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Filarial Diseases and the Nobel Prize for Medicine: Going Even Further for Neglected Patients

Claudia Pena Rossi of the Drugs for Neglected Diseases initiative reflects on the Nobel Prize winning work of William C. Campbell and Satoshi Ōmura and the current challenges in the fight against fiarial diseases.

The Nobel Prize for Medicine is certainly on the minds of many in Philadelphia as people arrive for the Annual Meeting of the American Society for Tropical Medicine and Hygiene (ASTMH). Our fellow scientists and researchers are electrified that such eminent researchers – William C. Campbell, Satoshi Ōmura, and Youyou Tu – received just recognition for their research. As we meet, we hope to take the opportunity to reflect on these discoveries as well as look forward to completing the task of eliminating fiarial diseases.

Part of the Nobel Prize this year awards a discovery which has and will continue to reduce the suffering of millions from filarial diseases, namely river blindness (onchocerciasis) and lymphatic filariasis, commonly known as elephantiasis.

A patient in Ghana showing lymphedema (swelling) of the leg. Image credit: DNDi/Cosmos/Sylvain Cherkaoui
A patient in Ghana showing lymphedema (swelling) of the leg.
Image credit: DNDi/Cosmos/Sylvain Cherkaoui

The story began when Dr. Ōmurao originally identified strains of Streptomyces bacteria in soil in the 1970s. These compounds were then chemically modified by Dr. Campbell’s team to become a potent veterinary drug against the parasitic helminth worms that cause filarial disease. Dr. Campbell suggested to use this drug, called ivermectin, in humans affected by river blindness.

The rest of the story is well-known in public health: The World Health Organization (WHO) and the World Bank teamed up with the pharmaceutical industry to implement large-scale mass drug administration (MDA) programs with ivermectin and other treatments.

Ivermectin was an incredible discovery. It is a safe and extremely effective drug that kills juvenile worms, or microfilariae. Mosquitoes and blackflies transmit filarial diseases by passing on microfilariae during their blood meals, so killing microfilariae can prevent new infections. Overall progress has been very impressive. Many formerly-endemic regions in Latin America, Africa, and Asia are reporting or will achieve in the coming years, the elimination of river blindness and lymphatic filariasis.

Yet millions of people in the poorest communities are still affected by these illnesses. River blindness remains the world’s second leading cause of blindness and causes a host of other debilitating symptoms, including intense itching. Lymphatic filariasis leads to massive swelling of legs and genitals and is the second cause of chronic disability worldwide.  Both diseases exact a terrible toll, with deep socio-economic impact while causing stigma, discrimination, and psychological scars on patients.

Ivermectin does have some limitations. It may cause severe side effects for those infected with another helminth worm known as Loa loa. Because of fear of adverse effects, MDA programs have been slowed down in co-endemic regions of some Central African countries. Another challenge: because ivermectin only kills juvenile worms, treatment has to be repeated every year, for the life span of the adult worm. Finally, the drug is only available through MDA programs and given once or twice a year. Because of this health providers do not often have access to the treatment for their patients.

New tools are needed to improve patient treatment and to support elimination goals through MDA strategies.

The great work started by Drs. Campbell and Ōmura continues, with a growing pipeline of new tools to fill the current gaps in our response to filarial diseases. Among those being discussed this week and next at ASTMH:

  • Macrofilaricidal” treatments: A drug that can kill adult filarial worms is needed. Macrofilaricidal drugs could be an essential case management tool for health workers in rural areas and is the goal of a research and development (R&D) program at the Drugs for Neglected Diseases initiative (DNDi). New treatments are also needed for areas where Loa-loa is co-endemic.
  • Endosymbiotic bacteria: One promising area of macrofilaricidal research are antibiotics that target the endosymbiotic Wolbachia bacteria that are essential to life cycle of filarial worms.
  • Diagnostics: Until recently, the only diagnostics available in the field for river blindness was a labor-intensive procedure known as a skin snip. New point-of-care tests were launched by PATH in 2014 and 2015.
  • Vaccines: A diverse group of stakeholders known as The Onchocerciasis Vaccine for Africa (TOVA) Initiative is investigating vaccine candidates to protect children, especially those living in Loa loa endemic areas.

More than 35 years have passed since the discovery of ivermectin, which has been instrumental in reducing the burden of these disease. But despite their shrinking numbers, patients suffering from filarial disease deserve a new dose of innovation, in the spirit of Drs. Campbell and Ōmura. With these new tools, we will surely be on the path to elimination.

An ASTMH Side Event on Monday, October 26th at the Perelman School of Medicine at the University of Pennsylvania will explore in-depth these new tools being developed for filarial diseases. More info here.

Top image credit: Christian Schnettelker, Flickr CC BY

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Dr. Claudia Pena Rossi is Head of the Filariasis Clinical Program at the Drugs for Neglected Diseases initiative.

 

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