Onderstepo01·t Journal of Veterinary Science and A ninwl Industry, rolllme 10, .Yimibel' J, January, 1938.
Printed in the rnion of South Africa by the Government Printer, Pretoria.
Surfen C. Therapy in Trypanosoma congolense Infection in Bovines and Ovines.
By S. W. J. YAN REN8BUHG, Section of "Jiedicine ancl Therapeutics, Onclerstepoort.
11nE only drugs that haxe up to the present been shO\nl to be effective in the treatment of T. con.r;olense infectious are the antimony cornpouncls.
Prior to the advent of Antirnosan reliance m1s placed on Potassium Antimony 1'aitrate. This drug howen1· iii not Yer~r satis- factory because it has to be aclministered by the inti aYenous route, 1Yhieh fador militates against its general application uurler ranch- ing conrl itions, especially when repe.atecl i 11jections are necessary.
Antiiuosan which is described as a complex of a Lrivalent anti n1011y preparation with a p_vrocatechin deri n1tiYP. 1rns s ubse- quen tly place<l on the market, a nrl this chug can be aclminisi ere cl either subcutaneously or in traYenously. Parkin (1930) concluded that .as far as ease of administration is concernerl Antirnosan is immeasurably superior to Potassium Antimony Tartrn te a ncl that sterillzation of boYines infected with '/'. conyoleuse is obtained by the subcutaneous injection of 0 gllls. Antimosan when giYen at four weekly i 11 tenals.
vVhile there can be no objection to Antimosan as regards efficacy and local tolerability the fact that i.t has to be repeated three or four Limes is cer!;ai.nly .a clisa1lvaniage. \Vhen therefore 8urfen U. was ma1le aYailahle "ith a claim ihat about 10 mg. per Kg. body\\·eight
~·iven in a single dose either intramuscularly or subcutaneously will be a cerLnin sterilizing rlose in animals infected '"ith T. congole11se, it was hoper1 that a drug hacl been proclucerl, ,,·hich would be as efficient as the antimony preparations while possessing none of tl1P
<lis.aclvantage::; of the latter.
Surfen C. (Hochst GG78) is a Bayer preparation and is stated to be an amino-quinoline derivative, easily soluble in \rnter. It is claimed that intramuscular injectio11s are 1rnll tolerated v<ithout producing any general or local reaction.
13
SUR.FE.'i" C. THERAPY l.N " THYPAXOSO~IA COKGOLEKSE ".
It is claim eel that " in cahes the early tr ea tmen t of a fresh oongolense infection with even a ,;ingle in tram uscula r injection of 5 mg. per Kg. effects a cure. In an infection existing for three months, three treatments each with 10 Jng. Surfen C. per Kg. effected a complete cure.
"In experiments on sheep infected with T. congolense it "·as found that 10 mg. per Kg. Surfen C. cures every stage of the infection both in early and late treatment. . . . Fresh artificial infections of 1'. congolense in which treatment is initiated imme- diately after the appearance of trypanosomes in the blood can be completely cured with two subcutaneous injections of 5 mg. per Kg.
given at an interval of one \Yeek. Also infections \Yhich harl existed for one and three and a half montll8 respectively were similarly treated \vith a single administration of double the above dose."
Surfen C. has been subjected to tests in various parts of the African Continent, but the reports regarding its efficacy ;md local tolerability are co11tlicting.
In Tanganyika, Hornby (19:J:~) concludes tlrnt "'l'he result "·hich mny be expecterl to follow a single inha1nuscular injection of Surf en C. is at least as good as the result to he expected from a course of five weekly injections of Antimosan or Tartar Emetic . . . . A local effed of slight s\\·elling and tenderness, with or "·ithout slight lameness, aml persisting for a fe,1· llays "·ns produce<l . . . . Post-mortem examination three to fiye clays after injection showed no definite necrosis; merely hyperaemia arnl discolouration of fascia, Subcutaneous injections produced severe swelliugs lasting for weeks and are contra-indicated."
M:ettarn (1934) u8e(l the llrug in ihe treatment of 19 head of cattle infectecl with T. con.r;olcnse in Uganda, \Yith the result thnt one animal diell, but the rest " cleare<l up ". He diYicled the close (100 c.r.) into brn parts and i.njectetl intramuscularl:v into either gluteal muscle and states that tbere is nonnnlly JlO local or systematic rnaehon. M:ettam Huhsequently (1933) coJ1dwlecl that "this drug i.s the best trypanocidal agent aYailable for the treatment of cattle
trypnnosome~. 'fhe nntimo11ials are mo,;t efficacious agairn:t 1'. co11- r;olense antl haYe but little nchon on 1'. ln11ce1. Sm·fen C. ou the other hand acts on all thrPe cattle tryp.anosornes. St.inrlanlization of the preparation b.\· the makers ancl the placing of it 011 the rnarket as cheaply as possible i:; m·gently neerlerl ".
After testing the drug on 14 horses in the Su<lau, Dennett (193G) oitates that it iR certnillly capable of curing nearly all, if not all, cases of T. congolense in horses, but he regards the extreme ,·.ariability of indiYiclual response to the drug as a serious cha,1·back.
A single injection frequently faib to sterilize ancl in one case as many .as eight injections totalling 28 · 70 gms. had to be giYen before sllbinocubtion sho,rnd the a ni.mal to have been sterilized. Trouble- some local swellings are stated to be an added clisnchantage.
His co-\\·orker Evans (1936) conclurles that in the case of cattle a single dose of Surfen C. offers as high a hope of effecting a complete cure as does a full course of Antimosan treatment.
S. W. J. VA~ ltEKSllUlW.
ln a memoramlum su lnuitted to the Conference for Co-ordination of 'l'setse and Trypanosome Research in East Afric;a ( Hl~G), Dan ks and Daubney, of Keuya, give the results obtained by tre.atrng bonues with different issues of Surfen C.: -
(1) Two treated, both relapsed.
(2) Two treated, both sterilized.
(~l) Five treated, four rela]JSe(1.
(4) Four treated, all reganled as c1ired.
Daubney is doubtful about the effect of the drug and believes that it has not yet been adequately stau<lardized.
Stewart (1935) after treating animals with antimosan, tartai emetic and Surfen C. in the Gold Coast, expresses the opinion that treatment by Surfen C. does not appear to be nearly as effective as tartar emetic .and other antimony preparations, though Surfen C.
appears to be useful after antimony treatment to prevent relapses.
In Nigeria, Lester (1934) fouud that with sheep infected with T. vivcw; and T. conr;olense a close of 10 rng. per Kg. proved to be more effective than a stan<lard close of tartar emetic, but three doses of Surfen C. given at "·eekly ini.enrals did not prevent relapse. Six bovines were giYe11 three ,,·eeldy closes of Snrfen C. (10 mg. per Kg.) and twelve were given single closes of the drug. The expe1·irnenfa were conqJlicatecl by an outbreak of rinderpest but from the point of view of a definite cure the results were not good .as the majority of animals relapsecl \Yi.thin .a fe"· "·eeks.
According to the 1905 report of the Veterinary Pathologist for Nigeria, six animals artificially infected \\·ith 1'. viva.?; which is the common trypanosome of cattle in Nigeria \Yere treated \Yith Surfeu C.
Two of these succumbed to trypanosomiasis, one co11 tin ued to show T. viva,v in sme.arn, arnl though smears from the other three \\'ere negative, they continued 1.o remain in a Yery emaciated condition.
Large swellings, especially after injection of the salt solution, are mentioned as an objection to the 11se of Surfeu C.
In a progress report on reseai:ch on trypanosomiasis in Southern Rhodesia, Bev.an (1937) states: " A number of drugs . . . have been tested as to their curative aud pre.-entive effects against various species of trypanosom es. The results in small animals have been disappointing. The so-called Surf en 0., much .-aunted as a remedy for T. congolen se infection elsewhere, has not proved .as successful against the local strains of trypanosome."
METHOD.
'l'he animals use<l in the experiments un<ler revie\Y \Yere all artificially infeci.erl ·,yith various strains of T. congolense and \Yere at no time exposed to natural iufection.
Three different issues of the drug \rnre used, and for 1.he purpose of differentiating bet,rnen these they are referred to as A, B and C.
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Batdr fl consisted of lhe powder made up rn ampoules each contai11ing 2·5 grns., ''"hich 'ms clissoh-ell in 100 c.c. sterile distilled water.
Batch B '"as in liquid form as a 2·5 p;;r cent. solution for intra- muscular injection.
Batch C "''rn a llO\\'Cler similar in a1qwina11('e to A lrnt sbtecl to he less initant. This \Ycis also inj0ded in a 2 · ;) lJer cent. solutioH
l l l sterile cli still ell water.
Iu Yiew of the seYere loea l an cl general reactio11s obtai necl by some of the other workern J,y ihe s11bc11taneon,; ancl intnn·enous injectious of tlie cln1g, it w.afl a~lmini;;tered only by the intramuscular route in the present serie,; of experirneuh. In boYines the injections
wen~ made into the glu ieal aJtcl sem i-1 end inos us muscles n n<l in sheep exdusiYely into the latter. X o h\'O i njectious "·ere made at the same place.
Temperatures of the animals v;·ere Li ken hY ice clail,v, arnl bloocl smears daily excepting· Sunclays. In i hose c·a~es in "·hich smear exainination \\':IS negnhrn for some iieriocl follo\\'ing treatmeut :suu- inoC'ula lions into cattle or sheep "·e1·e C'anied out, .and only \Yhe11 the latter yiehlerl negahrn results \\'81'8 the animalH in question pronounced sterilized.
The site of injection \\·as examined at frequent intenals to observe the local reaction, and h1·0 bovines ,1·ere subsequently killed for post-mortem examination ,of the injcctecl meas. The injection of the first full dose given to bovine 9 i 08 'ms made in one place, but subsequentl,\· all doses of 10 mg. per Kg. \Yere clivicle<l into two equal parts and "·ere injectecl at bYo rliffo1·e11t sites.
Loc.1 L 'l'oLERAnn.1 TY.
In sheep the injections caused sorne degree of s\1·elling accompanied by pain and larneuess, \1·hil'h JlCn;isic)<l for three or fom·
days. In only one ('ase (Sheep .J.00-:1-0 frt>atecl "·ith hatch 0) did the S\\'elling iwrsist for about b\'O months frnhseqllen1 to ihe i11jedio11.
The locnl reaction 11·as Ill uch uwre seYcre in bovines. I11tra- muscular injeciiou of lloses of ,-J mg. per li.g. Suden C. in a 2·5 per ceni. solution ]H'Oducecl in all cast's pa inhil S\1elli ngs ;1ccorn panied b:v l:uneness. The S\1·ellings persisted for some \H'eks or !:'\'en mmiths aft er iu.i ection and even tualh s ubsi cl ell gTalhially a 11 cl he ca rn e hard pernistent areas in tl1e skin at ihe site of injection.
Bovines 5189 ;rnd 0198 'vere slaughtered on 18th :'.'l'"ovember, 193G-over seven months after the last injection 1Yns rn:icle. Post- mortem examination sho,vecl localised schlerodenn i a '" i th "hrouic myositis, subcutaneous melanotic areas at the sites of injection, and infiltration of the pe1·i vascular tissue a ml i u te rfibrillar connective tissue 11·ith macrophages containing rlark br0\n1 granules.
There appearell to be HO rnriation in the intensity of the local reaction set up
uy
the three Latches of the drug.JG
S. W. J. VAN RENSBUllG.
'l'he intramuscular injection of Surfen C. in the recommended doses was not followed by any general symptoms.
DISCUSSION.
Full details concerning the experiments carried out to test the therapeutic value of Surfen C. in the treatment of 1'. congolense infection in bovines and ovines are given in Tables I and II. In the former it will be seen that the full recommended dose of 10 mg.
per Kg. w.as given in the first instance to bovine 5198. This failed to sterilize, and in vie"· of the very severe local reaction which it produced, an attempt was subsequently made to ascertain whether it was possible to obtain better results by administering smaller doses at varying intervals.
'l'his animal was, therefore, given two doses of 2·5 mg. per Kg.
each at an interval of twenty-four hours followed later by three similar closes. Thereafter two doses of 5 mg. per Kg. were given on two consecutive clays .and ultimately two injections, each con- sisting of 2·5 mg. per Kg. Surfen 0 . .and 15 c.c. Antimosan, all of which failed.
The initial treatment for bovine 5189 consisted of two doses of 2 · 5 mg. per Kg. within twenty-four hours. After this, treatment at longer intervals was tried, five doses each of 5 mg. per Kg. being given at intervals of seven days.
Over a period of seven months bovine 5198 thus received 10 injections totalling 37·5 mg. per Kg. Surfen 0. and 30 c.c. Anti- mosan without sterilizing, while 30 mg. per Kg. Surfen 0. admims- tered to 5189 in seven doses failed similarly.
Treatment at longer intervals, consisting of five doses Surfen C.
each of 5 mg. per Kg. applied at weekly intervals to bovine 5526 failed to produce even a temporary disappearance of the parasites.
The full dose of 10 mg. per Kg. was reverted to in the treat- ment of No. 6026. The first two injections failed and sterilization was only effected by the third which, incidentally, was respom;ihle for very marked swellings at the sites of injection.
In sheep initial treatment, consisting of two doses of 2 and 2·5 mg. per Kg. each given at twenty-four hours interval failed, while two injections of 5 mg. per Kg. given at a similar interval sterilized in one case (40933) and failed in another (41104).
As in the case of bovines, treatment at longer intervals with 5 mg. per Kg. given weekly failed (41104).
The full dose of 10 mg. per Kg. given all at once sterilir.ecl in one case ( 42768) but failed in brn others ( 41029 and 45354).
It is from the efficacy.
the drug 2
apparent that the workers who have recorded good results use of Surfen 0. are not all entirely convinced as to its Mettam and Daubney both draw attention to the fact that is not adequately standardized, and Danks and Daubney
17
!': CltJ.'E:K C. TIIEllAl'Y IK ' ' TRYl'.\KOSO)L\ CONGOLEXSE ".
are of opinion that later issues appear to be more effective. This view is not confirmed by the results of the present series of experi- ments, all three issues of the drug having failed equally badly.
'rhe animals in these tests were stabled, and whether this lack of exercise could iu any way have aggravated the local reactions cannot be rlefinitely stated at p1·esent. These reactions, however, were of such a serious nature th.at even if the drug "·as 100 per cent.
efficient therapeutically one \\'O"uld still he hesitant in recomrnemling its general use by the intramuscular route.
The damage done by the drug to the s11hcutis and the muscu- lature 'rnulrl sel'iously reel uce the value of treated .animals for slaughter purposes.
C0Ncr.us10Ns.
(1) 'l'he intramuscular injection of Surfen C. in the treatment of T. congolense infecti01, in bovines and ovines was found to be ineffective.
(2) The intramuscular injection of Surfen C. into bovines caused serious local reaction.
RRFERENCES.
BENNETT, S. C. J. (1936). The Treatment of Equine Trypanosoma congolense Infections with Surfen C. (Bayer). J. Comp. Path. and 'l'her., Vol. 49, pp. ]51-159.
BEVAN, L. E. vV. (1937). Progress Report on Research on Trypanosomiasis in Southern Rhodesia. Vet. Bee., Vol. 49, p. 770.
EVAKS, J. T. R. (1936). Trypanosoma congolense Infection in Cattle:
Treatment by Antirnosan and Surfen C. J. Comp. Path. and 'l'her., Vol. 49, pp. 160-162.
HORNBY, H. E. (1933). Annual Beport of the Department of Veterinary Science and Animcil H iisbandry, 'l'anaanyik,a Territory, 1933.
LES'fER, H . .M. 0. (1934). Report of the Tsetse Investigation. Nigeria Bev.
Jfed. and Henlth Services /01· year 1934, Appendix B, pp. 69-88.
::'IIETTAl\1, R. W. (1934). A.nnual Bevort of the Veterinary Department for 1934; Uganda Protectorntc.
MET'l;AM, R W. (1935). Anniw.l Beport of the Veterinary JJepartn1ent for the year ended 31st ])ec., 1935, Uganda Protectorate.
l'ARKIK, B. S. (1930). A study of Bovine Trypanosomiasis. ::dixteenth Beport of the Director of T'eterinary .Services n111l Animal Industry, pp. 21-53.
STE\VAltT, J. J,. (1930). Treatrneut of Trypanosumiasis Ly 'l'artar Emetic, Antimosan- Surfen C. in the Gold Coast. J. Comp. Path. and 1'her., Vol. 48, pp. 816-;318.
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Bovine No. Date Infrctccl. 5198 i 23.8.35 5189 2:1. 8.35 5526 28. 2.36 6026 12. 1.37
'11 AllLE l. Sm/ en C. Therapy in T. congolense Infection in Bov'ines. Try A
Dato panosomes ppearocl.
Dato Treated. ---·----------·- 2. 9.35 12.9.35 31.10.35 1.11. 35 20.11.35 21.11.35 22.11.35 11.12.35 12.12.35 9. 3.36 7. 4.36 31. 8.35 18.10.35 19.10.35 9. 3.:36 16. 3.36 23. 3.36 30. 3.36 7. 4.36 7. 3.36 11. 3.36 18. 3.36 25. 3.36 1. 4. 36 9. 4.36 21. 1.37 30. 1.37 19. 2.37 24. 4.37
Dose in mg. per Kg. 10 2·5 2·5 2·5 2·5 2·5 5 5 2·5
+
15c.c Antimosan 12 per cent. ,, 2·5 2·5 5 5 5 5 5 5 5 5 !5 6 10 10 10Batch of Drug Used. A. A. A. A. A. A. A. A. B. B. A. A. B. J3. J3. B. B. B. J3. B. B. J3. B. J3. c.
Smear Examination Negative. :From. 16. 9.35
}
6.11. 35 } 23.11.35 } 17.12.35} l f 1 }
19.10.35 9.3.36 26. 2.37 26. 4.37
I
To. 11.10.35 12 .11.35 5.12.35 31.12.35 13. 1.36 25. 5.36 13. 3.37RE~fARKS. --- Unsuccessful. Unsuccessful. U ns u ccessfu 1. Unsuccessfu I. U nsuccessfu 1. Unsueeessful. I Unsuccessful. Unsuccessful. Trypanosomcs failed to disappear.
Of] _, < Unsuccessful. <1 Trypanosomes failed to disappear. Unsuccessful. Unsuccessful. Steriliwd.
:.- '.?, ::::; t'1 './. [f. ~
,,
'::'!'J1ABLE II. S111fen C Thernpy in T. eongolense Infection in Sheev. Shee No. p Date Infected.
Date Trypanosorncs Date Appeared. Treated. ----------------------· ---- 4334 9 I 16.10.35 23 .10. :36 30.10.35 3 l.10. 36 22.11.35 23.11.35 4093 3 Hl.11.36 29. l L .:35 11.12.3.5 12.12.3.5 4110 4 lG .10. :~5 24.10.3.5 30.10.35 ;JL.10.35 11.12.35 12.12.35 9. 3.36 16. 3.36 23. 3.:36 30. :1.36 427() 8 19.11.35 20.12.36 9. :1.36 :2.11.36 4102 9 18. 8.3G 29. 8.36 8. 9.36 28.10.36 4535 4 22. 3.37 2. 4.37 24. 4.37
Dose in n1g. per ICg. 2 2 2·5 2·5 5 Ii 2·5 2·5 5 5 5 5 5 5 2·5 +-fic.c Antimosan 10 10 10 10 mg.
Batch Smear Examination Negative. of --- Drug
I
Used. ]from. To. A.}
1. 11. 3;) J 6. ll. :35 A. A. 'L •>9 11 'F 9.12.35 A.{ -·
-. . :
A. A. J 14.12.30 A.}
2.11.35 26. ll. 35 A. A. 'L 13 1•) 3~ 14. 1.36 A. J . ·---· 0 B. I 13. ~ 1:2. :1.36 31. 3.36 B. B.J
B. LO. 3.36 1. 4. 36 13. 4.11.36 B. 8. 9.36 :ZG. 9.:36 J3. - c. 26. 4.37 29. 4.:nRE~IARKS. ·--.. ·-~---- Unsuccessful. Sheep killed on 24. U. 35. Sterilized. Unsuccessful. U nsuccessfu I. Unsuccessful. Unsuccessful. Sterilized. Unsuccessful. Died on 29 .10. :rn. Unsuccessful.
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