Bee Pathology

We carry out applied science in honey bee biology in our work on bee pathology, and in particular, varroosis. Our goals are understanding the host-parasite relationship and developing chemical-therapeutical strategies against Varroa destructor.

Our activities include also services such as ongoing education for beekeepers and government authorities, public relations work, such as preparing scientific topics for museum exhibitions, and taking the initiative in the national and European Union drug approval matters.

Our current research projects on honey bees are:

1. Developing medicaments: Toxicology in Apis mellifera and the efficacy of potential active agents in fighting Varroa destructor
2. Galenics of varroacides: developing sugar substitutes as carrier for active ingredients in drugs orally toxic to bees
3. Sublethal effects of active ingredients of varroacides on the individual bee and bee colonies
4. Population dynamics of Varroa destructor

(1) Developing medicaments: Toxicology in Apis mellifera and the efficacy in fighting Varroa destructor

Our work involves optimizing varroosis treatment processes and developing medicaments and methods to their final application stage. To achieve this, substances are being screened and laboratory testing is being carried out: we investigate possible side effects for bees and the toxic effects of these substances on mites to establish an individual therapeutical dosage. The aspects residues in bee products as well as user and consumer safety are part of our work. Factors are being studied that influence the distribution and efficacy of the substances introduced into the complex system of the bee colony; these studies help develop more effective methods of applying the substances. Therapeutic dosages for colonies are then calculated and tested, first with standardized experimental populations, and secondly, under actual field conditions, at various locations, in order to establish both recommendations for use and to create a database according to the requirements for national or European registration for certification of these substances for use as veterinary drugs. To obtain approval as a veterinary drug, a dossier has to be established on effectiveness against the parasite, tolerability by bee colonies, residue situation and consumer safety according to the requirements of the national and European legislation.

Results of these activities are:

a) Formic acid, in the long-term evaporating form (vacuum evaporator), was approved as a veterinary drug in Germany on July 12th, 2000 (Bundesgesetzblatt Teil I, Nr. 31 vom 11. Juli 2000). Meanwhile it is also used in many countries worldwide as a medicament.

Due to a change in legislation it was possible to get formic acid freed from its ‘may be sold only in pharmacies’-status in Germany (Decision of Dec. 15, 2003 of the German Bundesrat). This means formic acid can be sold in beekeeper supply stores. But it is still a drug, with all requirements according to the standard approval status regarding quality, concentration, rules of application and packaging. The producer must be licensed to manufacture the medicament.

b) In cooperation with the Mayen Dept. of Bee Research (Fachzentrum Bienen und Imkerei Rheinland-Pfalz) and the German Beekeepers' Society (Deutscher Imkerbund e.V.), the formal application process for lactic acid, applied as a spray, has been initiated. The approval as a drug for bees followed on June 27, 2003 (Bundesgesetzblatt Teil I, Nr. 27 vom 26. Juni 2003). As formic acid, lactic acid could be freed from its ‘may be sold only in pharmacies’-status in Germany (Decision of Dec. 15, 2003 of the German Bundesrat).

c) Ethereal oils, especially thymol, are being investigated in cooperation with the Bee Research Institute Hohen Neuendorf (Länderinstitut für Bienenkunde). A standardized thymol mono-preparation was investigated for its acaricide effect, side effects, and residues in bee colonies in styrofoam hives in north-central Europe in order to complete the database for approval as a veterinary drug. Thymol was approved as a veterinary drug in 2006 under the trade name Thymovar.

d) Oxalic acid was developed to the final-use stage as a drug in bees by the European Working Group for Integrated Varroa Control (CA 3686). In all EU countries, government approval is only given to a new veterinary medicament for use in treating animal diseases after the EMA, the European Union’s Agency for Evaluating Medical Products, has determined the maximum residue limit (MRL) of the active ingredient allowed in the final food product according to European legislation. This procedure is meant to protect consumers from toxicologically critical residues in foods resulting from medicines used on animals. For oxalic acid no MRL was available. The MRL establishing procedure was started in cooperation with A. Imdorf (Agroscope Liebefeld-Posieux, Swiss Bee Research Centre), J.M Poul (Agence Française de Sécurité Sanitaire des Aliments) and A. Wibbertmann (Fraunhofer Institute for Toxicology and Experimental Medicine), carried out as a joint project of many European countries and successfully finished in December 2003: oxalic acid was listed in Annex II of Council Regulation (EEC) 2377/90 (Rademacher and Imdorf , 2004). This means that the substance is evaluated as not dangerous, and no residue limit is needed to protect the consumer. On this basis every European country can apply for approval and the Concept of Integrated Varroa Control, as recommended by the scientific institutes for bee research, can legally be implemented. It was the first time that scientific institutes and beekeeper organisations worked together on a European level to establish the legal basis for drug approval in bees.

For Germany the formal application process was initiated in May 2004. On December 23, 2005. Oxalic acid was approved by the “Bundesrat” on September 22, 2006, as a veterinary drug for Germany and published in the “Bundesgesetzblatt” in Oktober 2006 (Bundesgesetzblatt Teil I, Nr. 48 vom 26.Oktober 2006). The veterinary drug oxalic acid may be sold only in pharmacies; no prescription is required.

(2) Galenics of varroacides: developing sugar substitutes as carrier for active ingredients in drugs orally toxic to bees

In medical treatments of honey bee colonies against threats as Varroa destructor or other pathogens, one method is to apply an agent with contact toxicity by trickling into the hive. A combination with sugar water supports the distribution and effect of the agent, but also leads to ingestion by the bees. The aim of our studies was to find a substitute to sugar water, which should have the same properties but neither being ingested by the bees, nor being toxic to them. Toxicity and distribution of the substances were tested by single bee treatment and in small units in the laboratory and for visualising internal hive distribution of the substance a Macro CT scanner was used.

(3) Sublethal effects of active ingredients of varroacides on the individual bee and bee colonies

We investigated the effect of organic acids after individual dermal treatment on the pH of parts of the digestive system and the haemolymph. We applied 13C marked acid and use HPLC/MS detection measures.

Furthermore, we study the sublethal effects of organic acids on a number of bee behaviours such as division of labour, activity, olfactory learning and also the longevity. This includes field behavioural observations and training in a classical olfactory conditioning (PER).

(4) Population of dynamics of Varroa destructor

Mites' reproductive success and their behavior in the beehive determine their capacity to cause harm. Our work aims toward a better understanding of the parasite/host biology, in order to develop methods to limit the damage done to the bees.

Using long-term investigations of mite populations, we try to understand their growth as it is influenced by the surroundings and behavior patterns of both mites and bees. Here we study the individual reproduction rates of Varroa destructor, their increase during the yearly life cycle, individual mites' invasion strategies, and invasion pressure on the bee colony.

Selected publications

1. Rademacher, E. (1990) Die Varroatose der Bienen, 149 Seiten, Verlag Schelzky und Jeep. Wissenschaftl. Publ. Berlin, 4. überarbeitete Auflage
2. Rademacher, E. (1995) Eine neue Applikationsform der Ameisensäure (Teil I), ADIZ 7 (29), 6-9
3. Rademacher, E. (1996) Eine neue Applikationsform der Ameisensäure (Teil II), ADIZ 1 (30), 24-26
4. Rademacher, E. , Brückner, D., Otten, Ch., Radtke, J. (1999) Varroatose-Bekämpfung mit Ameisensäure im Applikator bei unterschiedlichen Betriebsweisen und Standortbedingungen, Dtsch. Bienenjournal 9 (7), 4-7
5. Pohl, F. und Rademacher, E. (2000) Medikamenteinsatz im Bienenvolk, Dtsch. Bienenjournal 5 (8), 23-27
6. Rademacher, E. (2000) Ameisensäure im Applikator zugelassen zur Bekämpfung der Varroatose Dtsch. Bienenjournal 8 (8), 6
7. Rademacher, E. and Radtke, J. (2001) Investigations on the use of Thymovar against varroatosis, Apidologie 32 (5), 488-489
8. Rademacher, E. (2001) Milchsäure als Varroatose-Bekämpfungsmittel, ADIZ/die biene /Imkerfreund 12 (35), 28
9. Mutinelli, F., Rademacher, E. (2002) European Legislation Governing the Use of Drugs in Bee Colonies to Control Varroosis: A Case Study, The Regulatory Affairs Journal,13 (5), 401-406
10. Mutinelli, F., Rademacher, E. (2003) The use of drugs to control varroosis in honey bee colonies and European legislation: the current situation, Bee World 84 (2), 55-59
11. Rademacher, E., Otten, Ch. (2003) Bundesrat stimmt Milchsäurezulassung zu, ADIZ/ Imkerfreund/ die biene 8, 17
12. Rademacher, E. (2004) Apothekenpflicht für Ameisensäure und Milchsäure aufgehoben, Dtsch. Bienenjournal 3, 18
13. Rademacher, E, Imdorf, A. (2004) Legalization of the use of oxalic acid in varroa control, Bee world, 85 (4), 70-72
14. Rademacher, E, Harz, M. (2006) Oxalic acid for the control of varroosis in honey bee colonies - a review, Apidologie 37, 98-120
15. Rademacher, E. (2006) Oxalsäure als Tierarzneimittel zur Bekämpfung der Varroose legal einsetzbar, ADIZ/die biene/Imkerfreund, 2,9
16. Rademacher, E, Harz, M. (2006) Effectiveness of Oxalic Acid for Controlling the Varroa Mite, American Bee Journal, 146, 7, 614-617
17. Rademacher, E. (2007) Mitautorin der Broschüre "Varroa unter Kontrolle", Hrsg. Arbeitsgemeinschaft der Institute für Bienenforschung, 23 Seiten, 1. Auflage 2001, 2. Auflage
18. Rademacher, E., Harz, M. (2009) Oxalic acids: Toxicology on Apis mellifera, in: Association of Institutes for Bee Research, Report of the 56th Seminar, Apidologie 40, 6, 651 – 669
19. Harz, M., Mueller, F., Rademacher, E. (2010) Organic acids: Acute toxicity on Apis mellifera and recovery in the haemolymph, Journal of Apicultural Research, Special Issue “Colony Losses”, 49(1): 95-96
20. Raddatz, M., Rademacher, E. (2010) Sublethal effects of oxalic acid on Apis mellifera L. (Hymenoptera:Apidae): Pharmacodynamics, in: Association of Institutes for Bee Research, Report of the 57th Seminar in Bochum, 23-25 March 2010, Apidologie 41 (6) 676-694
21. Rademacher, E., Harz, M. (2011) Application study: hop acids to control varroosis - laboratory trials, in: Association of Institutes for Bee Research, Report of the 58th Seminar in Berlin, 29-31 March 2011 Apidologie 42 (6) 771-796
22. Rademacher, E., Harz, M. (2011) Application study: hop acids to control varroosis - colony trials, in: Association of Institutes for Bee Research, Report of the 58th Seminar in Berlin, 29-31 March 2011 Apidologie 42 (6) 771-796
23. Rademacher, E., Harz, M. (2011) Standardisation of methods: bee and mite toxicity testing in the laboratory, in: Association of Institutes for Bee Research, Report of the 58th Seminar in Berlin, 29-31 March 2011 Apidologie 42 (6) 771-796
24. Blenau, W., Rademacher, E., Baumann, A. (2011) Plant essential oils and formamidines as insecticides/acaricides: what are the molecular targets?, Apidologie DOI: 10.1007/s13592-011-0108-7
25. Schneider, S.,Eisenhardt, D., Rademacher, E. (2011) Sublethal effects of oxalic acid on Apis mellifera L. (Hymenoptera: Apidae): changes in behaviour and longevity, Apidologie DOI: 10.1007/s13592-011-0102-0

For pdf see publications of the Menzel Group

Collaborations

• Bundesministerium für Gesundheit, Kommission F, Bonn/Berlin
• Bundesinstitut für Verbraucherschutz und Lebensmittelsicherheit, Berlin
• Bundesinstitut für Arzneimittel und Medizinprodukte, Bonn
• Europäische Kommission für Tierarzneimittelzulassung (EMA), London
• Naturwissenschaftliche Museen, Berlin
• Deutscher Imkerbund, Bonn
• Länderinstitut für Bienenkunde, Hohen Neuendorf
• Fachzentrum Bienen und Imkerei Rheinland-Pfalz, Mayen
• Forschungsstelle für Bienenkunde, Unviersität Bremen
• Commission of the European Communities: Concerted Action 3686, Coordination of integrated control of Varroa mites COLOSS, BEEDOC; Brüssel
• Agroscope Liebefeld-Posieux, Swiss Bee Research Center, Bern
• Agence Française de Sécurité Sanitaire des Aliments, Laboratoire d’Etudes et de Recherches sur les Médicaments Vétérinaires et les Désinfectants, Unité de Toxicologie Alimentaire, Fougeres Cedex, France
• Fraunhofer Institut für Toxicologie und Experimentelle Medizin, Hannover

External Funding

• Oxalic acid as a veterinary medicament used to fight Varrosis (Bayerisches Staatsministerium für Gesundheit, Ernährung und Verbraucherschutz)
• Bee and mite toxicology of selected substances (pharmaceutucal industry)
• Maximum residue limit (MRL) for oxalic acid (European Project)
• Approval procedures according to national legislation (Deutscher Imkerbund e.V.)
• Galenics (BMBF)
• Sublethal effects (Deutsche Bundesstiftung Umwelt)