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The stability and effectiveness of fumagillin in controlling Nosema ceranae (Microsporidia) infection in honey bees (Apis mellifera) under laboratory and field conditions

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Abstract

Honey bees play an important role in food production (honey, pollen etc.), and their pollinating activity is not only essential to maintain world agriculture production but also to ensure biodiversity in different ecosystems. Nosema ceranae is a highly prevalent worldwide pathogen for honey bees that has been related to colony losses. A commercial formulation that contains fumagillin dicyclohexylamine, Fumidil B®, can control N. ceranae infection. However, the effectiveness of Fumidil B® is affected by several factors, such as storage, treatment preparation, the quantity consumed by bees etc. Indeed, UV exposure (e.g. sunlight) drastically reduces the initial concentration of fumagillin within a few hours, while temperature affects its degradation. Although laboratory tests suggest that a semisolid mixture of honey and powdered sugar is the best option to apply fumagillin, its application in syrup (250 mL per dosage) is more effective for the treatment of infected colonies. The total amount of syrup containing fumagillin ingested by honey bees is a key factor in its efficacy, and it has been found that medicated patties were not fully consumed in field trials. In honey bee colonies, the dose of 120 mg/honey bee colony at the recommended posology is effective against depopulation and colony death due to N. ceranae after 1 year, without residues being detected in honey, although reinfection could be detected 4 months after treatment ended.

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Acknowledgements

The authors wish to thank the Spanish Ministry of Medio Ambiente, Medio Rural y Marino, the Consejería de Agricultura y Desarrollo Rural, and the Consejería de Educación y Ciencia for their financial support (projects RTA2008-0020-CO2-02 and API006-009, PAI09-0022-1264).

Conflicts of interest statement

Any mention of trade names or commercial products in this article is solely for the purpose of providing specific information.

Stabilité et efficacité de la fumagilline pour contrôler l’infection par Nosema ceranae (Microsporidia) chez les abeilles ( Apis mellifera ) en conditions de laboratoire et de terrain.

Nosema ceranae / fumagilline / stabilité / sirop / dosage / traitement / dépopulation de la colonie

Zusammenfassung–Die Stabilität und Effektivität von Fumagillin bei der Behandlung von Infektionen mit Nosema ceranae (Microsporidia) bei Honigbienen ( Apis mellifera ) unter Labor- und Freilandbedingungen. Das aus Aspergillus fumigatus gewonnene fumagillin ist als einzige Chemikalie zur Behandlung von Infektionen der Honigbiene mit Nosema zugelassen und wird innerhalb der EU als ein Arzneimittel für seltene Krankheiten betrachtet. Ausgehend von der Unsicherheit hinsichtlich der Wirksamkeit von fumagillin bei der Behandlung einer Infektion mit N. ceranae wurden in dieser Studie mehrere Faktoren untersucht. Die Stabilität von fumagillin wurde bei verschiedenen Konzentrationen unter Laborbedingungen getestet; dabei wurden der Einfluss verschiedener Arzneistoffträger (z.B. Zuckersirup oder –teig), verschiedener Temperaturen und der Einwirkung von UV-Strahlen untersucht. Zusätzlich wurden die Daten eines Feldversuchs an natürlicherweise mit N. ceranae infizierten Völkern ausgewertet, die wöchentliche Dosen von fumagillin in Sirup oder Zuckerteig erhielten. Diese wurden 4- bis 8-mal verabreicht, so dass die aufgenommene Gesamtmenge pro Volk bei 6 oder 8 g lag. Der Versuch schloss Kontrollgruppen ein, die Sirup ohne pharmakologische Inhaltstoffe erhielten. Während hohe Temperaturen (30–40°C) fortschreitende Degradation des fumagillins über 20 Tage hinweg verursachten, reduzierte die Einwirkung von UV-Strahlung die ursprüngliche Konzentration bereits innerhalb weniger Stunden drastisch. In der Beimischung zu Zuckerteig und bei Aufbewahrung in gefärbten Glasbehältern war es dagegen sowohl bei Kälte als auch bei Hitze sehr stabil, besonders auch bei höheren Konzentrationen. Nach vier Wochen war weniger als 10% Verlust zu verzeichnen. Obwohl sich in Labortests abzeichnete, dass eine Mischung aus Honig und Puderzucker zur Verabreichung des Medikaments am besten geeignet ist, war die Applikation in Sirup zur Behandlung infizierter Völker in Feldversuchen wirksamer. Die schlechteren Ergebnisse bei Anwendung von fumagillin in Honig–Zuckerteig wurden dadurch verursacht, dass die Bienen das Medikament nicht vollständig aufnahmen. Es ist sehr wichtig, für eine schnelle und vollständige Aufnahme des medikamentenhaltigen Futters zu sorgen um eine möglichst effektive Behandlung zu erreichen, besonders wenn man die Instabilität des fumagillins berücksichtigt. In der Tat scheint die aufgenommene fumagillin-haltige Futtermenge einen direkten Einfluss auf die Wirkung der Behandlung und das Überleben der Völker zu haben. Dementsprechend erschien die Behandlung am effektivsten wenn das Medikament in Sirup verabreicht wurde. Die beste Dosierung bestand aus einer Mischung von 30 mg fumagillin (1.5 g Fumidil B®) mit 250 mL Sirup, die einen Monat lang einmal wöchentlich verabreicht wurde. Nach dieser Behandlung wurden keine Rückstände im während der folgenden 4 Monate produzierten Honig entdeckt, wenn er aus dem Honigraum entnommen wurde.

Nosema ceranae / Fumagillin / Stabilität / Sirup / Honig-Zuckerteig / Dosierung / Behandlung / Völkerschwächung

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Authors and Affiliations

  1. Centro Apícola Regional, Bee Pathology Laboratory, Junta de Comunidades de Castilla-La Mancha, 19180, Marchamalo, Spain

    Mariano Higes & Raquel Martín-Hernández

  2. CINQUIMA Investigation Institute, Analytical Chemistry Group, Faculty of Sciences, University of Valladolid, 47011, Valladolid, Spain

    María J. Nozal, Ana Alvaro & José L. Bernal

  3. Statistics Department, CTI, Consejo Superior Investigaciones Científicas, 28006, Madrid, Spain

    Laura Barrios

  4. Departamenteo de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, 28040, Madrid, Spain

    Aranzazu Meana

  5. Institut for Industrial Fermentations (IFI), Consejo Superior de Investigaciones Científicas, 28003, Madrid, Spain

    José Bernal

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  1. Mariano Higes
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Correspondence to Mariano Higes.

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Higes, M., Nozal, M.J., Alvaro, A. et al. The stability and effectiveness of fumagillin in controlling Nosema ceranae (Microsporidia) infection in honey bees (Apis mellifera) under laboratory and field conditions. Apidologie 42, 364–377 (2011). https://doi.org/10.1007/s13592-011-0003-2

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