Seroprevalence study of Hantavirus infection in the community based population.

The genus Hantavirus, family Bunyaviridae, comprise at least 20 distinct viruses. Ten of these have been linked to specific human diseases. Hemorrhagic fever with renal syndrome has been recognized since the 1950s. Hantavirus pulmonary syndrome was recognized in the United States in 1993. Epizootiologic studies of Norway rats in the Baltimore area have shown that rodent infections with hantaviruses are common and geographically widespread with prevalence reaching 44% in tested rat populations. These viruses are antigenically related to the Seoul virus. Hantavirus infections in humans occur through transmission from a rodent reservoir, primarily by inhalation of virus laden rodent excreta. There is no evidence to support person-to-person transmission of any known Hantavirus. To establish the prevalence of Hantavirus infections in humans in the Baltimore area we collected sera from 1,212 persons attending a community based health care system. These were tested for antibodies against three reference Hantavirus strains: Hantaan (HTN), Seoul (SEO), and Convict Creek (HN017). HN017 was chosen to represent the SinNombre (SN-like) strains of Hantavirus. Sera from nine patients were positive to Hantavirus specific antibodies, HTN, and SEO by Enzyme Linked Imuno Sorbent Assay (ELISA). No sera were positive for HN017 antigen. All sera that were positive for HTN and SEO were tested by western blot for HTN. All nine sera were confirmed positive by western blot. This suggests that unrecognized infections with Hantaan or Seoul-like viruses occur in the Baltimore area in humans, although the prevalence rate in humans is low (0.74%). Epidemiologic monitoring may be warranted to establish the health implications of these infections.

Isolation of a Puumala-like virus from Mus musculus captured in Yugoslavia and its association with severe hemorrhagic fever with renal syndrome.

An outbreak of severe hemorrhagic fever with renal syndrome (HFRS) occurred in 1988 in Pozarevac, Serbia, Yugoslavia. The disease was diagnosed in 4 children and 1 adult, and 1 of the children died. Rodents were captured from the same area and virus isolation attempted. A hantavirus, POZ-M1, was isolated from lung tissues of hantavirus antigen-positive Mus musculus. Serology and restriction enzyme digestion of polymerase chain reaction-amplified segments from this virus showed that it was a strain of Puumala (PUU) virus, the causative agent of nephropathia epidemica. While Clethrionomys glareolus is the major rodent host for PUU virus, these results suggest that M. musculus may also play an important role in harboring and transmitting PUU-like viruses. The serologic association of this virus with patients with severe HFRS reaffirms that PUU-like viruses may cause severe disease in addition to the generally mild form normally associated with nephropathia epidemica.

Dobrava virus as a new Hantavirus: evidenced by comparative sequence analysis.

Dobrava virus, recently isolated from a yellow-neck mouse (Apodemus flavicollis), captured in a northern Slovenian village where severe cases of hemorrhagic fever with renal syndrome were recognized, was shown by serology and restriction enzyme digestion of PCR-amplified gene segments to be related to previously recognized hantaviruses. To investigate further the relationship of this new isolate to other hantaviruses, a portion of the medium (M) genome segment of Dobrava virus was amplified by PCR and the nucleotide sequence determined. Comparing the nucleotide sequence with the same gene region of other hantaviruses revealed an overall homology of 41.7%. A phylogenetic tree based on pairwise sequence similarity clearly showed that Dobrava virus is genetically distinct, and probably represents a new virus in the genus Hantavirus of the family Bunyaviridae.

Hemorrhagic fever with renal syndrome in Yugoslavia: epidemiologic and epizootiologic features of a nationwide outbreak in 1989.

A nationwide epidemic of hemorrhagic fever with renal syndrome (HFRS) occurred in Yugoslavia in 1989. Sera from 609 hospitalized patients, from all six Republics (Bosnia and Hercegovina, Croatia, Macedonia, Montenegro Serbia, Slovenia) and two Provinces (Kosovo and Vojvodina), who had signs and symptoms suggestive of HFRS, and sera and lung tissues from 544 small mammals belonging to 13 species were studied for evidence of hantavirus infection. Of the 226 patients with serologically confirmed HFRS, 182 resided in Bosnia and Hercegovina or in Serbia. The severity of disease differed from region to region, with an overall fatality of 6.6% (15/226). Patients from southern Yugoslavia tended to have more severe disease and exhibited two types of antibody patterns, while approximately equal numbers of clinically severe and mild cases of HFRS were registered in central Yugoslavia, where four types of antibody patterns were found. Two of these antibody patterns suggested the existence of hantaviruses which are antigenically distinct from those reported to date. Two seasonal peaks of disease, one during the summer and the other in late autumn, were found. Hantaviral antibodies and/or antigens were detected most often in the yellow-necked mouse (Apodemus flavicollis) (88/189), the wood mouse (Apodemus sylvaticus) (28/146), the striped field mouse (Apodemus agrarius) (10/64), the bank vole (Clethrionomys glareolus) (36/63), the house mouse (Mus musculus) (14/29), and the Norway rat (Rattus norvegicus) (14/21). Five other species of rodents and insectivores were infrequently infected.

Belgrade virus: a new hantavirus causing severe hemorrhagic fever with renal syndrome in Yugoslavia.

Two biologically and genetically distinct hantaviruses were isolated from blood and urine specimens collected from four Yugoslavian patients with clinically severe hemorrhagic fever with renal syndrome (HFRS). Viral isolates from three patients, designated strains Belgrade 1-3, were distinct from Hantaan, Seoul, Puumala, and Prospect Hill viruses as determined by plaque-reduction neutralization tests and restriction analysis of enzymatically amplified M-segment fragments. The fourth isolate, called Kraljevo, was indistinguishable from Hantaan virus. Strains Belgrade 1 and 2, like the Kraljevo strain, caused a fatal meningoencephalitis in newborn mice inoculated with 100 pfu of virus intracerebrally and intraperitoneally. Strain Belgrade 3 was much less neurovirulent, requiring 30,000 pfu of virus to cause fatal disease in mice. These data indicate that two distinct hantaviruses, one of which constitutes a new serotype, cause clinically severe HFRS in Yugoslavia.

[Epidemiologic characteristics of hemorrhagic fever with renal syndrome in a military population]. / Epidemioloske karakteristike hemoragicne groznice sa bubreznim sindromom u vojnickom kolektivu.

In the period 1952-1990 there have been recorded 84 patients with hemorrhagic fever with renal syndrome (HFRS): 81 soldiers and 3 officers of the Y.P.A. The largest number of cases was recorded in three epidemics, 61 or 72.6%. In 94% of cases the infection occurred during camping of units. The disease appeared in all months, but 57.2% of cases occurred in June and July. The mean lethality was 2.4%, in epidemics 1.6% and as sporadic cases 4.3%. In an army unit staying for six months in HFRS focus, 9.8% of soldiers were infected by the causative agent of this infection and only in one case the clinical picture of HFRS was manifested. Serologic tests (IIF and ELISA) confirmed the diagnosis of HFRS. Virus strains of Hantaan, Puumala and Seoul groups were used as antigens.

[Hemorrhagic fever with renal syndrome in Yugoslavia 1951-1988]. / Hemoragicna groznica sa bubreznim sindromom u SFRJ u periodu od 1951. do 1988.

Data on hemorrhagic fever with renal syndrome (HFRS) incidence in SFRY 1950-1988 were analysed. Information sources were published papers and official reports of Federal and Republic Institutions for Public Health. Indirect immunofluorescence technique was used in testing 1.842 organs of small wild mammals to the presence of HFRS viral antigen. This antigen was found in the lungs of 11 species. Average incidence of the carrier state was 10.4% Registered were 613 cases within the period 1951-1988. Morbidity rate was 0.05-10.6:1.00.000 for years. Disease have been registered during the whole year with maximum incidence rate in summer months. Men most capable of working were the most frequently affected: farmers, wood workers, soldiers. Average lethality was 5.2%.