7. Chemoprophylaxis at Mkwaja

Prophylactic and therapeutic regime
Trypanosomiasis diagnosis from blood smears
Environmental influences on number of treatments required
Effect of trypanocidal treatments required on performance
Conclusions

Prophylactic and therapeutic regime

The necessity for prophylactic treatment at Mkwaja, to enable cattle ranching to be undertaken in this situation, has been described in Chapter 3.

From 1973 to June 1980, breeding cows, heifers, bulls, young bulls and steers were maintained under Samorin prophylaxis (0.5 mg/kg bodyweight) administered on a herd basis, with the dates on which each herd was treated being recorded. Infection was monitored by a programme of blood sampling. Thick blood smears were used to establish whether infection was present and thin smears to identify the species of trypanosome. Between 30 and 40 animals per herd were tested, beginning 1 month after the last herd prophylaxis. This was repeated every 1 or 2 weeks depending on a subjective assessment of the level of challenge. Animals selected for blood sampling were not representative of the whole herd but included any animals which looked in poor condition. The results of the bood sampling, together with a subjective assessment of the health of the whole herd, were used to decide on the need for prophylaxis. If 20% of slides in a sample were trypanosome-positive this would result in treatment of that herd with Samorin. If less than 20% of slides were positive from a herd which was judged to be in generally good health, this would not result in immediate herd treatment, but in treatment of the individually positive animals with Berenil. However, a similar proportion of positive slides found in a herd where the animals appeared not to be in good health would result in treatment of all cattle with Samorin.

Blood samples were also taken from individual animals if they appeared to be sick on being counted in and out of the night paddocks. If a slide revealed parasitaemia, and the next Samorin treatment for the herd was not yet due, the animal would be treated with a curative dose of Berenil. Records for these treatments administered on an individual basis were not available but represented approximately 4% of the total number of treatments. Berenil was also used occasionally on a herd basis. This was either done strategically, when a particularly high infection rate was detected (e.g. August 1974), or to overcome periods of shortages of Samorin (e.g. 1978). When Berenil was used on a herd basis, the date of treatment for each herd was recorded. Calves received Berenil approximately once a month on a herd basis and were treated with Samorin just before weaning.

In June 1980 the criteria for herd treatment and the drug regime employed were changed. Beginning 2 months after the last prophylaxis, as soon as routine sliding indicated the first parasitaemia, all cows in a herd, together with their calves, were to be treated with Berenil (3.5 mg/kg bodyweight). Approximately 1 week later this was to be followed up with Samorin at 1.0 mg/kg. However, during late 1981 and 1982, due to drug shortages, treatment with Berenil often did not precede treatment-with Samorin. The records however showed the dates each herd received either Samorin or Berenil.

Trypanosomiasis diagnosis from blood smears

Table 18 shows the results of thick blood smear examinations from 1973 to 1982, grouped by area, location, year and season.

From more than 37000 thick blood smears examined, 10.6% were found to be positive for trypanosomes. In over 90% of the positive cases T. congolense was identified; T. vivax was identified in most of the remainder; T. brucei was found in only 1%. As the experimental studies reported in Chapter 3 show, the level of tsetse challenge at Mkwaja is so high that all cattle must eventually become infected. Thus the results given in Table 18 do not reflect the overall prevalence of trypanosomes, but rather the decision-making strategy of treating herds based on a 20% detection rate of trypanosomes in a sample, coupled with assessment of general herd condition. A higher proportion of positive smears were found in animals sampled in the northern area (11.7%) than in the southern area (9.7%). The 'maximum' and 'minimum' locations were N2 (17.4%) and S4 (7.8%). Year means ranged from 6.9% positive smears in 1978 to 18.7% in 1982. As far as seasonal effects were concerned, October to December (the short rainy season following a dry period) yielded the lowest percentage of positive smears (8.6%).

Table 18. Evaluation of thick blood smears from cattle, Mkwaja Ranch, 1973-82.

		Number of smears examined	Number positive for trypanosomiasis	% positive for trypanosomiasis
Total		37484	3974	10.6
Area
	Northern	16924	1979	11.7
	Southern	20560	1995	9.7
Location
	N1	13158	1325	10.1
	N2	3766	654	17.4
	S3	6757	787	11.6
	S4	9611	753	7.8
	S6	4192	455	10.9
Year
	1973	6101	736	12.1
	1974	5986	473	7.9
	1975	2558	267	10.4
	1976	3913	287	7.3
	1977	3660	275	7.5
	1978	3101	213	6.9
	1979	2493	323	13.0
	1980	2887	348	12.1
	1981	2985	343	11.5
	1982	3800	709	18.7
Season
	Jan. to Feb.	5502	574	10.4
	March to May	11624	1233	10.6
	June to Sept.	12788	1516	11.9
	Oct. to Dec.	7570	651	8.6

Environmental influences on number of treatments required

The numbers of trypanocidal drug treatments required annually, calculated from the numbers given from one calving to the next, were 4.4 ± 0.02 Samorin treatments with a coefficient of variation of 41% and 0.6 ± 0.01 Berenil treatments with a coefficient of variation of 124%. The significance of environmental influences on the numbers of Samorin and Berenil treatments required is indicated in Table 19. The actual effects related to year of calving, season of calving, age, sex of calf, and ranch area and location are presented in Table 20.

Year of calving. Cows calving from 1973 to 1978 were maintained under the same criteria for prophylactic treatment. In general, they were treated with Samorin when 20% trypanosome positive slides were detected in a 10% sample of animals from their herd, usually selected as the poorest looking individuals. Occasionally shortages of Samorin meant that Berenil was substituted. A change in criteria for treatment, instigated in 1980, affected all cows calving from 1979 onwards. In these years, as soon as the sample sliding indicated the first parasitaemia in a herd, all cows were treated with Samorin. It had been intended that they should additionally be treated with Berenil, but due to shortages this often did not take place.

As indicated in Table 20, there was a marked increase in the number of annual Samorin treatments during the period 1975 to 1978 (average of 4.8) compared with the period 1973 to 1974 (average 3.5). The number of Berenil treatments also increased from approximately 0.1 per year in 1973 to 1974 to 0.3 per year in 1975 to 1978. One possible explanation for the increase in the number of annual treatments between 1973 and 1978 is variation in tsetse challenge; precise information to confirm or disprove this is not available. On the other hand, the increase in the number of treatments from 1973 to 1978 could reflect a progressive reduction in the sensitivity of the trypanosome population to Samorin; however, for reasons discussed later in this chapter there is circumstantial evidence that Samorin resistance was not developing. The altered criteria for treatment affecting 1979 to 1981 carvings led to a further increase to 5.2 Samorin treatments and 1.8 Berenil treatments per year over that period.

Season of calving. There was no significant difference in number of Samorin treatments due to season of calving. There was some indication that cows calving from March to September had slightly more Berenil treatments than those calving during the remaining months of the year.

Age. There was no evidence of any differences in numbers of Samorin or Berenil treatments due to age of cows.

Sex of calf. The sex of a calf had no effect on the number of Samorin or Berenil treatments received by its dam.

Area or location. There was a marked difference between the northern and southern areas of the ranch in the number of Samorin treatments (4.3 in the north, 4.9 in the south) but no differences in the number of Berenil treatments. The major location difference was between locations N1 and N2 in the northern area (4.0 versus 4.5 for Samorin and 0.1 versus 1.3 for Berenil). Both area and location differences could have been influenced by bush clearance work which had taken place in the northern area but not in the southern and which was concentrated on the N1 location very much more than the N2 location. This bush clearance has had a considerable effect in reducing tsetse densities in the northern area and especially in location N1.

Table 19. Mean squares for number of Samorin and Berenil treatments required annually, Mkwaja Ranch, 1973-82.

Source	df	Number of Samorin treatments	Number of Berenil treatments	Total number of treatments
Year (A)	8	1892**	2978**	7319**
Season (B)	3	68**	411**	352**
Age	3	46**	830**	1132**
Sex of calf	1	0	2	0
Area (C)	1	4463**	22	5108**
Location/northern area	1	397**	1856**	4036**
Location/southern area	2	140**	394**	203**
A x B	24	423**	329**	770**
A x C	8	479**	407**	871**
B x C	3	262**	186**	614**
Remainder	11944	6	6	12

** = P < 0.01

Effect of trypanocidal treatments required on performance

Number of Samorin treatments required
Berenil treatment given
Interaction between Samorin and Berenil treatments: Its relevance to drug resistance
Timing of Samorin treatment

Table 21 summarises the significance of trypanocidal treatments required, and their interactions, on performance traits. The actual significance values are presented in Table 14.

The period from parturition to 240 days after parturition is the optimal period for evaluation of treatment effects in relation to calving interval (mean reconception period is 7.3 months), calf viability, pre-weaning growth and weaning weight (8 months), and cow productivity index (8 months).

In interpreting the effects of drug treatments and their interactions on performance traits, the strategy of the prophylactic regime has to be kept in mind. The number of Samorin treatments that animals received over the 240-day period from parturition was based on blood smear evaluations and assessments of herd condition. These almost certainly reflected the level of tsetse challenge that animals were subjected to in a particular geographical situation on the ranch, in a particular year, and at a particular season of the year. The basic strategy was to treat a herd as soon as a small proportion of animals had become affected by trypanosomiasis, and restore the health status of the herd as rapidly as possible.

Table 20. Estimated least squares means for number of Samorin and Berenil treatments required annually, Mkwaja Ranch, 1973-82.

Variable		Number of cows	Number of Samorin treatments	Number of Berenil treatments	Total number of treatments
Overall		11999	4.6	0.7	5.3
Year of calving
	1973	1516	3.4a	0.0a	3.4a
	1974	1829	3.5a	0.2b	3.7b
	1975	1670	4.4b	0.1a	4.6c
	1976	1550	4.7b	0.0a	4.7c
	1977	1172	4.5b	0.4c	5.0d
	1978	910	5.2c	0.4c	5.6e
	1979	842	5.3c	1.1d	6.4f
	1980	1503	5.1c	2.6f	7.7g
	1981	1007	5.0c	1.6e	6.6f
Season of calving
	Jan. to Feb.	874	4.6a	0.3a	4.9a
	March to May	1709	4.7a	0.9c	5.6c
	June to Sept.	7872	4.5b	1.1d	5.5c
	Oct. to Dec.	1544	4.5b	0.6b	5.1b
Age
	3 to 4 years	3591	4.5a	0.5a	5.0a
	5 to 6 years	3819	4.5a	0.9c	5.4c
	7 to 8 years	2777	4.6b	0.&	5.5c
	9 years end over	1812	4.6ab	0.7b	5.3b
Sex of calf
	Male	5912	4.6	0.7	5.3
	Female	6087	4.6	0.7	5.3
Area
	Northern	5365	4.2a	0.7	4.9a
	Southern	6634	4.9b	0.7	5.7b
Location/area
	North1	4130	4.0a	0.1a	4.1a
	North2	1235	4.5b	1.3b	5.8b
	South3	2847	5.0b	0.5a	5.5a
	South4	2812	5.1b	0.5a	5.6a
	South6	975	4.7a	1.2b	5.9b

Within variable groups, row means followed by the same letter do not differ significantly (P < 0.05). If no letter is used it indicates the variable group did not show a significant difference in the analysis of variance.

Number of Samorin treatments required

The effects of number of Samorin treatments required from parturition to 240 days after parturition on the performance traits of calving interval, calf viability, calf pre-weaning growth, calf weaning weight and cow productivity index are given in Table 22.

In general, performance deteriorated as the number of Samorin treatments required during the 240 days after parturition increased. This would be the logical expectation from the strategy of Samorin treatment as soon as a small proportion of animals in a herd had become affected by trypanosomiasis.

Number of Samorin treatments required had a significant interaction with Berenil treatment given and with age for some performance traits. No patterns could be identified for the interaction with age. The interaction with Berenil treatment given is discussed below.

Berenil treatment given

The effects of any Berenil treatments given from parturition to 240 days after parturition on the performance traits of calving interval, calf viability, calf pre-weaning growth, calf weaning weight and cow productivity index are given in Table 23.

Table 21. Summary of significance of trypanocidal treatments and their interactions on performance traits Mkwaja Ranch, 1973-82.

		Calving interval	Calf viability	Birthweight	Pre-weaning growth	Weaning weight	Cow productivity
Number of cow
	Samorin treatments		**		**	**
Timing of cow
	Samorin treatments		*	**	*	**
Cow Berenil treatment					*	*
Number of cow Samorin
	treatments x cow Berenil treatment				**	**	**
Timing of cow Samorin
	treatments x cow Berenil treatment			**			*
Area x timing of cow
	Samorin treatments			**
Area x cow Berenil treatment				**	*	**
Age x number of cow
	Samorin treatments				**	**
Age x cow Berenil treatment		*	**	**	**	**	**
Year x cow Berenil treatment		*		**	**	**	**

* = P < 0.05
** = P < 0.01

Table 22. Effects of number of Samorin treatments required from parturition to 240 days after parturition on performance traits, Mkwaja Ranch, 1973-82.

Trait	Significance in ANOVA	No. of Samorin treatments required
		1	2	3	4
Calving interval (days)	NS	511	499	504	505
Calf viability (%)	**	96.1	92.5	89.5	86.4
Pre-weaning growth (g/day)	**	460	451	438	436
Weaning weight (kg)	**	135.8	133.6	130.1	129.5
Cow productivity index (kg)	(*)	96.1	95.4	93.4	90.3

NS = Not significant
(*) = Approaching significance
** = P < 0.01

Performance deteriorated if any Berenil treatment was given during the 240 days after parturition. Again, this would be the logical expectation from the strategy of Berenil treatment, either as a substitute for Samorin (1973 to 1979) or in addition to Samorin (1980 to 1982), as soon as a small proportion of animals in a herd had become affected by trypanosomiasis.

Berenil treatment given had a significant interaction with number of Samorin treatments required, and with age, area and year of calving, for some performance traits. No patterns could be identified for the interactions with age, area and year of calving. The interaction with number of Samorin treatments required is discussed below.

Interaction between Samorin and Berenil treatments: Its relevance to drug resistance

The interaction constants between Berenil treatment given and number of Samorin treatments required, from parturition to 240 days after parturition, on the performance traits of calving interval, calf viability, calf pre-weaning growth, calf weaning weight and cow productivity index are given in Table 24. The numbers of records in each class are indicated in Table 25.

Table 23. Effects of Berenil treatment given between parturition to 240 days after parturition, on performance traits, Mkwaja Ranch, 1973-82.

Trait	Significance in ANOVA	No Berenil treatment given	Berenil treatment given
Calving interval (days)	(*)	494	515
Calf viability (%)	NS	89.5	88.6
Pre-weaning growth (g/day)	*	452	441
Weaning weight (kg)	*	133.6	130.9
Cow productivity index (kg)	NS	94.0	93.5

NS = Not significant
(*) = Approaching significance
* = P < 0.05

Table 24. Interaction constants between Berenil treatment given and number of Samorin treatments required from parturition to 240 days after parturition, on performance traits, Mkwaja Ranch, 1973-82.

Trait	Significance in ANOVA	No. of Samorin treatments required
		1	2	3	4
Calving interval (days)a	NS	- 12	1	7	4
Calf viability (%)b	(*)	+ 1.2	- 0.5	+0.3	-1.0
Pre-weaning growth (g/day)b	**	+14	+8	- 2	- 19
Weaning weight (kg)b	**	+ 3.3	+2.0	- 0.6	-4.7
Cow productivity indexb	**	+ 8.0	+0.5	- 2.5	- 6.0

^a Lowest value most desirable
^b Highest value most desirable
NS = Not significant
(*) = Approaching significance
** = P < 0.01

The interaction constants in Table 24 show that in all traits the use of Berenil treatment had the greatest relative effect on performance in the situation where only one Samorin treatment was required. The relative effect of Berenil treatment decreased as the number of Samorin treatments required increased.

This would suggest that at a location and time where only one Samorin treatment is required over the 240-day period, the level of trypanosomiasis risk must be relatively low, and therefore the average time for trypanosomiasis reinfection relatively long. A Berenil treatment given in this situation will have a curative effect and the treated animal is likely to remain uninfected for a relatively long period. In contrast, when a cow receives four or more Samorin treatments during the 240-day period, the level of challenge must be high, and the average time to trypanosomiasis reinfection relatively short. A Berenil treatment in such a case will also have a curative effect, but the treated animal is likely to become reinfected rapidly.

Cross-resistance between Samorin and Berenil is thought to be rare (Leach and Roberts, 1981). Thus in a situation where resistance to Samorin existed, it would be expected that use of an occasional Berenil treatment would be more effective than an additional Samorin treatment. In terms of maintaining overall productivity, Table 23 shows that the effects of an occasional Berenil treatment are very similar to those of a Samorin treatment (Table 22). Further, if resistance to Samorin was to develop, this would be expected in a high trypanosomiasis-risk situation where Samorin treatments are required very frequently, rather than in a low-risk situation where only infrequent treatments are necessary. Table 24 illustrates, however, that Berenil has relatively less impact in a high-risk than in a low-risk situation.

Table 25. Numbers of records in interaction classes between Berenil treatment given and number of Samorin treatments required, from parturition to 240 days after parturition, Mkwaja Ranch, 1973-82.

Trait	Berenil treatment given	No. of Samorin treatments required
		1	2	3	4
Calving interval	No	136	1896	3690	1754
	Yes	368	1501	1968	686
Calf viability	No	564	3024	5261	2560
	Yes	615	2393	2726	1123
Pre-weaning growth	No	537	2788	4646	2050
	Yes	557	2192	2510	995
Weaning weight	No	537	2788	4646	2050
	Yes	557	2192	2510	995
Cow productivity index	No	136	1896	3690	1754
	Yes	368	1501	1968	686

Table 26. Effect of timing in relation to calving date of first Samorin treatment required, on performance traits, Mkwaja Ranch, 1973-82.

Traits	Significance in ANOVA	Shortly beforea calving	Atb calving	Shortly afterc calving	Longer afterc calving
Calving interval (days)	NS	509	502	500	506
Calf viability (%)	*	92.4	90.9	90.7	90.4
Birthweight (kg)	**	25.9	25.4	25.2	25.6
Pre-weaning growth (g/day)	*	450	447	445	442
Weaning weight (kg)	**	133.5	132.4	131.7	131.4
Cow productivity index (kg)	NS	95.0	94.1	92.8	93.2

^a 30 to 11 days before parturition
^b 10 days before to 10 days after parturition
^c 11 days after to 30 days after parturition
^d 31 days after to 240 days after parturition
NS = not significant
* = P < 0.05
** = P < 0.01

Thus, the simultaneous evaluation of the effects of Samorin and Berenil treatments and their interaction, on the major performance traits, suggests that at Mkwaja over the period 1973 to 1982 there are no indications from productivity levels of any resistance to Samorin having developed.

Timing of Samorin treatment

The effects of four stages at which the first Samorin treatment was required on the performance traits of calving interval, calf viability, birthweight, pre-weaning growth, weaning weight and cow productivity index are shown in Table 26.

In general, performance was best if the first cow Samorin treatment took place shortly before calving, with a gradual falling-off as the first Samorin treatment date moved further away from the calving date. There was no indication that the use of Samorin in pregnant animals had any negative effect on performance. Timing of Samorin treatment had a significant interaction with Berenil treatment given and area, for some traits, but no patterns could be identified.

Conclusions

This work was carried out in a situation where it had been clearly shown that without chemoprophylactic treatments, animals would die (Chapter 3). The decision to treat animals, based on blood smear evaluation and assessment of herd condition, was such that the number of treatments required reflected the level of trypanosomiasis risk that animals were subjected to, at a particular time and location.

The number of treatments given increased from 1973 to 1981, and could have been related to reduced efficiency of the drug (not borne out by other circumstantial evidence), fluctuations in tsetse challenge (no precise information was available), or to changes in drug strategy (this was known to be the case from 1979 onwards).

Old cows required exactly the same number of treatments as young cows. In Chapter 6 it was shown that cows did not start becoming less productive until 9 years of age and over, consistent with numerous reports from non-trypanosomiasis situations. Thus, maintenance under continuous prophylactic treatment until 9 years of age did not lead to increased requirements for treatment or to an early decline in productivity.

The interaction effects on animal performance between Berenil and Samorin showed Berenil to be relatively more effective in a lower challenge situation than in a higher one. This indicated that, as cross-resistance between Berenil and Samorin is thought to be rare, maintenance under continuous Samorin prophylaxis had not led to the development of resistance to the drug.

There was no indication that the use of Samorin in pregnant animals had any negative effects. In fact a treatment between 30 days before and 10 days after parturition appeared beneficial.