# Evaluating the Efficacy of Common Treatments Used for _Vairimorpha_ (_Nosema_) spp. [PERSON]
## 1 Introduction  
The western honey bee, _Apis mellifera_, is an economically important pollinator in agricultural systems and faces stressors such as pathogens, parasites, and pests [1]. _Vairimorpha_ (formerly _Nosema_, [2]) spp. are microsporidian parasites that reproduce in the midgut of honey bees and have been shown to be detrimental to honey bee health [3, 4]. Infections with _Vairimorpha_ spp. alter behavior, reduce immunity to other pathogens, increase energetic demand, and lead to increased mortality of individuals bees [5, 6]. To date, three species of _Vairimorpha_ have been found to infect honey bees; _V. apis_, _V. ceranae_, and _V. neumanni_[7, 8, 9]. These species differ in virulence, geographic range, and clinical signs associated with infection in honey bees [10].  
In North America, fumagillin is the only approved antibiotic treatment for _Vairimorpha_ spp. infections [11]. Fumagillin is a non-specific antibiotic derived from _Aspergillus fumigatus_[12]. Historically, a product called Fumagilin-B (Medivet Pharmaceuticals Ltd., High River, AD, Canada) was the only fumagillin product used in North America. In 2018, Medivet ceased production of this treatment, and Fumadil-B (KBNP, Inc., Anyang, Republic of Korea) is now the commonly used fumagillin-based treatment. While fumagillin products have been shown by some to be effective at reducing _Vairimorpha_ spp. prevalence andintensity [13; 14], others have shown that treatment with fumagillin does not always control _Vairimorpha_ spp. infection [15; 16; 17; 18].  
Some researchers have proposed that proper honey bee nutrition can prevent negative impacts of _Vairimorpha_ spp. in honey bee colonies. Colonies with a high pollen diet have been shown to cope with _Vairimorpha ceranae_ infection better than colonies that consume less pollen [19; 20]. Furthermore, nutritional stress can change honey bee gut microbiota and suppress immune function, thus favoring _V. ceranae_ infection [21]. Manufacturers of certain natural plant products, such as Nozevit (Apivita, Varazdin, Croatia) and Honey-B-Healthy(Honey-B-Healthy, Inc, Cumberland, MD, USA), claim that treatments improve honey bee nutrition and ultimately colony survival following _Vairimorpha_ spp. infection [17; 22]. Similarly, another feeding supplement called HiveAlive(A) (Advance Science Ltd., Galway, Ireland) is purported to support good nutrition and intestinal well-being of honey bees, thereby reducing _V. ceranae_ infection over time [23]. Many beekeepers throughout the world feed Nozevit, Honey-B-Healthy(R), and HiveAlive(R) to their honey bee colonies several times each year with the intention of fortifying their immune response and protecting them from mortality caused by _Vairimorpha_ spp.  
In the present study, we tested _Vairimorpha_ spp. infection control in honey bees by treatments (both registered and unregistered for _Vairimorpha_ spp. control) commonly used by beekeepers. We conducted four separate experiments to test the efficacy of these treatments. In the first experiment, we compared the prevalence and intensity of _V. ceranae_ and the subsequent survival of caged honey bees exposed to _V. ceranae_ and treated with Fumagilin-B, Nozevit Plus, and Honey-B-Healthy(R). In the second experiment, honey bee colonies were treated during the winter with Fumagilin-B and HiveAlive(R) and sampled monthly until spring. In the third and fourth experiments, colonies were treated during the winter with Nozevit Plus and Fumagilin-B following label recommendations for either \"fall\" or \"spring\" treatments. The objective of these experiments was to evaluate the efficacy of different treatments to reduce the prevalence (proportion of individuals infected with _Vairimorpha_ spp.) and intensity (number of _Vairimorpha_ spp. spores per individual) of _Vairimorpha_ spp. infection, and to improve the health of honey bee colonies.