Onchocerciasis

Onchocerciasis: River Blindness

About the Disease

Onchocerca volvulus is second leading infectious cause of blindness worldwide and causes the disease onchocerciasis. The vector of O. volvulus is the black fly (genus: Simulium).


Project by Meredith Maxey [Honors Tutorial College/BIOS]  

References

Worldwide Magnitude
  • 17.7 million are infected with O. volvulus (worm that causes the disease)
  • 99% in Africa
  • 500,000 are visually impaired
  • 270,000 are blind
  • 123 million more are at risk in the 37 endemic countries

eyeball map illustration Picture:  Countries where onchocerciasis is found  Source

Symptoms

Visible “microfilariae” or tiny worms in the eye area

Migration of worm s to upper layers of skin

man with symptoms Blindness                          

Skin rashes/lesions

Skin atrophy

Intense itching

Skin depigmentation

Palpable nodules

 Picture:  Man afflicted with
skin nodules caused
by onchocerciasis 
Source

How does it cause blindness?

Microfilariae migrate to surface of cornea where they are attacked by the immune system.  Punctate keratitis, or inflammation of the cornea, then follows.  This condition can clear up.  However, if the infection is chronic, sclerosing keratitis will result.  Sclerosing keratitis makes the affected area become opaque.  Blindness results if the entire cornea becomes opaque.

Treatment
  • 1980s: Merck & Co. Inc developed Mectizan®                      

  • Derived from  Streptomyces avermitilis

  • Late 1980s: Merck & Co agreed to make donations to all who need the drug, for as long as needed.  This was called the Mectizan Donation Program (MDP).

  • The MDP is widely considered the stimulus for the current global initiative that is centered on providing community-based treatment.

Picture:  Lady dispensing doses of Mectizan.  Source

 
 
 
Ivermectin

This drug paralyzes microfilariae by interfering with their nervous system, but not the human hosts’.  This in turn will prevent the itching caused by the microfilariae.  The drug does not kill the adult worm, however.  It DOES prevent the production of offspring.  This in turn prevents morbidity and transmission.  Ivermectin is commonly known as Mectizan® and Stromectol®.

Mectizan

  • Dosing every 3 to 12 months
  • Merck has provided enough drugs for over 250 million doses
  • Current estimates = 30 million receiving Mectizan® annually
  • Carter Center involved with administration of over 78 million doses…
Onchocerca volvulus

Picture:  O. volvulus , the worm that causes onchocerciasis  Source

  • Second leading infectious cause of blindness worldwide           
  • O. volvulus  causes the disease onchocerciasis      
  • Vector of  O. volvulus  is the black fly (genus:  Simulium )
Life Cycle

Person typically needs to be bitten 100s of times by infected black flies before getting the disease.  This makes it an uncommon disease among visitors; they are not around the flies long enough to receive that many bites.  In Ethiopia, individuals have been found with over 20,000 bites. Female black fly takes blood meal.   Onchocerca volvu lus  larvae enter body through bite and the larvae migrate to subcutaneous tissue. Life cycle continued below. 

Right:  Ethiopia  Source

                                   

 

 

Picture below:  Life Cycle  Source    Form nodules and develop into adult worms

  • New worms = new nodules (2 to 3 worms per nodule)
  • Males can travel amongst nodules to mate

After mating, the resultant eggs develop into microfilariae (which are the larvae form of the nematode)

Microfilariae leave female one by one, up to 1000 per day

Microfilariae migrate around subcutaneous tissue

  • Their death causes characteristic rash/lesions/itching/depigmentation
  • Migration to eye causes blindness

When host is bitten by another fly, microfilariae transferred to fly

Develop into larvae in fly…as described below

Simulium 
  • Genus of black fly
  • O. volvulus  vector
  • Associated with fast-flowing bodies of water

Picture:  Prime example of where the black fly resides  Source

In  Africa, the vector species is  Simulium damnosum
Picture:  Simulium damnosum  Source


In the  Americas, on the other hand, there are three other species identified as vectors.  Those species are as follows:  Simulium metallicumSimulium ochraceum, and  Simulium exiguum.

O. volvulus  in  Simulium

Microfilariae advance to thoracic muscles

  • Differentiation in to L1 larvae within 28 hours            

First molt producing L2 larvae

  • within 96 hours

Second molt producing infective L3

  • Within 7 days
  • Migration to head and mouth

Eradication

Impacts of Blindness

Can be measured in QALYs

  • Quality-Adjusted Life Years
  • Used as an estimate of economic burden of life impairment

Can also be measured using DALYs

  • Disability-Adjust Life Years
  • Method for calculating losses/gains of life expectancy due to prevention, care, rehabilitation, etc

                                                     

Carter Center River Blindness Program                     

1996 – Eradication and control programs initiated in…

Six countries in the Americas (OEPA)

  • Focus on Eradication
  • Brazil, Colombia, Ecuador, Guatemala, Mexico, Venezuela

Five countries in Africa (WHO-APOC)

  • Focus on Control
  • Cameroon, Ethiopia, Nigeria, Sudan, Uganda
How does it work?

Partnership at all levels is necessary, and a few of the cooperating organizations are listed below (by continent)

Americas:

  • Lions Club International Foundation, CDC, Mectizan Donation Program, ministries of health, OEPA, Pan American Health Organization, academic institutions, community

Africa:

  • LCIF, ministries of health, United Nations, WHO, World Bank, UNICEF, APOC, community
Onchocerciasis Elimination Program of the Americas

Defined: “ the technical and coordinating body of a multinational, multiagency coalition working to end illness and transmission of onchocerciasis in [those six countries] by 2007.

 

OEPA History                                                       

Map Source

1992: OEPA started operations

  • Only 41,911 Mectizan treatments

2003: At least 85% treatment coverage in all six countries

  • 15 million estimated eradication cost
  • Gates Foundation initially gave $5 million and matched another 5 million that was made within four years (donations from over 70 sources made this possible)

2006: Percentages maintained, no new blindness

  • But… 500,000 at risk and 180,000 infected
Onchocerciasis Prevents People From…
  • Working

  • Harvesting their crops

  • Receiving an education

  • Taking care of their children

  • Using fertile lands near rivers

Who is most at risk?

Americas

  • Guatemala and Mexico                    

  • Coffee plantations

coffee plantation Picture:  A coffee plantation in Central America   Source

  • Ecuador and Colombia

  • Brazil and Venezuela

  • Yanomami population (Amazon)

Picture:  Yanomami People  Source

Africa

Poor, those who can’t escape/protect themselves from contaminated water

Brief History

1875: John O’Neill first observed microfilariae in West Africa

1925: In Sierra Leone, Donald Blacklock discovered the black fly as the transmission vector of  O. volvulus

1990s:  O. volvulus  eradication efforts begin

Diagnostic Lab Studies
  • Skin snips (3 to 5-mg) to count emerging microfilariae

  • Mazzotti test (DEC side effects, seldom used)

  • ELISAs (finger-stick sample)

    Picture:  An example of an ELISA plate  Source

  • More sensitive, less invasive than snips

  • Can’t distinguish past/current infections (main problem with them)

  • Polymerase Chain Reactions

  • Amplifies repetitive parasite DNA sequence

  • However, they are expensive and invasive

 
New Developments in Diagnostic Methods:
  • Rapid-format antibody card tests
  • Serum samples used to detect antibodies (IgG4) to antigen Ov16
  • Dipstick assay
  • Detect oncho-C27 antigen in tears and urine
  • Only takes 3 hours
  • Strips remain usable for up to 8 months
How big are these worms?

Picture:   O. volvulus  worms  Source

  • Adult females 45-50cm by 300 um

  • Adult males 20-40mm by 200um

  • Microfilariae 250um by 7um  

O. Volvulus  Incubation Period

Microfilariae usually found about 1 year after bite

  • In Guatemala, found in infants as young as 6 months of age   

  Map Source

  • Over 100 million microfilariae found in people suffering the most severe cases
  • Vector can be infectious 7 days after blood meal
  • Can’t transfer person to person
O. volvulus  Survival Rates in Host
  • Adults can live for 8-10 years in nodules (onchocercomas*)
    • concentric bands of fibrous tissue 

Picture:  Microscopic view of onchocercomas  Source

  • Not directly harmful
  • Microfilariae can survive for about 6 months
O. volvulus  & Immune System

Adults in nodules; immune system has limited access       

  • Surrounded by eosinophils and lymphocytes

Microfilariae induce inflammatory response              

  • Especially after their death
  • Wolbachia -derived antigens as a trigger (more on  Wolbachia  below)
Recent Research                                                            

Symbiotic relationship between  Wolbachia  bacteria and filarial nematodes (including  O. volvulus).   Recent research has shown that  Wolbachia  might be essential to the fertility of these nematodes.

Picture:  Black arrow is pointing to  Wolbachia   Source

The endotoxins released by the  Wolbachia  upon the death of the microfilariae are now suspected as the cause of most of the symptoms associated with onchocerciasis including blindness and corneal inflammation

 

Antibiotic therapy effective?  
Researchers studying whether giving antibiotics to patients (and thus killing the  Wolbachia ) would relieve symptoms…

 

Eradication

WHO Programs

African Program for Onchocerciasis Control (APOC)            Map:  APOC Countries  S ource

Onchocerciasis Control Program (OCP)

  • Both are/were funded by the World Bank with coverage of over 90 million people in 19 countries

1995: APOC stated focus on empowering the community to promote control efforts.  In the past 8 years, over 34 million have been treated

OCP – Vector Control

WHO launched in 1974 for West Africa

  • World Bank
  • United Nations
  • Food and Agricultural Organization

Coverage = 11 countries and 30 million people

OCP History

1974: Aircraft spray larvicide                 Picture:  Helicopter spraying larvicide  Source

1987: Mectizan administration incorporated

2002: OCP closed because transmission had ceased

  • Still an example of effective partnership
Treatment Summary        

 Graph:  Increase in millions of people treated through those three organizations  Source

 

The Future

 Much progress has been made. As you can see from the treatment summary, fertile lands will be able to be reclaimed and local economies revived if progress continues.