Human African Trypanosomiasis (HAT): A Scientific Overview

Image credit: Photo by Valentin Angel Fernandez

Human African Trypanosomiasis (HAT), also known as the Sleeping Sickness, is a disease caused by variants of the Trypanosoma brucei species complex. Primarily endemic in sub-Saharan Africa, HAT is transmitted through the bite of infected riverine or tsetse flies (Glossina spp.). T. brucei species thrive in the blood and tissue fluids of vertebrate hosts, and cause either a slow infecting progress (chronic) or rapid progression (acute). Apparently, it starts in the hemolymphatic stage and can advance to neurological stage, potentially leading to more severe symptoms, or death if left untreated. Significant progress has been made in controlling the disease, and efforts in learning its biology, modes of transmission, and elimination techniques are important in aiming to eradicate these parasites [1, 2, 4].

The disease stems from two specific variants, each with its own pattern of transmission, progression, and regional impact. At the core of sleeping sickness lie Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense — two parasitic subspecies responsible for acute and chronic complications seen across different regions of Africa [3, 4]. But how do these closely related parasites differ in impact and behavior? What are their key differences?

Trypanosoma brucei rhodesiense

Trypanosoma brucei rhodesiense is a zoonotic trypanosome and is one of the causative agents of HAT. Originating from East and South Africa,

its transmission primarily involves animal-to-human interaction via tsetse flies (Glossina spp.). Hosts infected with this parasite experience from acute complications with rapid symptoms such as headache, fever, and swollen lymph nodes. Its advance stage can also compromise the Central Nervous System (CNS) in a short period, usually within weeks to a few months [4, 5, 6].

T. b. rhodesiense infection to diagnosed patients progress in two stages. The level of parasitemia is typically high during the first stage of disease. Initially, patients suffer from symptoms including fever, lymphadenopathy, and pruritus. In the second stage of the disease, CNS parasitic invasion and cardiac-related complications occur. Due to its rapid progression, early diagnosis is necessary, as delayed response can result in severe health consequences, including death [7, 8, 9].

Trypanosoma brucei gambiense

Diagnosis of HAT relies on clinical assessment and laboratory confirmation. Due to high parasitemia in T. b. rhodesiense infections, microscopic examination of the blood from infected patient is typically performed to easily detect the parasite. On the other hand, detecting trypanosomes in T. b gambiense is more difficult due to lower parasitemia level. Hence, sensitive techniques including serological tests (CATT-antigen) are performed [8, 9]. Determination and disease staging is typically done by assessing white blood cell (WBC) count and trypanosomes through cerebrospinal fluid (CSF) examination. This is to ensure proper treatment and intervention against HAT cases [9,10].

Effective management of HAT requires stage-specific medication as treatment varies by subspecies and disease stage. For the initial stage of T. b. rhodesiense-associated HAT, suramin is typically administered, while pentamidine is used for T. b. gambiense-HAT infections. Late stages of HAT often present parasite invasion in the CNS. Melarsoprol, an arsenic-based drug is used as treatment against T. b. rhodesiense, whereas nifurtimox-eflornithine combination therapy (NECT) is often applied to T. b. gambiense-HAT. Recently, fexinidazole, an oral treatment, is gaining attention in treating T. b. gambiense-HAT, with positive effects in alleviating symptoms, particularly in children. However, safety and efficacy are still studied for further confirmation. While HAT poses serious health risks, survival outcomes have improved with prompt diagnosis and effective treatment [10, 12, 13].

With consistent control efforts and public health intervention, the prevalence of HAT has significantly declined over the decades. However, transmission still exists and remains a threat to certain African regions. Over 95% of reported HAT cases are caused by T. b. gambiense, generally considered the most common and persistent form of the disease in West and Central Africa, whereas T. b. rhodesiense accounts for less than 5% of reported cases in East and South Africa [11]. Clinical trial programs are consistently implemented against the disease. Moreover, at the end of the year 2020, the World Health Assembly approved a new road map for the years 2021–2030 that established new ambitious targets for neglected tropical diseases. Continued surveillance and targeted interventions are necessary to prevent re-emergence and work towards its elimination [5, 6, 11].

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References

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