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Keywords LEISHMANIASIS AFRICAN SLEEPING SICKNESS |
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Description Scientists found that extracts of two plants that grow in the Mojave Desert can kill the parasites that cause the diseases leishmaniasis and African sleeping sickness. |
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Newswise — Plants native to the Mojave Desert may one day help provide relief to millions of people who suffer from two prominent tropical diseases.
Scientists at Ohio State University found that extracts of the dotted dalea (Psorothamnus polydenius) and the Mojave dalea (Psorothamnus arborescens) can kill the parasites, which are a kind of protozoa, that cause the diseases leishmaniasis and African sleeping sickness. While both diseases are rare in North America, they are prevalent in dozens of countries worldwide, particularly developing nations. If left untreated, the diseases can be fatal.
The drugs currently used to treat both illnesses are costly and some are toxic, said Karl Werbovetz, a study co-author and an assistant professor of medicinal chemistry and pharmacognosy at Ohio State. Also, the chance of these parasites developing resistance to these medications is increasing.
"Most of the available drugs are given by injection over a long course of time," Werbovetz said. "We're hoping to develop those extracts into effective compounds that are cheap and readily available, and that can be taken by mouth."
Werbovetz conducted the study with Manar Salem, a doctoral candidate in medicinal chemistry and pharmacognosy. The two presented their findings on P. arborescens on March 16 in San Diego at the national meeting of the American Chemical Society. Their findings on P. polydenius appear in a recent issue of the Journal of Natural Products.
The researchers first screened hundreds of plant extracts to see which, if any, would kill Leishmania donovani and Trypanosoma brucei, the parasitic protozoa that cause leishmaniasis and African sleeping sickness, respectively. Leishmaniasis is transmitted by sand flies, while African sleeping sickness, or African trypanosomiasis, is transmitted by the tsetse fly.
The researchers conducted laboratory tests to determine which plant extracts would kill the protozoa but not harm healthy kidney cells cultured from the African Green Monkey.
Extracts from these related plants were among the best inhibitors of parasite growth while showing lesser effects on the kidney cells.
While there are several forms of leishmaniasis, the most common forms affect the surface of the skin (cutaneous leishmaniasis) or the internal organs (visceral leishmaniasis). Cutaneous leishmaniasis causes open sores and raised boils on the skin, while visceral leishmaniasis invades the liver and spleen and causes these organs to swell. People with the visceral form of the disease develop anemia and also lose a significant amount of weight. Visceral leishmaniasis is fatal in 90 percent of all cases left untreated.
About 2 million new cases of leishmaniasis are reported each year, according to the World Health Organization (WHO). Of those, at least half a million are visceral leishmaniasis. The disease is found in Mexico, Central and South America, Southern Europe, Asia, the Middle East, and Africa.
Also, several hundred U.S. soldiers stationed in the Middle East have developed cutaneous leishmaniasis.
"At last count, about 700 of our soldiers had the disease," Werbovetz said. "It's not an illness that people die from, and the troops can still perform their duties. But it does leave scars and can also make a person prone to infection."
Sleeping sickness affects people in mostly rural areas of sub-Saharan Africa. The disease usually begins with a high fever, a rash and swollen glands and, if left untreated, can progress into the brain, where it causes inflammation, coma and, eventually, death.
"The primary drug used to treat African sleeping sickness kills 5 percent of the people who take it – arsenic is one of its main ingredients," Werbovetz continued. "But left untreated, the disease kills 100 percent of those infected."
However, not only are the drugs used to treat African sleeping sickness expensive, they're not available everywhere they are needed.
According to the WHO, African sleeping sickness threatens over 60 million people in 36 countries of sub-Saharan Africa. Estimates on how many people develop the disease annually vary anywhere from 50,000 to 500,000, Werbovetz said.
"Real estimates are virtually impossible to come up with because of the rural nature of this disease," he said.
Leishmania spp.
(leishmaniasis)
Members of the genus Leishmania infect many vertebrates, including humans, dogs, and rodents. The life cycles of members of the genus involve a vertebrate host (e.g., the human) and a vector (a sand fly) that transmits the parasite between vertebrate hosts. In the vector the parasite takes on a characteristic morphological form known as the promastigote (see below), and it reproduces asexually in the vector's gut. When the vector bites the vertebrate host, promastigotes are injected into the vertebrate host. The promastigotes enter cells of the vertebrate host and change into a form called the amastigote (see below). The amastigote reproduces in the host's cells, and when the cell eventually dies the amastigotes are released and infect other cells ( view a diagram of the life cycle). The symptoms and pathology associated with leishmaniasis result from the amastigotes killing the host's cells.
There are many different "diseases" caused by Leishmania. In some diseases the amastigotes do not spread beyond the site of the vector's bite. This results in a "cutaneous leishmaniasis" (oriental sore, Jericho boil, Aleppo boil, or Dehli boil) that often heals spontaneously ( view geographic distribution). In other instances the amastigotes may spread to the visceral organs (liver, spleen), resulting in "visceral leishmaniasis" (kala-azar or Dum-Dum fever) ( view geographic distribution) or to the mucous membranes of the mouth and nose, resulting in "mucocutaneous leishmaniasis" (espundia or uta). Left untreated, these latter diseases result in high rates of mortality. The various types of leishmaniasis are confined primarily, but not exclusively, to Central and South America, central Africa, and parts of southern and central Asia.
Promastigotes of Leishmania sp. from culture. This is the life cycle stage that grows in the vector and that is injected into the human host when the vector feeds. The promastigotes are approximately 25 µm in length.
Amastigotes (*) of Leishmania donovani in the cells of a spleen. The individual amastigotes measure approximately 1 µm in diameter. The amastigotes reproduce asexually in these cells.
Amastigotes of Leishmania in a macrophage from a lymph node of a dog. Original image from Oklahoma State University Parasitology Teaching Resources Web Site.)
A macrophage filled with Leishmania amastigotes.
A cutaneous leishmaniasis lesion on the arm.
Cutaneous leishmaniasis of the face. (Original image from and copyrighted by Dermatology Internet Service, Department of Dermatology, University of Erlangen.)
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