Lymphatic Filariasis :Doxycycline

• Wolbachia endosymbionts of filarial worms had become the target in finding the therapeutic agents.
• Wolbachia bacteria are essential symbionts of the major pathogenic filarial nematode parasites of humans including 
• Wuchereria bancrofti
• Brugia malayi
• Onchocerca volvulus are important both as chemotherapeutic targets and disease-causing organisms.
• The most promising antiwolbachial agent is doxycycline, as its ability to clear infection and also ameliorate filarial pathology has consistently been proven by several investigators

Mechanism of Action

• Doxycycline is a bacteriostatic drug that inhibits protein synthesis in endosymbiotic bacteria referred to as Wolbachia present in filarial nematodes including Wuchereria bancrofti, Brugia malayi and Onchocerca volvulus.
• Doxycycline could be the missing link in our effort to eliminate filariasis as it depletes Wolbachia, kills adult worms, depletes baby worms and improves the condition of individuals with chronic stages of both onchocerciasis and lymphatic filariasis.

Effectiveness

• The macrofilaricidal activity of the 6 and 4-week regimens were comparable (92 and 83%, respectively), whereas there was no macrofilaricidal activity in the 3-week group.
• Wolbachia loads were only reduced by 80%, in contrast to the other regimens in which a more than 90% reduction of Wolbachia copy numbers were monitored by quantitative PCR.
• There seems to be a minimum cumulative dose of doxycycline required for a more than 90% Wolbachia reduction, which subsequently leads to a macrofilaricidal effect in lymphatic filariasis

Challenges

• Doxycycline is contraindicated in those with allergy or sensitivity to the drug, pregnant and lactating women and children below 8 years because of its deleterious effects on bone and tooth development
• The gold standard for doxycycline treatment in filariasis is a daily dose of 200 mg for 6 weeks. 
• This relatively long duration of treatment creates further logistical challenges as the treatment must constantly be monitored for adverse effects. Such long antibiotic regimes are likely to increase the pace of the development of resistance.

Reference:

The Case for Doxycycline in Our Battle against Filariasis. Kenneth Bentum, Sept 2015