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The study assessed an integrated trypanosomosis control strategy in drug-resistant hotspot villages of northern Togo. This strategy comprised (i) rational trypanocidal drug use in symptomatic cattle, (ii) vectors and ticks control by targeted bi-monthly insecticidal spraying of the lower body parts of cattle and (iii) strategic deworming with Albendazole in the beginning and the end of the rainy season. The program was implemented between June 2014 and October 2015 in four villages in northern Togo, which had been previously identified as drug resistant hotspots for diminazene diaceturate (DA) and isometamidium chloride (ISM). The integrated control strategy was implemented in eight cattle herds at risk of the disease from two villages. Twelve herds from two other villages served as controls where trypanosomosis management and deworming remained under control of the farmers. Trypanocidal drug use during the study period was recorded by the intervention team based on the farmers' reports and own observations. Cattle herds were followed-up for trypanosomosis symptoms which were recorded at 3 to 4-month intervals, while extensive trypanosome diagnostics and recording of the packed cell volume were done before and after the intervention. Intervention herds had a significantly lower risk of trypanosome infection with a risk ratio of 0.18 (95% CI: 0.04, 0.91; p = 0.03), but no significant effect on mean packed cell volume was observed. However, trypanocidal treatments per animal per year were lower in intervention herds compared to control herds (0.3 vs 5 for DA and 0.8 vs 2 for ISM). This study demonstrates that the implementation of an integrated best-bet strategy leads to a reduced trypanosome prevalence under lowered trypanocidal use., (Copyright © 2018 Elsevier B.V. All rights reserved.)

A study using a structured questionnaire was conducted in Busia District, Western Kenya and Kwale District, Coastal Kenya to obtain qualitative and quantitative information from 256 cattle owners about their production systems, their perceptions of the diseases encountered in their cattle, the drugs used, and other measures adopted to control trypanosomiasis in cattle. The predominant production system was mixed crop-livestock with farmers owning 2-11 local cattle on holdings between 2 and 5 ha. Approximately 15% of disease episodes in cattle were perceived to be trypanosomiasis, although the farmers' ability to make diagnoses was limited in that over half of the diagnoses were inconsistent with the clinical signs described. Drugs were generally obtained from agro-veterinary shops, and the farmers themselves administered slightly more than half of these. One third of drug treatments given to sick cattle were trypanocides, but over half of these trypanocidal treatments were given to cattle believed to have diseases other than trypanosomiasis.

Cattle from 50 farms in Mukono County, Uganda, were monitored for trypanosomes every second month over an 18-month period (1995-1996) by mini-anion exchange chromatography and haematocrit centrifugation techniques. Eighteen trypanosome isolates collected from cattle during this period were characterised in cattle, goats and mice for their sensitivity to homidium, isometamidium and diminazene; 10 of the isolates were selected randomly, 8 were from animals that had the highest serum isometamidium concentrations at the time the isolates were collected. All the isolates contained only Trypanosoma brucei and/or T. vivax. In nai;ve Boran (Bos indicus) cattle the isolates exhibited low pathogenicity and were sensitive to diminazene aceturate at 3.5 mg/kg body weight (bw) and isometamidium chloride at 0.5 mg/kg bw. In goats, 5 of 8 isolates were highly pathogenic, producing clinical signs indicative of central nervous system involvement within 60 days of infection; all such isolates contained T. brucei. However, all 8 populations were sensitive in goats to diminazene aceturate at 3.5 mg/kg bw. In contrast, 4 populations were refractory to treatment with isometamidium chloride at 0.5 mg/kg bw in at least 1 out of 3 goats each. Furthermore, 5 populations were refractory to treatment with homidium chloride at 1.0 mg/kg bw in a minimum of 2 out of 3 goats each. In mice, the 50% curative dose values for 11 Mukono isolates that contained T. brucei ranged from 0.30 to 1.89 mg/kg bw for diminazene aceturate, from 0.02 to 0.17 mg/kg bw for isometamidium chloride and from 0.90 to 4.57 mg/kg bw for homidium chloride. Thus, by comparison to reference drug-sensitive populations, all the stabilates were highly sensitive to diminazene and isometamidium, while some expressed low levels of resistance to homidium.

The trypanocidal activity of two commercially available isometamidium-based products, Samorin (Merial, USA) and Veridium (Sanofi Santé Nutrition Animale, France), used at a dose rate of 0.5 mg kg(-1) bodyweight, was compared in a field trial involving groups of approximately 30 zebu cattle in a trypanosomosis endemic part of south-western Kenya. The trial took place between April 1997 and March 1998 during a time of higher than normal rainfall that resulted in periods of high trypanosome challenge. The trial consisted of five consecutive prophylactic cycles, each of approximately 10 weeks duration. It was demonstrated that there was no significant difference in the prophylactic activity of the two isometamidium-based products, and no significant difference between the relative activity of three different batches of the product Veridium used during the course of the trial. There was some evidence that drug-resistant strains of trypanosomes may have been present, but it was concluded that isometamidium is still an effective trypanocidal drug in this location.

Two trials were carried out in order to compare the prophylactic effect of a subcutaneously implanted sustained release device (SRD) containing a mixture of a biodegradable copolymer, poly(caprolactone-co-L-lactide), and isometamidium (ISMM) with that obtained after intramuscular injection of the drug. In a first experiment under controlled conditions, two groups of cattle were treated with 0.5 mg/kg isometamidium either as a SRD or intramuscularly (i.m.), and exposed at monthly intervals to Glossina morsitans morsitans infected with Trypanosoma congolense. The average protection period was at least 24 months in the SRD treated against 5.7 months in the i.m. treated group. Using an ISMM enzyme-linked immunosorbent assay, the drug could be detected until 140 days post-treatment in the latter group, whereas in the former group, traces of the drug were detectable until 330 days after treatment. Furthermore, a field trial was carried out at the Madina Diassa ranch in Mali involving three groups of N'Dama cattle, each containing 23 or 24 animals. Two groups were treated with 1 mg/kg ISMM either as a SRD or i.m. and a third group served as untreated control. Twelve months after treatment, the cumulative infection rates were 56.5, 87.8 and 91.6% in the SRD implanted, the i.m. treated and the control groups, respectively. The ISMM concentrations were slightly lower than in the laboratory trial, but the overall pattern of drug disappearance from the sera of the SRD treated cattle was very similar in both trials. Statistical analysis showed that the incidence of trypanosomiasis was significantly lower in the SRD treated than in the i.m. treated group.

Susceptibility to trypanosome infections and tick infestations was assessed in 51 N'Dama, 48 Gobra zebu and 37 Gobra x N'Dama crossbred (F1) cattle exposed to field-tick infestations and natural high tsetse challenge over more than one year. From these cattle, 12 animals of each breed were randomly selected and examined parasitologically for trypanosome infections and packed cell volume (PCV) twice a week (high surveillance, group HS). In the remaining 100 cattle trypanosome infection and PCV were monitored monthly (low surveillance, group LS). Mortality rates were recorded in both groups. Tick infestation was quantified fortnightly from all animals in group HS and from four to seven randomly selected animals of each breed in group LS. In both HS and LS groups, trypanocidal drug treatment was administered to trypanosome positive animals with PCV equal to or less than 20% or when they showed clinical evidence (dullness, weight loss) of trypanosomosis. In both groups, N'Dama cattle exhibited a superior capacity to control trypanosome infections and limit tick burdens. Particularly, in group HS N'Dama cattle showed lower trypanosome infection rate, higher mean PCV value, lower requirement for trypanocide treatments and lower tick load than crossbred and Gobra cattle in the corresponding group (P < 0.05 or greater). This was also true in N'Damas in comparison with crossbreds in group LS. Unfortunately, the high mortality occurring in Gobra cattle in group LS did not allow within group comparative analysis between N'Dama, Gobra and crossbred cattle overall the study period. No death occurred in N'Dama cattle maintained under high surveillance of trypanosome infection, while approximately 8% of crossbreds and 50% of Gobras died of trypanosomosis. In group LS, all Gobra and more than 70% of crossbred cattle died. In this group, mortality in N'Dama was limited to less than 16%. In both groups, differences in mortality were significantly higher (P < 0.01) in Gobras than in N'Damas. Within breed, animals of the three breeds maintained under high surveillance of trypanosomal infection showed higher mean PCV values, lower tick burdens and required proportionally less trypanocide treatments than corresponding cattle in group LS. The infection rate in N'Dama under high surveillance was lower in comparison with N'Dama cattle in group LS. There was no significant difference in mortality between groups within the N'Dama breed. Conversely, mortality rates were lower in crossbred and Gobra in group HS than in respective cattle in group LS. It was concluded that cattle of the three breeds suffered from trypanosomosis and that trypanosome infections affected tick susceptibility. However, N'Dama showed a superior ability to limit both the pathological effects of trypanosomosis and the level of tick infestations. Therefore, considering the cost of labour and consumable equipment required for a high surveillance, use of multi-disease resistant N'Dama cattle is recommended for the low-input traditional African farming systems in areas where trypanosomosis, ticks and tick-borne diseases are constraints to livestock production. Additional comparative investigations are needed to assess the impact of high surveillance scheme of trypanosome infection in different production systems in trypanotolerant and trypanosusceptible cattle exposed to different gradients of tsetse challenge.

The duration of prophylaxis provided by isometamidium chloride and homidium bromide, each at a dose rate of 1 mg kg-1 bodyweight, was compared in a 12-month field trial involving groups of 30 zebu cattle in south-west Kenya. The trial took place between February 1990 and February 1991 and included several months of high trypanosome challenge. Cattle in the prophylaxis groups were retreated on a group basis when 10% of the group had become infected since the previous group treatment. On this basis the mean intervals between retreatment were 7.5 +/- 1.9 and 4.6 +/- 2.1 weeks for the isometamidium and homidium groups, respectively. Weight gains in the two groups were similar. In spite of the need for more frequent treatment in the homidium group as compared to the isometamidium group, total drug costs were lower in the former. There was evidence of Trypanosoma congolense resistant to homidium and some evidence of T. vivax resistant to isometamidium.

Fifteen Boran cattle from a trypanosomiasis-free area were injected intramuscularly with isometamidium chloride at a dose of 1 mg/kg body weight. Thereafter, the cattle were challenged at monthly intervals with Glossina morsitans centralis infected with one of three populations of Trypanosoma congolense (IL 3893, IL 3889 or IL 1180) until all animals became infected. Isometamidium concentrations in the sera of these cattle were measured using a competitive enzyme-linked immunosorbent assay over the first 105 days following treatment. All cattle challenged with IL 3893 or IL 3889 developed infection following the first challenge, at which time the mean serum drug concentration in all treated cattle was 6 ng/ml. Cattle challenged with IL 1180 became infected following 6 to 8 monthly challenges. The mean serum drug concentration in these cattle at the time of their third monthly challenge with IL 1180 was 0.75 ng/ml. Trypanosome populations IL 3893 and IL 3889 were considered to be highly resistant to isometamidium, while IL 1180, relatively sensitive. It was therefore concluded that T. congolense persisting at serum isometamidium concentrations greater than 0.75 ng/ml can be considered moderately resistant, while those persisting at concentrations greater than 6 ng/ml can be considered markedly resistant. These results will be most valuable in the investigation of isometamidium resistance of T. congolense in the field.

The duration of prophylaxis provided by 1 mg kg-1 bodyweight of homidium bromide was compared with that provided by 1 mg kg-1 bodyweight of isometamidium chloride in a 12 month field trial involving 90 Boran cattle exposed to trypanosome challenge on Galana Ranch in Kenya. Weekly trypanosome prevalences of over 30% were observed during 4 of the 12 months. During these periods of heavy challenge, parasites were detected 2-3 weeks after administration of both homidium bromide and isometamidium chloride. Both prophylactic drugs were administered, on a group basis, eight times over the 12 month trial and in addition individual infections were also treated with diminazene aceturate. Isometamidium chloride provided slightly longer periods of prophylaxis than homidium bromide, 28.4 days compared with 25.4 days. There was a highly significant difference in the productivity of the two groups during a period of poor grazing. 27% of the isometamidium chloride herd died from a severe wasting condition with substantial liver damage evident on post mortem. The condition was not observed in the homidium bromide herd. The surviving animals in the isometamidium chloride herd had a mean annual weight gain of 24 kg less than that recorded in the homidium bromide herd.

An investigation was conducted on the therapeutic and prophylactic activity of isometamidium chloride (SamorinR) in Boran (Bos indicus) cattle against a Trypanosoma congolense clone, IL 3270. This clone was derived, without drug selection, from a stock originally isolated in Burkina Faso and has previously been shown to be resistant to isometamidium in both cattle and mice using an infection and treatment regimen. A group of 5 cattle were treated intramuscularly with 1.0 mg kg-1 isometamidium chloride and 28 days later challenged with Glossina morsitans centralis infected with T. congolense IL 3270. All 5 cattle and 17 untreated cattle challenged on the same day became parasitaemic by day 16 post challenge, indicating that prophylaxis did not extend to 28 days post treatment. The cattle were then treated with isometamidium chloride at one of the following doses and by different routes of administration; 1.0 or 2.0 mg kg-1 intramuscularly, 0.25, 0.5, 0.75 or 1.0 mg kg-1 intravenously. Infections relapsed in all cattle at an interval of 12-21 days following treatment, with the exception of those treated with 2.0 mg kg-1 intramuscularly in which the development of relapse infections was delayed. Similar studies were also conducted with a highly sensitive clone of T. congolense, IL 1180. Infections in cattle with this clone were eliminated by intravenous treatment with 0.25 mg kg-1 isometamidium chloride or intramuscular treatment with 0.5 mg kg-1 isometamidium chloride. Thus, although intravenous administration of isometamidium eliminated a fully sensitive infection, treatment by this route appeared not to enhance the therapeutic efficacy of the drug in the treatment of a T. congolense clone which expresses a high level of resistance.

One hundred and forty six calving interval records were built up from 64 N'Dama cows maintained for 3.5 years under a high natural tsetse challenge in Zaire. Matching health and performance data were recorded monthly to allow simultaneous evaluation of the effects of different criteria of trypanotolerance represented by time detected parasitaemic, parasitaemia score and packed red cell volume percent (PCV) on reproductive performance, calf weaning weight and cow productivity. Control of development of anaemia, measured by PCV value during trypanosome infection, had the major effect on all three performance traits. The repeatability of this criterion (0.33) was almost equal to that of calf weaning weight, indicating PCV measurement might be suitable for identification of more trypanotolerant animals. Simultaneous evaluation of the relative effects of control of development of anaemia in both the pre-weaner calf and its dam, on calf performance, suggested that its measurement in an animal might be feasible at an early post-weaner stage. Guidelines for work to develop practical field tests for trypanotolerance involving post-weaners maintained for varying lengths of time in high natural challenge situations are suggested.

Homidium bromide was used in a strategic chemoprophylactic regime to control trypanosomiasis in Boran cattle in Kenya. Trypanosome infection rates in cattle receiving homidium bromide prophylaxis were compared with those in control cattle which received no prophylaxis but were treated with diminazene aceturate when infected. Homidium bromide was administered twice during the year after which no infections were detected for periods of nineteen weeks and seventeen weeks respectively. The drug sensitivity of the infecting trypanosomes is believed to be a major factor in determining the duration of prophylaxis.

Definitions of the term 'challenge' as applied to the African trypanosomiases are reviewed. Data from one West and one East African site show simple linear relationships between the incidence of trypanosomiasis in both humans and animals, and either the amount of man-tsetse contact, or the Apparent Density of flies. Data from a number of East African sites are analysed and show a linear relationship between the mean Berenil Index of cattle and the logarithm of the challenge, where challenge is the simple product of Apparent Density and mean fly infection rate. Apparent Density is a more variable element of total challenge than is infection rate. The results of field studies are analysed to show that Berenil has a short prophylactic effect, lasting for about 22 days in cattle. When allowance is made for this effect there is a direct, apparently linear relationship between the daily probability of infection of cattle and total challenge, the latter varying over almost three orders of magnitude. Variations in tsetse fly density account for about 50% of the variability of Apparent Density. Hence the latter is a crude estimate of the former. Seasonal and density-related changes in the availability of flies to human catchers could account for the inadequacies of the fly-round technique in assessing fly density and/or challenge. Evidence at present available suggests that trypanotolerant cattle are more likely to be an economic alternative to drug-treated zebu at higher rather than lower challenge levels. Whether either type of animal could profitably be raised in areas of the highest challenge and without some form of tsetse control remains an open question.