Hantaviruses are found globally and may cause hemorrhagic fevers with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). Various aspects can influence the epidemiology and transmission of hantaviruses, corresponding to the environment, climate, human behavior in epidemic regions, and ecology of rodent hosts.

In a recent The Lancet Infectious Diseases study, scientists review previous publications to higher understand the clinical outcomes and management of Hantavirus infection in humans.

Study: Hantavirus in humans: a review of clinical elements and management. Image Credit: ALPA PROD / Shutterstock.com

What are hantaviruses?

Hantaviruses belong to the family Hantaviridae and the genus Orthohantavirus. These virus particles are between 80-120 nanometers (nm) in diameter and possess a negative-strand ribonucleic acid (RNA) genome.

The viral genome is split into three segments, including small (S), medium (M), and enormous (L) segments. The S segment encodes the nucleocapsid protein, whereas the M and L segments encode the envelope glycoproteins and viral RNA-dependent RNA polymerase, respectively.

Although rodents are the natural host for Hantavirus, this virus has also been detected in moles, bats, fish, reptiles, and shrews. Natural hosts infected with Hantavirus don’t manifest significant biological effects. Typically, rodents excrete Hantaviruses in urine, saliva, and feces. 

Humans might be infected with Hantaviruses through inhalation of secreted viruses or rodent bites. There stays an absence of research available on the duration of viability of those viruses within the environment.

One previous study indicated that Puumala virus (PUUV) survives at room temperature for five days in a wet environment and 24 hours in dry conditions. Comparatively, the Hantaan virus (HTNV) stays viable in wet conditions for eight days at 20°C and nine days at 37°C.

Pathogenesis and clinical symptoms

Hantaviruses goal endothelial cells of capillaries and small vessels to reinforce their vascular permeability. In HFRS, changes in endothelial permeability can alter platelet function and coagulation.

Histopathological studies have indicated that HFRS-causing hantaviruses modify renal medulla capillaries, while HCPS-causing hantaviruses affect pulmonary capillaries.

Each HCPS and HFRS are characterised by strong inflammation that affects vascular endothelial cells and contributes to the event of renal failure.

Based on chest X-rays or computed tomography (CT) scans, all patients with HCPS and most with HFRS exhibit respiratory symptoms corresponding to hypoxia. A few of the common symptoms of HFRS include coagulation dysregulation, acute kidney injury, and vascular permeability.

HFRS infection is split into five stages, starting with febrile, hypotensive, oliguric, diuretic, and convalescent. The disease progression and severity rely upon the variety of hantavirus and the person’s immunity.

After the incubation period of two to 6 weeks, acute onset of high fever, nausea, headache, abdominal pain, and back pain have been reported. As well as, hypotension is often induced as a result of vascular leakage.

Patients with severe HFRS exhibit menorrhagia, metrorrhagia, petechiae in skin or mucosa, gastrointestinal bleeding, and epistaxis. Each adults and youngsters experience similar clinical manifestations of HFRS.

Each the respiratory and cardiovascular systems are primarily targeted by HCPS-causing hantaviruses. A few of the outstanding symptoms of HCPS include headaches, abdominal pain, chills, myalgias, diarrhea, arthralgia, retro-ocular pain, and vomiting. Infrequent respiratory symptoms, corresponding to nasal congestion and odynophagia, have also been reported.

Diagnosis

It will be important to distinguish between HFRS and HCPS, particularly within the prodromal phase. Urine dipstick evaluation is incessantly used to substantiate a suspected case of HFRS.

These tests are sometimes followed by serological evaluation, corresponding to enzyme-linked immunosorbent assay (ELISA). Here, immunoglobulin M (IgM) antibodies against the Hantavirus nucleocapsid protein are detected on the onset of the febrile prodrome, while IgG antibodies are found at the top of the febrile prodrome. 

Immunochromatographic IgM assays are conducted to detect HFRS attributable to PUUV, HTNV, and Dobrava virus (DOBV). Each IgG and IgM ELISAs are used to detect acute infection.

Neutralizing antibody assays are used to find out monoclonal antibody levels, in addition to the immunity conferred by each vaccines and natural infection. Reverse transcription-quantitative polymerase chain response (RT-qPCR) assays are used to diagnose PUUV and DOBV within the early phase of infection. Next-generation sequencing has also been used to review viral genomic epidemiology.

Treatment

So far, no specific antiviral or immunomodulatory treatments can be found for Hantavirus infection. One clinical trial conducted in China revealed that intravenous ribavirin reduced mortality linked to HFRS. One other trial contradicted this finding and reported that ribavirin was not effective when HFRS was attributable to PUUV.

One clinical trial conducted in Chile revealed that high-dose intravenous methylprednisolone was ineffective against HCPS within the cardiopulmonary phase.

Hantavirus infection might be managed through careful monitoring of clinical symptoms, blood pressure, fluid and electrolyte balance, and urine tests. Common treatments include analgesics, oxygenation against hypoxia, correction of electrolyte imbalances, and intravenous fluids to stop hypotension. About 15% of patients infected with PUUV require dialysis.

During severe infections that cause kidney failure and acute respiratory distress syndrome, renal alternative therapy and mechanical ventilation could be required. Animal models have revealed that favipiravir may very well be effective against the Sin Nombre virus (SNV) when administered before the onset of viremia. Icatibant acetate, which is a bradykinin receptor antagonist, was found to be effective within the treatment of severe HFRS.

Journal reference:

• Vial, A. P., Ferres, M., Vial, C., et al. (2023) Hantavirus in humans: a review of clinical elements and management. The Lancet Infectious Diseases. doi:10.1016/S1473-3099(23)00128-7