Human African trypanosomiasis (also known as African sleeping sickness) is a parasitic disease transmitted by tsetse flies of the genus Glossina, and caused by a group of parasites known as trypanosomes. This disease is found in equatorial Africa and follows a patchy distribution depending on the presence of vector and characteristic topographical features.
This disease has negatively influenced both the economic and cultural progress of sub-Saharan Africa. Approximately 60 million people in 36 nations are at risk of infection, and the incidence has been steadily increasing from the mid-1960s to the end of 20th century; nevertheless, increased awareness and surveillance have led to a drop in the number of cases in recent years.
Causative agent and its life cycle
Two distinct kinetoplastid flagellates can cause human African trypanosomiasis: Trypanosoma brucei var. gambiense and Trypanosoma brucei var. rhodesiense, which are both subspecies of Trypanosoma brucei. The third subspecies, Trypanosoma brucei var. brucei, infects several animal species, but not humans.
As their names imply, the aforementioned two human subspecies are distinguished by their geographical distribution (Rhodesia is the former name for Zimbabwe). Therefore Trypanosoma brucei var. gambiense is found in west and central Africa, whereas Trypanosoma brucei var. rhodesiense can be found in east and southern Africa.
African trypanosomes alternate between a mammalian host and a tsetse fly vector (both dry and wet flies). Development in the fly embarks when an uninfected fly bites an infected vertebrate, ingesting trypomastigote forms of the parasite. In the gut of the tsetse flies they differentiate into procyclic trypomastigotes, and then into epimastigotes upon reaching the salivary glands. Before infecting mammalian host, they must mature into metacyclic trypomastigotes.
Surface coat of the blood stage trypomastigotes is composed from a single protein known as variant surface glycoprotein (VSG), with each of the species of African trypanosomes containing over a thousand copies of VSG genes and pseudogenes. This enables them to establish a long-term chronic infection in the infected host.
Disease course and symptoms
Initial lesion at the bite site is represented by chancre, which is characterized by erythema, tenderness, heat and edema. The infection itself can range from asymptomatic to a severe fulminating disease, with Trypanosoma brucei var. gambiense ordinarily causing a slow progressing disease, and Trypanosoma brucei var. rhodesiense more rapid course that invades the central nervous system in weeks to months.
The disease course is often broken down into two stages. The first stage is also called the hemolymphatic stage due to a spread of parasites through the bloodstream and lymphatics into organs such as liver, spleen, endocrine glands and heart. The second stage arises when these flagellates enter the central nervous system, which is also known as meningoencephalitic stage.
Determination of the stage by examination of the cerebrospinal fluid must therefore always be pursued once parasites have been detected in other body fluids. The criteria for diagnosing the meningoencephalitic stage are an elevated leucocyte count and elevated protein concentration in the fluid (detection of trypanosomes is not essential for the diagnosis).
Akin to different epidemiological and clinical characteristics of Trypanosoma brucei var. gambiense and Trypanosoma brucei var. rhodesiense, the treatment regimens for these two subspecies also differ. The choice of adequate therapy is highly reliant on the subspecies involved and the stage of the disease.
Trypanosoma brucei var. rhodesiense is preferably treated with polyanionic compound suramin in the early stage, or arsenic compound melarsoprol in the late stage of the disease. On the other hand, Trypanosoma brucei var. gambiense is treated with antimicrobial pentamidine or suramin in the early stage, and melarsoprol in the late stage.
One of the newest compounds that can be used in the monotherapy for the treatment of Trypanosoma brucei var. gambiense is the drug α-difluoromethylornithine, more commonly known just as eflornithine. The drug irreversibly inhibits the function of the enzyme ornithine decarboxylase, which in turn reduces trypanosomal proliferation.
Other drugs can also be used in the treatment of African sleeping sickness, such as nifurtimox and fexinidazole, and combination treatments are also employed. New drugs that are effective and safe, but that will not facilitate the development of cross resistance are urgently needed in our treatment armamentarium.