Angiostrongyliasis in the Americas

The helminth Angiostrongylus costaricensis Morera & Cespedes, 1971 is endemic to the Americas and is responsible for a pathological abdominal syndrome, caused by the presence of the adult helminth in the mesenteric arteries. This is microscopically characterized by eosinophilic infiltration, vascular abnormality and a granulomatous reaction (GraeffTeixeira et al., 1987). The disease was first reported in humans by Cespedes et al. (1967) and Morera (1967) in Costa Rica. The adult worm was subsequently described from specimens recovered during surgical procedures by Morera & Cespedes (1971). The parasite’s current distribution ranges from the southern United States to northern Argentina (Morera, 1988), with human cases having been reported in Costa Rica, Honduras, Colombia, Martinique, Dominican Republic, Puerto Rico, Nicaragua, Mexico, Venezuela, Guadalupe, El Salvador, Panama and Brazil (Kaminsky, 1995).


Introduction
Abdominal angiostrongyliasis, a parasitic disease originally from the Americas, and eosinophilic meningoencephalitis, from Asia, are caused by two species of angiostrongilids nematodes, belonging to the family Metastrongylidae Leiper, 1908. In both cases, rats are the main definitive hosts and snails are the intermediate hosts (Acha & Szyfres, 2003).
The helminth Angiostrongylus costaricensis Morera & Céspedes, 1971 is endemic to the Americas and is responsible for a pathological abdominal syndrome, caused by the presence of the adult helminth in the mesenteric arteries. This is microscopically characterized by eosinophilic infiltration, vascular abnormality and a granulomatous reaction (Graeff-Teixeira et al., 1987). The disease was first reported in humans by Céspedes et al. (1967) and Morera (1967) in Costa Rica. The adult worm was subsequently described from specimens recovered during surgical procedures by Morera & Céspedes (1971). The parasite's current distribution ranges from the southern United States to northern Argentina (Morera, 1988), with human cases having been reported in Costa Rica, Honduras, Colombia, Martinique, Dominican Republic, Puerto Rico, Nicaragua, Mexico, Venezuela, Guadalupe, El Salvador, Panama and Brazil (Kaminsky, 1995).
In turn, Angiostrongylus cantonensis, the agent that causes eosinophilic meningoencephalitis, was first described in Canton, China, by Chen (1935), and is now dispersed to various Pacific islands, Australia, Africa, and more recently, the Americas (Foronda et al., 2010). It is believed that the initial dissemination to islands in the Pacific resulted from the introduction of naturally infected rats in containers coming from Asia (Diaz, 2008). The growing flows of global trade and tourism, as well as the spread of habits and customs among countries, have enabled the dispersion of the definitive and intermediate hosts of A. cantonensis (Cross, 1987). Currently there are reports of human infection in the United States (New et al., 1995), Cuba , Jamaica (Slom & Johnson, 2003), Ecuador (Dorta-Contreras et al., 2010) and Brazil (Lima et al., 2009.) In particular the introduction of the Achatina fulica in Brazil (Thiengo et al., 2007) and Pomacea canaliculata (Lamarck, 1822)in China are examples of the importance of exotic snails in the spread of this helminthiasis (Lv et al., 2008).
This chapter focuses on the taxonomy, life cycle, endemic and exotic intermediate hosts, natural vertebrate hosts and geographical distribution of these Angiostrongylus species together with diagnosis, treatment and prophylaxis of the diseases borne by them.

Systematic and general morphology
The system for classifying the Angiostrongylus genus basically relies on the morphological characteristics of the rays of the copulatory bursa, host group specificity and/or place where the adult worms are located in the host. Dougherty (1946) considered the following genera to be synonyms for the genus Angiostrongylus Kamensky, 1905: Haemostrongylus Railliet andHenry, 1907;Parastrongylus Bayle, 1928;Rodentocaulus Shul'ts, Orlov and Kutas, 1933;Pulmonema Chen, 1935;andCardionema Yamaguti, 1941. Drozdz (1970) separated species of the genus Angiostrongylus into two subgroups based on morphological characteristics of the caudal bursa and systematized them into two subgenera -Angiostrongylus and Parastrongylus -based on the morphology of the lateral rays of the caudal bursa. Angiostrongylus has a ventrolateral ray arising independently from the mediolateral and posterolateral rays, which emerge as a single trunk, and is a parasite of the right heart and pulmonary artery of carnivores. In contrast, the subgenus Parastrongylus parasitizes rodents and has as taxonomic characteristics the lateral rays arising in a common trunk and a cleft at the same level. A third subgroup, parasitizing insectivores, was classified as belonging to the genus Stefanskostrongylus, comprising species with lateral rays similar to the subgenus Parastrongylus, but without the gubernaculum. Anderson (1978) accepted such systematic criteria but did not mention biological aspects such as host specificity or site of infection. Furthermore, Chabaud (1972) proposed eight different genera based on the morphology of the bursal rays, types of hosts and infection site. Ubelaker (1986) reorganized the Angiostrongylidae into six genera, based on bursal morphology and on specific host groups. Nevertheless, the host-specificity criteria need to be studied further since infection has been reported of non-human primates and carnivores by A. costaricensis (Miller et al., 2006).
In this chapter we accept the classification of Dougherty (1946). To date, 18 species of Angiostrongylus have been reported around the world. Four species have been described infecting carnivores: Angiostrongylus vasorum Baillet, 1866; Angiostrongylus raillieti Travassos, 1927; Angiostrongylus gubernaculatus Dougherty, 1946;and Angiostrongylus chabaudi Biocca, 1957. In rodents, 14 species have been described: Angiostrongylus taterone Baylis, 1928;A. cantonensis;Angiostrongylus sciuri Merdevenci, 1964;Angiostrongylus mackerrasae Bhaibulaya, 1968; Angiostrongylus sandarsae Alicata, 1968;Angiostrongylus petrowi Tarjymanova and Tschertkova, 1969; Angiostrongylus dujardini Drozdz and Doby, 1970;Angiostrongylus schmidti Kinsella, 1971;A. costaricensis;Angiostrongylus malaysiensis Bhaibulay and Cross, 1971;Angiostrongylus ryjikovi Jushkov, 1971; Angiostrongylus siamensis Ohbayashi, Kamiya, and Bhaibulaya, 1979;Angiostrongylus morerai Robles, Navone, and Kinsella, 2008;and Angiostrongylus lenzii Souza et al., 2009. Angiostrongylus costaricensis was described from three female specimens and one male specimen, recovered from a patient during surgery. Chabaud (1972) raised the species to the new genus Morerastrongylus, but this proposal was not accepted by Anderson (1978) in revising the classification of nematodes. A. costaricensis (Figs. 1-3; 7) is a filiform nematode. The cephalic end is round and the esophagus is club-shaped (Fig. 1). The copulatory bursa is slightly asymmetric and well developed. The dorsal ray is short and bifurcates into arms terminating in sharp tips. On its ventral side, behind its bifurcation, there is a conspicuous papilla. The lateral rays emerge from a common trunk, widely separated from the ventral rays, and the mediolateral and the posterolateral rays are fused in their proximal half. The anterolateral ray is thicker and separates form the common trunk just after its emergence from the trunk. The externodorsal ray arises close the lateral trunk and is well separated from the dorsal ray. Its distal end is knoblike. The ventral rays are fused except at the tips and the ventrolateral ray is slightly longer than the ventrolateral one. A gubernaculum is present with two branches that come together just before they terminate in the cloaca (Fig. 7). Behind the cloacal opening, there are three papillae. The spicules are slender, striated and of equal size. The caudal extremity of the female is roughly conical, with a small projection at the tip (Fig. 3) (Morera, 1973).
Angiostrongylus cantonensis was initially described as Pulmonema cantonensis Chen, 1935, a new genus, from specimens recovered from the lungs of naturally infected rats (Rattus norvegicus and Rattus rattus) collected in Canton, China. The adult worms of cantonensis 8) are characterized by a filiform body in both sexes, tapering at the anterior end. Females are larger and more robust than males. The cephalic vesicle is absent, the oral aperture is simple, circular and surrounded by six papillae (two dorsal, two lateral and two ventral) and two lateral amphids. The esophagus is claviform and the excretory pore is posterior to the esophagus (Fig. 4). The nerve ring is anterior to the middle of the esophagus, the male caudal bursa is small and slightly asymmetric, the ventroventral rays are smaller than the ventrolateral ones, with a common origin, bifurcated at the proximal half and do not reach the bursal margins. The dorsal ray is thick, bifurcating into three branches, with digititoform externodorsal rays separated at the base. The right mediolateral ray is thinner than the left one, with the right mediolateral and posterolateral rays bifurcating at the middle of the trunk and the left mediolateral and laterolateral rays at the distal third. The lateral rays arise from a common trunk, with the ventrolateral ray being cleft-shaped and smaller than the other lateral rays (Fig. 5). The gubernaculum is conspicuous and curved. Uterine tubules spiral around the blood-filled intestine, easily seen through the transparent cuticle. The tail is long and rounded without cuticle expansion and papillae, and is slightly ventrally curved ( Fig. 6) .

Life cycle of main species of Angiostrongylus infecting man
Species of Angiostrongylus cause a nematode infection in domestic dogs and wild mammals (Anderson, 1978). Some species can accidentally infect humans, causing characteristic clinical symptoms of the disease: A. cantonensis and A. costaricensis, which respectively cause eosinophilic meningoencephalitis and abdominal disease in humans (Graeff-Teixeira et al., 1991a;Wang et al., 2008). The biological cycle of these helminths requires an intermediate host, usually a snail, and a definitive host, most often a wild rodent. Humans participate in the biological cycle as accidental hosts, since the cycle does not complete itself in people.
Infection by A. costaricensis happens when the definitive host ingests the snail, which can be infected with third stage larvae (L 3 ), or food contaminated with snail mucus. The larvae migrate to the ileocecal region, penetrating the intestinal wall and entering the lymphatic vessels, where they molt twice before migrating to the mesenteric arteries, where they reach sexual maturity. The females release eggs, which are carried by the bloodstream, causing embolisms in the arterioles and capillaries of the intestinal wall. The eggs hatch when they reach the first larval stage (L 1 ), penetrating the intestinal lumen, where they are released in the feces. To continue the cycle, the L 1 larvae must be ingested or actively penetrate the tissue of the intermediate host (Thiengo, 1996). After 19 days of the initial infection, the larvae will have molted twice (passing through the L 2 and L 3 stages, the latter of which is the infective stage for the definitive host). The wild rodents become infected by ingesting parasitized snails, mainly the species Vaginulus (Sarasinula) plebeius in Costa Rica (Morera, 1970) or Phyllocaulis variegatus (Semper, 1885) in Brazil (Graeff-Teixeira et al., 1989). The main rodent hosts are Sigmodon hispidus (Morera et al., 1970) and Oligoryzomys nigripes (Graeff-Teixeira et al., 1990) in these two countries, respectively. The worms reach sexual maturity in the mesenteric arterioles of the rodent S. hispidus, where they lay their eggs. The L 1 larvae are found in the feces 24 days after experimental infection (Morera, 1973;Motta & Lenzi, 1995).
Humans become infected by eating raw infected snails or food contaminated by snail mucoid secretions containing L 3 larvae. Although the helminth reaches sexual maturity and releases eggs that stimulate a granulomatous reaction in the infected person intestinal wall due to their degeneration, it does not produce L 1 larvae, thus interrupting the biological cycle. www.intechopen.com The nematode A. cantonensis is commonly known as the lungworm because its niche in the adult phase is in the pulmonary arteries of the definitive host, in general the rodents R. rattus and R. norvegicus. In experimental infection of R. norvegicus, the female worm lays eggs inside the pulmonary arterioles, where they develop into the first-stage larvae (L 1 ), which then move to the interior of the alveoli. The larvae then migrate to the pharynx and are swallowed, pass through the gastrointestinal tract and are eliminated in the feces (Bhaibulaya, 1975;Yousif & Ibrahim, 1978). Land or freshwater snails are the principal intermediate hosts. They can become infected by ingestion of or penetration by L 1 larvae. The helminths then molt two times and become infective L 3 larvae, generally within 21 days after infection. Rats become infected by ingesting the intermediate hosts infected by L 3 larvae. These larvae then penetrate the intestinal wall and enter the bloodstream a few hours after being ingested. They reach the pulmonary circulation from the heart and are dispersed to various other organs by the arterial circulation. Many reach the brain and molt again, becoming L 4 larvae. The fifth molting into L 5 occurs in the subarachnoid space, from where after developing they migrate to the pulmonary arteries where they are found as of 25 days after infection. The worms then reach sexual maturity at around 35 days and the L 1 larvae can be found in the rodent's feces as of 42 days after the exposure to the previous generation of L 1 larvae (Weinstein et al., 1963;Bhaibulaya, 1975).
Humans become infected by eating raw or undercooked snails and slugs or through paratenic hosts (crabs, freshwater shrimps). In humans, the young larvae reach the brain, where they die rather than migrating further and terminating their development. This causes eosinophilic meningoencephalitis, which has neurological symptoms. Normally the infection is regenerative and does not kill the victim, but the parasitism can be serious enough to kill when there is massive exposure to infective L 3 larvae (Lima et al., 2009) (Fig. 9).

Endemic and exotic mollusks as intermediate hosts
The life cycle of A. cantonensis (Fig. 9) involves different species of terrestrial and freshwater gastropods as intermediate hosts. Mollusks become infected either by ingestion of L 1 present in the rat feces or by penetration of these larvae through the body wall or respiratory pores.
In the mollusk tissues the L 1 molts twice (L 2 and L 3 ) and the period necessary for the development is around 15 days. Details of the life cycle may be seen in Cheng & Alicata, 1965, Chao et al. 1987 (Wallace and Rosen,1969;Malek and Cheng, 1974;Caldeira et al., 2007;Thiengo et al., 2010).
It is noteworthy in the epidemiology of the transmission of A. cantonensis the occurrence of paratenic hosts (or carrier hosts) such as land crabs, freshwater prawns, frogs and planarians. Those are passive hosts where the parasite does not undergo any development. However, they play an important role as they improve parasite opportunities (in time and space) to get the definitive host.
In China where P. canaliculata and A.fulica are widespread in the south of the country, the number of cases of eosinophilic meningoencephalatis has been increasing, and the transmission is linked to both species (Lv et al., 2008(Lv et al., , 2009). In the last years, various outbreaks have been reported and the transmission in most of the cases was directely related to the consumption of P. canaliculata, considered currently the main cause of the spread of angiostrongyliasis in China (Lv et al. 2011).
The first cases of eosinophilic meningitis recorded to South America were to Brazil in 2007 and in 2008 and A. fulica was considered the vector for three out of the four reported cases. One of the cases reported to Pernambuco, Northeastern region, was attributed to the ingestion of undercooked P. lineata specimens (Caldeira et al., 2007;Lima et al., 2009;Thiengo et al., 2010). In fact, specimens of A. fulica have been found infected with A. cantonensis larvae from two of the main Brazilian regions, South and Southeast, in the last five years . Hence, the emergence of eosinophilic meningitis is a matter of concern in Brazil as it is currently experiencing the explosive phase of the invasion of A.fulica, recorded in 24 out the 26 states and the Federal District (Thiengo et al., 2007, Zanol et al., 2010.
The life cycle of A. costaricensis is quite similar to that of A. cantonensis, although paratenic hosts do not occur.
To continue the cycle, the L 1 larvae must be ingested or actively penetrate the tissue of the intermediate host (Thiengo, 1996). After 19 days of the initial infection, the larvae will have molted twice (passing through the L 2 and L 3 stages, the latter of which is the infective stage for the definitive host). The wild rodents become infected by ingesting parasitized snails, mainly the species Vaginulus (Sarasinula) plebeius in Costa Rica (Morera, 1970) or Phyllocaulis variegatus (Semper, 1885) in Brazil (Graeff-Teixeira et al., 1989;Motta & Lenzi, 1995). www.intechopen.com

Parasitism by Angiostrongylus costaricensis and Angiostrongylus cantonensis in naturally infected rat populations
The nematode A. costaricensis has little specificity for its definitive host. The main hosts involved in its life cycle in nature are rodents of the Cricetidae family, although rodents of the Heteromydae and Muridae families have also been found to be infected ( Table 2). The rodent S. hispidus has been indicated as the principal natural host due to its abundance, parasite prevalence rates in Panama and aspects of its ecology (Rodríguez et al., 2000).

Sigmodon hispidus
Cricetidae Costa Rica; Panamá; United States Morera, 1970;Tesh et al., 1973;Ubelaker & Hall, 1979 Rattus rattus Muridae Costa Rica; Panamá; Puerto Rico; Guadoulupe Morera, 1970;Tesh et al., 1973;Andersen et al., 1986;Juminer et al., 1993; Other mammals have also been found naturally infected, such as the coati Nasua narica bullata in Costa Rica, in which parasitism by A. costaricensis was confirmed after experimental infection of S. hispidus from isolation of L 1 larvae obtained from the host's feces, and in specimens of the marmoset Saguinus mystax imported from Peru after histopathological examination, which demonstrated the presence of the adult worm in the lamina propria of the host's mesenteric artery.
In Brazil, only two species of cricetids rodents, O. nigripes and Sooretamys angouya, are involved in transmission of A. costaricensis, in the Southern region of the country (Graeff-Teixeira et al., 1990). Although no evidence has been found of the participation of wild rodents in the Southeastern region (Graeff-Teixeira et al., 2010), there are various reports of abdominal angiostrongyliasis in the Midwestern and Southeastern regions (Pena et al., 1995;Magalhães et al., 1982).
In the Americas in general, the presence of R. rattus and R. norvegicus infected by A. cantonensis confirms the endemism of this zoonosis in Cuba, the United States, Jamaica, Puerto Rico, Dominican Republic, Haiti and Brazil (Table 3). The infection rate of these rodents is highly variable (Wang et al., 2008) and does not suggest specificity among the murids. Some findings of infected rodents in urban areas are associated with epidemiological investigations after the occurrence of cases of eosinophilic meningoencephalitis, such as in Cuba, Jamaica and Brazil Lindo et al., 2002;Simões et al., 2011).   and/or by recent invasion of the African snail A. fulica, some two decades ago (Thiengo et al., 2007).
In the United States (Ubelaker & Hall, 1979;Hulbert et al., 1992), Colombia (Malek, 1981), Panama (Tesh et al., 1973) and Caribbean islands (Juminer et al., 1993;Jeandel et al., 1998), reports of the presence of the parasite in the definitive host preceded the finding of cases of abdominal angiostrongyliais. It is thus possible that the distribution of this zoonosis in the Americas and the world at large is more ample than currently known.
Angiostrongyliais caused by A. cantonensis was originally reported in Asia. It has been postulated that this zoonosis spread to the Americas in the twentieth century , where there have been reports of sporadic outbreaks. The first report of eosinophilic meningoencephalitis occurred in Cuba , followed by United States (News et al., 1995), Jamaica (Barrow et al., 1996), Brazil (Lima et al., 2009) and more recently Ecuador (Dorta-Contreras et al., 2011). After the reports of parasitism in humans, the naturally infected definitive host was identified, except in Ecuador. In contrast, in Puerto Rico, Dominican Republic and Haiti, only the parasite infecting snails and/or rats has been reported (Andersen et al., 1986;Vargas et al., 1992;Raccurt et al., 2003), with no cases of diseased reported so far.

Diagnostic methods for detection of abdominal angiostrongyliasis and eosinophilic meningoencephalitis
Abdominal angiostrongyliasis is caused by the presence of A. costaricensis worms in the mesenteric arteries of the ileocecal plexus, where they cause a predominantly eosinophilic granulomatous reaction in the mesentery, intestinal wall and lymph nodes. Although it is not generally a serious disease and frequently clears up spontaneously, its evolution to occlusion or perforation of the intestine can lead to death (Palomino et al., 2008). The main clinical signs include acute eosinophilic abdominal pain and occasionally fever (Morera, 1995). Palpation of the tumoral mass in the lower right abdominal quadrant, vomiting and anorexia suggest parasitism, but definitive diagnosis is only confirmed by observation of the worms inside the arteries after histological examination of biopsy material (Graeff-Teixeira et al, 1991). Laboratory diagnosis includes the serological latex agglutination test (Morera & Amador, 1998), enzyme-linked immunosorbent assay (ELISA) Graeff-Teixeira et al., 1997) and indirect immunofluorescence assay (Abrahams-Sandi et al., 2011). Nevertheless, the choice of the antigen and specificity of the tests need improvement.
Presumptive diagnosis of angiostrongyliasis caused by A. cantonensis is mainly based on the clinical signs presented by the patients, which include eosinophilic meningitis, eosinophilic encephalitis and ocular angiostrongyliasis. The symptoms in general are not very specific and can include headache, vomiting, fever, history of paresthesia and neck stiffness (Sawanyawisuth & Sawanyawisuth, 2008). Results of laboratory analysis of the blood and cerebrospinal fluid showing readings of eosinophils above 10%, including serological tests, despite their low sensitivity (Eamsobhana & Yong, 2009), along with diagnosis by cerebral imaging, help to confirm the infection (Kampittaya et al., 2000). The information reported by the patient, such as ingestion of the intermediate host snail or raw or undercooked paratenic hosts, is important to substantiate the diagnosis of eosinophilic meningoencephalitis caused by A. cantonensis. Confirmation of the parasitism by observation of the worm in the cerebrospinal fluid is not common (Yii, 1976;Punyagupta et al., 1975). More recently, infection has been confirmed by the presence of the helminth's DNA in the cerebrospinal fluid by real-time polymerase chain reaction (PCR) (Lima et al., 2009). The inflammatory process of the subarachnoid space and meninges is accompanied by intense eosinophilia and associated with an elevation in the number of eosinophils in the peripheral blood and cerebrospinal fluid (Tseng, et al., 2011).

Treatment of the infections and prophylaxis
The use of anthelmintics such as diethylcarbamazine, thiabendazole and levamisole to treat abdominal angiostrongyliasis is not recommended, because it can induce erratic migration of the worms and/or worsening of the lesions due to the inflammatory response to the death of the helminths at the infection sites (Morera & Bontempo, 1985). Therefore, any time possible, the treatment of choice is surgery (Cépedes et al., 1967).
The main procedure to treat eosinophilic meningoencephalitis is based on reduction of the symptoms by the use of analgesics and/or corticoids and careful removal of the cerebrospinal fluid (CSF) at frequent intervals (Slom et al., 2003). The combined use of albendazole and prednisolone for two weeks has been shown to be safe and effective (Chotmongkol et al., 2004). Generally, infections caused by A. cantonensis are slight or selflimiting and the prognosis is good. In a few weeks most of the symptoms disappear and rarely leave prolonged effects.
Prophylaxis for angiostrongyliasis requires some precautions: (a) consume snails or animals that can be intermediate or paratenic hosts only after adequate cooking; (b) do not consume raw vegetables that have not been hygienized by soaking in a sodium hypochlorite solution; (c) control the populations of snail vectors and synanthropic rats near houses and in planted fields; and (d) provide information to people on the ways A. costaricensis and A. cantonensis are transmitted as well as the measures to follow to minimize the risk of infection by the parasite.

Conclusion
Under public health point of view, the spread of A. costaricensis and A. cantonensis in the New World and the presence of rats and snails in the peridomestic area poses substancial risk for future outbreaks. Therefore, reinforce the need to awareness the population about the risk of contracting angiostrongyliasis and healthcare providers should consider these parasites in the American continent to detect in time and adequate medical response. Moreover, surveillance and control of intermediate and definitive host as well as health education should be done to avoid human infections.
As for eosinophilic meningitis the epidemiology of its transmission has got importance for travel medicine currently. The increasingly widespread travel of people worldwide has led to the detection of many imported cases of this zoonosis and noteworthy for the differential diagnosis of neurological disease in travel medicine (Graeff-Teixeira et al., 2009). www.intechopen.com