SÃO PAULO, SP (FOLHAPRESS) – Experiments with mice at the USP (University of São Paulo) revealed one of the mechanisms that causes malaria acute respiratory syndrome (ARDS). This type of complication has no early diagnosis and mortality reaches 80% of affected patients.
Research published in the journal Cell Death & Disease has also shown that intervention in this process reduces mortality, thus paving the way for work that seeks new treatments in humans.
Plasmodium berghei was tested on mice known as DBA / 2 infected with the ANKA parasite. The model mimics several aspects of human syndrome, such as pulmonary edema, bleeding, pleural effusion, and poor blood oxygenation (hypoxemia).
In the article, scientists describe that apoptosis (a kind of programmed cell death) helps in the development of the syndrome by facilitating the rupture of the alveolar capillary barrier in the lungs, where carbon dioxide is exchanged with oxygen.
That is, after apoptosis, the increased vascular permeability caused by touching infected erythrocytes (red blood cells) with cells lining the blood vessels (endothelium) increases. These cells differentiate and enlarge the “holes” between them, thus allowing fluid to pass through the extravascular environment and causing pulmonary edema.
Mice with ARDS showed greater apoptosis in both endothelial and inflammatory cells (leukocytes) compared to animals that did not develop the syndrome and those that were not infected with Plasmodium (control group).
According to the study, caspans (a family of proteins that regulate the processes of cell death and inflammation) are responsible for the mechanisms of cell death. When ZVAD-fmk was treated with a caspase inhibitor, the group observed a reduction in apoptosis and a reduction in edema formation. As a result, the mortality of sick animals decreased: their respiratory capacity and lung injuries improved.
“In addition to helping to understand one of the mechanisms that lead to acute respiratory failure syndrome and increased vascular permeability, we have demonstrated that intervention in this process can help reduce mortality in malaria cases,” he summarized. Agência FAPESP to Sabrina Epiphanio, Professor and Head of Research at the USP Faculty of Pharmaceutical Sciences.
The first authors of the article, Michelle Klein Sercundes and Luana dos Santos Ortolan, were Epiphany’s graduate students (master’s, doctoral, and postdoctoral). The team, which also includes researchers from the Institute of Biomedical Sciences (ICB-USP) and the ABC Federal University (UFABC), received support from FAPESP through five projects (13 / 20718-3, 15 / 06106-0, 20/20). 06747-4, 20 / 03175-0 and 20 / 03163-1).
“There is not much in vivo research on this type of respiratory syndrome. Few groups work in this direction, hence the originality of the results obtained,” says Epiphanio, who has been researching the subject for almost 15 years (read more: agencia. FAPESP.br/ 12124 /) .
Malaria-related SDRA is a serious disease that affects between 5% and 20% of people infected with Plasmodium, and about 80% of them die with intensive care despite hospital treatment. The pathogenesis of the disease, that is, the way it affects the body, is still little studied and there is no evidence to detect the problem early. There are still difficulties in learning in humans.
The new case “Acute respiratory syndrome caused by malaria is similar to that of Covid-19,” the professor explained.
Due to the pandemic, malaria prevention, diagnosis and treatment programs have been disrupted in several countries, resulting in an increase in cases and deaths between 2019 and 2020. The WHO (World Health Organization) report reported 14 million new malaria records and 69,000 deaths, two. one-third of the deaths resulting from these interruptions.
In 97 countries, which are considered endemic, the disease puts 40% of the world’s population at risk. In Brazil, 99% of malaria cases are concentrated in the Amazon region. In 2020, there were more than 140,000 indigenous registries in the country, 80% of which were confirmed in 37 municipalities, according to a report by the Ministry of Health. During that period, 42 people were killed.
Considered to be one of the most infectious diseases affecting mankind, Malaria has Plasmodium as its agent, with five different types of protozoa known. The most widespread are falciparum – a more aggressive and recently approved vaccine – and vivax, which accounts for 84% of Brazilian records. All can lead the patient to develop ARDS.
Transmission occurs through the bite of a female Anopheles mosquito when it is infected. And the clinical manifestations are high fever, chills, tremors, sweating and headache. There is also nausea, vomiting, fatigue and lack of hunger. Treatment is performed with anti-malarial drugs, provided by SUS (Integrated Health System), which prevent the development of parasites.