PLANT BIOLOGY
ANIMAL BIOLOGY
SUBSCRIPTION
E-SUBSCRIPTION
 
MAP
MAIN PAGE

 

 

 

 

Engashev S.V., Belova L.M., Gavrilova N.A., Zabrovskaia A.V., Smirnova L.I., Engasheva E.S., Dyachkova Ju.A. The Protostop drug effectiveness in diarrhea of mixed parasitic-bacterial etiology in calves. Sel'skokhozyaistvennaya Biologiya [Agricultural Biology], 2024, Vol. 59, № 2, p. 355-365.
(how to cite this article)

doi: 10.15389/agrobiology.2024.2.355eng

UDC: 636.2:619:615.246

 

THE PROTOSTOP DRUG EFFECTIVENESS IN DIARRHEA OF MIXED PARASITIC-BACTERIAL ETIOLOGY IN CALVES

S.V. Engashev1 ✉, L.M. Belova2, N.A. Gavrilova2,
A.V. Zabrovskaia2, L.I. Smirnova2, E.S. Engasheva1, Ju.A. Dyachkova2

1AVZ Ltd, 4/2, Igarskiy pr-d, Moscow, Russia 129329, e-mail admin@vetmag.ru;
2Saint-Petersburg State University of Veterinary Medicine, 5, ul. Chernigovskaya, St. Petersburg, 196084 Russia, e-mail beringa20@mail.ru (✉ corresponding author), larissabelova2010@yandex.ru, nadezhda.gavrilova65@mail.ru, lubov965@rambler.ru, yulya.shcherbina.96@mail.ru

ORCID:
Engashev S.V. orcid.org/0000-0002-7230-0374
Smirnova L.I. orcid.org/0000-0002-4367-83876
Belova L.M. orcid.org/0000-0003-4473-1940
Engasheva E.S. orcid.org/0000-0002-4808-8799
Gavrilova N.A. orcid.org/0000-0001-5651-5976
Dyachkova Ju.A. orcid.org/0000-0003-2976-1279
Zabrovskaia A.V. orcid.org/0000-0003-2655-7555

Final revision received February 01, 2023
Accepted March 03, 2023

 

In cattle breeding, diseases of the gastrointestinal tract (GIT) of calves with diarrheal syndrome, which are widespread almost everywhere and involve most of the livestock, remain a serious problem. Gastrointestinal diseases of calves of mixed, parasitic-bacterial and parasitic-viral etiology are often noted, a combination of Cryptosporidium spp. with Escherichia coli, enterobacteria of the genus Salmonella, Klebsiella have been detected. Thereof, it is optimal to use broad-spectrum drugs that have antimicrobial and antiprotozoal effects. This article presents for the first time the effect of the drug paromomycin sulfate on pathogens of gastrointestinal diseases of both parasitic and bacterial origin. The minimum inhibitory concentration (MIC) of paromomycin sulfate has been established for pathogens of gastrointestinal tract diseases of calves of bacterial etiology, i.e., Salmonella Dublin, Escherichia coli with hemolytic properties, Klebsiella pneumoniae, Proteus vulgaris, Citrobacer freundii. The aim of study was to examine the therapeutic effectiveness of the drug Protostop (the active substance is paromycin sulfate) for diseases of the gastrointestinal tract with diarrheal syndrome in calves. The research was carried out at a cattle farm (Leningrad Province, Lomonosovsky District) in July-August 2021. The experiments involved calves (Bos taurus) of the black-white breed, up to 5 months old, weighing from 30 to 50 kg. Fecal samples weighing 20-40 g were taken from the rectum of calves with clinical signs of gastrointestinal dysfunction. To detect oocysts of Cryptosporidium spp. fecal smears were prepared on a glass slide, and stained using a Diakhim-Kit for Ziehl-Neelsen staining (NPF Abris+, Russia). Microscopy was performed using a Primo Star microscope (Carl Zeizz, Germany). To establish the quantitaty and species of enterobacteria, 10-fold dilutions of feces in saline solution were sown in 0.05 ml quantities on the Endo nutrient medium (LLC Research Center for Pharmacotherapy, Russia). To assess the therapeutic effectiveness of the drug Protostop (powder, 1 g of the drug contains 100 mg of paromomycin sulfate; AVZ Ltd, Russia), animals in whose feces consist oocysts of Cryptosporidium spp., strains of hemolytic E. coli and opportunistis microorganisms were selected. We formed 5 groups of animals of 10 animals in each (4 experimental, 1 control). All calves in experimental groups were given the drug Protostop individually, orally, once a day. Before use, a single dose of the drug was dissolved in water by adding the liquid to the powder. Animals from the 1st group received the drug at a dose of 250 mg/kg of body weight for 3 days, calves from the 2nd group were given the drug at the same dose for 5 days. Animals of the 3rd and 4th groups received Protostop at a dose of 350 mg/kg body weight, respectively, for 3 and 5 days. Calves from the control group were treated with an analog drug Parofor 70 (powder, 1.0 g of the drug contains 100.0 mg of paromomycin sulfate; Biovet AD, Bulgaria). The drug was administered at a dose of 350 mg/kg body weight orally once a day for 5 days. During a clinical examination on the 3rd, 5th, 10th and 14th days from the start of treatment, the health condition of the animals, their consumption of water and feed, the presence of changes in the function of the GIT, the condition of the mucous membranes and coat were examined. Coprological studies for the presence of oocysts of Cryptosporidium spp. were carried out on the 8th and 12th days of treatment, bacteriological on the 10th day after the end of treatment. To assess the health condition, blood samples for examination was taken in all groups. The MIC of paromomycin sulfate, the active substance of the drug Protostop, was determined by the method of serial dilutions according to GOST R ISO 20776-1-2010. Strains for which the MIC of paromomycin did not exceed 4 μg/ml were classified as susceptible, and those above 4 μg/ml were classified as resistant. A parasitological study revealed more than 25 oocysts of Cryptosporidium spp. in the feces of calves in the field of view, which indicated a high intensity of invasion. A bacteriological study revealed Escherichia coli strains with hemolytic activity and other strains of opportunistic microflora. After treatment, all calves in the experimental groups showed significant improvements in their health condition: the animals became more active, diarrhea stopped, and the feces became a mushy consistency, characteristic of cattle feces. The drug Protostop had a pronounced therapeutic effect at a dose of 350 mg/kg of animal weight, administered orally with water, once a day, for a course of 5 days. 8 days after the start of treatment according to the indicated regimen, there were no Cryptosporidium spp. oocysts in the feces; 10 days after the end of treatment, strains of hemolytic Escherichia coli and other opportunistic enterobacteria were absent in a 1:10 dilution of feces. The therapeutic effectiveness of the drug Protostop at the indicated dosage and duration of use is higher than the effectiveness of the drug Parofor 70 at a dose of 350 mg/kg. The MIC of paromomycin for Salmonella Dublin and Citrobacter freundii strains was 2 μg/ml, which allows them to be classified as microbiologically susceptible to this drug. The remaining strains were microbiologically resistant, for hemolytic Escherichia coli strains the MIC ranged from 128 to more than 256 µg/ml, for Klebsiella pneumoniae, Proteus vulgaris MIC was more than 256 µg/ml.

Keywords: paromomycin, cryptosporidiosis, minimal inhibitory concentration, Escherichia coli, calves, gastrointestinal diseases, gastrointestinal tract.

 

REFERENCES

  1. Cho Y.-I., Yoon K.-J. An overview of calf diarrhea — infectious etiology, diagnosis, and intervention. J. Vet. Sci., 2014, 15(1): 1-17 CrossRef
  2. Klimova E.S., Mkrtchyan M.E., Maksimova E.V., Reshetnikova A.D. Mezhdunarodnyy vestnik veterinarii, 2020, 3: 24-29 CrossRef (in Russ.).
  3. Musaeva M.N., Budulov N.R., Abdulmagomedov S.Sh., Musaev Z.G. Rossiyskiy parazitologicheskiy zhurnal, 2013, 3: 64-66 (in Russ.).
  4. Levine N.D. Taxonomy and review of the coccidian genus Cryptosporidium (protozoa, apicomplexa). The Journal of Protozoology, 1984, 31(1): 94-98 CrossRef
  5. Vereshchak N.A., Poryvaeva A.P., Pechura E.V., Krasnoperov, A.S. Voprosy normativno-pravovogo regulirovaniya v veterinarii, 2016, 4: 87-90 (in Russ.).
  6. Kirillov E.G. Uchenye zapiski Kazanskoy gosudarstvennoy akademii veterinarnoy meditsiny im. N.E. Baumana, 2014, 1: 128-131 (in Russ.).
  7. Starikova O.V., Voronkova, Yu.V., Kovshirina I.I., Shubina N.I. Vestnik Rossiyskoy akademii meditsinskikh nauk, 2017, 72(6): 420-427 CrossRef (in Russ.).
  8. Chalmers R.M., Davies A.P. Minireview: Clinical cryptosporidiosis. Experimental Parasitology, 2010, 124(1): 138-146 CrossRef
  9. Conrady B., Brunauer M., Roch F.-F. Cryptosporidium spp. Infections in combination with other enteric pathogens in the global calf population. Animals, 2021, 11(6): 1786 CrossRef
  10. Bartels C.J.M., Holzhauer M., Jorritsma R., Swart W.A.J.M., Lam T.J.G.M. Prevalence, prediction and risk factors of entropathogens in normal and non-normal faeces of young Dutch dairy calves. Preventive Veterinary Medicine, 2010, 93(2-3): 162-169 CrossRef
  11. Delling C., Daugschies A. Literature review: coinfection in young ruminant livestock—Cryptosporidium spp. and its companions. Pathogens, 2022, 11(1): 103 CrossRef
  12. Lee S.-H., Kim H.-Y., Choi E.W., Kim D. Causative agents and epidemiology of diarrhea in Korean native calves. J. Vet. Sci., 2019, 20(6): e64 CrossRef
  13. de la Fuente R., Luzon M., Ruiz-Santa-Quitria J.A., Garcı́a A., Cid D., Orden J.A., Garcı́a S., Sanz R., Gomez-Bautista M. Cryptosporidium and concurrent infection with other major enteropathogens in 1 to 30-day-old diarrheic calves in central Spain. Veterinary Parasitology, 1999, 80(3): 179-185 CrossRef
  14. Brar A.P.S., Sood N.K., Kaur P., Singla L.D., Sandhu B.S., Gupta K., Narang D., Singh C.K., Chandra M. Periurban outbreaks of bovine calf scours in Northern India caused by Cryptosporidium in association with other enteropathogens. Epidemiology & Infection, 2017, 145(13): 2717-2726 CrossRef
  15. Cho Y.-I., Han J.-I., Wang C., Cooper V., Schwarz K., Engelken T., Yoon K. Case-control study of microbiological etiology associated with calf diarrhea. Veterinary Microbiology, 2013, 166(3-4): 375-385 CrossRef
  16. Garcı́a A., Ruiz-Santa-Quitria J.A., Cid D., Orden J.A., Sanz R., Gomez-Bautista M., de La Fuente R. Rotavirus and concurrent infection with other enteropathogens in neonatal diarrheic calves dairy calves in Spain. Comparative Immunology, Microbiology and Infectious Disease, 2000, 23(3): 175-183 CrossRef
  17. Al Mawly J., Grinberg A., Pratelly D., Moffat J., Marshall J., French N. Risk factors for neonatal calf diarrhea and enteropathogen shedding in New Zealand dairy farm. The Veterinary Journal, 2015, 203: 155-160 CrossRef
  18. Hall G.A., Reynolds D.J., Parsons K.R., bland A.P., Morgan J.H. Pathology of calves with diarrhea in southern Britain. Research in Veterinary Science, 1988, 45(2): 240-250 CrossRef
  19. Göhring F., Möller-Holtkamp P., Daugschies A., Lender M. Co-infection with Cryptosporidium parvum and other enteropathogenes support the occurrence and severity of diarrhea in suckling calves. Tierarztl. Umsch., 2014, 69(4): 112-120.
  20. Seabloom E.W., Borer E.T., Gross K., Kending A.E., Lacroix C., Mitchell C.E., Mordecai E.A., Power A.G. The community ecology of pathogens. Coifection, coexistence and community composition. Ecology Letters, 2015, 18(4): 401-415 CrossRef
  21. Bartels C.J.M., Holzhauer M., Jorritsma R., Swart W.A.J.M., Lam T.G.G.M. Prevalence, prediction and risk factors of enteropathogenes in normal and non-normal faeces of young Dutch dairy calves. Preventive Veterinary Medicine, 2010, 93(2-3): 162-169 CrossRef
  22. Almawly J., Prattley D., French N.P., Lopez-Villalobos N., Hedgespeth B., Grinberg A. Utility of halofuginone lactate for the prevention of natural cryptosporidiosis of calves, in the presence of co-infection with rotavirus and Salmonella Typhimurium. Veterinary Parasitology, 2013, 197(1-2): 59-67 CrossRef
  23. Miyamoto Y., Eckmann L. Drug development against the major diarrhea-causing parasites of the small intestine, Cryptosporidium and Giardia. Frontiers in Microbiology,2015, 6: 1208 CrossRef
  24. Masood S., Maqbool A., Khan U.J., Chaudhry Z.I., Anjum A.A. Anti-cryptosporidium activity of albendazole, metronidazole and paromomycin in experimentally infected cattle. Pakistan J. Zool.,2013, 45(4): 935-940.
  25. Nasir A., Avais M., Khan M.S., Khan J.A., Hameed S., Reichel M.P. Treating Cryptosporidium parvum infection in calves. Journal of Parasitology, 2013, 99(4): 715-717 CrossRef
  26. Constable P.D. Treatment of calf diarrhea: antimicrobial and ancillary treatment. Veterinary Clinics of North America: Food Animal Practice, 2009, 25: 101-120 CrossRef
  27. ECDC (European Centre for Disease Prevention and Control), EFSA (European Food Safety Authority), and EMA (European Medicines Agency). ECDC/EFSA/EMA second joint report on the integrated analysis of the consumption of antimicrobial agents and occurrence of antimicrobial resistance in bacteria from humans and food-producing animals — Joint Interagency Antimicrobial Consumption and Resistance Analysis (JIACRA) Report. EFSA Journal, 2017, 15(7): 4872 CrossRef
  28. Karaiskos I., Lagou S., Pantikis K., Rapi V., Poulakou G. The “old” and the “new” antibiotics for MDR gram-negative pathogens: from whom, when, and how. Frontiers in Public Health, 2019, 7: 151 CrossRef
  29. Theuretzbacher U., Van Bambeke F., Canton R., Giske Ch. G, Mouton J.W., Nation R.L., Paul M., Turinge J., Kahlmeter G. Reviving old antibiotics. Journal of Antinicrobial Chemotherapy, 2015, 70(8): 2177-2181 CrossRef
  30. Geurden T., Claerebout E., Dursin L., Deflandre A., Bernay F., Kaltsatos V., Vercruysse J. The efficacy of an oral treatment with paromomycin against an experimental infection with Giardia in calves. Veterinary Parasitology, 2006, 135(3-4): 241-247 CrossRef
  31. Prakticheskoe rukovodstvo po antimikrobnoy khimioterapii /Pod redaktsiey L.S. Strachunskogo, Yu.B. Belousova, S.N. Kozlova [Practical guide to antimicrobial chemotherapy. L.S. Strachunskiy, Yu.B. Belousov, S.N. Kozlov (eds.)]. Smolensk, 2007 (in Russ.).
  32. Heller M.C., Chigerwe M. Diagnosis and treatment of infectious enteritis in neonatal and juvenile ruminants. Veterinary Clinics of North America: Food Animal Practice, 2018, 34(1): 101-117 CrossRef
  33. Hu Y., Lui L., Zhang X., Feng Y., Zong Zh.In vitro activity of neomycin, streptomycin, paromomycin and aparmycin against carbapenem-resistant Enterobacteriaceae clinical strains. Frontiers in Microbiology, 2017, 8: 2275 CrossRef
  34. GOST R 54627-2011. Zhivotnye sel’skokhozyaystvennye zhvachnye. Metody laboratornoy diagnostiki gel’mintozov [GOST R 54627-2011. Agricultural ruminant animals. Methods for laboratory diagnosis of helminth infections]. Moscow, 2013 (in Russ.).
  35. Laboratornaya diagnostika gel’mintozov, protozoozov: metodicheskie ukazaniya [Laboratory diagnosis of helminthiasis, protozoan infections: guidelines]. Moscow, 2014 (in Russ.).
  36. Golubeva I.V., Kilesso V.A., Kiseleva B.S., Pryamukhina N.S., Tatarinova S.D., Khomenko N.A., YushchenkoG.V. Enterobakterii: rukovodstvo dlya vrachey /Pod redaktsiey V.I. Pokrovskogo [Enterobacteriaceae: guide for doctors. V.I. Pokrovskiy (ed.)]. Moscow, 1985 (in Russ.).
  37. GOST R ISO 20776-1-2010. Klinicheskie laboratornye issledovaniya i diagnosticheskie test-sistemy in vitro. Issledovanie chuvstvitel’nosti infektsionnykh agentov i otsenka funktsional’nykh kharakteristik izdeliy dlya issledovaniya chuvstvitel’nosti k antimikrobnym sredstvam [GOST R ISO 20776-1-2010. Clinical laboratory studies and in vitro diagnostic test systems. Study of the sensitivity of infectious agents and assessment of the functional characteristics of products for testing sensitivity to antimicrobial agents]. Moscow, 2011 (in Russ.).
  38. Zabrovskaya A.V., Smirnova L.I., Shavrov S.S. Voprosy normativno-pravovogo regulirovaniya v veterinarii, 2021, 4: 60-63 CrossRef (in Russ.).
  39. Chekole W.S., Adamu H., Sternberg-Lewrein S., Magnusson U., Tessema T.S. Occurrence of Escherichia coli pathotypes in diarrheic calves in a low-income setting. Pathogens, 2023, 12: 42 CrossRef
  40. Konishcheva A.S., Pleshakova V.I., Leshcheva N.A. Vestnik Omskogo GAU, 3(43), 2021: 70-77 CrossRef (in Russ.).
  41. Chen W., Matsushita T., Shcherbakov D., Boukari H., Vassela A., Böttger E.C., Crich D. Synthesis, antiribosomal and antibacterial activity of 4’-O-glycopyrankisyl paromomycin aminoglycoside antibiotics. MedicinalChemistryCommunication,2014, 5: 1179-1187 CrossRef
  42. Rekomendatsii. Opredelenie chuvstvitel’nosti mikroorganizmov k antimikrobnym preparatam. Versiya 2021-01 [Recommendations. Determination of the sensitivity of microorganisms to antimicrobial drugs. Version 2021-01]. Available https://www.antibiotic.ru/files/321/clrec-dsma2021.pdf (in Russ.).
  43. Aydogdt U., Isik N., Ekici O.D., Yildiz R., Sen I., Coskun I. Comparison of the effectiveness of halofuginone lactate and parpmomycin in the treatment of calves naturally infected with Cryptosporidium parvum. Acta Scientiale Veterinariae,2018, 46(1): 1524 CrossRef
  44. Hameed O.A. A review of cryptosporidium infection in neonatal lambs and camel calves. Journal of Infectious Diseases & Research,2020, 3(2): 109-110.

 

back

 


CONTENTS

 

 

Full article PDF (Rus)

Full article PDF (Eng)