Friday, December 13, 2013

WITH PRESENT KNOWLEDGE , CAN WE SUCCEED IN CONTROLLING SCHISTOSOMIASIS IN INDIA

This is the second lecture delivered in the winter course at IVRI,Izatnagar on 11th Dec 2013 and i am reproducing the same here . I will appreciate to receive any comments which may further the subject .It will be my pleasure if any research organisation is interested to collaborate in this endeavor. 

                                                                M C AGRAWAL
                              FORMER NATIONATIONAL FELLOW AND EMERITUS SCIENTIST
                                 COLLEGE OF VETERINARY SCIENCE AND A H , JABALPUR 482001
                                                             drmcagrawal@gmail.com    


It is heartening to note that one part of this winter course is to teach molecular techniques about control of parasitic diseases .In the past also, there had been some advance courses and discussion about control of parasitic diseases . But whether these discussions and advance courses can lead to  control of parasitic diseases ? Obviously, the answer is no. Now, with the changing time, it becomes imperative to know why we need to control parasitic diseases, which diseases are given priorities , and how we can control  these parasitic diseases.  And this is what I am going to discuss ; thus my lecture will not be a mere academic exercise of citing references  from some research papers. There is now time ,we should discuss how we may try to control parasitic diseases and what should be our research priorities that may help in achieving these goals.   
                If we analyze disease control program of our country, it will be clear that the country has given top priority ,logically ,for controlling those infectious diseases that are affecting human population. Thus there are central government’s programs for controlling tuberculosis, malaria, filariasis, guinea worm or naru  ,polio (small pox already eradicated ) etc Interestingly, almost no attention is paid on zoonotic aspects of these diseases  or medical faculty has  not taken diseases where animals are playing a crucial role in their maintenance. For example, we have not taken sincere  steps for controlling rabies .This reflects how wide apart are the two professions (medical and veterinary) which are supplementary to each other  to combat zoonotic infections of the country.
                When we come to animal diseases ,the control programs have been launched only to limited diseases like Rinder-pest, FMD, anthrax with vaccination programs of these and other infectious animal diseases. These are also the diseases ,where the veterinary hospitals ,districts and states generate the data and pass on to government of India.
                Has government of India ever launched any control program related to any parasitic disease of our domestic animal ? Here I mean control program like that of Rinder-pest or FMD . To my knowledge, there was or is  none. No doubt there have been some vaccination programs for controlling parasitic diseases . The one was about lung-worm vaccination for controlling lung-worm infection of sheep and goats ,particularly in Jammu & Kashmir , Himachal Pradesh ( now, vaccine production has been stopped by IVRI though infection is still existing ).  The other is Theileria vaccine produced by NDDB and supplied for controlling theileriosis among cross bred cattle . Again , this is not a infection which is affecting all our domestic animals. Thus we have attempted to control a infection (lung-worm) which is restricted to certain states or a infection which is affecting limited number of our domestic animals. And we have shied  away in paying our attention to the parasitic diseases which are affecting almost all domestic animals and existing in  all the states. Therefore, we have come to a crucial point where we need answer of above questions - why we need to control parasitic diseases, which diseases are given priorities , and how we can control  these parasitic diseases.  And my this short lecture will try to discuss some of these points with the hope that you , our young Parasitologists ,will devote some time to find answers of these and related  questions which are important for controlling parasitic diseases in the country. Answer of these questions are important as you will agree with me that all your research efforts will not fructify unless and until you attempt to control the parasitic infections in our country, thereby reduce mortality and animal production losses.
WHERE IS THE DATA :
If you go to any funding agency or even any government, the obvious question will be why we wish to control the particular parasitic disease. Naturally, you will put up the data about mortality and pathology of that parasitic disease . By the way, from where have you collected these data ? From some research paper or a review article or from a book ?  And how they have calculated these data  ?
I am sure that your data have not been collected from veterinary hospitals of the state or Animal Husbandry department of the country . And when these data have not been collected from the villages whether they are representing correct scenario of the infection is debatable.
VETERINARY RECORDS :
What I have said above, is all because of my experiences . While working on my book “Schistosomes and schistosomiasis in South Asia” (Agrawal,2012) ,I tried to collect the data of nasal and hepatic schistosomiasis from veterinary hospitals and veterinary diagnostic laboratories (division level),state and central governments ;  as ,in my opinion, compilation of data from these sources is important since research journals fail to provide a detailed view of the infection ; these journals have not reported each and every outbreak or prevalence of the infection in each animal species from each geographical area .
                To my dismay, I could not collect any data, related to schistosomiasis, from any of above  source ,details have been discussed in my book .Here, it will be suffice to mention :
·         There is no direction from the government to keep record of parasitic diseases and details thereof. Neither any data are passed to state or central government .
·         The veterinary hospital registers are maintained in such a way that you cannot extract any information from them. Even it is difficult to differentiate between new and repeat cases, cattle and poultry  (I have written about this topic which has been published in the news letter of National Academy of Veterinary Sciences when Dr S K Ranjan was the President).
·         The veterinary diagnostic laboratories are vague in their reporting and counter checking is missing . While reporting coprological results (generally by direct wet smear method ) ,generally positive cases are reported  as “positive for helminth or fluke or roundworm eggs” . Thus they have not differentiated the eggs where it was easy to differentiate .
It is clear that we need changes in above system and a fresh outlook  is needed to the problem so that  we will be able to  collect the data related to parasitic diseases.
WHICH PARASITIC DISEASES TO CONTROL ON PRIORITY :
This is an important question  that if we decide to control parasitic diseases what should be our priorities ?
Answer of this  question , at first hand, appears simple i.e.  the parasitic disease which is causing greatest mortality and highest pathogenecity in domestic animals should be  attended first. But how we will reach to this conclusion when we have not generated data in this regards. And when we are attempting to generate the data, are we using sensitive and specific methodologies  ? This aspect is important else our results will not be accurate. While deciding importance of the disease, we have to examine its prevalence in each animal species, age and sex wise ; the seasons when disease is occurring; animal husbandry practices  and  geographical areas where infection is existing.
With the above, two more important aspects are also linked . One is the mortality occurring in the infected animals. It may happen, looking to Indian conditions, that the animal is not infected with single parasitic infection but multiple infections and in such cases we have to device methods for ascribing death etiology . The other aspect is related to pathology of the infection which is reflected to animal production losses. No doubt we will need new methodologies to decide the above facts and these may change as per advancement of our knowledge and environment. If we will not follow new techniques , there are all chances of making mistakes as has been done while reporting schistosomiasis in post-mortem cases ( Rathore,1998).
PRIORITY AMONG HELMINTHIC DISEASE :
As my present discussion is related to schistosomiasis, I may raise a question to you – which is the most important helminthic disease of our domestic animals ? Some of you will answer - haemonchosis, or gastro-intestinal nematodiasis, others may answer fasciolosis , or amphistomosis ; while some of you will say nasal schistosomiasis but  a few or none will ascribe hepatic schistosomiasis as the most important helminthic problem of our domestic animals . May I ask the reasons for your such conclusion ?
Those who are ascribing fasciolosis as most important helminthic disease will put forward their slaughter house experience where most of the livers yield adult Fasciola gigantica  .Further, the faecal examination shows presence of Fasciola eggs in many cases ( its different that we are not differentiating eggs of Fasciola from those of amphistomes ). And those who are new to Indian  parasitology will cite the reference of a foreign veterinary book where fasciolosis is considered as most important helminthic disease of domestic animals.
Those who are ascribing amphistomosis as most important will support their argument that every rumen in slaughter house possess one or other species of amphistomes and almost all faecal samples are positive for amphistome eggs.
Against these arguments ,we do not have such visibility of hepatic schistosomiasis hence can not be considered as most important helminthic disease in India. I have discussed this topic elsewhere ( Agrawal,1999 2003) but will like to draw your attention to the need of employing correct techniques for reaching a correct decision. As time does not permit me to go into details of such discussion, I will mention only silent points emphasizing how important it is to use a correct technique and unbiased attitude for reaching to a correct conclusion.  I am mentioning some facts for your consideration and further investigations :
·         Fasciola gigantica, the only existing Fasciola  species in India , spreads through Lymnaea auricularia or Lymnaea acuminata which is a strict fresh water aquatic snail (unlike to amphibian  Lymnaea truncatula –intermediate host for F.hepatica) and survives only in perennial water sources hence animals will get infection only from perennial water sources.
·         F.hepatica  is more damaging to domestic animals than F.gigantica .
·         Against one species of Fasciola, there are at-least five schistosome species (Schistosoma indicum,S.spindale,S.incognitum, Orientobilharzia dattai and S.nasale) which are affecting our domestic animal species.
·         Schistosome infections spread through Indoplanorbis exustus and Lymnaea luteola – both species are capable to survive not only in perennial water sources but also in temporary water bodies thereby giving higher geographical spread.
·         A large number of amphistome species (40-42) are existing in the country (Dutt,1980) some of which have been synonymized. However, only four genera have been incriminated in pathogenesis to domestic animals .
·         In amphistomosis , it is only young animals which suffer and that too only from immature amphistomosis.
·         Many fresh water snails are acting as intermediate hosts for amphistomes hence their geographical spread is as large as that of schistosomes.
Now you have  to determine ,using new methodologies, which helminthic disease is more important in our domestic animals. Here, you might have noted one more fact  ; this importance will vary as per our husbandry practices. All these fluke infections are important only in grazing animals with limited effect in stall fed. Thus our priorities will vary as per animal species, husbandry practices and geographical areas. Therefore, you will identify  those parasitic diseases to be given national importance and those with regional importance etc. 
HOW TO CONTROL SCHISTOSOMIASIS :
We have come to the last part of our lecture .And that is if we decide to control any parasitic disease in our domestic animal , how we can control  it . I will take references from schistosomiasis which have been discussed in more details in my book (Agrawal,2012). Indeed, this is the only helminthic disease that has been given so much importance and where so many countries agreed to launch control program in collaboration with WHO (1985) . Ironically , India has not participated in such program.  Interestingly, WHO have not touched zoonotic aspects of the infection while attempting control program of human schistosomiasis . The review of this  program may high light our short comings  which are important to get rid of for achieving any success in controlling any parasitic disease and also  animal schistosomiasis in India or South Asia.
MULTIPLE APPROACH :
No disease can be controlled by following a single step approach , how so ever,  effective it may be . The infection has to be tackled from all aspects so that prevalence of it may be reduced to the levels where further transmission becomes difficult .Following multiple approaches were followed in schistosomiasis :
·         Chemotherapy
·         Health education
·         Snail control through use of molluscicides
·         Environmental modifications
You will realize that such program is not possible without a large team and funds  which a department of Parasitology of an institute cannot afford .  No doubt , this control program of schistosomiasis was able to reduce prevalence rate as well as pathogenesis ,as the latter is directly proportion to the intensity of the infection; and the success was  both due to  political will and scientific team work . Here, it will be prudent to discuss scientific reasons for their success and how it will fit in our program of controlling animal schistosomiasis in India. One important difference has to be remembered that while following any control program ,we have to monitor  not one but more than one animal species.
CHEMOTHERAPY :
The most important reason of the success ,perhaps, was mass treatment of the population with a most effective schistosomicide (Praziquantel) whose single oral dose @ 40-60 mg/kg body weight was 80-95% effective in urinary and hepatic schistosomiasis . Since the weight of children varied between 20-50 kg, the dose of Praziquantel was cost effective, beside easy in administration .
When we compare this scenario with that of India,  our schistosome species  are different from those dealt by WHO hence there are all differences in schistosome bionomics . And praziquantel against any of these Indian schistosome species (S.indicum,S.incognitum, S.spindale ) has not proved as effective as reported against S.haematobium or S.mansoni . In fact, our experimental work on pig- S.incognitum model has failed to reduce schistosomes to a significant level  with presence of left over schistosome population as high as 40% ( Shames et al 2000)  A same scenario was observed when the drug was tried in other experimental models ,with schistosome reduction ranging from 50-65% (left over fluke population between 50-35% ) ,  but using other Indian schistosome species. Ironically, no available flukicide (including anthiomaline ) was found to lead to a significant reduction in schistosome population in any experimental model, tried in our laboratory or by other workers ( Agrawal ,2012).
Therefore, it is not advisable to use Praziquantel or any other flukicide in any mass treatment program which has failed to reduce schistosome population to a significant level in our animals. This is because such use will lead to the high probability of development of resistance of left over schistosome population against praziquantel .
One more hindrance in using praziquantel for mass treatment in animal schistosomiasis is with regards to its cost for treating bovines against schistosomiasis. In one field trial against nasal schistosomiasis in Balaghat district of Madhya Pradesh , 60 tablets of Prazi Plus@ , which works out approximately to 20 mg/kg body wt was effective in eliminating completely clinical symptoms of snoring disease from 14 out of 18 cattle. However, cost of one treatment comes to Rs 1500/ per animal as market cost of two tablets is Rs 50/ (Agrawal, 2012) .
DIAGNOSTIC METHOD :
While implementing any control program, it is important to monitor the rate of infection and its  intensity in the given population prior and after the treatment. This monitoring is possible  by using a simple, rapid, economic but sensitive parasitological  diagnostic technique that may detect, light ,moderate and heavy infections. In WHO case , Kato-Katz technique was applied that fulfilled all the above criteria and was able even to detect light infections ( 24-96 epg) with presence of 1-4 eggs/slide, made of 41.7 mg of faeces (WHO,1985).  In contrast , a very low epg ,ranging between 2-4 in ruminants and 10-50 in pigs has been reported by almost all the Indian workers (Agrawal,2012) ; for this reason almost all egg detection methods have poor efficacy ,cannot be employed in control program, hence  warranting further work on this issue . We may also undertake further research on hatching process, as this has proved superior over egg detection methods.
 SNAIL CONTROL :
The snail control ,in WHO  program , was undertaken by using Niclosamide which has proved highly effective in killing the intermediate hosts i.e. Bulinus and Biomphalaria . Ironically , Niclosamide is not available in Indian markets and has to arrange its import from other country. We were able to procure Niclosamide and undertook  both experimental and field trials on fresh water snails , observing its high efficacy in killing Lymnaea luteola, Indoplanorbis exustus and Gyraulus but without affecting other water fauna and flora (Agrawal et al ,2005, Agrawal 2012).

However, ecological conditions of fresh water snails in India ,differ from those of other endemic countries. In India, these are the ponds, tanks and other water sources, both perennial and temporary , which are inhabited  by these fresh water snails, where as in endemic countries these were the rivers where snails are  surviving. Thus , we have more wide spread population of the snails , making our efforts more difficult while attempting snail control.

BIOLOGICAL CONTROL :
As use of chemical molluscicides may  cause environmental pollution , efforts are being made to find other alternatives for snail control . Work is being carried out to find Plant molluscicides which are more eco-friendly . Likewise, search is being made to find natural enemies of the snails that may be used as biological control agents for reducing snail population. However, it must be remembered that the biological enemy or competitor should not be introduced from outside the country/area as they may prove harmful afterwards as experienced by WHO (1985).
One natural enemy of young fresh water snails has been identified by us (Agrawal,2012) in the form of nymphets of dragonfly which co-habitat with the snails under same ecological conditions ; these nymphets are carnivorous in nature ,devouring young snails with their life span ranging from 1-3 years ( hence once introduced in the ponds, there is no need of re-introduction every year ). There is the need to develop the techniques for mass production of these nymphets which also feed on mosquito’s larvae (Agrawal 2012). Here is the importance and need of your molecular techniques which may pave the way of producing eggs and nymphets in large number , for their use in controlling snails or mosquito larvae.   
HYPER-PARASITISM  :
                As stated above,  Praziquantel  and  anthiomaline  are not able to kill a significant number of Indian schistosomes, which is not the case with S.haematobium or S.mansoni. There are also chances of development of resistance of the schistosome population  ,left over after wide use of these less effective  drugs. Therefore, there is the need to think alternatives against chemotherapy for parasitic diseases.
One promising area of research might be searching hyper-parasites of schistosomes or of  any other parasite which is causing disease in man and his animals. As you are aware these hyper-parasites are those organisms which parasitize on the parasite itself e.g. schistosomes . This hyper-parasite  may be a bacteria or a virus or even a fungus. We have to search those hyper parasites which are lethal to these parasites and should be host specific thereby eliminating our animals or human beings in causing any harm .  
NEED OF A NATIONAL INSTITUTE OF PARASITOLOGY :
With this lecture, I tried to discuss how ill equipped we are for launching a state or national level control program against any parasitic disease of our domestic animals. There is the need to re-think on our research programs and to develop methodologies which may help directly or indirectly in controlling parasitic diseases of the nation . But it will be a bad idea not to take any control measure and waiting for developing proper techniques or drugs  prior launching any control program . Notwithstanding these facts , management of animal excreta may greatly help in controlling parasitic diseases. If we start collecting all cattle dung to fill our gobar gas plants or to convert it into vermin-compose , this will not only control parasitic diseases but will also improve rural economy.
At last, I once again emphasize the need of a National Institute of Parasitology in country for paying proper attention on the parasitic diseases ,which are causing not only mortality but also production losses thereby affecting adversely national economy. I am avoiding repetition  what I have already said during  my lecture of Dr SC Parija oration gold medal award  in 2012 at Indore and  which has been published  in  Para Sight  2 Volume 2 ,issue 1 of IAAVP            and is also posted on my blog www.indianschistosomiasis.blogspot.com
SUMMARY :  
Launching of control program for any animal  disease which is causing mortality and production losses is important for any country . Ironically , the government of India  has launched control programs for viral and bacterial diseases but there is no control program ,ever launched by any government against any parasitic disease of our domestic animals. Neither , there is any system of collecting data ,related to animal parasitic diseases, from our veterinary hospitals and veterinary diagnostic laboratories . Therefore, it becomes difficult to answer- why we need to control parasitic diseases, which diseases are given priorities , and how we can control  these parasitic diseases ?
When we come to the question of how we can control animal schistosomiasis in India , we observed that our diagnostic technique is not sensitive due to low egg production of Indian schistosomes and requires further research. Likewise, the most effective Praziquantel drug is not able to kill significant number of Indian schistosomes with 35-50% left over blood-flukes . To circumvent this situation, it will be prudent to find out hyper-parasites of schistosomes and other parasites which will selectively kill these without harming their hosts. However, it will be futile to wait for developing proper techniques. Instead , animal excreta may be collected at mass scale and may be used in gobar gas plants or for preparing vermin-compose which will not only reduce prevalence of  parasitic diseases but will also improve rural economy.  The author has again emphasized opening a national institute of parasitology so that a holistic view may be developed towards parasitic diseases ,existing in the country .
REFERENCES :
Agrawal, M.C. 1999. Schistosomosis : an underestimated problem in animals in South Asia. World Animal Review 92 : 55-57.
Agrawal,M.C. 2003. Epidemiology of fluke infections . In (ed Sood ML)  Helminthology in India .Inrtenational Book Distributors, Deharadun . Page 511—542
Agrawal MC.  2012.  Schistosomes and schistosomiasis in South Asia. Springer India Pvt Ltd , New Delhi.
Agrawal MC ,Singh KP, George J and Gupta S 2005. Niclosamide trials on Indoplanorbis existus and Lymnaea luteola under different conditions. J Parasit Dis 29: 53-58

Dutt SC 1980. Paramphistomes and paramphistomiasis of domestic animals of India. Punjab Agriculture University, Ludhiana . Page 162.
Rathore BS  1998 . An epidemiological study on buffalo morbidity and mortality based on four year observations on 18630 buffaloes maintained at 28 livestock farms in India. Indian J Comp Microbiol.  19 :43-49
Shames N,Agrawal MC and Rao KNP 2000. Chemotherapeutic efficacy of praziquantel and closantel in experimental porcine schistosomiasis. Indian J Anim Sci 70 : 797-800
WHO  1985. The control of schistosomiasis. Technical report series 728. World Health Organization ,Geneva Page 113