Читать книгу Parasitology - Alan Gunn - Страница 113

Tstetse flies have an extremely effective immune system that usually kills any trypanosomes present within their blood meal soon after it is ingested. Nevertheless, if a tsetse fly is susceptible to infection, the ingestion of even a single trypanosome is sufficient to ensure it becomes a vector (Maudlin and Welburn 1989). Once infected, a tsetse fly remains infected for the rest of its life. Although trypanosomes grow and reproduce in tsetse flies, they do not appear to cause them much, if any, harm. However, the trypanosomes do alter the protein composition and antihaemostatic properties of tsetse fly saliva. This reduces the saliva’s capacity to prevent blood coagulation and vasoconstriction. This results in the flies spending more time probing for a blood vessel. This may either provide more time for parasite transmission to take place or encourage the tsetse fly to move more frequently between hosts. The mechanism(s) by which the parasites alter the composition of the tsetse fly saliva are uncertain, but they may trigger a stress response that decreases certain gene expressions (Van Den Abbeele et al. 2010).

At the time of writing, five drugs had approval for the treatment of HAT: pentamidine, suramin, melarsoprol, eflornithine, and nifurtimox. Pentamidine and suramin are used to treat first‐stage HAT whilst melarsoprol (Mel B), eflornithine, and nifurtimox are used for second‐stage HAT. None of the drugs is ideal, and some have serious side effects. For example, suramin can cause anaphylactic shock and kidney failure, whilst melarsoprol can cause seizures and kills 1 in 20 of the patients who receive it. Although the risks might sound unacceptable, in the absence of treatment, there is an extremely high chance that a patient with HAT will die of the disease. Nifurtimox has the advantages of being easier to administer and less toxic than the other drugs but is prescribed as a combination therapy with eflornithine rather than on its own.

A novel group of chemicals called the benzoxaboroles are highly effective at treating stage 2 HAT but currently they still require registration (Jacobs et al. 2011). They also show potential for the treatment of animal trypanosomiasis (Akama et al. 2018). Not only can benzoxaboroles be taken orally (suramin and melarsoprol must be given as a series of intravenous injections) but they also do not produce the harmful side effects of current drugs. The benzoxaboroles also include chemicals that show promise for the treatment of malaria, cryptosporidiosis, filarial nematodes, and bacteria (Lunde et al. 2019; Sonoiki et al. 2017). Consequently, it may eventually become possible to treat co‐infections with a single safe drug.