Study: Human Orthohantavirus disease prevalence and genotype distribution in the U.S., 2008–2020: a retrospective observational study. Image Credit: CI Photos / Shutterstock
Scientists at the U.S. Centers for Disease Control and Prevention (CDC) have conducted a study to determine the prevalence and genotype distribution of human Orthohantavirus disease in the United States.
The study is published in The Lancet Regional Health.
Background
Hantaviruses are negative-sense multi-segmented viruses that typically infect rodents. However, spillover hantaviral infection can occur in humans upon exposure to infected rodent’s excreta or due to rodent bites. Human-to-human transmission has only been documented for a single viral species, i.e., Orthohantavirus andesense, in South America.
Old World hantaviruses predominantly circulate in Europe and Asia and have been found to cause hantavirus hemorrhagic fever with renal syndrome. On the other hand, New World hantaviruses predominantly circulate in North and South America and have been found to cause hantavirus cardiopulmonary syndrome.
Currently, hantavirus infection is a nationally noticeable disease in the United States. Health departments from various corners of the country report acutely infected hantavirus cases to the CDC’s national hantavirus surveillance registry. However, a significant challenge noted in the study is the lack of standardized serological or PCR testing across the U.S., which has led to discordant results between CDC-developed assays and commercial diagnostic tests.
Reporting criteria of positive cases are based on clinical symptoms and laboratory diagnostic results, including immunoglobulin M (IgM) positive, IgG positive with rising titers, immunohistochemistry positive, or polymerase chain reaction (PCR) positive.
CDC reference testing has revealed that IgM false-positive results have been observed from commercial diagnostic assays. This suggests that some acute hantavirus cases may be overestimated in states that do not confirm positive results with reference testing.
In this observational study, scientists have determined the prevalence and genotype distribution of human hantavirus disease in the United States from 2008 to 2020.
Study design
The scientists analyzed multiple datasets, including acute hantavirus cases reported by health departments from 1993 to 2020 and from 2008 to 2020, as well as hantavirus acute and convalescent diagnostic testing performed at CDC from 2008 to 2020.
Suspected hantaviral samples submitted to CDC were tested for New World Orthohantavirus- and Old World (O.W.) Orthohantavirus-reactive IgM (acute samples) and IgG (convalescent samples) antibodies. A critical aspect of the study was the sequencing of hantavirus-positive samples to identify specific viral variants and their geographical distribution.
Hantavirus-positive samples were analyzed using next-generation sequencing, and available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the United States.
Important observations
Between 1993 and 2020, 833 human hantavirus cases were detected, and 335 cases were detected between 2008 and 2020 in the United States. Of these, the CDC identified 115 New World hantavirus-positive samples, representing 29.2% of the total cases detected.
Of these cases, 98 were reported by state, tribal, local, and territorial health departments. This represented 29% of total acute confirmed cases reported by health departments.
Among New World hantavirus cases identified by the CDC, about 85% were detected during acute disease. However, some convalescent cases were detected in Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont. These regions were not typically associated with hantavirus infections.
Among hantavirus cases detected in the United States between 1993 and 2020, about 95% were identified in the west of the Mississippi, and 45% were identified in the Four Corners region. Some cases were also identified in the upper Midwest, mid-Atlantic, and Northeastern regions. In contrast, only a few cases were identified in Southeastern regions.
Among New World hantavirus cases detected between 2008 and 2020, about 68% occurred between March and August.
The study also identified specific viral variants associated with distinct geographical regions. The geographical distribution of Orthohantavirus sinnombreense species was determined by sequencing PCR-positive cases. This led to the detection of the Sin Nombre virus primarily in the west of the Mississippi and Ohio Rivers, the Monongahela virus in the Northeastern and Mid-Atlantic regions, and the New York virus in Long Island. However, there was a significant gap in viral sequence data from the Northwestern and Central U.S. Only one case of Sin Nombre virus infection was identified in Indiana.
Study significance
The study provides an updated view of human hantaviral cases' spatial and temporal distribution in the United States.
Nearly 95% of cases were identified west of the Mississippi between March and August. In contrast, only 45% were identified in the Southwest Four Corners region, traditionally associated with hantaviral infections.
The study highlights the need for more standardized diagnostic testing algorithms across the U.S. to reduce discordance between different testing methods. A low prevalence of hantaviral disease has been observed in the southeastern and lower mid-Atlantic U.S. This could be due to a lack of spillover human cases or underreporting or under-testing human cases because of mild or asymptomatic infections.
Since these regions are within the home range of known hantavirus rodent vectors, rigorous monitoring of spillover human cases is needed to prevent potential public health threats. The study highlights the need for more standardized diagnostic testing algorithms across the U.S. to reduce discordance between different testing methods.
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