Sleeping Sickness: Part 3

*Note: Short post this weekend due to spotty time-management skills on the part of the writer. Lay off, I’m learning! (But, seriously, I’ll try to add more later in the week.)

The Discovery

Although the symptoms of Sleeping Sickness have been recorded since 1742 and Trypanosomes have been on the collective science-people radar since 1843, they weren’t found in humans until 1901. Between 1900 and 1920 a severe sleeping sickness outbreak occurred in Uganda and lead to over 200,000 deaths. During that time scientific teams were sent from five different European countries to investigate the cause of the outbreak.

Meanwhile and previously, in 1895, Scottish pathologist David Bruce discovered (and named) T. brucei in cattle. Then, during the (first) Uganda epidemic, in 1901, Dr. R. M. Forde discovered “actively moving worm-like bodies” in the blood of a sick 42-year-old male. These “worm-like bodies” were found to be Trypanosoma brucei and the following year J. Everett Dutton named them Trypanosoma brucei gambiense. *Note: The sick Englishman is described as having “enjoyed good health, except for very occasional slight attacks of malarial fever” (perspective, anyone?). While this pathogen was discovered, it was only known as “Trypanosoma fever” at first and was thought to be mild and not connected to sleeping sickness. However, in 1903, like an artist framing a masterpiece (or a stubborn child who always has to have the last word) Bruce discovered not only that T. brucei is the cause of sleeping sickness, but also that it is transmitted by the Tsetse fly.

Sleeping Sickness: Part 2

The Disease

As one might suspect, there are situations when having a tiny animal swimming around in your bloodstream or your spinal fluid can be… problematic. Trypanosomes, while cute (yes they are, don’t talk to me), are not exactly kittens. The first stage of sleeping sickness isn’t that bad, comparatively. Fevers, headaches, joint pains, itchiness, and in some cases a sore may not be fun, but they still beat the second stage symptoms. Plus, it’s better to have early symptoms and begin treatment than to go symptom-free (or close) until the really scary stuff starts happening. The second stage, which begins when the parasite enters the central nervous system, is characterized by some pretty scary neurological symptoms. The most characteristic of these, from which the disease gets its common name, is a disruption in the sleep cycle. Patients with later stage sleeping sickness experience insomnia in the evening, but can’t be roused during the day. In addition, mood swings, depression, loss of coordination, and death. There’s also a difference between T. b. gambiense and T. b. rhodesiense. While the former is the most common, the latter is much more severe.

The Treatment

While there is no cure for Sleeping Sickness, there are a number of drugs used to treat the disease once symptoms occur. Some of these drugs are used to treat the disease in the first stage and are quite a bit safer than those used to treat the second stage. After all, the drugs used to treat the second stage have to be able to make their way into the central nervous system and that is always a sketchy situation. At least we are replacing ‘fire in the veins‘ with safer alternatives. Treatments also depend on whether the disease is caused by T. b. gambiense or T. b. rhodesiense. The best drug for treating early stage infections by T. b. gambiense is Pentamidine. This drug can also be used as a preventative, but as it is toxic, that it is not widely recommended. In fact, as with most vector-borne diseases, insect control is the best sort of preventative.

The Location

The Tsetse fly, quaint as it is with its mammalian impostering, is not terribly well-traveled (maybe it gets sea sick?). While the fly (and the disease) has been found in at least 36 different countries in Africa, the majority (approximately 70%) of cases occur in the Democratic Republic of Congo and a few surrounding countries. Since large mammals can act as reservoir hosts, areas where people rely heavily of agriculture and livestock for subsistence become ideal spots for the pathogen and the fly. This is a problem because, in many of these areas, it is the poor that are most heavily impacted. Historically, diseases that impact the poor are the most neglected, though there are programs at work to try and counter that fact. Still, even with more research attention, there are always economic losses attributed to serious illness.

Sleeping Sickness: Part 1

The Parasite

The causative agent of Sleeping Sickness is the single-celled protozoan parasite, Trypanosoma brucei brucei, which is a close relative of the pathogen that causes Chagas Disease (in fact, other common names for Sleeping Sickness and Chagas Disease are African Trypanosomiasis and American Trypanosomiasis, respectively). There are two sub-species of T. brucei that cause Sleeping Sickness in humans, Trypanosoma brucei gambiense (responsible for 98% of cases) and Trypanosoma brucei rhodesiense. These parasites are members of a group known as the hemoflagellates or ‘blood and tissue’ protozoans. This is because they can be found in circulating blood or, in the case of American trypanosomes, cardiac (heart) tissue of their hosts.

The Fly

The causative agent of Sleeping Sickness is a bizarre little relative of the house fly in the genus Glossina, most commonly known as the Tsetse fly. These flies have one of the strangest reproductive strategies in the insect world. One might almost say they think they’re people. They give birth to live young, they only give birth to one ‘baby’ at a time, and they even feed their young through a system of tubes that provide ‘milk’ proteins to growing larvae. While most insects produce high numbers of offspring and bank on a little cannon fodder, Tsetse flies take the more mammalian approach of caring for young until they’re less vulnerable. This process is surprisingly time consuming and energetically expensive for an insect.

While the ‘why’ of evolution is always tricky question to answer, susceptibility of larvae to pathogens and predators may provide one possible explanation for the unique reproductive strategy. The larvae are 3^rd or 4^th instars before they emerge from the female and they pupate almost immediately upon being born, limiting the chance for any pathogens or predators to take advantage of them in a vulnerable state. Still, both males and females are blood-feeders, a risky business in itself, with females requiring even more blood for the production of offspring.

[Note: much of the information in this section comes from my insect physiology course notes].

The Cycle

The life cycle of human African Trypanosomes begins with the taking of a blood meal by the Tsetse fly, which is when the protozoans are injected into the bloodstream of the host where they are carried to other parts of the body. They then multiply by a process called binary fission while in the blood, spinal fluid, or lymph. Another Tsetse fly may then take a blood meal and pick up new protozoans, which will then multiply (again by binary fission) in the midgut of the Tsetse fly. These will then travel from the midgut to the salivary glands, multiply once more, and wait for the fly to take another blood meal. Then the cycle begins, again. While humans are the primary host for T. brucei gambiense, it may also be found in animal reservoirs and T. brucei rhodesiense prefers large animals.