Understanding Human African Trypanosomiasis: A Sleeping Sickness

Introduction

Human African trypanosomiasis is a neglected endemic illness more prevalent in sub-Saharan Africa. It is a parasitic disease caused by the trypanosome species and transmitted by the tsetse fly bites. It is also a sleeping sickness disease because the patients usually suffer from disturbed sleep patterns. It differs from American trypanosomiasis, or Chagas disease, caused by Trypanosoma cruzi and transmitted by the kissing bug. Africa has witnessed three significant epidemics, the most devastating between 1896 and 1906, which saw several fatalities and mortalities. However, due to coordinated international efforts and combination approaches, the disease was well controlled by 1920. However, its re-emergence in 1970 has been a significant public health concern. WHO and other national and international organizations have devised positive programs to help reverse the curve and eliminate the disease.

What Is Sleeping Sickness?

Sleeping sickness, or African trypanosomiasis, is a parasitic condition caused by two known species, Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. It is transmitted by the bite of the tsetse fly. This condition is not fatal if diagnosed and treated early. However, any delay will affect the central nervous system as the parasite can cross the blood-brain barrier. It may cause confusion, lethargy, and disturbed sleep. Severe cases may result in convulsions and death.

How Has Sleeping Sickness Impacted Globally?

• Sleeping sickness is a tropical condition that is endemic in 36 sub-Saharan African countries.

• Several epidemics have occurred in Africa, the latest between 1970 and 1990.

• It is estimated that around three million people reside in moderate to very high-risk areas.

• Infection in children accounts for roughly around 20 percent.

• Disease controls have usually been followed by deadly epidemics.

• The cases have progressively decreased from less than 10000 in 2009 to 663 in 2020.

• Fifty-five million people were estimated at risk between 2016 and 2020.

What Are the Types of African Trypanosomiasis?

There are two primary forms of human African trypanosomiasis. They are:

Trypanosoma Brucei Rhodesiense:

• Found in 13 countries of east and southern Africa.

• Accounts for 3 percent of reported cases.

• Results in acute infection.

• Symptoms observed within weeks after infection.

• Disease progresses rapidly and involves the central nervous system.

Trypanosoma Brucei Gambiense:

• Found in 24 countries of west and central Africa.

• Accounts for 97 percent of reported case.

• Results in chronic infection.

• Can remain symptomless for months and years.

• At the time of diagnosis patient is already in an advanced stage with central nervous system involvement.

How Is Sleeping Sickness Transmitted?

The infection is transmitted by the bite of an infected tsetse fly. However, there are other modes of transmission, such as:

• Vertical transfer from the mother to the fetus as the parasite can cross the placental barrier.

• Accidental picks with contaminated needles.

• Sexual contact.

• A community spread through another insect bite.

What Is the Pathophysiology of This Disease?

The tsetse fly gets infected by an infected human or animal that can harbor this parasite. The infected fly introduces the parasite into the host when it bites. Upon biting, the parasite, loaded in the fly's saliva, is introduced into the host's skin. This form of the parasite is infective and is known as metacyclic trypomastigotes. Once they enter the bloodstream, the parasites transform into slender trypomastigotes that can rapidly diffuse to other body fluids, such as lymph and spinal fluid, through the blood, where they continue to multiply. When taking a blood meal on the infected host, a tsetse fly can get infected with these trypomastigotes in the bloodstream. These trypomastigotes transform into procyclic trypomastigotes in the fly's midgut and leave the midgut as epimastigotes. The epimastigotes reach the fly's salivary gland and attach themselves there, continuing to multiply. Subsequently, the epimastigotes transform into metacyclic trypomastigotes, the infective form, and get ready to be introduced into the new host in the next blood meal.

What Are the Signs and Symptoms Associated With This Disease?

There are two major stages in this condition. They are:

First Stage:

• Also known as the haemolymphatic stage.

• Begins soon after the metacyclic trypomastigotes enter the body and multiply.

• It begins with an inflammatory reaction under the skin.

• Results in swelling of the skin and enlargement of neck nodes.

• Other symptoms in this phase are fever, malaise, headache, itching, and joint pain.

Second Stage:

• This is also known as the neurological phase.

• This phase begins when the parasite crosses the blood-brain barrier and reaches the spinal fluid and lymphatic fluid.

• Affects the central nervous system resulting in disorientation, altered behavior, poor coordination, slurred speech, and disturbed sleep (patients sleep throughout the day and none at night). Delay in treatment could result in fatality.

How Is Sleeping Sickness Diagnosed?

Early diagnosis is essential to prevent the disease from progressing to the neurological phase. Unfortunately, since this is a rural tropical disease, most cases go undiagnosed due to poor or nil medical support and awareness. Screening programs in endemic areas can help check for clinical signs such as skin inflammation, lymph node enlargement, or other altered neurological signs. In addition, prophylactic blood smears can be taken in the suspected zone to check for parasites. Diagnostic tests include the following:

• Antibody blood test to check for the presence of the parasite.

• Lumbar puncture to assess the progression of the disease. Assessing the spinal fluid through lumbar puncture can help identify the spread of the parasite to the spinal fluid. Staging can also be done using a lumbar puncture.

Stage 1: When there are no trypomastigotes or five or lesser WBCs (white blood cells) in the wet preparation of the spinal fluid, it is considered stage 1.

Stage 2: The presence of trypomastigotes or more than five white blood cells is considered stage 2.

How Is Sleeping Sickness Treated?

Sleeping sickness is curable if diagnosed early. Treatment depends on the stage of the disease. The neurological stage requires aggressive and prolonged therapy. The four main drugs used in treating are:

• Pentamidine: Used primarily to treat the first stage of Trypanosoma brucei gambiense. This drug is safe with not many adverse effects.

• Suramin: Used in treating the first stage of Trypanosoma brucei rhodesiense. Urinary tract infections and allergic reactions are minor side effects.

• Melarsoprol: Used in treating the second stage of Trypanosoma brucei rhodesiense. Increasing resistance is observed with this drug. It can cause severe side effects, including reactive encephalopathy.

• Eflornithine: Used to treat the second stage of Trypanosoma brucei gambiense. It causes less severe side effects like vomiting, anemia, or diarrhea

• Nifurtimox: A combination therapy of Nifurtimox and Eflornithine has proved more productive as it drastically reduces treatment time.

• Fexinidazole: This drug is more effective against Trypanosoma brucei gambiense. It is considered a first-line drug in the first stage. This drug was introduced in 2019, and its application in rhodensiense is still under clinical trial.

How Can Sleeping Sickness Be Prevented?

• Presently there are no vaccines to prevent human African trypanosomiasis. Therefore, prevention generally aims at minimizing the vector contact (tsetse fly).

• Limiting the amount of skin exposure by wearing long-sleeved clothes.

• Clothes in neutral colors can help distract the tsetse fly.

• Avoiding bushes and such places, which are the resident habitat of the tsetse fly.

• Insect repellent might prove beneficial.

• Population screening as fewer infected people means fewer infected tsetse fly, and thus the cycle could be halted.

• Regular use of insecticides at home and on agricultural lands.

Conclusion

Human African trypanosomiasis is an endemic condition with a good prognosis if diagnosed and treated early. The cure rate is over 90 percent. However, patients presenting in stage 2 require rigorous treatment and monitoring to avert fatalities. Several studies on novel drugs are under trial with the drugs for neglected diseases initiative (DNDi). However, though clinical trials are successful, immediate implementation of these drugs is impossible. Hence, community involvement and superior screening techniques should emphasize prevention and control. World Health Organisation (WHO) aims to completely eradicate this tropical disease by 2030 though logistical issues and the uncommon nature of this disease pose a real challenge.