- Email: [email protected]
Treatment of Theileria annulata infection in calves with parvaquone
Research in Veterinary Science 1985, 39, 1-4
Treatment of Theileria nnnulata infection in calves with parvaquone N. McHARDY, D. w. T. MORGAN, Coopers Animal Health Ltd, Berkhumsted, Hertfordshire
Fifteen calves were infected by the injection of stabilate o f a suspension of Hyalomma anarolicum anntolicum ticks infected with the Ankara strain of Theileria annulata. Three were kept untreated, as controls, and they all died of theileriosis. Three groups of four calves were trealed intramuscularly with parvaquone (Clexon; Wellcome) when early signs of theileriosis were clinically apparent. One group received 20 mg (kg bodyweight)-' of parvaquone 10 days after infection. Two of these calves were clinically cured and two died of theileriosis. The remaining two groups of four calves received two doses of parvaquone, each of 10 mg (kg bodyweight)-', either on days 10 and 11 o r days 10 and 12. Three calves in each group were clinically cured while one in each group died of theileriosis. Total parasitological cure was not achieved in any of the calves. No symptoms of toxicily due to parvaquone treatment were observed. THERE are several reports of the efficacy of parvaquone (993C, Clexon; Wellcome) in the treatment of Theileriu parva infection o f cattle using single doses of 20 mg kg-' or two doses of 10 mg kg-', administered by the intramuscular route. The compound has been tested under both experimental conditions (McHardy 1979, Dolan 1981, McHardy et a1 1983) and in field trials (Kirui et al 1983). Far less work has been done on the effect of parvaquone in cattle infected with T annularu. Gill et al (1981), using the Hissar strain, reported that a single dose of 20 mg kg- cured all four calves treated on the day of artificial infection and all four treated on day TS3. Day TS3 is the third day on which the temperature(T1 was 39.5"C or above, and macroschizonts (S) were observable in stained lymph node smears. All four untreated calves died. Three of four calves which received 10 mg kg- on day TS3 and TS6 were cured. Sultan et al(1981) infected four calves by the injection of a stabilate of Hyaiomma anarolicurn anatolicurn ticks infected with T annulatu, and four by the attachment of live ticks. Two calves in each group were treated with parvaquone, 20 mg kg-', when they became clinically ill with theileriosis. Both artificially infected calves and one naturally infected
'
calf were cured while another naturally infected calf died. The remaining four calves served as untreated controls, and all of them died of theileriosis. The present trial examined the effect of a preparation of parvaquone in cattle artificially infected with the Ankara strain of T annulata.
Materials and methods
Cattle Fifteen calves, male and femaIe, of mixed Bos taurus breed, weighing 55 to 118 kg were used. They were housed in a tick-proof unit and fed on a standard diet of concentrates with hay and water available ad libitum.
Infecrion The calves were infected on day 0 by the subcutaneous injection in front of the right ear of0025 m1 of stabilate 23 of a homogenate of H a anarolicum ticks infected with the Ankara strain of Tannulato.
Trearmenr groups Groups were assigned to each treatment before the trial began. Groups 2, 3 and 4 were injected intramuscularly with a solution of parvaquone, 150 mg ml-I, dissolved in a mixture of N-methyl-2-pyrrolidone (25 per cent) polysorbate 80 (3 per cent) sorbitan mono-oleate (7 per cent) and fractionated coconut oil to 100 per cent (Clexon; Wellcome). Injections were delivered intramuscularly on the right side of the neck.
Group I . Three calves were kept as untreated conrroIs. Group 2. Four calves were given 20 mg kg-' parvaquone on day 10. Group 3. Four calves were given 10 mg kgparvaquone on day 10 and day 11. Group 4. Four calves were given 10 mg kg-' parvaquone on day I0 and day 12.
'
Observufions
Results
Rectal temperature was taken daily around 09.00. A 5 ml sample of jugular blood was taken into lithium heparin for the assessment of packed cell volume (PCV) and preparation of blood smears to estimate piroplasm parasitaernia on day 0 and daily from day 5. Biopsy smears for the assessment of macroschizont and microschizont parasitosis were taken from the right parotid and left prescapular lymph nodes respectively from day 5 and day 7. Macroschizont parasitosis was scored on a 0 t o 3 scale for each node; 0 represented no schizonts seen after a search of 10 minutes, 1 was assigned when schizonts were present but difficult to find. A score o f 2 represented up to 5 per cent o f lymphoid cells infected while 3 was greater than 5 per cent infection. The maximum score for two nodes was, therefore, 6. The presence of microschizonts was noted, but not scored. Following treatment, a proportion of schizonts was degenerate and the score was reduced accordingly. Thus, the score for a heavily infected node in which most of the schizonts were degenerate was halved to 1 . 5 . Similarly, piroplasm parasitaemia was scored as the percentage of erythrocytes containing a piroplasm, and reduced pro rata when pycnotic piroplasms were seen. Thus, a blood smear in which I0 per cent of the erythrocytes contained piroplasms which were all pycnotic was scored as 5 per cent. The general condition o f the cattle was monitored daily and any animal which died was examined post monem.
The results are summarised in Table 1.
Group I . Untreated confrofs
All three calves developed, and died of, typical theileriosis characterised by oedematous lungs, enlarged lymph nodes and, in cases which were not acute, anaemia, in 2 0 - 7 SD 5 3 - 5 1 days. Schizonts were first seen in parotid node smears on day 5 or 6 and in prescapular nodes o n days 9 to 11. Piroplasms were first seen in blood smears on days 8 and 9. Packed cell volume (PCV) was 31 to 40 per cent at infection. On day 10, when treatment was given to the remaining groups, macroschizont parasitosis was scored 3 in the parotid nodes of all three calves, and I in the prescapular nodes of two. The prescapular node of the third calf became positive on day 1 1 . pcv on day 10 was 2 8 . 3 per cent -c 7-64 and temperature was 4009OC 2 0.36, having been variable up to this time. Macroschizont and microschizont parasitosis En the parotid nodes became massive around day 14, but remained low in the prescapulars. Piroplasm parasitaemia developed progressively to a maximum of 55.3 per cent a 6.1 l and pcv fell progressively to a minimum of 14.3 per cent + 3-51 just before death. Maximum temperature was 4193°C + 0 - 2 3 around day 15 but fell to about 40-5°C for a few days before death.
TABLE 1: Summary of observations {group means) on calves infected with ThePwEeannuletaand treated with panmquone, 20 mg kg x 1 or 10 mg kg x 2 intramuscularly
'
Untreated controls Number of deaths Days to death
Pawaquone treatment 2 0 m g k g - I lOrngkg 10mgkg day 10 days 10 b 11 days 10 & 12
3/3 17,21.24
2/4 15.19
1/4 17
114 21
-
0.25 1.O 22.5 39.3
0.5
0.5
3.7
1.0 24.7 39.1
Dav 10 Macroschizont score Parasitaemia % PCV % Temperature After day 12 Maximum rnacroxhizont score Maximum piroplasrn parasitaemia % Minimum PCV % Maximum temperature Day 28 Schizont score Parasitaemia % PCV
Oh
Temperature
25 38.3
Purvaquone creafment of Theileria annulata Group 2. Parvaquone 20 mg kg-
',day I0
All four calves appeared to respond rapidly to treat ment and showed no signs of drug toxicity. While two remained healthy, one died on day 15, and one died on day 19with symptoms or theileriosis similar t o those in the controls. Parasitosis was well controlled in the lymph nodes examined, being no higher than score 1 after day 16. Piroplasm parasitaemia did not exceed 5 per cent in any of the calves, and PCV fell below 23 per cent (to 18 per cent) in only one calf. In the caIr which died on day 15, the minimum pcv was 34 per cent . Its lungs were oedematous and its lymph nodes enlarged. No signs of drug toxicity or intercurrent infection were seen. Temperature was well controlled in all but the one calf which died on day 15; a deposit of drug was found at the injecrion site in this calf at post mortem examination. Group 3. Parvaquone, 10 rng kg- I, days I0 and I I Development of infection was essentially similar to that in group 2. One calf died of thcileriosis but without anaemia on day 17 and, again, no signs of drug toxicity were observed in any of the calves. One calf recovered rapidly while two made slow recoveries, having shown apparently good control of organisms following treatment. Schizonts and piroplasrns became degenerate by the day following first treatment and remained at low levels until death or cure. Few healthy schizonts were seen after treatment and piroplasm parasitaemia reached a maximum of 4.0 per cent k 4.0 healthy parasites. pcv reached minima of 17, 19 and 27 per cent in the survivors, but 34 per cent in the one which died. Temperature was well cor~trolledin all calves except the one which died. Group 4. Parvaquone, 10 mg kg-', days 10 and 12
One calf died of theileriosis without anaemia on day 2 1, two made good recoveries while one recovered having shown a recrudescence of schizonts to score 3 with microschizonts present in the parotid node from days 20 to 24, but without a concomitant rise in schizont number in the prescapular node or in the number of piroplasms. Treatment again caused degeneration of schizonts and piroplasms within 24 hours. While major recrudescences of schizonts occurred in the parotid nodes of the calf which died and one other, they had been eliminated from prescapular nodes in all four calves by day 14. Piroplasms attained maxima of 4 . 5 per cent 2 4.04, the highest being 10 per cent on day 19 in the calf which subsequenrly developed schizont recrudescence. PCV minima were 19 per cent and 30 per cent in the two good responders, 38 per cent in the one which died and 17 per cent in the one
3
which relapsed. Temperature was well controlled in all four. Discussion
Mortality from T annulata infection among Bos ruurus cattle in the field may reach 70 per cent
(Uilenberg 1981). The fact that all the controls in this trial died of acute theileriosis may indicate that the challenge was particularly severe. At the time of treatment, however, symptoms of t heileriosis were not severe, although clinically clearly apparent. The response to treatment in all three groups was essentially similar. lnitial control was good but recrudescences of varying severity then ensued. Two doses of 10 mg kg-' parvaquone gave rather better results than one dose of 20 mg kg-' and is the recommended regimen for the treatment of Tparvu infection. Plasma levels of parvaquone in cattle infected with T purva, measured by a bioassay method, showed that this course of treatment resulted in schizonticidal concentrations of drug which lasted for four days from the first treatment (McHardy and Mercer 19851, while a single dose of 20 mg kg-', although producing a higher peak concentration, lasted for only about three days. I t is interesting to note that the untreated controls died with symptoms primarily attributable to both schizont parasitosis (pulmonary and lymphoid lesions) and piroplasm parasitaemia (anaemia). The treated calves which died generally showed only pulmonary and lymphoid lesions but no anaemia. This suggests that death was due, primarily, to schizont parasitosis. The results reported here indicate that further doses of 10 mg kg- parvaquone could have increased the cure rate, particularly if given before signs of recrudescence were seen, so as to depress further the development of schizonts. Since the infection in this trial was apparently more severe than that commonly encountered in the field, it is possible that a total dose of 20 mg kg-' parvaquone, given early in the clinical syndrome, would be effective in field cases of Tannulata infection. The results or Gill et a1 (1981) and Sultan et al (198 1 ) were very similar to those reported here. They both used Indian isolates of T annuluca whereas a Turkish isolate was used in this study. This indicates that strains from widely different locations respond similarly to treatment with parvaquone. Gill et al (1981) round that an interval of three days between doses of I0 mg kg- parvaquone gave perhaps poorer results than a single dose o f 20 mg kg- I . The bioassay of plasma from treated cattle (McHardy and Mercer 1985) may offer an explanation for this. Drug levels may have fallen below inhibitory levels bet ween doses, so permitting recrudescence which was incompletely con trolled by the second dose.
'
It appears, therefore, that a total dose of 20 rng kg-' parvaquone, given within 48 hours, is an effective treatment for most early clinical cases of T annulato infection, but funher treatment should be given promptly if a clear improvement in the clinical condition of the animal is not seen. Further work is required to study the effect of additional treatment with parvaquonr in cattle showing delayed recrudescence of infection. Acknowledgements
We would like t o thank the staff of the Wellcome Research Laboratories, especially Mr M. P. Trevithick and Mr P. J. Matthews, for their expert technical help, and Mr C. G. D. Brown, Centre for Tropical Veterinary Medicine, Edinburgh, for provision of the stabjlate.
Eds A. D. Irvin, hi. P.Cunningharn and A. S. Ynunp. The Hague. Xfartinus Nijhoff. pp 186-208 GILL. B. S.. BHATTACHARYULU. Y.. SINGH. A.. KAUR. D. .&: GILL. H. S. (19811 Advancer i n the Control of Theilcrioci\. Eds A. D. Irvin, b?. P. Cunningham and A. S. Young. The Hague, Maninus Nijhofi. pp 218-222 KIRUI. N. H. A.. KIBOR. A. C . . MWlMURI. F. h.1.. KOSRER. J. K.. OLUBAYO, R. 0.. INJAIRU. R. %I.& KARIUKI. I). P. ( 1983) A'F~~VU I,'e~erinarian7. 13- 14 McHARDY. N. (1979) Jr~urnalof rhe South Afriron I'ererinur.~ Assnriarion 59. 321-322 SlcHARDY. N.. HUDSON. A. T.. MORGAN, D. W . T.. RAE. D. G . & DOLAK. T. T. (19R3) Rer~clrrhin Veferinarv Science 55.347-352 McHARDY. N. & MERCER. J. P. (1984) K ~ n y aC'eterinuriun 8, 9-11 SULTAN. B. A., LATIF. R. M. A. & ALTAIF, K. 1. (1981) Advancer in he Control o f Theileriosis. Eds A. D. Irvin. Xi. P. Cunningham and A. S. Young. Thc Hague, !blartinu< Nijhoff. p 223 UILENBERG. G. (1981) Diseases of Cat~lein the Tropics. Ed%X I . Rir~icand I.Mclnryre. The Hague. Martinus Nijhoff. pp 41 1 - 4 3
References DOLAN. T. T. (1981) Advances in the Control of Theilerio5is.
Received for publication k?u.v 1, 1984
Treatment of Theileria nnnulata infection in calves with parvaquone N. McHARDY, D. w. T. MORGAN, Coopers Animal Health Ltd, Berkhumsted, Hertfordshire
Fifteen calves were infected by the injection of stabilate o f a suspension of Hyalomma anarolicum anntolicum ticks infected with the Ankara strain of Theileria annulata. Three were kept untreated, as controls, and they all died of theileriosis. Three groups of four calves were trealed intramuscularly with parvaquone (Clexon; Wellcome) when early signs of theileriosis were clinically apparent. One group received 20 mg (kg bodyweight)-' of parvaquone 10 days after infection. Two of these calves were clinically cured and two died of theileriosis. The remaining two groups of four calves received two doses of parvaquone, each of 10 mg (kg bodyweight)-', either on days 10 and 11 o r days 10 and 12. Three calves in each group were clinically cured while one in each group died of theileriosis. Total parasitological cure was not achieved in any of the calves. No symptoms of toxicily due to parvaquone treatment were observed. THERE are several reports of the efficacy of parvaquone (993C, Clexon; Wellcome) in the treatment of Theileriu parva infection o f cattle using single doses of 20 mg kg-' or two doses of 10 mg kg-', administered by the intramuscular route. The compound has been tested under both experimental conditions (McHardy 1979, Dolan 1981, McHardy et a1 1983) and in field trials (Kirui et al 1983). Far less work has been done on the effect of parvaquone in cattle infected with T annularu. Gill et al (1981), using the Hissar strain, reported that a single dose of 20 mg kg- cured all four calves treated on the day of artificial infection and all four treated on day TS3. Day TS3 is the third day on which the temperature(T1 was 39.5"C or above, and macroschizonts (S) were observable in stained lymph node smears. All four untreated calves died. Three of four calves which received 10 mg kg- on day TS3 and TS6 were cured. Sultan et al(1981) infected four calves by the injection of a stabilate of Hyaiomma anarolicurn anatolicurn ticks infected with T annulatu, and four by the attachment of live ticks. Two calves in each group were treated with parvaquone, 20 mg kg-', when they became clinically ill with theileriosis. Both artificially infected calves and one naturally infected
'
calf were cured while another naturally infected calf died. The remaining four calves served as untreated controls, and all of them died of theileriosis. The present trial examined the effect of a preparation of parvaquone in cattle artificially infected with the Ankara strain of T annulata.
Materials and methods
Cattle Fifteen calves, male and femaIe, of mixed Bos taurus breed, weighing 55 to 118 kg were used. They were housed in a tick-proof unit and fed on a standard diet of concentrates with hay and water available ad libitum.
Infecrion The calves were infected on day 0 by the subcutaneous injection in front of the right ear of0025 m1 of stabilate 23 of a homogenate of H a anarolicum ticks infected with the Ankara strain of Tannulato.
Trearmenr groups Groups were assigned to each treatment before the trial began. Groups 2, 3 and 4 were injected intramuscularly with a solution of parvaquone, 150 mg ml-I, dissolved in a mixture of N-methyl-2-pyrrolidone (25 per cent) polysorbate 80 (3 per cent) sorbitan mono-oleate (7 per cent) and fractionated coconut oil to 100 per cent (Clexon; Wellcome). Injections were delivered intramuscularly on the right side of the neck.
Group I . Three calves were kept as untreated conrroIs. Group 2. Four calves were given 20 mg kg-' parvaquone on day 10. Group 3. Four calves were given 10 mg kgparvaquone on day 10 and day 11. Group 4. Four calves were given 10 mg kg-' parvaquone on day I0 and day 12.
'
Observufions
Results
Rectal temperature was taken daily around 09.00. A 5 ml sample of jugular blood was taken into lithium heparin for the assessment of packed cell volume (PCV) and preparation of blood smears to estimate piroplasm parasitaernia on day 0 and daily from day 5. Biopsy smears for the assessment of macroschizont and microschizont parasitosis were taken from the right parotid and left prescapular lymph nodes respectively from day 5 and day 7. Macroschizont parasitosis was scored on a 0 t o 3 scale for each node; 0 represented no schizonts seen after a search of 10 minutes, 1 was assigned when schizonts were present but difficult to find. A score o f 2 represented up to 5 per cent o f lymphoid cells infected while 3 was greater than 5 per cent infection. The maximum score for two nodes was, therefore, 6. The presence of microschizonts was noted, but not scored. Following treatment, a proportion of schizonts was degenerate and the score was reduced accordingly. Thus, the score for a heavily infected node in which most of the schizonts were degenerate was halved to 1 . 5 . Similarly, piroplasm parasitaemia was scored as the percentage of erythrocytes containing a piroplasm, and reduced pro rata when pycnotic piroplasms were seen. Thus, a blood smear in which I0 per cent of the erythrocytes contained piroplasms which were all pycnotic was scored as 5 per cent. The general condition o f the cattle was monitored daily and any animal which died was examined post monem.
The results are summarised in Table 1.
Group I . Untreated confrofs
All three calves developed, and died of, typical theileriosis characterised by oedematous lungs, enlarged lymph nodes and, in cases which were not acute, anaemia, in 2 0 - 7 SD 5 3 - 5 1 days. Schizonts were first seen in parotid node smears on day 5 or 6 and in prescapular nodes o n days 9 to 11. Piroplasms were first seen in blood smears on days 8 and 9. Packed cell volume (PCV) was 31 to 40 per cent at infection. On day 10, when treatment was given to the remaining groups, macroschizont parasitosis was scored 3 in the parotid nodes of all three calves, and I in the prescapular nodes of two. The prescapular node of the third calf became positive on day 1 1 . pcv on day 10 was 2 8 . 3 per cent -c 7-64 and temperature was 4009OC 2 0.36, having been variable up to this time. Macroschizont and microschizont parasitosis En the parotid nodes became massive around day 14, but remained low in the prescapulars. Piroplasm parasitaemia developed progressively to a maximum of 55.3 per cent a 6.1 l and pcv fell progressively to a minimum of 14.3 per cent + 3-51 just before death. Maximum temperature was 4193°C + 0 - 2 3 around day 15 but fell to about 40-5°C for a few days before death.
TABLE 1: Summary of observations {group means) on calves infected with ThePwEeannuletaand treated with panmquone, 20 mg kg x 1 or 10 mg kg x 2 intramuscularly
'
Untreated controls Number of deaths Days to death
Pawaquone treatment 2 0 m g k g - I lOrngkg 10mgkg day 10 days 10 b 11 days 10 & 12
3/3 17,21.24
2/4 15.19
1/4 17
114 21
-
0.25 1.O 22.5 39.3
0.5
0.5
3.7
1.0 24.7 39.1
Dav 10 Macroschizont score Parasitaemia % PCV % Temperature After day 12 Maximum rnacroxhizont score Maximum piroplasrn parasitaemia % Minimum PCV % Maximum temperature Day 28 Schizont score Parasitaemia % PCV
Oh
Temperature
25 38.3
Purvaquone creafment of Theileria annulata Group 2. Parvaquone 20 mg kg-
',day I0
All four calves appeared to respond rapidly to treat ment and showed no signs of drug toxicity. While two remained healthy, one died on day 15, and one died on day 19with symptoms or theileriosis similar t o those in the controls. Parasitosis was well controlled in the lymph nodes examined, being no higher than score 1 after day 16. Piroplasm parasitaemia did not exceed 5 per cent in any of the calves, and PCV fell below 23 per cent (to 18 per cent) in only one calf. In the caIr which died on day 15, the minimum pcv was 34 per cent . Its lungs were oedematous and its lymph nodes enlarged. No signs of drug toxicity or intercurrent infection were seen. Temperature was well controlled in all but the one calf which died on day 15; a deposit of drug was found at the injecrion site in this calf at post mortem examination. Group 3. Parvaquone, 10 rng kg- I, days I0 and I I Development of infection was essentially similar to that in group 2. One calf died of thcileriosis but without anaemia on day 17 and, again, no signs of drug toxicity were observed in any of the calves. One calf recovered rapidly while two made slow recoveries, having shown apparently good control of organisms following treatment. Schizonts and piroplasrns became degenerate by the day following first treatment and remained at low levels until death or cure. Few healthy schizonts were seen after treatment and piroplasm parasitaemia reached a maximum of 4.0 per cent k 4.0 healthy parasites. pcv reached minima of 17, 19 and 27 per cent in the survivors, but 34 per cent in the one which died. Temperature was well cor~trolledin all calves except the one which died. Group 4. Parvaquone, 10 mg kg-', days 10 and 12
One calf died of theileriosis without anaemia on day 2 1, two made good recoveries while one recovered having shown a recrudescence of schizonts to score 3 with microschizonts present in the parotid node from days 20 to 24, but without a concomitant rise in schizont number in the prescapular node or in the number of piroplasms. Treatment again caused degeneration of schizonts and piroplasms within 24 hours. While major recrudescences of schizonts occurred in the parotid nodes of the calf which died and one other, they had been eliminated from prescapular nodes in all four calves by day 14. Piroplasms attained maxima of 4 . 5 per cent 2 4.04, the highest being 10 per cent on day 19 in the calf which subsequenrly developed schizont recrudescence. PCV minima were 19 per cent and 30 per cent in the two good responders, 38 per cent in the one which died and 17 per cent in the one
3
which relapsed. Temperature was well controlled in all four. Discussion
Mortality from T annulata infection among Bos ruurus cattle in the field may reach 70 per cent
(Uilenberg 1981). The fact that all the controls in this trial died of acute theileriosis may indicate that the challenge was particularly severe. At the time of treatment, however, symptoms of t heileriosis were not severe, although clinically clearly apparent. The response to treatment in all three groups was essentially similar. lnitial control was good but recrudescences of varying severity then ensued. Two doses of 10 mg kg-' parvaquone gave rather better results than one dose of 20 mg kg-' and is the recommended regimen for the treatment of Tparvu infection. Plasma levels of parvaquone in cattle infected with T purva, measured by a bioassay method, showed that this course of treatment resulted in schizonticidal concentrations of drug which lasted for four days from the first treatment (McHardy and Mercer 19851, while a single dose of 20 mg kg-', although producing a higher peak concentration, lasted for only about three days. I t is interesting to note that the untreated controls died with symptoms primarily attributable to both schizont parasitosis (pulmonary and lymphoid lesions) and piroplasm parasitaemia (anaemia). The treated calves which died generally showed only pulmonary and lymphoid lesions but no anaemia. This suggests that death was due, primarily, to schizont parasitosis. The results reported here indicate that further doses of 10 mg kg- parvaquone could have increased the cure rate, particularly if given before signs of recrudescence were seen, so as to depress further the development of schizonts. Since the infection in this trial was apparently more severe than that commonly encountered in the field, it is possible that a total dose of 20 mg kg-' parvaquone, given early in the clinical syndrome, would be effective in field cases of Tannulata infection. The results or Gill et a1 (1981) and Sultan et al (198 1 ) were very similar to those reported here. They both used Indian isolates of T annuluca whereas a Turkish isolate was used in this study. This indicates that strains from widely different locations respond similarly to treatment with parvaquone. Gill et al (1981) round that an interval of three days between doses of I0 mg kg- parvaquone gave perhaps poorer results than a single dose o f 20 mg kg- I . The bioassay of plasma from treated cattle (McHardy and Mercer 1985) may offer an explanation for this. Drug levels may have fallen below inhibitory levels bet ween doses, so permitting recrudescence which was incompletely con trolled by the second dose.
'
It appears, therefore, that a total dose of 20 rng kg-' parvaquone, given within 48 hours, is an effective treatment for most early clinical cases of T annulato infection, but funher treatment should be given promptly if a clear improvement in the clinical condition of the animal is not seen. Further work is required to study the effect of additional treatment with parvaquonr in cattle showing delayed recrudescence of infection. Acknowledgements
We would like t o thank the staff of the Wellcome Research Laboratories, especially Mr M. P. Trevithick and Mr P. J. Matthews, for their expert technical help, and Mr C. G. D. Brown, Centre for Tropical Veterinary Medicine, Edinburgh, for provision of the stabjlate.
Eds A. D. Irvin, hi. P.Cunningharn and A. S. Ynunp. The Hague. Xfartinus Nijhoff. pp 186-208 GILL. B. S.. BHATTACHARYULU. Y.. SINGH. A.. KAUR. D. .&: GILL. H. S. (19811 Advancer i n the Control of Theilcrioci\. Eds A. D. Irvin, b?. P. Cunningham and A. S. Young. The Hague, Maninus Nijhofi. pp 218-222 KIRUI. N. H. A.. KIBOR. A. C . . MWlMURI. F. h.1.. KOSRER. J. K.. OLUBAYO, R. 0.. INJAIRU. R. %I.& KARIUKI. I). P. ( 1983) A'F~~VU I,'e~erinarian7. 13- 14 McHARDY. N. (1979) Jr~urnalof rhe South Afriron I'ererinur.~ Assnriarion 59. 321-322 SlcHARDY. N.. HUDSON. A. T.. MORGAN, D. W . T.. RAE. D. G . & DOLAK. T. T. (19R3) Rer~clrrhin Veferinarv Science 55.347-352 McHARDY. N. & MERCER. J. P. (1984) K ~ n y aC'eterinuriun 8, 9-11 SULTAN. B. A., LATIF. R. M. A. & ALTAIF, K. 1. (1981) Advancer in he Control o f Theileriosis. Eds A. D. Irvin. Xi. P. Cunningham and A. S. Young. Thc Hague, !blartinu< Nijhoff. p 223 UILENBERG. G. (1981) Diseases of Cat~lein the Tropics. Ed%X I . Rir~icand I.Mclnryre. The Hague. Martinus Nijhoff. pp 41 1 - 4 3
References DOLAN. T. T. (1981) Advances in the Control of Theilerio5is.
Received for publication k?u.v 1, 1984