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Andrew R. Moorhead - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and side effects of doxycycline versus minocycline in the three dose Melarsomine canine adulticidal heartworm treatment protocol
    Parasites & Vectors, 2018
    Co-Authors: Molly D. Savadelis, Adrian J. Wolstenholme, M.t. Dzimianski, Katherine M. Day, Jenna L. Bradner, Andrew R. Moorhead
    Abstract:

    The American Heartworm Society currently recommends the use of a monthly macrocyclic lactone, a 28-day course of 10 mg/kg doxycycline BID, and the 3-dose protocol of Melarsomine dihydrochloride for the treatment of canine heartworm disease. Doxycycline is necessary for the reduction of the bacterium Wolbachia, found in all heartworm life-stages. Previous price increases and decreasing availability prompted us to evaluate alternative tetracycline antibiotics, i.e. minocycline, for the reduction of Wolbachia during canine heartworm treatment. Thirty-two heartworm-positive dogs were randomized to receive 10 mg/kg or 5 mg/kg of either doxycycline or minocycline for 28 days BID, for a total of 8 dogs per experimental group. All dogs received 6 months of Heartgard Plus® (ivermectin/pyrantel) and the 3-dose protocol of 2.5 mg/kg Melarsomine dihydrochloride. Blood samples were collected prior to the initiation of treatment, every 7 days throughout tetracycline treatment, and then monthly thereafter until the dog tested negative for the presence of heartworm antigen. DNA was isolated from circulating microfilarial samples and qPCR was performed on each sample. A greater number of dogs in the 10 mg/kg doxycycline and minocycline treated groups experienced gastrointestinal side effects as compared to the 5 mg/kg doxycycline and minocycline treated groups. All eight dogs in the 10 mg/kg doxycycline-treated group tested negative for the presence of Wolbachia DNA by 28 days post-tetracycline treatment. A total of two dogs in both the 5 mg/kg doxycycline- and 10 mg/kg minocycline-treated groups and three dogs in the 5 mg/kg minocycline-treated group remained positive for the presence of Wolbachia DNA by the end of tetracycline treatment. No lung pathology was assessed in this clinical trial, therefore the clinical effect of the remaining Wolbachia DNA in the 10 mg/kg minocycline-, 5 mg/kg doxycycline- and 5 mg/kg minocycline-treated groups cannot be determined. Owner compliance in the proper administration of these tetracyclines may be impacted by the increased severe gastrointestinal side effects reported for the 10 mg/kg doxycycline- and minocycline-treated groups. We recommend that veterinarians prescribe the recommended 10 mg/kg doxycycline for canine heartworm treatment and reduce the dosage to 5 mg/kg in cases of severe gastrointestinal side effects in order to improve owner compliance in administration of medications.

  • Efficacy and side effects of doxycycline versus minocycline in the three-dose Melarsomine canine adulticidal heartworm treatment protocol
    BMC, 2018
    Co-Authors: Molly D. Savadelis, Adrian J. Wolstenholme, M.t. Dzimianski, Katherine M. Day, Jenna L. Bradner, Andrew R. Moorhead
    Abstract:

    Abstract Background The American Heartworm Society currently recommends the use of a monthly macrocyclic lactone, a 28-day course of 10 mg/kg doxycycline BID, and the 3-dose protocol of Melarsomine dihydrochloride for the treatment of canine heartworm disease. Doxycycline is necessary for the reduction of the bacterium Wolbachia, found in all heartworm life-stages. Previous price increases and decreasing availability prompted us to evaluate alternative tetracycline antibiotics, i.e. minocycline, for the reduction of Wolbachia during canine heartworm treatment. Methods Thirty-two heartworm-positive dogs were randomized to receive 10 mg/kg or 5 mg/kg of either doxycycline or minocycline for 28 days BID, for a total of 8 dogs per experimental group. All dogs received 6 months of Heartgard Plus® (ivermectin/pyrantel) and the 3-dose protocol of 2.5 mg/kg Melarsomine dihydrochloride. Blood samples were collected prior to the initiation of treatment, every 7 days throughout tetracycline treatment, and then monthly thereafter until the dog tested negative for the presence of heartworm antigen. DNA was isolated from circulating microfilarial samples and qPCR was performed on each sample. Results A greater number of dogs in the 10 mg/kg doxycycline and minocycline treated groups experienced gastrointestinal side effects as compared to the 5 mg/kg doxycycline and minocycline treated groups. All eight dogs in the 10 mg/kg doxycycline-treated group tested negative for the presence of Wolbachia DNA by 28 days post-tetracycline treatment. A total of two dogs in both the 5 mg/kg doxycycline- and 10 mg/kg minocycline-treated groups and three dogs in the 5 mg/kg minocycline-treated group remained positive for the presence of Wolbachia DNA by the end of tetracycline treatment. Conclusions No lung pathology was assessed in this clinical trial, therefore the clinical effect of the remaining Wolbachia DNA in the 10 mg/kg minocycline-, 5 mg/kg doxycycline- and 5 mg/kg minocycline-treated groups cannot be determined. Owner compliance in the proper administration of these tetracyclines may be impacted by the increased severe gastrointestinal side effects reported for the 10 mg/kg doxycycline- and minocycline-treated groups. We recommend that veterinarians prescribe the recommended 10 mg/kg doxycycline for canine heartworm treatment and reduce the dosage to 5 mg/kg in cases of severe gastrointestinal side effects in order to improve owner compliance in administration of medications

  • assessment of parasitological findings in heartworm infected beagles treated with advantage multi for dogs 10 imidacloprid 2 5 moxidectin and doxycycline
    Parasites & Vectors, 2017
    Co-Authors: Molly D. Savadelis, M.t. Dzimianski, Cameon M Ohmes, Joe Hostetler, Terry Settje, Robert Zolynas, Andrew R. Moorhead
    Abstract:

    Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles. This study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer’s recommendations and read using a spectrophotometer at 490 nm. All dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10–12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0–2 adult worms/dog, with five dogs having no adult heartworms present. The average adult heartworm recovery was 0.6/dog in the treated group. This treatment regimen demonstrated a 95.9% efficacy in eliminating adult heartworms (P < 0.0001). This study demonstrated that this treatment regimen successfully eliminated D. immitis microfilariae by 21 days post-treatment, reduced heartworm antigen concentration over time, and had a 95.9% efficacy in the elimination of mature adult heartworms. Based on this study, we conclude that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug Melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects.

  • the emergence of macrocyclic lactone resistance in the canine heartworm dirofilaria immitis
    Parasitology, 2015
    Co-Authors: Adrian J. Wolstenholme, Christopher C. Evans, Pablo D Jimenez, Andrew R. Moorhead
    Abstract:

    Prevention of heartworm disease caused by Dirofilaria immitis in domestic dogs and cats relies on a single drug class, the macrocyclic lactones (MLs). Recently, it has been demonstrated that ML-resistant D. immitis are circulating in the Mississippi Delta region of the USA, but the prevalence and impact of these resistant parasites remains unknown. We review published studies that demonstrated resistance in D.immitis , along with our current understanding of its mechanisms. Efforts to develop in vitro tests for resistance have not yet yielded a suitable assay, so testing infected animals for microfilariae that persist in the face of ML treatment may be the best current option. Since the vast majority of D. immitis populations continue to be drug-sensitive, protected dogs are likely to be infected with only a few parasites and experience relatively mild disease. In cats, infection with small numbers of worms can cause severe disease and so the clinical consequences of drug resistance may be more severe. Since Melarsomine dihydrochloride, the drug used to remove adult worms, is not an ML, the ML-resistance should have no impact on our ability to treat diseased animals. A large refugium of heartworms that are not exposed to drugs exists in unprotected dogs and in wild canids, which may limit the development and spread of resistance alleles.

M.t. Dzimianski - One of the best experts on this subject based on the ideXlab platform.

  • efficacy and side effects of doxycycline versus minocycline in the three dose Melarsomine canine adulticidal heartworm treatment protocol
    Parasites & Vectors, 2018
    Co-Authors: Molly D. Savadelis, Adrian J. Wolstenholme, M.t. Dzimianski, Katherine M. Day, Jenna L. Bradner, Andrew R. Moorhead
    Abstract:

    The American Heartworm Society currently recommends the use of a monthly macrocyclic lactone, a 28-day course of 10 mg/kg doxycycline BID, and the 3-dose protocol of Melarsomine dihydrochloride for the treatment of canine heartworm disease. Doxycycline is necessary for the reduction of the bacterium Wolbachia, found in all heartworm life-stages. Previous price increases and decreasing availability prompted us to evaluate alternative tetracycline antibiotics, i.e. minocycline, for the reduction of Wolbachia during canine heartworm treatment. Thirty-two heartworm-positive dogs were randomized to receive 10 mg/kg or 5 mg/kg of either doxycycline or minocycline for 28 days BID, for a total of 8 dogs per experimental group. All dogs received 6 months of Heartgard Plus® (ivermectin/pyrantel) and the 3-dose protocol of 2.5 mg/kg Melarsomine dihydrochloride. Blood samples were collected prior to the initiation of treatment, every 7 days throughout tetracycline treatment, and then monthly thereafter until the dog tested negative for the presence of heartworm antigen. DNA was isolated from circulating microfilarial samples and qPCR was performed on each sample. A greater number of dogs in the 10 mg/kg doxycycline and minocycline treated groups experienced gastrointestinal side effects as compared to the 5 mg/kg doxycycline and minocycline treated groups. All eight dogs in the 10 mg/kg doxycycline-treated group tested negative for the presence of Wolbachia DNA by 28 days post-tetracycline treatment. A total of two dogs in both the 5 mg/kg doxycycline- and 10 mg/kg minocycline-treated groups and three dogs in the 5 mg/kg minocycline-treated group remained positive for the presence of Wolbachia DNA by the end of tetracycline treatment. No lung pathology was assessed in this clinical trial, therefore the clinical effect of the remaining Wolbachia DNA in the 10 mg/kg minocycline-, 5 mg/kg doxycycline- and 5 mg/kg minocycline-treated groups cannot be determined. Owner compliance in the proper administration of these tetracyclines may be impacted by the increased severe gastrointestinal side effects reported for the 10 mg/kg doxycycline- and minocycline-treated groups. We recommend that veterinarians prescribe the recommended 10 mg/kg doxycycline for canine heartworm treatment and reduce the dosage to 5 mg/kg in cases of severe gastrointestinal side effects in order to improve owner compliance in administration of medications.

  • Efficacy and side effects of doxycycline versus minocycline in the three-dose Melarsomine canine adulticidal heartworm treatment protocol
    BMC, 2018
    Co-Authors: Molly D. Savadelis, Adrian J. Wolstenholme, M.t. Dzimianski, Katherine M. Day, Jenna L. Bradner, Andrew R. Moorhead
    Abstract:

    Abstract Background The American Heartworm Society currently recommends the use of a monthly macrocyclic lactone, a 28-day course of 10 mg/kg doxycycline BID, and the 3-dose protocol of Melarsomine dihydrochloride for the treatment of canine heartworm disease. Doxycycline is necessary for the reduction of the bacterium Wolbachia, found in all heartworm life-stages. Previous price increases and decreasing availability prompted us to evaluate alternative tetracycline antibiotics, i.e. minocycline, for the reduction of Wolbachia during canine heartworm treatment. Methods Thirty-two heartworm-positive dogs were randomized to receive 10 mg/kg or 5 mg/kg of either doxycycline or minocycline for 28 days BID, for a total of 8 dogs per experimental group. All dogs received 6 months of Heartgard Plus® (ivermectin/pyrantel) and the 3-dose protocol of 2.5 mg/kg Melarsomine dihydrochloride. Blood samples were collected prior to the initiation of treatment, every 7 days throughout tetracycline treatment, and then monthly thereafter until the dog tested negative for the presence of heartworm antigen. DNA was isolated from circulating microfilarial samples and qPCR was performed on each sample. Results A greater number of dogs in the 10 mg/kg doxycycline and minocycline treated groups experienced gastrointestinal side effects as compared to the 5 mg/kg doxycycline and minocycline treated groups. All eight dogs in the 10 mg/kg doxycycline-treated group tested negative for the presence of Wolbachia DNA by 28 days post-tetracycline treatment. A total of two dogs in both the 5 mg/kg doxycycline- and 10 mg/kg minocycline-treated groups and three dogs in the 5 mg/kg minocycline-treated group remained positive for the presence of Wolbachia DNA by the end of tetracycline treatment. Conclusions No lung pathology was assessed in this clinical trial, therefore the clinical effect of the remaining Wolbachia DNA in the 10 mg/kg minocycline-, 5 mg/kg doxycycline- and 5 mg/kg minocycline-treated groups cannot be determined. Owner compliance in the proper administration of these tetracyclines may be impacted by the increased severe gastrointestinal side effects reported for the 10 mg/kg doxycycline- and minocycline-treated groups. We recommend that veterinarians prescribe the recommended 10 mg/kg doxycycline for canine heartworm treatment and reduce the dosage to 5 mg/kg in cases of severe gastrointestinal side effects in order to improve owner compliance in administration of medications

  • assessment of parasitological findings in heartworm infected beagles treated with advantage multi for dogs 10 imidacloprid 2 5 moxidectin and doxycycline
    Parasites & Vectors, 2017
    Co-Authors: Molly D. Savadelis, M.t. Dzimianski, Cameon M Ohmes, Joe Hostetler, Terry Settje, Robert Zolynas, Andrew R. Moorhead
    Abstract:

    Anecdotal reports support the position that the adulticidal heartworm treatment utilizing doxycycline and Advantage Multi®/Advocate® for Dogs (10% imidacloprid + 2.5% moxidectin) has successfully converted antigen-positive dogs to antigen-negative. To date, no controlled experimental studies have demonstrated the adulticidal efficacy of this treatment regimen. The aim of this study was to evaluate the parasitological and clinical efficacy of Advantage Multi® for Dogs (IMD + MOX) and doxycycline in heartworm-infected beagles. This study utilized 16 dogs, 8 dogs in each of non-treated control and treated groups. A total of 16 adult Dirofilaria immitis (Missouri strain) were surgically transplanted into the jugular vein of each study dog. The treatment regimen of monthly IMD + MOX topically (per labeled dosage and administration) for 10 months and 10 mg/kg doxycycline BID orally for 30 days was initiated 30 days post-surgical transplant. Echocardiograms, radiographs, complete blood counts, clinical chemistry profiles, heartworm antigenemia and microfilaremia were evaluated every 4 weeks. Serum samples were assayed for heartworm antigen using the DiroCHEK® heartworm antigen test. The DiroCHEK® was performed according to the manufacturer’s recommendations and read using a spectrophotometer at 490 nm. All dogs tested positive for the presence of heartworm antigen post-surgical transplant and prior to treatment. Heartworm antigen levels began declining in treated dogs 3 months post-treatment. Non-treated control dogs remained antigen-positive. No microfilariae were detected in treated dogs after 21 days post-treatment. At necropsy, adult heartworms were recovered from all non-treated control dogs with a range of 10–12 adult worms/dog for an average recovery of 10.6 adult heartworms/dog. In the IMD + MOX- and doxycycline-treated dogs, the range of adult heartworms recovered was 0–2 adult worms/dog, with five dogs having no adult heartworms present. The average adult heartworm recovery was 0.6/dog in the treated group. This treatment regimen demonstrated a 95.9% efficacy in eliminating adult heartworms (P < 0.0001). This study demonstrated that this treatment regimen successfully eliminated D. immitis microfilariae by 21 days post-treatment, reduced heartworm antigen concentration over time, and had a 95.9% efficacy in the elimination of mature adult heartworms. Based on this study, we conclude that this treatment regimen is a relatively quick, reliable and safe option to treat canine heartworm infection as compared to other treatment regimens involving macrocyclic lactones, when the approved drug Melarsomine dihydrochloride is unavailable, contraindicated or declined by an owner unable to afford the more costly treatment or concerned about the potential side effects.

  • evaluation of lung pathology in dirofilaria immitis experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of Melarsomine dihydrochloride
    Veterinary Parasitology, 2011
    Co-Authors: Laura D Kramer, M.t. Dzimianski, P. Supakorndej, N. Supakorndej, Giulio Grandi, B Passeri, P Gianelli, Marco Genchi, Abdelmoneim Mansour, S.d. Mccall
    Abstract:

    Abstract Adulticide therapy in heartworm ( Dirofilaria immitis )-infected dogs can lead to thromboembolism, which can seriously compromise post-treatment health status. Lung pathology following adulticide therapy was evaluated in three groups of experimentally infected dogs. Group 1 was treated with doxycycline at 20 mg/kg per os once daily for 30 days post infection followed by an intramuscular injection of Melarsomine dihydrochloride (2.5 mg/kg) at Week 12, followed 1 month later by two injections 24 h apart. Group 2 was treated as described for Group 1, with the addition of ivermectin at 6 mcg/kg given monthly per os for 24 weeks post-infection. Group 3 received Melarsomine alone, as described above. All dogs were necropsied at Week 24 and lung pathology was evaluated. Lesion criteria included perivascular inflammation and endothelial proliferation. Lesions were scored by two independent pathologists who were blinded as to treatment. Results indicate that doxycycline treatment alone or combined with ivermectin had lower lesion scores than lungs from dogs who had received Melarsomine alone. Dogs that received the combined doxycycline/ivermectin protocol and treated with adulticide showed less severe arterial lesions and the virtual absence of thrombi.

  • Heartworm and Wolbachia : therapeutic implications
    'Elsevier BV', 2008
    Co-Authors: J.w. Mccall, C. Genchi, L. Kramer, J. Guerrero, M.t. Dzimianski, P. Supakorndej, A.m. Mansour, S.d. Mccall, N. Supakorndej, G. Grandi
    Abstract:

    A safer, more effective adulticidal treatment and a safe method for reducing microfilaremia and breaking transmission of heartworm disease early in the treatment are needed. The present study evaluated efficacy of ivermectin (IVM) and doxycycline (DOXY) alone or together (with or without Melarsomine [MEL]) in dogs with induced adult heartworm infection and assessed the ability of microfilariae from DOXY-treated dogs to develop to L3 in Aedes aegypti mosquitoes and subsequently to become reproductive adults in dogs. Thirty beagles were each infected with 16 adult heartworms by intravenous transplantation. Six weeks later, dogs were ranked by microfilarial count and randomly allocated to 6 groups of 5 dogs each. Beginning on Day 0, Group 1 received IVM (6 mcg/kg) weekly for 36 weeks. Group 2 received DOXY (10 mcg/(kg day)) orally Weeks 1-6, 10-11, 16-17, 22-25, and 28-33. Groups 3 and 5 received IVM and DOXY according to doses and schedules used for Groups 1 and 2. At Week 24, Groups 3 and 4 received an intramuscular injection of MEL (2.5 mg/kg), followed 1 month later by two injections 24 h apart. Group 6 was not treated. Blood samples were collected for periodic microfilaria counts and antigen (Ag) testing (and later immunologic evaluation and molecular biology procedures). Radiographic and physical examinations, hematology/clinical chemistry testing, and urinalysis were done before infection, before Day 0, and periodically during the treatment period. At 36 weeks, the dogs were euthanized and necropsied for worm recovery, collection of lung, liver, kidney, and spleen samples for examination by immunohistochemistry and conventional histological methods. All dogs treated with IVM + DOXY (with or without MEL) were amicrofilaremic after Week 9. Microfilarial counts gradually decreased in dogs treated with IVM or DOXY, but most had a few microfilariae at necropsy. Microfilarial counts for dogs treated only with MEL were similar to those for controls. Antigen test scores gradually decreased with IVM + DOXY (with or without MEL) and after MEL. Antigen scores for IVM or DOXY alone were similar to controls throughout the study. Reduction of adult worms was 20.3% for IVM, 8.7% for DOXY, 92.8% for IVM + DOXY + MEL, 100% for MEL, and 78.3% for IVM + DOXY. Mosquitoes that fed on blood from DOXY-treated dogs had L3 normal in appearance but were not infective for dogs. Preliminary observations suggest that administration of DOXY + IVM for several months prior to (or without) MEL will eliminate adult HW with less potential for severe thromboembolism than MEL alone

Marc Desquesnes - One of the best experts on this subject based on the ideXlab platform.

  • Melarsomine dihydrochloride as treatment of experimental trypanosoma evansi infection among pigs in southern philippines
    2017
    Co-Authors: A P Dargantes, Neil Anthony A Dalangan, Marianne April A Vicente, Shiela L Dumuk, Joseph Rizalyndo P Dargantes, Max Francis G Talle, Marc Desquesnes
    Abstract:

    The study was carried out to assess the efficacy of Melarsomine dihydrochloride (Cymelarsan®) against experimental Trypanosoma evansi infection (surra) in pigs. Specifically, the study aimed to: (a) determine the time of disappearance of T. evansi from the blood of pigs after treatment with two different doses of Melarsomine dihydrochloride; (b) compare the bodyweight and rectal temperature of control pigs and those infected and treated with Melarsomine dihydrochloride; (c) observe any apparent side effects of Melarsomine dihydrochloride among treated pigs; and, (d) compare the efficacy of two different doses of Melarsomine dihydrochloride. Sixteen, apparently healthy, 40-50 days old pigs (piglets) were used in the study. The piglets were randomly allocated into four treatments with 4 animals each group: T0= uninfected-untreated; T1=infected-untreated; T2= infected, treated with Melarsomine dihydrochloride at 0.25 mg kg-1 bodyweight (BW); and, T3= infected, treated with Melarsomine dihydrochloride at 0.5 mg kg-1 BW. Each animal in Treatments 1-3 was inoculated with approximately 100,000 T. evansi (Mindanao isolate). Single intramuscular treatment with the drug was done two weeks after infection. Parasitemia was monitored daily after inoculation and at 1, 3 and 24 hours, and every 3-4 days for 90 days post treatment (pt) using microhematocrit centrifugation technique (MHCT) and/or mouse inoculation test (MIT). Rectal temperatures were monitored daily for 3 days prior to inoculation and every 3-4 days after inoculation, and weekly, pt, for 4 weeks. Bodyweights were taken prior to inoculation and treatment, and weekly, pt, for 4 weeks. Trypanosomes were not detected in the blood of pigs an hour, pt. There were no significant differences on the bodyweights among pigs and rectal temperatures of T. evansi-infected pigs returned to normal after Melarsomine treatment. Side effects were not observed among Melarsomine-treated pigs. Pigs treated with 0.5 mg kg-1 BW dose were free of trypanosomes within the 90-day observation period, while two pigs had relapsed infection on days 72 and 81, pt. It is concluded that a single intramuscular injection of Melarsomine dihydrochloride at 0.5 mg kg-1 BW is effective against T. evansi infection in pigs and could be safely used to treat surra in pigs in Mindanao while the lower dose is only 50% effective. Further studies should be done with Melarsomine for treatment of surra in other animal species in southern Philippines.

  • zoonotic trypanosomes in south east asia attempts to control trypanosoma lewisi using veterinary drugs
    Experimental Parasitology, 2016
    Co-Authors: Marc Desquesnes, Sarawut Yangtara, Pawinee Kunphukhieo, Piangjai Chalermwong, Sathaporn Jittapalapong, Stephane Herder
    Abstract:

    A growing number of atypical human infections due to the livestock parasite Trypanosoma evansi, or to the rat parasite Trypanosoma lewisi, are reported in humans in Asia. In some cases, clinical evolutions request treatments, however, so far, there were very few attempts to control T. lewisi using trypanocidal drugs. In a study published elsewhere, the efficacy of human trypanocides is evaluated in laboratory rats, and it concludes that none of them is able to cure rats experimentally infected with T. lewisi. Control of T. lewisi in rat would be a step for identification of drugs against this parasite. In the present study, 4 veterinary drugs: diminazene aceturate, isometamidium chloride, Melarsomine hydrochloride and quinapyramine sulfate and chloride, were evaluated at low and high doses, in intra-muscular injections to normal rats experimentally infected with a stock of T. lewisi from Thailand. None of these treatments being efficient, a trial was also made using Melarsomine hydrochloride in T. evansi infected rats and in mixed T. lewisi and T. evansi infected rats, in order to demonstrate the efficacy of the drugs under the present protocol. T. evansi was cleared from the rat's blood the day after the treatment, while, T. lewisi remained unaffected until the end of the experiment. These observations clearly demonstrated the efficacy of Melarsomine hydrochloride against T. evansi and its inefficacy against T. lewisi. In conclusion none of the veterinary drugs was efficient against this stock of T. lewisi. Other protocols using higher doses or other drugs and T. lewisi stocks should be investigated in further studies. The control of T. lewisi infection in Wistar rats, using veterinary trypanocidal drugs, remains so far unsuccessful.

  • an evaluation of Melarsomine hydrochloride efficacy for parasitological cure in experimental infection of dairy cattle with trypanosoma evansi in thailand
    Parasitology, 2011
    Co-Authors: Marc Desquesnes, Ketsarin Kamyingkird, Timothee Vergne, Nachai Sarataphan, Rodtian Pranee, Sathaporn Jittapalapong
    Abstract:

    Melarsomine hydrochloride can cure Trypanosoma evansi infection in camels at a dose of 0·25 mg/kg, but at that dose relapses occur in cattle. In our study, the efficacy of an intramuscular injection of Melarsomine hydrochloride at 0·5 mg/kg was assessed in 3 normal and 3 splenectomized dairy cattle experimentally infected with a stock of T. evansi from Thailand. The animals were monitored for 5 months by haematocrit centrifugation, blood- or cerebrospinal fluid-mouse inoculation, polymerase chain reaction, the card agglutination test (CATT) for T. evansi, and the enzyme-linked immunosorbent assay‑T. evansi. Parasitological and DNA tests became and remained negative just after treatment. By the end of the experiment, CATT was negative and ELISA scores were below or very close to the cut-off value. One of the splenectomized cattle died from anaplasmosis during the experiment, but tested negative for surra. It was concluded that the parasites had been cleared from the cattle, and Melarsomine hydrochloride at 0·5 mg/kg can be recommended for treatment against T. evansi infection in dairy cattle in Thailand. Further work is necessary to validate the efficacy of the treatment in the event of confirmed CSF-infection.

  • development and application of an antibody elisa to follow up a trypanosoma evansi outbreak in a dromedary camel herd in france
    Veterinary Parasitology, 2009
    Co-Authors: Marc Desquesnes, Stephane Herder, Geraldine Bossard, Delphine Patrel, Olivier Patout, Sophie Thevenon, Djamila Pavlovic, Sophie Ravel, Elisabeth Lepetitcolin
    Abstract:

    An outbreak of trypanosomosis was observed for the first time in metropolitan France in October 2006, when five camels were proved to be infected by Trypanosoma evansi using parasitological methods. The parasite was isolated and used to produce a soluble antigen for antibody-enzyme linked immunosorbent assay (ELISA) in a protocol derived from a method previously developed for sheep and humans but using protein A conjugate. The animals were treated on three instances, alternatively with Melarsomine hydrochloride and quinapyramine and followed up on a monthly basis for 2 years with various diagnostic techniques including parasitological, serological and DNA-based methods. Initially, five animals were detected as being positive using ELISA with 83.3% concordance to parasitological tests. Immediately after the first treatment, parasites and DNA disappeared in all animals; antibody levels decreased regularly until ELISA became negative 3-4 months later. Ten months after the first treatment, parasites and antibodies were detected again in one of the camels previously found to be infected. A retrospective study indicated that the weight of this animal had been underestimated; consequently, it had received underdosages of both trypanocides. However, since hypotheses of re-infection or relapse could not be fully substantiated, it is not known whether the ELISA results for this animal were true- or false-negative over a 7-month period. The study confirmed the value of this ELISA using protein A conjugate to detect antibodies directed against T. evansi in camels and the need to use several diagnostic techniques to optimize detection of infected animals. A warning is raised on surra, a potentially emerging disease in Europe.

  • first outbreak of trypanosoma evansi in camels in metropolitan france
    Veterinary Record, 2008
    Co-Authors: Marc Desquesnes, Stephane Herder, Geraldine Bossard, Delphine Patrel, Olivier Patout, Elisabeth Lepetitcolin, Sophie Thevenon, David Berthier, Djamila Pavlovic, R Brugidou
    Abstract:

    The first outbreak of trypanosomosis caused by Trypanosoma evansi in camels in France was reported on a farm in the Aveyron Department. Five camels were imported from the Canary Islands to the farm in early July 2006, and trypanosomes were observed on a stained blood smear from one of them, which died in October. On further investigations, trypanosomes were observed in the blood of five camels, three of them indigenous to the farm and two that had been imported. On the basis of microscopical examination (morphological criteria and measurements) and serological results based on the card agglutination T evansi test and PCR typing, the parasites were identified as T evansi. After treatment with Melarsomine, the infected camels rapidly became negative by parasitological tests and were negative two to four months later by serological tests. The parasite was probably transmitted by tabanids and Stomoxys calcitrans, which were abundant in July to September 2006. No parasites were observed in other animals on the farm or on neighbouring farms, but some of the sheep on these farms were positive by PCR or serology.

John W Mccall - One of the best experts on this subject based on the ideXlab platform.

  • wolbachia and its influence on the pathology and immunology of dirofilaria immitis infection
    Veterinary Parasitology, 2008
    Co-Authors: Laura D Kramer, John W Mccall, C. Genchi, Giulio Grandi, M Leoni, B Passeri, Michele Mortarino, C Bazzocchi
    Abstract:

    Abstract Since the definitive identification in 1995 of the bacterial endosymbiont Wolbachia that resides in different tissues of the filarial worm Dirofilaria immitis, there has been increasing interest to understand whether and what role it plays in the pathogenesis of and immune response to heartworm infection. The present study evaluated the effects of treatments on lung pathology in 20 beagle dogs experimentally infected with D. immitis. Dogs in Group 1 were treated with doxycycline (10 mg/kg/day) orally from weeks 0–6, 10–12, 16–18, 22–26, and 28–34. Dogs in Group 2 served as infected, non-treated controls. Dogs in Group 3 were given doxycycline as described for Group 1 combined with weekly oral doses of ivermectin (6 mcg/kg) for 34 weeks and intramuscular (IM) Melarsomine (2.5 mg/kg) at week 24, followed by two additional Melarsomine injections 24 h apart 1 month later. Group 4 received only Melarsomine as described for Group 3. Lung lesion criteria, scored by two independent blinded pathologists, included perivascular inflammation and endothelial proliferation. Doxycycline treatment alone had no effect on lesion scores, whereas the combination of doxycycline and ivermectin resulted in less severe perivascular inflammation. All lungs were evaluated for positive immunostaining for the Wolbachia surface protein (WSP). Control dogs showed numerous thrombi, intense perivascular and interstitial inflammation and, occasionally, positive staining for WSP. Interestingly, dogs receiving doxycycline/ivermectin/Melarsomine showed significantly less severe arterial lesions and the virtual absence of thrombi.

  • the safety net story about macrocyclic lactone heartworm preventives a review an update and recommendations
    Veterinary Parasitology, 2005
    Co-Authors: John W Mccall
    Abstract:

    Abstract A number of safe, effective, and convenient heartworm preventatives are currently available for virtually all canine and feline pets. Yet, a 2001 survey of over 18,000 veterinary clinics in the United States identified more than 240,000 dogs and 3000 cats infected with Dirofilaria immitis. This high level of owner compliance failure is alarming. Prolonged administration of some of the macrocyclic lactone (ML) preventatives kills young larvae, older larvae, “immatures,” young adults, and/or old adults. Efficacy of 95% or more requires dosing for 9–30 months, with older worms being more difficult to kill. Of the various MLs, ivermectin (IVM) has the most potent safety-net and adulticidal activity, milbemycin oxime has the least, and selamectin and moxidectin injectable lie somewhere in between. The unique effects of IVM are related to the age of the heartworms at initiation of treatment. The earlier treatment is started, the more stunted and smaller the worms and the shorter their survival time. Conversely, the later treatment is started, the longer the worms live, and the more likely the dog will be antigen- and microfilariae-positive. Drug effects do not appear to be enhanced by increasing the dosage or administering at shorter intervals, and it appears that continuous monthly treatment is needed to produce the full effects of the drug. The American Heartworm Society (AHS) recognizes the safety-net (or reach-back effect) and adulticidal properties of some MLs, particularly IVM. The AHS 2003 (American Heartworm Society, 2004. 2003 Updated guidelines for the diagnosis, prevention, and management of heartworm (Dirofilaria immitis) infection in dogs. In: McCall, et al., (Eds.), Proceedings of the Symposium Session on Recent Advances in Heartworm Disease, The 19th International Conference of the World Association for the Advancement of Veterinary Parasitology, New Orleans, LA, 10–14 August, 2003. Vet. Parasitol. 125, 105–130) canine guidelines state that it is beneficial to administer prophylactic doses of IVM before treatment with Melarsomine. Results of laboratory studies suggest that less active dogs are at low risk of severe thromboembolism and death. However, heartworm-positive working dogs might be more at risk. Worsened radiographic and echocardiographic images in a client-owned dog given IVM monthly for 2 years with greatly restricted exercise suggests that such treatment of dogs with clinical, radiographic, and/or echocardiographic evidence of heartworm disease as well as for asymptomatic working dogs is contraindicated. Furthermore, until further data are available, such treatment of even the less active asymptomatic dog should be administered only with much caution and with examination by a veterinarian at least once every 4–6 months. IVM clearly provides potent “safety-net” activity against older larvae, immatures, and young adults in cases of owner compliance failure, even when the owner and veterinarian are not aware that the animal is infected, and offers much promise as a unique “soft-kill” treatment for young, and possibly older adult heartworms, with reduced risks.

  • use of Melarsomine dihydrochloride rm 340 for adulticidal treatment of dogs with naturally acquired infections of dirofilaria immitis and for clinical prophylaxis during reexposure for 1 year
    Veterinary Parasitology, 1994
    Co-Authors: Tom L Mctier, John W Mccall, M.t. Dzimianski, Jeanpierre Raynaud, James E Strickland
    Abstract:

    Heartworm-infected dogs were treated therapeutically with a new heartworm adulticide (Melarsomine dihydrochloride, RM 340) and then put on a Strategic Program with treatment every 4 months for clinical prophylaxis to take advantage of the drug's potent activity against 4-month-old immature as well as adult Dirofilaria immitis. Ten random-source dogs with naturally acquired heartworm infections (microfilariae- and antigen-positive) were given Melarsomine (2.2 mg kg-1 twice 3 h apart) by i.m. injection in the lumbar muscles to clear their existing infections. They were then placed outdoors (August 1988) in a high-risk area in Georgia (USA) for heartworm transmission and given Melarsomine at the same posology every 4 months (Strategic Program) for 12 months as a clinical prophylactic measure. Five nontreated heartworm-naive beagles placed at this site during the same period served as 'controls' to monitor heartworm transmission. After exposure for 12 months, the ten treated and five 'control' dogs were taken indoors and held for 5 months. Microfilaremia and antigenemia levels were monitored in both groups by testing at 4-5 month intervals throughout the study and the intensity of infection was determined at necropsy. Microfilaremia levels in treated dogs dropped dramatically following the initial therapeutic treatment and remained either negative or low. Only two of the five 'control' dogs became microfilaremic, and this occurred near the end of the study. Nine of the ten treated dogs were antigen-negative 4 months after the initial therapeutic treatment, and all of them were antigen-negative at all bleedings thereafter. Four of the five 'control' dogs were antigen-positive at necropsy, and only one of these was positive 4 months earlier. Based on these antigen data, the initial treatment cleared 90% of the dogs of worms, and no worms were detected in any of the treated dogs thereafter. However, it is possible that undetectable immature heartworms were present. Although all of the treated dogs were antigen-negative at necropsy, three of them had a total of eight heartworms, seven of which were clearly immature, as determined by worm length measurements, and the remaining worm was a young adult female that was probably too young to be detected. All of the five 'control' dogs had heartworms (average 7.4; range 1-16), and about half of these worms were clearly immatures. Therapeutic treatment followed by strategic treatment with Melarsomine every 4 months during reexposure was at least 89.2% effective overall.(ABSTRACT TRUNCATED AT 400 WORDS)

  • clinical prophylactic activity of Melarsomine dihydrochloride rm 340 against dirofilaria immitis in heartworm naive beagles exposed to natural infection in three southeastern states
    Veterinary Parasitology, 1994
    Co-Authors: John W Mccall, M.t. Dzimianski, Tom L Mctier, Jeanpierre Raynaud, Robert A Holmes
    Abstract:

    Melarsomine dihydrochloride (RM 340), a drug being developed as an adulticide for treatment of heartworm (Dirofilaria immitis) infection in dogs, was safe and highly effective as a clinical prophylactic agent against naturally acquired infections using Strategic and Tactical Treatment Programs. The Strategic Program involved treatment every 4 months (three series of treatments per year), disregarding the mosquito season (MS), to clear the existing infection at each treatment. The Tactical Program consisted of two series of treatments per year, 4 months apart, with the first one given about the middle of the MS (August) and the second one given after the end of the MS (December). Melarsomine was administered as two i.m. injections (lumbar muscles) of 2.2 mg kg-1 given 3 h apart. A total of 90 heartworm-naive beagles and a number of microfilaremic 'seed' dogs were used. Three similar experiments (30 beagles per experiment) were conducted at selected areas (Georgia, Florida, Louisiana) known to be enzootic for heartworm. At each site, 30 beagles were allocated to six groups of five dogs each, and four of these groups were placed outdoors in April of 1988. Two groups (control and treated) were exposed for 12 months, and the treated group was given Melarsomine at 4, 8, and 12 months after exposure was started (Strategic Program). Another group was exposed for 8 months and treated with Melarsomine at 4 and 8 months (Tactical Program). One group of tracer (sentinel) beagles was exposed from April to August 1988, one group from August to December 1988, and another from December 1988 to April 1989. April-August and August-December tracers served as controls for the tactically treated dogs. After exposure, all dogs were held indoors for 5 months before necropsy. Blood was collected at 4-5 month intervals and examined for microfilariae (MF) and adult heartworm antigen (enzyme-linked immunosorbent assay, ELISA). Treatment by the Strategic Program was 99% effective, with only one of the total of 15 treated dogs harboring any worms (a single female) at necropsy. Thirteen of the 14 control dogs (93%) exposed for 12 months became infected, with average worm recoveries of 6.8, 5.4, and 25.2 (range 1-45) for the Georgia, Florida, and Louisiana sites, respectively. All of the 13 heartworm-infected control dogs were antigen-positive, and 12 of these were also MF-positive, while none of the strategically treated dogs was either antigen- or MF-positive at necropsy. Tactical treatment of the total of 14 dogs twice per year was 100% effective.(ABSTRACT TRUNCATED AT 400 WORDS)

Laura D Kramer - One of the best experts on this subject based on the ideXlab platform.

  • efficacy of imidacloprid 10 moxidectin 2 5 spot on advocate advantage multi and doxycycline for the treatment of natural dirofilaria immitis infections in dogs
    Veterinary Parasitology, 2019
    Co-Authors: Marco Genchi, Alice Vismarra, Chiara Lucchetti, Antonio Viglietti, Serena Crosara, Giacomo Gnudi, C Quintavalla, Roland Schaper, Laura D Kramer
    Abstract:

    Abstract Heartworm infection (also known as dirofilariosis due to Dirofilaria immitis) in dogs causes chronic pulmonary disease that, if left untreated, can lead to right-side congestive heart failure. Currently, the only registered drug for adulticide therapy in dogs with heartworm disease (HWD) is Melarsomine dihydrochloride. The recent targeting of the bacterial endosymbiont Wolbachia, through antibiotic therapy of the infected host, has offered an interesting alternative for the treatment of HWD. Recent reports of the adulticide activity of an ivermectin/doxycycline combination protocol has lead the American Heartworm Society (AHS) to include in its guidelines that, in cases where arsenical therapy is not possible or is contraindicated, a monthly heartworm preventive along with doxycycline for a 4-week period might be considered. In the present study, 20 dogs with confirmed natural D. immitis infection were included following owner consent. Fourteen dogs were treated with a topical formulation containing 10% w/v imidacloprid and 2.5% w/v moxidectin (Advocate®, Advantage Multi®, Bayer), monthly for nine months, associated to doxycycline (10 mg/kg/BID) for the first 30 days. Six dogs were treated with Melarsomine (Immiticide®, Merial) (2.5 mg/kg) at enrollment, followed one month later by two injections 24 h apart. The presence of circulating antigens and the number of microfilariae (mf) were evaluated at the moment of enrollment and then at 1, 2, 3, 4, 5, 6, 7, 8, 12, 18, 24 months post enrollment. Echocardiogram and radiographs were performed at month 0, 6, 12, 18, 24. Monthly moxidectin combined with 30 days of doxycycline eliminated circulating microfilariae within one month, thus breaking the transmission cycle very quickly. Furthermore, dogs treated with the combination protocol started to become negative for circulating antigens at 4 months from the beginning of treatment and all except one were antigen negative at 9 months. All dogs treated with Melarsomine were antigen negative by 5 months from the beginning of the treatment. No dogs showed worsening of pulmonary patterns or criteria indicative of pulmonary hypertension 12 to 24 months after. For the criteria mf concentration, antigen concentration, radiography and echocardiography at 12, 18 and 24 months the non-inferiority for the moxidectin group could be proven for a non-inferiority margin of 15% for the rate difference. Dogs treated with moxidectin and doxycycline became negative for microfilariae and antigens sooner when compared to Melarsomine in the present study and to dogs treated with doxycycline combined with ivermectin in studies previously published.

  • evaluation of lung pathology in dirofilaria immitis experimentally infected dogs treated with doxycycline or a combination of doxycycline and ivermectin before administration of Melarsomine dihydrochloride
    Veterinary Parasitology, 2011
    Co-Authors: Laura D Kramer, M.t. Dzimianski, P. Supakorndej, N. Supakorndej, Giulio Grandi, B Passeri, P Gianelli, Marco Genchi, Abdelmoneim Mansour, S.d. Mccall
    Abstract:

    Abstract Adulticide therapy in heartworm ( Dirofilaria immitis )-infected dogs can lead to thromboembolism, which can seriously compromise post-treatment health status. Lung pathology following adulticide therapy was evaluated in three groups of experimentally infected dogs. Group 1 was treated with doxycycline at 20 mg/kg per os once daily for 30 days post infection followed by an intramuscular injection of Melarsomine dihydrochloride (2.5 mg/kg) at Week 12, followed 1 month later by two injections 24 h apart. Group 2 was treated as described for Group 1, with the addition of ivermectin at 6 mcg/kg given monthly per os for 24 weeks post-infection. Group 3 received Melarsomine alone, as described above. All dogs were necropsied at Week 24 and lung pathology was evaluated. Lesion criteria included perivascular inflammation and endothelial proliferation. Lesions were scored by two independent pathologists who were blinded as to treatment. Results indicate that doxycycline treatment alone or combined with ivermectin had lower lesion scores than lungs from dogs who had received Melarsomine alone. Dogs that received the combined doxycycline/ivermectin protocol and treated with adulticide showed less severe arterial lesions and the virtual absence of thrombi.

  • wolbachia and its influence on the pathology and immunology of dirofilaria immitis infection
    Veterinary Parasitology, 2008
    Co-Authors: Laura D Kramer, John W Mccall, C. Genchi, Giulio Grandi, M Leoni, B Passeri, Michele Mortarino, C Bazzocchi
    Abstract:

    Abstract Since the definitive identification in 1995 of the bacterial endosymbiont Wolbachia that resides in different tissues of the filarial worm Dirofilaria immitis, there has been increasing interest to understand whether and what role it plays in the pathogenesis of and immune response to heartworm infection. The present study evaluated the effects of treatments on lung pathology in 20 beagle dogs experimentally infected with D. immitis. Dogs in Group 1 were treated with doxycycline (10 mg/kg/day) orally from weeks 0–6, 10–12, 16–18, 22–26, and 28–34. Dogs in Group 2 served as infected, non-treated controls. Dogs in Group 3 were given doxycycline as described for Group 1 combined with weekly oral doses of ivermectin (6 mcg/kg) for 34 weeks and intramuscular (IM) Melarsomine (2.5 mg/kg) at week 24, followed by two additional Melarsomine injections 24 h apart 1 month later. Group 4 received only Melarsomine as described for Group 3. Lung lesion criteria, scored by two independent blinded pathologists, included perivascular inflammation and endothelial proliferation. Doxycycline treatment alone had no effect on lesion scores, whereas the combination of doxycycline and ivermectin resulted in less severe perivascular inflammation. All lungs were evaluated for positive immunostaining for the Wolbachia surface protein (WSP). Control dogs showed numerous thrombi, intense perivascular and interstitial inflammation and, occasionally, positive staining for WSP. Interestingly, dogs receiving doxycycline/ivermectin/Melarsomine showed significantly less severe arterial lesions and the virtual absence of thrombi.