Sleeping sickness or African trypanosomiasis is a parasitic disease in humans. Caused by trypanosome protozoa and transmitted by the tsetse fly, the disease is endemic in certain regions of Sub-Saharan Africa, covering about 36 countries and 60 million people.
It is estimated that 300,000-500,000 people are infected, and about 40,000 die every year. Three major epidemics have occurred in the past hundred years, in 1896-1906, 1920, and 1970.
Symptoms begin with fever, headaches, and joint pains. If untreated, the disease slowly overcomes the defences of the infected person, and symptoms spread to anaemia, endocrine problems, and cardiovascular and kidney disorders.
The disease then enters a neurological phase when the parasite passes through the blood-brain barrier. The symptoms of the second phase is what gives the disease its name: besides confusion and reduced coordination, the sleep cycle is disturbed with bouts of lethargy punctuated with manic periods progressing to daytime somnolence and nighttime insomnia.
Without treatment, the disease is fatal, with progressive mental deterioration leading to coma and death. Damage caused in the neurological phase can be irreversible.
The disease is found in two forms, depending on the parasite, either Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. T. b. gambiense is found in central and western Africa; it causes a chronic condition that can extend in a passive phase for months or years before symptoms emerge. T. b. rhodesiense is found in southern and eastern Africa; its infection emerges in a few weeks and is more virulent and faster developing.
The primary condition is treated with either suramine (T. b. rhodesiense) or pentamidine (T. b. gambiense). Advanced cases can be treated with melarsoprol or eflornithine. All these drugs, especially melarsoprol, have many undesirable side-effects, and the treatment regime is often difficult to enforce.
The condition has been present in Africa from at least the 14th century. The causative agent and the vector were not identified until 1902-1903, and the differentiation between protozoa was not made until 1910. An arsenic based drug, atoxyl, was the first effective drug, developed by Paul Ehrlich and Kiyoshi Shiga, from trypan red in 1906.
After patients became blind due to incorrect dosages of atoxyl, the organo-arsenical melarsoprol (Arsobal) was developed in the 1940s. It was effective, but 3-10% of those injected had reactive encephalopathy (convulsions, progressive coma, or psychotic reactions), and 10-70% died; it could cause brain damage in those that survived the encephalopathy.
Treatment of the primary condition began in the 1920s with suramine. Eflornithine (difluoromethylornithine (DFMO)), the most modern treatment, was developed in the 1970s by Albert Sjoerdsmanot and underwent clinical trials in the 1980s. It was approved by the FDA in 1990; production halted in 1999 but was revived by Aventis.