Use of Ov16-Based Serology for Post-Elimination Surveillance of Onchocerciasis in Ecuador.

Onchocerciasis is a blinding disease caused by the filarial parasite Onchocerca volvulus, with a worldwide distribution. Onchocerciasis has been targeted for regional elimination based on annual and semiannual mass drug administration (MDA) with ivermectin in endemic communities over several years. This strategy in Ecuador led to the interruption of transmission and suspension of ivermectin MDA in 2009 with certification of elimination in 2014. In the present study, we analyzed sera collected in 2018 from 123 children aged 5-9 years from formerly hyperendemic communities in the Esmeraldas focus, Ecuador, for the presence of antibodies to Ov16 antigen. All samples were negative, indicating no evidence of transmission since MDA was stopped. Ov16-based serology offers an economic and practical alternative for measuring vector infectivity for post-certification surveillance in formerly endemic countries where expertise and capacity to reliably measure fly infectivity rates are costly to maintain.

Elimination of onchocerciasis in Ecuador: findings of post-treatment surveillance.

BACKGROUND: The Esmeraldas focus of onchocerciasis in Ecuador expanded geographically during the 1980s and was associated with severe ocular and skin disease. Mass drug administration (MDA) with ivermectin started in 1991, initially once but later twice a year, in the principle endemic focus followed by all satellite foci. Treatment was stopped in 2009 when entomological assessments determined that transmission of Onchocerca volvulus had been interrupted. METHODS: Three years after the cessation of ivermectin treatment in 2012, as defined by the WHO guidelines for onchocerciasis elimination, blackfly collections were done in four sentinel sites in former hyperendemic areas. The presence of infective larvae in local vectors, Simulium exiguum and Simulum quadrivittatum, was assessed by detection of O. volvulus DNA by PCR. Additional flies captured in four extra-sentinel sites located in former hyper- and mesoendemic dispersed isolated areas were also assessed. RESULTS: The results from 68,310 captured blackflies, 40,114 from four sentinel villages in the previously hyperendemic areas (Corriente Grande, El Tigre, San Miguel on Río Cayapas and Naranjal on Río Canandé) and 28,197 from extra-sentinel locations, were all negative for the presence of O. volvulus. These extra-sentinel sites (Hualpí on Río Hoja Blanca, Capulí on Río Onzole, La Ceiba on Río Tululví and Medianía on Río Verde) were included to provide additional evidence of the impact of MDA on the transmission of O. volvulus in isolated endemic areas. CONCLUSIONS: Our data indicate that transmission of O. volvulus has been stopped in all endemic areas in Ecuador, including all satellite foci outside the main focus. These findings indicate that a strategy of ivermectin distribution twice a year to over 85% of the treatment-eligible population was effective in eliminating the infection from Ecuador in a focus with a highly competent primary vector, S. exiguum, and where the infection rates were equal to or greater than observed in many onchocerciasis foci in Africa.

Impact of long-term treatment of onchocerciasis with ivermectin in Ecuador: potential for elimination of infection.

BACKGROUND: Onchocerciasis is a leading cause of blindness worldwide, hence elimination of the infection is an important health priority. Community-based treatment programs with ivermectin form the basis of control programs for the disease in Latin America. The long-term administration of ivermectin could eliminate Onchocerca volvulus infection from endemic areas in Latin America. METHODS: A strategy of annual to twice-annual treatments with ivermectin has been used for onchocerciasis in endemic communities in Ecuador for up to 14 years. The impact of ivermectin treatment on ocular morbidity, and O. volvulus infection and transmission was monitored in seven sentinel communities. RESULTS: Over the period 1990-2003, high rates of treatment coverage of the eligible population were maintained in endemic communities (mean 85.2% per treatment round). Ivermectin reduced the prevalence of anterior segment disease of the eye to 0% in sentinel communities and had a major impact on the prevalence and transmission of infection, with possible elimination of infection in some foci. CONCLUSION: The distribution of ivermectin in endemic communities in Ecuador might have eliminated ocular morbidity and significant progress has been made towards elimination of the infection. A strategy of more frequent treatments with ivermectin may be required in communities where the infection persists to achieve the objective of elimination of the infection from Ecuador. The elimination of the infection from an endemic country in Latin America would be a major public health achievement and could stimulate the implementation of elimination strategies in other endemic countries.

Comparison of two single-day regimens of triclabendazole for the treatment of human pulmonary paragonimiasis.

A well-tolerated single-day treatment regimen is required for the community-based treatment of pulmonary paragonimiasis. To identify an optimal single-day treatment regimen, an open clinical trial was performed to compare the efficacy of 2 single-day regimens of triclabendazole. From 1991 to 1993, a total of 154 Ecuadorian patients were allocated to receive either a single dose or 2 doses of 10 mg/kg triclabendazole. Treatment with both regimens was associated with a rapid parasitological response (determined by clearance of Paragonimus eggs from sputum), resolution of most clinical symptoms and radiological signs, and only mild adverse effects. At 3 months after treatment, the cure rate (clearance of eggs from sputum) was 90.9% in the 2-dose group and 84.4% in the single-dose group. Re-treatment with a second 2-dose regimen was curative in all remaining patients by 1 year of follow-up. Our findings show that both single-day treatment regimens of triclabendazole were highly effective in the treatment of pulmonary paragonimiasis and suggest that patients should be re-examined at 3 months to determine the need for repeat treatment.

Interruption of infection transmission in the onchocerciasis focus of Ecuador leading to the cessation of ivermectin distribution.

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.

Community participation eliminates yaws in Ecuador.

Yaws is no longer a national and international health priority for intervention, but there is still a negative perception of the disease in the few affected communities. A survey in 1988 in the northern region of Ecuador documented a prevalence of 16.5% of clinical cases and 96.3% of serological cases. A continuous, long-term community-based surveillance programme was therefore put in place focusing on yaws as one of the sentinel diseases. The results of this intervention are reported here. In 1993, a second survey showed a reduction in the prevalence of clinical cases to 1.4% and of serological cases to 4.7%. Between 1993 and 1998, no other clinical cases were detected and the serological prevalence in 1998 was 3.5%, corresponding with clinical cases of primary or congenital syphilis, latent yaws under follow-up, and individuals with low serological titres indicating a 'serological scar'. These data indicate that yaws has been eliminated. Another important outcome of the intervention is the increased self-confidence in the communities that health problems can be tackled.

Association of transient dermal mastocytosis and elevated plasma tryptase levels with development of adverse reactions after treatment of onchocerciasis with ivermectin.

To investigate the role of mast cells in treatment-associated adverse reactions in patients with onchocerciasis, changes in plasma tryptase levels and skin mast cell counts were examined in 2 groups of Onchocerca volvulus-infected subjects after ivermectin treatment. After treatment, an increase in tryptase levels was observed concurrent with the onset of blood eosinopenia and preceding the appearance of plasma eosinophil-derived neurotoxin (EDN) and interleukin-5. Tryptase levels were correlated with development of peripheral eosinopenia and markers of eosinophil activation and degranulation. Dermal mast cell numbers increased transiently at 24 h after treatment, preceding the onset of dermal eosinophil infiltration and the development of clinically apparent inflammation. Local reactions were strongly correlated with levels of plasma tryptase and EDN, and the severity of systemic reactions was correlated with levels of tryptase, EDN, and interleukin-5. The data indicate that mast cells play a role in initiation of tissue inflammatory reactions after ivermectin treatment of onchocerciasis.

Onchocerca volvulus glycolytic enzyme fructose-1,6-bisphosphate aldolase as a target for a protective immune response in humans.

To identify potential vaccine candidates for the prevention of infection with the filarial nematode Onchocerca volvulus, we screened an O. volvulus L3 stage cDNA library with sera from putatively immune (PI) subjects, and a prominent immunogenic clone of 1,184 nucleotides was identified. It contained an open reading frame of 363 amino acids encoding the glycolytic enzyme fructose 1,6 bisphosphate aldolase (Ov-fba-1). Immunolocalization experiments demonstrated that the protein was most abundantly expressed in metabolically active tissues, including body wall muscle and the reproductive tract of adult female worms. Immunoelectron microscopy of L3 demonstrated binding in the region where the cuticle separates during molting, in the channels connecting the esophagus to the cuticle, and in the basal lamina surrounding the esophagus and the body cavity. Among subjects from areas where this organism is endemic specific humoral and cellular immune responses to recombinant protein were observed in both PI and infected subjects, whereas responses were not observed among subjects who had not been exposed to O. volvulus. Despite the absence of differential responsiveness in parasite-exposed human populations, when the recombinant was tested for protective efficacy in a mouse chamber model, a reduction in survival of larvae by ca. 50% was seen. This observation provides support for the further study of this parasite enzyme as a vaccine candidate in larger animal models.

Onchocerciasis in Ecuador: the situation in 1989

Details are given of the prevalence rates of onchocerciasis from the most recent surveys (1989) conducted in northern Ecuador. The disease has intensified and dispersed considerably due to migration of infected individuals and the presence of a highly efficient vector. Comparison of these data with those from two previous surveys carried out in 1982/83 and 1986 and correlated with entomological findings highly the danger of the formation of new foci of onchocerciasis in areas currently free of the disease. Recommendations are made for further entomological studies in areas either recently or likely to be affected by the disease where potential vectors are unknown or different to those registred in the Santiago focus. Invermectin treatment with local vector control in specific areas is advocated to reduce the disease to a low level of public health importance

Onchocerciasis in Ecuador: changes in prevalence of ocular lesions in Onchocerca volvulus infected individuals over the period 1980-1990

Trends in prevalence rates of onchocercal ocular lesions were examined over the period 1980 to 1990 using data from two cross-sectional surveys. There was evidence for increasing prevalence of anterior chamber microfilariae, iridocyclitis, optic atrophy, and chorioretinopathy. Large increases in prevalence, in particular, were seen for posterior segment lesions: optic atrophy increased from 2,7 per cent to 6.4 per cent and chorioretinopathy from 8.8 per cent to 35.6 per cent. Greatest increases in these lesions were seen in the Chachi which was attributed to the large increases in prevalence of microfilariae in the anterior chamber particularly in those aged 30 years or greater. The study findings suggest that ocular onchocerciasis is evolving in parallel with the well documented parasitological changes.

Estudios comparativos clínicos y epidemiológicos de la oncocercosis entre dos grupos raciales del área hiperendémica de Ecuador / Comparative clinical and epidemiological studies between 2 racial groups in the hyperendemic area of onchocercosis in Ecuador

Se evaluó la importancia de los factores raciales en la epidemiología y las manifestaciones clínicas de la oncocercosis en la raza negra y la raza indígena Chachi, dos grupos étnicos diferentes del área hiperendémica del foco oncocercótico ecuatoriano. Los Chachi presentaron una significativa mayor densidad de microfilarias en la piel. De los negros, 72,2 por ciento presentaron lesiones oncocercóticas en la piel comparado con 56,4 por ciento en los Chachi. Se encontró mayor prevalencia de nódulos palpables en los Chachi (51,4 por ciento vs. 43,0 por ciento). La presencia de microfilarias en la cámara anterior del ojo fue más frecuente en los Chachi (51,9 por ciento vs. 34,2 por ciento), pero se evidenció una mayor prevalencia de corioretinitis y atrofia del nervio óptico en los negros (17,6 por ciento vs 11,2 por ciento y 8,5 por ciento vs. 0,5 por ciento, respectivamente)

Onchocerciasis in Ecuador: prevalence of infection on the Ecuador-Colombia border in the Province of Esmeraldas

The prevalence of onchocerciasis infection was determined in communities on 7 rivers located in the northern area of the canton San Lorenzo, province of Esmeraldas. Diagnosis of the infection was obtained by skin biopsies and recombinant-antigen based-serology. No evidence of infection was detected in 9 communities studied along the Rio Mataje, which forms the frontier between Ecuador and Colombia, nor in 10 adjacent communities located on 5 interior rivers. Evidence for Onchocerca volvulus infection was found in 4 communities on the Rio Tululvi with the following prevalence: La Boca (3,5 per cent by biopsy and 3,9 per cent by serology), Guayabal (9,1 per cent by both biopsy and serology), La Ceiva (51,5 per cent by biopsy and 53 per cent by serology), and Salidero (4 per cent by biopsy and 7,7 per cent by serology). A few individuals in these communities were seropositive for O. volvulus in the absence of detectable dermal microfilariae: these might harbor very light or prepatent infections. No clinical disease attributable to onchocerciasis was found. The infected communities will be included in the ivermectin-based National Control Program for the disease, with no evidence of the infection having extended north of the Ecuadorian-Colombian border.

Chagas disease in Ecuador: evidence for disease transmission in an indigenous population in the Amazon region

Two well-defined synthetic peptides TcD and PEP² were used in a sero-epidemiological study for detection of Trypanosoma cruzi infections in an indigenous group in the Amazon region of Ecuador. Of the 18 communities studied along the Rio Napo, province of Napo, 15 (83.3 per cent) were found to be positive for T. cruzi infection. Of the 1,011 individuals examined 61 (6.03 per cent) resulted positive. A prevalence of infection of 4.8 per cent was found in children aged 1-5 years. The prevalence of infection increased with age, with adults 50 years or older showing a maximum prevalence of 18.8 per cent. Autochthonous transmission of T. cruzi is present among this isolated indigenous population.

Antibody isotypes, including igG subclasses, in Ecuadorian patients with pulmonary Paragonimiasis

An ELISA test was developed to detect Paragonimus-specific antibodies, including IgG subclasses, using P. mexicanus crude water-soluble antigens. The test was standardized to detect antibodies in sera of Ecuadorian patients with pulmonary paragonimiasis and negative controls from the endemic area. The detected mean levels of IgG (0.753, SEM: 0.074) and IgM (0.303, SEM: 0.033) were significantly elevated (P<0.05). Within the IgG subclasses, IgG4 showed the highest detected mean level (0.365, SEM: 0.116) and the other three subclasses showed considerably lower mean levels (IgG1, 0.186 SEM: 0.06; IgG2, 0.046 SEM: 0.01; IgG3, 0.123 SEM: 0.047). The number of P. mexicanus eggs found in sputum of infected individuals showed a positive correlation with the level of antibodies detected for IgM, IgG and its subclasses (P<0.001). The relevance of these findings in Ecuadorian patients suffering from pulmonary paragonimiasis is discussed.

Gastrointestinal illness associated with balantidium coli infection in rural communities in Ecuador

Un brote de enfermedad gastrointestinal caracterizada por diarrea y heces con sangre fueron investigadas en 4 comunidades diferentes en la provincia de Zamora Chinchipe en Ecuador. Un total de 322 personas fueron examinadas; trofozoitos de Balatidium coli fueron vistos en las heces de 62 de ellas (19,3 por ciento), de estas personas, en el 70,2 por ciento de las personas que tenían diarrea y en el 20.9 por ciento de las que tenían heces sanguinolientas. Así, demostramos una gran asociación entre infección por B. coli y diarrea (p<0,0005). La más alta prevalencia de infección fue vista en niños entre los 6 a 10 años de edad. El orígen de la infección parece provenir de los cerdos, los cuales viven dentro de las casas en pésimas condiciones de higiene. La balantidiasis fue tratada con una combinación de metronidazol y tetraciclina obteniéndose rápida curación

Esparganosis humana en el Ecuador: informe de un caso en la provincia de Esmeraldas / Human sparganosis in Ecuador: report of a case in the province of Esmeraldas

Se informa el segundo caso de esparganosis humana en Ecuador, en un paciente de sexo masculino, indígena Chachi, procedente de la provincia de Esmeraldas, quien presentó una nodulación localizada en la región escapular izquierda. En su extirpación se demostró la presencia de un céstodo clasificado com Spirometra, no siendo posible determinar la especie

Deficiencia de glucosa-6-fosfato dehidrogenasa en poblaciones ecuatorianas de raza negra / Deficiency of glucose-6-phosphate dehydrogenase in ecuadorian population of black race

Se determina el índice de deficiencia de la enzima G6PD, en los eritrocitos de individuos masculinos de raza negra, que habitan en áreas geográficas distintas del Ecuador. En La Costa, se escogieron dos grupos de poblaciones negras, de la provincia de Esmeraldas; el primero, comprende habitantes negros de raza pura de la cuenca del Santiago, el segundo mulatos de la ciudad de Esmeraldas. En la Sierra, se estudiaron habitantes negros de la provincia de Imbabura, particularmente del Valle del Chota. Se examinaron un total de 1054 muestra de sangre: 750 en la provincia de Esmeraldas y 304 en Imbabura; 135(12.8%) individuos presentaron deficiencia de G6PD; 67(14.2%) pertenecen a la cuenca del Santiago; 50(18.1%) son de la ciudad de Esmeraldas y 18(5.9%) del Valle del Chota. Se consideran ciertos factores, que pueden influir en los diferentes índices de deficiencia, detectados en las zonas estudiadas y la probable protección que brinda la deficiencia de G6PD, hacia las infecciones maláricas por p. falciparum

Criptosporidiosis humana en el Ecuador / Human cryptosporidiosis in Ecuador

Presentamos el primer reporte de criptosporidiosis humana asociado con diarrea en Quito, Ecuador. Utilizando la técnica de DMSO-ácido-resistente, hemos podido demostrar la presencia de oocitos de Criptosporidium asociado con dos casos de gastroenteritis aguda. Es importante que se considere a este parásito como posible agente etiológico en diarreas de inicio agudo, prolongadas y acuosas con una mayor frecuencia en los niños. De ahí que recomendamos la búsqueda rutinaria de este parásito en todos los laboratorios clínicos

Evaluación de las aglutinaciones febriles en salmonelosis / Evaluation of febrile agglutininations in salmonellosis

Un total de 170 personas fueron evaluadas para las aglutinaciones Eberth H y Eberth O. De ellos, hubieron 9 con tifoidea, 17 con fiebre y/o diarrea sin tifoidea y 14 sanos. La sensibilidad y especificidad de las aglutinaciones en pacientes con tifoidea fue: Eberth H (77.8% y 70.8% respectivamente) y Eberth O (66.7% y 82.9% respectivamente). En pacientes con fiebre y/o diarrea sin tifoidea, titulaciones falsos positivos fueron obtenidos en 29.4% de los casos para Ebert H y 17.7% para Ebert O. En personas sanas de Quito y Lago Agrio, las aglutinaciones "normales" eran diferentes para las dos zonas (P<0.05 para Eberth H y P<0.002 para Eberth O). Estos resultados indican que hay variaciones significativas entre distintas poblaciones lo que hace aún más relativa la interpretación correcta de las aglutinaciones, Eberth H y Eberth O en la evaluación de pacientes sospechosos de tifoidea

Diarrea aguda asociada a Campylobacter y otros agentes patógenos in Quito, Ecuador / Acute diarrhea associated with Campylobacter and other pathogens in Quito, Ecuador

En Quito, Ecuador, de julio a diciembre de 1984 se examinaron las heces de 100 niños de 1 a 24 meses de edad que sufrían diarrea aguda, con el fin de determinar la presencia de agentes enteropatógenos. En el 50% de los niños se identificaron uno o más microorganismos. Se aisló Campylobacter fetus en el 23% y se identificaron rotavirus en el 21%; también se encontraron Shigella sonnei (8%), Shigella flexneri (3%), Shigella boydii (1%), Salmonella enteritidis (3%) y parásitos enteropatógenos (6%), predominantemente Giardia lamblia y Entamoeba histolytica. En el 24% se detectaron infecciones combinadas provocadas por dos o más agentes enteropatógenos. Se estableció una relación entre la incidencia de cada microorganismo y la edad de los niños. Campylobacter fue el más frecuente entre los niños de 19 a 24 meses, mientras que los rotavirus se identificaron con mayor frecuencia entre los de 13 a 18 meses. En el 52,8% de los niños de 1 a 12 meses no se identificó un agente etiológico y se encontraron parásitos enteropatógenos solo entre los de más edad. Se presentó enteritis inflamatoria en el 61% de los niños con diarrea aguda, caracterizada por la presencia de moco, leucocitos o eritrocitos detectables en el examen microscópico de las heces