South american hemorrhagic fever syndromes

The "South American Hemorrhagic Fever Diseases" are, like other diseases (e.g. Lymphocytic Choriomenigitis, Lassa Fever), caused by Arena viruses (family of the New World Arena viruses).

The Junin, Machupo, Guanarito and Sabia viruses belong to the New World arena virus family and occur in South America. These arena viruses cause various hemorrhagic fever diseases:

• Argentine Hemorrhagic Fever (AHF)
• Bolivian hemorrhagic fever
• Venezuelan haemorrhagic fever (VHF)
• Brazilian haemorrhagic fever (BHF)

The name arenavirus is derived from a characteristic dark granulation (arenosus = sandy) of the viruses in electron microscopic images. These are shown as ribosomes, which are included in the sprouting of the viruses.

The arena viruses consist of a lipid shell and are pleomorphic with an average diameter of 50-300nm. They contain 2 RNA segments, the L- du the S-segment, which contain the information for structural proteins (nucleocapsid protein and glycoproteins) and an enzyme (viral polymerase). In the finished virus, the nucleocapsid is stored protectively around the RNA. The glycoproteins G1 and G2 are anchored in the lipid envelope. They serve for the absorption and release of the L and S segments into the cytoplasm and are thus essential for recognition and penetration into the host cell. The reproduction of the viruses in the cell takes place via a viral polymerase.

Arena viruses are basically spread by infected rodents. These rodents can be persistently (permanently) infected and excrete the virus over a long period of time. The virus is spread within different rodent populations horizontally (to the same generation) and not vertically to the offspring. Transmission to humans occurs mostly via excrements and secretions (stool, urine and saliva). The virus is either absorbed through small injuries in the skin or it enters the respiratory tract through inhalation of contaminated dust particles and aerosols. The infection dose for humans and animals is estimated to be 1-10 viruses. It has been shown that the viruses are stable in the environment for several hours.

Incubation period: 1-2 weeks.

The disease usually begins insidiously with malaise, fever and myalgia. It is often followed by pain in the loins, stomach and eyes, combined with photophobia, constipation, nausea and vomiting. The fever remains relatively constant at 40°C. At

Argentine hemorrhagic fever and Brazilian hemorrhagic fever (BHF) are characterized by conjunctivitis and facial erythema, as well as erythema of the neck and thorax (50% of patients). Relative bradycardia is frequently observed. After about 6 days of illness, the disease begins to subside in 70-80% of patients. In a smaller part of the patients a complicative second phase occurs. It is characterized by skin and organ bleeding and acute neurological symptoms (see the diseases in detail). Pulmonary edema, bacterial superinfections, hypovolemic shock are the main causes of death in AHF and BHF. The mortality rate is high at 15-30%.

Laboratory diagnosis of arena viruses should in principle be carried out under biosecurity level 4 conditions, in particular if the virus needs to be cultured. For serological and molecular biological tests, the samples can be inactivated beforehand and processed at lower safety levels.

RT-PCR (detection of RNA using molecular biological techniques) is a reliable method and allows early and rapid diagnosis of South American arena viruses.

Virus isolation from the blood on cell cultures is possible during the acute phase of infection (8-14 days after infection).

Virus isolation from throat swabs, urine, cerebrospinal fluid and other fluids has also been described.

The virus can be identified in cell culture by immunofluorescence.

For antibody detection, an immunofluorescence assay (IFA) is also performed, whereby sera are tested on infected and inactivated cells.

The antibodies against Machupo virus or Guanarito virus do not appear until 12-30 days after the onset of the disease and are usually already associated with an improvement in the clinical course.

Infections with the South American hemorrhagic fever viruses are mainly treated symptomatically. In many patients, light sedation (sedation) and pain treatment with opiates is recommended. Bleeding should be treated by transfusions of platelets and coagulation factors.

Control of the electrolyte and fluid balance, if necessary controlled balancing.

Infusions of immunoplasmas (plasma from convalescent patients) were therapeutically successful. The mortality rate could be reduced from 10% to 1% if treatment was given within the first 8 days of illness.

A commercial immunoglobulin for the therapy of AHF does not yet exist.

The antiviral drug ribavirin seems to have a positive influence on the outcome of Junin and Machupo virus infections at least.

Animal experiments could be carried out on different types of AHF. Animal experiments with the viral agent favipiravir were successful in various arena virus infections (Gowen BB et al. 2017; Furuta Y et al. 2013), so that it can be assumed that this drug is also used in humans (see also Favipiravir).

Blunt trauma that could cause new bleeding must be avoided at all costs (no unnecessary transport. Furthermore no intramuscular injections; no intake of acetylsalicylic acid.

South American arena viruses are highly infectious and can be transmitted via aerosols. The viruses are relatively stable as aerosols. Most arena viruses can be propagated to high concentrations in cell cultures. They cause severe disease symptoms and can be transmitted from person to person. They therefore fulfil important criteria for use as biological weapons.

1. Gowen BB et al (2017) Enhanced protection against experimental Junin virus infection through the use of a modified favipiravir loading dose strategy. Antiviral Res 145:131-135.
2. Tani H et al (2018) Arenavirus research and antiviral candidate. Uirusu 68:51-62.
3. Furuta Y et al (2013) Favipiravir (T-705), a novel viral RNA polymerase inhibitor. Antiviral Res 100:446-454.