Trypanosomiasis

Author: MBLOSGTU

Introduction

African trypanosomiasis—commonly known as sleeping sickness—has been recognized since the fifteenth century. Active research began with European colonial expansion, and the link between the causative parasite, Trypanosoma brucei, and its vector, the tsetse fly, was only established in the late nineteenth century.

The disease remains a major public health hazard today. Its impact on communities is often measured in disability-adjusted life years (DALYs), with human sleeping sickness alone responsible for 1.78 million DALYs.

Despite more than 100 years of study, Trypanosomiasis remains intractable due to financial and political constraints in Africa and a lack of adequate administrative infrastructure for new control measures.

Epidemiology

Human trypanosomiasis is characterized by long periods of endemicity in specific foci, interspersed with short-term epidemics. Factors influencing transmission include:

• Tsetse Fly Factors: Vectorial capacity, degree of anthropophily, longevity, and dispersal of Glossina species.
• Human & Animal Reservoir Factors: Place of residence, agricultural and water-related activities, plus the nature of the animal reservoir.

The disease is found exclusively in sub-Saharan Africa between latitudes 14° N and 29° S. The at-risk population is estimated at about 60 million, and roughly 300,000 new cases occur annually—although sadly less than 10% of these reach medical attention.

Pathogenesis

Early in the infection, the cardiovascular and lymphatic systems become involved, resulting in perivascular cellular infiltration, haemorrhage, and oedema.

Widespread meningeal inflammation soon follows along with injury to the choroid plexus. This breakdown permits parasites to enter the cerebrospinal fluid (CSF) and infiltrate periventricular areas, aided by the relatively thin blood–brain barrier.

Although trypanosome entry into the CSF occurs early, the parasites typically remain undetectable for weeks (in T. brucei var. rhodesiense) or even months (in T. brucei var. gambiense).

As the disease progresses, vasogenic oedema develops along with changes in brain tissue density and electrolyte levels. Damage to the blood–brain barrier becomes more pronounced as trypanosomes infiltrate cerebral regions where the barrier is naturally less robust (e.g., the pineal gland or median eminence). Endotoxaemia is commonly seen in the blood and CSF in late-stage disease.

Clinical Manifestations

The clinical presentation of trypanosomiasis varies between West and East African forms:

West African Trypanosomiasis

This form is primarily transmitted by tsetse flies such as G. palpalis palpalis, G. palpalis gambiensis, G. fuscipes fuscipes, and G. tachinoides, which inhabit forests and wooded areas along rivers. The favorable conditions in these areas restrict human infection mainly to the tropical rain forests of Central and West Africa.

East African Trypanosomiasis

In East Africa, the disease is essentially zoonotic. Humans typically acquire the infection from tsetse flies living in the savanna that feed on a wide variety of domestic and wild animals. The bushbuck is considered a major reservoir, with domestic animals—such as cattle, dogs, sheep, and goats—also playing important roles. Infection, which tends to affect predominantly adult men, usually occurs when individuals enter woodland areas harboring these flies.

While the signs and symptoms of both forms are similar, East African trypanosomiasis tends to be more acute with clinical manifestations appearing within days to weeks, and death following within weeks to months. West African trypanosomiasis usually follows a more indolent course, with an incubation period stretching from months to years.

During the haemolymphatic stage, a chancre (a tender, erythematous swelling) develops 2–3 days after a tsetse bite—more common in T. brucei var. rhodesiense—and typically subsides within 3 weeks. Posterior cervical lymphadenopathy (known as Winterbottom’s sign) is commonly observed in West African trypanosomiasis; in East African disease, lymphadenopathy tends to be more generalized.

Other common symptoms include fever, arthralgia, headache, and myalgia. For many patients, the fever presents as recurrent episodes aligned with waves of parasitaemia, each bout lasting 1–3 days. As the disease advances to the meningoencephalitic stage, neurological phenomena—including disturbances in the circadian sleep–wake cycle (hence “sleeping sickness”), hyper-reflexia, coordination disorders, tremors, convulsions, changes in consciousness, and mood or behavioural alterations—emerge. Additional features of the haemolymphatic stage may include anaemia, hepatosplenomegaly, and characteristic cutaneous ring-like patches termed “trypanids.”

Laboratory Diagnosis

Diagnosis and staging of African trypanosomiasis involve direct examination of body fluids:

• Blood: Examination for the presence of trypanosomes.
• Lymph Gland Aspirates: Particularly useful in suspects of gambiense trypanosomiasis.
• Cerebrospinal Fluid (CSF): Analysis for trypanosomes, cell count (including Morula cells), raised protein levels, and IgM concentration is crucial to determine central nervous system involvement and guide further treatment with more toxic drugs.

Parasite Detection

Direct demonstration of the parasite in body fluids is the most definitive method of diagnosis:

• In early T. brucei var. rhodesiense infection, trypanosomes may be detected in serous fluid aspirates from the trypanosomal chancre.
• In acute illness, blood films (wet films for motility visualization, as well as thin and thick smears fixed with methanol and stained with Field’s or Giemsa) are used. Detection limits can range from 17 to 33 parasites/ml, with wet films detecting around 25 parasites/ml.
• Multiple samples and concentration techniques are often necessary because the parasite load in blood can be very low.
• Capillary tube centrifugation (microhaematocrit technique) and the quantitative buffy coat technique (using acridine orange) both have detection limits of about 16 parasites/ml.
• Examination of CSF using a double centrifugation technique can enhance sensitivity to as low as 1 parasite/ml. Additionally, a raised CSF leukocyte count (> 5/mm³), the presence of morula cells, and increased protein levels support the diagnosis of cerebral trypanosomiasis.

Indirect Diagnosis

Given the often low density of trypanosomes in body fluids, indirect methods are sometimes required. These involve detection of antibodies, antigens, or nucleic acids.

Antibody Tests

Several antibody detection methods have been developed, including:

• ELISA
• Immunofluorescence
• Immune trypanolysis
• Direct agglutination
• Indirect haemagglutination
• Latex agglutination
• Western blot
• Dot-blot

The Card Agglutination Test for Trypanosomiasis (CATT) employs fixed, stained intact trypanosomes of variable antigen type LiTat 1.3 as its reagent.

Antigen Tests

Various antigen-detection systems are under development, including direct, indirect, and sandwich ELISA methods.

The Card Indirect Agglutination Test for Trypanosomiasis (TrypTect CIATT) uses antibodies coupled to latex beads to detect circulating trypanosomal antigens in the patient’s blood.

PCR techniques have also been developed for both CSF and blood, reporting sensitivity thresholds around 1 parasite/ml, although further validation is needed before routine use.