RESUMEN
INTRODUCTION: A clinically significant endemic focus of onchocerciasis existing in Esmeraldas Province, coastal Ecuador has been under an ivermectin mass drug administration program since 1991. The main transmitting vector in this area is the voracious blackfly, Simulium exiguum. This paper describes the assessments made that support the decision to cease mass treatment. METHODOLOGY AND PRINCIPLE FINDINGS: Thirty-five rounds of ivermectin treatment occurred between 1991-2009 with 29 of these carrying >85% coverage. Following the guidelines set by WHO for ceasing ivermectin distribution the impact on parasite transmission was measured in the two vector species by an O-150 PCR technique standard for assessing for the presence of Onchocerca volvulus. Up to seven collection sites in three major river systems were tested on four occasions between 1995 and 2008. The infectivity rates of 65.0 (CI 39-101) and 72.7 (CI 42-116) in 1995 dropped to zero at all seven collection sites by 2008. Assessment for the presence of antibodies against O. volvulus was made in 2001, 2006, 2007 and 2008 using standard ELISA assays for detecting anti-Ov16 antibodies. None of total of 1810 children aged 1-15 years (between 82 and 98% of children present in the surveyed villages) tested in the above years were found to be carrying antibodies to this antigen. These findings were the basis for the cessation of mass drug treatment with ivermectin in 2009. SIGNIFICANCE: This fulfillment of the criteria for cessation of mass distribution of ivermectin in the only known endemic zone of onchocerciasis in Ecuador moves the country into the surveillance phase of official verification for national elimination of transmission of infection. These findings indicate that ivermectin given twice a year with greater than 85% of the community can move a program to the final stages of verification of transmission interruption.
Asunto(s)
Filaricidas/administración & dosificación , Insectos Vectores/parasitología , Ivermectina/administración & dosificación , Oncocercosis/transmisión , Simuliidae/parasitología , Adolescente , Animales , Anticuerpos Antihelmínticos/sangre , Niño , Preescolar , Ecuador/epidemiología , Humanos , Lactante , Recién Nacido , Oncocercosis/epidemiología , Oncocercosis/parasitología , Oncocercosis/terapia , Servicios Preventivos de Salud/métodosRESUMEN
The goal of elimination of the human filariases would benefit greatly from the use of a macrofilaricidal agent. In vivo trials in humans and many experimental animal models suggest that flubendazole (FLBZ) is a highly efficacious macrofilaricide. However, since serious injection site reactions were reported in humans after parenteral FLBZ administration, the search for alternative pharmaceutical strategies to improve the systemic availability of FLBZ and its metabolites has acquired urgency in both human and veterinary medicine. The goal of the current work was to compare the systemic exposure of FLBZ formulated as either an aqueous hydroxypropyl-ß-cyclodextrin (CD) or aqueous carboxymethyl cellulose (CMC) suspension or a Tween 80-based formulation (TWEEN) in rats and jirds (Meriones unguiculatus). Healthy animals of both species were allocated into four experimental groups of 44 animals each: FLBZ-CD oral and FLBZ-CDsc, treated with the FLBZ-CD formulation by the oral or subcutaneous routes, respectively; FLBZ-TWEENsc, dosed subcutaneously with the FLBZ-TWEEN formulation; and FLBZ-CMC oral, treated orally with the FLBZ suspension. The FLBZ dose was 5 mg/kg. FLBZ and its hydrolyzed (H-FLBZ) and reduced (R-FLBZ) metabolites were recovered in plasma samples collected from rats and jirds treated with the different FLBZ formulations. In both species, FLBZ parent drug was the main analyte recovered in the bloodstream. In rats, FLBZ systemic exposure (AUC 0-LOQ) was significantly (P < 0.05) higher after the FLBZ-CD treatments, both oral (4.8 ± 0.9 µg.h/mL) and subcutaneous (7.3 ± 0.6 µg.h/mL), compared to that observed after oral administration of FLBZ-CMC suspension (0.93 ± 0.2 µg.h/mL). The same differences were observed in jirds. In both species, parenteral administration of FLBZ-TWEEN did not improve the systemic availability of FLBZ compared to FLBZ-CDoral treatment. In conclusion, formulation approaches that enhance the availability of flubendazole in the rat and jird may have therapeutic implications for a drug with poor or erratic bioavailability.
Asunto(s)
Antinematodos , Mebendazol/análogos & derivados , 2-Hidroxipropil-beta-Ciclodextrina , Animales , Antinematodos/sangre , Antinematodos/química , Antinematodos/farmacocinética , Carboximetilcelulosa de Sodio/química , Química Farmacéutica , Gerbillinae , Mebendazol/sangre , Mebendazol/química , Mebendazol/farmacocinética , Ratas , Ratas Wistar , beta-Ciclodextrinas/químicaRESUMEN
The objective of this study was to examine nodules from Mexico, Guatemala, and Ecuador collected over a one-year period (2001) to determine the effects of semi-annual ivermectin treatments on Onchocerca volvulus macrofilarial populations. Nodules were sectioned, stained with hematoxylin and eosin, and histologic findings were compared between countries and with historical data prior to the introduction of ivermectin into the region. Nodules from Ecuador had 10 times more dead or moribund worms than the historical control (66.6% versus 6.5%); nodules from patients from Mexico and Guatemala did not differ from the control. More than 80% of the female worms in each country were uninseminated and producing unfertilized oocytes. Nodules containing males differed in each country from the historical control (P < 0.0001), with presence of males ranging from 19.7% in Mexico to 13.6% in Ecuador versus 73% in the control. Nodules with females producing active microfilariae ranged from 7.8% (Mexico) to 2.7% (Ecuador) versus 60% in the historical control (P < 0.0001). Nodules from Ecuador and Mexico were significantly smaller in size than those from Guatemala or historical controls (P < 0.0005). These results depict a deteriorating condition of adult O. volvulus populations in Mexico, Guatemala and Ecuador, indicating that semi-annual ivermectin treatment of >/=6 years has had a profound effect on survival and reproduction of this species.
Asunto(s)
Filaricidas/administración & dosificación , Ivermectina/administración & dosificación , Onchocerca volvulus/aislamiento & purificación , Oncocercosis/epidemiología , Oncocercosis/prevención & control , Adulto , Animales , Ecuador/epidemiología , Femenino , Guatemala/epidemiología , Humanos , Estudios Longitudinales , Masculino , México/epidemiología , Onchocerca volvulus/efectos de los fármacosRESUMEN
Five monoclonal antibodies (MAbs) directed against antigens of Mycobacterium leprae were tested for their ability to bind to components of tissue sections prepared from biopsies taken from patients with various forms of leprosy. Immunoperoxidase was the most successful marker system used, although immunofluorescence and alkaline phosphatase were also successful in certain cases. Positivity was high with all five antibodies successfully staining those sections containing a bacterial index of 3+ or more; sections with 0 bacterial counts also had areas staining positively with two of the MAbs. The positive staining in the tissues was confined to areas infiltrated by inflammatory cells; however it was not identifiable as being associated with individual bacteria. These findings suggest that immunostaining with specific monoclonal antibodies can help to identify leprosy in diagnostic samples in which acid-fast bacilli are not identifiable by standard histochemical means. Immunohistochemical techniques are likely to be valuable in studies of the distribution of M. leprae antigens and their association with individual tissue elements
Asunto(s)
Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Mycobacterium leprae/genética , Mycobacterium leprae/inmunologíaRESUMEN
Se describe la utilización de la dietilcarbamicina (DEC) en loción al 2% aplicada en una pequeña área de piel, como prueba para el diagnóstico de oncocercosis. Consideramos que esta técnica puede ser útil en investigaciones epidemiológicas a gran escala, pues tiene menos posibilidades de inducir daño ocular en pacientes portadores de la enfermedad y permite identificar a la gran mayoría de estos
Asunto(s)
Humanos , Dietilcarbamazina , Oncocercosis/diagnóstico , EcuadorRESUMEN
Las diferentes respuestas inmunológicas a la Onchocerca volvulus causan una variación considerable en las manifestaciones clínicas de la oncocercosis humana. Las lesiones oncocercóticas son el resultado de las reacciones inflamatorias e involucran mecanismos inmunológicos, los cuales están asociados con la destrucción y la muerte del estado microfilario. Esta destrucción involucra los eosinófilos y pueden ser mediados por los anticuerpos asociados a la superficie antígena de la microfilaria y aumentar su valor como complemento. Sin embargo este no parece ser un estado inmune común entre pacientes con oncocercosis y su variación es observada en la sintomatología clínica
Asunto(s)
Humanos , Oncocercosis/inmunología , Piel/patologíaRESUMEN
Se presenta el caso de una paciente de 32 años de edad, procedente de área endémica para oncocercosis; el hallazgo de biopsia de piel 18 meses después de la primera consulta médica revela microfilaria de Onchocerca en el área afectada, que se limita a la pierna izquierda, el cuadro se acompañó de hiperpigmentación y edema, característico de la dermatitis reactiva (sowdah) descrita como entidad peculiar del foco Arabigo. La respuesta al corto tratamiento con dietilcarbamazina y corticosteroides fue satisfactoria