An international team of researchers has found what might be a cure for river blindness and elephantiasis. In their paper published in the journal Science Translational Medicine, the group describes their search for a drug that could kill the parasitic worms behind the diseases, what they found, and how well it worked when tested with animals.
Parasites called filarial worms are responsible for causing the parasitic diseases onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis), both diseases are relatively rare. Both tend to occur in poverty-stricken regions in Africa and are quite debilitating. One can lead to blindness, the other to serious skin deformations. Drugs are available that kill the worms during their larval stage, but until now, there were no known ways to kill the mature parasite.
For nearly a half-century scientists have unsuccessfully sought ways to kill filarial worms inside the body. They have found drugs that are able to slow the damage the worms cause, but patients must take them for years or decades. In recent years, researchers discovered that a type of beneficial symbiotic bacteria called Wolbachia infect the worms. Thus, killing the bacteria would indirectly kill the worms.
To that end, the researchers screened over 2,600 drugs looking for one that would prove fatal to Wolbachia. They found one called tylosin A. During initial testing of the drug in mice, the researchers found that it did not absorb into tissue very well. The team made modifications to the drug to overcome that problem. They began full testing of the drug in mice and gerbils—a two-week treatment regimen resulted in reduction of the worms by 90 percent.
The team has begun testing the drug in rats and dogs, and reports that thus far, they have not seen any cardiovascular side-effects. They note that it is still too early to tell if the drugs will be effective in humans because the worms congregate in different body locations depending on the host.
Lymphatic filariasis, commonly known as elephantiasis, is a neglected tropical disease. Infection occurs when filarial parasites are transmitted to humans through mosquitoes. Infection is usually acquired in childhood causing hidden damage to the lymphatic system.
The painful and profoundly disfiguring visible manifestations of the disease, lymphoedema, elephantiasis and scrotal swelling occur later in life and can lead to permanent disability. These patients are not only physically disabled, but suffer mental, social and financial losses contributing to stigma and poverty.
Currently, 856 million people in 52 countries are living in areas that require preventive chemotherapy to stop the spread of infection.
The global baseline estimate of people affected by lymphatic filariasis was 25 million men with hydrocele and over 15 million people with lymphoedema. At least 36 million people remain with these chronic disease manifestations. Eliminating lymphatic filariasis can prevent unnecessary suffering and contribute to the reduction of poverty.
Elephantiasis: Cause and transmission
Lymphatic filariasis is caused by infection with parasites classified as nematodes (roundworms) of the family Filariodidea. There are 3 types of these thread-like filarial worms:
Wuchereria bancrofti, which is responsible for 90% of the cases
Brugia malayi, which causes most of the remainder of the cases
Brugia timori, which also causes the disease.
Adult worms lodge in the lymphatic vessels and disrupt the normal function of the lymphatic system. The worms can live for approximately 6–8 years and, during their life time, produce millions of microfilariae (immature larvae) that circulate in the blood.
Mosquitoes are infected with microfilariae by ingesting blood when biting an infected host. Microfilariae mature into infective larvae within the mosquito. When infected mosquitoes bite people, mature parasite larvae are deposited on the skin from where they can enter the body. The larvae then migrate to the lymphatic vessels where they develop into adult worms, thus continuing a cycle of transmission.
Lymphatic filariasis is transmitted by different types of mosquitoes for example by the Culex mosquito, widespread across urban and semi-urban areas, Anopheles, mainly found in rural areas, and Aedes, mainly in endemic islands in the Pacific.
Lymphatic filariasis infection involves asymptomatic, acute, and chronic conditions. The majority of infections are asymptomatic, showing no external signs of infection while contributing to transmission of the parasite. These asymptomatic infections still cause damage to the lymphatic system and the kidneys, and alter the body’s immune system.
When lymphatic filariasis develops into chronic conditions it leads to lymphoedema (tissue swelling) or elephantiasis (skin/tissue thickening) of limbs and hydrocele (scrotal swelling). Involvement of breasts and genital organs is common. Such body deformities often lead to social stigma and sub-optimal mental health, loss of income-earning opportunities and increased medical expenses for patients and their caretakers. The socioeconomic burdens of isolation and poverty are immense.
Acute episodes of local inflammation involving skin, lymph nodes and lymphatic vessels often accompany chronic lymphoedema or elephantiasis. Some of these episodes are caused by the body’s immune response to the parasite. Most are the result of secondary bacterial skin infection where normal defences have been partially lost due to underlying lymphatic damage. These acute attacks are debilitating, may last for weeks and are the primary cause of lost wages among people suffering with lymphatic filariasis.
Onchocerciasis (river blindness)
Onchocerciasis is an eye and skin disease caused by a worm (filaria) known scientifically as Onchocerca volvulus. It is transmitted to humans through the bite of a blackfly (simulium species). These flies breed in fast-flowing streams and rivers, increasing the risk of blindness to individuals living nearby, hence the commonly known name of “river blindness”. Within the human body, the adult female worm (macrofilaria) produces thousands of baby or larval worms (microfilariae) which migrate in the skin and the eye.
Consequences of Onchocerciasis
The death of microfilariae is very toxic to the skin and the eye, producing terrible itching and various eye manifestations (lesions). After repeated years of exposure, these lesions may lead to irreversible blindness and disfigurative skin diseases sometimes named “leopard” skin and “lizard” skin.
In some West African communities, about 50% of men over the age of 40 years had been blinded by the disease. Finally, people fled the fertile river valleys to settle in less productive upland country. Hence the annual economic losses were estimated, in the 1970s, at US$ 30 million.
Where is onchocerciasis distribued?
The distribution of onchocerciasis is linked to the location of blackflies which are naturally found close to the fast-running streams and rivers in the inter-tropical zones. Therefore, about 90% of the disease occurs in Africa. Onchocerciasis is also found in six countries in Latin America and in Yemen in the Arabian Peninsula, where the disease is believed to be exported by the slave trade.
Image: This image shows the typical symptoms of podoconiosis, including swollen, thickened lower limbs with a warty and mossy appearance. This is an advanced form of elephantiasis.