To fill the gaps in knowledge about yellow fever (FJ), an organization of Brazilian researchers affiliated with the Department of Pathology of the University of São Paulo School of Medicine (FM-USP), the Hospital das Clínicas (HC, the complex hospital controlled by FM-USP), the Heart Institute (InCor, linked to the HC), and the Emílio Ribas Institute of Infectious Diseases (IIER) to examine the pathogenesis of central fever-related lesions yellow.
The team was headed by Fernando Rabioglio Giugni, cardiologist, and Amaro Nunes Duarte-Neto, infectologist and pathologist; any of the paintings at FM-USP.
There is still no express remedy for yellow fever. Patients receive extensive health support, including blood transfusions, mechanical ventilation and treatment for seizures, but the mortality rate in severe cases is high, over 35%. »
The research was supported by FAPESP in the context of the Thematic Project on “The use of modern autopsy techniques to investigate human diseases (MODAU)”.
An article published recently in the journal EBioMedicine (an online open-access journal published by The Lancet Group) presents a retrospective autopsy study of cases from the 2017-19 Brazilian YF epidemic, with detailed descriptions of clinical and laboratory data, as well as macroscopic and microscopic aspects of cardiac tissue from patients who died during the period in São Paulo state. This was the worst YF epidemic reported anywhere in the world since the start of the twenty-first century, and both HC and IIER specialized in treatment of the disease at the time.
The yellow fever virus basically affects the liver, causing severe acute hepatitis due to direct damage to hepatocytes in 5 to 30% of cases. Hepatitis in yellow fever can be fulminant, with symptoms including nausea, vomiting, jaundice, bleeding disturbances (mucous membranes, gastrointestinal). , pulmonary and cerebral hemorrhages) and hepatic coma.
Organs other than the liver are also affected by yellow fever, including the kidneys, brain, lungs, spleen, pancreas, and heart. It’s not understood exactly how the virus damages those organs. For example, patients with yellow fever are known to have refractory hypotension (shock) and, in severe cases, cardiac arrhythmias such as bradycardia (slow pulse), described as accompanied by fever by the Louisiana physician Jean Charles Faget (1818-1884) in the mid-nineteenth century (and known as Faget’s sign).
The main ones observed by the researchers were myocardial fibrosis and enlargement of cardiomyocytes (heart muscle cells) in 93. 2% of cases, and (in 91. 8%) alterations of the vascular endothelium, the inner lining of blood vessels, causing bleeding, edema and small amounts of blood. clots in the heart. They also detected fiber necrosis in 68. 5%, viral myocarditis in 12. 3%, and secondary myocarditis due to bacteria and fungi in 6. 8%.
The cardiac conduction system, which generates the electrical stimulus that makes the center beat properly, was affected by 11. 0%, with edema, hemorrhage and inflammation, demonstrating for the first time the anatomical substrate of the arrhythmias discovered in human yellow fever.
Yellow fever viral RNA was detected in 95. 7% of cases using complex molecular biology techniques, as well as viral antigens in endothelial and inflammatory cells, indicating a direct action of the virus on the central tissue. The main inflammatory cells discovered in cases of myocarditis were activated macrophages.
Proteomics research showed higher levels of interferon-gamma-induced protein 10 (IP-10, also known as CXCL-10), a chemokine produced by macrophages that attracts more inflammatory cells to the site of any injury caused by the virus. Proteins have already been described in patients with COVID-19, dengue and Zika, and are associated with a worse prognosis.
“The importance of this study is that it allows us to better perceive what happens in the center of patients with severe yellow fever and subjects with severe reactions to the vaccine, since these alterations would possibly be masked or underestimated due to the fulminant hepatitis typical of yellow fever, the disease,” Duarte-Neto said.
Damage to the myocardium is common in severe cases of yellow fever, due to multifactorial mechanisms that come with directly virus-induced damage, endothelial cell damage, and an inflammatory reaction (myocarditis).
“With this understanding, it is possible to implement diagnostic and healing measures to save and treat the core damage related to yellow fever,” he said.
A total of 696 cases of YF were notified in São Paulo state between 2017 and 2019, with 232 deaths (33.3%). The main factors that contributed to establishment of the epidemic were environmental alterations, expansion of urban areas into Atlantic Rainforest remnants where circulation of the virus was increasing, and unvaccinated people going into the forest.
Yellow fever is now considered a re-emerging disease in Brazil (and Latin America in general). Vaccination is recommended nationwide, but a significant number of vulnerable people have not received the vaccine, especially in densely populated areas and non-endemic urban areas, which could suffer outbreaks if the virus spreads, such as in São Paulo, and even across the country. Southeastern Brazil in the late 2010s.
The disease has two major bureaucracies of transmission. In the jungle (wild) transmission cycle, humans become inflamed by the bite of Haemagogus and Sabethes mosquitoes. In the urban transmission cycle, the virus is transmitted through the Aedes aegypti mosquito. The 2017-2019 outbreak in São Paulo is considered an epidemic. due to jungle transmission.
Rare cases of post-vaccination headaches are called yellow fever vaccine-related viscerotropic diseases (YEL-AVD), related to the 17DD substrains of the vaccine used in South America.
São Paulo Research Foundation (FAPESP)
Giugni, F. R. , et al. (2023). Understanding Yellow Fever-Related Myocardium: A Study post-mortem. eBioMedicine. is What je. org/10. 1016/j. ebiom. 2023. 104810.
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