Hantavirus prevalence in the IX Region of Chile - Research

Emerging Infectious Diseases, July, 2003 by Marlis Tager Frey, Pablo C. Vial, Constanza H. Castillo, Paula M. Godoy, Brian Hjelle, Marcela G. Ferres

An epidemiologic and seroprevalence survey was conducted (n=830) to assess the proportion of persons exposed to hantavirus in IX Region Chile, which accounts for 25% of reported cases of hantavirus cardiopulmonary syndrome. This region has three geographic areas with different disease incidences and a high proportion of aboriginals. Serum samples were tested for immunoglobulin (Ig) G antibodies by enzyme-linked immunosorbent assay against Sin Nombre virus N antigen by strip immunoblot assay against Sin Nombre, Puumala, Rio Mamore, and Seoul N antigens. Samples from six patients were positive for IgG antibodies reactive with Andes virus; all patients lived in the Andes Mountains. Foresting was also associated with seropositivity; but not sex, age, race, rodent exposure, or farming activities. Exposure to hantavirus varies in different communities of IX Region. Absence of history of pneumonia or hospital admission in persons with specific IgG antibodies suggests that infection is clinically inapparent.

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Hantaviruses, RNA-containing viruses, compose a genus within the family Bunyaviridae. The natural reservoirs of the pathogenic New World hantaviruses are rodents of the family Muridae, subfamily Sigmodontinae, in which a chronic and asymptomatic infection develops (1). Hantavirus is a zoonosis transmitted from rodents to humans by inhaling contaminated aerosols from feces, urine, and saliva of infected mice (2).

Human infection with hantaviruses have been associated with two diseases. One is the hemorrhagic fever with a renal syndrome (HFRS) caused by Hantaan, Puumala, Seoul, and Dobrava/Belgrade viruses, first recognized during the Korean War in 1950 to 1953. HFRS occurs mainly in Asia and Europe; death rates range from 0.1% to 15% (3,4). The other disease, a severe respiratory illness known as hantavirus cardiopulmonary syndrome (HCPS), occurs in the Americas and has a death rate of 40% (1,5-7). We prefer the term hantavirus cardiopuhnonary syndrome to an alternative term, hantavirus pulmonary syndrome, because most deaths associated with HCPS are related to cardiac failure rather than pulmonary failure, and this aspect of the syndrome remains underappreciated by practitioners and others.

HCPS has been identified in several countries in North and South America and is caused by different hantaviruses: Sin Nombre in North America, Juquitiba virus in Brazil (8), Laguna Negra virus in Paraguay and Bolivia (9,10), Andes in Argentina and Chile (11,12), Choclo virus in Panama (13), and several subspecies or viral genotypes of Andes virus in Argentina (e.g., Oran, Lechiguanas, et al.) (14-16).

In 1995, Andes virus was first identified in the Argentinean Patagonia and was recognized in central and southern regions of Chile. The reservoir is the long-tailed pygmy rice rat (Oligoryzomys longicaudatus), a species that occurs primarily in temperate forest (17).

Since HCPS emerged in Chile, 287 cases have been confirmed as of March 2003, causing a substantial impact on the public health system; the death rate for HCPS in Chile has exceeded 40%. In addition to the 287 cases of HCPS, 17 cases of mild infection with no cardiopulmonary involvement have been reported, demonstrating that hantavirus infection may have variability in its expression. Serologic studies have established both clinically asymptomatic infections and symptomatic infections not recognized at the time as hantavirus infection (18-23).

The phenomenon of clinically nonapparent infections varies in different areas and populations of the Americas. In the United States, the proportion of infection versus disease is thought to be close to 1% (i.e., disease develops in most of the infected patients, and human population seroprevalence varies between 0.2% to 1.7%) (4,24,25). Seroprevalence studies in South America, however, have shown that some populations have had much more frequent exposure to hantaviruses in the absence of known clinical manifestations, as seen in some populations native to Paraguay and Northern Argentina (40% and 17%, respectively) (26), the general population in Aysen, Southern Chile (2.0% and 13.1% in urban and rural areas, respectively) (27), Silo Paulo and Bahia, Brazil (1.23 % and 13.1%, respectively) (28,29), and recently in Panama (30%) (13). The populations with the highest seroprevalence were indigenous persons rather than those of European ancestry.

Two hypotheses have been proposed to explain these phenomena. The first one presumes that strains in South America are of lesser pathogenicity, though in many cases nonpathogenic viruses have yet to be detected in local rodent populations. The second hypothesis involves the existence of at least two variables: the nature of the exposure and genetic constitution of the host population. The high seroprevalence seen in Paraguay (26) could be caused by a higher resistance in the aboriginal population and greater exposure to the virus in some regions. The prevalence and high case-fatality ratios seen in North America might be the result of a lower exposure, a lesser genetic resistance to disease, or both.