Biology 103
2005 Final Paper
On Serendip

Onchocherciasis, commonly referred to as river blindness, is the world's second leading infectious cause of blindness. This disease is endemic in thirty-six countries, thirty of which are in sub-Saharan Africa, the remaining six in Latin America, Yemen, and the Arabian peninsula. A total of 18 million people are infected with the disease, 99% of the cases being reported in Africa. Of those infected by the disease, over 6.5 million people suffer from severe itching or dermatitis, 800,000 people are visually impaired, and over 270,000 are blind (1). While scientists and humanitarians worldwide have worked to develop drugs, surgical methods, and pesticide spraying techniques to control the virulence of this disease, there is currently no cure. Furthermore, some of the drugs that have been administered have caused side effects as harmful as the disease itself. However, the problems behind eradicating onchocherciasis seem to extend beyond the limitations of Western medicine, including weak infrastructure and a lack of leadership and education in African countries.

Onchocerciasis is commonly referred to as river blindness because the blackfly that carries the disease breeds in fast flowing rivers and streams in inter-tropical zones. Therefore, the rich fertile river valleys in sub-Saharan Africa are perfect breeding grounds for the blackfly to flourish. In fact, in some West African countries, about 50% of the men over 40 years old are blind as a result of the disease (2). The life-cycle of the disease begins when a parasitized female blackfly takes a blood-meal from a human host. The host's skin is pulled apart by the fly's teeth and sliced by its mandibles. A pool of blood is pumped into the blackfly, saliva passes into to the pool, and the infected Onchocerca larvae are transmitted from the blackfly into the host's skin.

The larvae then migrate to the subcutaneous tissue, which contains fat and connective tissue that surrounds larger blood vessels and nerves. In the subcutaenous tissue, the larvae form thick, fibrous, nodules called onchocercomas where they spend one to three months maturing and where they can live for up to fourteen years (2). Within ten to twelve months after the initial infection, adult female worms start producing microfilariae. The microfilariae have pointed tails, elongated posterior nuclei and paired anterior nuclei. Each female can produce between 1000 and 1900 microfilariae per day. The maximum production of these offspring occurs during the first 5 years of the female worm's reproductive life (3).

The eggs containg the microfilariae mature internally within the female worm and are then released from her body one at a time. These microfilariae then migrate from the nodules to the skin where they wait to be taken up by a black fly. When the infected host is bitten by another female fly, microfilariae are transferred from the host to the blackfly, where they develop into infective larvae, and the life-cycle of onchocerciasis continues (3).

In response to the migration of microfilariae to the skin, white blood cells release cytokines that damage the surrounding tissue and cause inflammation. This kills the microfilariae but it is also the cause of the morbidity associated with the disease. When the microfilariae die, the infected human's skin can become swollen and thick, a condition often called lizard skin and the skin can become lax as a result of the loss of elastic fibers, prominently found in the areas around the scrotum (often called the 'hanging groin' effect). Lesions, intense itching, and skin depigmentation are other common side effects of the disease (2).

The most serious side effect of onchocerciasis is blindness, another consequence of the immune system's reaction to the microfilariae. The microfilariae migrate to the surface of cornea, where they are killed by the immune system. In the damaged area, punctuate keratitis occurs (inflammation of the cornea), which will clear up if the inflammation decreases. However, if the infection is chronic, sclerosing keratitis can occur, making the affected area opaque. Over time, the entire cornea can become opaque, causing blindness (4).

Larvicide spraying is one effort that has been used to combat the transmission of ochocerciasis. This was first done by the Onchocerciasis Control Programme (OCP), a group that combined efforts with the World Health organization and three other United Nations agencies in the early 1970's to assist these ailing countries. The OCP sprayed larvicide over fast flowing rivers in eleven countries in West Africa to control black fly populations. The goal of larvicide spraying was to kill the larvae of the blackfly before it became adult, thereby controlling the black fly vector populations. Each week breeding sites in rivers and streams were "bombed" with the aerial application of larvicide. While this operation was relatively successful in controlling the disease in the open savanna, due to the difficulties concerning aerial access, it could not be used in rainforest areas (5).

In terms of drug distribution, Diethylcarbamazine (DEC), was administered to treat ochocerciasis in endemic areas. It was developed during the Second World War and was given to Australian and American soldiers fighting in the Pacific islands that were infected lymphatic filariasis (caused by thread-like parasitic worms that damage the human lymphatic system). In many cases, the drug would slow and even stop the progression of filariasis. After the war, DEC was used to treat onchocerciasis and was found to have a temporary holding effect on the disease. However, this drug is no longer recommended to distribute to onchocerciasis patients because of reported serious side effects, including irreversible eye damage, rash, peeling of the skin, diarrhea, and kidney damage. Severe side effects are attributed to the sudden death of billions of microfilariae, also known as the Mazzotti reaction (2).

Suramin is another drug that has been used to try to control the effects of onchocerciasis. Suramin is administered by intravenous injection, given in six incremental weekly doses. It is most effective in treating trypanosomiasis (sleeping sickness), attacking the parasites as they circulate in the bloodstream. When Suramin was administered to onchocerciasis patients it was effective in killing the adult worm. However, because of its intrinsic toxicity, severe adverse effects were reported, including thrombocytopenia (presence of relatively few platelets in blood), neutropenia (a haematological disorder), photophobia (excessive sensitivity to light), foreign body sensation, edema (swelling of any organ or tissue due to accumulation of excess fluid), cornea deposits, and a high incidence of optic atrophy (6).

Nodulectation was a surgical procedure used to try to permanently eradicate the disease from the infected human. In a nodulectomy, the nodules which harbor female Onchocerca volvulus are surgically removed from the skin of infected humans. These procedures are performed in hopes of interrupting the transmission of the disease by removing the parasites from the human population. Unfortunately, while nodulectomies do assist in reducing the intensity of the disease, new nodules continue to appear in the infected human from the maturation of the microfilariae (7).

In 1988, Merck & Co. instituted the Mecitzan Donation Program (MDP), a program that worked together with ministries of health and other non-governmental development organizations to provide free Mecitzan to those who needed it in endemic areas. It is currently the most effective drug on the market for controlling and limiting the transmission and adverse side effects of onchocerciasis. Mecitzan is tablet that must be administered once a year and is derived from the compound Streptomyces avermitilis, a bacteria that causes nematode paralysis by impairing neuromuscular function. As a result, Mecitzan is effective in paralyzing the microfilariae. However, the drug does not kill the adult worms, but only prevents it from producing additional offspring. While the drug is effective in minimizing the terrible side effects of the disease, it is by no means a cure, as it fails to fully eradicate the parasite from the infected human. Furthermore, severe adverse neurological reactions, including several deaths, have been reported in persons with a high intensity of Loa loa infection, (a skin and eye disease caused by the nematode worm). This has seriously affected Mecitzan treatment programs in areas potentially co-endemic for Loa loa, including most of Central Africa (2).

While the world has worked diligently to develop new medical treatments and other strategies to defeat onchocerciasis, the disease is still ravaging these underdeveloped areas. Although pesticide spraying, nodulectomies and the distribution of Mecitzan has controlled the spread of the disease, hundreds of thousands of Africans are still blind and suffering. Furthermore, it has also been found that drugs such as Suramin and DEC can have the same toxic effects as the disease itself. It is unbelievable to me that it is so difficult to battle a worm and a fly. It is certainly ironic that something so small, something that we view to be so insignificant, can have such deleterious effects upon countries that are already struggling to survive.

While the failure of Western science to produce a cure for onchocerciasis is certainly a major reason why many of these countries are struggling to overcome it, a closer examination illustrates that severe internal problems are also barriers that need to be conquered in order to destroy the disease. Teshome Gebre, an Ethiopian who has attended many public health conferences all over the United States, asserts that, "the [Ethiopian] economy goes from bad to worse...development resources are not utilized...there is poor management, poor government. We fight among ourselves instead of tackling our common problems" (8).

Gebre's statement leaves one to ponder the social and cultural barriers that are holding these underdeveloped countries back. The lack of education, unity, and stable leadership seem to only help in the spread of disease. As a result, I think that the world should not just focus on scientific advances, but also on instituting programs to rebuild the infrastructure of these countries. Perhaps it is necessary to look beyond the scope of biology and science, as it is obviously not curing this disease, and delve further into rebuilding cultural relations and infrastructures of these countries. The synergy of education, reorganization of politics and leadership, and continued medical research could be a more effective means of permanently defeating this scourge and improving the general welfare of the lives of African citizens.

Sources

1) Division of Parasitic Disease Website, Provides information on disease, symptoms, transmission and treatment options.

2) World Health Organization Website , Includes information on how it is caused, its transmission, and prevention and control methods.

3) written by Jason F Okulicz, MD, Physician, Department of Internal Medicine, Wilford Hall Medical Center. , extensive disease information

4) encyclopedia article, information on parasite life cycle and symptoms and treatment of the disease.

5) Worldbank website , disease information and treatment options.

6) Optometry website , information on Suramin

7) Research at the University of Tübingen , information on nodulectomies.

8) Carter Center Website, provides disease information and what its organization does to help stop its transmission. Also has article from The Houston Chronicle.


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