Rojas et al. Parasites Vectors (2021) 14:374 https://doi.org/10.1186/s13071-021-04875-3 Parasites & Vectors REVIEW Open Access Abdominal angiostrongyliasis in the Americas: ffty years since the discovery of a new metastrongylid species, Angiostrongylus costaricensis Alicia Rojas1* , Arnaldo Maldonado‑Junior2, Javier Mora1, Alessandra Morassutti3, Rubens Rodriguez3, Alberto Solano‑Barquero1, Anamariela Tijerino4, Marianela Vargas4 and Carlos Graef‑Teixeira5 Abstract Angiostrongylus costaricensis is a zoonotic parasitic nematode described for the frst time in 1971 by Pedro Morera and Rodolfo Céspedes in Costa Rica. This parasite causes an infection known as abdominal angiostrongyliasis, afect‑ ing mainly school‑aged children and young adults. Infection with A. costaricensis has been associated with a myriad of rodent and mollusk species in the Americas and the Caribbean, as its natural hosts and reservoirs. In this commem‑ orative review, we highlight the extensive research collected through a 50‑year journey, which includes ecological, pathological, and molecular studies on A. costaricensis and its implicated disease. We also identify major knowledge gaps in its evolutionary history, the ecological role of imported and invasive mollusk species, and immune response. We propose that the advent of ‑omics analyses will allow us to gather novel information regarding A. costaricensis biology and infection dynamics, as well as to promote the design of much‑needed sensitive and specifc diagnostic tools. Keywords: Angiostrongylus costaricensis, Abdominal angiostrongyliasis, Eosinophilic enteritis, Zoonosis, Helminthiasis Background mollusks and rodents as intermediate and defnitive Angiostrongylus costaricensis is a zoonotic parasitic hosts, respectively. nematode that causes eosinophilic enteritis in humans, known as abdominal angiostrongyliasis (AA). Since its History of Angiostrongylus costaricensis description in 1971 in Costa Rica, it has been reported Te frst case of AA in humans was described in 1952 in from the southern regions of the United States to most a seven-year-old child from Costa Rica sufering from Latin American countries and several Caribbean islands. severe abdominal pain with thickened intestinal serosa Te interest and concern that has promoted the study of [1, 2]. Even though the etiological agent could not be A. costaricensis derive from the severe pathology that AA identifed at that time, the child was treated by surgi- represents in humans, especially to school-age children cal ileocecal resection and recovered completely. Over and young adults, and the intricate life cycle that involves the next 16 years, 63 similar cases were received by the reference pathology laboratory from Costa Rica (Servi- cios de Anatomía Patológica, Hospital San Juan de Dios, *Correspondence: [email protected] and Caja Costarricense de Seguro Social) [1, 3], mainly 1 Laboratory of Helminthology, Centro de Investigación en Enfermedades Tropicales, University of Costa Rica, San José, Costa Rica derived from school-age children from all regions of Full list of author information is available at the end of the article the country. Most cases were characterized by severe © The Author(s) 2021. 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The Creative Commons Public Domain Dedication waiver (http:// creat iveco mmons. org/ publi cdoma in/ zero/1. 0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Rojas et al. Parasites Vectors (2021) 14:374 Page 2 of 19 abdominal pain in the right iliac fossa with fever and from other members of the genus, including the size anorexia [3]. Analyses of the intra-abdominal masses of the spicules and the presence of a terminal spine in recovered from these patients showed thickening in the females and a gubernaculum in males [4]. In that study, appendix, hardening of an edematous intestinal wall, and the authors highlighted that humans were not the natu- yellowish granulomatous infltration that led to partial ral hosts of the parasite, since larvae were not excreted to complete obstruction and necrosis. Complete blood in feces. Angiostrongylus costaricensis was compared to counts were characterized by leukocytosis and eosino- Angiostrongylus cantonensis, the other species infecting philia that ranged from 11 to 81% of total leukocytes. In humans, and they hypothesized that the novel A. costari- these cases, a detailed morphological analysis based on censis was potentially better adapted to humans than the histopathology sections with the presence of male and congeneric species, since adults were found within arteri- female adult nematodes led to a preliminary identifca- oles and larvated eggs were detected across tissue layers. tion of metastrongylid worms [2]. Contrarily, during the eosinophilic encephalitis caused by Pedro Morera (Fig. 1) and Rodolfo Céspedes, two sci- A. cantonensis, third-stage larvae (L3) do not develop fur- entists from the University of Costa Rica and the San ther and remain inside brain arterioles [5]. Te following Juan de Dios Hospital, Costa Rica, respectively, fnally year, the frst AA case outside Costa Rica was described characterized the nematode specimens obtained from in Honduras by Edgardo Sierra and Pedro Morera [6]. clinical cases. In their report published in 1971, they Dr. Pedro Morera concentrated all his eforts on elu- described a new species in the genus Angiostrongylus, cidating the natural intermediate and defnitive hosts of and proposed the name A. costaricensis. Tis characteri- A. costaricensis in parallel with the description of human zation was based on several morphological diferences AA cases [7, 8]. In 1970, the cotton rat (Sigmodon hispi- dus) and the black rat (Rattus rattus) were found with A. costaricensis worms in their mesenteric arteries. How- ever, the strong tissular reaction described in human cases was not observed in the animals. Instead, larvated eggs and L1 larvae were observed in the rat’s intestinal mucosa and L1 were shed in their feces [8]. In addition, the terrestrial slug Sarasinula plebeia (syn. Vaginu- lus plebeius) was identifed as the intermediate host of the parasite after the recovery of L3 larvae from tissue digests [7]. Tese novel fndings directed the reconstruc- tion of A. costaricensis’s life cycle by performing experi- mental infections of laboratory-raised S. hispidus with L3 obtained from naturally infected S. plebeia. Te careful analysis of the development of L1, L2, and L3 stages in slugs and the maturation of L3 into adults in rats led to a more detailed redescription of A. costaricensis in 1973 [9]. Fifty years after its original description, A. costaricen- sis has been reported in a myriad of rodent and slug spe- cies in more than ten countries in the Americas and still compromises the health of hundreds of individuals. Distribution and epidemiology Angiostrongylus costaricensis has been reported in 24 geographic sites from the Americas and the Carib- bean [10] (Fig. 2), either in their rodent defnitive hosts, causing AA in humans, or in mollusk intermediate hosts. Te parasite has been detected in the USA [11, Fig. 1 Pedro Morera, Emeritus Professor at the University of Costa 12], Mexico [13], Guatemala [14], Honduras [6, 15], El Rica and Past President of the World Federation of Parasitologists. Salvador [16], Nicaragua [17], Costa Rica [9], Panama Together with Marta Conejo‑Víquez and Arnoldo Castro‑Araya, were [18], Colombia [19], Venezuela [20], Peru [21], Ecuador pioneers in the study of the Angiostrongylus costaricensis life cycle, [22], Brazil [23], Argentina [24], Cuba [25], the Domini- pathology, and ecology. Photo credit: Marcia Krauze Diehl. This photo is licensed under the Creative Commons CC BY license can Republic [26], Martinique [27], Haiti [28], and Gua- deloupe [29]. Tese geographical locations meet abiotic Rojas et al. Parasites Vectors (2021) 14:374 Page 3 of 19 Fig. 2 Geographical distribution of Angiostrongylus costaricensis in the Americas. This parasite has been detected in North and Central America in the USA (Los Angeles, Miami, Texas) [11, 53], Mexico (not specifed in which location) [13], Guatemala (Chiquimula, Ciudad de Guatemala, El Progreso, Guastatoya, Jalapa, Jutiapa, Suchitepequez) [41], Honduras (Comayagua, Cortés, El Paraíso, Francisco Morazán, Olancho) [45], El Salvador (not specifed), Nicaragua (León) [17, 62], Costa Rica (Alajuela, Cartago, Guanacaste, Heredia, Limón, Puntarenas, San José) [37], and Panama (not specifed) [18]. In South America, A. costaricensis has been reported in Colombia (Caquetá, Huila, Putumayo, Tolima, Valle, Vaupés) [19], Venezuela (not specifed) [20], Ecuador (Guayaquil) [22], Perú (Iquitos)