Thursday, September 6, 2012

WHY SCHISTOSOMIASIS SHOULD STILL BE STUDIED IN INDIAN CONTINENT



M. C . AGRAWAL
Former Emeritus Scientist , and ICAR National Fellow
Department of Parasitology , College of Veterinary Science and AH
Jabalpur 482001 MP
I feel privileged that the selection committee of Indian Academy of Tropical Parasitology considered me suitable for Dr SC Parija oration award for the year 2012 and express my gratitude for this kind gesture. I have selected the topic schistosomiasis for my discussion not only because I have worked over the subject throughout my life but also as I consider that it has the capacity to cover all the fields of life sciences where all three faculties zoology, veterinary and medical may work together to solve the problem and is a good model for teaching Parasitology. Another reason for selecting this topic is as I am witnessing standstill of research work on schistosomiasis in India after my retirement and termination of ICAR NATP scheme on Diagnosis of parasitic diseases where Jabalpur and Hisar centers were working on schistosomiasis. With the help of my colleagues, I have compiled almost all the research on schistosomes and schistosomiasis carried out in the country in last 100 years in a book form (Agrawal, 2012) but this must be considered not a stop but a comma , to start the research with a new perspective ,new vigor and with new design to handle the problem . In this lecture, I will touch a few topics where research is needed in schistosomiasis with regards to India or South Asia.
ZOOLOGY FACULTY : This is a pure science discipline where Parasitology is supposed to deal basic problems of a parasite like taxonomy , evolution , life cycle etc.
Species identification : The first species of Schistosoma namely Schistosoma haematobium was identified in 1852 in an Egyptian boy and other species ,S.mansoni , was recognized as a separate species ,due to different egg morphology in 1903. India was not far behind in this research as in the year 1886, Bomford could record presence of schistosomes in two bullocks in Calcutta (Agrawal 2012) and in 1906 , Montgomery was able to describe three schistosome species (S.indicum,S.spindale S.bomfordi ) ,simultaneously , from India. Further, Chandler (1926) described a new species ,S.incognitum, from West Bengal on the grounds of recovering morphologically different eggs from human excreta while Rao (1933) created a new species, S.nasalis, on the basis of different location (nasal cavity ) causing nasal schistosomiasis in bovines. It’s a different story that both the new Indian species (S.incognitum and S.nasalis) did not get reference in the monograph written by Bhalerao in the year 1935 who accepted existence of S.haematobium, S.indicum,S.spindale,S.bomfordi ,S.japonicum and S.bovis in India.
In the year 1952, Gadgil and Shah recorded urinary schistosomiasis in village Gimvi of Ratnagiri district, Maharashtra and as per host and location specification of the parasite, they identified it as S.haematobium though later work revealed that Ferrissia tenuis and not Bulinus snails were acting its intermediate host extending the possibility of considering it a new Schistosoma species. Since then no new species under genus Schistosoma has been discovered from India although Orientobilharzia dattai (Ornithobilharzia dattai ) is the last mammalian blood fluke that was discovered by Dutt and Srivastava in 1952  . Does it mean that we have ---------------------------------------------------------------------------------------------------
Present address : ¾,Datt Arcade Phase Three, South Civil Lines, Jabalpur 482001 MP
identified all the Schistosoma species existing in the country ? Contrarily,  the number of Schistosoma species is continuing to swell day by day internationally and at present there are 22 valid Schistosoma species without any new contribution from this country (Agrawal,2012) .
It is not that there is no probability of existing of any new schistosome species in India but the fact is that no serious attention is paid on the topic by Indian taxonomists. Mammalian schistosome cercariae have been recovered from Lymnaea aurricularia whose adults are still not confirmed. We have reported S.bovis like eggs in the albino mice ,experimentally infected with cercariae recovered from Indoplanorbis exustus with male flukes of disputed morphology (Agrawal 2012) . There is also a report of finding oval shaped, spined schistosome eggs from two human stools from Andhra Pradesh whose species have yet not be identified (Bidinger and Crompton, 1989 ) . Rajkhowa et al ( 2005 ) claimed recovering S.bovis eggs from the faecal samples of Mithun from NorthEastern states ; as S.bovis is not existing in this part of geography , it is a case of miss-identity and the eggs might be belonging either to S.spindale or to a new blood fluke species.
Thus, it appears that new mammalian schistosome species are existing in the country and awaiting their discovery. However, any future research should not be carried out exclusively on traditional morphological ground but some more new parameters should be incorporated in such studies. These may be electron microscopy to study minute morphological details, some biochemical parameters like iso-enzymic studies and biological studies to know the differences in patent period ,both in intermediate and final hosts and differences in host susceptibilities . Inclusion of more than one parameter in any future study is essential to confirm any new schistosome species as the differences between known and new species may be overlapping and may not remain beyond controversy if only morphological data are depended on . It may not be out of place to mention that since long S.japonicum was considered a single Schistosoma species , than a species complex and now it has ramifications with identification of separate new species like S.mekongi, S.malayalensis, S.sinensium when detailed studies were carried out on S.japonicum species complex.
Life –Cycle : In fact , we know details only of five schistosome species that are existing in India i.e. S.indicum,S.spindale,S.nasale,S.incognitum and Orientobilharzia dattai. We do not know details of other blood flukes which are discovered from the country , long back. These are Orientobilharzia bomfordi (syn S.bomfordi), Orientobilharzia harinasutai, Bivitellobilharzia nairi, and S.haematobium (?) from Gimvi village . Even intermediate host of none of these blood flukes are known from India though Lymnaea gibsoni is the intermediate host for O.harinasutai in Thailand and Bulinus species are the snails for S.haematobium in other countries . As O.bomfordi and B.nairi have been discovered from India itself with no report of their occurrence in any other country , we are completely ignorant which snail species is acting as intermediate host for these two schistosomes .
Among these blood flukes, B.nairi is exclusively occurring in the elephants and on evolution consideration , blood flukes of proboscides i.e. elephants, should be considered as oldest blood flukes of the mammals . It is amazing how this blood fluke is maintaining itself in nature for thousand years , surviving exclusively in elephant and whose intermediate host is yet elusive from catch suggesting that not many snails are being infected with the fluke at a given period of time. The case of Gimvi fluke is again interesting which confirms its existence in the country but with affirmation of absence of Bulinus species from the continent. For this reason, Ferrissia tenuis was suggested its intermediate host by providing experimental proof but un- answering some questions. An important question is that this snail species is existing in many other parts of the country than why other regions have not been surveyed for positivity of the snail with this blood fluke species or why snails of other regions were considered resistant to this or any other schistosome species(Agrawal 2012).
When we are not aware about the snail species of these blood flukes , there is no question of knowing other details which are important to understand epidemiology of the infection. Once the intermediate host is known for these blood fluke species, further studies are to be undertaken to know susceptible age of snails , mortality of infected snail, pre-incubation period , shedding period of the cercariae , infectivity of cercariae to final host species ,biology of the snail species, etc. In fact, a detailed study on the life cycle of the blood fluke will be possible once intermediate host is identified for these blood flukes.
MEDICAL FACULTY : It appears that ICMR has never involved itself seriously in tackling the problem of schistosomiasis in India. In the start of twentieth century , when first and second world wars caused influx of troops from endemic countries , this was the Indian Army which requested Indian scientists to investigate the chances of spread of schistosomiasis in the country because of returning of soldiers from endemic countries . When the scientists confirmed no chance of spread of the infection in man because of absence of desired snail species in India, a complacent view was created considering man safe from this menace in India . But not much later, Gadgil and Shah (1952) confirmed an endemic focus of urinary schistosomiasis in Gimvi village of Maharashtra state where almost one third population showed signs of the infection. It was also confirmed that a local snail species is responsible for maintaining the infection in the village ; neither there was any restriction on migration of human population to other parts of the country nor the snail species (Ferrissia tenuis ), suspected for existence of the schistosome , are existing exclusively in and around Gimvi village . Even then, it’s surprising why Indian scientists considered the incidence as an isolated one with no probability of its spreading or occurring in any other part of the country. If it’s true that S.haematobium (?) was confined only in Gimvi village , it will be an unique example in the history where a new schistosome species could exist only in a very small geographical area otherwise schistosomes are notorious in engulfing large part of the geography .
Even in post independence period , reports appeared where human stools were shown positive for schistosome eggs . We may mention here at least two reports –one of Dhanda (1956) from Northern India and other from Andhra Pradesh. The former report considered, eggs belonging to S.haematobium, perhaps a miss identity while second report , prepared with the help of British expert on schistosomes (Crompton), abstained itself in naming the schistosome species . Further, it’s difficult to ignore some reports of pre-independent India where positive men have never left the country suggesting acquiring the infection from Indian soil itself ((Baugh,1978). All these evidences strongly support existence of foci of human schistosomiasis in the country which are awaiting investigations from our scientists.
Perhaps a more direct proof of human suffering has come in recent years when scientists (Narain et al 2000, Agrawal et al 2000 a,2000b Rao et al 2007) reported wide prevalence of cercarial dermatitis in rural population. This malady is prevalent in almost all the villages in Madhya Pradesh, Chhattisgarh, Assam , where surveys were made, and whose population is dependent on local ponds for their domestic needs . It is also widely prevalent in rural professionals like fisherman, boatman ,water chest nut growers or laborers etc. No further studies have been made in this direction. Whether , cercarial dermatitis is first or last stage of schistosomiasis in these cases is not known i.e. if schistosomulae are killed in skin itself or are able to migrate to lung , liver and mesentery of human beings with possibility of their survival for long time in certain hosts specially immuno -deficient human beings. It may be emphasized that cercarial dermatitis is caused not only by avian schistosome cercariae but mammalian schistosome cercariae are also responsible for causing it. Therefore ,there is all the possibility of survival of schistosomes in human body in many such cases as some cases showed presence of humoral antibody by CHR test (Agrawal et al 2006) and a single step kit, imported from Netherland, revealed schistosome antigens in the urine of five human beings having history of cercarial dermatitis raising question if active schistosomiasis is existing in India (Agrawal et al 2007) . Again , avian schistosome cercariae may not always be least pathogenic as cercariae of Trichobilharzia rhahnati are not only responsible for cercarial dermatitis but possess the character of migrating to nervous system , including brain, leading to nervous symptoms; we are completely ignorant about this phenomenon in India. Therefore, it is not wise to ignore the cases of cercarial dermatitis in rural population and a more concrete plan should be formulated to investigate these cases employing all modern techniques.
VETERINARY FACULTY: As a maximum number of mammalian schistosome species, reported from any single country, are occurring in India , infecting domestic as well as wild animals, it is obvious that ICAR has more responsibility of solving the problem and should pay more attention on the infection ,particularly when it is causing considerable mortality and animal production losses not because of a single host species but many domestic animal species. However, ICAR has not paid desired attention to contain the infection and I am not aware if any research scheme of ICAR on schistosomiasis is under operation at present . I may mention a few problems in present day discussion .
Our domestic animals (sheep ,goat ,cattle ,buffalo ,dog) are susceptible to more than one schistosome species , but it is our domestic pig which is susceptible only to S.incognitum and no other schistosome species has been recovered from it from India. The pig during its scavenging visits all local ponds, sewage areas , stagnant water sources hence its natural of its exposure to all types of schistosome cercariae , prevalent in that area . But the animal has an innate resistance to all schistosome species except that of S.incognitum . Study of this phenomenon may lead to identification of some host factors responsible for making pig resistant to all schistosome species except that of one species.
Another interesting case relates to Camel which appears quite resistant to schistosome infections as there appears no report of schistosomiasis (with one exception) in this host species. Whether it is because of different grazing habit of the camel which keeps it away from schistosomiasis or it is resistant to all species of the schistosomes will be worth investigating subject.
There are reports of outbreaks of schistosomiasis in sheep ( Lodha et al 1981, Chandra et al 2003 ) and cattle ( Kulkarni et al 1954 ,Singh et al 2000) from different parts of the country. These outbreaks have revealed a high morbidity as well as a high mortality leading to heavy economic losses to the country. Yet no detailed studies have been undertaken to understand these out breaks and how they can be controlled.
A perturbing fact is about failure of diagnosing schistosomiasis in our domestic animals even when intensity of the infection is causing production losses and mortality (Agrawal,1999) .This is further substantiated by a research paper of Chandra et al (2003) who examined some serum samples of sheep , dispatched from Karnataka and Andhra Pradesh ,suspecting death due to Rinder pest . All the samples were negative for this or any other viral or bacterial infection and further scrutiny of the cases led to diagnosis of schistosomiasis in all the sheep flocks of these two states but exhibiting symptoms simulating to Rinder pest. Even in an old outbreak of schistosomiasis in cattle due to S.spindale, the symptoms were resembling those of Rinder pest ( Kulkarni et al 1954) suggesting how diagnosis is being confused ; it further warns that schistosomiasis should be taken seriously by our veterinarians and all attention should be paid to develop efficient diagnostic methods for schistosomiasis in our domestic animals considering the low egg output by the Indian schistosomes.
Nasal schistosomiasis or snoring disease is affecting cattle in whole of the country but nothing substantive has been done to control this ailment . Neither any effective molluscicide to control snail population nor any vaccine has been tried even on a pilot basis. The only methodology ,followed in the field, is treating individual cases with Anthiomaline or Praziquantel which suppresses the symptoms temporarily with their recurrence after 3-4 months of time.
However, none of these drugs and also the recently tried Triclabendazole (Singh and Agrawal 2005) are able to kill any Indian schistosome species to a significant level. It must be emphasized that both Anthiomaline and triclabendazole are being used in bovines extensively in Indian continent ; the former for treating nasal schistosomiasis and latter for fascioliasis . As both the drugs have some killing effect on schistosome species, the extensive field use of these two drugs is leading slow exclusion of susceptible schistosome population from the nature and what will left after some time will be a resistant population of schistosomes to any of these drugs. To this can be added the misery that even the most effective schistosomicide Praziquantel , is not effective in killing any Indian schistosome species to the significant level ,even in present day scenario . Thus , this is a future warning of the things which may come in our way , if immediate attention is not paid on this topic.
NATIONAL INSTITUTE OF PARASITOLOGY : What may be the way to solve above and many other problems ,related to parasitic diseases of man and animals in the Indian continent. In my opinion, there is an urgent need to start an autonomous central government sponsored national institute of Parasitology . It will be important to have persons from all three faculties (zoology, medical and veterinary ) in its staff with mandate of dealing the problems of parasitic diseases of man and animals and asking deputation of imminent scientists from all where to solve the problem of parasitosis . It may sound odd that India does not have any national institute to deal with parasitic diseases although confronted with so many parasitic diseases whereas some European countries, like Britain , Denmark etc have international institutes of Parasitology though these countries do not face big problems on parasitic diseases.
REFERENCES
Agrawal, M.C. 1999. Schistosomiasis an underestimated problem in South East Asia. World Animal Review. 92:55-57
Agrawal M C 2012. Schistosomes and schistosomiasis in South Asia. Springer (India) Pvt Ltd, New Delhi page 351
Agrawal, M.C., Gupta S. & George, J. 2000 Cercarial dermatitis in India. Bulletin of the World Health Organisation. 78; 278
Agrawal, M.C.,Sirkar S.K. and Pandey, S 2000. Endemic form of Cercarial dermatitis ( Khujlee) in Bastar area of Madhya Pradesh.Journal of Parasitic Diseases 24: 217-218.
Agrawal,MC, Rao VG, Vohra S,Singh BK,Gupta S,Singh KP,Bhoneley M,Ukey MJ and Anvikar AR 2006 Cercarian hullen reaction for the assessment of human schistosomiasis in India. Journal of Parasitic Diseases 30 ; 181-183
Agrawal MC, Rao VG,Vohra S, Bhondeley M,Ukey MJ,Anvikar AR and Yadav R 2007. Is active human schistosomiasis present in India ? Current Science 92 : 889
.Baugh SC 1978. A century of schistosomiasis in India: Human and Animal. Revista. Iberica de Parasitologia, 38: 435-472
Bhalerao GD 1935. Helminth parasites of the domesticated animals in India. Scientific monograph number 6. Imperial Council of Agricultural Research New Delhi page 365.
Bidinger PC and Crompton DWT 1989. A possible focus of schistosomiasis in Andhra Pradesh, India. Transactions of Royal Society of Tropical Medicine and Hygiene 83: 526
Chandler, A. C. 1926.A new schistosome infection of man with note on other human fluke infection in India. Indian Journal of Medical Research 14: 179-183.
Chandra D, Singh KP, Singh R, Samanta S and Rasool AR 2003. Schistosomosis in sheep flocks in southern states of India. Indian Journal of Veterinary Pathology 27: 93-94
Dhanda I 1956. Infestation with ova morphologically resembling Schistosoma haematobium. Journal of Indian Medical Association. 26: 407-408
Dutt S.C and Srivastava H D 1952. On the morphology and life history of a new mammalian blood fluke Ornithobilharzia dattai n.sp (Preliminary report ).Parasitology 42 : 144-150
Gadgil, R.K. and Shah, S.N. 1952. Human schistosomiaisis in India. Journal of Medical Science.6:760-763
Kulkarni HV, Rao SR and Chudhari PG 1954. Unusual outbreak ofschistosomiasis in bovines due to Schistosoma spindale associated with heavy mortality in Bombay state. Bombay Veterinary College Magazine 4: 3-15
Lodha K.R, Raisinghani P.M, Sharma, G.D.,Pant U.V, Arya P.L. and Vyas U.K. 1981 Note on an outbreak of ovine pulmonary schistosomiasis in the arids of Rajasthan . Indian Journal of Animal Sciences 51 ; 382-385
Montgomery RE 1906. Observations on Bilharziasis among animals in India. Journal of Tropical Veterinary Science 1: 15-46 ; 138-174
Narain, K, Mahanta, J. Dutta R. and Dutta P. 1994. Paddy field dermatitis in Assam: A cercariae dermatitis. Journal of Communicable Diseases 26 ; 26-30.
Rajkhowa S, Bujarbaruah K.M, Rajkhowa C and Thong K 2005. Incidence of intestinal parasitism in Mithun (Bos frontalis ). Journal of Veterinary Parasitology 19: 39-41
Rao MAN 1933. Bovine nasal granuloma in the Madras presidency with a description of the parasite. Indian Journal of Veterinary Science and Animal Husbandry 3: 29-38
Rao V.G. Dash A.P.,Agrawal M.C,Yadav RS,Anvikar AR,Vohra S,Bhondeley MK, Ukey MJ,Das SK,Minocha RK and Tiwari BK 2007. Cercarial dermatitis in central India : an emerging health problem among tribal communities .Annals of Tropical Medicine and Parasitology 101 : 409-413

Singh B.K. and Agrawal M.C. 2005 Triclabendazole on bovine hepatic schistosomosis. Indian Journal of Animal Sciences. 75 ; 654-655

Singh R, Chandra D, Rathore BS, Singh KP and Mehrotra ML 2000. Investigation of mortality in cattle and buffaloes with particular reference to hepatic schistosomosis in cattle. Indian Journal of Veterinary Pathology. 24: 8-11

No comments: