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Public health importance of Angiostrongylus cantonensis and its relatives
PorositologyToday,vol.3, no. I2, I 987
367
Public Health Importance of Angiostrongylus cuntonensis and its Relatives J.H. Cross Species ofAngiostrongylus are fairly common nematode parasites ofa variety ofsmall mammals, but some species - particular/y A. cantonensis and A. costaricensis - are increasingly seen as human infections. The worms make use ofa range of aquatic, amphibious or terrestrial gastropod molluscs as intermediate hosts, which become infected by ingestion of eggs shed in the faeces of infected mamma/s. Paratenic hosts, including crustaceans, amphibians and reptiles, are known for most Angiostrongylus species, and can also be a source ofthe infective third-stage larvae that initiate mammalian infections. Approximately 20 species of Angiostrongy/us have been reported from insectivores, canines, felines and rodents, but few of the species infecting rodents appear to be pathogenic or potentially pathogenic to humans. A. costaricensis, recently revlewed by Moreral, is found in the Americas and causes abdominal anglostrongyliasls in man, while A. cantonensis IS responsible for eosinophilic meningitis or meningoencephalitis in widely scattered parts of the world (Fig. I ). Although not parasitologically confirmed, A. mackerrasse and A. malaysiensis may be responsible for eosinophllic meningitis in Australia and Southeast Asia, respectively. Human Infections A. cantonensis -the rat lung-worm was first found in rats in south China in 1935 and two years later In rats on Taiwan. The first parasitologically confirmed human infection was from Taiwan in 1945. The public health importance of cerebral angiostrongyliasis was not recognized however, until I962 when Rosen and his associates reported the parasite in the brain of a Filipino who died in Hawal?. The geographic distribution of A. cantonensis in rodents of the genera Rattus and Bandicota is extensive. Initial reports were from Asia and the Pacific Islands, and recently from the Ivory Coast in Africaj, Samoa and Fiji in the Pacific4,5, Puerto Rico m the Caribbean6, and Louisiana in the USAT. The parasite is now known from a very wide area ofthe tropics and subtropics (Fig. I). Larval and occasionally adult A. cantonensis have been recovered from the central nervous system (CNS), cerebrosplnal fluid (CSF), eyes and lungs of humans from Hawaii, Japan, mainland China, Taiwan, Thailand, Vietnam,
Malaysia, Indonesia, Vanuatu, American Samoa and the Ivory Coast. Unconfirmed human angiostrongyllasis has been reported from these countries, as well as from Tahiti and many other Pacific Islands, Hong Kong, the Philippines, Papua New Guinea, Australia, New Caledonla, India, La Reunion, Mauritius and Cuba. One suspected case IS reported from Puerto RICO where enzyme-linked lmmunosorbent assays detected high antlbody titres to A. cantonensis antigen in the patient’s serum (M. Marcial-Rojas and G.V. Hillyer, unpublished). Human Infections have not been documented for A. mackerrasse and A. malaysiensis. Eosinophilic meningitis is occaslonally reported from Australia where A. mackerrasse is found In rats, but the cause of the human disease has not been verified. A. malaysiensis has been reported from Malaysia, Thailand and Indonesia, but this species has not been recovered from humans with the disease. However, three cases of eosinophillc meningltts from Sarawak, Malaysia may have been caused by A. malaysiensis*. In experimental infections in monkeys, A. malaysiensis third-stage larvae were found to migrate to the CNS, but the infections were of short
P
duration. In comparative studies, A. cantonensis killed monkeys whereas A. malaysiensis did not9. Clinical Angiodrongyliasis Humans acquire angiostrongyliasis by ingestion of an intermediate or paratenic host infected with third-stage larvae of the parasite. A. cantonensis larvae move quickly from the intestinal tract to the CNS and damage the CNS tissue. Patients usually suffer from fever and headache, along with nausea, vomiting, stiff neck, paresthesias, paralysis of eye muscles and somnolence. The CSF contains leukocytes - most of which are eosinophils. Occasionally, young adult worms are found in the CSF. The incubation period is variable, with symptoms reported as early as one day to as long as 36 days. The severity of disease is associated with the number of third-stage larvae that reach the CNS and most of the pathology is attributed to dead worms. An inflammatory reaction develops with characteristic leukocytic infiltration and a preponderance of eosinophils in the meninges and CNS parenchyma. Granulomatous lesions, with necrotic debris, develop around dead worms. Taiwan’0 and Thailand’ I continue to report the disease, with the most severe cases occurring in Taiwan aborigines, from whom young adult worms are most often recovered from the CSF. Thailand rarely reports recovery of worms from CSF, but both areas
*.wmi
Fig. 1. Angiostrongylus cantonensis in humans (A), and in snails and/or rats (0).
*
PorosrtologyToday,vol. 3, no. 12, I 987
368 report recovery of worms from the eye. Blindness may develop, but it is a rare sequela. Deaths are usually the result of massive infections. In one fatal case on Taiwan, worms were found throughout the CNS, young adult and adult worms were found In the pulmonary arteries at autopsy, and more than 600 worms were recovered from the brain and spinal cord after soaking in saline overnight. In most cases however, the disease is self limited with complete recovery. Diagnosis is commonly based upon symptoms, and eosmophilic pleocytosls and an association with, or the ingestion of, an intermediate or paratenic host - a history of eating molluscs is frequently suggestive of infection. In most cases diagnosis is presumptive but is confirmed by the recovery of worms from the CSF, eye or CNS at autopsy. In recent years, physicians on Taiwan have improved their recovery rate by having the patient sit in an upright posltion for some time before sampling the CSF (E.R. Chen, unpublished). Serological tests support the clinical diagnoses4,12”3, and the recent development of monoclonal antibodies for the detectton of antigens in CSF seems to be promising (S.N. Chen, unpublished). Cysticercosis, gnathostomiasis and paragonimiasis must be also considered in the differential dlagnosis of eosinophillc meningitis. Although anthelmintics such as thlabendazole and levamisole have been used to treat angiostrongyliasis, the results have been questionable. Most clinicians in the Pacific and Asia recommend only supportive measures. Anthelminthics kill the worms, and since most of the pathology is attributed to dead or dying worms, the specific drugs should be used with caution. Epidemiology Angiostrongyliasls is acquired by the intentional or unintentional ingestion of third-stage larvae in raw or undercooked intermediate or paratenic hosts. Some infections have been acquired by drinking water in which larvae had been released from dead snails, and others by eating infected Intermediate or paratenic host for medicinal purposes. Habits, practices and customs of population groups in endemic areas are usually responsible for transmission. Most Infections in Taiwan occur In aboriginal children less than I4 years old and generally during the rainy months of the year. Aborigtnes in southern Taiwan eat the giant African snail, Achotina fulica (Fig. 2), more often than Chinese living on the Island. Furthermore, it is also suspected
Fig. 2. Achatina fulica, the giant African snail, is a common intermediate host ofAngiostrongylus cantonensis. Spread ofthe parasite was once attributed to disseminationofthis snail, but this idea no longer seems applicable in many new areas where the parasite, but not the snail, has been found. Instead, infected rats travelling as stowaways on ships moy be responsible for spreading the parasite.
that the Infections among children are acquired while playing in the kitchen or backyard where the snails are prepared for a meal. In Japan, most cases of eoslnophilic meningitis are from Okinawa and Mlyako Island where there IS a custom of using raw slugs, snails, and fresh toad and frog livers for the treatment of asthma and fever. In a rare occurrence, three US Marines ate raw A. fulico snails during survival training on Okinawa and all developed symptoms of eosinophilic meningitis14. In Thailand, the disease is commonly seen in adult males, and snails of the genus Pilo are considered the major source of infection. The snails are chopped into small pieces, mixed with vegetables and eaten raw. Males often eat the snail dishes while drinking alcohol. In Malaysia, A. fulrca is not eaten by humans, but Pilo scutota IS often eaten by Chinese and Indians to treat various illnesses. Malaysian slugs also shed thirdstage larvae in mucus on lettuce and other vegetation’s, and it has been suggested that contaminated lettuce may be a source of InfectIon. In the Pacific Islands, cases of angiostrongyliasis are linked to ingestion of fresh water shrimp or sauces prepared from the shrimp. In New Caledonia however, where raw molluscs and freshwater shrimp are not eaten, InfectIons are attributed to eating fresh vegetation containing infected planarians or tiny fragments of infected planarians on the vegetables16. An outbreak In Korean fishermen visiting American Samoa was
attributed to A. fulica which the fishermen purchased from a Samoan vendor4. In some areas of the Pacific, the Islanders eat land and coconut crabs which serve as transport hosts for A. cantonensrs. Without question, A. cantonensis is spreading. Several of the new areas in which A. cantonensrs has now been repot-ted were once considered free of the parasite. Rats In Egypt, Fiji, Samoa and other Pacific islands, as well as Puerto RICO and New Orleans were once reported to be free of A. cantonenSIS;now rat infections are documented and human infections are beginning to appear. Human infections usually follow rat infections, although It may take many years, as In mainland China where a human infection was first confirmed in 1984’7. Although spread of the parasite was once attributed to dissemination of the giant African snail’* (Fig. 2), this hypothesis does not appear applicable in the new areas, as the snail has not been found In many of these new locatlons. However, indigenous molluscs have been found either Infected or susceptible to Infection. Rats, travelling as stowaways on ships, may be an important mode of spread of the parasite. Terrestrial molluscs seem to be universally susceptible and once Infected rats arrive at a new port, indigenous molluscs easily become infected. Since many societies do not eat raw snails, infections may be acquired by accidental means: therefore, awareness of the presence of the disease by physicians and public health officials IS imperative.
Parasitology Today, vol. 3, no. I2,
I 987
References Morera, P. ( I 985) Porasitoi. Today I, l73- I75 Rosen, L., Chappell, R., Laquer, G.L., Wallance, G.D. and Welnsteln. P.P. ( 1982) /. Am. Med. Assoc. I79,62C-624 Nozals, J.P., Moreau, J,, Morller, G., Kouame. J, and Boucet, J. ( 1980) Bull. Sot. Pothol. Exot. Fil. 73, 179-182 Kllks, M.M., Kroenke, K. and Hardman, J.M. (1982)Amj Trop.Med.Hyg.31, I 114-l 122 Uchlkawa, R., Takagl, M., Matayoshl, S. and Sato, A. ( I 984)j Helmmthol. SE,23 I-234 Anderson, E., Gubler, D.J., Sorensen, K., Beddard. J,and Ash, L. (I 986)Am 1. Trap. Med. Hyg. 32,3 19-322 Campbell, B.G. and LIttIe, M.D. (I 986) Annu. Meet. Am. Sot. Trop. Med. Hyg , Denver, CO, Dec.7-I I, 1986 Llm. B.L. and Ramachandran. C.P. (1979) In
369 Angiostrongyliosrs in Eastern Asia and Australra (Cross, J.H., ed.), pp. 26-48, NAMRU-2-SP-44 9 Cross, J.H. ( 1979) In Angiostrongyliasis ,n Eastern Asia and Australia (Cross, J.H., ed.), pp. I I 8127, NAMRU-2-SP-44 IO Cheng, C.W., Sato. J. and Chen, E.R.
(I 984)
01987.Eisewr
Publrattons, CambrIdge
0 l69-4758/87/80200
C.C. Thomas, SprIngfield
RyukyuMed. J. 7, I-9
II
Jaroonvesama, N.. Charoenlarp, K., Buranasln, P.. Zaraspe, G. and Cross, J.H. (I 985)Southeast Asian]. Trop. Public Health 16, I IO- I I 2 I2 Cross, J.H. and Chl, J.C.H. (I 982) Southeast Asian]. Trop. Public He&h I3,73-76 I3 Ko, R.C., Chlu, M.C., Kum, W. and Chan. S.H. (1984) Trans.R. Sot. Trap. Med. Hyg. 78, 354-
355 I4 Cross, J.H. (I 978) SoutheastAsian/. Trop. Public Heolth9. 161-170 I5 Heyneman, D. and Llm. B.L. (1967) 158, 1057-1058
Scrence
Interaction of Malaria with Mosquitoes
Sir-We read with great interest the recent article on the pathology of malaria-Infected mosquitoes by colleague Maler and co-workers’. Although our experience IS ltmlted to the infection ofAnophe/es stephensi and An. gambiae with Plasmodium folcrparum, we would like to comment on three aspects of this article. Firstly, as stated, exflagellation occurs wlthln I O-l 2 minutes at 26°C inslde the mosquito midgut aided by mosquito factors but probably not by factors released by digestjon of the blood meal since digestion normally begins several hours later2. Furthermore, we cannot confirm that either exflagellation or the development of the ookinetes in any way leads to morbidity or mortality of the mosquito. Secondly, the mode of penetratton of the mosquito midgut IS not as clearcut as stated. Maler et al. I compare the behavlour of ooklnetes with merozoltes which penetrate red cells by invaglnatlon of the cell membrane3. They suggest that ooklnetes, in contrast, localize directly In the midgut cell cytoplasm without a parasltophorous vacuole. In this way the parasite would have to break through two membranes, firstly on enteringthe cell and secondlyon exltlng. This penetratton process might Indeed damage the eplthelial cell layer and be responsible for early death of mosquitoes as observed with P. berghei. But when compared with sporozoltes and merozoites, which both penetrate their host cells by lnvagtnation of the plasmalemma and develop lntracellularly In a parasitophorous vacoule3,4, It seems InconsIstent for the ookinete to break through a cell only to exit again and start development extracellularly. Indeed for P. berghe,, ectoplc development (I.e. not extracellularly beneath the basal lamina) has been occaslonally describeds, although this has never been observed for P. folciparum6 whose ookinetes localize beneath the basal
I6 Ash, L.R. ( 1976) Rev. Biol. Jrop. 24, I63- I74 I7 Yang, S.Q. et al. ( 1984) Chinon Univ. Med. College(Guongzhou,PRC): Case Rep., pp. l-8 I8 Ala&a, J. and Jlndrak, K. (I 970) Angrostrongylosisin the Pacific ond SoutheastAsia IO5 pp.,
Fig. I. Ookinete (young oocyst) ofPlasmodium falciparum 48 h after the infective bloodmeal localized beneath the basal /amino at the border oftwo midgut epithelial cells ofan A. gambiae mosquito. Bar - I pm. (Bl - basal lamina; BM - basal membrane; EC - epithelial cell; 0 - ookinete/oocyst) lamlna (Fig. I ) apparently after taking an intercellular route7. Finally, we have compared the mortality of heavily infected An. stephensi and An. gambiae with those given an uninfected bloodmeal. Our mosquitoes are not malntalned under sterile conditions, and we could find no significantly higher mort&y of Infected mosquitoes when compared to mosquitoes given an uninfected blood meal. J.F.C.M. Meis 1. Ponnudurai Department of Medical Parasitology Univerxty of Nljmegen 6500 HB, The Netherlands
Reply Sir - We divided
the developmental
time of
Plasmodium in the mosquito in five phases to explain where we would expect damage to the host. The first of these phases is the time from exflagellation to ookinete formation where antibodies, leucocytes from the vertebrate blood, erythrocyte factors, mosquito factors, enzymes and perhaps other unknown factors are active. We think that this phase needs more attention and future work will show if, as we speculate, the presence of the parasites may influence the mosquito at that time.
John Cross is Professor of Preventive Medicine at the Unfformed Services University of the Health Sciences, 4301 Iones Bridge Road, Bethesda, MD 208 14-4799, USA. The opinions or assertrons contained herein are the private ones of the author and are not to be construed as official or reflectrng the views of the United States Deportment of Defense or the Unifirmed Services University of the Health Sciences.
The apparent behaviour of the ookinete in the mosquito midgut cell was demonstrated by Fig. I of our review 1.The ookinete is situated In the cytoplasm and not engulfed in a parasitophorous vacoule as are merozoites in red blood cells. We never found ookinetes migrating extracellularly through the gut wall-instead they have to break through two membranes, entering and exiting the midgut cell. This means there is a high risk of damaging these cells8,9 especially when masses of bacteria are present at the same timelo,’ I, which is often the case in mosquitoes which are not bred under sterile conditions. This mode of host-cell penetration IS similar to that of sporozoites invading the salivary gland cellsl2. After penetration of these cells by sporozoites. the basement membrane is found to be disrupted and the cytoplasm is vesiculated. Often the infected cells are deformed and swollen. To summarize we believe that all stages of malaria parasites penetrate the host cells, but there are two different modes of invasion: in the insect host the parasites (ookinetes and sporozoites) break through the host cell membrane; in the vertebrate host the parasites penetrate by invaginatlon (see also Ref. I 3). Ponnudurai, Meis and co-workers7,14 presented some very interesting pictures of migrating ookinetes of P. fo/ciparum~4~~5, but as is often the case with EM studies the course of the cell membrane IS not represented completely. Further studtes on this aspect of parasite life cycle thus seem to be necessary, especially in view of the unusual ‘ectopic’ oocyst development described in mosquitoes infected with P. bergheis. Perhaps different penetrating mechanisms occur in different systems. Prevention of damage to the host cells by passing in between the cells could appear as the behaviour of a well-adapted parasite species, whereas a species penetrating intracellularly seems less well adapted. W. Maier lnstltut fur Medizlnlsche Parasltologle Unlversltdt Bonn Sigmund Freud Str. 25 5300 Bonn I FRG
367
Public Health Importance of Angiostrongylus cuntonensis and its Relatives J.H. Cross Species ofAngiostrongylus are fairly common nematode parasites ofa variety ofsmall mammals, but some species - particular/y A. cantonensis and A. costaricensis - are increasingly seen as human infections. The worms make use ofa range of aquatic, amphibious or terrestrial gastropod molluscs as intermediate hosts, which become infected by ingestion of eggs shed in the faeces of infected mamma/s. Paratenic hosts, including crustaceans, amphibians and reptiles, are known for most Angiostrongylus species, and can also be a source ofthe infective third-stage larvae that initiate mammalian infections. Approximately 20 species of Angiostrongy/us have been reported from insectivores, canines, felines and rodents, but few of the species infecting rodents appear to be pathogenic or potentially pathogenic to humans. A. costaricensis, recently revlewed by Moreral, is found in the Americas and causes abdominal anglostrongyliasls in man, while A. cantonensis IS responsible for eosinophilic meningitis or meningoencephalitis in widely scattered parts of the world (Fig. I ). Although not parasitologically confirmed, A. mackerrasse and A. malaysiensis may be responsible for eosinophllic meningitis in Australia and Southeast Asia, respectively. Human Infections A. cantonensis -the rat lung-worm was first found in rats in south China in 1935 and two years later In rats on Taiwan. The first parasitologically confirmed human infection was from Taiwan in 1945. The public health importance of cerebral angiostrongyliasis was not recognized however, until I962 when Rosen and his associates reported the parasite in the brain of a Filipino who died in Hawal?. The geographic distribution of A. cantonensis in rodents of the genera Rattus and Bandicota is extensive. Initial reports were from Asia and the Pacific Islands, and recently from the Ivory Coast in Africaj, Samoa and Fiji in the Pacific4,5, Puerto Rico m the Caribbean6, and Louisiana in the USAT. The parasite is now known from a very wide area ofthe tropics and subtropics (Fig. I). Larval and occasionally adult A. cantonensis have been recovered from the central nervous system (CNS), cerebrosplnal fluid (CSF), eyes and lungs of humans from Hawaii, Japan, mainland China, Taiwan, Thailand, Vietnam,
Malaysia, Indonesia, Vanuatu, American Samoa and the Ivory Coast. Unconfirmed human angiostrongyllasis has been reported from these countries, as well as from Tahiti and many other Pacific Islands, Hong Kong, the Philippines, Papua New Guinea, Australia, New Caledonla, India, La Reunion, Mauritius and Cuba. One suspected case IS reported from Puerto RICO where enzyme-linked lmmunosorbent assays detected high antlbody titres to A. cantonensis antigen in the patient’s serum (M. Marcial-Rojas and G.V. Hillyer, unpublished). Human Infections have not been documented for A. mackerrasse and A. malaysiensis. Eosinophilic meningitis is occaslonally reported from Australia where A. mackerrasse is found In rats, but the cause of the human disease has not been verified. A. malaysiensis has been reported from Malaysia, Thailand and Indonesia, but this species has not been recovered from humans with the disease. However, three cases of eosinophillc meningltts from Sarawak, Malaysia may have been caused by A. malaysiensis*. In experimental infections in monkeys, A. malaysiensis third-stage larvae were found to migrate to the CNS, but the infections were of short
P
duration. In comparative studies, A. cantonensis killed monkeys whereas A. malaysiensis did not9. Clinical Angiodrongyliasis Humans acquire angiostrongyliasis by ingestion of an intermediate or paratenic host infected with third-stage larvae of the parasite. A. cantonensis larvae move quickly from the intestinal tract to the CNS and damage the CNS tissue. Patients usually suffer from fever and headache, along with nausea, vomiting, stiff neck, paresthesias, paralysis of eye muscles and somnolence. The CSF contains leukocytes - most of which are eosinophils. Occasionally, young adult worms are found in the CSF. The incubation period is variable, with symptoms reported as early as one day to as long as 36 days. The severity of disease is associated with the number of third-stage larvae that reach the CNS and most of the pathology is attributed to dead worms. An inflammatory reaction develops with characteristic leukocytic infiltration and a preponderance of eosinophils in the meninges and CNS parenchyma. Granulomatous lesions, with necrotic debris, develop around dead worms. Taiwan’0 and Thailand’ I continue to report the disease, with the most severe cases occurring in Taiwan aborigines, from whom young adult worms are most often recovered from the CSF. Thailand rarely reports recovery of worms from CSF, but both areas
*.wmi
Fig. 1. Angiostrongylus cantonensis in humans (A), and in snails and/or rats (0).
*
PorosrtologyToday,vol. 3, no. 12, I 987
368 report recovery of worms from the eye. Blindness may develop, but it is a rare sequela. Deaths are usually the result of massive infections. In one fatal case on Taiwan, worms were found throughout the CNS, young adult and adult worms were found In the pulmonary arteries at autopsy, and more than 600 worms were recovered from the brain and spinal cord after soaking in saline overnight. In most cases however, the disease is self limited with complete recovery. Diagnosis is commonly based upon symptoms, and eosmophilic pleocytosls and an association with, or the ingestion of, an intermediate or paratenic host - a history of eating molluscs is frequently suggestive of infection. In most cases diagnosis is presumptive but is confirmed by the recovery of worms from the CSF, eye or CNS at autopsy. In recent years, physicians on Taiwan have improved their recovery rate by having the patient sit in an upright posltion for some time before sampling the CSF (E.R. Chen, unpublished). Serological tests support the clinical diagnoses4,12”3, and the recent development of monoclonal antibodies for the detectton of antigens in CSF seems to be promising (S.N. Chen, unpublished). Cysticercosis, gnathostomiasis and paragonimiasis must be also considered in the differential dlagnosis of eosinophillc meningitis. Although anthelmintics such as thlabendazole and levamisole have been used to treat angiostrongyliasis, the results have been questionable. Most clinicians in the Pacific and Asia recommend only supportive measures. Anthelminthics kill the worms, and since most of the pathology is attributed to dead or dying worms, the specific drugs should be used with caution. Epidemiology Angiostrongyliasls is acquired by the intentional or unintentional ingestion of third-stage larvae in raw or undercooked intermediate or paratenic hosts. Some infections have been acquired by drinking water in which larvae had been released from dead snails, and others by eating infected Intermediate or paratenic host for medicinal purposes. Habits, practices and customs of population groups in endemic areas are usually responsible for transmission. Most Infections in Taiwan occur In aboriginal children less than I4 years old and generally during the rainy months of the year. Aborigtnes in southern Taiwan eat the giant African snail, Achotina fulica (Fig. 2), more often than Chinese living on the Island. Furthermore, it is also suspected
Fig. 2. Achatina fulica, the giant African snail, is a common intermediate host ofAngiostrongylus cantonensis. Spread ofthe parasite was once attributed to disseminationofthis snail, but this idea no longer seems applicable in many new areas where the parasite, but not the snail, has been found. Instead, infected rats travelling as stowaways on ships moy be responsible for spreading the parasite.
that the Infections among children are acquired while playing in the kitchen or backyard where the snails are prepared for a meal. In Japan, most cases of eoslnophilic meningitis are from Okinawa and Mlyako Island where there IS a custom of using raw slugs, snails, and fresh toad and frog livers for the treatment of asthma and fever. In a rare occurrence, three US Marines ate raw A. fulico snails during survival training on Okinawa and all developed symptoms of eosinophilic meningitis14. In Thailand, the disease is commonly seen in adult males, and snails of the genus Pilo are considered the major source of infection. The snails are chopped into small pieces, mixed with vegetables and eaten raw. Males often eat the snail dishes while drinking alcohol. In Malaysia, A. fulrca is not eaten by humans, but Pilo scutota IS often eaten by Chinese and Indians to treat various illnesses. Malaysian slugs also shed thirdstage larvae in mucus on lettuce and other vegetation’s, and it has been suggested that contaminated lettuce may be a source of InfectIon. In the Pacific Islands, cases of angiostrongyliasis are linked to ingestion of fresh water shrimp or sauces prepared from the shrimp. In New Caledonia however, where raw molluscs and freshwater shrimp are not eaten, InfectIons are attributed to eating fresh vegetation containing infected planarians or tiny fragments of infected planarians on the vegetables16. An outbreak In Korean fishermen visiting American Samoa was
attributed to A. fulica which the fishermen purchased from a Samoan vendor4. In some areas of the Pacific, the Islanders eat land and coconut crabs which serve as transport hosts for A. cantonensrs. Without question, A. cantonensis is spreading. Several of the new areas in which A. cantonensrs has now been repot-ted were once considered free of the parasite. Rats In Egypt, Fiji, Samoa and other Pacific islands, as well as Puerto RICO and New Orleans were once reported to be free of A. cantonenSIS;now rat infections are documented and human infections are beginning to appear. Human infections usually follow rat infections, although It may take many years, as In mainland China where a human infection was first confirmed in 1984’7. Although spread of the parasite was once attributed to dissemination of the giant African snail’* (Fig. 2), this hypothesis does not appear applicable in the new areas, as the snail has not been found In many of these new locatlons. However, indigenous molluscs have been found either Infected or susceptible to Infection. Rats, travelling as stowaways on ships, may be an important mode of spread of the parasite. Terrestrial molluscs seem to be universally susceptible and once Infected rats arrive at a new port, indigenous molluscs easily become infected. Since many societies do not eat raw snails, infections may be acquired by accidental means: therefore, awareness of the presence of the disease by physicians and public health officials IS imperative.
Parasitology Today, vol. 3, no. I2,
I 987
References Morera, P. ( I 985) Porasitoi. Today I, l73- I75 Rosen, L., Chappell, R., Laquer, G.L., Wallance, G.D. and Welnsteln. P.P. ( 1982) /. Am. Med. Assoc. I79,62C-624 Nozals, J.P., Moreau, J,, Morller, G., Kouame. J, and Boucet, J. ( 1980) Bull. Sot. Pothol. Exot. Fil. 73, 179-182 Kllks, M.M., Kroenke, K. and Hardman, J.M. (1982)Amj Trop.Med.Hyg.31, I 114-l 122 Uchlkawa, R., Takagl, M., Matayoshl, S. and Sato, A. ( I 984)j Helmmthol. SE,23 I-234 Anderson, E., Gubler, D.J., Sorensen, K., Beddard. J,and Ash, L. (I 986)Am 1. Trap. Med. Hyg. 32,3 19-322 Campbell, B.G. and LIttIe, M.D. (I 986) Annu. Meet. Am. Sot. Trop. Med. Hyg , Denver, CO, Dec.7-I I, 1986 Llm. B.L. and Ramachandran. C.P. (1979) In
369 Angiostrongyliosrs in Eastern Asia and Australra (Cross, J.H., ed.), pp. 26-48, NAMRU-2-SP-44 9 Cross, J.H. ( 1979) In Angiostrongyliasis ,n Eastern Asia and Australia (Cross, J.H., ed.), pp. I I 8127, NAMRU-2-SP-44 IO Cheng, C.W., Sato. J. and Chen, E.R.
(I 984)
01987.Eisewr
Publrattons, CambrIdge
0 l69-4758/87/80200
C.C. Thomas, SprIngfield
RyukyuMed. J. 7, I-9
II
Jaroonvesama, N.. Charoenlarp, K., Buranasln, P.. Zaraspe, G. and Cross, J.H. (I 985)Southeast Asian]. Trop. Public Health 16, I IO- I I 2 I2 Cross, J.H. and Chl, J.C.H. (I 982) Southeast Asian]. Trop. Public He&h I3,73-76 I3 Ko, R.C., Chlu, M.C., Kum, W. and Chan. S.H. (1984) Trans.R. Sot. Trap. Med. Hyg. 78, 354-
355 I4 Cross, J.H. (I 978) SoutheastAsian/. Trop. Public Heolth9. 161-170 I5 Heyneman, D. and Llm. B.L. (1967) 158, 1057-1058
Scrence
Interaction of Malaria with Mosquitoes
Sir-We read with great interest the recent article on the pathology of malaria-Infected mosquitoes by colleague Maler and co-workers’. Although our experience IS ltmlted to the infection ofAnophe/es stephensi and An. gambiae with Plasmodium folcrparum, we would like to comment on three aspects of this article. Firstly, as stated, exflagellation occurs wlthln I O-l 2 minutes at 26°C inslde the mosquito midgut aided by mosquito factors but probably not by factors released by digestjon of the blood meal since digestion normally begins several hours later2. Furthermore, we cannot confirm that either exflagellation or the development of the ookinetes in any way leads to morbidity or mortality of the mosquito. Secondly, the mode of penetratton of the mosquito midgut IS not as clearcut as stated. Maler et al. I compare the behavlour of ooklnetes with merozoltes which penetrate red cells by invaglnatlon of the cell membrane3. They suggest that ooklnetes, in contrast, localize directly In the midgut cell cytoplasm without a parasltophorous vacuole. In this way the parasite would have to break through two membranes, firstly on enteringthe cell and secondlyon exltlng. This penetratton process might Indeed damage the eplthelial cell layer and be responsible for early death of mosquitoes as observed with P. berghei. But when compared with sporozoltes and merozoites, which both penetrate their host cells by lnvagtnation of the plasmalemma and develop lntracellularly In a parasitophorous vacoule3,4, It seems InconsIstent for the ookinete to break through a cell only to exit again and start development extracellularly. Indeed for P. berghe,, ectoplc development (I.e. not extracellularly beneath the basal lamina) has been occaslonally describeds, although this has never been observed for P. folciparum6 whose ookinetes localize beneath the basal
I6 Ash, L.R. ( 1976) Rev. Biol. Jrop. 24, I63- I74 I7 Yang, S.Q. et al. ( 1984) Chinon Univ. Med. College(Guongzhou,PRC): Case Rep., pp. l-8 I8 Ala&a, J. and Jlndrak, K. (I 970) Angrostrongylosisin the Pacific ond SoutheastAsia IO5 pp.,
Fig. I. Ookinete (young oocyst) ofPlasmodium falciparum 48 h after the infective bloodmeal localized beneath the basal /amino at the border oftwo midgut epithelial cells ofan A. gambiae mosquito. Bar - I pm. (Bl - basal lamina; BM - basal membrane; EC - epithelial cell; 0 - ookinete/oocyst) lamlna (Fig. I ) apparently after taking an intercellular route7. Finally, we have compared the mortality of heavily infected An. stephensi and An. gambiae with those given an uninfected bloodmeal. Our mosquitoes are not malntalned under sterile conditions, and we could find no significantly higher mort&y of Infected mosquitoes when compared to mosquitoes given an uninfected blood meal. J.F.C.M. Meis 1. Ponnudurai Department of Medical Parasitology Univerxty of Nljmegen 6500 HB, The Netherlands
Reply Sir - We divided
the developmental
time of
Plasmodium in the mosquito in five phases to explain where we would expect damage to the host. The first of these phases is the time from exflagellation to ookinete formation where antibodies, leucocytes from the vertebrate blood, erythrocyte factors, mosquito factors, enzymes and perhaps other unknown factors are active. We think that this phase needs more attention and future work will show if, as we speculate, the presence of the parasites may influence the mosquito at that time.
John Cross is Professor of Preventive Medicine at the Unfformed Services University of the Health Sciences, 4301 Iones Bridge Road, Bethesda, MD 208 14-4799, USA. The opinions or assertrons contained herein are the private ones of the author and are not to be construed as official or reflectrng the views of the United States Deportment of Defense or the Unifirmed Services University of the Health Sciences.
The apparent behaviour of the ookinete in the mosquito midgut cell was demonstrated by Fig. I of our review 1.The ookinete is situated In the cytoplasm and not engulfed in a parasitophorous vacoule as are merozoites in red blood cells. We never found ookinetes migrating extracellularly through the gut wall-instead they have to break through two membranes, entering and exiting the midgut cell. This means there is a high risk of damaging these cells8,9 especially when masses of bacteria are present at the same timelo,’ I, which is often the case in mosquitoes which are not bred under sterile conditions. This mode of host-cell penetration IS similar to that of sporozoites invading the salivary gland cellsl2. After penetration of these cells by sporozoites. the basement membrane is found to be disrupted and the cytoplasm is vesiculated. Often the infected cells are deformed and swollen. To summarize we believe that all stages of malaria parasites penetrate the host cells, but there are two different modes of invasion: in the insect host the parasites (ookinetes and sporozoites) break through the host cell membrane; in the vertebrate host the parasites penetrate by invaginatlon (see also Ref. I 3). Ponnudurai, Meis and co-workers7,14 presented some very interesting pictures of migrating ookinetes of P. fo/ciparum~4~~5, but as is often the case with EM studies the course of the cell membrane IS not represented completely. Further studtes on this aspect of parasite life cycle thus seem to be necessary, especially in view of the unusual ‘ectopic’ oocyst development described in mosquitoes infected with P. bergheis. Perhaps different penetrating mechanisms occur in different systems. Prevention of damage to the host cells by passing in between the cells could appear as the behaviour of a well-adapted parasite species, whereas a species penetrating intracellularly seems less well adapted. W. Maier lnstltut fur Medizlnlsche Parasltologle Unlversltdt Bonn Sigmund Freud Str. 25 5300 Bonn I FRG