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A Parasitic Nematode, Wolbachia Bacteria, and Onchocerciasis

Linda Crampton is a writer and teacher with a first-class honors degree in biology. She often writes about the scientific basis of disease.

An adult black fly with the nematode that causes river blindness emerging from an antenna (magnified 100 times)

An adult black fly with the nematode that causes river blindness emerging from an antenna (magnified 100 times)

What Is Onchocerciasis or River Blindness?

Onchocerciasis or river blindness is a serious disease that causes skin and eye inflammation. The skin inflammation results in severe, debilitating itching and changes in appearance. The eye inflammation sometimes leads to blindness.

The disease is triggered by the bite of a black fly, which is a blood-sucking insect in the family Simuliidae. The fly isn't the direct cause of the disease, however. Its bite inserts a parasitic nematode—a type of roundworm—into its victim's body. This leads to the often devastating symptoms of the disease. A bacterium named Wolbachia that lives inside the nematode is thought to contribute to the symptoms. The technical term for the illness is derived from Onchocerca volvulus, the nematode's scientific name.

The black fly breeds in fast-flowing rivers. Onchocerciasis is also known as river blindness because it affects people who live near rivers or streams. Most victims of the disease live in Africa south of the Sahara, but some people in Central and South America and in Sudan and Yemen have been affected as well.

The Global Burden of Disease Study estimated in 2017 that there were 20.9 million prevalent O. volvulus infections worldwide: 14.6 million of the infected people had skin disease and 1.15 million had vision loss

— World Health Organization (WHO)

What Are Nematodes?

Nematodes belong to the phylum Nematoda. They are also known as roundworms. Their bodies are worm-like in shape, but the animals aren’t internally segmented and aren’t closely related to earthworms, which belong to a different phylum. Some roundworms are much longer than earthworms, but others are much shorter. Many are microscopic.

Nematodes are abundant animals. They are found in many different habitats and climates. Some are parasites and others are free living. A significant number cause disease in humans. Examples include hookworms, pinworms, whipworms, and Ascaris, which causes a disorder called ascariasis.

A soybean cyst nematode and an egg (colourized scanning electron micrograph)

A soybean cyst nematode and an egg (colourized scanning electron micrograph)

Onchocerca Infection and Nourishment

When a black fly in the genus Simulium bites a human, larvae of Onchocerca volvulus escape from the fly's saliva and enter the person's bloodstream. The larvae then leave the person's blood and enter the skin, settling in subcutaneous tissue (located just below the skiin) or the hypodermis (the deepest layer of the skin). Here they complete their development to adulthood inside nodules. The adult nematodes in the nodules may live for as long as fifteen years.

The adult worms are long and slender. Mature females are 33 to 50 cm in length (1.1 to 1.6 feet) but only 0.27 to 0.40 millimeters (0.011 to 0.016 inches) in width. Males are shorter and narrower than females. They reach only 5 cm in length.

The nematodes are believed to either ingest blood or to absorb blood nutrients through their skin. Nodules contain lots of blood vessels to nourish the roundworms. It's thought that the worms stimulate the formation of these blood vessels.

Production of Microfilariae

Male and female nematodes mate inside the nodules, producing eggs that hatch into tiny microfilariae. One female can release 1000 or more microfilariae per day. Each one may live for as long as two years. The female roundworm is capable of producing eggs for about nine to eleven years and possibly for longer.

The microfilariae leave the nodules and travel through the subcutaneous tissue. They may eventually reach the eye, where they may affect vision. In a severe infection, they may also enter the blood, urine, or sputum.

Researchers have discovered that microfilariae cause most of the harmful effects of the disease when they die. The body mounts a very strong inflammatory response at this time, which is a major contributor to the problem.

An Onchocerca volvulus microfilaria has a curved and pointed tail.

An Onchocerca volvulus microfilaria has a curved and pointed tail.

The Parasite in the Black Fly's Body

When a black fly bites an infected person and sucks up some of the person's blood, it withdraws microfilariae from the victim's body. These enter the black fly's gut along with the blood. The microfilariae then travel through the wall of the gut and settle in the thoracic muscles of the insect. Here they change into different larval forms, as shown in the illustration below. The larvae eventually migrate to the fly's head and mouth parts and may infect a new person when the fly bites another human.

Though the second-stage larva (L2) does exist, it isn't shown in the illustration. L1 to L3 larvae are found in the black fly's body. The fly sends the L3 form into a person's blood. This form then becomes an adult inside the person and produces microfilariae. Some of these enter a fly's body during a bite and the cycle begins again.

Release of a Bacterium Named Wolbachia

When microfilariae die inside humans, a bacterium called Wolbachia is released from the bodies of the nematodes. This bacterium normally lives inside the cells of the worms and may play an essential role in their development. It's thought that instead of being a parasite in the roundworm's body, Wolbachia may actually be helpful for the animal. It's classified as an endosymbiont, or an organism that lives inside another one. Endosymbionts are generally not parasites. At least in some of its other hosts, however, Wolbachia has certain features that resemble those of parasites.

It's thought that the bacterium may play a role in the river blindness disease process in humans. The release of Wolbachia from the dead microfilariae may be part of the reason for the body's inflammatory response and could contribute to the unpleasant and potentially debilitating symptoms of onchocerciasis. The study of Wolbachia's role in river blindness is of more than academic interest. It could lead to better treatments for the disease.

Wolbachia wasn't discovered until 1924. It has since been found in many invertebrates, especially insects. Despite the fact that it consists of a single cell, it controls its insect host to favour its own reproductive success. It's hard for scientists to study the bacterium because it isn't easy to keep alive outside of its host. Wolbachia is an interesting and significant organism.

Wolbachia (the large, roughly circular structures) inside the cell of an insect

Wolbachia (the large, roughly circular structures) inside the cell of an insect

The bacterial endosymbionts are essential for normal development of larvae and embryos and may support the long-term survival of adult worms.

— Francesca Tamarozzi et al, Clinical Microbiology Reviews (with respect to Wolbachia)

Possible Symptoms of Onchocerciasis

One of the first symptoms of onchocerciasis is a skin rash with intense itching. The itching can make sleeping extremely difficult. Lacerations may appear on the skin as the person frantically scratches. There may also be visible nodules where the adult roundworms congregate.

Later there may be other skin changes, which may be disfiguring. The changes may not be the same in everyone and may change over time in a single person. Some people develop thickened areas of skin. In some cases, the skin loses its elasticity and develops hanging folds. Sometimes white patches form where pigment has been lost. In other cases, patches with too much pigment appear. The resulting colour pattern is sometimes called "leopard skin." Dry and scaly skin referred to as "lizard skin" develops in some people.

The most serious effects of the infection are the life-altering itching and the eye disease. The inflammation damages the normally transparent layer over the surface of the eye, or the cornea, as well as injuring deeper parts of the eye. The changes may eventually prevent the person from seeing. The blindness is usually the last symptom to appear and develops in adults and older people rather than in children. The Sightsavers website states if a person is infected at birth and is untreated, they have a high chance of being blind by the time they reach forty years of age.

Social Effects of the Disease

It's usually impossible for people in infected areas to avoid contact with a river or stream. River blindness generally develops in rural areas where the people are dependent on the land and water for their survival. They catch fish from the river and also use it to wash or to collect water for their village. They are repeatedly being exposed to black flies, which are most common around the water.

Severe onchocerciasis is disabling for the affected person, but it has also damaged communities. Sometimes villages with good farmland have been abandoned due to the prevalence of the disease. Young and healthy people have been especially keen to leave an affected community. This has meant fewer workers to care for crops and famine or poverty for the remaining members of the group. Children have been unable to go to school because they have to look after blind relatives. Sometimes the whole community has moved to an upland area, which is further away from the black flies but has less productive soil than the valley. This has cause increased hardship for the group.

Onchocerciasis Treatment

The treatment for Onchocerciasis is a medication called ivermectin or Mectizan® (a brand name for the drug). The medication kills the nematode microfilariae that are responsible for the disease symptoms. It doesn't kill the adults, however. An antibiotic that kills Wolbachia is sometimes administered after the Mectizan in order to kill bacteria released from the microfilariae. The antibiotic is often doxycycline. Ivermectin gradually kills the existing microfilariae and also suppresses their production for several months.

Mectizan has been donated by its manufacturer, Merck, since 1987. Merck has pledged to provide the drug for as long as necessary and in whatever quantity is needed. The medication stops the itching and prevents further eye damage. Since it kills the microfilariae that enter black flies when they suck up human blood, it also stops the transmission of the disease. The medication is given to all members of a community, even those that aren't infected. Although Mectizan is free, there is still a cost involved in transporting the drug to all the areas that need it.

One or two doses of Mectizan are required each year for at least least ten to fifteen years (the estimated lifespan of the worms). The CDC and WHO recommendations with respect to these numbers are slightly different, as shown in the quotes below. It's uncertain if treatment can then be stopped or if there is a danger of reinfection. The evidence suggests that in at least some areas it's safe to stop treatment at that time, as long as a patient is not exhibiting any symptoms.

In 2018, a drug called moxidectin was approved for river blindness treatment by the FDA (Food and Drug Administration) in the United States. The drug appears to be even more effective than ivermectin.

WHO recommends treating onchocerciasis with ivermectin at least once yearly for between 10 to 15 years.

— World Health Organization

Ivermectin Creation and Effects

The process that led to the creation of ivermectin is interesting. The medication is derived from a chemical created by a soil bacterium. The two scientists who made the discovery received a Nobel Prize for Physiology or Medicine in 2015. The forerunner of the drug was actually discovered in the 1970s, however.

Satoshi Ōmura is a Japanese microbiologist who has investigated a soil bacterium named Streptomyces. The genus was already known when he began his research, but Ōmura discovered some new strains that produced medicinal chemicals. He was able to culture these strains in the laboratory. A strain of Streptomyces avermitilis seemed to be the most promising with respect to producing medicines.

William C. Campbell is a parasite biologist in the United States. He obtained the Streptomyces strain from Ōmura and found that a chemical that it produced killed parasites in animals. The chemical was named avermectin. It was then modified to make it even more effective and called ivermectin. Ivermectin was later found to be beneficial for human diseases because it killed the parasites involved in river blindness and in a disease called lymphatic filariasis.

Omura and Campbell's Nobel Prize for Physiology or Medicine was a joint award with Tu Youyou, a Chinese scientist. She received her award for the discovery that artemisinin was an effective treatment for malaria.

The recommended treatment is ivermectin, which will need to be given every 6 months for the life span of the adult worms (i.e., 10–15 years) or for as long as the infected person has evidence of skin or eye infection.

— Centers for Disease Control and Prevention (CDC)

River Blindness Treatment Problems

Ivermectin is a very useful drug for river blindness, but it's not perfect. One problem is that it cannot be used to treat people infected with the Loa loa parasite, another type of roundworm, since in these people the drug may be deadly. Other control methods have to be used in areas affected by Loa loa.

Black flies have been killed by insecticides in some areas as a control mechanism for onchocerciasis, but this method also has problems. The insecticide is expensive and needs to be applied repeatedly. In addition, there are concerns about the safety of pesticides for human health and for the environment.

Disease Risk

River blindness is most common in rural villages that are located by rivers or streams that are infested with black flies. Health experts say that temporary visitors are not likely to develop the disease, since the appearance of symptoms and the severity of river blindness depend on the number of black fly bites received. The risk increases slightly for visitors who stay in an infected area for longer than normal, such as aid workers, field scientists, and military personnel. Visitors are advised to use protection methods such as insect repellents and bed nets.

Eliminating River Blindness

Eliminating river blindness from the planet is a wonderful goal but an ambitious task. In some parts of the world, the task is progressing well, while in others more work is needed. Mectizan is an effective treatment (at least at the moment). Merck's generosity has been essential in the treatment plan so far.

Another helpful component in the elimination program has been the determination of certain people in Africa to solve the problem. These people include not only doctors, health workers, and health organizations, but also community representatives. The local people have helped to educate their communities about the medication. In some cases, they are in charge of distributing the Mectizan and maintaining written records related to the distribution.

Progress in Defeating the Disease

The Carter Center is an organization whose aim is to encourage peace and reduce disease. It was founded by former U.S. President Jimmy Carter and his wife Rosalynn. According to the center, transmission of river blindness ended in 2013 in Columbia, in 2014 in Ecuador, in 2015 in Mexico, and in 2016 in Guatemala. The effort to prevent transmission is continuing in Brazil, Ethiopia, Nigeria, Sudan, Uganda, and Venezuela.

Some people in Yemen have a form of onchocerciasis, but the civil war there has caused aid problems. Nevertheless, in January, 2019, almost half a million people received treatment by Mectizan. The number was estimated to be 90% of the people who were infected. Interestingly, WHO says that in Yemen the severe skin problems caused by the parasite exist, but there is no record of vision loss caused by the nematode. The local disease is known as onchodermatitis. It seems that there are still things to learn about the parasite and its effects.

Most of the world's cases of river blindness occur in Africa. Even here, progress is being made. In some previously affected parts of Africa, new cases are no longer appearing and the focus has shifted to helping people who have already become blind. In other areas, the disease is still being transmitted.

A common symbol of onchoceriasis is a child leading a blind adult around with a stick. The child holds one end of the stick and the adult holds the other. Hopefully, this sad symbol will gradually fade as the disease continues to be eliminated from the world.

References

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2012 Linda Crampton

Comments

Linda Crampton (author) from British Columbia, Canada on December 27, 2012:

Thanks for the visit, Peg. I appreciate your comment. I hope you had a wonderful Christmas and that the new year is very happy for you, too!

Peg Cole from Northeast of Dallas, Texas on December 27, 2012:

This is a fascinating article about River Blindness and its causes. I learned a lot from your well presented information. Hard to believe we still have so much medical distance left to travel to cure and prevent diseases like this one.

Hope you had a great Christmas and wishing you a Happy New Year!

Linda Crampton (author) from British Columbia, Canada on December 26, 2012:

I hope that you had a great Christmas too, drbj, and that the upcoming new year is wonderful for you as well! Thank you very much for the visit and the comment.

drbj and sherry from south Florida on December 26, 2012:

What a terrible disease, Alicia. Nice to know that Merck is involved in providing free medication for those afflicted living in rural villages. Perhaps one day soon onchocerciasis may be eliminated as a result of their assistance.

Hope you had a very merry Christmas. Know that the New Year is going to be wonderful for you. Trust me.

Linda Crampton (author) from British Columbia, Canada on December 23, 2012:

Thanks for the comment, Bill. I hope that you and Bev have a very merry Christmas too! Thank you for your friendship as well. It has been wonderful reading your hubs and getting to know you.

Bill Holland from Olympia, WA on December 23, 2012:

Nasty stuff, and good information!

Wishing you a very Merry Christmas, Alicia. Thank you for your friendship this past year.

bill