# Concurrent therapeutic and behavioral interventions are associated with a reduced number of emerging Dracunculus medinensis worms in dogs in Chad

## TL;DR

Combining drug treatment and behavior change in dogs significantly reduced Guinea worm infections in Chad.

## Contribution

This study demonstrates that concurrent use of flubendazole and proactive tethering reduces Guinea worm infections in dogs more effectively than either method alone.

## Key findings

- Using flubendazole and proactive tethering together reduced dog infections by 83% compared to baseline.
- Flubendazole alone reduced infections by 63%, while proactive tethering alone reduced them by 55%.
- Combined interventions showed effects 22 months after initial drug administration.

## Abstract

Dracunculus medinensis (Guinea worm; GW) is a parasitic nematode that causes dracunculiasis (Guinea worm disease; GWD). The annual incidence of GWD in humans has been reduced by over 99.9% globally since the 1980s thanks to the implementation of complementary interventions. Dogs are now the primary hosts of GW and impede eradication efforts. The antihelmenthic drug, flubendazole (FLBZ), was suggested as a possible therapeutic intervention after it was found to be partially effective at reducing fertility of D. medinensis in experimentally infected ferrets. A 2019 clinical trial of FLBZ in Chad found no statistically significant difference in GW infections between treated and control dogs, but longer term effects may be observed if FLBZ reduced fertility of D. medinensis. This study leveraged surveillance data from the National Guinea Worm Eradication Program of the monthly count of D. medinensis worms in dogs between January 1, 2019, and September 30, 2021, for 56 villages to examine whether FLBZ would have an observable effect over 33 months and in the presence of another intervention, proactive tethering. We fit hypothesis-informed models of the combined interventions using negative binomial generalized linear mixed models. We averaged the top models together and predicted the number of D. medinensis infections per month for an average village. Based on the model predictions, we observed a clear delineation of effects between March and August 2021, approximately one year after most villages initiated proactive tethering and approximately two years after a few villages initiated FLBZ treatment. During this period, the predicted number of dog infections were reduced by 83% (95% CI, 76% to 88%) when using FLBZ and proactive tethering concurrently, by 63% when using FLBZ alone (95% CI: 44% to 75%), and by 55% when using proactive tethering alone (95% CI: 52% to 58%) compared to baseline control methods. When used together, proactive tethering and FLBZ may be important tools in reducing the village-level D. medinensis burden in dogs.

Guinea worm disease is caused by the nematode Dracunculus medinensis and is classically transmitted to the host by drinking water containing copepods infected with third-stage infectious D. medinensis larvae. Guinea worm disease in humans has been reduced by over 99% since it was targeted for eradication, but increased Guinea worm infections in dogs pose a challenge to the eradication of the disease. Flubendazole is a therapeutic intervention that was found to inhibit embryogenesis of D. medinensis in a ferret model, but a previous clinical trial of flubendazole in dogs found no difference in emerging D. medinensis worms between treated and control dogs. We sought to examine the effects of flubendazole alone and in the presence of another intervention, proactive tethering, by using village level data instead of dog level data. We found that flubendazole alone and when used along with proactive tethering resulted in the lowest number of D. medinensis in dogs beginning 22 months after the first injection of flubendazole. Understanding the individual and concurrent effects of intervention strategies may better inform eradication efforts.