Читать книгу Parasitology - Alan Gunn - Страница 111

Trypanosoma brucei is responsible for the disease Human African Trypanosomiasis (HAT), or more colloquially, ‘sleeping sickness’ and the wasting disease in cattle known as ‘nagana’. It was often stated that HAT is invariably fatal in the absence of treatment. However, it is now apparent that some people remain asymptomatic after contracting an infection (Kennedy and Rogers 2019) although it is uncertain how frequently this occurs. Some people become seronegative whilst others remain seropositive, but, in both instances, it is impossible to detect the parasites with the usual diagnostic tests. Those who become seronegative have presumably repelled the parasites and cleared them from their body, but those who remain seropositive are presumably tolerant of their infection. This begs the question of where the infection in the seropositive individuals is residing. It now looks likely that the trypanosomes are located within the skin rather than the vasculature (Capewell et al. 2016). Furthermore, the parasites within the skin can infect tsetse flies when they feed. It is uncertain whether infected but asymptomatic individuals represent a significant reservoir of infection for tsetse flies.

HAT is predominantly a disease afflicting poor people living in rural environments in some of the more politically unstable parts of Africa. Consequently, there is widespread under‐reporting of the disease. In 2006, the WHO estimated there to be 20,000 cases of HAT every year, although a few years later Brun et al. (2010) suggest that there are between 50,000 and 70,000 cases. Nevertheless, despite the difficulties of working in the affected regions, control programmes are proving effective, and by 2015, there were fewer than 3,000 reported cases (Büscher et al. 2017).

There are three morphologically identical sub‐species of T. brucei: Trypanosoma brucei brucei, T. brucei gambiense, and T. brucei rhodesiense. The different sub‐species vary in their geographical distribution, ability to infect mammalian hosts and their pathology, but they are all transmitted by various tsetse fly species (e.g., Glossina palpalis) with different species being of particular importance as vectors in different areas. Tsetse flies are only found in sub‐Saharan Africa within the latitudes 14° North and 29° South – an area that encompasses about 10 million km². Because of their absolute dependence upon tsetse flies to effect transmission, the parasites are also limited to this region. Tsetse flies have specific environmental requirements to complete their life cycles and therefore do not exploit urban environments. Consequently, people acquire HAT when they work in the fields or visit the countryside/game reserves. An increase in the number of cases of HAT among people living in the Nkhotakota wildlife reserve in Malawi since 2015 was attributed to an increase in the tsetse fly population following the relocation of hundreds of elephants to the reserve. The elephants were moved to both help conserve their numbers and improve the local economy by promoting wildlife tourism.

Trypanosoma brucei brucei is essentially a parasite of wild and domestic animals, and it does not infect humans. Wild game (e.g., kudu [Tragelaphus strepsiceros], warthog [Phacochoerus aethiopicus]), and some native cattle breeds (e.g., N’Dame, Muturu, Masai Zebu) are ‘trypanotolerant’ and infections do not always lead to serious disease symptoms. By contrast, T. brucei brucei causes serious disease in many introduced varieties of domestic animals and they succumb to a condition called ‘nagana’ – a word derived from the Zulu language that means ‘to be in low or depressed spirits’. It also severely affects horses, sheep, goats, and dogs, and these often suffer an acute disease that culminates in the death of animal within 20 days to a few months of becoming infected. In cattle, T. brucei brucei tends to cause chronic disease that lasts several months, and the infected animal may ultimately recover.

Trypanosoma brucei rhodesiense has a close genetic relationship to T. brucei brucei and occurs mainly East Africa – principally Tanzania and Uganda. In addition to infecting humans, it also parasitizes many wild game animals. Consequently, T. brucei rhodesiense is a zoonotic disease with numerous reservoirs of infection. Rhodesiense HAT is usually an acute infection although in some geographical regions a less severe disease occurs.

Trypanosoma brucei gambiense is the principal cause (~90% of cases) of HAT. Gambiense HAT usually follows a chronic course over a period of years, and severe nervous system impairment only ensues in the late stages of the disease. It occurs mainly in West and Central Africa with most cases in Democratic Republic of Congo, Angola, and Sudan. Although T. brucei gambiense infects various wild animals, the importance of zoonotic transmission in the epidemiology of gambiense HAT is uncertain.

Within the mammal host, the trypomastigotes of T. brucei exhibit various morphological forms although they all have a prominent undulating membrane (Figures 4.8 and 4.9). The slender forms are 25–35 μm in length, have a pointed posterior end, and a long free flagellum. The mitochondrion of the slender form is poorly developed. It has few cristae and lacks a functional cytochrome chain and tricarboxylic acid cycle (TCA or Krebs’ cycle). The slender forms multiply by longitudinal fission until a critical parasite density is reached at which point, they form intermediate forms and then stumpy forms. The stumpy forms are about 15 μm long, they have a broad, blunt posterior end, and lack a free flagellum. The mitochondrion of the stumpy form is more developed than in the slender form and has many cristae, but the cytochrome chain is still absent, and the TCA cycle is incomplete. Intermediate forms averaging 23 μm in length also exist, which have a blunt posterior end and a free flagellum. The stumpy forms do not divide further in the mammalian host. However, their physiological changes prepare them for the very different conditions, they will experience in the gut of their tsetse fly vector. The density‐dependent physiological changes are a consequence of quorum sensing – a phenomenon more usually associated with bacteria. In trypanosomes, quorum sensing operates through peptidase enzymes released by the parasites breaking down host proteins to release oligopeptides (Rojas and Matthews 2019). The identity of the oligopeptides is currently uncertain, but they bring about changes in gene expression within the parasites that result in them changing to the stumpy form. The stimulus is not species specific and in experimental co‐infections, the density of Trypanosoma congolense modulates the population density at which T. brucei differentiates into stumpy forms.

Figure 4.8 Life cycle stages of Trypanosoma brucei gambiense. (a) Long and short forms in the blood. (b) Trypomastigote forms in the tsetse fly midgut (~2 days post infection). (c) Slender form in the proventriculus of the tsetse fly (10–15 days post infection). (d) Crithidial stages in the tsetse fly salivary gland (15–25 days post infection). (e) Infectious stage in the salivary glands 20–30 days post infection.

Source: Redrawn from Chandler and Read (1961), © Wiley‐ Blackwell.

Figure 4.9 Light microscope photograph of trypomastigote stages of Trypanosoma brucei. Note the prominent undulating membrane.