Control of ticks and tick-borne diseases in Africa through improved diagnosis and utilisation of data on acaricide resistance.

A meeting, sponsored by the Bill and Melinda Gates Foundation (BMGF) and organised by Clinglobal, was held at The International Livestock Research Institute (ILRI) in Nairobi, Kenya, from 19th - to 21st October 2022. The meeting assembled a unique group of experts on tick control in Africa. Academia, international agencies (FAO and ILRI), the private Animal Health sector and government veterinary services were represented. The significant outcomes included: (i) a shared commitment to standardisation and improvement of acaricide resistance bioassay protocols, particularly the widely used larval packet test (LPT); (ii) development of novel molecular assays for detecting acaricide resistance; (3) creation of platforms for disseminating acaricide resistance data to farmers, veterinary service providers and veterinary authorities to enable more rational evidence-based control of livestock ticks. Implementation of enhanced control will be facilitated by several recently established networks focused on control of parasites in Africa and globally, whose activities were presented at the meeting. These include a newly launched community of practice on management of livestock ticks, coordinated by FAO, an African module of the World Association for the Advancement of Veterinary Parasitology (WAAVP-AN) and the MAHABA (Managing Animal Health and Acaricides for a Better Africa) initiative of Elanco Animal Health.

Two-Staged Total Knee Arthroplasty in Juvenile Rheumatoid Arthritis with Severe Flexion Deformity: A Case Report.

CASE: Juvenile rheumatoid arthritis (JRA) is associated with severe flexion contracture of the knees disabling a patient's ability to walk. Although various treatment modalities are available in the literature, we report a 2-stage procedure in a case of a 22-year-old female JRA patient with bilateral severe flexion deformity of the knee: stage 1-correction of the flexion contracture deformity by ring fixators and stage 2-total knee arthroplasty (TKA) for arthritis. To the best of our knowledge, no such approach has been reported previously. CONCLUSIONS: An Ilizarov ring fixator is a safe technique for gradual correction of a severe flexion deformity. Subsequent TKA can be performed as a standard procedure.

Monitoring the resistance of Rhipicephalus microplus to amitraz, flumethrin, coumaphos, and ivermectin on cattle farms in Mexico.

The prevalence, resistance ratios and factor associated with Rhipicephalu microplus populations resistant to amitraz, flumethrin, coumaphos, and ivermectina (IVM) in Mexico were studied. Field tick populations were collected from 54 farms in 15 different states of Mexico. The dose-response bioassays were carried out using the larval immersion test (amitraz and IVM) and the modified larval packet test (flumethrin and coumaphos) against R. microplus. Mortality data were subjected to probit analysis to calculate lethal concentrations at 50%. A logistic regression model was used to evaluate the relation between resistance and possible associated factors. The phenotype was defined as high resistant (HR), low resistant (LR) or susceptible (S). The overall prevalence of cattle farms with R. microplus resistant to coumaphos, amitraz, flumethrin and IVM were 25.9, 46.2, 31.5 and 68.5%, respectively. For coumaphos, 74.1, 22.2, and 3.7% were classified as S, LR, and HR, respectively, whereas, for amitraz, 53.7, 24.1, and 22.2% of phenotypes were S, LR, and HR, respectively, for flumethrin 68.5, 14.8, and 16.7% were S, LR and HR respectively, and for IVM, 31.5, 46.3, and 22.2% were S, LR, and HR, respectively. We identified that cattle farms without acaricide rotation program (OR: 7.66, CL95%: 1.70-34.47, P: 0.008) had a higher probability of developing R. microplus resistant to amitraz. We concluded that amitraz and IVM resistance in R. microplus is frequent, but mainly at a low level in cattle farms of Mexico. Cattle farms without acaricide rotation program had higher probability of developing R. microplus resistant to amitraz.

Strategies for the control of Rhipicephalus microplus ticks in a world of conventional acaricide and macrocyclic lactone resistance.

Infestations with the cattle tick, Rhipicephalus microplus, constitute the most important ectoparasite problem for cattle production in tropical and subtropical regions worldwide, resulting in major economic losses. The control of R. microplus is mostly based on the use of conventional acaricides and macrocyclic lactones. However, the intensive use of such compounds has resulted in tick populations that exhibit resistance to all major acaricide chemical classes. Consequently, there is a need for the development of alternative approaches, possibly including the use of animal husbandry practices, synergized pesticides, rotation of acaricides, pesticide mixture formulations, manual removal of ticks, selection for host resistance, nutritional management, release of sterile male hybrids, environmental management, plant species that are unfavourable to ticks, pasture management, plant extracts, essential oils and vaccination. Integrated tick management consists of the systematic combination of at least two control technologies aiming to reduce selection pressure in favour of acaricide-resistant individuals, while maintaining adequate levels of animal production. The purpose of this paper is to present a current review on conventional acaricide and macrocyclic lactone resistance for better understanding and control of resistant ticks with particular emphasis on R. microplus on cattle.

Field Evaluation of the Effectiveness of an Oral Toltrazuril and Iron Combination (Baycox® Iron) in Maintaining Weaning Weight by Preventing Coccidiosis and Anaemia in Neonatal Piglets.

Effectiveness of an oral combination of toltrazuril and iron dextran (Baycox(®) Iron) to maintain weaning weight by preventing coccidiosis caused by Isospora suis and iron-deficiency anaemia in neonatal piglets was investigated on three commercial pig farms with a history of coccidiosis: two in Mexico and one in Brazil. On day (SD) 2 of life, piglets were randomised within litter by bodyweight to treatment or control group. On SD 3 piglets allocated to the control group (CG) each received 1 mL Baycox(®), containing 50 mg/mL toltrazuril orally and commercially available iron (200 mg/piglet) by intramuscular injection. Piglets allocated to the treatment group (TG) each received 1 mL toltrazuril and iron combination orally (Baycox(®) Iron) containing 50 mg/mL toltrazuril and 228 mg iron as iron dextran. All piglets had access to creep feed. 6493 piglets completed the study. Bodyweight at weaning on SD 21 of piglets treated with the oral toltrazuril and iron combination was confirmed to be non-inferior to the control treatment with <1 % difference between group mean body weights. Faecal samples from at least 10 % of litters on SD 14 demonstrated control of coccidiosis. Haemoglobin levels on SD 21 were lower in the oral toltrazuril and iron combination treated piglets compared to control levels but above minimum haemoglobin levels to maintain health. There was no difference in mortality between the two groups. This large scale field evaluation clearly demonstrated the effectiveness of a combination of oral toltrazuril and iron (Baycox(®) Iron) in maintaining body weight at weaning compared to conventional treatment. The combination was effective in preventing coccidiosis and anaemia and thus provides a valuable alternative that reduces stressful events in neonatal piglets. There were no product related adverse events.

Unraveling novel TF-miRNA regulatory crosstalk in metastasis of Soft Tissue Sarcoma.

Cancer metastasis is a disease of extreme clinical relevance, as it is responsible for more than 90% of cancer-associated mortality. The molecular mechanism and critical regulators involved in this complex multi-stage process of metastasis is poorly deciphered in soft tissue sarcomas (STS), a heterogeneous group of rare tumors with high metastatic potential. Therefore, we aimed at identifying miRNA and transcription factor (TF) regulatory networks and paths in STS metastasis. We integrated mRNA and miRNA expression profiles with curated regulations (TF→gene, TF→miRNA, miRNA→gene) from different databases and constructed a potentially active regulatory sub-network in STS metastasis. From functional and topological analysis, we found nine novel regulators of Notch signaling sub-network which are conjectured to play critical role in metastasis of STS. This illustrated that the sub-network is promising for identification of critical regulators. Further analysis deploying our developed tool 'RiNAcyc' and computing coverage ratio of known STS associated genes and miRNAs identified a 15 node active path. This potential path highlights the crucial role of BMP2, hsa-miR-24, AP2 and MYC as the up-stream regulators of the path and hsa-miR-215 and TYMS as potential indicator of chemotherapeutic benefit in STS metastasis.

The effects of a pour-on formulation of fluazuron 2.5 % and flumethrin 1 % on populations of Rhipicephalus decoloratus and Rhipicephalus microplus both on and off bovine (Bonsmara breed) hosts.

The present study demonstrated the efficacy of a pour-on formulation of fluazuron 2.5 % and flumethrin 1 % (Drastic Deadline eXtreme®) against Rhipicephalus decoloratus and Rhipicephalus microplus on cattle on pasture previously grazed by experimentally infested animals. Six tick-free cattle were placed on the pasture and treated 7 days later (Day 0) with the pour-on. They were retreated on Days 63, 126 and 189 and monthly tick counts were done. Mean numbers of adult R. decoloratus and/or R. microplus decreased from 53 and 14 on Days 56 and 112 respectively to 2 or less on all other occasions including Day 254. Compared to the numbers of R. decoloratus and/or R. microplus larvae collected from vegetation in the previous year, larval numbers declined by 40.7 % on Day 28, and thereafter reduction remained between 84 % and 100 %. Pairs of tracer calves placed on the pasture for 7 days each month were then held in pens and adult ticks that detached collected. Reduction in the numbers of R. decoloratus collected from tracer animals was 75 % on Day 56 and remained above 93 % except for Day 224 when it temporarily decreased to 78.5 %. Reduction in the numbers of R. microplus was 97.5 % on Day 28 and remained above 98 % until the conclusion of the study on Day 254. Treatment with the pour-on formulation of fluazuron and flumethrin resulted in a marked decrease in the numbers of R. decoloratus and/or R. microplus on treated cattle followed by a reduction in the numbers of larvae questing on the vegetation and ticks picked up by tracer calves. No other potential host species for R. decoloratus and/or R. microplus were present in the camps.

Comparison of three different treatment schedules for praziquantel (Cestocur®, Bayer) in the treatment of tapeworm infections (Moniezia spp.) and their impact on body weight gains in a German sheep flock.

In an observational study, three different treatment schedules with praziquantel were assessed in a Merino land sheep flock from southern Germany. The herd had a known history of severe recurrent Moniezia spp. infections. After turnout to pasture, three hundred lambs between 8 and 14 weeks old were weighed and randomly allocated to three different groups. They were treated with praziquantel (Cestocur®) at a dose of 3.75 mg/kg body weight using the following schedules: group 1 treated four times at monthly intervals (Days 1, 31, 59, 91); group 2 treated three times at six-week intervals (Days 16, 59, 105), group 3 treated twice at an eight-week interval (Days 31, 91). Based on faecal examinations, all lambs were negative for Moniezia spp. on Day 1. At study end (Day 126), higher body weights were seen in group 1 (49.9 ± 5.8 kg; 49.9 kg) than in group 2 (48.7 ± 5.5 kg; 49.0 kg) and in group 3 (47.5 ± 5.4 kg; 47.5 kg) (mean ± SD; median). Overall weight gains were significantly higher in group 1 (22.5 ± 1.8 kg; 22.3 kg) compared to group 2 (20.8 ± 1.4 kg, 21.0 kg; p < 0.0001) and group 3 (19.3 ± 2.2 kg, 19.6 kg; p < 0.0001). The results show that praziquantel treatments applied early in the grazing season and in monthly intervals were more beneficial for body weight developments in lambs than applied at six-weekly or eight-weekly intervals.

The effects of flumethrin (Bayticol® pour-on) on European ticks exposed to treated hairs of cattle and sheep.

Tick infestations in cattle and sheep pose serious health problems when agents of diseases are transmitted. In addition, blood feeding of ticks induces enormous economic losses due to reduced weight gain of infested animals. The present study was designed to investigate the effects of exposure to hairs clipped from cattle and sheep treated with flumethrin (Bayticol®) on European ticks. The dose used was 10 ml/100 kg body weight for both animal species. At intervals of 7 days (days 7, 14, 21, 28 and 35), hairs were cut off from treated and untreated animals along the backline and from the feet just above the claws. These hairs were mingled with stages of the tick species Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus. It was found that in the cases of I. ricinus and D. reticulatus, all specimens died within 5-12 h when coming into contact with cattle hair from the feet or back of animals treated 3 weeks ago and within 6 to 9 h after contact to sheep hair from back or feet. After 4 weeks, the specimens of both tick species that had contact with hair of treated sheep and cattle, independent from the origin backline or feet, were dead after 8 h except for one tick that had contact to hair from feet of cattle. It remained fully motile after a 12-h contact even for the observation time on another 5 days. When having contact to hair of animals treated 5 weeks before, several specimens of Ixodes and Dermacentor survived an exposition of 12 h. There were more survivors in the case of ticks tested on hair of the feet than in the case of contacts with hair of the backline. The exposure of R. sanguineus to hair obtained from animals treated 2 weeks earlier resulted in death in 2-4 h. However, most R. sanguineus ticks when coming in contact with treated hairs (collected from animals treated 3, 4 or 5 weeks earlier) from back or feet survived for atleast 5 days even after exposure for 12 h. These experiments confirmed the positive protection results obtained in former studies with typical cattle ticks in the tropics and/or subtropics. In addition to the killing effects described above, it was noted that flumethrin had a significant repellent effect. If ticks were mingled with treated hair, they tried to flee away and did not seek shelter inside the hair as the controls did in untreated hair.

Comparative efficacy of trichlorphon and trichlorphon/ivermectin combination treatment against anthelmintic-resistant cattle nematodes in Argentina.

Twenty-four Holando Argentino male calves were treated orally with 50 mg/kg body weight trichlorphon (TCF); 0.2 mg/kg body weight subcutaneous ivermectin (IVM); a combination of TCF+IVM at the same doses and administration routes; or remained untreated (control group). All calves were necropsied at day 14 post treatment for counting and identification of worms from abomasum, small and large intestines and lungs to determine the absolute efficacy (controlled efficacy test) for each treatment. Using the faecal egg count reduction test, the efficacy was 63.7 % for TCF, 72.3 % for IVM and 99.2 % for TCF+IVM. The absolute efficacy of IVM and IVM+TCF was 100 % against Haemonchus placei, Trichostrongylus axei and Ostertagia ostertagi (p < 0.05). TCF showed a similar level of efficacy except against O. ostertagi (84.7 %). Efficacy of the treatments against Cooperia oncophora/pectinata/mcmasteri was 80.4 % for IVM, 95.7 % for TCF and 99.6 % for TCF+IVM; against Trichostrongylus colubriformis was 79 % for IVM, 86.2 % for TCF and 94.1 % for TCF+IVM; against Nematodirus helvetianus was 0 % for IVM, 100 % for TCF and 93.8 % for TCF+IVM. The efficacies of TCF, IVM and TCF+IVM were 100 % against Oesophagostomum radiatum and Trichuris spp. The efficacy of TCF against Dictyocaulus viviparus was 52 % and 100 % for IVM and IVM+TCF, respectively. This is the first report of Trichostrongylus colubriformis and Nematodirus helvetianus resistant to ivermectin treatment in cattle of Argentina. The TCF+IVM combination could be an alternative for the control and treatment of nematode infections including IVM-resistant strains.

The efficacy of trichlorphon and naphthalophos against multiple anthelmintic-resistant nematodes of naturally infected sheep in Argentina.

An anthelmintic efficacy trial was conducted in sheep harbouring anthelmintic-resistant worms in Argentina. Seventy lambs were selected from a flock that had been grazed on pastures infected with trichostrongyles previously shown to be resistant to the main anthelmintic groups. Lambs were allocated to comparable groups of ten animals each and treated with trichlorphon (50 mg/kg body weight (b.w.) orally); naphthalophos (50 mg/kg b.w. orally); ivermectin (0.2 mg/kg b.w. subcutaneously); fenbendazole (5 mg/kg b.w. orally); levamisole (8 mg/kg b.w. subcutaneously) and closantel (10 mg/kg b.w. orally). There was also an untreated group. The dose selection was based on manufacturer's recommendations.Faecal samples were collected 0 and 10 days post treatment to estimate efficacy (faecal egg count reduction). Six animals from each group were necropsied at day 10 for enumeration/identification of worms from the abomasum, small and large intestines to determine the absolute efficacy of each agent (controlled efficacy test). Trichlorphon and naphthalophos were effective (> 99 %) against Haemonchus contortus (p < 0.05).Naphthalophos also showed efficacy against Trichostrongylus axei (99.3 %), Teladorsagia circumcincta (97.8 %), Trichostrongylus colubriformis (99.2 %), Cooperia punctata/curticei/pectinata (90.4 %), Nematodirus spathiger (89.2 %) and Oesophagostomum venulosum/columbianum (93.7 %). Fenbendazole and levamisole showed efficacy (> 95 %) against all nematodes except T. colubriformis. The efficacy of ivermectin was low against H. contortus (23 %) and Cooperia spp. (46.3 %). Closantel showed low efficacy against T. axei (64.4 %), H. contortus (80.6 %) and T. colubriformis (59.5 %).When anthelmintic resistance is widespread, trichlorphon treatment is appropriate if H. contortus is present; however, naphthalophos represents an effective therapeutic alternative for incorporation into worm control programmes.

Anthelmintic efficacy of oral trichlorfon solution against ivermectin resistant nematode strains in cattle.

Infected calves from two different rural estates in Brazil were studied to assess the anthelmintic efficacy of oral trichlorfon against naturally occurring ivermectin resistant parasitic nematode strains. In experiment I, infected animals were from a region where ivermectin resistant populations of Haemoncus placei, Cooperia punctata, Cooperia spatulata and Trichuris discolor have recently been identified. Six calves with natural gastrointestinal nematode infections were treated with 48.5mg/kg aqueous trichlorfon administered orally and six calves acted as a non-treated control group. In experiment II 24 naturally infected calves were selected to enter one of four treatment groups, six animals each received: 48.5mg/kg oral trichlorfon; 200 microg/kg subcutaneous 1% ivermectin; 630 microg/kg subcutaneous 3.15% ivermectin; or no treatment (control group). Gastrointestinal helminths were counted and identified post-mortem at 7 days (trichlorfon and 1% ivermectin treated and untreated animals) or 14 days (3.15% ivermectin treated and untreated animals) after administration of the test agents. Experiment I identified a high level efficacy for oral trichlorfon against four helminth species that have previously been shown to be ivermectin resistant in this geographical region: percentage efficacy was 99.82% against adult H. placei, 99.18% against C. punctata, 99.33% against C. spatulata, 81.06% against T. axei, 98.46% against Oesophagostomum radiatum and 100% against T. discolor. Trichlorfon also showed activity against the ivermectin (1% and 3.15%) resistant helminth species identified in experiment II, attaining efficacy levels of 99.17% against H. placei, 98.46% against C. punctata and 100.00% against T. discolor. These findings indicate that oral trichlorfon is an effective treatment option in the management of cattle infected with ivermectin resistant helminths.