Stuart T. Nichol

A mysterious respiratory illness with high mortality was recently reported in the southwestern United States. Serologic studies implicated the hantaviruses, rodent-borne RNA viruses usually associated elsewhere in the world with hemorrhagic fever with renal syndrome. A genetic detection assay amplified hantavirus-specific DNA fragments from RNA extracted from the tissues of patients and deer mice (Peromyscus maniculatus) caught at or near patient residences. Nucleotide sequence analysis revealed the associated virus to be a new hantavirus and provided a direct genetic link between infection in patients and rodents.

Two men from northwestern Missouri independently presented to a medical facility with fever, fatigue, diarrhea, thrombocytopenia, and leukopenia, and both had been bitten by ticks 5 to 7 days before the onset of illness. Ehrlichia chaffeensis was suspected as the causal agent but was not found on serologic analysis, polymerase-chain-reaction (PCR) assay, or cell culture. Electron microscopy revealed viruses consistent with members of the Bunyaviridae family. Next-generation sequencing and phylogenetic analysis identified the viruses as novel members of the phlebovirus genus. Although Koch's postulates have not been completely fulfilled, we believe that this phlebovirus, which is novel in the Americas, is the cause of this clinical syndrome.

BACKGROUND: In May 1993 an outbreak of severe respiratory illness occurred in the southwestern United States. A previously unknown hantavirus was identified as the cause. In Asia hantaviruses are associated with hemorrhagic fever and renal disease. They have not been known as a cause of human disease in North America. METHODS: We analyzed clinical, laboratory, and autopsy data on the first 17 persons with confirmed infection from this newly recognized strain of hantavirus. RESULTS: The mean age of the patients was 32.2 years (range, 13 to 64); 61 percent were women, 72 percent were Native American, 22 percent white, and 6 percent Hispanic. The most common prodromal symptoms were fever and myalgia (100 percent), cough or dyspnea (76 percent), gastrointestinal symptoms (76 percent), and headache (71 percent). The most common physical findings were tachypnea (100 percent), tachycardia (94 percent), and hypotension (50 percent). The laboratory findings included leukocytosis (median peak cell count, 26,000 per cubic millimeter), often with myeloid precursors, an increased hematocrit, thrombocytopenia (median lowest platelet count, 64,000 per cubic millimeter), prolonged prothrombin and partial-thromboplastin times, an elevated serum lactate dehydrogenase concentration, decreased serum protein concentrations, and proteinuria. Rapidly progressive acute pulmonary edema developed in 15 of the 17 patients (88 percent), and 13 patients, all of whom had profound hypotension, died (case fatality rate, 76 percent). Increases in the hematocrit and partial-thromboplastin time were predictive of death. CONCLUSIONS: Infection with a newly described hantavirus causes the hantavirus pulmonary syndrome, which is characterized by a brief prodromal illness followed by rapidly progressive, noncardiogenic pulmonary edema.

An outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States was etiologically linked to a newly recognized hantavirus. Knowledge that hantaviruses are maintained in rodent reservoirs stimulated a field and laboratory investigation of 1696 small mammals of 31 species. The most commonly captured rodent, the deer mouse (Peromyscus maniculatus), had the highest antibody prevalence (30%) to four hantavirus antigens. Antibody also was detected in 10 other species of rodent and in 1 species of rabbit. Reverse transcriptase-polymerase chain reaction (RT-PCR) products of hantavirus from rodent tissues were indistinguishable from those from human HPS patients. More than 96% of the seropositive P. maniculatus were positive by RT-PCR, suggesting chronic infection. Antibody prevalences were similar among P. maniculatus trapped from Arizona (33%), New Mexico (29%), and Colorado (29%). The numeric dominance of P. maniculatus, the high prevalence of antibody, and the RT-PCR findings implicate this species as the primary rodent reservoir for a new hantavirus in the southwestern United States.

Vet Med Today: Zoonosis Update 883 R Valley fever virus is a mosquito-borne pathogen of livestock and humans that historically has been responsible for widespread and devastating outbreaks of severe disease throughout Africa and, more recently, the Arabian Peninsula. The virus was first isolated and RVF disease was initially characterized following the sudden deaths (over a 4-week period) of approximately 4,700 lambs and ewes on a single farm along the shores of Lake Naivasha in the Great Rift Valley of Kenya in 1931. Since that time, RVF virus has caused numerous economically devastating epizootics that were characterized by sweeping abortion storms and mortality ratios of approximately 100% among neonatal animals and of 10% to 20% among adult ruminant livestock (especially sheep and cattle). Infections in humans are typically associated with selflimiting febrile illnesses. However, in 1% to 2% of affected individuals, RVF infections can progress to more severe disease including fulminant hepatitis, encephalitis, retinitis, blindness, or a hemorrhagic syndrome; among severely affected persons who are hospitalized, the case fatality ratio is approximately 10% to 20%. Rift Valley fever epizootics and epidemics can rapidly overwhelm the capacities of the public health and veterinary medical communities to provide rapid diagnostic testing and adequate medical care for affected humans and other animals, which can number in the tens if not hundreds of thousands. Veterinarians, other health personnel, farmers, and abattoir workers also are at high risk of infection from direct contact with infected animals and patients; indeed, many historical outbreaks of RVF disease in Africa were initially detected because of illnesses among veterinarians and their assistants after they performed necropsies on infected animals. In 2008, several veterinarians, staff, and veterinary students at a South African veterinary college were infected after handling and performing necropsies Rift Valley fever virus