Onderstepoo1't J ou1'nal of Vete1'ina1'y Science and Animal lndust1'y, Volume I, Numbe1' 1, 1933.
The Chemotherapy of Oesophagostomiasis in Sheep.
By H. 0. MONNIG, B.A., Dr.Phil., B.V.Sc., Veterinary Research Officer, Ondcrstepoort.
I. INTRODUCTION AND GENERAL DISCUSSION.
BEFORE the introduction of the Government Wireworm Remedy as a chemo- therapeutic agent for the control of Haemonchosis in sheep, the position with respect to this parasite had become so acute in many parts of South Africa, that sheep farming was a rather hopeless venture, as a large percentage of the lamb crop was lost annually. It was soon found, that regular dosing at intervals of about three weeks, as indicated by the life-history of the parasite, not only controlled the wireworm in a very effective m'1nner, but also brought about a marked improvement with respect to other worm parasites. The sheep, having obtained relief from the most serious of its internal parasites, was able to combat the rest on account of its increased vigour and the improvement in its general condition. It is a well known fact, that those farmers who have practised such regular dosing, are not greatly concerned about worms in sheep any longer.
Unfortunately the high price of wool some years ago brought about a great increase of sheep farming, in many cases by farmers who had little knowledge of worm diseases and took little trouble to acquire this knowledge. At the same time the way for further trouble was being paved by much overstocking.
The result is, that the nodular worm, Oesophagostomum columbianum, has been able to develop in sheep that were not treated for wireworm and, aided by overstocked pastures, it has become so prevalent in many areas that, even though the sheep m'1y now be regularly treated for wireworms in some cases, the infection with nodular worm is too severe for the sheep to overcome. The nodular worm is at present rapidly becoming as great a menace to the sheep industry as the wireworm was formerly.
Investigations in connection with the chemotherapy of this parasitic disease were started by the writer in 1922, but the work was interrupted and restarted in 1927, since which time a large number of tests have been m'1de.
Although no :finality has been reached, it i~; considered desirable to publish what information has been obtained in the course of the work, as it may give other investigators some useful information, especially with regard to the exact nature of the problem.
In this paper treatment by administration of drugs per os only will be dealt with.
It was realised from the beginning, that the difficulty would be to get the drug to the worms. Several methods were tried to attain this object and it will be seen that there are several quite useful drugs, but that it appears to be a waste of time and material to proceed with such tests until the fundamental problem has been solved. This is the physiology of deglutition in the sheep.
In other words, a method of drug administration will :first have to be found, which will cause the sheep to swallow the m'1terial directly to the abomasum.
CHEMOTHERAPY OF OESOPIIAGOSTOMIASIS.
It became quite clear during the course of the work that, when a suitable drug is swallowed into the abomasum, it can effectively deal with the nodular worm but, when it is swallowed into the rumen and becomes diluted in the large quantity of ingesta, eventually being passed on in small quantities with food, the result will be nil.
Since ordinary dosing will cause the drug to•be swallowed either into the rumen or the abomasum, a drug may be tested on several sheep, which may all swallow it to the rumen. The result will be negative and the drug may be discarded as useless, although it may be quite effective when swallowed into the abom1sum. It is therefore clear, that such testing is misleading and a waste of energy and material.
Several authors have published the results of their investigations with regard to the administrations of drugs into the abomasum. Their work was carried out chiefly in connection with fluids. For the treatment of nodular worm in sheep a fluid drug is not as suitable as a powder, mainly on account of the factor of absorption. It will be seen, that fairly insoluble drugs seem to offer the greatest possibility of success. The problem thus presents itself in the first instance as a question of administering a powder into the abometsum and investigations with this object in view have been in progress here for some time.
This question of dosing into the abom1sum is the most important problem to be solved in connection with the treatment of sheep for gastro-intestinal worms. It would appear from the work of Green (1918) and Veglia (1918) on the chemotherapy of haemonchosis and from the wide experience gained in the treatment of sheep for this disease, that in this case it makes no great difference whether the drug employed reaches the abomasum in a concentrated form or in small quantities from the rumen and reticulum over a prolonged period. Green (1918) states, in connection w1th the Government ·wireworm Remedy, "It seem> probable that whenever the dose goes wholly into the rumen the concentration in the abom'lsnm rarely exceeds ·001-·002 per cent As203 at any tim;. That so low a concentration, even after prolonged action, is effective in destroying the wireworms is not absolutely certain, but is highly probable Veglia's observations, and the uniformly successful results of dosing on the large scale in the field, suggest that the wireworms are destroyed irrespective of the path taken by the dose, and are, therefore, susceptible to slow intoxication by very low concentration of arsenic." This rem ;ely, of course, contains, besides arsenic, also a large proportion of copper sulphate, which was, however, not considererl in the paper referred to.
·In spite of these findings, it does appear desirable to dose such drugs also into the abomasum, as that would probably allow a decrease to be effected in the dose rate, resulting in greater safety. With the present state of affairs the dosage must be sufficiently high to be effective in those cases in which the drug is swallowed to the rumen, while it must be as small as possible to be safe.
It is further quite obvious, that the solution of this problem will do away with some of the difficulties experienced in the treatment of infections with small strongyles (T1·ichost1·ongylus, Ostertagia, etc.) and tapeworms in sheep.
The question of preliminary starvation necessarily crops up and will be dealt with briefly. There are two aspects to be considered : the necessity of starvation of sheep in a general way and the role of starvation in the technique of administering drugs into the abomasum. With regard to the first point, the writer has several years ago discussed the theoretical aspect of the matter and tested dosing without starvation for wireworms on a large scale (Monnig,
H. 0. MONNIG.
1929 a anrl. b), with the result that this method is now generally recommended and practised with great success. The method has been criticised, especially by le Roux (1932), but the occurrences on which he bases his criticism were complicated by other factors and do not allow a definite decision on the question of starvation. Since that time several carefullv controlled tests have been motde, for instance, regular three weekly dosing ~ithout starvation of 90 young sheep running on infected pasture for a period of almost a year, and the results have proved the method to be satisfactory. Even though it may eventually be shown, that such closing is not quite as effective as with preliminary starva- tion, which the writer doubts, it would seem more rational to remove a slightly sm'tller number of the worms and avoid starvation with its effect on the sheep and other incidental disadvantages, than to remove a few more worms and have all the disadvantages, especially since regular dosing is the only satisfactory method of treatment and with such a procedure 100 per cent. efficacy is not necessary.
The importance of this question becom3s evident when the second point is considered, namely the role of starvation in the technique of administering drugs into the abomasum. Whether starvation will assist in inducing sheep to swallow into the abomasum is not definitely settled, but it does not seem to be of any consequence. Theoretically, starvation of sheep is apparently believed to cause a decrease of the abom'tsal contents or even to empty this organ of ingesta. The facts of this m1tter will be tliscussed again later. Supposing, however, that this is true, it does not appear to be desirable to administer an irritant or corrosive drug into an empty abomasum and hence starvation would seem-, to be contraindicated in such a method of dosing, especially as we know that the abomasal contents will not dilute the drug to such an extent that it becom3s ineffective against wireworms. In the case of treatment for nodular worm, the drug, after being swallowed into the abom'tsum must be passed on as rapidly as possible to the colon. Starvation tends to cause stagnation of the stomach contents and is, therefore, contraindicated, as it would retard the passage of the drug on its way to the nodular worm, even if the sheep be fed immediately after closing.
The facts with regard to the fate of ingesta in the different compartments of the ruminant stomotch, as affected by starvation, have been studied in th investigations of Green and Veglia referred to above. Green states: "Accord- ing to Veglia's observations rumination was m'trked after a feed, but became more and me>re remittent as the starvation period lengthened, until after seven- teen hours it practically ceased. At the same time the semi-solid contents of the rumon were not reduced to the extent which might have been expected, but m<tintained a minimum average bulk, and in some cases rem'tined as high as 4-5 Kilos after seventeen to twentv-four hours starvation. The contents of the rum3n and reticulum in sheep killed two to four hours after feeding were in general not much greater than in those killed after a day's starvation, ani!
individual variation sm:>thered all clear differences. The contents of the abom'tsum varied more, and, although in some cases the bulk after long starva- tion was suggested as lower than after short starvation, the differences were by no means so m'trked as might have been expected, but were, on the whole of an arbitrary character. The extreme range in the abomasal contents was 25 c.c. to 940 c.c. for seventeen sheep killed two to four hours after feeding, and 55 c.c. to 360 c.c. for twenty-seven sheep killed after seventeen to twenty- four hours starvation." The writer can fully endorse these statements from his experience. It seems as if the ruminant stom'tch normally retains a fairly large minimum bulk even after prolonged starvation and that the content of
CHEMOTHERAPY O:f' OESOPHAGOSTOMIASIS.
the abomasum is very variable as stated by Green. Starvation thus causes stagnation and not an emptying of the stomach. If these facts are correct, and they must, if exceptional, produce a very large proportion of exceptional cases, starvation is certainly contraindicated when the drug has to be passed on rapidly from the abomasum, as in the treatment of oesophagostomiasis.
II. EXPERIMENTAL WORK.
The nature of the problem is now clear and it will be obvious that the tests of drugs to be recorded here are of a preliminary nature only. It will t.herefore be attempted to summarise the results as briefly as possible.
The technique employed throughout the tests is that described by the writer (1931). In short, the sheep are infected with larvae of Oesophctgostomum columbianum and when the worms are adult the nature and degree of infection are determined by faeces cultures and egg counts. In the tests recorded below egg counts were, as a rule, not made as the tests were preliminary "feelers."
The selected sheep are treated and the faeces examined daily for at least a week or until no more worms are passed. Faeces cultures and egg count~ are again made a fortnight after treatment to determine the remaining infection.
Since purgation mechanically removes some nodular worms from sheep, tests in which the drugs caused purgation are not taken into account as the effects cannot be ascribed directly to the drug. Any other course would be misleading, since the drug cannot be depended upon to cause purgation regularly and removal of the worms by purgation is neither dependable nor desirable in many cases.
(a) SoLUBLE DRuGs.
Little need be said under this heading. It is well known that relatively soluble drugs which have been tested so far have had no effect. Tests made by the writer with such drugs gave the same result. The following table shows the results obtained with a few of the drugs selected from the list of relatively soluble and fluid drugs tested : -
TABLE I.
I No.
Drug. Dose in Gm.
l
Sheep. of Effect. Remarks.Aluminium chloride ...
I
2 2 -
Protargol. ...... 1 2 -
Pyrethrum ....... I 2·75 7 -
Thymol. ............ 4 1 -
{:!-Naphthol. .......... 1 1 Slight. No toxic effects in any Sod. cacodylate ... 0 ·5 and l 2 -
of these cases.
Benzol sulphochloride ... land 2 c.c. 2 - Naphthalene tetrachloride .. 0·5 and l gm. 2 -
Kamala ... 3 2 -
Nicotine salicylate ... 0·25 l - I
Nicotine tartrate ...... 0·5 1 - j
-- - In this and the following tables the effect is given as " slight" when a small number of the worms present were passed, "fair" when about half or more were passed and " good " when all or almost all were passed.
H. 0. MONNIG.
(b) SOLUBLE AND OTHER DRUGS WITH AsTRINGENT AND LAXATIVE.
The idea is to reduce absorption by means of an astringent and to promote rapid passage to the colon by means of a laxative. It is not an easy matter to purge sheep, at least not without very variable results. Consequently a laxative as indicated here will usually not cause purgation ; at most the faeces will become soft. (The writer has had the most uniform results in purging sheep by the administration of 100 gm. magnesium sulphate and 30 gm. sodium chloride in 500 c.c. water by ,o:tomach tube into the rumen).
TABLE II.
DRUGS GIVEN WITH l GM. PoTASSIUM ALuM.
Drug.
Thy;noL ..... . Pwnc amd ... . Atoxyl. ........ . Tartaric emetic ......... . Copper arsenite ... .
~ercurochrome ... . Lead arsenate ... . Government iVireworm
Remedy ... .
Dose in Gm.
0·5 0·5 0·5 0·5 0·5 0·25 0·5
No.
of Sheep.
TABLE III.
Effect. Remarks.
l ~No.
toxic effects in anyJ
of theee '"''"·DRuGs GIVEN WITH l GM. SomuM Au.:M.
Drug.
Ammon. sulphate ... . Gentian violet ...... . Trypan blue ........ . Potassium iodide ...... . Santonin ... . Pot. ferro cyanide ... . Pot. thiocyanate ...... . Antimony trioxide ... . Calomel.. ........ .
~ercuric sulphate .. .
Dcise in Gm.
l l l l l l l l 0·5 0·5
No.
of Sheep.
l l l l l l l l l l
TABLE IV.
Effect.
Slight.
Slight.
Fair.
I Remarks.
ll
I ~No toxic effects in any
I of these cases.
j
DRuGs GIVEN WITH l GM. TAKNIC Acm.
Drug.
Ammon. sulphate ... . Gentian violet ..... . Trypan blue ... . Potassium iodide ....... . Santonin ... . Pot. ferrocyanide ... . Pot. thiocyanate ... . Antimony trioxide .... . Calomel. ....... . Mercuric sulphate ... .
Dose in Gm.
l l l l l l l l 0·5 0·5
No.
of Sheep.
11
Effect.
Slight. Slight.
Slight.
Slight.
Fair.
Remarks.
Died of gastroenteritis.
!._: r
GIIE:MOTJllm.U'Y OF OESOrH.-\GOSTOMIASIS.
TABLE
v.
DRUGS GIVEN WITH 0 ·5 GM. CALO:viEL.
Dose No.
I
Drug. in of
I
Effect. Remarks.
Gm. Sheep.
(1-Naphthol. ... 1
I
1 -l
Copper tartrate ........... 1 2 Slight to 0.
Arsenious sulphide ...... 1 7 Good (1),
l
No tmUo ""oo" in~y
Fair (3), Nil (3).
Picric acid ........... 0·5 2 -
Trypan blue ... 1 2 - I of these cases.
Potassium iodide ...... 1 1 - I
Sulphur .................... 2 & 5 2 -
I
Barium arsenate .......... 1 2 Fair.
Bismuth carbonate ... 2
!
2 - )
TABLE VI.
DRuGs GIVEX WITH 0 ·5 GM. CALOMEL+l G~r. Sommr ALUM.
Dose
I
No.
Drug. in of Effect. Remarks.
Gm. I Sheep.
Trypan blue ............ 1
I
3 Slight (1),I
Nil (2).
I
Tartar emetic ............ 0·5 & 1
I
3 Slight (2),
Nil (1). [No toxic effects in any Santonin ................... 1 & 2 3 Slight (2), of these cases.
I
Nil (1). I
Calomel and alum alone ... 0·5 & 1 3 Slight (2),
J
Nil (1).
Discussion.- On the whole this line of attack does not appear very promising.
The drugs that gave the best results were relatively insoluble, like Mercuric sulphate and Barium arsenate, which also produced similar results when given alone.
(c) RELATIVELY INSOLUBLE DRUGS.
The feeding habits of the worm will naturally play an important part in the chemotherapy against it. Observations have been made by the writer on the feeding habits and the question is being further investigated. It seems as if the worm ejects through its mouth a digestive fluid, probably secreted by the oesophageal glands. The attack is probably directed mainly against the mucous membrane of the colon, although the worms are never found to adhere to it. The pre-digested material is then ingested by the parasite. This seems
H. 0. :l.fONNIG.
to be the method of feeding of this worm and would be comparable to the feed- ing habits of other worms like the small strongyles of the horse, according to Wetzel (1930) and P1·olept~ts obt~t.sus according to Schuurmans-Stekhoven and Botman (1932), although these worm> attach themselves to the mucous mem- brane.
Apart therefore from the possibility of getting relatively insoluble chemicals to reach the colon, the feeding habits of the worm would apparently enable it to swallow small particles or solutions of drugs present in the contents of the colon and the drugs m1y then act on the worm. This expectation appears to have been realised in the tests with relatively insoluble drugs and so far the best results have been obtained with this method of treatment. The drugs used singly are given in the following table : -
Drug.
Antimony arsenate ... .
"
oxalate ...... . '' ... . trisulphide ..... . , pentasulphide ... . Arsenic bisulphide ...... . trisulphide ... .
"
, pentoxide .... . Barium arsenate .......... . carbonate ........ . '' ... . , chromate ..... . Bismuth carbonate ... .
subg~llate ....... . subnitrate ... . , trisulphide ... . Calomel. ............. . Calcium citrate .... . fluoride ...... , . '' ... . ,, ox~ato ....... . Copper arsenate ........ .
" ... .
arsenite ... . ,, ··· ... . carbonate ...... .
,,
oxide (CuC) ... ''···
.. . sulphide (Cu,S) .... . tartrate.. . . . .. . thiocyanate ... .TABLE VII.
RELATIVELY !~sOLUBLE DRUGS.
No.
Dose in Gm. of
0·5 & l.. ... . 2 ....... . 1 & 2 ... . 4 ........ . l. ... . l. ....... . l. ..... ..
0·25 ... . 0·3 ........ . 0·6 ..... . l. ... . 1·3 ... . 0·5 .......•. l. ......... . l. ... ..
2 ...... ..
1 & 2 ....... . l. ......... . 2 ...... . 4 .......... . 1 & 3 ....... . l. ... . 1 & 2 ... . 0·5 .... . l. ......... . l. ... . 2 .......... . 1, 2 & 4 .... . 0·5 ...... . l. ......... . 2 ........ . 0·5 ..... . l. .... . 0·5 ........ . l. ... . 2 ..... . 0 ·75 ....... . 0·5,1.1·5 .. . l. ..... . l. .......... .
Sheep.
6 1 3 1 l 1 l 5 6 3 15 1 3 7 3 2 4 2 2 2 2 3 2 4 1 :3 2 4 2 2 1 3 3 1 2 2 l :3
f) 4
Effect.
Slight (1), nil (5) ... . Fair ..... .
Slight ...... . Slight ......... . Good (5) ....... . Good (2), Nil (4) ... . Fair (1), nil (2) .... . Good (10), nil (5) .. . Good ... . Good (2) ... . Good (1), slight (3) ..
Slight (J), nil (2) ... ,
Slight (1), nil (1) ... . Fair (2) ... .
Slight (2), nil (l) ....
Slight (2), nil (l).
Slight ( l), nil ( 1) ....
Remarks.
Died of gastroenteritis.
I
Variable action is pro- )> bably due to direc-J
tion taken at deglu- tition.Died of poisoning.
2 died of worms.
Fair (2), nil (1) ... 1
Slight (1).... 2 died of worms.
Good ............. . Fair (1), nil (1) .....
Good ( l), nil (4) ....
CIIKIIOTliER.-IPY OF OESOPHAGOSTOMIASIS.
TABLE No. VII- (continued).
No.
Drug. Dose in Gm. of Effect. Remarks.
Sheep.
Ferric acetate ... . Hexachlorethane ... .
l. ... 2 Slight (1), nil (1) ....
2, 4, 6, 8 ... 4 Lead sulphide ... . 1 & 2 ...... 3
, tartrate .......... . )fercuric arsenate ... .
1 & 2 ... 4 Slight (1), nil (3) ....
0·5 & l. ... 3
oxide (yellow) ... . 0·5 ......... 1 Good ....... Died of poisoning.
1 ... 2 Good ... 1 died of poisoning.
oxide (red) ...... . sulphide (red) .... . sulphide (black) .. ..
1 ... 2 Fair ... 1 died of poisoning.
0·5 & l.. .... 3 Slight (1), nil (2) ....
0·5 & l. ... 2 , thiocyanate ... .
Mercurous iodide ....... . , sulphate ... . Metachloral. ........ .
0·5 & 1 ... 2 Both died of worms.
l. ... 2 Good ..... Died of poisoning.
0·5 ... 2 Good (1), fair (1) ... Died of poisoning.
0·5, 1, 2 .... 0 3 Naphthalene ..... .
Phosphorus (red) ... . Salol. ........... .
1 ........ 1 Slight ..........
0·5 ......... 1 .Fair ..... Died of poisoning.
0·5 ... 2
1 .... 6 Slight (2), nil (4) .....
1 & 2 ...... 2 '' ... .
Sodium fluoride ... .
fluosilicate.... . .. . 1 ... 1
2 ........... 2 Good (1), nil (1) ....
3 ......... 1 Good ...
4 ......... 1 Good ... Died of "debility."
4 c.c ......... 2 Slight (1), nil (1) ....
Tet;achlorethylenc ... .
5 c.c ..... 3 Fair (1), nil (3) ...
10 c. c ........ 3 .Fair (2), nil (1) ...
0·5 ... 1 Thymol 'biniodide.·.· ... .
1 ..... 5 "Fair (1), nil (4) ...
Discussion.- It is fairly obvious from these results, that there is a factor which causes very unexpected variations in the effects of the drugs. For instance, the very first drug tried against this parasite was Arsenious sulphide
(As2S3 ). Two sheep were dosed with 0 ·25 gm. each and both passed all their
nodular worms. Since that time the drug has s:.Jmetimes acted in a similar way and in other cases not at all, even in 1 gm. doses. Fifteen sheep received 1 gm. and of these ten passed all the worms while five passed none. Had the drug been tested on the latter five only it may have been discarded as useless.
Most drugs in the above list were tested on less than five sheep. One hesitates to draw any conclusion from the negative results obtained with many of them.
The most promising drugs under these conditions seem to be Arsenious sulphide and Sodium fluosilicate, while copper and mercury salts may prove useful, but the latter are rather toxic. The mercury salts were expected to give good results, since they would be excreted in the colon if they became absorbed.
On the whole, however, one must conclude that, as stated before, the result may be misleading and quite useful drugs may not have shown up.
"Debility" as used in these tables means the general exhaustion causecl by the nodular worm.
The following combinations of drugs were tested :-
TABLE VIII.
Drug.
As2S3+ Barium arsenate ....
+Bismuth carbonate ..
+ "
+ , subnitrate.
+ Copper tartrate ...
+ ., "
+Kamala ..... . +Mercurous iodide ... . + , sulphate.
+~fercuric sulphide (hl.) + {1-Naphthol ........ . +Picric acid ....... . +Potassium iodide ... . +Sodium fluosilicate ..
+Trypan blue ... . . , +Copper tartrate+
Mercurous sulphate.
, +Copper tartrate+
Calomel.. ......... . , +Calomel+Mercurous sulphate ........ . ., +Calomel+Potassium iodide+ Tannic acid.
Bismuth carbonate+ Barium arsenate ............ . Copper tartrate+:vi'ercurous sulphate ......... . Copper tartrate+Barium arsenate ......... . Mercuric oxide (red)+ Bar- ium arsenate ........... . Sodium fluosilicate+Mer-
curic oxide (red) ........ . Sodium fluosilicate+San-
tonin ............... .
Dose in Gm.
0·5+0·5.
2+ 1 ....... . 4+0·5 ... . 0·5+1. .... . 0·5+0·6 ... . I+ l .. ..
I+ J. ... . 0·5+0·25 .. . 0·75+0·25 ..
0·.5+0·5 ... . 0·5+ 1 ..... . 0·5+0 5 ... . 0·5+ 1. .... . 1+2 ... . 0·5+ 1-.... . 1+1+0·25 ..
0 5+1+0·5.
0 :'5+0·5+ 1+1 2+ 0 5 ..... . 0 75+0·25 ...
0·25+0·75 ..
2+0·15 ..... 2+ 2 .... .
No.
of Sheep.
3 4 2 3 2 5 1 2 2 2 2 2 2
±
2 2 2 3 2 2
2 2 2 4
Effect.
Slight (1), nil (2) ....
Fair (1), nil (3) ..
Good (2), nil (3).
Good (1), fair (1) ...
!<'air ....
Good (2), nil (2) ....
Slight. . ...
Slight (2), nil (1) ....
Good (1), nil (l) ....
Good ( 1), nil (l) ... . Good (1), fair (1) ... ..
Good ............. . ]'air (l), slight (1) .. . Good ....... .
H. 0. MONNIG.
Remarks.
1 died of "debility."
Discussion.- The same remarks that were made with reference to Table VII coulcl be made here. The impression was obtained that arsenious sulphide, in combination with some metallic salts, tends to form sulphides of these metals and that the efficacy of both components is reduced.
SUMMARY.
(I) The problem of chemotherapy in oesophagostomiasis ca.nnot be solved satisfactorily nntil a m~thocl of dosing sheep into the abomasum has been found.
With ordinary closing useful drugs m"-y be swallowed into the rumen and will then not act.
(2) The results obtained with 72 different drugs aml various combinations of these, tested on 308 sheep, are tabulated and briefly discussed.
(3) The best results were obtained with relatively insoluble drugs. which are most likely to reach the colon and which m'1y apparently be ingested by the parasites.
( 4) The most promising drug~ ~tppear to be arsenious sulphide and sodium fluosilicate, while certain compounds of copper and mercury may be useful.
CHEMOTHERAPY OF OESOPHAGOSTOMIASIS.
BIBLIOGRAPHY.
GREEN, H. H. ( 1918). "The fate of ingested and injected arsenic in sheep, with special reference to treatment of Haemonchosis." 5th and 6th Bept. Di1·. Vet. Res., Union S. Afr., pp. 483-538.
LE ROUX, P. L. (1932). "Some observations on three communications dealing with the treatment of gastro-intestinal strongylosis of sheep." Vet. Jl., Vol. 88, No. 5, pp.
205-206.
MONNIG, H. 0. (l929a). "The closing of sheep with Government Wireworm Remedy."
Jl. S. Aj1-. Vet. Med. Ass., Vol. 1, No.2, pp. 93-95.
MONNIG, H. 0. (l929b). "Report on the closing of sheep with Government Wireworm Remedy without preliminary starvation." Farming in S. Afr., Vol. 4, No. 45, pp.
469-47l.
MONNIG, H. 0. (1931). "The specific diagnosis of nematode infestation in sheep." 17th Rept. Di1·. Vet. Ser. and Anirn. Indust., UnionS. Afr., pp. 256-266, 11 Figs.
SCHUURMANS-STEKHOVEN, Jnr., J. H., & BOTMAN, Th. P. J. (1932). " Zur Ernah- rungsbiologie von Proleptus obtusus Duj. und die von diesem Parasiten hervorgerufen€n reaktiven Aenderungen des Wirtsgewebes." ZscM. f. Pamsitenk., Vol. 4, Part 2, pp.
220-239.
VEGLIA, F. (1018). "Chemotherapy of Haemonchosis in sheep." 5th and 6th Rep. Dir.
Vet. Res., Union S. Afr., pp. 375-482.
WETZEL, R. (1930). " Zur Ernahrungsweise und pathogenen vYirkung der Kleinen Strongyliden cler Pfercle." Miessner-Festsclmjt" (reprint). 14 pp., M. & ff. Schaper, Hannover.
