Efficacy of test and treat with doxycycline on palpable nodules, microfilarial load and Wolbachia density in onchocerciasis infected persons in communities with persistent transmission in South-West Cameroon
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Introduction
Onchocerciasis is targeted for elimination with community-directed treatment with ivermectin (CDTI). Alternative strategies are needed in areas where transmission persists despite long-term CDTI and/or are co-endemic with loiasis. This study assessed the efficacy of 35-day treatment with 100mg doxycycline on Wolbachia density at 6 months and microfilaridermia and palpable nodules at 30 months post-treatment.
Methods
A treatment follow-up study was conducted in 20 high-transmission onchocerciasis communities in a co-endemic loiasis area of South-West Cameroon. Community-based directly observed treatment with 100mg doxycycline was administered to community members aged ≥9 years. Wolbachia clearance at 6-months and treatment efficacy on microfilaridermia and palpable nodules were assessed at 30-months post treatment. Factors associated with reductions in microfilaridermia post treatment, including adherence to doxycycline treatment were assessed with mixed-effects logistic regression.
Results
Over 92% (2835/3080) of eligible participants took 35 days of 100mg doxycycline over 5 or 6 weeks. This regimen achieved a 62.8% microfilaridermia reduction and 99% palpable nodule reduction in the 720 participants included at follow-up. Wolbachia depletion was observed in 92% of skin samples at 6 months post treatment. The most important factor associated with microfilaridermia after 30 months was having missed at least 7 doxycycline consecutive doses (OR 3.11, 95%CI: 1.17-8.26). Incomplete treatment to a lesser extent was not associated with reduced efficacy at follow-up.
Conclusion
This large-scale community intervention shows that a 5-week treatment with 100mg doxycycline is feasible and has high curative efficacy against adult O. volvulus as measured by the dramatic reduction in the proportion of palpable nodules at 30-months post treatment. The high efficacy shows the tremendous potential of anti- Wolbachia drugs as part of the arsenal for onchocerciasis elimination and paves the way for the next generation of anti- Wolbachia drugs with shorter treatment courses, which will facilitate the implementation of alternative strategies to accelerate onchocerciasis elimination.
Key questions box
What is already known?
The mutualistic symbiosis of Wolbachia bacteria with their filarial nematode hosts has been exploited as a drug target, to deliver safe curative therapy, which provides an important alternative strategy to facilitate elimination of onchocerciasis transmission. Alternative strategies are required in areas where existing treatment strategies are failing or compromised by safety risks where co-endemic loiaisis occurs.
What are the new findings?
Community-based test and treat with doxycycline for 5 weeks achieved a 63% reduction in microfilaridermia and a 99% reduction in palpable adult parasite nodules 30-months post treatment.
What do those findings imply?
This study provides the first evidence of a complete curative reabsorption of subcutaneous adult parasite nodules and validates anti- Wolbachia therapy as an effective cure for onchocerciasis and a feasible alternative strategy to facilitate onchocerciasis elimination.
