African trypanosomiasis (sleeping sickness) is a protozoal disease that is caused by a complex or group of parasites in the genus Trypanosoma. Sleeping sickness occurs in parts of the African continent, and the disease accounts for over a million cases of infections and associated disabilities in persons in this region. African trypanosomiasis has enormous economic and medical consequences; and disability and death can result if the disease is not properly treated. Poverty, lack of proper research facilities and political will/constraints are some of the reasons there is that have allowed the disease to continue unabated in some parts of the African continent. Trypanosoma species are found in the Phylum Euglenozoa, Subphylum Kinetoplasta, Class Trypanosomatidea, Order Trypanosomatida, and Genus Trypanosoma. Sleeping sickness is caused by a group of Trypanosoma species including:
- Trypanosoma brucei gambiense (causes chronic African trypanosomiasis)
- Trypanosoma brucei rhodesiense (causes acute African trypanosomiasis)
- Trypanosoma brucei brucei (infects only animals)
Type and morphology of Trypanosoma
Trypanosoma brucei complex parasites are haemoflagellates (i.e. they are blood-borne protozoa, and thus live in the blood cells and lymph nodes of their host). The three members of the Trypanosoma brucei complex (T. b. gambiense, T. b. rhodesiense and T. b. brucei) are morphologically and phenotypically similar and identical. But they also differ genetically. Trypanosoma brucei complex exhibit two clinical forms: the trypomastigote and epimastigote forms, and they are characterized by the possession of a mitochondrion-kinetoplast structure which is distinct amongst the three parasites in the Trypanosoma brucei complex. Trypomastigotes are the infective stage of the parasite (which are usually found in the insect vector that transmits the protozoa to humans), and they are spread to humans during a blood meal. In African trypanosomiasis (sleeping sickness), the trypomastigotes after been picked by the insect vector during a blood meal develops in the midgut and later moves to the salivary gland of the insect from where it is transmitted to humans after series of transformations. African forms of Trypanosomes are also saddled with flagella which allow them to undergo locomotion.
Vector, reservoir and habitat of Trypanosoma
The insect vector for African trypanosomiasis (sleeping sickness) is tse-tse flies which are found in the woodland savanna, lakesides, riversides, and the humid forests of the African continent. Tse-tse fly species in the genus Glossina are chiefly responsible for the transmission of Trypanosoma parasites that causes sleeping sickness to human populations. Glossina species of tse-tse fly that transmits Trypanosoma parasites to humans include G. palpalis, G. fuscipes, G. pallidipes, G. tachinoides, G. morsitans and G. swynnertoni. The reservoir for the African Trypanosoma forms include cattle, humans, rodents , antelopes, wild animals, giraffe and some domestic animals (goat). Travelers, honey and bee collectors, hunters, game and forests keepers/wardens and people who come into tse-tse fly infested regions/countries are always at risk of acquiring Trypanosoma parasites through the bite of the insect vector for the disease. It is noteworthy that unlike other insect vectors (female Anopheles mosquitoes that transmits Plasmodium parasites that cause malaria) where only the female insect vector is principally responsible for passing on the parasite to the human host via a blood meal, both the male and female tse-tse flies in the genus Glossina suck and take blood meal, and are implicated in the transmission of the African Trypanosoma forms to their susceptible human hosts.
Clinical signs and symptoms of African trypanosomiasis
Sleeping sickness usually has two clinical features which are the encephalitic stage (which affects the central nervous system) and the haemolymphatic stage (which affects the blood, spleen and the lymph nodes). The clinical signs and symptoms of sleeping sickness include chancre (a painful swelling on the skin following the bite of an infected tse-tse fly), The incubation period of the disease can last from several weeks to years. Recurrent fever, shoulder and neck pain, persistent headache, somnolence, oedema of the face and limbs. The swelling of the spleen and lymph nodes may occur in some cases of African trypanosomiasis. Sleeping sickness is a wasting disease, thus if the disease remain untreated, it could result in death.
Pathogenesis of African trypanosomiasis
African trypanosomiasis occurs following the inoculation of any of the trypomastigotes of Trypanosoma brucei complex (T. b. rhodesiense and T. b. gambiense) species into the host’s skin by the bite of an infected tse-tse fly in the genus Glossina. This occurs as the infected tse-tse fly takes a blood meal from a human host (Figure 1). Once the Trypanosome parasite gains entry into the host’s body, they undergo a localized multiplication at the site of inoculation, and this result to painful swellings and lesions (known as chancre) on the skin. After successful multiplication of the trypomastigote at the site of entry, the infective trypomastigotes are introduced into the general circulation of blood through the lymphatic systems. This marks the onset of the haemolymphatic stage of the disease (the period in which the blood, spleen and the lymph nodes becomes affected). The parasites spread to the heart, bloodstream, the lymph nodes, and finally to the central nervous system (CNS). The infective trypomastigotes of Trypanosome species that causes sleeping sickness multiply extracellularly in the blood and lymphoid tissues of the human host.
The invasion of the CNS by infective trypomastigotes of African Trypanosome forms marks the beginning of the encephalitic stage of the disease (the episode in which the central nervous system of the host becomes affected). This results to damages in the nervous system that culminates to diverse nervous anomalies such as mental dullness, inflammation of the meninges (meningoencephalitis), apathy, coma, and the sleeping sickness syndrome that characterizes the disease. The neurological damage that results from CNS invasion by African Trypanosome forms is also due in part to the immune response of the host to the parasite. Sleeping sickness (somnolence) is a characteristic syndrome of African trypanosomiasis; and it causes incontinence, mouth drooling (uncontrolled mouth salivation), insensitivity to pain, sleeplessness and excessive sleeping, thus the name sleeping sickness.
Trypanosome species that cause sleeping sickness can appear in the cerebrospinal fluid after some weeks of infection, and they are congenital in nature and can be transmitted to the foetus in vivo (African trypanosomiasis can be passed on from mother to unborn child) via the placenta. Congenital infections of African trypanosomiasis occur majorly in highly-endemic areas of the disease (in parts of East Africa and West Africa). If left untreated, sleeping sickness can result to death few years after initial infection.
Figure 1: Life cycle of African Trypanosomiasis. 1. During a blood meal on the mammalian host, an infected tsetse fly (genus Glossina) injects metacyclic trypomastigotes into skin tissue. The parasites enter the lymphatic system and pass into the bloodstream. 2. Inside the host, they transform into bloodstream trypomastigotes. 3. They are carried to other sites throughout the body, reach other blood fluids (e.g., lymph, spinal fluid), and continue the replication by binary fission. 4 & 5. The entire life cycle of African Trypanosomes is represented by extracellular stages. The tsetse fly becomes infected with bloodstream trypomastigotes when taking a blood meal on an infected mammalian host. 6. In the tse-tse fly’s midgut, the parasites transform into procyclic trypomastigotes and multiply by binary fission. 7. They leave the midgut, and transform into epimastigotes. 8. The epimastigotes reach the fly’s salivary glands and continue multiplication by binary fission. Humans are the main reservoir for Trypanosoma brucei gambiense, but this species can also be found in animals. Wild game animals are the main reservoir of T. b. rhodesiense. The entire life cycle of the parasite in the insect vector (Glossina tsetse fly) takes approximately 3 weeks. CDC
Laboratory diagnosis of African trypanosomiasis
African trypanosomiasis is diagnosed in the laboratory by the demonstration of trypanosomes in body fluids including blood, cerebrospinal fluid (CSF) and lymph node aspirates. Thick smears, wet and thin smears can be used to detect African trypanosome forms from any of these fluids (though the number of parasites may vary and can be low in some cases). The parasite can be microscopically detected in both thick blood smears (Figure 2) and thin blood smears respectively (Figure 3). Some of the techniques used in the laboratory diagnosis of sleeping sickness include:
- Microscopical examination of blood specimen for trypanosomes i.e. the motile trypomastigotes (Figure 4).
- Microscopical examination of cerebrospinal fluid (CSF) to detect the parasites trypomastigotes or trypanosomes (Figure 4). CSF is obtained via lumber puncture; and the specimen should be examined without delay because trypanosomes have short life span in aspirated CSF. Examination of CSF is undertaken to demonstrate invasion of the central nervous system by the parasite.
- Microscopical examination of lymph node aspirates from enlarged lymph glands especially in early episodes of sleeping sickness.
- Serological tests that detect parasites antigen in blood specimen by way of agglutination, antibody detection, or detection of the parasites DNA can also be used to diagnose African trypanosomiasis.
- Culture of African forms of trypanosomes is not reliable, and thus unnecessary for clinical diagnosis of the disease. Culture is therefore irrelevant for the routine diagnosis of sleeping sickness.
The collection of CSF specimen by lumbar puncture from a patient for the laboratory diagnosis of sleeping sickness should only be undertaken after a day or two of treatment of the disease to kill the motile trypomastigotes in the blood. The rationale for this is to avoid the accidental introduction of motile trypomastigotes into the central nervous system (CNS) during lumbar puncture.
Figure 2: Subspecies (ssp) of T. brucei (arrowhead) in Giemsa-stained thick blood smears. CDC
Figure 3: T. brucei ssp (arrowhead) in Giemsa-stained thin blood smears. CDC
Figure 4: T. brucei ssp trypomastigotes (arrowheads) in Giemsa-stained blood smear. CDC
Treatment of African trypanosomiasis
The treatment of sleeping sickness is usually started with the intravenous administration of suramin injection (a polysulphonated naphthylamine derivative of trypan red). Suramin, a trypanocidal agent (drug that kills trypanosomes) in addition to pentamidine isethionate are usually booth used singly for the treatment of haemolymphatic stages of African trypanosomiasis (the episodes of the disease that does not involve the CNS). Both suramin and pentamidine isethionate are protein-bound trypanocidal agents and cannot be used to treat meningoencephalitic stages of sleeping sickness because the drugs do not cross the blood-brain-barrier (BBB) of the patient where CNS invasion by trypanosomes is evident. For encephalitic stages of the disease, melarsoprol (an arsenical compound) and eflornithine (a novel trypanocidal agent) are used to treat trypanosomal meningoencephalitis because both agents cross the BBB. Eflornithine has proven to be effective against both the CNS and blood stages of the T. b. gambiense and even the haemolymphatic episodes of T. b. rhodesiense which appears in the CSF much earlier than T. b. gambiense. Eflornithine also has a lesser untoward effect than suramin, pentamidine isethionate and melarsoprol; and is mostly used for treating African trypanosomiasis because of this characteristic. African forms of Trypanosomes undergo series of mutations that allows it to change its protein coat. This has made it difficult to develop effective vaccine against the parasite.
Control and prevention of trypanosomiasis
The effective control and prevention of sleeping sickness and the parasite that cause the disease is dependent upon a proper understanding of the parasites life cycle and that of the insect vector (tse-tse flies in the Glossina genus) that transmits the protozoan. Increasing public awareness of the disease through targeted advocacy especially in rural areas and amongst tourists and travelers visiting Trypanosome or tse-tse infested regions is very important to preventing the disease. Also, prompt and accurate treatment of infected individuals of the disease to prevent CNS invasion by the Trypanosome parasite and adequate control of the insect vector of the parasite is crucial to controlling and preventing African trypanosomiasis. Though some insect repellants may be ineffective in tse-tse fly infested areas, insecticides and other useful chemicals should always be applied to control and minimize the population of the insect vector. Vehicles entering and leaving tse-tse fly infested areas should be properly sprayed with insecticides; and all breeding sites for tse-tse flies should be destroyed. Screens and traps should also be used in tse-tse fly infested areas to catch and trap the insect vector and destroy them as they engage in flight. Funding and research should be directed to regions endemic with the disease as they may be economically disadvantaged to meet up with the financial resources and technical know-how as to how to control and contain the disease to the barest level.
Taylor LH, Latham SM, Woolhouse ME (2001). Risk factors for disease emergence. Philos Trans R Soc Lond B Biol Sci, 356:983–989.
Stedman’s medical dictionary, 27th edition. Philadelphia: Lippincott, Williams and Wilkins.
Summers W.C (2000). History of microbiology. In Encyclopedia of microbiology, vol. 2, J. Lederberg, editor, 677–97. San Diego: Academic Press.
Schneider M.J (2011). Introduction to Public Health. Third edition. Jones and Bartlett Publishers, Sudbury, Massachusetts, USA.
Roberts L, Janovy J (Jr) and Nadler S (2012). Foundations of Parasitology. Ninth edition. McGraw-Hill Publishers, USA.
Rothman K.J and Greenland S (1998). Modern epidemiology, 2nd edition. Philadelphia: Lippincott-Raven.
Principles and practice of clinical Parasitology. Edited by Stephen H. Gillespie and Richard D. Pearson. John Wiley and Sons Ltd. Chichester, New York.
Nelson K.E and Williams C (2013). Infectious Disease Epidemiology: Theory and Practice. Third edition. Jones and Bartleh Learning
Mandell G.L., Bennett J.E and Dolin R (2000). Principles and practice of infectious diseases, 5th edition. New York: Churchill Livingstone.
Molyneux, D.H., D.R. Hopkins, and N. Zagaria (2004) Disease eradication, elimination and control: the need for accurate and consistent usage. Trends Parasitol, 20(8):347-51.
Lucas A.O and Gilles H.M (2003). Short Textbook of Public Health Medicine for the tropics. Fourth edition. Hodder Arnold Publication, UK.
MacMahon B., Trichopoulos D (1996). Epidemiology Principles and Methods. 2nd ed. Boston, MA: Little, Brown and Company. USA.
Leventhal R and Cheadle R.F (2013). Medical Parasitology. Fifth edition. F.A. Davis Publishers,
Lee JW (2005). Public health is a social issue. Lancet. 365:1005-6.
John D and Petri W.A Jr (2013). Markell and Voge’s Medical Parasitology. Ninth edition.
Gillespie S.H and Pearson R.D (2001). Principles and Practice of Clinical Parasitology. John Wiley and Sons Ltd. West Sussex, England.