A study carried out by an international team of researchers with the support of FAPESP shows that infection with the Chikungunya virus can cause even more serious manifestations than the typical symptoms of the disease such as acute fever, headache, rash, and severe joint and muscle pain.
The analysis was carried out by 38 researchers affiliated with the Federal University of Ceará (UFC), the University of São Paulo (USP) and the Brazilian Ministry of Health, as well as Imperial College London and Oxford University in the UK.
Their main discovery was that chikungunya can infect the central nervous system and affect cognitive and motor functions.
“The study produced important new information about the disease and the virus. Not only did we confirm that the virus can infect the central nervous system, but we also found that the disease is more deadly to young adults than it is to children and the elderly, like this outbreaks of the disease are usually predicted, “said William Marciel de Souza, co-author of an article on the study published in Clinical Infectious Diseases.
Souza is a researcher at the Ribeirão Preto Medical School (FMRP-USP) of the University of São Paulo. “The study also showed that during the acute or subacute phase of the disease [20-90 days after infection] Patients with diabetes appear to be seven times more likely to die than non-diabetics, “he said.
The study was carried out under the auspices of the Brazilian-UK Center for the Discovery, Diagnosis, Genomics and Epidemiology of Arboviruses (CADDE). It also comes from Souza’s postdoctoral research, part of which he pursued at Oxford University in the UK with support from FAPESP via a research internship abroad. Researchers involved in the project worked on the project, which was also supported by the Brazilian National Council for Scientific and Technological Development (CNPq).
Worst outbreak in America
The study was based on a retrospective analysis of clinical and epidemiological data, as well as blood, CSF, and tissue samples from patients who died during the 2017 outbreak in the Brazilian state of Ceará, the worst chikungunya outbreak in America. Ceará reported 194 deaths related to Chikungunya and 105,229 suspected cases (1,166 per 100,000 population) in 2017.
The researchers used records submitted by the Ceará State Health Ministry’s death verification service during the outbreak. To determine the cause of death in 100 cases, they analyzed blood serum and cerebrospinal fluid samples using RT-PCR and MinION genome sequencing techniques, immunohistochemistry, and ELISA assays to detect antibodies to Chikungunya.
The virus is transmitted by women from two species of mosquitoes, Aedes aegypti and Aedes albopictus. Most chikungunya patients show acute symptoms such as high fever, headache, joint and muscle pain, nausea, fatigue, and rash for three weeks after infection. Some then move into the subacute phase where symptoms persist. Joint pain can last longer than three months, indicating a transition to the chronic phase that can take years.
All of the evidence from the laboratory tests and clinical records indicated that in most cases of suspected death from chikungunya, the patient had a central nervous system infection.
Joint pain was the most common symptom as evidenced by the name of the disease, which refers to a distortion caused by pain [in the East-African Kimakonde language], but we have also identified serious problems in the nervous system due to chikungunya. “
William Marciel de Souza, co-author
Viral RNA was found in cerebrospinal fluid from 36 patients and in four brain tissue samples. “The presence of the virus in the infected brain tissue is clear evidence that it is able to cross the blood-brain barrier that protects the central nervous system and cause infections in the brain and spinal cord,” said Souza.
In addition to new features of infection with this virus, the researchers also found that the risk of death in the subacute phase was seven times higher in patients with diabetes than in those without diabetes.
Her autopsy and histopathological analysis of fatal cases suggested viral infection as the cause of circulatory and fluid disorders in the brain, heart, lungs, kidneys, spleen and liver.
“The study confirmed some previous clinical evidence of death from chikungunya and also brought out new aspects of the disease and its lethality. This new information, obtained from a careful analysis of the Ceará outbreak, will help identify the factors that cause the disease Cause severity and also to do further research to develop better treatments in the future, “said Luiz Tadeu Moraes Figueiredo, professor at FMRP-USP and co-author of the article.
Figueiredo is involved in research supported by the São Paulo Research Foundation (FAPESP) on high throughput sequencing (HTS) to identify and characterize viruses without the need for virus isolation or cell culture. He is particularly interested in MinION genome sequencing, which is faster and cheaper than other approaches. The technology also reads RNA and DNA in real time and in a single step.
Based on their analysis, the study’s authors concluded that, contrary to the profile typical of arbovirus epidemics, the elderly and children are not at a higher risk of dying from chikungunya than other age groups. In the 2017 outbreak, most of the fatalities were middle-aged.
“We normally associate arbovirus with hospitalizations and deaths in the elderly and infected children, but our analysis of these 100 fatal cases found that the majority [over 60%] Of those with central nervous system infections, adults aged 40 and over were adults, “Souza said, adding that patients aged 3 days to 85 years were among the remaining fatal victims.
The results show that impaired or suppressed immunity in such outbreaks is not necessarily the main cause of susceptibility to the disease. “Many of the victims were healthy young adults under 40 and most had no comorbidities,” he said. “The analysis has added another level to our knowledge of the disease and can be extremely important for clinical practice. This age group, which is also at a high risk of death, deserves even more attention.”
Research Foundation São Paulo (FAPESP)
Silva de Lima, ST, et al. (2020) Deadly Consequences of Chikungunya Virus Infection in Brazil. Clinical Infectious Diseases. doi.org/10.1093/cid/ciaa1038.