Research Agenda for Global Blindness Prevention:

Clinical Conditions: 3. Onchocerciasis

Research opportunities

• Short-Term (primarily operational research, much of which is already ongoing)
  
  
• Medium-Term (primarily delivery of drugs)
  
  
• Long-Term

Global programs over the last three decades have dramatically reduced the incidence of new infections with onchocera volvulus and their progression to blindness.

Through a combination of environmental interventions and widespread treatment with Mectizan, onchocerciasis should cease to be a cause of new blindness reaching a level of "public health significance" by 2010.

This does not mean that further research is not needed.

Most modeling studies suggest that at present coverage rates (65%), it will take 40 years before Mectizan distribution can be safely discontinued.

At 80-85% coverage, which may prove possible with more intensive and effective delivery systems, the program must still be sustained for more than 25 years.

In addition, new drugs are needed that will:

1. Have safe and effective macrofilaricidal activity. Their use would dramatically shorten the need for sustained, repeated microfilaricidal administration
   
   
2. Provide a backup to Mectizan should microfilaria develop resistance
   
   
3. Prove safer for use in populations with heavy, co-existing infections
   
   
4. Allow for treatment of children and pregnant women, thereby increasing coverage (leaving a smaller reservoir of persistent infection).

To enhance and sustain large-scale treatment (to exceed 80 million people annually) requires alternatives to, or strengthening of, the present system of "Community Directed Treatment Intervention" (CDTI).

A potentially important and recent observation (Science, March 8, 2002, "The Role of Endosymbiotic Wolbachia Bacteria in the Pathogenesis of River Blindness") suggests that Wolbachia, an endosymbiotic bacterium present in all developmental stages of O. volvulus, are required for production of microfilaria and for much of the inflammatory reaction associated with microfilarial death. As these bacteria are susceptible to antibiotics, it may open a new approach to control of onchocerciasis.

Short-Term

(primarily operational research, much of which is already ongoing):

• Investigate serious side-effects of Mectizan among populations in loa loa endemic areas
• Determine the role of interactions between Mectizan, alcohol consumption, and exposure to other toxic substances and serious side-effects observed in those under treatment (especially encephalopathy

Medium-Term

(primarily delivery of drugs):

• Develop ways to ensure long-term sustainability and to increase coverage/compliance of Mectizan treatment programs
  
  
• Identify issues related to the use of CDD (volunteer community distributors) and complementary programs addressing other needs that might be added onto this unique delivery system (reaching otherwise underserved populations)
  
  
• Follow up preliminary data that suggests increasing the frequency of Mectizan dosing might further block embryogenesis (more fully blocking transmission). Comparisons between alternative treatment regimens might identify ways to reduce the duration required by intervention programs.

Long-Term:

• Develop a safe macrofilaricide
  
  
• Develop an alternative to Mectizan in case resistance should develop
  
  
• Delineate the role of Wolbachia in the pathogenesis of river blindness, and the potential role of alternative interventions (antibiotics that destroy the bacteria; drugs that block its inflammatory effects; etc.)
  
  
• Evaluate the long-term impact of Mectizan on the incidence and severity of retinitis/optic neuritis

Next: 4. Xerophthalmia

Also see: Table of Contents of the Research Agenda for Global Blindness Prevention