I thought donating blood was a way to show my love, but unexpectedly it almost killed someone

In April 1988, an American girl named A followed her parents into a hospital in New York. The reason for the visit may not seem too serious from a modern medical perspective—she had a fever of 38.3°C. However, due to A’s health condition over the past year, her parents took any discomfort she had very seriously.

At only 11 years old, Xiao A had been fighting Hodgkin's lymphoma for more than a year. During this year, she had almost non-stop radiotherapy, chemotherapy, and blood transfusions. In May 1987, she underwent a splenectomy. Although her health was gradually improving, these treatments almost destroyed her immune system, and normal inflammatory reactions such as fever could be a hurdle that she could not overcome.

This time, the situation was not optimistic. After she was hospitalized, she developed high fever, convulsions, generalized edema, and dyspnea, and was immediately diagnosed with acute myocarditis. After ruling out all kinds of speculation, the doctor collected her bone marrow fluid and found a parasite about 20 μm in length.

She was subsequently diagnosed with Trypanosoma cruzi infection.

Trypanosoma cruzi found in the bone marrow fluid of Little A | Annals of Internal Medicine 1989

Although the results were obvious, the doctors still found it baffling: How could little A, who had been staying in the United States, be infected with this parasite that is only prevalent in South America?

Trypanosoma cruzi originated in South America

At that time, people had already known that the disease was caused by Trypanosoma cruzi. Trypanosoma cruzi is mainly transmitted by a type of insect called Triatomine bugs (Triatomine subfamily, family Assassinidae). These insects generally live in animal nests or near human homes, hiding during the day and active at night. Triatomine bugs can deliver trypanosomes in the blood of infected people to new hosts through bites, and direct blood transmission between infected people can also have a pathogenic effect.

Cone bugs | www.fda.gov

The disease caused by Trypanosoma cruzi was discovered and named by Brazilian doctor Carlos Chagas in 1909, so it is also called Chagas Disease or American trypanosomiasis. Both humans and animals are potential hosts of this trypanosome. After being infected, humans will enter an acute inflammatory phase lasting two months. Most people do not have obvious symptoms, but there are also cases where erythema or nodules appear. A few acute symptoms include fever, muscle pain, swollen lymph nodes, coma, etc. According to statistics, 10% of cases eventually die from myocarditis or meningitis during the acute phase.

The first case of Chagas disease in Chagas, Berenice | Archives of the Instituto Oswaldo Cruz. (https://internal-journal.frontiersin.org/articles/10.3389/fpubh.2019.00166/full)

After the first patient, Berenice, was discovered in Brazil, doctors found patients with Chagas disease in many countries in South America. However, perhaps because cone bugs are more likely to reproduce in places with poor sanitary conditions, the areas where people first discovered that Chagas disease was prevalent were mostly poor and backward villages or areas with chaotic socioeconomic conditions. Because of this, this disease is always associated with poverty and chaos in people's first impression, and people naturally think that as long as they are not in such an environment, the disease will not come to them.

Little A, who had never been to South America and had never come into contact with the cone bug carrying Trypanosoma cruzi, was infected with Chagas disease. The doctors' ideas for tracing the pathogen went around in circles and finally shifted to the path of blood transfusion infection.

Sure enough, after tracing back to the source, doctors discovered that these Trypanosoma cruzi originated from the last platelet transfusion that Xiao A received in February 1988. The blood donor who provided her with life-saving blood was a Chagas disease patient who came to the United States from Bolivia in South America 15 years ago.

This result also made American doctors at the time break out in a cold sweat. Xiao A's case was published in the Annals of Internal Medicine that year, followed by an article by Louis Kirchhoff, an American doctor who specializes in Chagas disease, titled "Is Trypanosoma cruzi a major threat to our blood supply?", calling on the entire medical community to pay attention to the safety of testing blood sources.

Kirchhoff published an article in the Annals of Internal Medicine in 1989, calling on the entire medical community to pay attention to the safety of blood testing.

But in fact, this blood donor from Bolivia is also innocent. In the 15 years since she came to the United States, she may never have known that she had been carrying this parasite that is deadly to others.

In fact, 70% of people infected with Trypanosoma cruzi may never know that they are carriers of the disease. This has to do with the infection mechanism of Trypanosoma cruzi: after the acute phase of massive reproduction and severe inflammatory response in the host, most Trypanosoma cruzi will hide in cells and live in a low-key manner; a small part remains in the blood and does not cause the immune system to hunt it down - this is the asymptomatic period of "coexistence" with the parasite. They may make a comeback when the host becomes immunocompromised, but for most lucky people, the presence of Trypanosoma cruzi is so low that it can be a symbiont with the host for a lifetime.

Fortunately, they are also unlucky. Although they are healthy, they may infect others without knowing it, just like Xiao A in this article. Another example is that after her case attracted the attention of the American medical community, they finally developed a sensitive and rapid blood test for Trypanosoma cruzi in 1998. When this blood test was applied to the stored blood samples, it was found that 1,300 of them were from people infected with Chagas disease.

Over the past decade, how many people have been infected by these "toxic" blood samples?

For this latent infectious disease, the problem is often not detected until it is too late. It is estimated that there are about 300,000 Chagas disease patients in the United States today.

What did we do?

Little A was lucky. She survived the acute phase by increasing the dose of nifurtimox, a special medicine for treating parasitic infections, and interferon-γ, which enhances immune response. Fortunately, we already have drugs such as benznidazole and nifurtimox for the treatment of Chagas disease. Once infected, as long as the drug is used as soon as possible, the possibility of worsening symptoms and damage to the body can be minimized.

However, their effects are not as good as we expected. Both drugs have serious side effects, and they can only be used to relieve acute inflammation, and it is difficult to eradicate Trypanosoma cruzi. To make matters worse, people have found in recent years that some mutants of Trypanosoma cruzi have developed cross-resistance to benznidazole and nifurtimox. Once this drug-resistant mutation takes hold, we will be helpless against cases like Xiao A. Cases of Chagas disease have gradually been discovered in Europe, Canada, and recently in Japan. Therefore, global attention and cooperation are urgent.

Some mutants of Trypanosoma cruzi have developed cross-resistance to the effective drugs benznidazole and nifurtimox, so people must come up with new countermeasures as soon as possible | Pixabay

People are actually taking action.

With the "precedent" of Xiao A and many other people who were infected due to blood transfusions, the World Health Organization mentioned in the "Ten-Year Goals for Tropical Disease Prevention and Control 2021-2030" the need to fully block the transmission of Trypanosoma cruzi during organ transplantation, blood transfusion, and between mothers and children.

The international nonprofit DNDi (Drugs for Neglected Diseases Initiative) will report on the progress of a new drug they have been developing for Chagas disease by the end of the year. This approved African trypanosomiasis drug is called fexinidazole, and it has been shown in mouse models to kill strains of Trypanosoma cruzi that are resistant to benznidazole, so people have high expectations for its Phase II clinical trial that will be completed in Spain this year.

Just on November 4, the Global Health Innovation and Technology Fund (GHIT) also announced that it would invest a total of 750 million yen in DNDi. Three of the six projects invested in are about the genetic sequencing of Trypanosoma cruzi and the screening of new drugs (the other three are the development of malaria drugs and vaccines and the diagnosis of tuberculosis). This shows the level of attention that Chagas disease is currently receiving.

It is also gratifying that the National Institutes of Health of the United States also confirmed a grant of US$300,000 in September this year to support the development of a new Chagas disease detection technology specifically to overcome the problem of its difficulty in prevention and control during the incubation period. This technology is expected to detect a very small amount of biological information of Trypanosoma cruzi through blood samples, thereby determining whether the patient has been completely cured - higher detection sensitivity can not only help us achieve more rigorous epidemic screening, but also provide accurate feedback for drug development.

At present, the most effective preventive measure is to control various pathogen transmission media and call on the public to pay wide attention. If we are temporarily unable to do anything about the parasites that have already hidden in the bodies of infected people, at least we can prevent them from infecting more people by strengthening screening and blocking transmission.

Chagas disease awareness poster posted on a wall in Guyana, South America | Wikimedia Commons, Alex Kwok / CC BY-SA 3.0 (https://creativecommons.org/licenses/by-sa/3.0)

In areas where the trypanosome-carrying cone bugs are prevalent, the main focus is to improve living conditions and house structures, such as applying lime on the walls, repairing roofs or cracks to prevent cone bugs from breeding indoors, etc. Using mosquito nets and spraying insecticides can prevent the spread of vectors and prevent food and water sources from being infected by cone bug excrement. There are no cases of infection with American Chagas disease in my country, so the threat from cone bugs is not great. However, we should also fully quarantine the floating population and livestock to prevent human-to-human and animal-to-human transmission.

With the intensification of globalization and population mobility, there are no real "corners" in the world. All local epidemics can hardly be called truly "local". If each epidemic is not taken seriously and prevented, it may eventually affect everyone. Although many of the projects mentioned above are still in progress and even seem to be "not even a scratch", if the attention and practical efforts to this disease have become a kind of global consensus, we can also see some hope for human beings to eradicate it in the future.

Nine thousand years later

In fact, the first batch of Trypanosoma cruzi that entered human blood appeared much earlier than people imagined.

In the early 20th century, scientists discovered mummies of the Chinchorros, the indigenous people of South America, in the Atacama Desert of South America. These mummies can be traced back to 9,000 years ago, 2,000 years earlier than the mummies of ancient Egypt. With the development of molecular biology technology, people have also found residual ancient DNA in these mummies - in addition to human DNA sequences, there are also gene fragments of Trypanosoma cruzi.

This means that Trypanosoma cruzi had already infected these South American indigenous people 9,000 years ago. They probably just arrived in South America to settle down and intervene in the local ecosystem. Trypanosoma cruzi came to humans through the original transmission chain between local wild animals (Sylvatic Cycle), and finally established this 9,000-year-long human-to-human transmission chain (Domestic Cycle).

It took nearly nine thousand years to discover the true identity of this parasite, and less than a hundred years to develop a drug that would save patients from death. How long will it take to completely eradicate it?

At least I hope that in another nine thousand years, if people find Trypanosoma cruzi again in the remains left by us today, they can smile calmly and regard it as a completely defeated enemy of ancient times.

References

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