What is Human African Trypanosomiasis (Sleeping Sickness)?
African Sleeping Sickness, also known as Human African Trypanosomiasis (HAT), is a serious illness that can be deadly. It’s caused by tiny organisms called protozoans, specifically Trypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. These organisms are transferred to humans by the bite of a tsetse fly.
This disease is most commonly found in sub-Saharan Africa, but it can also affect people who have traveled to these regions. The parasites lead to different types of illnesses, depending on whether they are of East African or West African origin. East African HAT is caused by T. brucei rhodesiense, while West African HAT is caused by T. brucei gambiense. Both versions of the disease have two stages: the first affects the blood and lymph system (hemolymphatic stage), and the second involves the brain and spinal cord (meningoencephalitic stage).
HAT is categorized as a neglected tropical disease and poses a significant health risk in rural areas of Africa.
What Causes Human African Trypanosomiasis (Sleeping Sickness)?
The types of protozoa known as T brucei gambiense and T brucei rhodesiense cause a disease called Human African Trypanosomiasis (HAT), which is often spread by the tsetse fly. Rare cases of the disease also spread from one human to another during pregnancy or via blood transfusions.
Trypanosoma is a single-celled parasitic organism that requires two hosts to complete its life cycle. When this parasite enters the human body, it has two main forms: one is long and slender and can divide and multiply, while the other is short, “stumpy,” and doesn’t multiply. The slender form can swim around in the bloodstream or lymphatic system (the body’s disease-fighting network of organs and tissues) and invade various organs, including the brain and spinal cord.
The transformation from slender to stumpy form is kickstarted when the parasitic cell count or ‘parasitemia’ reaches a certain level in the body. The slender parasites then start to produce increased amounts of a substance called ‘stumpy induction factor (SIF)’, which triggers the transformation. Hence, the change in body shape helps in regulating the population of parasites in the host body. Even though short-lived, stumpy trypanosomes are more capable of infecting the tsetse fly.
When a tsetse fly bites an infected human or animal, the fly gets infected by either the stumpy or slender form of the parasite. Inside the fly, the parasites begin to multiply, eventually moving to the fly’s salivary glands. Most of the long parasites die off, while the short ones remain attached to the glands. Some of these short parasites can multiply further, while some swim freely around and develop the ability to infect humans, thus completing the life cycle in the fly.
The parasite is usually passed on to the next host about two weeks after the fly’s infected blood meal. If animals are infected, a condition called “nagana” occurs, which can have a significant impact on agriculture.
Risk Factors and Frequency for Human African Trypanosomiasis (Sleeping Sickness)
HAT, or Human African Trypanosomiasis, is a condition found in 36 countries across sub-Saharan Africa. The disease has two versions: West African HAT and East African HAT, each with it’s own characteristics and geographical distributions. The Great Rift Valley in Africa serves as a geographic separator between these two versions of the disease.
- West African HAT is caused by a parasite, T brucei gambiense, transmitted by Glossina palpalis type of insects, both common in this region. These insects are primarily found near water sources, putting those who live or work in these areas at risk.
- Humans are the only reservoirs of West African HAT, causing 98% of HAT cases.
- This version of HAT is rarely seen in tourists but common in refugees and immigrants. The Democratic Republic of Congo hosts majority of these cases, about 80%.
- The World Health Organization (WHO) is working to stop the transmission of West African HAT by 2030.
- East African HAT, on the other hand, grows from T brucei rhodesiense, transmitted by Glossina morsitans type of insects. These species are more prevalent in East Africa.
- Unlike its West African counterpart, T brucei rhodesiense’s main reservoirs are cattle and other mammals. Thus, the disease mainly affects wild animals and cattle, especially in Uganda and Kenya.
- G morsitans insects live in dry, wooded areas and don’t bite humans as frequently as other mammals.
- Majority of East African HAT cases occur in Zimbabwe, Tanzania, Zambia, and Malawi.
In the late 1800s and early 1900s, HAT caused epidemics that resulted in nearly a million deaths. Despite efforts to eradicate the disease in the 1960s, the disease reappeared due to a combination of increasing population and decreased surveillance. Estimates suggest that there were around 300,000 HAT cases in sub-Saharan Africa in 1998. By 2012, HAT cases had reduced to 7000 owing to increased screening and treatment, and by 2022, there were less than a thousand cases reported.
Despite these efforts, HAT remains prevalent in rural and impoverished areas, and the number of cases is likely underreported.
Signs and Symptoms of Human African Trypanosomiasis (Sleeping Sickness)
The disease known as HAT occurs in two stages. The first stage involves the blood and lymphatic system, while the second stage signifies that the disease has spread to the central nervous system (CNS). The earliest symptom of HAT is a skin sore at the spot where the disease enters the body. However, this only occurs in certain types of HAT, and doesn’t always show up in others. After this, people may experience fever, headaches, itchy skin, and swollen lymph nodes. These fevers might last up to a week and then disappear, only to show up again as the disease continues to multiply in the blood.
The location of the swollen lymph nodes differs between the two types of HAT. Some types of HAT cause swelling at the back of the neck, while others cause swelling in the groin, under the jaw, and under the arm. Liver and spleen enlargement, along with issues with the hormone-producing glands, occur more frequently in the first stage of one type of HAT disease than the other. Disruptions with the hormones controlling the thyroid, reproduction, and stress response can happen more frequently in one type of HAT disease due to the parasite infiltrating these glands.
When the disease invades the CNS in the second stage, significant symptoms occur. People often have issues with their sleep cycle, leading to the name “African sleeping sickness.” This includes sleeping during the day and staying awake at night alongside fragmented sleep with frequent short periods of rapid eye movement. Other symptoms affecting the nervous system include shaking, muscle weakness, involuntary movements, stiffness, and changes in reflexes. Changes in mental state and mood can also occur, such as aggression, lack of interest, psychosis, or irritation.
Unlike another disease caused by a type of Trypanosoma parasite, Chagas disease, the heart is less frequently involved in certain types of HAT. About half of those affected may develop heart rhythm abnormalities, but these changes are usually not clinically significant. Severe inflammation of the heart tissues is rare. However, for another type of HAT, severe inflammation of the tissues surrounding the heart may occur.
HAT can present differently in travelers, often showing up as skin sores and more severe internal organ problems. A temporary rash may occur in people with lighter skin tones, characterized by redness, itching, and a bullseye appearance. Infections with both types have shorter incubation periods.
If either form of HAT is left untreated, the final stage of the disease is a coma followed by death. One type of HAT infection can lead to death more quickly within weeks to months, while death from an untreated other type of HAT infection usually occurs about three years after the disease enters the body.
Testing for Human African Trypanosomiasis (Sleeping Sickness)
The preferred way of diagnosing T. brucei rhodesiense infection, known to cause high levels of parasites in the blood, is by simply analyzing a sample of peripheral blood. On the other hand, diagnosing T. brucei gambiense infection might require more sensitive testing methods because it doesn’t always lead to an obvious increase in the number of parasites in the blood.
A “card-agglutination test for trypanosomiasis” (CATT) is often the first step in screening for suspected cases. This test uses a blood sample, either taken from a vein or a finger-prick, to identify the presence of T. brucei gambiense antigens. Although this test can correctly identify an infection 91% of the time, it can’t be used alone for a confirmed diagnosis, especially in areas with low prevalence. More sensitive screening tests, like immuno-fluorescence or enzyme-linked immunosorbent assays, can be used in regions where the disease is not commonly found.
Diagnosing this disease involves several steps such as reviewing the patient’s medical history, including any travels to areas with high incidence of the disease, directly spotting the parasite under a microscope, and incorporating additional blood tests. Blood, lymph node fluid, or cerebrospinal fluid (CSF) could be checked under a microscope to find the parasites, but the accuracy of the test would largely depend on the skill and experience of the laboratory technician.
Commonly-used blood tests often have low sensitivity, but some specific techniques, like small anion exchange and capillary tube centrifugation or a buffy coat examination, can increase detection rates. If available, PCR can also help diagnose the disease.
Checking the CSF can help confirm whether the disease has advanced to stage 2 in suspected patients; however one needs to be aware that parasites may not always be present in the CSF. According to the World Health Organization (WHO), having more than 5 white blood cells per μL of CSF is considered a sign of stage 2 disease.
If it’s suspected that a patient with T. brucei gambiense infection has severe Stage 2 disease, or if they shouldn’t receive fexinidazole, a type of drug, then a CSF evaluation would be recommended. Symptoms raising a suspicion for severe Stage 2 disease might include confusion, abnormal behavior, erratic or impaired speech, imbalance, abnormal movements, muscular weakness, and seizures.
Contrarily, the World Health Organization advises that patients with the T. brucei rhodesiense infection should have a cerebrospinal fluid evaluation as it influences treatment decisions directly. This policy is being updated as fexinidazole, a medication that works for both early-stage and mild late-stage disease, is becoming more widespread.
Treatment Options for Human African Trypanosomiasis (Sleeping Sickness)
The approach to treating Human African Trypanosomiasis (HAT), also known as African sleeping sickness, depends on various factors. This includes the cause of the disease, the stage of infection, personal patient details, as well as any existing health conditions. HAT requires immediate treatment to minimize the complications and to stop the disease from spreading.
For a type of HAT found in West Africa, the drug, Fexinidazole, is typically used. This treatment can be taken orally, which makes it much easier for communities with limited medical resources. People most likely to receive this treatment are adults and children over 6 years who weigh more than 20kg. However, the drug can cause side effects such as nausea, loss of appetite, sleep issues, vibrations in the body and can interfere with liver health or cause allergies. A smaller group of patients, such as young children or those with specific medical constraints, might be given an alternative drug, Pentamidine.
A more severe stage of HAT, called stage-2, can also be treated with Fexinidazole. However, the medication Nifurtimox-eflornithine combination therapy (NECT) may be used, especially in children and adults who weigh less than 20 kg, or when a specific cell count in the cerebrospinal fluid (CSF) is high. If the normal treatments are not effective, another medication, Melarsoprol, can be used, but with caution, as it can cause fatal side effects.
The treatment for the East African variant of HAT is similar. Fexinidazole is primarily used again, with Suramin as an alternative. Second-stage disease might require the use of Melarsoprol instead, but it’s not preferred because it can have severe side effects, including a fatal condition known as encephalopathic syndrome.
After the treatment, patients need regular check-ups to make sure the disease does not come back. These check-ups typically take place every 6, 12, 18, and 24 months after treatment concludes. If the disease returns, the person might need another round of treatment. Patients who receive alternative treatments generally do not need as many follow-ups, given the high efficacy rate of those medicines.
What else can Human African Trypanosomiasis (Sleeping Sickness) be?
Relapsing fevers, which come and go, can be a symptom of many different diseases and often suggest the presence of a parasite in the body. Below are some parasitic infections that may cause these kinds of fevers. Knowing if a person has spent time in places where these infections are common, checking if there are issues with blood clotting, and looking out for mental confusion or other changes in brain function during later stages can help differentiate African sleeping sickness from these other illnesses.
- Malaria
- Typhoid fever
- Viral hepatitis
- Ehrlichiosis (a tick-borne disease)
- Dengue fever
- Brucellosis (an infection from unpasteurized milk or undercooked meat)
- Babesiosis (another tick-borne disease)
- Yellow fever
African sleeping sickness can also affect the skin, but the signs can be mistaken as symptoms of other diseases, including:
- Drug rash
- Eschar (a piece of dead tissue) related to Boutonneuse fever, which is another type of tick-borne disease
- Allergic reaction to an insect bite
What to expect with Human African Trypanosomiasis (Sleeping Sickness)
Proper treatment can definitively cure over 95% of patients with the first and second stages of T brucei gambiense disease. On the other hand, those with the second stage of T brucei rhodesiense disease face a 5% to 10% risk of death during or after treatment with a medication called melarsoprol.
Seeking medical help early can significantly lower death rates. However, if diagnosis and treatment are delayed, the illness can be deadly. The prognosis for untreated Human African trypanosomiasis (HAT), which is the disease caused by T. brucei, is extremely poor, and death is inevitable.
When melarsoprol was the only medication available, the death rates were higher, with 4% to 12% of deaths resulting from the treatment rather than the disease itself. This has changed thanks to the approval of a new drug called fexinidazole by the European Medicines Agency for use in treating T brucei rhodesiense disease, which has led to less use of melarsoprol.
Possible Complications When Diagnosed with Human African Trypanosomiasis (Sleeping Sickness)
Most individuals who undergo treatment for the first stage of Human African Trypanosomiasis (HAT) usually don’t face any complications post-treatment. However, if you’ve had treatment for the second stage of HAT, you might experience enduring neurological problems. Research suggests that about 12 to13 years after the treatment for the second stage of HAT, about 7.8% of people reported having issues with sleep during the night and 3.9% reported having trouble sleeping during the day. Around 11% of people experienced headaches.
It was also found that issues like speech difficulties, muscle weakness, and changes in personality generally lessen following treatment. At the follow-up check-up 12 to 13 years after treatment, no increased risk was observed.
Common Long-term Effects:
- Nighttime sleep difficulties (7.8% of patients)
- Daytime sleep problems (3.9% of patients)
- Headaches (11% of patients)
- Speech difficulties
- Muscle weakness
- Personality changes
Preventing Human African Trypanosomiasis (Sleeping Sickness)
Implementing strict control programs is key to reducing cases of Human African trypanosomiasis (HAT), a disease spread by a parasite called T. brucei. These control programs often include active screening campaigns, where mobile teams test and treat people in areas where the disease is common. This approach helps stop the life cycle of the parasite and reduces the number of people who get the disease. At present, there isn’t a vaccine available to prevent HAT.
If you live in or travel to areas where HAT is common, it’s important to avoid places that are known to have lots of tsetse flies, the insects that spread the disease. Wearing long-sleeved tops, long pants, and sleeping under nets treated with insecticide can help lower the risk of tsetse fly bites. As for cattle, treating them with insecticides can help control outbreaks of the disease, specifically the T. brucei rhodesiense strain, further lowering the risk of human infection.
