The prevalence of Ascariasis

162

Parasitology Today, vol. 4, no. 6, 1988

24 Edman, J.D. and Webber, L.A. (1975) Mosq. News 35,508--512 25 Day, J.F. and Edman, J.D. (1983) J. Parasitol. 69, 163-170 26 Day, J.F., Ebert, K.M. and Edman, J.D. (1983) J. Med. Entomol. 20,120-127 27 Rossignol, P.A. et al. (1985) Proc. Natl Acad. Sci. USA 82, 7725-7727 28 Ribeiro, J.M.C., Rossignol, P.A. and Spielman, A. (1984)J. Exp. Biol. 108,1-7 29 Rossignol, P.A., Ribeiro, J.M.C. and Spielman, A. (1984) Am.J. Trpp. Med. Hyg. 33, 17-20 30 Ribeiro, J.M.C., Rossignol, P.A. and Spielman, A. (1985)J. InsectPhysiol. 31,689--692 31 Rossignol, P.A., Ribeiro, J.M.C. and Spielman, A. (1986) Ara. J. Trap. Med. Hyg. 35,277-279 32 Griftiths, R.B. and Gordon, R.M. (1952) Ann. Trap. Med. 46, 311-319 33 Carter, R. and Graves, P.M. in Textbook of Malaria (Wernsdorfer, W. and McGregor, I.A., eds), pp 253-305, Churchill Livingstone (in press) 34 Graves, P.M.etal.Parasitology(inpress) 35 Burkot, T.R., Williams, J.L. and Schneider, I. (1984) Trans. R. Sac. Trap. Med. Hyg. 78,339-341 36 Mendis, K.N. et al. (1987) Infect. lmmun. 55,369-372 37 Graves, P.M. et al. (1988) Parasite Immunol. 10, 209218 38 Cattani, J.A. et al. (1986) Am. J. Trap. Med. Hyg. 35, 3-15 39 Wilkinson, R.N., Noeypatimanondh, S. and Gould, D.J. (1976) Trans. R. Sac. Trap. Med. Hyg. 70, 306307 40 Rutledge, L.C., Gould, D.J. and Tantichareon, B. (1969) Trans. R . Sac. Trap. M ed. Hyg. 63,613--619 41 Carter, R. and Gwadz, R.W. (1980) in Malaria (Vol. 3) (Krier, J.P., ed.), pp 263-297, Academic Press

42 Cantrell, W. and Jordan, H.B. (1946)J. Infect. Dis. 78,153-159 43 Jeffery, G.M. and Eyles, D.E. (1954) Am. J. Trop. Med. Hyg. 3,219-224 44 Jeffery, G.M. and Eyles, D.E. (1955) Am. J. Trop. Med. Hyg. 4,781-789

45 Boyd, M.F., Stratman-Thomas, W.K. and Muench, H. (1936)Am.J. Trop. Med. 16, 133-138 46 Young, M.D. et al. (1948) Am. J. Trop. Med. 28, 303-311 47 Earle, W.C. et al. (1939) Puerto Rico J. Public Health Trop. M ed. 14, 391--406 48 Hill, R.B., Cambournac, F.J.C. and Simoes, M.P. (1943)Am.J. Trop. Med. Hyg. 23,147-162 49 Miller, M.J. (1958) Trans. R. Soc. Trop. Med. Hyg. 52, 152-168 50 Covell, G. (1960)Bull. WHO 22,605-619 51 Molineaux, L. and Gramiccia, G. (1980) The Garki Project, pp 253-259, WHO, Geneva 52 Barber, M.A. (1936)Am.J.Hyg. 24,45-56 53 Collins, F.H. et al. (1984) Am. J. Trop. Med. Hyg. 33, 538-543 54 Jeffery, G.M. et al. (1959) Ann. Trop. Med. Parasitol. 54, 51-58 55 Ungureanu, E.R. et al. (1976) Trans. R. Soc. Trop. Med. Hyg. 70,482-483 56 Shute, P.G. et aL (1976) Trans. R. Soc. Trop. Med. Hyg. 70,474-481 57 Pringle, G. (1966) Trans. R. Soc. Trop. Med. Hyg. 60, 626-632 58 Burkot, T.R. et al. Am. J. Trop. M ed. Hyg. (in press) 59 Boyd, M.F., Stratman-Thomas, W.K. and Kitchen, S.F. (1936)Am.J. Trop.Med. 16,157-158 60 Macdonald, G. (1955)Proc. R. Soc. Med. 48,295-302 61 Barber, M.A. and Rice, J.B. (1935) Ann. Trop. Med. 29, 329-348

The Prevalence of Ascariasis D.W.T. Crompton Department of Zoology, Universityof Glasgow GlasgowG 12 8QQ, UK

The common roundworm, Ascaris lumbricoides, /s probably the most prevalent human intestinal helminth. Previous estimates of world prevalence rangefrom around 650 million to 1000 million. By a detailed literature search, David Crompton now confirmsthe upperfigureestimating a worm prevalence of 1008 million representing about 22% of the world population. The infection is knownfrom 153 out of 218 recognizedcountries. • . . . . . . . . . . . . I, L H / ~ E K I C U S T E R E S , errant Anatomical ~

/'~rv~ti~,. t~ ltOundWorm~ d in+human/n~d/~ + B~ Edward Tyfon~ bt. D,[Col, Meal.L~d. aec non,.Rc~i f ~ i c r , Soc, ~ , . +.

Fig. I. Reproductionof the first pageof Edward Tyson'spaperentit/ed ~Lumbricus reres, or some anatomical observations on the round warm bred in human bodies." This illustration was kindly preparedby the Special Collections Departmentof the Library orthe University af Glasgow.

The scientific study ofAscaris lumbricoides was promoted by Edward Tyson some three centuries ago when he demonstrated that this worm was totally different in its structure and anatomy from earthworms1. Tyson was a physician who described A. lumbricoides as "that common round worm which children usually are troubled with" (Fig. 1). He was writing about children in London who no doubt then lived in communities characterized by poverty, poor nutrition, inadequate hygiene and sanitation, scarcity of health services, and apathy and indifference to their needs. Nowadays in the UK, less than 1000 cases of infection attributed to A. lumbricoides are being reported annually for a population of more than 50 millionz. Ascariasis has declined to an insignificant level as a consequence of developments in our health care and improvements in our standard of living. Such cases as are reported ~) 1988,ElsevierPublications,Cambridge0169-4758/88/$0200

Parasitology Today, vol. 4, no. 6, 1988

may be due to roundworms acquired through contact with pigs. The matter that concerned Tyson, however, still prevails in many parts of the world where millions of people - especially children - still suffer the burden of ascariasis. The infection persists in adults, but the evidence strongly suggests that children bear the brunt of the acute and chronic morbidity due to the presence of the adult stages of A. lumbricoides in the small intestine (see Box 1). E s t i m a t e s o f the globalI p r e v a l e n c e

The challenging article by Stall in 19473 proposed that about 644 million people out of a global population of about 2167 million were infected with A. lumbricoides. These figures suggested that about 30% of the world's population had ascariasis although it is common practice today to claim that about a quarter of the world's population has the infection. Some of the typical estimates of the global prevalence of ascariasis are given in Box 2. D i s t r i b u t i o n o f ascariasis

By computer-based literature searches, mainly covering publications from 1975 to the present, we compiled a list of countries in which ascariasis is known to occur (see Box 3 and centre pages). The results of this survey apply to established populations of permanent residents; data from studies of recent immigrants, refugees and travellers were not inchlded (see below). The Times Concise Atlas of the World (1986) ~° lists 218 states and countries ranging from China with a population of more than a billion to the British Indian Ocean Territory with no permanent inhabitants. There is no doubt that ascariasis occurs to varying; degrees in 153 of these countries, and failure to find a reference to ascariasis in other countries does not mean that the infection has been eliminated from them. The information can also be organized according to the list of countries as used by the US Department of Health and H u m a n Services u , in which case ascariasis is found to exist in 151 out of 208 states and territories (Box 3). A more informative view of the global prevalence and distribution of ascariasis is given by classifying the occurrence of the disease according to the socioeconomic indicators used by U N I C E F lz. This is also shown in Box 3 with reference to the 130 countries that support over 90% of the world's population. A more detailed account of sources of data on ascariasis prevalence will be pub-

163

lished later this year*, and the manner in which these prevalence values were calculated has recently been discussed here 9. By excluding the available information for the USSR and European countries and using data obtained from 83 of the remaining countries with populations of at least 2 million each, we estimate the global prevalence at 1008 million cases ofascariasis (Box 3). This figure, derived independently from the others shown in Box 3 and not by extrapolation from the value of Stall 3, indicates that about 22% of the world's population is infected with A. lumbricoides. A considerable number of diagnostic surveys have been made during the last decade by health workers in countries that have received immigrants and refugees. These provide evidence that A. lumbricoides is travelling from endemic areas to regions now largely free from the infection. Immigrants can be treated and the sanitary conditions of their new environments will often provide protection from reinfection with Ascaris and other soiltransmitted helminths. However, this may not be the case for many of the world's 12 million refugees 2~ who usually live in squalid camps despite the efforts of

Box 1. Biology of Ascaris lumbricoides and A s e s

Life history

Prepatent t~rioa Patentperiod Adult worms Population biology Disease

Diagno~ Treatment

Direct, man is usual host; second stage larva protected by eggshell is the infective stage.

30+2°Cand after 45-55 daysat 17_+1°C. Lasts about 70 days. Infectivelarvaem liver 4 days p (Female worm): About 12 (~18) months; about 240 000 eg,~ her female her day.

Parasitology Today, vol. 4, no. 6, 1988

164

I) Stdl(19,tT~

Totalpopulation Numberof ascaria~ %PrevalenCe

Lat/n N.America A 143.5 130.8 3.0 2.1

42.0 32.1

59.0 39.9

45.0 8.8

494.9 40.5

0.5 5.0

644.4 29.7

t7.0

324.0

401.0

600.5

2383.'5

21.0

3967.0

5.0 2.1

104.0 32.1

159.0 39.7 c

54.0 9.0

946.0 39.7

1.0 4.8

1269.0 32.0

(3) 800-1000, Walsh and Warren (1979~

(4) 986,PetersandGillies(198t) 6

(5) 650, blarkell and Voge (1982) 7. Attributed t o ~ O Statistics for 1975

(6) 800--1000,Poinur(1983)S.Attributedto~O Sta~sdcs for 1977-78

Prevalence is known to be higher in countries with a humid rather than dry climate 23 and seasonal ascariasis can usually be shown to be synchronized with changes in rainfall and h u m i d i t y 24. Paradoxically Patterns within the prevalence of however, confidence in generalizations ascariasis Some general features emerge about the like these can be undermined by another distribution of ascariasis prevalence. unshakeable generalization: wherever Typically, prevalence is higher in children detailed studies are carried out, the distrithan in adults 9, and is-often higher in bution of ascariasis prevalence is observed females than in males (D.W.T. Crompton to be patchy, erratic, uneven and unpreand J.M. Robb, unpublished; Refs 9, 22). dictable. Values for its prevalence in Usually more ascariasis occurs in rural Nigeria for example, range from 0.9% to rather than urban communities (D.W.T. 98.2% according to data obtained from 35 Crompton and J.M. Robb, unpublished). surveys involving 126 535 subjects 9. Similarly, within Maharashtra State in so I India, prevalence values range from 8.0% to 90.6% based on data obtained from 11 surveys encompassing 124 550 subjects 4O (D.W.T. Crompton and J.M. Robb, unpublished). Prevalence values of 76%, 35 42%, 33% and 0% were recorded recently from stratified samples of preschool chil30 dren in four Ghanaian villages25, and no evidence of A. lumbricoides was obtained from a survey of 595 subjects in Zimbabwe although 20 other species of intestinal parasite were present in this community 26. Much of the explanation for this patchy prevalence may eventually be attributed to the diversity of human cultural and behavioural activities, because numerous 0 associations can be found between the 0 4 8 1'2 1'6 2'0 24 prevalence of ascariasis and human factors. For example, ascariasis is more comTIME (MONTHS) mon in Bantu people compared with Fig. 2. The impact of mass chemotherapy on the prevalence ofAscaris lumbricoides in Pygmies from the same region 27, and is rural village communities in South Korea. The curves illustrate the effects of chemotherapy given at 2-, 4-, 6- and 12-month intervals and the results were obtained by more common in Indian rather than detecting eggs in stool samples. (Redrawn from Anderson 34 and based on the work ofSea Chinese people living under similar condiet al.43,) - ~ - -~ 12 months, ~ - 6 months,-II- - 4 months,-E]- - 2 months. tions in Malaysia 2s. Prevalence tends to be relief agencies. Perhaps this special population group should be specifically targeted for regular anthelmintic treatment.

Parasitology Today, vol. 4, no. 6, 1988

165

higher in children from large families 29 and even the order in which a child is born may influence the child's chances of becoming infected 3°.

Intensity of ascariasis If prevalence data was the only factor influencing public health priorities, then it could not be denied that ascariasis deserved immediate attention. The same would be true for hookworm disease, trichuriasis and strongyloidiasis, because polyparasitism with soil-transmitted helminthiases is normal in regions where ascariasis is endemic 9. But the prevalence data alone do not focus attention on the full public health significance of Ascaris or the other soil-transmitted helminths, and there is an urgent nee,d for much more information about the intensity of these infections. Recent studies show that the morbidity of ascariasis and the regulation of Ascaris populations are related to the intensity of the infection or worm burden 31-39. The relationship between intensity and morbidity is not unexpected - numerous experimental studies of intestinal nematodes have clearly shown that the greater the worm burden, the more severe the lesion as expressed by sJignsand symptoms of disease 32'39. Not surprisingly, mortalit3, appears similarly linked to intensity, but the data are too sparse, inaccurate and unreliable to permit solid confirmation of this proposition. Clinicians, perhaps through their primary concern for individual patients rather than populations, tend to argue that even one A. lumbricoides can kill. This may be the case should a solitary worm enter the liver, pancreas or heart, but emphasis on the likelihood of death being due to one worm is misplaced. Although a single bullet may kill its target, 50 are much more likely to do so! As with many other species of helminth, the frequency distribution of numbers ofA. lumbricoides ]per host tends to be highly aggregated or overdispersed 34, meaning that only a small proportion of individuals in an infected community will harbour large worm burdens. These heavily infected individuals;- usually children - will suffer most chronic disease and be vulnerable to the life-threatening aspects of ascariasis 39, and there is statistical evidence to show that such hosts are predisposed to these heavy infections 38. Strategies for ascariasis control Ascariasis gradually declined to its present insignificant level in Britain as the

standard of living improved owing to national prosperity, installation of safe drinking water supplies and modern sanitation, provision of sewage treatment plants and the availability of health care. Ascariasis has also been successfully controlled in Japan 4° and Israel 41. In both these countries, legislation was passed to prevent the use of night soil as a fertilizer for crops and to ensure that untreated water was not used for irrigation. National or vertical control programmes seem to require this level of political commitment and even legislation if they are to succeed. The other arm of Ascaris control involves chemotherapy, which can be used in three main ways in addition to individual treatment of cases that may present to health workers. Mass chemotherapy seeks to make the anthelmintic drug available to everyone in an endemic area; targeted chemotherapy aims to make the drug available to an accessible group identified as being particularly at risk

i

World Prevalence of Ascariasis >70% 50%-70%

Io%-5o%

I % - 10% <1% N D - Data not available

This map has been compiled through comput mainly covering the period 1975-1987. This searc for cases of ascariasis in 153 out of 218 states c global distribution are to be found in Refs I, 2 and. Excluding Europe, there are 83 countries with The estimated number of ascariasis cases in tht Taking the world population as 4653 million, this i of 22%. References: I Crompton, D. W. T. and Tulley, J,J, (1987) Parasit, (1985) in Handbook of Experimental Pharmacology 77 (Vanden B, P. G., eds), pp 183-406, Springer Verlag; 3 Crompton, D. W. T., I~ (1988) Ascariasis and its Prevention and Control, Taylor and Francis (i

I literature searches, far revealed evidence tories. (Details of this ation of 3691 million. ~tries is 1008 million. ts a global prevalence 3, 123-127; 2 Janssens, P. G. Thienpont, D. and Janssens, • C. and Pawlowski, Z. S., eds

Parasitology Today, vol. 4, no. 6, 1988

168

*This article isbased on

information to be included in Ascariasis and its Prevention and Control

to be published in 1988 by Taylor and FrancisLtd, Rankine Road, Basingstoke, Hants RG24 OPR,UK. The book will contain the full proceedings of a conference on The Prevention and Control of Ascariasiswhich took

place at Penang,Malaysia, in February 1988, organized by the Parasitic DiseasesProgramme, WHO, and the Department of Zoology, University of Glasgow, with the financial and administrative support of ICI Pharmaceuticals.

(such as pre-school children and children of school age), while selective chemotherapy would involve treating those individuals identified to be predisposed to heavy infections. One attraction of smaller scale chemotherapy programmes is that the drugs can be used in communities where prevalence is known to be high. Moreover, theoretical studies show that the period over which chemotherapy should be applied, and the interval between doses, can be calculated in order to bring about a sustained effect on the infection42. This approach has drawn attention to the crucial aim of a control programme to lower the intensity of the infection, rather than specifically reduce prevalence (see Fig. 2; Ref. 43). There are other important questions related to chemotherapy implementation at a public health level. First is the difficult question of immunity - could anthelmintic treatment disrupt the naturally acquired immunity and so risk higher intensities of infection if treatment is interrupted? Second is the possibility of selection for drug-resistant parasites, although this may be unlikely given the relatively long generation time (and consequent slow rate of genetic turnover) of the parasite 44. The third important question concerns the risk of reinfection after treatment, which should be minimized by educational campaigns and improved sanitation. As with most public health interventions, strong community cooperation needs to be enlisted to ensure good compliance with the programme, and financial and administrative support must be sufficient to ensure continuity of the intervention. Much of this discussion may read as if the decision-makers within the public health systems of developing countries are just about to declare war on ascariasis. That is not the case, and "give us the stools and we'll finish the job" is not their battle cry. Public health planners in developing countries must use their limited resources to provide health care for diarrhoeal diseases, malaria, measles, AIDS, nutritional needs and so on. Thus until the morbidity attributable to ascariasis is better quantified and the economic benefits of its control can be forecast, this infection is likely to remain fairly low on the list of priorities for health care. But there is another appeal to be made to the decision-makers, which depends on drawing their attention to the idea that integration of ascariasis control into an established health care programme can

improve compliance and community concern for health care in general. This strategy has been used to considerable effect by the Japanese Organization for International Cooperation in Family Planning (JOICFP) 45. Experience from a region where ascariasis is endemic shows that people detest A. lumbricoides, so that the easy expulsion of worms after a single oral dose of anthelmintic forms a compelling illustration of the benefits provided by medical care. Providing for this perceived need of local people, and their own sense of relief at the removal of their worms, are factors that can be used in the initiation of primary health care and to strengthen existing programmes. For the next few years, integrated programmes may offer the best practical strategy to improve health care and reduce the burden of ascariasis and other soiltransmitted helminthiases46. Meanwhile research into the basic biology of these parasites and their relationships with man needs to be supported 47. References 1 Tyson, E. (1683)Phil. Trans. 13,152-161 20wen, R.R. (1986)J. R. Sac. Hlth. 106,41-43 3 Stall, N.R. (1947)J. Parasitol. 33,1-18 4 Peters, W. (1978)Syrup. Br. Sac. Parasitol. 16, 25-40 5 Walsh, J.A. and Warren, K.S. (1979) New Engl. J. Med. 301,967-974 6 Peters, W. and Gilles, H.M. (1981)A ColonrAtlas of Tropical Medicine and Parasitology (2nd edn) Wolfe Medical PublicationsLtd, London 7 Markell, E.K. and Voge, M. (1982)Medical Parasitology (Sth edn) W.B. SanndersCo., Philadelphia 8 Poinar, G.O. (1983) The Natural History of Nematodes, Prentice-HallInc., EnglewoodCliffs,NJ 9 Crompton, D.W.T. and Tulley, J.J. (1987) Parasitology Today 3,123-127 10 The Times Concise Atlas of the World (1986) Times Books Ltd, London 11 Centers for Disease Control (1985) Health lnformation for International Travelers, Centers for Disease Control, Atlanta 12 UNICEF (1985) TheStateof the World'sChildren1986, Oxford UniversityPress 13 WHO (1981) WHO Chronica135,223-226 14 Stephenson, L.S. et al. (1983)J. Trap. Pediatr. 29, 175-184 15 Kan, S.P. and Poon, G.K. (1987)Public Health 101, 243-251 16 Bundy, D.A.P. (1986) Trans. R. Sac. Trap. Med. Hyg. 80,706-718 17 Young, M.E. and Prost, A. (1985) World Bank Staff Working Paper 767, World Bank, Washington 18 Camillo-Coura, L.F. in Ascamsis and its Prevention and Control (Crompton, D.W.T., Nesheim, M.C. and Pawlowski, Z.S., eds), Taylor and Francis Ltd, London (in press) 19 Janssens, P.G. (1985) in Handbook of Experimental Pharmacology 77 (Vanden Bossche, H., Theinpont, D. and Janssens, P.G., eds), pp 183--406, Springer Verlag, Berlin 20 Crompton, D.W.T., Nesheim, M.C. and Pawlowski, Z.S. (eds), (1985) Ascariasis and its Public Health Significance, Taylor and Francis Ltd, London 21 WHO (1987) WorldHealthJuly, 12-15 22 Cross, J.H. et al. (1975) Southeast Asian J. Trap. Med. Public Health 6, 52--60 23 WHO (1967) Technical Report Series 379, WHO, Geneva 24 Gelpi, A.P. and Mustafa, A. (1967) Am.ft. Trap. Med.

Parasitology Today, vol. 4, no. 6, / 988 Hyg. 16, 646--657 25 Annan,A. etal. (1986) Parasitology92, 209-217 26 Goldsmid, J.M. et al. (1976) Cent. Afr. J. Med. 22, 91-95 27 Pampiglione, S. and Ricciardi, M.L. (1974) Riv. Parasit. 35,161-188 28 Kan, S.P. (1982)Med.J. Ma,!ays. 37, 180-190 29 Prakash, D. etal. (1980) Int.J. Parasitol. 4, 59--60 30 Adekunle, L.V., Bammeke, A.O. and Lucas, A.O. (1986)J. R. Soc. Hlth. 106,66-68 31 Crompton, D.W.T. (1985) Parasitology Today 1, 47-52 32 Stephenson, L.S. (1987) Impact of Helminth lnfections on Human Nutrition, Taylor and Francis Ltd, London 33 Carrera, E., Nesheim, M.C. and Crompton, D.W.T. (1984)Am.J. Clin. Nutr. 39, 255-264 34 Anderson, R.M. (1980) in .Ascariasis and its Public Health Significance (Crompton, D.W.T., Nesheim, M.C. and Pawlowski, Z.S., eds), pp 39--67, Taylor and Francis Ltd, London 35 Thein Hlaing et al. (1984) Trans. R. Soc. Trop. Med. Hyg. 78,497-504 36 Nesheim, M.C. (1984)Federation Proceedings 43,235238 37 Crompton, D.W.T. (1986) Trans. R. Soc. Trop. Med. Hyg. 80,697-705 38 Haswell-Elkins, M.R., Elkins, D.B. and Anderson,

169

Acknowledgements R.M. (1987)Parasitology95,323-337 39 Pinus, J. (1985) in Ascariasis and its Public Health It is a pleasure to thank T. Significance (Crompton, D.W.T., Nesheim, M.C. and Abell and S.E.Arnold for Pawlowski, Z.S., eds), pp 161-166, Taylor and Fran- their help during my time cis Ltd, London at the Molteno Institute, 40 Yokogawa, M. (1985) in Ascariasis and its Public Cambridge, and C.A. Health Significance (Crompton, D.W.T., Nesheim, M.C., Pawlowski,Z.S., eds), pp 265-277, Taylor and Greig, J.M. Robb andJ.J. TuUey for their willing Francis Ltd, London 41 Shuval, H.I., Yekutiel, P. and Fattal, B. (1985) Water assistancein Glasgow. Thanks are also due to Sci. Technol. 17,433-442 42 Anderson, R.M. in Ascariasis and its Public Health J. Broad, E. Certain, A. Significance (Crompton, D.W.T., Nesheim, M.C., Davis, C.W. Gordon, Pawlowski, Z.S., eds), Taylor and Francis Ltd., Lon- D.A.D. Mclntosh, A.B. don (in press) O'Neil, Z.S. Pawlowski, 43 Seo,B.S. etaL (1980)KoreanJ. Parasitol. 18,145-151 E.J.Denton and M.L.N. 44 Coles, G.C., Pawlowski, Z.S. and Lloyd, S. (1985) in Ascariasis and its Public Health Significance (Cromp- Murthy. The work has ton, D.W.T., Nesheim, M. C., Pawlowski, Z.S., been made possible through the financial eds), pp 282-283, Taylor and Francis Ltd., London support of Technical 45 Trainer, E.S. (1985) WorldHealthForum6, 248-254 46 WHO (1987) Technical Report Series 749, WHO, ServicesGrants from the Geneva WHO. 47 Crompton, D.W.T. in Bailliere's Clinical Tropical Medicine and Communicable Diseases 2:3 (Pawlowski, Z.S., ed.), Bailliere Tindall Limited, London (in press)

Role of the RGD sequence in Parasite adhesion to Host Cells M.A. Ouaissi For many protozoan parasites, one of thefirst events in the process of infection is attachment to the surface of host cells. This adhesion phase usually involves ligand-receptor interactions, and has stimulated interest in the biochemical characterization of those host cell and parasite surface components involved. In this article, Ali Ouaissi discusses the strategy employed by pathogens such as Trypanosoma cruzi, Trichomonas, Leishmania and Treponema pallidum, in binding to their host cells"fibronectin receptors. Two systems appear available - to bind to the dimeric cell surface fibronectin through the Arginine-Glycine-Aspartic acid (RGD )* sequence that is not occupied by the host cell surface receptors, or to present a surface antigen representing a "fibronectin-like" molecule containing the R G D sequencedirectly to the host cellfibronectin receptors.

Some kind of attachment is a prerequisite for the establishment and maintenance of pathogen populations in their mammalian host. The general approach to understand mechanisms of host cell recognition and attachment by the pathogen is based upon consideration of initial protein interactions, although several studies have also focused on the potential role of sugar residues as ligands for the attachment of protozoan parasites, bacteria and some viruses 1-3. Interest has '.also developed in the possible role offibronectin (Fn) in host cell-pathogen interactions. Fibronectins are a group of glycoproteins found in plasma and other body fluids and secreted by a variety of cells of epithelial and mesenchymal origin 4. T]hey represent one of the major components of the extracellular matrix. The fibronectin molecule consists of highly structured domains containing binding sites for the macromolecules that ~) 1988,ElsevierPublications,CambridgeO169-4758/881502.00

interact with it s . All the cell attachment activity of the molecule seems to be carried by an RGDS amino acid sequence (Arg-Gly-Asp-Ser) 6'7. However, the serine residue seems to play a minor role - if any - in the attachment of cells, and it appears that the RGD sequence is the active site (see Box 1). The RGD sequence is common to a growing list of proteins including many extracellular matrix molecules that can also mediate cell attachment s. The RGD sequence is also present in the ~.-phage receptor on Escherichia coli, Sindbis virus coat protein, ~t-lytic protease, and testisspecific basic protein. In fact, 183 RGD sequences are found in the library of sequences compiled by the National Biomedical Research Foundation s . Our interest in the function of Fn in host-parasite relationships developed in the context of studies on the interactions of Trypanosoma cruzi with host fibroblasts.

Unite Mixte INSERM 167-CNRS 624 Institut Pasteur I rue du Prof. Calmette 59019 Lille, France *Amino acids are often given three-letter abbreviations such as Ala for alanine, Arg for arginine, and so on. For convenience, a one letter code is also used: A - Alanine R-Arginine N-Asparagine D - Aspartic acid B - Asparagine or Aspartic acid C - Cysteine Q - Glutamine E - Glutamic acid Z - Glutamine or Glutamic acid G - Glycine H - HistJdine I - Isoleucine L - Leucine K - Lysine M -Methionine F - Phenylalanine P - Proline S- Serine T - Threonine W - Tryptcyphan Y- Tyrosine V - Valine [See Biochem. J. (I 972) 127, 753-756, andJ. Biol. Chem. (I 983)258, 8.]