An invisible problem: arenavirus resurfaces in Brazil after 20 years

Brazil must be vigilant and prepared for the emergency. We are the country with more cases of arenavirus with ten species, among which, the Sabiá, Xapuri and Aporé

On January 20, the Ministry of Health confirmed the death of a man due to Brazilian hemorrhagic fever, caused by an arenavirus, the sabiá virus. The victim, a resident of Sorocaba, vacationed in Eldorado, in the Vale do Ribeira region, in the south of the state of São Paulo. Between the onset of symptoms on December 30 and death on January 11, the patient passed through three different hospitals, the last being the Clinics Hospital of the University of São Paulo Medical School (HCFM USP). There was no history of international travel and the place of origin of the contamination has not yet been confirmed. The Ministry of Health classified the case as a serious public health event.

The doctor at the USP Medical School and coordinator of the special techniques laboratory at Albert Einstein Hospital, head of the team that discovered the virus, Dr. João Renato Rebello Pinho, explains that the diagnosis was made by the international viroma/metagenomics methodology, used by the Albert Einstein Hospital from a patient admitted to the Infectious Diseases Ward of the FMUSP Clinics Hospital. This patient was part of the PROADI project, with the Ministry of Health entitled Studies of the clinical and epidemiological characteristics of acute hepatities in Brazil. After researching conventional agents related to acute hepatitis by serological and molecular methods (yellow fever, viral hepatitis, leptospirosis, dengue, zika, chikungunya, among other diseases), the case remained undiagnosed. “It was then decided to make use of this new standardized exam in AE Hospitals laboratory. The technique consists of extracting the RNA present in the patients blood serum and then the human RNAs are removed, leaving only those from viruses. Then the RNA is transformed into DNA, amplified and then the sequencing is done. Bioinformatics was used to analyze the sequence and determine the result. The finding, a species of the genus Mammarenavirus, of the Arenaviridae family, better known as arenavirus, was a surprise”, highlights the pathologist. The result was confirmed by the Medical Research Laboratory of the Institute of Tropical Medicine, USP Medical School Clinics Hospital and by the Adolfo Lutz Institute. “The virus identified has an 88% sequence similarity to the Sabiá virus, but it is not exactly the same. It is a new virus. We believe it may be a variant of Sabiá, but this is still under investigation”, points out Dr. Rebello.

The risk of contamination by this virus in the laboratory is so high that upon identifying it, the researchers were no longer authorized to work with samples from the patients. Work with this type of virus can only be carried out in laboratories with a maximum level of safety and there are none of this sort in Brazil. The Sabiá virus is in the same risk class as the dreaded African Ebola virus. In this category, the highest is number 4, rank of viruses that cause hemorrhagic fevers and the coronavirus SARS. Number 4 viruses are those that have a high lethality, that are transmitted through the air and that can pass from one person to another. Among arenaviruses, this form is rare. Samples will be sent to the United States Center for Disease Control and Prevention (CDC), one of the main epidemiological centers in the world and also one of the few to have a laboratory with security level 4, samples of the potentially lethal viruses are stored.

The head of the Laboratory of Hantaviroses and Rickettsioses of the Oswaldo Cruz Institute (IOC/Fiocruz), Dra. Elba Lemos, notes that as few laboratories have the capacity to carry out the tests that led to the identification of the case in São Paulo, the possibility of other cases of arenavirus in Brazil, which may have been mistaken for other diseases, needs to be considered. “Thus, as the clinical picture of hemorrhagic fevers is similar to that of other arboviruses, especially yellow fever and dengue fever, these cases may go unnoticed, especially in a country like Brazil, a place constantly struck by epidemics such as dengue, chikungunya, yellow fever, and where not always is possible to have confirmatory laboratory diagnosis”, he emphasizes. As arenaviruses that cause human disease are found in wild rodents kept in the wild, health professionals need to be alerted to the risk of this zoonosis in patients with occupational or tourist exposure to rodents or their excreta. Therefore, according to Dr. Lemos, surveillance and differential diagnosis are fundamental. “We have viruses and wild rodents in abundance and people in the areas where they exist. Most people have never heard of arenavirus, but they are here, causing high-lethal disease that, although they are associated with isolated cases or small outbreaks, represent a major public health problem”, he says.

Arenaviruses are viruses transmitted by the faeces and excretions of different species of wild rodents, which live in forests, but also in rural and peri-urban areas. These rodents infest grain deposits and grain crops, and infection of humans working in these areas becomes possible. The disease differs from leptospirosis, transmitted to humans by the urine of rodents, mainly during the floods, and caused by the bacteria Leptospira. According to the president of the Brazilian Society of Tropical Medicine (SBMT) and professor at the State University of Pará, Dr. Pedro Vasconcelos, despite the low occurrence, hemorrhagic fever draws attention due to the severity. The virus is adapted to the rodents immune system without causing disease, but it usually causes disease with extreme severity and is fatal in many cases, when it infects humans.

Dr. Vasconcelos is categorical in stating that there is no risk of an epidemic of Sabiá fever, but new cases may appear, including subclinical infections that usually do not progress with severity. “The disease is not very prevalent in part due to the lack of knowledge in the diagnosis – only made by specialized laboratories. It is important to note that, in addition, arenaviruses that cause disease in humans are classified as viruses with biosafety level 4 (NB4) at the same level as Ebola and Marburg and other viruses with a high percentage of morbidity and mortality. Thus, the limitation in research and studies aimed at detecting these viruses, suggests that these viruses are more rare than they really should be”, adds the virologist.

Also according to the president of the BSTM, the absence of cases may be due to several factors including, the rarity of the disease, the absence of human contact with rodents infected by the virus, difficulty in recognizing suspected clinical cases, and the difficulty in carrying out specific laboratory diagnosis. However, as Brazil borders three countries where hemorrhagic fevers caused by arenaviruses are endemic (Argentina, Bolivia and Venezuela), and there are other arenaviruses (without causing disease in humans) in Brazil, there is a possibility of sporadic cases, as well as a possible (more unlikely) introduction of exotic arenaviruses in our territory, says Dr. Vasconcelos Arenavirus genetically related to Sabiá arenavirus caused an outbreak in Bolivia in 2019. Three people died, and the virus responsible for the symptoms was the Chapare arenavirus. Finally, it is important to note that arenaviruses are not related to the coronavirus that has recently caused severe pneumonia and deaths in Chinese territory.

Brazilian hemorrhagic fever 

Brazilian hemorrhagic fever was first identified in the state of São Paulo, in the early 1990s. The victim reported traveling to the municipality of Cotia, in the interior of the state, ten days before the onset of symptoms. After the death, it was identified that it was a new virus of the family Arenaviridae, which was called Sabiá virus, due to the name of the neighborhood where the patient probably became infected. In total, four cases were reported in humans, three cases acquired in the wild in the state of São Paulo and one due to infection in the laboratory, in Pará, besides one laboratory case in the USA.

The disease is considered to be extremely rare and highly lethal. The fatality rate is estimated to be from 20% to 60%. There is no vaccine or specific treatment, which is performed according to the patients presented clinical condition. Human exposure to arenaviruses occurs mainly through inhalation of aerosols containing viral particles from the urine, feces or saliva of infected wild rodents, or from bites. Dr. Lemos recalls that Brazil is the country with the largest number of arenaviruses: ten species, among which are the mammarenavirus Sabiá, first identified in 1990 in a fatal case and the Xapuri and Aporé viruses, recently recognized as species by the International Committee for Viral Taxonomy. These last two were discovered last year by Dr. Elba Lemos and received the names in reference to the locations in Acre and Mato Grosso do Sul where they were identified from the blood sample of wild rodents. “The doctoral thesis entitled ARENAVIRUS IN BRAZIL: ECO-EPIDEMIOLOGY AND THE ASPECTS OF ITS OCCURRENCE IN THE FAMILY AGRICULTURE EXPANSION PROCESS authored by Jorlan Fernandes, guided by me, was awarded as the best CAPES Medicina II thesis of 2018. With this thesis we identified five arenaviruses, three new ones, two of which were accepted as new species (Apore – Mato Grosso do Sul, in a rodent, potential causative of the human diseases. the in same clade as the Sabiá), and Xapuri – Acre (in a rodent, potential causative of the human disease – in the same clade as the Sabiá), besides Amapari and Cupixi – in Amapá, Flexal – Pará – Pinhal – São Paulo, Oliveros – Mato Grosso do Sul, Latino – Mato Grosso do Sul, Rio Preto (still in final characterization) in rodents captured in MG, GO and MS. The Latino and Oliveros viruses had never been described in Brazil. Thus, with the results of this thesis, Brazil went from five to ten arenaviruses in its territory”, adds Dr. Lemos.

Prevention can be done by avoiding contact with wild rodents and using Personal Protective Equipment (PPE) when facing risk exposure situations. Detergents, common disinfectants (with sodium hypochlorite, glutaraldehyde, 70% ethyl alcohol and lysoform in the composition) and ultraviolet light are able to inactivate the virus.…