“With these new data, we have hope that we may be able to finally eliminate the disease [African Sleeping Sickness] once and for all.”
- Dr. Antoine Tarral, Head of Human Trypanosomiasis Clinical Program, Neglected Disease Initiative
“Is Trypanosoma cruzi closer than we think, and what should we do about it?”
- Claire Panosian Duncan, professor of medicine and infectious diseases, David Geffen School of Medicine, UCLA
Trypanosoma brucei gambiense, the cause of African sleeping sickness, and T. cruzi, the etiology of Chagas disease, are two protozoans that are big threats in the tropical world. Both of these parasites have been in the news recently: T. brucei gambiense because a new “miracle drug” (acoziborole) was found to cure 95% of people with African sleeping sickness; and T. cruzi because of an alarming expansion of its insect vector—the “kissing bug”—in the southern U.S. (The Center for Disease Control and Prevention (CDC) estimates that T. cruzi afflicts more than 300,000 people living in the U.S.) In this week’s Germ Gem post, I focus on these two protozoans.
A synopsis of parasites. The authors of the book “Parasites” describe them “as blood suckers, freeloaders, scroungers, flunkies, deadbeats, and the worst kind of groupies.” We humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa. If you’re like most people, you probably view parasites with disgust.
But like beauty, ghastliness, is in the eye of the beholder. In the eyes of this beholder, it was when I was a medical student that I first contemplated the amazing (I dare say, elegant) life cycles of parasites and was attracted to a career in infectious diseases.
What is trypanosomiasis? Three species of parasites called trypanosomes are pathogenic to humans: Trypanosoma gambiense andT. rhodesiense in Africa and T. cruzi in America. Superficially, African trypanosomiasis (sleeping sickness) and American trypanosomiasis (also called Chagas disease) appear to be similar. Both are caused by single-celled flagellates that are morphologically indistinguishable; are transmitted by the bites of arthropods; and are marauders mainly in low-income, tropical countries. But that’s where the similarities end.
African trypanosomiasis. Depending on the subspecies of parasite involved, human African trypanosomiasis takes two forms Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense. The insect vector for both forms of African trypanosomiasis is the tsetse fly.
Trypanosoma brucei gambiense is found in 24 countries in west and central Africa. This form of the disease currently accounts for 97% of reported cases of sleeping sickness. A person can be infected for months or even years with this parasite without exhibiting major signs or symptoms of the disease. When evident symptoms emerge, the patient is often already in an advanced disease stage where the central nervous system is affected. (In late stages of disease, sleep patterns are grossly disturbed, thus the nickname “sleeping sickness.”)
Trypanosoma brucei rhodesiense is found in 13 countries in eastern and southern Africa. This form of disease represents under 3% of reported cases of patients who develop more acute clinical manifestations.
In recent years, 7,000-10,000 new cases of West African trypanosomiasis have been reported annually to the World Health Organization (WHO). Many cases, however, are not recognized or reported, and the true number of annual cases is likely to be higher.
West African trypanosomiasis is a vicious disease characterized in its early stages by fever, severe headaches, irritability, extreme fatigue, swollen lymph nodes, and aching muscles and joints. Following invasion of the central nervous system, progressive confusion, personality changes, and other neurologic problems ensue which, if untreated, result in mortality close to 100%.
Treatment of African sleeping sickness. Antitrypanosomal treatment is indicated for all persons diagnosed with African trypanosomiasis. Choice of therapy depends on the infecting subspecies of the parasite and on the disease stage.
Recently, a new oral drug acoziborole has emerged that is 95% effective at curing sleeping sickness with just one dose. In November, 2022, the Lancet Infectious Diseases published the results of clinical trials for acoziborole. According to Dr. Antoine Tarral, Head of the WHO’s Trypanosomiasis Clinical Program, this drug has the potential to revolutionize treatment of sleeping sickness, thereby helping the WHO reach its goal of eliminating sleeping sickness by 2030.
American trypanosomiasis. This form of trypanosomiasis is also called Chagas disease, named after the Brazilian physician Carlos Chagas who in 1909 discovered that the disease is caused by T. cruzi. The insect vector (triatome bugs) of Chagas disease are found only in the Americas (mainly in rural areas of Latin America).
Blood-sucking triatome bugs get infected by biting an infected animal or person. Once infected, the bugs pass the parasites in their feces into the bite wound. These insects are referred to as “kissing bugs” because they often bite the face near the mouth and after biting [“kissing”] you, deposit their T. cruzi-containing poop into the wound. (Talk about adding insult to injury!)
About 6–7 million people worldwide are estimated to be infected with T. cruzi. The disease is found mainly in endemic areas of 21 continental Latin American countries, where it is mostly transmitted to humans and other mammals by contact with feces of triatomine bugs. T. cruzi can, however, also be transmitted by consumption of food or beverages contaminated with the parasite.
Chagas disease presents in two phases. The initial acute phase lasts for about two months after infection. During the acute phase, a high number of parasites circulate in the blood, but in most cases symptoms are absent or mild and nonspecific. The first characteristic visible sign of infection can be a skin lesion or a purplish swelling of an eyelid. Additionally, some patients can present with fever, headache, enlarged lymph glands, pallor, muscle pain, difficulty in breathing, swelling, and abdominal or chest pain.
During the chronic phase of infection, the parasites are hidden mainly in the heart and muscle of the gastrointestinal tract. One to three decades later, up to 30% of patients suffer from cardiac disorders including cardiomegaly, and up to 10% suffer from digestive symptoms (typically due to enlargement of the esophagus or colon). In later years the infection can cause the destruction of the heart muscle with consequent cardiac arrhythmias or progressive heart failure and sudden death. Of the 300,000 people living in the U.S. with Chagas disease, the CDC estimates it causes about 10,000 deaths per year.
Chagas disease was once entirely confined to continental rural areas of the Region of the Americas. Due to increased population mobility over recent decades, most infected people now live in urban settings. As a result, the infection has been detected increasingly in the U.S. and Canada as well as in many European and some African, Eastern Mediterranean and Western Pacific countries.
Vector creep. A large majority of Latin Americans who are living with Chagas disease in the U.S. are members of the Latinix diaspora. But mounting concern is surfacing about the apparent emigration of kissing bugs across the southern border of the U.S. and climate change appears to be playing a role.
In a January 8, 2023 article in MedPageToday, “Kissing Bug Confidential: Priorities for Managing Chagas Disease,” infectious diseases specialist Dr. Claire Panosian Dunavan discusses findings by several research groups demonstrating that up to 30% of kissing bug species in some southern states harbor T. cruzi. It is not known whether infected people brought the parasite with them or if they picked it up locally. But, as she points out, the vast majority of infected human hosts don’t know they harbor “a ticking protozoan time-bomb that confers a 1 in 3 chance of robbing them of their health and shortening their life.” In her article, Dr. Dunavan also points out the profound implications of this worrisome development for clinicians, public health officials, and educators, as well as residents of these southern states.
Treatment of Chagas disease. Antiparasitic treatment is indicated for all cases of acute or reactivated Chagas disease and for chronic T. cruzi infection in children up to age 18. Treatment is also strongly recommended for adults up to 50 years old with chronic infection who do not already have advanced heart enlargement (cardiomyopathy). For adults older than 50 years with chronic T. cruzi infection, the decision to treat with antiparasitic drugs should be individualized, weighing the potential benefits and risks for the patient.
Two drugs are used to treat T. cruzi infection, nifurtimox and benznidazole. Determining what drug to use and obtaining the drugs are complicated and need to be carefully reviewed with an experienced clinician. Also, side effects are fairly common with both drugs and tend to be more frequent and more severe with increasing age. Clearly, better therapeutic agents are needed. (Something akin to the single dose acoziborole for African trypanosomiasis would be a godsend.)
Paying more attention to neglected tropical diseases. The WHO and the CDC recognize that tropical diseases are huge and underfunded areas of public health. Both organizations offer programs for “Neglected Tropical Diseases” that address health needs of people living in tropical countries. African trypanosomiasis and American trypanosomiasis are among the 20 tropical diseases covered in these programs. (The Bill & Melinda Gates Foundation recently awarded four grants totaling $68.2 million to help accelerate research on neglected tropical diseases, including trypanosomiasis.)
In 2009, the not-for-profit organization, “Drugs for Neglected Diseases initiative” (DNDi), a partnership between NGOs, governments, pharmaceutical companies, and the WHO, was launched. The DNDi discovers, develops, and delivers treatments for patients with neglected tropical disease around the world. It played an important role in the development of acoziborole for treatment of African sleeping sickness.
Because we live in such a small world, where “the global is local, ”these programs are paying off in serving people living in many tropical and non-tropical countries around the world.