Abstract

Emergence and re-emergence of viral zoonoses pose a serious threat to human and animal health. Hantaviruses are enveloped negative (-) single-stranded RNA viruses that belong to Hantaviridae family, which are transmitted to humans through inhalation and are harbored by small rodents. Humans can develop two clinical syndromes as a result of hantavirus infection: haemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), which are caused by Old World and New World hantaviruses, respectively. Infections with the hantavirus are rather common in peoples in parts of Asia, Europe, and South America, although they appear to be less common in North America. Globally, 200,000 peoples are affected with Hantaviruses every year. The clinical manifestations of HFRS range from asymptomatic to mild to moderate to severe. In general, HFRS produced by Hantaan, Amur, and Dobrava viruses is more severe, with fatality rates ranging from 5 to 15%, whereas Seoul, Puumala, and Saaremaa viruses induce mild types of disease with mortality rates of less than 1%, resulting in HCPS. For hantavirus identification, a variety of techniques are utilized, including polymerase chain reaction (PCR), focus reduction neutralization test (FRNT), enzyme-linked immunosorbent assay (ELISA), immunoblot assay (IBA), immunofluorescence assay (IFA), and other molecular approaches. Because no effective medication or vaccination has been licensed by the FDA, the greatest defense is to avoid contact with rodents and clean up rodent habitats safely.

1. Introduction

Emerging and re-emerging diseases caused by a variety of pathogens are a significant cause of morbidity and mortality in humans as well as in animals worldwide ^{1, 2}. Hantaviruses, also known as Orthohantaviruses, are an emerging public health issue that appears to be spread by small rodents. It is estimated that Hantavirus are responsible to affect around 200,200 people globally annually ³. The disease has been reported from many countries of the world ^{4, 5, 6, 7}. Hantaviruses are negative (-) ssRNA encapsulated viruses that belong to the family Hantaviridae ⁸. Hantavirus infection garnered international notice during the Korean War (1950–1953), despite the fact that a condition resembling it was documented 900 years before in Chinese texts ⁹. Hantaviruses prevalent in Europe and Asia, commonly known as Old World Hantaviruses, cause HFRS ¹⁰, whereas Hantavirus Pulmonary Syndrome (HPS) is caused by New World Hantaviruses found in America ¹¹.

Humans are not in the native host range of hantaviruses, and the infection is usually caused by inhaling virus-containing aerosols from rodent excretions such urine, feces, and saliva ^{12, 13}. People who live or work in close proximity to infected rodents are more likely to become infected, with animal trappers, mammalogists, forestry workers, farmers, and military personnel being the most vulnerable ¹⁴.

Hantavirus ecology and geographic distribution are linked to the spread of their natural reservoir ⁹. Over 28 hantaviruses that cause disease in humans have been detected around the world, ranging from acute renal failure to pulmonary oedema and severe hemorrhagic sickness. Because Hantaviral infections are often unrecognized and unreported in many areas, new hantaviruses may go unidentified ¹⁵. The objective of this review is to discuss the growing importance of Hantavirus infection as a global public health issue.

2. Etiology

Hantaviruses are members of the Orthohantavirus genus, which belongs to the family Hantaviridae and the Bunyavirales order ¹⁶. They are enclosed RNA viruses with a diameter of 80 to 120 nm and a spherical form. The genome is made up of three single-stranded negative sense RNAs that share a 30-terminal sequence of genome segments. The nucleoprotein (N), envelope glycoproteins (Gn and Gc), and the L protein, or viral RNA-dependent RNA polymerase, are encoded by the three segments, S (small), M (medium), and L (large) ¹⁷. Hantaviruses have been detected in rodents of family Muridae and the subfamilies Murinae, Arvicolinae, and Sigmodontinae in Asia, Europe, and the Americas ¹⁵. Heat (30 minutes at 60°C), detergents, UV irradiation, organic solvents, and hypochlorite solutions are all effective in inactivating Hantaviruses ¹⁸.

3. Transmission

Hantaviruses are thought to be spread by aerosolized rat excreta. Close contact between infected and naive rodents is likely to be the mode of transmission. Hantaviruses can be found in the saliva, feces, and urine of rodents. Fighting, biting, and sexual activity have all been suggested as possible modes of transmission. Hantavirus infection has recently been documented in a variety of domestic animal species (e.g., pigs, cats, rabbits, and dogs) ^{12, 19}. Hantaviruses are considered to be transmitted to humans by contact with diseased rats or their excreta ¹². Inhaling aerosolized dust from rat urine, droppings, or nests disturbed in an enclosed location appears to cause many diseases. Hantaviruses can also enter the body through broken skin, the conjunctiva, and other mucous membranes, as well as rodent bites and ingestion. In South America, the possibility of transmission through breast milk has been hypothesized ¹⁶. Cat can get infected from the rodents and act as a potential reservoir. There seems to be hardly any published information of human-to-human transmission ¹².

4. Epidemiology

Murid rodents (order Rodentia; family Muridae; subfamilies Murinae, Arvicolinae, and Sigmodontinae) are the principal natural reservoir for hantaviruses ²⁰. Humans are not in the natural host range of Hantaviruses; thus, the infection happens accidentally. People who live or work in close proximity to diseased rodents are more likely to become infected ^{12, 21}. Old World viruses such as Hantaan, Puumala, Dobrava-Belgrade, Seoul, Amur-Soochong, and Gou viruses cause HFRS and are primarily carried by Murinae rodents in Europe and Asia; New World viruses such as SNV, New York-1 virus (NY-1V), and ANDV that cause HPS and are primarily carried by Sigmodontinae sub-family members in America; Hantaviruses reported both in Old or New World and related with mild disease include PUUV or Prospect Hill virus (PHV) and Tula virus (TULV) (non-virulent hantaviruses) are hosted by Arvicolinae rodents ²².

Hantaviruses are found all over the world, but their distribution is constrained by the geographic range of their reservoir hosts ¹⁶. The genus Hantavirus is divided into two groups: Old World hantaviruses and New World hantaviruses. Human HFRS is caused by pathogenic Old-World hantaviruses such as Amur virus, Seoul virus, and HTNV, the most epidemiologically important species in Asia, with mortality rates of up to 15%, and Dobrava virus (DOBV), Tula virus (TULV), and Puumala virus (PUUV) in Europe; the latter is the main Hantavirus species in Europe and causes nephropathiaepidemica (NE), a milder variant of HFRS ^{14, 20}. In the early 1990s, the first pathogenic New World Hantavirus (Sin Nombre virus) was found in the United States' Four Corners region ²³. New World hantaviruses are the cause of about 300 cases of HPS in North and South America each year, with mortality rates of up to 50% ²⁴. The first serological evidence of hantavirus infections was discovered in Africa in 1984 ²⁵. Human hantavirus infections have been confirmed using serological tests since then ²⁶. In endemic areas, several factors such as ecology of rodents, environment, human behaviors may influence the transmission and epidemiology of Hantaviruses ²⁷.

5. Clinical Spectrum

Humans can develop one of two clinical syndromes as a result of hantavirus infection: HFRS or HCPS, which are caused by Old World or New World hantaviruses, respectively ²⁸. The clinical manifestations of HFRS range from asymptomatic to mild, moderate, and severe, depending in part on the disease's causative agent ¹¹. A typical HFRS course can be broken down into five stages: febrile, hypotensive, oliguric, polyureic, and convalescent. After a 2- to 4-week incubation period, the sickness manifests itself with a high fever, chills, headache, backache, abdominal aches, nausea, and vomiting. Visual disturbances (blurred vision) and somnolence are common complaints ²⁹. The clinical course of HCPS is divided into three stages: prodromal, cardiopulmonary, and convalescent, with symptoms ranging from mild hypoxia to respiratory failure with cardiogenic shock ³⁰. In HPS, pulmonary symptoms are the most common. Similar to the prodromal stage of HFRS, this syndrome is characterized by a vague illness that lasts 3 to 5 days. Cough and tachypnea are generally followed by pulmonary edema and indications of hypoxia, indicating respiratory distress and hypotension. There may also be cardiac irregularities such as bradycardia, ventricular tachycardia, or fibrillation ¹⁶.

In their reservoir hosts, hantaviruses are not associated with overt illness. However, studies have found that some wild mice and voles had poorer survival rates and weight growth. When domesticated rodents are experimentally infected with some viruses, they may develop clinical symptoms or lesions. In some of these experiments, infant rats and mice acquired severe diseases, including deadly meningoencephalitis. In most investigations, rats and mice above the age of 2-3 weeks were unharmed, while other species, such as Syrian hamsters, have shown varied clinical symptoms, including pulmonary and renal dysfunction. Laboratory rodents are given relatively high doses of virus by injection, which may or may not mirror natural hantavirus exposure. No clinical signs or lesions have been reported in pet rats naturally infected with Seoul virus ¹⁶.

6. Diagnosis

Clinical and epidemiological data, as well as laboratory tests, are used to diagnose HFRS and HCPS ³¹. Serology is used to diagnose acute hantavirus infections since nearly all patients exhibit IgM and, in most cases, IgG antibodies in their serum at the onset of symptoms. Indirect IgM and IgG ELISAs, as well as IgM capture ELISAs, which offer higher specificity than indirect ELISAs, are the most often used serological assays. Indirect immunofluorescence assays are also commonly employed in diagnostics; however, their specificity is lower ³². RT-PCR identification of the hantavirus genome in blood or serum samples can also confirm hantavirus infection. To identify viraemia, both standard and quantitative RT-PCR are utilized ³³. Although the presence of viraemia varies, if an acute sample is available, viral RNA may typically be found. Furthermore, the presence of viral RNA has proven hantavirus infection even before the appearance of particular antibodies ³⁴. The importance of kidney biopsy in the diagnosis of Hantvirus hemorrhagic fever with renal syndrome has been described by Lupusoru and co-investigators ³⁵.

7. Treatment

There are currently no antiviral drugs that can be used to treat hantavirus infections. ³. Patients with HFRS or HPS are treated with supportive therapies to keep their symptoms under control, which can be life-threatening. Patients are usually monitored and cared for in an emergency department or intensive care unit until their immune systems have eliminated the virus and the convalescent phase begins ¹⁸. In some cases of HFRS, ribavirin has been reported to be beneficial. In a recent clinical experiment in South America, the administration of antiserum against hantaviruses appeared to be promising ¹¹.

8. Prevention and Control

Preventive methods include avoiding contact with hantavirus-infected rodents and their excrement, urine, significant emissions, and tissues ^{8, 12}. Depending on the conditions, this could include gloves, rain boots, goggles, coveralls or an entire suit, as well as a respirator ^{12, 36}. Rodent-proofing of homes, decrease of rodent cover surrounding houses, minimizing of food available for rats, capturing of rodents in and around dwellings, and careful disposal of deceased rodents are all CDC recommendations ³⁷. Anyone who develops a febrile infection on a regular basis with early signs of hantavirus pulmonary syndrome or hemorrhagic fever with renal syndrome should seek medical attention right once and advise their doctor about the global risk. While treating patients infected with ANDV, both all-encompassing precautions and droplet preventive measures are currently recommended ³⁸. Apart from usual precautions, effective vaccines may be the only approach to reduce the risk of hantavirus disease. Commercial inactivated vaccines for HFRS caused by the Hantavirus and/or the Seoul virus are available in South Korea and China ¹⁶.

9. Conclusion

Hantavirus infections are one of an emerging zoonotic infectious disease. Small rodents host hantaviruses, which enter the human body through inhalation. Hantaviruses are old viruses, despite the fact that some have recently been discovered. However, environmental changes may impact the geographic distribution, abundance, and dynamics of the carrier rodent species, and hence the epidemiology of hantavirus disease. Despite the fact that we can only speculate on the extent of future environmental and climatic changes, hantavirus infections will continue to be a public health issue. As a result, more study into the pathophysiology, diagnosis, antiviral, and vaccine development of hantaviruses is required.

Contribution of Authors

Both authors contributed equally.

Conflict of Interest

No conflict of interest.

References