Cystic Echinococcosis: An Impact Assessment of Prevention Programs in Endemic Developing Countries in Africa, Central Asia, and South America

Table 7

Appraisal summary of Article Meeting Inclusion Criteria [2].

Population:	(i) Study location: Rio Chico Abajo (Department Ñorquinco), Anecón Grande (Department Pilcaniyeu), Mamuel Choique (Department 25 de Mayo), and Nahuel Pan (Department Bariloche) in the Province of Rio Negro, Patagonia region, Argentina; (ii) Small ruminant farmers in Rio Chico; (iii) Human population: Mapuche native communities (Anecón Grande and Nahuel Pan) living on reserves, with a Lonco (cacique), common property land
Sample size:	(i) Sheep: 2009, 79 farmers (8483 sheep); 2017 (3898 sheep). Randomized farm selection; (ii) Dogs: 2009 (309 dogs); 2017 (221). Total dogs Praziquantel (PZQ) treated: 11, 500. Non-randomized sampling of high dog population areas (judgment sampling) and voluntary dog owner participation (convenience sampling); (iii) Humans: non-randomized selection of 84 children from a school within vaccination area
Program outputs:	Definitive host control (dogs): 1980 four government departments launched dog de-worming program. Health centre at each study site (except Nahuel Pan): (i) Rio Chico and Mamuel Choique: health workers conducted home visits to administer PZQ, by combining tablets with minced meat; (ii) Anecón Grande: health worker travelled by horse to deliver PZQ, but dog owners administered; (iii) Nahuel Pan: dog owners collected PZQ from local health center to administer; Intermediate host control: (i) Sheep: 29, 323 doses of EG95 vaccine administered between December 2009 and January 2017 in Rio Chico (17, 894); Nahuel Pan (1056); Mamuel Choique (2220); and Anecón Grande (8153); (ii) Vaccination coverage: dose 1: 83.5%; 2: 80.1%; and 3: 85.7% (57.3% average vaccination coverage). Three doses over 12 months: (1) 30 days of age; (2) 60 days, before weaning; and (3) booster injection at 1-1.5 years of age; (iii) Vaccine prepared and donated by the University of Melbourne (50 or 100 dose vials plus an adjuvant); (iv) Administration method: vaccine reconstituted with distilled water and injected subcutaneously (dose: 50 μg of EG95 protein in 2 ml volume). Ear tags placed on vaccinated. Veterinarians administered for one week every December and January from 2009; (v) Local health care workers and national AM radio sent reminders to ensure farmers gathered all sheep prior to vaccination weeks; (vi) Animals who escaped or failure to gather not vaccinated; (vii) Children (6–14 years old): ultrasound screening and albendazole treatment from 1997; (viii) Community education campaign: health workers and veterinarians delivered. Aimed at schoolchildren and rural residents
Study design:	Quasi-experimental, non-randomized before and after study
Program outcomes and/or impact:	Cystic Echinococcosis (CE) prevalence tested pre-program: (i) Dogs: CoproELISA confirmed by Western Blot (WB) of dog fecel samples and arecoline purgation test; (ii) Sheep: ELISA test on sera from sheep confirmed by WB. Necropsies of adult sheep, confirmed by histology; Post-program (2009-2017) follow-up (100% sheep vaccination coverage expected): (i) 2011 serology: ELISA/WB 2-year-old sheep (); (ii) 2015 necropsy sheep; (iii) 2017 veterinarians performed arecoline purgation tests to detect E. granulosus worms in vomit and Coproantigen ELISA testing of fecel samples (from 2003); (iv) Serology (double diffusion 5, ELISA) initially. From 1997: US screening of children (6–14 years old) replaced ELISA. Albendazole treatment also delivered
Main findings:	Sheep: (i) 2011 Serology-ELISA/WB 2-year-old sheep(): significant difference detected between baseline number originally sampled and post-program impact (); (ii) Necropsy sheep: 56.3% 6-year-old sheep (2009) reduced to 21.1% (2015). Statistically significant decrease (, ). Cysts per animal decreased size <1 cm; (iii) Infected sheep: 84.2% (2009) reduced to 22.2% (2017). A statistically significant decrease (, ); (iv) Important to administer 3 vaccination doses: after the third EG95 vaccine, serum IgG increased to levels higher than those observed after the second. Antibody serum levels were maintained for 5 years, ensuring coverage against slow progression of fertile cysts; Dogs: (i) Arecoline purgation test: 4.5% (2009) to 4.3% (2017) infected. No statistically significant difference (, ); (ii) CoproELISA Infected dogs: 9.6% infected (2009) to 3.7% (2017). Statistically significant (, ); (iii) CoproELISA farms with infected dogs: 20.3% (2009) to 8.9% (2017). Not statistically significant decrease (, ); Children (6–14 years): (i) US Rio Negro province: prevalence decreased 5.6% (1984/6) to 0.12% (2015); Children and adults in high-risk regions (e.g., Rio Chico Abajo, Mamuel Choique, and Anecón Grande): (i) 38 new cases (1995-2015): cumulative incidence rate 7800 per 100,000 inhabitants; (ii) 2016 only 1 (1.1%) asymptomatic CE case (10 cm lung cysts); Behavioral risk factors: (i) Home slaughter of adult sheep and goats; (ii) Livestock viscera fed to dogs; (iii) Poor slaughterhouse disposal, hygiene, and standards; (iv) Death of infected livestock in fields/poor carcass disposal; Barriers: (i) Ecological conditions suitable for E. granulosus lifecycle (e.g., temperature and humidity); (ii) Low socioeconomic conditions; (iii) Aggregation of small productive units with home slaughter; (iv) Poor sanitary infrastructure; (v) Harsh climate and lack of road infrastructure limited farm access during autumn and winter; (vi) Failure to deliver all vaccination doses attributed to poor animal handling facilities and communication gaps between control staff and residents; (vii) Unsustainable dog de-worming programs (4-12 times per year) and sheep vaccination programs (twice yearly). Attributed to difficulties accessing remote rural areas and few skilled health or veterinary workers; (viii) Vaccination alone not recommended. Combined program with regular de-worming and health education recommended
Limitations:	(i) Failed to deliver 3 vaccination doses to 40% of sheep who escaped or failed to present at vaccination times; (ii) Selection bias: non-randomized sample selection of children from one school; (iii) Sample size calculations for each species treated prevalence separately. However, calculation based upon paired data (discordant pairs) for each species may be more suitable for two prevalence values in a before and after study; Confounding variables: (i) No clear distinguishment between owned and stray dogs. Only reference to “roaming dogs”; (ii) Older, unvaccinated sheep, purchased from areas outside vaccination zones, may limit program outputs; (iii) Sheep housed in mixed ages and sexes may have affected transmission and prevalence rates; (iv) Variation between health workers or dog owner PZQ administration; (v) Program outcomes not tested (e.g., health education effects on behavioral change); (vi) Goats excluded from vaccination program, as low prevalence in goats (unpublished study) and little local slaughter. However, one CE infected dog lived on a property that exclusively housed goats