Hantavirus Infection: An Overview
Shid Shubangi J.*, Sapate Rohit B., Raut Indrayani D., Dhadde Gurunath S., Mali Hanmant S., Joshi Saurabh, Shaikh Bilal
Rajarambapu College of Pharmacy, Kasegaon (MS) India.
*Corresponding Author E-mail: shubhangishid@gmail.com
ABSTRACT:
Hantavirus form an independent genus within Bunyaviridae family. Currently, there are >20 known sero/genotypes and several more are now being under examination. Each type of Hantavirus tends to be unique and specific to a particular host of rodents. In term of the target organs and severity of disease various forms of Hantaviruses are associated with a variety of disease. It recognises two major diseases: HPS and Haemorrhagic fever with renal syndrome (HFRS). Hantavirus is increasing throughout the world and new strains of Hantavirus have been progressively observed worldwide, which represents public health issues of rising global concern. The amount recognised virus types continue growing, and so does the spectrum of hanta virus disease. There is evidence in the British Isles of Hantavirus causing human disease, but at present it remains a mostly uncharacterized disease, due to its asymptomatic and non-specific mild infection and shortage of simple standardised laboratory diagnosis in hospital, Hanta viral infection may be underestimated, especially in developing countries. The present perception is outlined in this analysis on general properties, classification, laboratory diagnostics, treatment and prevention of Hantaviruses and hanta viral infection.
INTRODUCTION:
Hantaviruses belonging to the Bunyaviridae family, the Hantavirus genus are enveloped, single-stranded, negative sense RNA viruses1. Transmission between rodents and from rodents to the humans normally occurs by aerosolized excreta inhalation2. Hantaviruses grow recurrent infections in their host species (rodents of the Muridae and Cricetidae families).3 however it causes 2 diseases in humans: hemorrhagic fever with renal syndrome (HFRS) in Eurasia, Northern and Southern American Hantavirus (cardio) pulmonary syndrome4. Each and every year 60,000-100,000 HFRS cases worldwide, cases have been reported, mostly from People’s Republic of China5.
To date, in China 7 Hantavirus sero/genotypes have been reported.6 of these, only Apodemusagrarius mice-carried Hantaan virus (HTNV) and Rattusnorvegicus rat-carried Seoul virus (SEOV) are responsible for HFRS7-8. HFRS continues to be a severe public health scenario in China9. They usually cause infection in rodents, but do not cause disease in them. As early as 1913; Russian clinical records from far eastern Siberia define the human viral disease presently recognised as hemorrhagic fever with renal syndrome (HFRS). Dr. Ho Wang Lee (1982) reported a Chinese medical account of a similar disease dating to around A.D. 960. This is not strange in opinion of its unique renal complication and even the fact that etiologic agent of HFRS managed to prove to be a zoonotic virus that causes chronic infection with urinary excretion in the murid rodent, Apodemusagrarius10. In much of Northern and Eastern Asia this mouse is the most common wild rodent and sometimes invades cultivated fields, gardens, haystacks and even human dwellings11. Social conflict has played a prominent role in elucidating the aetiology, clinical evolution, epidemiology, and ecology of HFRS. Field nephritis, which occurred during World War I in both Allied and German powers in Flanders, may have caused by Hantavirus that is now believed to occur in Western Europe and Scandinavia (Bradford 1916; Arnold 1944). After having invaded Manchuria (Kitano 1944), Japanese military doctors discovered the disease in the mid 1930s, Finnish and German troops were infected during World War II (Stuhlfauth 1943; Hortung 1944), and UN forces first discovered the original and actual hantavirus during Korean Conflicts in 1951 (Smadel 1953)12.
General properties of hantavirus:
Structure:
Hantaviruses are enveloped RNA viruses with a negative-sense, tri-segmented genome. The large (L), medium (M) and small (S) segments code for viral RNA-dependent-RNA polymerase, glycoprotein precursor (GPC) which is processed into the two envelope glycoproteins (GnandGc) and the nucleocapsid (N) protein respectively13.
Hantavirus N Protein:
In infected cells and virions, the most abundant viral protein is the Hantavirus N protein. There is a strong and rapid immune response to this protein. The N protein amino-terminus containing 100 amino acids is extremely antigenic and thus used in diagnostic assays14. In the N-terminal region, B-cell epitopes are found, while T-cell epitopes are randomly distributed throughout the protein. The amino acid sequence of N protein is generally maintained between different strains of given Hantavirus serotype. In Escherichia coli, baculovirus and yeast expression systems, recombinant N proteins can be commercially developed. Such recombinant proteins are used instead of native proteins in diagnostic assays15.
Hantavirus glycoprotein:
G1 and G2 surface glycoproteins are expressed as a polyprotein precursor, a GPC that is degraded by cellular proteases. These glycoproteins interact with surface receptors, β3 integrinsand facilitate entry of hantaviruses16.
Classification of hantaviruses:
Phylogenetic analysis of the N protein classifies Hantaviruses into four main groups:
· Group A: Murinae-borne species, HTNV, Seoul virus (SEOV), Thailand virus (THAIV) and Dobrava/Belgrade virus (DOBV) causing HFRS in Asia
· Group B: Arvicolinae-borne species such as Puumala virus (PUUV), aetiological agent of nephropathia epidemica (NE), a mild form of HFRS in Europe
· Group C: Sigmodontinae and Neotominae-borne species such as SNV, ANDV and others causing HCPS in the Americas
· Group D and E comprising shrew, mole and bat-borne species16.
· In the history of Hantavirus research, TPMV holds a special place. It was the first-ever Hantavirus to be isolated from a shrew (insectivore) captured in Vellore, South India in 196417. Initially assumed to be an arbovirus, its recognition belied the long-held perspective that only rodents are hosted by Hantaviruses18-21.
Hantavirus related clinical syndromes:
· Haemorrhagic fever with renal syndrome
The clinical course separated into five stages: febrile, hypotensive, oliguric, polyuric and convalescent. An incubation period of 2-4 w is febrile stage or phase is then followed by of about 3-7 d, characterised by fever, headache, vomiting, stomach pain, back and visual disturbances. At the end of this process, petechiae on the palate and conjunctival suffusion can be seen. It can last from the few hours to 2 d for the hypotensive (shock) period22-24.
· Hantavirus cardiopulmonary syndrome:
This is more severe than HFRS. A standard HCPS course comprises three phases: prodromal, cardiopulmonary and convalescent25 Symptoms of non-specific flu such as fever, chills, malaise, headache, vomiting, stomach pain and diarrhoea describe the prodromal process.26-28
Laboratory Diagnosis:
Laboratory Diagnosis an Important laboratory finding in both HFRS and HCPS29S include thrombocytopenia, leukocytosis, elevated haematocrit, haematuria, proteinuria and serum creatinine29. Early signs being non-specific, clinical findings are not enough to diagnose Hantavirus infections. Serology is the mainstay of laboratory diagnosis of Hantavirus infections. On onset of symptoms, almost all patients have detectable anti-hantavirus IgM and/or IgG levels.30-31
Epidemiology and Transmission:
Hantaviruses were detected in rodents of the subfamilies Murinae, Arvicolinae, Sigmodontinae and at least one Insectivore (Suncusmurinus)41. Murinae are the largest number of Old World rodents and are the reservoirs of HNTV, DOBV, SAAV, SEOV and Amur viruses that cause HFRS and other non-human disease hantaviruses. Arvicolinae are voles and the reservoirs for PUUV, which has been correlated with mild HFRS in Europe, also for Prospect Hill virus and relevant viruses in the United States, that haven't been demonstrated to cause human infection32-36.
Sigmodontinae are the largest group of New World rats and mice that are the hosts of SNV and numerous other New World viruses. Each subfamily of rodents carries phyelogenetically different viruses, some of which may be human pathogens, and some are not human pathogens. The phylogenetic interrelationships between the viruses and those of their predominant host, with rare exceptions display significant concordance between the viruses37-44. All known hantaviruses, except TPMV and the A variety of freshly discovered viruses including Tangganya virus (TGNV), Seewis virus (SWSV), Ripley virus (RPLV) and the Cao Bang virus (CBNV), have their own murid rodents host. However, Hantavirusesother than these viruses have been detected in insectivores such as Suncusmurinus, in bats, cats and birds. Serological evidence of hantavirusinfection was also demonstrated in dogs and pigs. It is not clear whether these species are persistently infected or just spill over hosts, i.e., a secondary host infected through contact with the primary host41.
Transmissions:
It is suspected that transmission of Hantavirus occurs primarily through contact with contaminated animal excreta, such as saliva, urine and faeces. Though the erosol route of infection is undoubtedly the most common means of transmission among rodents and to humans, virus transmission by bite occurs among rodent sand may also result in human infection42.
Epidemiological features:
Hanta viral infections are predominant in rural areas, though HFRS caused by SEOV occurs in urban areas. Asymptomatic or non-specific mild infections result in the number of infections with Hantavirus being underestimated. The ratio of sub-clinical to clinical infection is 5:1 to 10:1 in Europe the ratio could be high 14:1 to 20:1 for some Hantaviruses. An eight-year study in Finland found that the average ratio of HFRS cases diagnosed was 13% only (4% to 30% for different areas) and leaving at least 70% of the PUUV infection undiagnosed as they were subclinical or had only mild or atypical symptoms44.
Fig No. 1: Rodent borne disease
Clinical Management:
Currently, there is no specific therapy available for both HFRS and HPS; therefore, the Cornerstone of treatment remains supportive measures. The management must include early admission to an intensive care unit where blood and tissue oxygenation, cardiac output, central blood pressure and cerebral pressure can be monitored. It is very necessary to maintain the balance of fluids. For HFRS treatment, one or two haemodialysis sessions are normally required, while mechanical ventilation is critical for HPS patients when pressure is indicated and sufficient use is required. Extracorporeal membrane oxygenation has found useful as a rescue therapy in patients with severe HPS. Although corticosteroids are not standard of care in treatment of hanta viral infection, steroid was used to treat severe HFRS and HPS cases.
Laboratory Diagnostics:
The diagnosis of hantavirus infections is based on clinical and epidemiological information and laboratory tests. It is almost impossible in the individual case with moderate to mild clinical symptoms to diagnose Hantavirus infection. A broad range of technologies have been used to detect hantavirus antibodies using cultured and/or purified native-virus preparations or recombinant proteins expressed in bacteria, yeast or insect cells. For the identification of particular IgM or low-avidity IgG antibodies, both indirect fluorescent assays (IFA) and enzyme immunoassays (EIA) are commonly used. Methods for detecting IgM are important tools for the diagnosis of acute infections, particularly in endemic regions with a high prevalence of IgG due to previous infections.
· RT-PCR can help detect viral RNA in blood and tissues and is the criterion standard for diagnosis. Diagnostic sensitivities specificities of 100% and 94%, respectively, have been reported.
Control and Prevention:
There isn’t a vaccine for Hantavirus. Steps that you should take to decrease your HPS risk include:
· Keep away from areas where droppings are left by rodents
· Wear latex gloves and goggles to protect the face and nose when exposed to mouse droppings.
· Using disinfectant to sanitise mouse dropping areas so that contaminated dust does not disperse into the air.
· Seal holes in and around your home to keep rodents from entering
· To minimise the population, capture rodents in and around your home
· Stop leaving food at home and while camping.
· Air out the environment before entering spaces believed to have rodents in them
No specific treatment, cure or vaccine for hanta virus infection is available. However, we know that they will do well if infected patients are diagnosed early and receive medical attention in an intensive care unit. In intensive care, patients are incubated and oxygen therapy is administered to assist them during extreme respiratory distress.
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Received on 15.09.2021 Modified on 14.12.2021
Accepted on 22.01.2022 ©Asian Pharma Press All Right Reserved
Asian J. Pharm. Res. 2022; 12(2):150-154.
DOI: 10.52711/2231-5691.2022.00023