Analysis of vaccination strategy against cystic echinococcosis developed in the Province of Río Negro, Argentina: 12 years of work.

Cystic echinococcosis (CE) is a zoonosis caused by species of the complex Echinococcus granulosus, sensu lato in their larval stage. It is an endemic disease in the province of Río Negro, where small farmers generally have both sheep and goats. Lamb vaccination with EG95 was incorporated in 2009 with very good results: in fact, it contributed to a significant drop in prevalence of infection in both sheep and goats, when determined by necropsy and serology in 2018. In the design of the activity, it was decided not to vaccinate goats in order to minimize the operational requirements of vaccination and comments from producers about the rarity of observing hydatid cysts in goat viscera were considered. OBJECTIVE: To identify causes which can still generate infection in dogs, and to detect species/genotypes in circulation in the province of Río Negro. MATERIALS AND METHODS: In indigenous reserves comprised within the area of lamb vaccination with 3 doses of EG95, (dose 1 in December, dose 2 in January and dose 3 in December of the year following, at the time of application of dose 1 to the new lambs). Prevalence in adult goats and sheep was determined by necropsy and serology (ELISA). Infective species/genotypes present in the work area and in the rest of the province of Río Negro were identified by Cox1 mitochondrial gene sequencing. Epidemiological analysis was completed with surveys among farmers about slaughter habits for human consumption. RESULTS: Through serology and necropsy, infection rates in vaccinated and nonvaccinated sheep were significantly different (21% versus 66%). Non-vaccinated sheep and non-vaccinated goats were also significantly different in that there was less infection in goats compared to sheep (7% versus 66% for necropsy, 30% versus 61% for serology); After many years of sheep vaccination the infection positives were low, and differences between vaccinated sheep and non-vaccinated goats turned out non-significant (21% versus 7%). With reference to epidemiology and control along the period 2018-2022, PZQ dosing of dogs 4 times a year was maintained, and 2 extra deworming tasks were introduced together with dose 1 and 2 of EG95, performed by the veterinary vaccination team, ensuring the ingestion of PZQ by dogs. Assessment of animal slaughter for consumption in 41 producers showed that 21 of them slaughter a monthly average of 18 goats (an average of 0.43 goat per month per farm) and 36 in all slaughter 35 old sheep in a year (average of 0.85 sheep per month per farm). With respect to identification of species/genotypes as from 2010, genotypes G1 have been found in 11 sheep (out of which 6 belong to vaccination zone) and genotypes G7, in one pig. A goat cyst within vaccination zone turned out unfertile and it was not possible to sequence it. CONCLUSION: Design and implementation of a vaccine programme combined with the use of PZQ resulted as cost-effective, since it was possible to maintain the vaccine over time, with clear impact on prevalence decrease in sheep and goats.

Prevalence of human cystic echinococcosis in the towns of Ñorquinco and Ramos Mexia in Rio Negro Province, Argentina, and direct risk factors for infection.

BACKGROUND: Cystic echinococcosis (CE) is a parasitic zoonosis caused by infection with the larval stage of Echinococcus granulosus (s.l.). This study investigated the prevalence and potential risk factors associated with human CE in the towns and rural areas of Ñorquinco and Ramos Mexia, Rio Negro province, Argentina. METHODS: To detect abdominal CE cysts, we screened 892 volunteers by ultrasound and investigated potential risk factors for CE using a standardized questionnaire. Prevalence ratio (PR) with 95% confidence intervals (CI) was used to measure the association between CE and the factors investigated, applying bivariate and multivariate analyses. RESULTS: Abdominal CE was detected in 42/892 screened volunteers (4.7%, 95% CI 3.2-6.1), only two of whom were under 15 years of age. Thirteen (30.9%) CE cases had 25 cysts in active stages (CE1, CE2, CE3a, according to the WHO Informal Working Group on Echinococcosis [WHO-IWGE] classification). The most relevant risk factors identified in the bivariate analysis included: living in rural areas (P = 0.003), age > 40 years (P = 0.000), always drinking water from natural sources (P = 0.007), residing in rural areas during the first 5 years of life (P = 0.000) and having lived more than 20 years at the current address (P = 0.013). In the multivariate final model, the statistically significant risk factors were: frequently touching dogs (P = 0.012), residing in rural areas during the first 5 years of life (P = 0.004), smoking (P = 0.000), age > 60 years (P = 0.002) and living in rural areas (P = 0.017). CONCLUSIONS: Our results point toward infection with CE being acquired since childhood and with constant exposure throughout life, especially in rural areas with a general environmental contamination.

Integration of animal health and public health surveillance sources to exhaustively inform the risk of zoonosis: An application to echinococcosis in Rio Negro, Argentina.

The analysis of zoonotic disease risk requires the consideration of both human and animal geo-referenced disease incidence data. Here we show an application of joint Bayesian analyses to the study of echinococcosis granulosus (EG) in the province of Rio Negro, Argentina. We focus on merging passive and active surveillance data sources of animal and human EG cases using joint Bayesian spatial and spatio-temporal models. While similar spatial clustering and temporal trending was apparent, there appears to be limited lagged dependence between animal and human outcomes. Beyond the data quality issues relating to missingness at different times, we were able to identify relations between dog and human data and the highest 'at risk' areas for echinococcosis within the province.

Identification of potential 'hot spots' of cystic echinococcosis transmission in the province of Río Negro, Argentina.

Cystic echinococcosis (CE) is a parasitic zoonosis caused by Echinococcus granulosus. The control program of CE of Rio Negro province, Argentina, involves annual surveillance using ultrasound (US) screening in school children, and five-year cross-sectional surveys to detect livestock farms with parasitized dogs by coproELISA with confirmation tests (Western Blot or PCR). Control program is based on deworming of dogs with praziquantel and the aim is to identify areas at risk of Cystic echinococcosis transmission to humans, using all available data sources. The information was spatially distributed in 13 program areas and, at a smaller geographical scale, in 80 Primary Health Care Centers. CoproELISA surveys involved three randomized sampling periods (2003-05, 2009-10, 2017-18), with 1790 canine fecal samples. The US surveys were conducted in 2003-08, 2009-16 and 2017-18 in 34,515 children. Heat maps were created at the smallest geographic scale with QGIS 3.4.6. For the consecutive sampling periods, prevalence of positive canine fecal samples from livestock farms were 14.7, 12.1 and 7.8%, respectively, and children prevalence was 0.4, 0.2 and 0.1%, respectively. The study has been developed on a scale according to which the temporal-spatial distribution of CE allows to adjust control strategies in those areas of potential transmission of the zoonosis to humans.

Epidemiology, diagnosis, treatment and follow-up of cystic echinococcosis in asymptomatic carriers.

Background: Río Negro Province is endemic for cystic echinococcosis (CE). A CE control program includes early diagnosis in humans. During 1980-1996, screening was done with serology and surgery was the unique choice of treatment. Since 1997, ultrasound (US) has been the method of choice for screening, and new choices of treatment for asymptomatic carriers are discussed in the CE guidelines. Methods: Between 1997 and 2016, 42 734 abdominal USs were performed, 192 new asymptomatic cases were diagnosed and underwent a protocol according to the size, location and type of cyst. Treatment options included active surveillance (US monitoring, 83 [43.3%]), antiparasitic (albendazole, 92 [47.9%]) and surgery (17 [8.8%], including percutaneous treatment). Results: After 7.7 y of follow-up, of the cases under active surveillance, 28 (33.7%) had to change treatment: 5 (6%) to surgery and 22 (26.5%) to albendazole. Of the patients treated with albendazole, 3 (3.2%) were operated on and 13 (14%) were treated with a second cycle of albendazole. Conclusion: As a result of the present study, resolution of CE in a non-surgical way with albendazole is confirmed to be effective in asymptomatic carriers with CE1 or CE3a cysts. An update eliminates the strategy of active surveillance in type CE1 cysts <3 cm and is replaced by treatment with antiparasitic in all asymptomatic cases with CE1 or CE3a cysts <10 cm. The update also limits follow-up to 12-18 months to evaluate those cases with non-response to antiparasitic and switch to a surgical option.

Pilot field trial of the EG95 vaccine against ovine cystic echinococcosis in Rio Negro, Argentina: 8 years of work.

Cystic echinococcosis (CE) is endemic in the Rio Negro province of Argentina. After 30 years of control using praziquantel in dogs the transmission rate to humans and sheep has decreased significantly, however transmission persists. The objective of the study was to assess the inclusion of the EG95 for sheep in the control program and to determine the vaccine's operative feasibility in field conditions. An intervention study was defined in Rio Negro Province in Argentina comprising, in total, an area of 5820 Km2. Lambs received two vaccinations with the EG95 vaccine followed by a single booster injection when the animals were 1-1.5 years of age. Vaccination of lambs born into one trial site was introduced and continued for 8 years. Evidence for Echinococcus granulosus transmission was monitored before and after vaccination by coproantigen ELISA in faecal samples of dog, purgation of dogs to detect E. granulosus worms, necropsy on adult sheep and by ultrasound screening in children of 6-14 years old. 29,323 doses of vaccine were applied between 2009 and 2017, which a vaccination coverage of 80.1%/85.7% (57.3% average for fully vaccinated). Before the introduction of the vaccine 56.3% of the 6-year-old sheep were infected with E. granulosus at necropsy and 84.2% of the farms had infected sheep; 4.3% of the dogs were positive for E. granulosus infection using the arecoline test, and with coproELISA 9.6% of dog fecal samples were positive and 20.3% of the farms had infected dog.After the vaccine was introduced, 21.6% of sheep older than 6 years were found to be infected at necropsy and 20.2% of the farms were found to be infected; in dogs, 4.5% were found positive for E. granulosus using arecoline purgation and with coproELISA 3.7% of samples were positive, with 8.9% of farms having a positive dog. In 2016 only one case of E. granulosus infection was diagnosed by US screening in a 6-14 years old child. Included in the analysis are discussions of difficulties experienced in the field which affected correct vaccine administration as well as social features and practices that may impact on echinococcosis control and the EG95 vaccination program in Rio Negro. Vaccination of sheep with the EG95 vaccine provides a valuable new tool which improves the effectiveness of CE control activities. Vaccination was effective even in a difficult, remote environment where only approximately half the lambs born into the communities were fully vaccinated.

Cystic echinococcosis in South America: a call for action.

Cystic echinococcosis (CE) or hydatidosis, a parasitic zoonosis caused by a cestode of the family Taeniidae, species Echinococcus granulosus, is endemic in Argentina, Chile, Peru, Uruguay, and southern Brazil. This report presents CE figures for these five countries in 2009 - 2014 and proposes indicators to measure national control programs. Nearly 5 000 new CE cases were diagnosed annually in the five countries during the study period. The average case fatality rate was 2.9%, which suggests that CE led to approximately 880 deaths in these countries during the 6-year period. CE cases that required secondary or tertiary health care had average hospital stays of 10.6 days, causing a significant burden to health systems. The proportion of new cases (15%) in children less than 15 years of age suggests ongoing transmission. Despite figures showing that CE is not under control in South America, the long-standing implementation of national and local control programs in three of the five countries has achieved reductions in some of the indicators. The Regional Initiative for the Control of CE, which includes the five countries and provides a framework for networking and collaboration, must intensify its efforts.

[Conditions for the transmission of Hantavirus in Rio Negro, Argentina]. / Condiciones para la transmision del hantavirus en zona andina de Río Negro, Argentina.

Hantavirus Pulmonary Syndrome (HPS) is a disease of viral etiology that affects humans causing severe acute respiratory symptoms. In Patagonia the disease is caused by the Andes Virus (AND) and transmitted by the rodent Oligoryzomys longicaudatus. The aim of this study was to identify those human activities that increase the risk of exposure to rodents, what we call "contagious scenarios". A retrospective study was performed with data obtained from cases in Rio Negro, which included clinic-epidemiological records and ecological/environmental assessment reports. The following variables were considered: age, sex, season, percentage of urbanization, geographic location, human settlements in rodent infested areas, probable source of exposure, type of activity and level of sanitary development. In total 32 cases were studied. Exposure was verified in 18 (56.2 %) cases in rural areas and 10 cases (31.3%) in small rural towns. In relation to anthropogenic environment, 24 (75%) cases were reported in developed settlements and 8 cases (25%) were related to slightly modified areas. Major exposition in El Bolson identified 8 cases of indoor activities of the total 18 reported in the area (44.5%), while in Bariloche 8 (57.1%) cases out of 14 were reported in outdoor surroundings. In general, activities that generated greater risk were work-related, accounting for 23 (71.9%) cases while 7 were related to recreational activities (28.1%). The identification of "contagious scenarios" at local level provided information for an effective application of available resources in terms of prevention and sanitary education.

Condiciones para la transmision del hantavirus en zona andina de Río negro, Argentina

El Síndrome Pulmonar por Hantavirus (SPH) es una enfermedad de etiología viral que causa en el hombre un cuadro respiratorio grave. En Patagonia, la enfermedad es causada por el virus Andes Sur (AND), transmitido por el roedor Oligoryzomys longicaudatus. El objetivo del presente trabajo fue identificar las actividades del hombre que favorecen su exposición a roedores, denominados escenarios de contagio. Se realizó un estudio retrospectivo a partir de información recolectada en investigaciones de casos ocurridos en Río Negro, mediante Fichas Clínico-Epidemiológicas e informes de evaluación ecológico/ambiental. Se definieron como variables a ser consideradas: edad, sexo, época del año, grado de urbanización, localización geográfica, integración del hombre al hábitat de roedores, fuente probable de exposición, actividad humana y nivel de saneamiento. Se estudiaron 32 casos. La exposición rural se verificó en 18 (56.2%) de los casos y 10 (31.3%) en paraje rural (grupo de viviendas en zona rural). En relación al ambiente antropogénico 24 (75%) resultaron en ambientes modificados por el hombre y 8 (25%) en áreas poco modificadas. El sitio de exposición de mayor importancia en El Bolsón fue el interior de edificaciones en 8 de los 18 casos allí registrados (44.5%), mientras que en Bariloche fueron ambientes de exterior con 8/14 (57.1%) casos. La actividad de riesgo fue laboral en 23 (71.9%) de los casos y recreacional en 7 (28.1%). Determinar los escenarios de contagio a nivel local ha aportado información para aplicar todos los recursos disponibles en materia de prevención y educación sanitaria.

Hantavirus Pulmonary Syndrome (HPS) is a disease of viral etiology that affects humans causing severe acute respiratory symptoms. In Patagonia the disease is caused by the Andes Virus (AND) and transmitted by the rodent Oligoryzomys longicaudatus. The aim of this study was to identify those human activities that increase the risk of exposure to rodents, what we call "contagious scenarios". A retrospective study was performed with data obtained from cases in Rio Negro, which included clinic-epidemiological records and ecological/environmental assessment reports. The following variables were considered: age, sex, season, percentage of urbanization, geographic location, human settlements in rodent infested areas, probable source of exposure, type of activity and level of sanitary development. In total 32 cases were studied. Exposure was verified in 18 (56.2 %) cases in rural areas and 10 cases (31.3%) in small rural towns. In relation to anthropogenic environment, 24 (75%) cases were reported in developed settlements and 8 cases (25%) were related to slightly modified areas. Major exposition in El Bolson identified 8 cases of indoor activities of the total 18 reported in the area (44.5%), while in Bariloche 8 (57.1%) cases out of 14 were reported in outdoor surroundings. In general, activities that generated greater risk were work-related, accounting for 23 (71.9%) cases while 7 were related to recreational activities (28.1%). The identification of "contagious scenarios" at local level provided information for an effective application of available resources in terms of prevention and sanitary education.

[Cystic echinococcosis in dogs and children in the province of Río Negro, Argentina]. / Vigilancia de la equinococosis quística en perros y niños en la provincia de Río Negro, Argentina.

Cystic echinococcosis (CE) is an endemic disease in the province of Río Negro, Argentina. The control program against CE has developed monitoring surveillance systems. Currently, the coproELISA/Western blot (WB) test is used to determine transmission in livestock farms (epidemiological units or EU) from collected dry field-dispersed dog feces. The objective was to evaluate the prevalence of CE on livestock farms and its relationship with CE cases in children aged 0-14 years. Canine fecal samples were obtained from randomly selected livestock farms and processed by the coproELISA/WB test. Furthermore, new cases in children in the same age group mentioned above were identified. In 278 EU, 571 samples of canine feces were obtained. There were 37 positive samples for coproELISA/WB (6.5%) and the presence of transmission was demonstrated in 37 EU (13.3%). There were no significant differences (p=0.9) with the survey conducted in the period 2003-2004 while there were significant differences (p=0.02) with the EU survey of native populations conducted in 2009-2010. With respect to animal density in the work area, the EU yielding negative results had an average of 2 dogs (SD 2.1) per EU while in the EU having positive results the average was 3 dogs (SD 4.2), showing statistically significant differences (p=0.02). In children under 15 years of age, 12 cases were diagnosed. This study has identified, on average, that the cases of hydatid disease are closer in the positive fields than in the negative fields (p=0.00307).The coproELISA/WB test allowed to identify the dispersion of CE on livestock farms and its relationship with the occurrence of cases in children in 2009-2010.

Vigilancia de la equinococosis quística en perros y niños en la provincia de Río Negro, Argentina / Cystic echinococcosis in dogs and children in the province of Río Negro, Argentina

La equinococosis quística (EQ) es una enfermedad endémica en la provincia de Río Negro, Argentina. El programa de control de esta afección desarrolla sistemas de vigilancia epidemiológica basados en las técnicas de coproELISA/Western blot (WB) en muestras de heces de perros recolectadas del suelo, a fin de determinar establecimientos ganaderos (unidades epidemiológicas o UE) con transmisión presente. El objetivo de esta investigación fue evaluar la prevalencia de EQ en establecimientos ganaderos y su relación con la presencia de casos de EQ en niños de 0 a 14 años. Se seleccionaron aleatoriamente UE donde se obtuvieron muestras de materia fecal canina, las que fueron procesadas mediante coproELISA/WB. Asimismo, se identificaron casos nuevos ocurridos en niños del rango etario señalado. Se obtuvieron 571 muestras de 278 UE; 37 (6,5 %) fueron positivas a coproELISA/WB de 37 (13,3 %) UE con transmisión presente. Las diferencias con el relevamiento efectuado en el período 2003-2004 resultaron no significativas (p = 0,9), mientras que las diferencias con el relevamiento efectuado en UE de poblaciones originarias en 2009-2010 resultaron significativas (p = 0,02). Con relación a la densidad animal en el área de trabajo, las UE que dieron un resultado negativo tuvieron un promedio de 2 (DE: 2,1) perros por UE, en las UE con infección presente el promedio fue de 3 (DE 4,2), esta diferencia fue estadísticamente significativa (p = 0,02). Se diagnosticaron 12 casos en niños menores de 15 años. Se estableció que los casos de hidatidosis, en promedio, se situaron a menor distancia de los campos positivos a coproELISA/WB que de los campos negativos (p= 0,00307). La prueba de coproELISA/WB permitió identificar la dispersión de EQ en establecimientos ganaderos y analizar su relación con la ocurrencia de casos en niños.

Cystic echinococcosis (CE) is an endemic disease in the province of Río Negro, Argentina. The control program against CE has developed monitoring surveillance systems. Currently, the coproELISA/Western blot (WB) test is used to determine transmission in livestock farms (epidemiological units or EU) from collected dry field-dispersed dog feces. The objective was to evaluate the prevalence of CE on livestock farms and its relationship with CE cases in children aged 0-14 years. Canine fecal samples were obtained from randomly selected livestock farms and processed by the coproELISA/WB test. Furthermore, new cases in children in the same age group mentioned above were identified. In 278 EU, 571 samples of canine feces were obtained. There were 37 positive samples for coproELISA/WB (6.5%) and the presence of transmission was demonstrated in 37 EU (13.3%). There were no significant differences (p=0.9) with the survey conducted in the period 2003-2004 while there were significant differences (p=0.02) with the EU survey of native populations conducted in 2009-2010. With respect to animal density in the work area, the EU yielding negative results had an average of 2 dogs (SD 2.1) per EU while in the EU having positive results the average was 3 dogs (SD 4.2), showing statistically significant differences (p=0.02). In children under 15 years of age, 12 cases were diagnosed. This study has identified, on average, that the cases of hydatid disease are closer in the positive fields than in the negative fields (p=0.00307).The coproELISA/WB test allowed to identify the dispersion of CE on livestock farms and its relationship with the occurrence of cases in children in 2009-2010.