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The discovery of Angiostrongylus cantonensis as a cause of human eosinophilic meningitis
Parasitology Today, vol. 7, no. 6, 1991
6 Kemp, D.]., Coppel, FLL. and Anders, R.F. (I 987)Annu. Rev M~croblal. 4 I, 181-208 7 Beard, CA, Wnghtsman, RA and Manning, I.E (I 988)MoLBi~hem. Parasitol. 28, 227-234 8 Van Voorhis, W.C. and Eisen H. (I 989)] Exp. Med. 169,641~$52 9 Requena,J.M et el. (1988)Nucleic Acids Res. 16, 1393-1406 10 Engman,D.M. et al. (1989)Mol. Biochem.Parasstal 37,285-288 I I Schllman,A.G. et al (I 990) NucleicAods Res. 18, 3399 12 ,/kslund,Let al ( 1991) Mal. fhochem Parasitol. 45, 345-348 13 Pollevick,G.D. et al. Mol. Biochem Paras~toL(in press) 14 Iba6ez,C.F et al ( 1988)Mal.B~ochem Parasitol 30, 27~-34 15 Lafa~lle,J.J.etal. (I 989) IVlol Biochem. Paras~tol. 35, 127-136 16 Levin, M.I. et al (1989)Am..I. Trap. Meal IHyg 4 I, 530-539 17 Haft, D.F et al (1989) Infect Immun. 57,
1959-1967 18 Peterson, D.S. Fours, D.L and Mann,ng,J.E. (1989)E.MBO]. 8,3911-3916 19 Kahn, S., Van Voorhis. W.C. and Eisen, H. (1990)]. Exp Me(/ 172,589-597 20 Schneider. A. et aL (1988) Science 241, 459462 21 Affranchino, J.L. el al (1989) Mol Biochem.
Parasital. 34,221-228
151
22 Bontempi, E, Mart,nez, J. and Cazzulo, J.J. (I 989)M01.B~ochem.Parasitol 33, 43-47 23 Souto-Padr6n, T. et aL (1990)], Cell Sci. 96, 485-490 24 Ruiz,A.M. et al (1985)ActaTrap 42, 299-309 25 Piras, M.M., Rodriguez, O.O. and Piras, R. (1981 ) EXp.Parasltol. S I, 59-73 26 Souto-Padr6n, T. et aL (1989) Eur.]. Cell Biol. 50, 272-278 27 Murta, A.C.M. etal. (1990)M01. Biochem.Parasttol. 43, 27-38 28 Scharfste~n,J. et al. (1985)Am.] Trap.Med Hyg 34, 1153-1159 29 Cazzulo,J.I.et al ( 1989)M01. Biochem Parasitol.
33, 33-42 30 Cazzulo,J.J.et aL (1990) Biochtm. Bnaphys.Acta 1037, 186-191 31 Z~ngales,B. etal. (1985)MoL Biachem.Parasttol. 16,21-34 32 QuaissL AM, Cornette, J. and Capron, A. ( 1986)M01 Biochem. Parasltol. 19,201-21 I ]3 Engman,DM. etal. (1989)]. B~ol. Chem. 264, 18627-1863 I 34 Roditi,I. Carrington, M. and Turner, M. (1987) Nature 325, 272-274 35 Wallis,A.E. and McMaster,W.R. ( 1987)]. Exp. Mad 166, 1814-1824 36 Reyes, M.B. etal. (1990) Proc. Ned Acad. So. USA 87, 2846-2850 37 Paranhos,GS. et al (I 990) Exp. ParasitoL 7 I, 284-293 38 Israelski, D.M., Sadler, R and Araujo, F.G.
(I 988)Am.] Trap.Meal Hyg. 78,445-455 39 Basombrio, M.A. and Arredes, H. (1987) ]. Parositol.73,236-238 40 Okanla, E.O., Stumpf, J.L. and Dusanlc, D.G. (1982)1nt]. ParasitoL 12, 251-256 41 Scott, M.T. and Snary, D. (1979) Nature 282, 73-74 42 Ruiz,AM. etal. (1990)Mol. Biochem. Paras~tol.
39, 117-126 43 Peterson,DS., Wrightsman,R.A and Manning, J.E(1986)Nature 322,566-568 44 Takle, G.B. etal. (1989)M01. Biochem Parositol. 37, 57-64 45 Eakin, A.E. et al (1990)Mol. Biochem Paros~tol.
39, 14 46 Lizardi. P. et el. (1985) Vaccines (Lerner, T.J.. Chanock, C. and Brown, DD., eds), pp 67-70, Cold SpringHarbor Laboratory 47 Bua,J.et el. ( 1991) Exp. Parasltol. 72, 54-62 48 Wrightsman, RA., Leon, W. and Manning,J.E. (1986)Infect. Immun. 53,235-239 49 Macina, R.A et al (1989) FE.BS Lett. 257, 365-368
Carlos Frasch and Juan Cazzulo are at the Instituto de Investlgaciones Bioquimicas, Fundoclan Campomar, Antonio Machodo 15 I. 1405 Buenos A~res, Argentina and Lena/~slund and UIf Pettersson are at the Department ofMedical Genetics, Biomedical Center, University otUppsala, Uppsala, Sweden.
The Discovery of Angiostrongylus cantonensis as a Cause of Human Eosinophilic Meningitis J.E. Alicata The theoretical and subsequent confirmation in 1961 of the rot lungworm, A n g i o s t r o n g y l u s cantonensis, as the causative a g e n t of eosinc$)hilic meningitis is one of the remarkable parasitological findings of the twentieth century. Here, Joseph Alicota briefly summarizes the early history a n d his epidemiologicol studies on the relationship between the parasite a n d the epidemics of encephalitis that swept through O c e a n i a after the Second World War.
During 1944 in Taiwan, Nomura and Lin ~ were the first to find young adult nematodes, which they called H a e m o strongylus rotti, in the cerebrospinal fluid recovered from a male patient with symptoms of meningitis, They did not definitely associate this parasite with the disease but it was suspected that the raw food eaten by the patient before the onset of illness might have been contaminated by rats. Their report, written in Japanese, was only translated into English in 1964 (Ref. 2) after it was suspected that the nematode A. can,:onensis was the (~)[99I, k,sewerSoeeceP(Jbhst~trsLtd (UK)01694707/9It$0200
cause of eosinophilic meningitis in Tahiti 3 5 In 1948, Bailey6 and t w o associates of the United States Naval Medical Institute were assigned to the island of Ponape in Micronesia to identify an epidemic form of encephalitis but their clinical and laboratory investigations failed to identify the etiological agent. In 1955, Mackerras and Sandars 7 worked on the life history of the rat lungworm, A. cantonensis, and found that garden snails and slugs served as intermediate hosts. On infection of the definitive rat host the larvae obligatorily migrate to the brain and, while there, the growing parasites produce an extensive eosinophilic inflammatory reaction, Four weeks later, the worms migrate to the lungs, where they reach sexual maturity (Fig. I). During 1961, in an epidemiological study of eosinophilic meningitis in Tahiti, Rosen, Laigret and Bories 8 theorized that the disease was caused by a helminth parasite of the skipjack tuna or other pelagic fish eaten raw in the area. However, it soon occurred to me that
this was unlikely to be the case in Hawaii, where many local people habitually consume raw fish and show no evidence of meningitis. I reasoned also that ifa w o r m parasite was the cause of human encephalitis, it had to be one that obligatorily invaded the central nervous system of mammals. The only nematode in the Pacific that met that description was A. cantonensis. In 1960 this parasite had been found by Ash 9 for the first time in Hawaii while assisting in a survey of parasites in wild animals. With the discovery of the rat lungworm in Hawaii and with the eosinophilic cerebral syndrome known to be produced in the rat host 7, I became aware of its potential medical importance 4.S. In 1961, Horio and Alicata I° and Alicata4 reported that a Japanese worker in Hawaii had wilfully ingested t w o Veronicella slugs for their presumed medicinal properties, Nine days later the patient had aching feelings and paresthesia of the ears, shoulders and arms. A spinal tap one month later revealed a leukocyte cell count of 284 mm 3, of which 25%
152
Parasitology Today, vol. 7. no. 6. 1991
ingested by the rat migrate to / ~ the brain and reach young / It, / adulthood ,n four weeks Then / ~1 / they m~grateto the pulmonary / I IL / arter,es and after two more / Eggs hatch in the ~ I weeks start laying eggs / lungs and the ~ I / young first-stage / i larvae are e x p e l l e d / | I~ \ with the faeces of | F ~ v a e Infecta ~ the rat / mo/l~mterrr~dlate ~ ..... / hostanc~each the~ / k mfectlve(th=rd)stagem ~ / about two weeks \ / /
/
Carriers
infection
- -
/
/
./ I I ,/ Y
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1 r " Pa w ~ ,f'~'~'\ /~/ ~"
~ "
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~ t L.rab . , . I r l d ~ i /......v".~l~.. \1 O, estive \,,.-1~", ~ ---IP' Bra,n Planarian il ~ ~ /I
t
eosinophilic meningitis, 28 reported eating raw prawns a few days before illness and two affirmed that they usually ate salad greens (Fig. land Ref. 13). Research activities were later extended to various areas of the Pacific and parts of South Asia, Africa and the Americas H-~6. The rat lungworm was found in all the islands where eosinoph~lic meningitis had been reported. It was not found in East Africa ~5 nor in Central or South America ~6. However, the disease has been reported in Cuba ~n 1981 and the parasite found in both New Orleans and Puerto Rico in 1986 (Refs 17-20). There are also isolated reports of the parasite from Sapporo, northern Japan2~, Egypt 22 and the Ivory Coast 23.
Mode of Dispersal Fig. I. Life cycle of the rat lungworm, Angiostrongylus cantonensis, and avenues of human infection.
were eosinophils. Veronicella slugs subsequently collected in the same area as those obtained by the patient revealed numerous infective larvae of A. cantonensls.
In 196 I, R. Chappel reported to me 4 that he had found cross-sections of a nematode in a portion of the preserved brain of a Filipino who had died in 1960 at the Hawaii State Hospital with various symptoms, including eosinophilic meningitis. Subsequently, the remaining brain was submitted to Leon Rosen for further examination. In dissecting the brain under a stereoptic microscope, Rosen found several young adult nematodes, which were identified by M.B. Chitwood as those ofA cantonensis 8' i
Experimental Findings To confirm the suspicion that A. cantonensis would develop in a primate, several hundred infective larvae were fed to a young squirrel monkey and six laboratory-raised rats 4. At necropsy after five days, developing third-stage larvae were observed in press preparations of the brain tissue from the monkey and from four of the rats. Six weeks post-infection, the remaining two rats had adult worms inthe pulmonary arteries. A few months later, when aMacac a r h e ~ monkey was pipette-fed several hundred infective A. cantonensis larvae ~2, a spinal tap at 35 days post-infection revealed cloudiness of the cerebrospinal fluid and a leukocyte cell count of 4800 mm -3, of which 90% were eosinophils. The animal subsequently died and histological sectioning of the formalized brain revealed cross-sections of a nematode.
When the brain was fully dissected, nematodes were found and identified as A. cantonensis. These experiments showed that primates could develop eosinophilic encephalitis by ingesting infective third-stage larvae of this parasite.
Epidemiological Findings Studies during 1961 showed that, of 70 rats trapped in and around Papeete, 62 (88.5%) harbored the lungworm, A. cantonensis. Infective larvae of this parasite were found also in samples of local land snails, slugs and planarians, as originally reported in Hawaii 4. At first, important sources of infection in Tahiti were thought to originate in land snails and planarians on lettuce sold in the city market, and in local drinking water contaminated by rats or vector species. However, the lettuce was rarely found to be a source of vectors and local people rarely consumed raw salads. Examination of several samples of sediment from drinking water collected overnight from indoor faucets during a heavy rainfall revealed several small, immature freshwater prawns ~3, the adults of which were known to be consumed uncooked on the island. The stomach contents of 300 prawns bought in a local market in Papeete revealed 12 (4%) that harbored infective larvae of A. cantonensis. Since about 12 000 pounds of prawns were sold in the city in 1961 and consumed raw, largely at parties, weddings and feasts, it appeared likely that these were the chief source of mass infection. In addition, in a survey of 30 people who had confirmed cases of
The mode of geographical dispersal of the rat lungworm is unknown but it has been suspected that the giant African snail, Achatina fulica, has played an important role 2° as it is not unusual in endemic areas for a snail of this species to harbor between 10 000 and 39 000 infected larvae. This snail travels widely, is saprophitic and feeds on all kinds of decaying vegetation and mammalian excreta. Apparently with human assistance, A. fulica spread eastward from East Africa to Madagascar before 1800, thence to Malaya in 1919, eastern China in 193 I, Taiwan in 1932, Okinawa in 1934, from Taiwan to Hawaii in 1936 and from Okinawa to Mlcronesia in 1938 (Ref. 20) and was found in American Samoa in about 1975 (Fig. 2 and Ref. 24). Southeast Asia appears to be the ancestral habitat of the rat lungworm. This opinion is substantiated by recent reports that eosinophihc meningitis produced by this parasite is common and widespread in Thailand and Indonesia2S'~6. The achatinid snail is an ideal ~ntermediate host for A. cantonensis and, on reaching Southeast Asia, presumably was able not only to build up the infection locally but also to disperse ~t to various locales in Asia and the Pacific islands. Humans have also dispersed the infected achatinid snails directly because of their value as food and supposed medicinal properties, and indirectly by shipping operations, which probably helped to introduce infected rats or snails from endemic to nonendemic areas s'2°. For example, one report indicates that during the first half of this century there was an importation of about 10000 contract laborers from Indochina and Indonesia for work in the nickel mines and agriculture in New Caledonia2728; it is probable that
Parasitology Today, vol. 7, no. 6, 1991
153
f
~Japan
Okmawa
India 1847
Thailand
• 1934
China 1931
-...~® Hawaii% 1936
,Philippines A 1942 Palau ~ 1938
" ~ Ponape Truk ~ 1938 1938 New Guinea
Africa Sumatr~ 1931 Java 1922
~
F--o Mauritius 1800 :lagascar 1800
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Solomons s~ Samoa - ~ _ ~ "/New ~r:~ /~''~. ~ /C)Hebrides kS)
~
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®
Rarotonga®..~.1-"
J
....
%"
® New Caledonia
Fig. 2. Map showing routes and approximate dates of dispersal ofAchatina fulica from East Africa to the Pacific islands (solid arrows) (adapted from Ref. 20) and the theoretical routes of dispersal of the rat lungworm from Southeast Asia to islands of the South Pacific and Australia (broken arrows). Locations where lungworms have been found in rats (plain stars) and where eosinaphilic meningitis has been reported (circled stars) are also shown. infected rats w e r e introduced as stowaways with this traffic. After becoming established, the parasite was probably similarly spread along oceanic trade routes to various South Pacific islands. A. fulica has subsequenty been found in Australia, N e w Caledonia, N e w Hebrides and Tahiti (Fig. 2 and Ref. 29). Prospects for Control
The best ways to avoid infection are: ( I ) to avoid eating uncoo
2 Beaver, P.C. and Rosen, L. (I 964) Am. J. Trap. Med. Hyg. 13,589-590 3 Alicata, J.E. and Jindrak, K. (1970) in Angiostrongylasts ~n the Pacific and Southeast Asia (Anderson, H.H., ed.), pp 105, Charles C Thomas 4 Alicata,i.E. (1962) Can J. Zool. 40, 5-8 5 Alicata,J.E.( 1986)].Wash.Acad. Sci.78, 38-46 6 Bailey,C.A. (1948) US Naval A4ed.Res.Inst. Pro]. NM0050077, 1-32 7 Mackerras,M.J.and Sandars,D.F. (1955) Austr. ]. Zaol. 3, 1-25 8 Rosen,L., Laigret,J. and Bories,S. ( 1961) Am.]. Hyg. 74, 26-4 I 9 Ash, L.I~( 1962)].Parasitol 48, 66-88 10 Horio, S.H.and Alicata,J.E.(1961 ) Hawa, Meal. ].21, 139-140 II Rosen, L. et aL (1962) Am. Med. Assoc. 179, 620- 624 12 Alicata, J.E., Loison, L. and Cavallo, A. (1970) J. Paras~tol.49, 156-157 13 Alicata, J.E. and Brown, R.W. (1962) Can. ]. Zool 40, 755-760 14 Ahcata,J.E.( 1969)J.Trap.Meal. Hyg. 72, 53-73 15 Alicata,J.E.(1966) Can.J.Zool. 44, 1041- 1049 16 Alicata,J.E.(I 967)J. ParasitoL 53, I I 18 17 Pascual,J.E.,Bouli, R.P.and Aguilar, P.H. ( 1981) Am J. Trap.Med. Hyg. 30, 960-962 18 Campbell, B.J. and Little, M.B. (1986) Annual Meeting of the American Society for Tropical Medicineand HygieneAbstr. No. 137 19 Anderson, E.et al (I 986)Am.J. Trap.Med. Hy'g. 35.319-322 20 Mead, A.R. (1961) The Giant African Snail: A Problem of Fconomtc A4alacology,Universlty of ChicagoPress 21 Ohbayashi, M. and Orihara, M. (I 986) ]pn. ]. Parositol. 17.5-9 22 Yous,f, F. and Ibrahim, A. (1978) Z Parasitenk. 56,71-80 23 Noza~s,J.P. et al. (1980) Bull. Sac.Pathol.E.xot.
73, 179-182 24 Beck,M.J.,Cardma,T.M. and Alicata,J.E,(1980) Hawaii Med. ]. 39, 254-257 25 Punyagupta,S. et al. (1970) Am. J. Trap Meal. Hyg. 19,950--958 26 Carney, W.P, and Stafford, E.E. (1979) in US Naval iVled.Res.NAMRU-2- Sp-44 , pp 14-25 27 Dewey, A.G. (1964) SouthPac.Bull. I 0, 18-26 28 Felix, D and MacTaggert, W.J. 0964) Pac. VJewDoint5, 78-83 29 Caiman, P.H.(1977) Malacologia I 0, 77-78 30 Ahcata,J.E.(1963) South Pac Comm. (Noumea) Tech.Pap 179, I-9 31 Hadfield, M.G. ( 1986)Malacologia27, 67-8 I 32 Cowie, R.H. (1990 ) Hawaii. ShellNews Honolulu 9,5
Joseph Alicata is Emeritus Professor of Parasitology at the Department of Animal Sciences, University of Hawaii, Honolulu, HI 96822, USA. His address for correspondence is 1434 Punahou St, Apt 736, Honolulu, HI 96822, USA.
L e t t e r s to t h e E d i t o r Parasitology Today welcomes letters to the editor. Please address letters to: Dr Caroline Ash
Parasitology Today Elsevier Trends Journals 68 Hills Road Cambridge CB2 I LA, UK and mark clearly whether they are intended for publication.
6 Kemp, D.]., Coppel, FLL. and Anders, R.F. (I 987)Annu. Rev M~croblal. 4 I, 181-208 7 Beard, CA, Wnghtsman, RA and Manning, I.E (I 988)MoLBi~hem. Parasitol. 28, 227-234 8 Van Voorhis, W.C. and Eisen H. (I 989)] Exp. Med. 169,641~$52 9 Requena,J.M et el. (1988)Nucleic Acids Res. 16, 1393-1406 10 Engman,D.M. et al. (1989)Mol. Biochem.Parasstal 37,285-288 I I Schllman,A.G. et al (I 990) NucleicAods Res. 18, 3399 12 ,/kslund,Let al ( 1991) Mal. fhochem Parasitol. 45, 345-348 13 Pollevick,G.D. et al. Mol. Biochem Paras~toL(in press) 14 Iba6ez,C.F et al ( 1988)Mal.B~ochem Parasitol 30, 27~-34 15 Lafa~lle,J.J.etal. (I 989) IVlol Biochem. Paras~tol. 35, 127-136 16 Levin, M.I. et al (1989)Am..I. Trap. Meal IHyg 4 I, 530-539 17 Haft, D.F et al (1989) Infect Immun. 57,
1959-1967 18 Peterson, D.S. Fours, D.L and Mann,ng,J.E. (1989)E.MBO]. 8,3911-3916 19 Kahn, S., Van Voorhis. W.C. and Eisen, H. (1990)]. Exp Me(/ 172,589-597 20 Schneider. A. et aL (1988) Science 241, 459462 21 Affranchino, J.L. el al (1989) Mol Biochem.
Parasital. 34,221-228
151
22 Bontempi, E, Mart,nez, J. and Cazzulo, J.J. (I 989)M01.B~ochem.Parasitol 33, 43-47 23 Souto-Padr6n, T. et aL (1990)], Cell Sci. 96, 485-490 24 Ruiz,A.M. et al (1985)ActaTrap 42, 299-309 25 Piras, M.M., Rodriguez, O.O. and Piras, R. (1981 ) EXp.Parasltol. S I, 59-73 26 Souto-Padr6n, T. et aL (1989) Eur.]. Cell Biol. 50, 272-278 27 Murta, A.C.M. etal. (1990)M01. Biochem.Parasttol. 43, 27-38 28 Scharfste~n,J. et al. (1985)Am.] Trap.Med Hyg 34, 1153-1159 29 Cazzulo,J.I.et al ( 1989)M01. Biochem Parasitol.
33, 33-42 30 Cazzulo,J.J.et aL (1990) Biochtm. Bnaphys.Acta 1037, 186-191 31 Z~ngales,B. etal. (1985)MoL Biachem.Parasttol. 16,21-34 32 QuaissL AM, Cornette, J. and Capron, A. ( 1986)M01 Biochem. Parasltol. 19,201-21 I ]3 Engman,DM. etal. (1989)]. B~ol. Chem. 264, 18627-1863 I 34 Roditi,I. Carrington, M. and Turner, M. (1987) Nature 325, 272-274 35 Wallis,A.E. and McMaster,W.R. ( 1987)]. Exp. Mad 166, 1814-1824 36 Reyes, M.B. etal. (1990) Proc. Ned Acad. So. USA 87, 2846-2850 37 Paranhos,GS. et al (I 990) Exp. ParasitoL 7 I, 284-293 38 Israelski, D.M., Sadler, R and Araujo, F.G.
(I 988)Am.] Trap.Meal Hyg. 78,445-455 39 Basombrio, M.A. and Arredes, H. (1987) ]. Parositol.73,236-238 40 Okanla, E.O., Stumpf, J.L. and Dusanlc, D.G. (1982)1nt]. ParasitoL 12, 251-256 41 Scott, M.T. and Snary, D. (1979) Nature 282, 73-74 42 Ruiz,AM. etal. (1990)Mol. Biochem. Paras~tol.
39, 117-126 43 Peterson,DS., Wrightsman,R.A and Manning, J.E(1986)Nature 322,566-568 44 Takle, G.B. etal. (1989)M01. Biochem Parositol. 37, 57-64 45 Eakin, A.E. et al (1990)Mol. Biochem Paros~tol.
39, 14 46 Lizardi. P. et el. (1985) Vaccines (Lerner, T.J.. Chanock, C. and Brown, DD., eds), pp 67-70, Cold SpringHarbor Laboratory 47 Bua,J.et el. ( 1991) Exp. Parasltol. 72, 54-62 48 Wrightsman, RA., Leon, W. and Manning,J.E. (1986)Infect. Immun. 53,235-239 49 Macina, R.A et al (1989) FE.BS Lett. 257, 365-368
Carlos Frasch and Juan Cazzulo are at the Instituto de Investlgaciones Bioquimicas, Fundoclan Campomar, Antonio Machodo 15 I. 1405 Buenos A~res, Argentina and Lena/~slund and UIf Pettersson are at the Department ofMedical Genetics, Biomedical Center, University otUppsala, Uppsala, Sweden.
The Discovery of Angiostrongylus cantonensis as a Cause of Human Eosinophilic Meningitis J.E. Alicata The theoretical and subsequent confirmation in 1961 of the rot lungworm, A n g i o s t r o n g y l u s cantonensis, as the causative a g e n t of eosinc$)hilic meningitis is one of the remarkable parasitological findings of the twentieth century. Here, Joseph Alicota briefly summarizes the early history a n d his epidemiologicol studies on the relationship between the parasite a n d the epidemics of encephalitis that swept through O c e a n i a after the Second World War.
During 1944 in Taiwan, Nomura and Lin ~ were the first to find young adult nematodes, which they called H a e m o strongylus rotti, in the cerebrospinal fluid recovered from a male patient with symptoms of meningitis, They did not definitely associate this parasite with the disease but it was suspected that the raw food eaten by the patient before the onset of illness might have been contaminated by rats. Their report, written in Japanese, was only translated into English in 1964 (Ref. 2) after it was suspected that the nematode A. can,:onensis was the (~)[99I, k,sewerSoeeceP(Jbhst~trsLtd (UK)01694707/9It$0200
cause of eosinophilic meningitis in Tahiti 3 5 In 1948, Bailey6 and t w o associates of the United States Naval Medical Institute were assigned to the island of Ponape in Micronesia to identify an epidemic form of encephalitis but their clinical and laboratory investigations failed to identify the etiological agent. In 1955, Mackerras and Sandars 7 worked on the life history of the rat lungworm, A. cantonensis, and found that garden snails and slugs served as intermediate hosts. On infection of the definitive rat host the larvae obligatorily migrate to the brain and, while there, the growing parasites produce an extensive eosinophilic inflammatory reaction, Four weeks later, the worms migrate to the lungs, where they reach sexual maturity (Fig. I). During 1961, in an epidemiological study of eosinophilic meningitis in Tahiti, Rosen, Laigret and Bories 8 theorized that the disease was caused by a helminth parasite of the skipjack tuna or other pelagic fish eaten raw in the area. However, it soon occurred to me that
this was unlikely to be the case in Hawaii, where many local people habitually consume raw fish and show no evidence of meningitis. I reasoned also that ifa w o r m parasite was the cause of human encephalitis, it had to be one that obligatorily invaded the central nervous system of mammals. The only nematode in the Pacific that met that description was A. cantonensis. In 1960 this parasite had been found by Ash 9 for the first time in Hawaii while assisting in a survey of parasites in wild animals. With the discovery of the rat lungworm in Hawaii and with the eosinophilic cerebral syndrome known to be produced in the rat host 7, I became aware of its potential medical importance 4.S. In 1961, Horio and Alicata I° and Alicata4 reported that a Japanese worker in Hawaii had wilfully ingested t w o Veronicella slugs for their presumed medicinal properties, Nine days later the patient had aching feelings and paresthesia of the ears, shoulders and arms. A spinal tap one month later revealed a leukocyte cell count of 284 mm 3, of which 25%
152
Parasitology Today, vol. 7. no. 6. 1991
ingested by the rat migrate to / ~ the brain and reach young / It, / adulthood ,n four weeks Then / ~1 / they m~grateto the pulmonary / I IL / arter,es and after two more / Eggs hatch in the ~ I weeks start laying eggs / lungs and the ~ I / young first-stage / i larvae are e x p e l l e d / | I~ \ with the faeces of | F ~ v a e Infecta ~ the rat / mo/l~mterrr~dlate ~ ..... / hostanc~each the~ / k mfectlve(th=rd)stagem ~ / about two weeks \ / /
/
Carriers
infection
- -
/
/
./ I I ,/ Y
/t /
1 r " Pa w ~ ,f'~'~'\ /~/ ~"
~ "
1 " •
I
~ t L.rab . , . I r l d ~ i /......v".~l~.. \1 O, estive \,,.-1~", ~ ---IP' Bra,n Planarian il ~ ~ /I
t
eosinophilic meningitis, 28 reported eating raw prawns a few days before illness and two affirmed that they usually ate salad greens (Fig. land Ref. 13). Research activities were later extended to various areas of the Pacific and parts of South Asia, Africa and the Americas H-~6. The rat lungworm was found in all the islands where eosinoph~lic meningitis had been reported. It was not found in East Africa ~5 nor in Central or South America ~6. However, the disease has been reported in Cuba ~n 1981 and the parasite found in both New Orleans and Puerto Rico in 1986 (Refs 17-20). There are also isolated reports of the parasite from Sapporo, northern Japan2~, Egypt 22 and the Ivory Coast 23.
Mode of Dispersal Fig. I. Life cycle of the rat lungworm, Angiostrongylus cantonensis, and avenues of human infection.
were eosinophils. Veronicella slugs subsequently collected in the same area as those obtained by the patient revealed numerous infective larvae of A. cantonensls.
In 196 I, R. Chappel reported to me 4 that he had found cross-sections of a nematode in a portion of the preserved brain of a Filipino who had died in 1960 at the Hawaii State Hospital with various symptoms, including eosinophilic meningitis. Subsequently, the remaining brain was submitted to Leon Rosen for further examination. In dissecting the brain under a stereoptic microscope, Rosen found several young adult nematodes, which were identified by M.B. Chitwood as those ofA cantonensis 8' i
Experimental Findings To confirm the suspicion that A. cantonensis would develop in a primate, several hundred infective larvae were fed to a young squirrel monkey and six laboratory-raised rats 4. At necropsy after five days, developing third-stage larvae were observed in press preparations of the brain tissue from the monkey and from four of the rats. Six weeks post-infection, the remaining two rats had adult worms inthe pulmonary arteries. A few months later, when aMacac a r h e ~ monkey was pipette-fed several hundred infective A. cantonensis larvae ~2, a spinal tap at 35 days post-infection revealed cloudiness of the cerebrospinal fluid and a leukocyte cell count of 4800 mm -3, of which 90% were eosinophils. The animal subsequently died and histological sectioning of the formalized brain revealed cross-sections of a nematode.
When the brain was fully dissected, nematodes were found and identified as A. cantonensis. These experiments showed that primates could develop eosinophilic encephalitis by ingesting infective third-stage larvae of this parasite.
Epidemiological Findings Studies during 1961 showed that, of 70 rats trapped in and around Papeete, 62 (88.5%) harbored the lungworm, A. cantonensis. Infective larvae of this parasite were found also in samples of local land snails, slugs and planarians, as originally reported in Hawaii 4. At first, important sources of infection in Tahiti were thought to originate in land snails and planarians on lettuce sold in the city market, and in local drinking water contaminated by rats or vector species. However, the lettuce was rarely found to be a source of vectors and local people rarely consumed raw salads. Examination of several samples of sediment from drinking water collected overnight from indoor faucets during a heavy rainfall revealed several small, immature freshwater prawns ~3, the adults of which were known to be consumed uncooked on the island. The stomach contents of 300 prawns bought in a local market in Papeete revealed 12 (4%) that harbored infective larvae of A. cantonensis. Since about 12 000 pounds of prawns were sold in the city in 1961 and consumed raw, largely at parties, weddings and feasts, it appeared likely that these were the chief source of mass infection. In addition, in a survey of 30 people who had confirmed cases of
The mode of geographical dispersal of the rat lungworm is unknown but it has been suspected that the giant African snail, Achatina fulica, has played an important role 2° as it is not unusual in endemic areas for a snail of this species to harbor between 10 000 and 39 000 infected larvae. This snail travels widely, is saprophitic and feeds on all kinds of decaying vegetation and mammalian excreta. Apparently with human assistance, A. fulica spread eastward from East Africa to Madagascar before 1800, thence to Malaya in 1919, eastern China in 193 I, Taiwan in 1932, Okinawa in 1934, from Taiwan to Hawaii in 1936 and from Okinawa to Mlcronesia in 1938 (Ref. 20) and was found in American Samoa in about 1975 (Fig. 2 and Ref. 24). Southeast Asia appears to be the ancestral habitat of the rat lungworm. This opinion is substantiated by recent reports that eosinophihc meningitis produced by this parasite is common and widespread in Thailand and Indonesia2S'~6. The achatinid snail is an ideal ~ntermediate host for A. cantonensis and, on reaching Southeast Asia, presumably was able not only to build up the infection locally but also to disperse ~t to various locales in Asia and the Pacific islands. Humans have also dispersed the infected achatinid snails directly because of their value as food and supposed medicinal properties, and indirectly by shipping operations, which probably helped to introduce infected rats or snails from endemic to nonendemic areas s'2°. For example, one report indicates that during the first half of this century there was an importation of about 10000 contract laborers from Indochina and Indonesia for work in the nickel mines and agriculture in New Caledonia2728; it is probable that
Parasitology Today, vol. 7, no. 6, 1991
153
f
~Japan
Okmawa
India 1847
Thailand
• 1934
China 1931
-...~® Hawaii% 1936
,Philippines A 1942 Palau ~ 1938
" ~ Ponape Truk ~ 1938 1938 New Guinea
Africa Sumatr~ 1931 Java 1922
~
F--o Mauritius 1800 :lagascar 1800
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Solomons s~ Samoa - ~ _ ~ "/New ~r:~ /~''~. ~ /C)Hebrides kS)
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"~, Tahiti
®
Rarotonga®..~.1-"
J
....
%"
® New Caledonia
Fig. 2. Map showing routes and approximate dates of dispersal ofAchatina fulica from East Africa to the Pacific islands (solid arrows) (adapted from Ref. 20) and the theoretical routes of dispersal of the rat lungworm from Southeast Asia to islands of the South Pacific and Australia (broken arrows). Locations where lungworms have been found in rats (plain stars) and where eosinaphilic meningitis has been reported (circled stars) are also shown. infected rats w e r e introduced as stowaways with this traffic. After becoming established, the parasite was probably similarly spread along oceanic trade routes to various South Pacific islands. A. fulica has subsequenty been found in Australia, N e w Caledonia, N e w Hebrides and Tahiti (Fig. 2 and Ref. 29). Prospects for Control
The best ways to avoid infection are: ( I ) to avoid eating uncoo
2 Beaver, P.C. and Rosen, L. (I 964) Am. J. Trap. Med. Hyg. 13,589-590 3 Alicata, J.E. and Jindrak, K. (1970) in Angiostrongylasts ~n the Pacific and Southeast Asia (Anderson, H.H., ed.), pp 105, Charles C Thomas 4 Alicata,i.E. (1962) Can J. Zool. 40, 5-8 5 Alicata,J.E.( 1986)].Wash.Acad. Sci.78, 38-46 6 Bailey,C.A. (1948) US Naval A4ed.Res.Inst. Pro]. NM0050077, 1-32 7 Mackerras,M.J.and Sandars,D.F. (1955) Austr. ]. Zaol. 3, 1-25 8 Rosen,L., Laigret,J. and Bories,S. ( 1961) Am.]. Hyg. 74, 26-4 I 9 Ash, L.I~( 1962)].Parasitol 48, 66-88 10 Horio, S.H.and Alicata,J.E.(1961 ) Hawa, Meal. ].21, 139-140 II Rosen, L. et aL (1962) Am. Med. Assoc. 179, 620- 624 12 Alicata, J.E., Loison, L. and Cavallo, A. (1970) J. Paras~tol.49, 156-157 13 Alicata, J.E. and Brown, R.W. (1962) Can. ]. Zool 40, 755-760 14 Ahcata,J.E.( 1969)J.Trap.Meal. Hyg. 72, 53-73 15 Alicata,J.E.(1966) Can.J.Zool. 44, 1041- 1049 16 Alicata,J.E.(I 967)J. ParasitoL 53, I I 18 17 Pascual,J.E.,Bouli, R.P.and Aguilar, P.H. ( 1981) Am J. Trap.Med. Hyg. 30, 960-962 18 Campbell, B.J. and Little, M.B. (1986) Annual Meeting of the American Society for Tropical Medicineand HygieneAbstr. No. 137 19 Anderson, E.et al (I 986)Am.J. Trap.Med. Hy'g. 35.319-322 20 Mead, A.R. (1961) The Giant African Snail: A Problem of Fconomtc A4alacology,Universlty of ChicagoPress 21 Ohbayashi, M. and Orihara, M. (I 986) ]pn. ]. Parositol. 17.5-9 22 Yous,f, F. and Ibrahim, A. (1978) Z Parasitenk. 56,71-80 23 Noza~s,J.P. et al. (1980) Bull. Sac.Pathol.E.xot.
73, 179-182 24 Beck,M.J.,Cardma,T.M. and Alicata,J.E,(1980) Hawaii Med. ]. 39, 254-257 25 Punyagupta,S. et al. (1970) Am. J. Trap Meal. Hyg. 19,950--958 26 Carney, W.P, and Stafford, E.E. (1979) in US Naval iVled.Res.NAMRU-2- Sp-44 , pp 14-25 27 Dewey, A.G. (1964) SouthPac.Bull. I 0, 18-26 28 Felix, D and MacTaggert, W.J. 0964) Pac. VJewDoint5, 78-83 29 Caiman, P.H.(1977) Malacologia I 0, 77-78 30 Ahcata,J.E.(1963) South Pac Comm. (Noumea) Tech.Pap 179, I-9 31 Hadfield, M.G. ( 1986)Malacologia27, 67-8 I 32 Cowie, R.H. (1990 ) Hawaii. ShellNews Honolulu 9,5
Joseph Alicata is Emeritus Professor of Parasitology at the Department of Animal Sciences, University of Hawaii, Honolulu, HI 96822, USA. His address for correspondence is 1434 Punahou St, Apt 736, Honolulu, HI 96822, USA.
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