Hantavirus infections: A growing global health concern

Table 1 Critical comparison of hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome pathogenesis and clinical outcomes

Parameter	HFRS	HPS
Major viral group	Old World hantaviruses	New world hantaviruses
Main target organ	Kidney and vascular system	Lung and cardiovascular system
Key pathology	Increased vascular permeability with renal endothelial dysfunction	Pulmonary capillary leakage and myocardial depression
Dominant clinical feature	Fever, hemorrhage, thrombocytopenia, acute kidney injury	Fever, rapidly progressive pulmonary edema, shock
Mortality	Usually < 1%-12%, depending on strain	Often 30%-50%
Immune mechanism	Cytokine-mediated endothelial activation and renal inflammation	Strong inflammatory response causing pulmonary vascular leakage
Treatment response	Ribavirin may help if given early	Ribavirin benefit is limited or unclear
Main reason for difference	Longer disease evolution allows earlier antiviral intervention	Rapid cardiopulmonary phase occurs when immunopathology dominates

HFRS: Hemorrhagic fever with renal syndrome; HPS: Hantavirus pulmonary syndrome.

Table 2 Classification and geographic distribution of major hantaviruses

Virus name (orthohantavirus)	Primary reservoir host	Geographic distribution	Associated disease	Approximate case fatality rate	Human-to-human transmission
HTNV	Apodemus agrarius (Striped field mouse)	China, Korea, Russia	HFRS	5%-12%	No
PUUV	Myodes glareolus (Bank vole)	Northern and Central Europe	HFRS/nephropathia epidemica	< 1%	No
SEOV	Rattus norvegicus, Rattus rattus	Worldwide (Urban areas)	HFRS	~ 1%	No
DOBV	Apodemus flavicollis	Balkans, Eastern Europe	Severe HFRS	Up to 10%	No
SNV	Peromyscus maniculatus (Deer mouse)	North America (United States, Canada)	HPS	30%-40%	No
ANDV	Oligoryzomys longicaudatus	Argentina, Chile	HPS	35%-50%	Yes (documented)
BCCV	Sigmodon hispidus (Cotton rat)	Southeastern United States	HPS	~ 30%	No
BAYV	Oryzomys palustris (Marsh rice rat)	Southern United States	HPS	Variable	No
LANV	Calomys laucha	Paraguay, Bolivia	HPS	~ 20%-30%	No
PHV	Microtus pennsylvanicus (Vole)	North America	Non-pathogenic	Not applicable	No

HTNV: Hantaan virus; PUUV: Puumala virus; SEOV: Seoul virus; DOBV: Dobrava-Belgrade virus; SNV: Sin Nombre virus; ANDV: Andes virus; BCCV: Black Creek Canal virus; BAYV: Bayou virus; LANV: Laguna Negra virus; PHV: Prospect Hill virus; HFRS: Hemorrhagic fever with renal syndrome; HPS: Hantavirus pulmonary syndrome.

Table 3 Diagnostic methods for hantavirus infection

Diagnostic method	Target detected	Diagnostic accuracy	Field/clinical utility	Limitations	Optimal timing of use
ELISA (IgM/IgG detection)	Anti-hantavirus antibodies	High sensitivity	Widely available, cost-effective, suitable for screening large populations	Possible cross-reactivity with other viral antigens	Acute and convalescent phases
IFA	Viral antibodies	High specificity	Reliable confirmation method; useful for sero-epidemiological studies	Labor-intensive, requires fluorescence microscopy	Acute phase confirmation
NeutralizationTest (PRNT/FRNT)	Neutralizing antibodies	Very high specificity (gold standard)	Confirms protective immunity and virus strain identification	Requires BSL-3 Laboratory, expensive, technically demanding	Research and confirmatory diagnosis
Immunochromatographic rapid tests	IgM/IgG antibodies	Moderate sensitivity	Rapid, easy to perform, suitable for field settings	Reduced accuracy and cross-reactivity issues	Early screening in endemic regions
RT-PCR	Viral RNA (S, M, L segments)	Very high sensitivity during viremia	Rapid and highly specific detection; useful for early diagnosis	Limited detection window; requires molecular laboratory	Early acute phase (viremic stage)
NGS	Whole viral genome	Very high accuracy	Enables strain identification, mutation analysis, and outbreak tracking	High cost, complex bioinformatics analysis	Research and surveillance
Microarray analysis	Multiple viral sequences	High sensitivity	Simultaneous detection of diverse pathogens	Expensive and technically complex	Advanced research settings
Virus isolation in cell culture	Live virus	Highly specific	Enables functional studies and antiviral testing	Time-consuming; requires BSL-3 containment	Research applications
IHC	Viral antigens in tissues	High specificity	Useful in post-mortem or biopsy samples	Requires skilled personnel and tissue preparation	Severe or fatal cases

ELISA: ; IFA: Indirect immunofluorescence assay; PRNT: Plaque reduction neutralization test; FRNT: Focus reduction neutralization test; RT-PCR: Reverse transcription-polymerase chain reaction; NGS: Next-generation sequencing; BSL: Biosafety level; IHC: Immunohistochemistry.