to distort the disease's epidemiological pattern in the country, and gender-linked differences in access to health care appear to exist. As a consequence, no relief is provided for this source of human suffering, and socioeconomic repercussions for households are significant. Preventive measures by the Colombian Ministry of Health (MOH) systematically underestimate the magnitude of intra- and peridomiciliary transmission, and female patients are excluded from active case detection. Further research should be devoted to this phenomenon. The MOH should be encouraged to improve leishmaniasis control programs, especially with regard to active case detection, training, and teaching, so that quicker diagnosis can be performed. Meanwhile, the MOH should retrain its health personnel.
Asunto(s)
Leishmaniasis Cutánea/epidemiología , Adolescente , Adulto , Niño , Preescolar , Colombia/epidemiología , Femenino , Humanos , Lactante , Recién Nacido , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/transmisión , Masculino , Estudios Retrospectivos , Factores de Riesgo , Distribución por SexoRESUMEN
Parasitologic confirmation of cutaneous leishmaniasis is obligatory before chemotherapy can be considered. Direct microscopic examination of scrapings taken from indurated borders of ulcers has been routinely used as primary method of diagnosis. In this report we compared the sensitivity of examination of dermal scrapings taken from the bottoms of ulcers (BDS) with that of dermal scrapings taken from indurated active margins of lesions (MDS) in a total of 115 patients. The sensitivities of the microscopic examination were 90.4 and 78.3% for BDS and MDS samples, respectively. When the PCR method was used with a group of 40 patients, we also observed a higher sensitivity when BDS samples were examined (80.8% in BDS samples versus 57.7% in MDS samples). The improvement of the diagnostic sensitivity in the BDS samples appears to be related to the higher parasite load and more easily detectable morphology of amastigotes in the centers of the ulcers. Other parasitologic diagnostic methods, such as culture and histopathologic examination of biopsies, are less sensitive (67.5 and 64.3%, respectively). Aspirate culture, however, was shown to be the most sensitive method for the diagnosis of patients with chronic ulcers. When microscopic examinations of both MDS and BDS samples are combined, the sensitivity of diagnosis may rise up to 94%. We therefore recommend this method as a primary routine procedure for diagnosis of cutaneous leishmaniasis.
Asunto(s)
Leishmaniasis Cutánea/diagnóstico , Úlcera Cutánea/patología , Animales , Biopsia , Colombia , Humanos , Leishmania/clasificación , Leishmania/aislamiento & purificación , Leishmaniasis Cutánea/patología , Reacción en Cadena de la Polimerasa/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Piel/patología , Pruebas Cutáneas , Úlcera Cutánea/parasitologíaRESUMEN
Multilocus genotyping of microbial pathogens has revealed a range of population structures, with some bacteria showing extensive recombination and others showing almost complete clonality. The population structure of the protozoan parasite Plasmodium falciparum has been harder to evaluate, since most studies have used a limited number of antigen-encoding loci that are known to be under strong selection. We describe length variation at 12 microsatellite loci in 465 infections collected from 9 locations worldwide. These data reveal dramatic differences in parasite population structure in different locations. Strong linkage disequilibrium (LD) was observed in six of nine populations. Significant LD occurred in all locations with prevalence <1% and in only two of five of the populations from regions with higher transmission intensities. Where present, LD results largely from the presence of identical multilocus genotypes within populations, suggesting high levels of self-fertilization in populations with low levels of transmission. We also observed dramatic variation in diversity and geographical differentiation in different regions. Mean heterozygosities in South American countries (0.3-0.4) were less than half those observed in African locations (0. 76-0.8), with intermediate heterozygosities in the Southeast Asia/Pacific samples (0.51-0.65). Furthermore, variation was distributed among locations in South America (F:(ST) = 0.364) and within locations in Africa (F:(ST) = 0.007). The intraspecific patterns of diversity and genetic differentiation observed in P. falciparum are strikingly similar to those seen in interspecific comparisons of plants and animals with differing levels of outcrossing, suggesting that similar processes may be involved. The differences observed may also reflect the recent colonization of non-African populations from an African source, and the relative influences of epidemiology and population history are difficult to disentangle. These data reveal a range of population structures within a single pathogen species and suggest intimate links between patterns of epidemiology and genetic structure in this organism.
Asunto(s)
Evolución Molecular , Frecuencia de los Genes , Malaria Falciparum/epidemiología , Repeticiones de Microsatélite , Plasmodium falciparum/genética , África/epidemiología , Animales , Evolución Biológica , Variación Genética , Genotipo , Geografía , Humanos , Desequilibrio de Ligamiento , Papúa Nueva Guinea/epidemiología , Plasmodium falciparum/clasificación , Probabilidad , América del SurRESUMEN
To evaluate sex-specific differences in gene flow between Native American populations from South America and between those populations and recent immigrants to the New World, we examined the genetic diversity at uni- and biparental genetic markers of five Native American populations from Colombia and in published surveys from native South Americans. The Colombian populations were typed for five polymorphisms in mtDNA, five restriction sites in the beta-globin gene cluster, the DQA1 gene, and nine autosomal microsatellites. Elsewhere, we published results for seven Y-chromosome microsatellites in the same populations. Autosomal polymorphisms showed a mean G(ST) of 6.8%, in agreement with extensive classical marker studies of South American populations. MtDNA and Y-chromosome markers resulted in G(ST) values of 0.18 and 0.165, respectively. When only Y chromosomes of confirmed Amerind origin were used in the calculations (as defined by the presence of allele T at locus DYS199), G(ST) increased to 0.22. G(ST) values calculated from published data for other South American natives were 0.3 and 0.29 for mtDNA and Amerind Y chromosomes, respectively. The concordance of these estimates does not support an important difference in migration rates between the sexes throughout the history of South Amerinds. Admixture analysis of the Colombian populations suggests an asymmetric pattern of mating involving mostly immigrant men and native women.
Asunto(s)
ADN Mitocondrial/genética , Variación Genética/genética , Indígenas Sudamericanos/genética , Filogenia , Caracteres Sexuales , Cromosoma Y/genética , África , Censos , Colombia , Emigración e Inmigración , Europa (Continente) , Femenino , Frecuencia de los Genes/genética , Pool de Genes , Globinas/genética , Antígenos HLA-DQ/genética , Cadenas alfa de HLA-DQ , Haplotipos/genética , Humanos , Lingüística , Masculino , Repeticiones de Microsatélite/genética , Familia de Multigenes/genética , Polimorfismo de Longitud del Fragmento de Restricción , América del SurRESUMEN
Leishmaniasis is widespread in Colombia and is found in 30 of 32 Departments. More than 200 infection zones have been reported from different regions, which vary from sea-level to an altitude of 2,300 m along the Atlantic Coast, Pacific coast, Amazon basin, Cauca and Magdalena valleys. We report 76 Leishmania stocks isolated from humans, dogs and phlebotomine hosts. Isoenzyme electrophoresis revealed 16 zymodemes, which could be divided into four phylogenetic complexes, i.e., L. braziliensis, L. amazonensis, L. guyanensis/panamensis and L. infantum. Three zymodemes became integrated into the subgenus Leishmania and the other zymodemes into the subgenus Viannia. Cutaneous infections were due to the L. braziliensis (9.2%) and L. guyanensis/panamensis (85.54%) complexes. Mucous secondary involvement was due to the L. braziliensis and L. guyanensis/panamensis complexes. In this work the specific status of L. (V.) guyanensis and L. (V.) panamensis is discussed.
Asunto(s)
Leishmania/clasificación , Animales , Colombia , Enfermedades de los Perros/parasitología , Perros , Electroforesis en Gel de Almidón , Humanos , Focalización Isoeléctrica , Isoenzimas/análisis , Leishmania/enzimología , Leishmania/genética , Leishmaniasis/parasitología , Leishmaniasis/veterinaria , Filogenia , Polimorfismo Genético , Psychodidae/parasitologíaRESUMEN
Hexane, ethyl acetate and methanol extracts of Annona muricata pericarp were tested in vitro against Leishmania braziliensis and L. panamensis promastigotes, and against cell line U-937. The ethyl acetate extract was more active than the other extracts and even of Glucantime used as reference substance. Its fractionation led to the isolation of three acetogenins--annonacin, annonacin A and annomuricin A.
Asunto(s)
4-Butirolactona/análogos & derivados , Antiprotozoarios/farmacología , Leishmania/efectos de los fármacos , Extractos Vegetales/farmacología , Plantas Medicinales , 4-Butirolactona/química , Animales , Antiprotozoarios/toxicidad , Línea Celular/efectos de los fármacos , Furanos/química , Humanos , Lactonas/química , Extractos Vegetales/toxicidadRESUMEN
Five newly discovered endemic foci for paragonimiasis in Colombia are described for the first time. The disease was diagnosed in 24 people from the Embera Indian communities located at the Colombian Pacific Coast and investigated in 1993-98. We also describe the clinical, epidemiological and treatment response aspects. In these foci an Aroapyrgus sp. snail different from A. colombiensis was found to be the first intermediate host, and the crab Hypolobocera emberarum nsp. the second intermediate host.
Asunto(s)
Braquiuros/parasitología , Paragonimiasis/epidemiología , Caracoles/parasitología , Adolescente , Adulto , Animales , Niño , Preescolar , Colombia/epidemiología , Femenino , Interacciones Huésped-Parásitos , Humanos , Masculino , Persona de Mediana Edad , Paragonimiasis/terapia , Paragonimus/aislamiento & purificaciónRESUMEN
The safety and immunogenicity of an intramuscular (i.m.) and intradermal (ID) formulation of autoclaved Leishmania (Leishmania) amazonensis vaccine was evaluated in 296 volunteers in a randomized, placebo-controlled, double-blind trial in Colombia. There were 4 vaccination groups: i.m. vaccine, i.m. 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 i.m. vaccine group and by 25% and 5% of the i.m. placebo group 80 days and 1 year after vaccination, respectively. A significant increase in mean Leishmania-antigen lymphocyte proliferation indexes was observed after i.m. vaccine immunization, but not after i.m. placebo immunization, 80 days and 1 year after vaccination. Significant levels of IFN gamma but not IL-10 were observed 1 year after vaccination in the i.m. vaccine group compared to the i.m. placebo group. The good safety profile and evidence of Th1 immune reactions due to i.m. vaccination in this phase-I/II study suggest that a population-based phase-III efficacy trial of the i.m. vaccine should be initiated.
Asunto(s)
Leishmania mexicana/inmunología , Leishmaniasis Cutánea/prevención & control , Vacunas de Productos Inactivados , Adyuvantes Inmunológicos , Animales , Formación de Anticuerpos , Método Doble Ciego , Estudios de Seguimiento , Humanos , Leishmaniasis Cutánea/inmunologíaRESUMEN
The value of Colombian phlebotomine eggs for species determination was studied with a scanning electron microscope. The species diversity and medical importance of the verrucarum group were the bases to select Lutzomyia youngi, Lutzomyia evansi, Lutzomyia columbiana and Lutzomyia longiflocosa. The egg surface was poligonal. Lutzomyia youngi, and Lutzomyia columbiana had pentagonal or hexagonal patterns; Lutzomyia evansi elongated polygons and Lutzomyia longiflocosa irregular polygonal sculpturing, frequently rectangular. Egg scanning electron microscopy is reliable to identify species of the verrucarum group.
Asunto(s)
Huevos , Psychodidae/clasificación , Animales , Femenino , Microscopía Electrónica/métodos , Psychodidae/ultraestructuraRESUMEN
Canine dirofilariasis is widespread in urban areas of central and northern Colombia. Previously we detected specific antibodies against complex antigens from Dirofilaria immitis adult worms in individuals from an isolated Tikuna Indian community in the Colombian Amazon. In this study a 56 kDa polypeptide from the adult D. immitis excretory/secretory (E/S) products is identified by Western blot, isolated by elution from polyacrilamide gels and applied in an ELISA-based test for the detection of specific IgG. Eleven of 74 serum samples analysed were positive by ELISADi56. Positive individuals came from five different areas of Colombia. The highest number of positives was found in the Amazon (4), followed by Bogotà (3). The physicians of the area must be alerted regarding the existence of human D. immitis infections and include dirofilariasis in the differential diagnosis of pulmonary nodules.
Asunto(s)
Anticuerpos Antihelmínticos/sangre , Dirofilaria immitis/inmunología , Dirofilariasis/epidemiología , Animales , Western Blotting , Colombia/epidemiología , Enfermedades de los Perros/epidemiología , Perros , Ensayo de Inmunoadsorción Enzimática , HumanosRESUMEN
Three cases of coinfection with Leishmania and Sporothrix spp in the same lesion are described. The patients had ulcers with erythematous borders and regional lymphadenopathy. The diagnosis of leishmaniasis was accomplished by direct visualization of the amastigotes or culture of the promastigotes, or both. The diagnosis of sporotrichosis was proved in two cases by culture of Sporothrix schenckii and by the histopathologic features in one case. All patients had a positive sporotrichin test. Two patients responded successfully to oral potassium iodide. One patient received oral itraconazole 100 mg/day because of intolerance to iodides and was cured. To our knowledge coinfection with Leishmania and Sporothrix spp has not been reported. The use of empirical treatments for leishmaniasis such as poultices or puncturing of the lesion with thorns or woods splinters might introduce Sporothrix and explain the coinfection.
Asunto(s)
Leishmaniasis Cutánea/complicaciones , Esporotricosis/complicaciones , Adulto , Femenino , Humanos , Leishmaniasis Cutánea/diagnóstico , Leishmaniasis Cutánea/tratamiento farmacológico , Masculino , Esporotricosis/diagnóstico , Esporotricosis/tratamiento farmacológicoRESUMEN
Recently, Y chromosome markers have begun to be used to study Native American origins. Available data have been interpreted as indicating that the colonizers of the New World carried a single founder haplotype. However, these early studies have been based on a few, mostly complex polymorphisms of insufficient resolution to determine whether observed diversity stems from admixture or diversity among the colonizers. Because the interpretation of Y chromosomal variation in the New World depends on founding diversity, it is important to develop marker systems with finer resolution. Here we evaluate the hypothesis of a single-founder Y haplotype for Amerinds by using 11 Y-specific markers in five Colombian Amerind populations. Two of these markers (DYS271, DYS287) are reliable indicators of admixture and detected three non-Amerind chromosomes in our sample. Two other markers (DYS199, M19) are single-nucleotide polymorphisms mostly restricted to Native Americans. The relatedness of chromosomes defined by these two markers was evaluated by constructing haplotypes with seven microsatellite loci (DYS388 to 394). The microsatellite backgrounds found on the two haplogroups defined by marker DYS199 demonstrate the existence of at least two Amerind founder haplotypes, one of them (carrying allele DYS199 T) largely restricted to Native Americans. The estimated age and distribution of these haplogroups places them among the founders of the New World.
Asunto(s)
Variación Genética , Indígenas Sudamericanos/genética , Repeticiones de Microsatélite , Filogenia , Cromosoma Y/genética , Colombia , Marcadores Genéticos , Haplotipos , Humanos , MasculinoRESUMEN
The kinetoplastid membrane protein-11 (KMP-11) is a major target of the humoral immune response during Leishmania-infections. The majority of sera from visceral leishmaniasis, mucocutaneous leishmaniasis and even some cutaneous leishmaniasis patients contain detectable IgG antibodies against KMP-11. We also provide evidence that this protein may act as a potent antigen in T. cruzi infections, since most Chagas sera show immunological cross-reactivity. Therefore, KMP-11 cannot be used as a specific diagnostical tool for the serodiagnosis of leishmaniasis in those regions where both, Leishmania and T. cruzi infections overlap geographically. When analyzing the subclass specificity of the antibody response to KMP-11 we observed the following order of reactivity: IgG1 > > IgG3 > IgG2 > IgG4, which is similiar to that seen in crude parasite extract. The mapping of antigenic determinants by using synthetic 20-mer peptides revealed the existence of predominantly conformational epitopes in leishmaniasis, while 50% of sera from Chagas patients reacted with a particular KMP-11 peptide. These results therefore suggest the presence of disease-specific B-cell epitopes.