Hantavirus pulmonary syndrome in a Chilean patient with recent travel in Bolivia.

A case of hantavirus pulmonary syndrome (HPS) was serologically confirmed in a critically ill patient in Santiago, Chile. The patient's clinical course had many similarities to that of other HPS patients in North and South America but was complicated by acute severe renal failure. The patient's history included self-reported urban and probable rural rodent exposure during travel in Bolivia. Comparison of a viral sequence from an acute-phase serum sample with other known hantaviruses showed that the hantavirus nucleic acid sequence from the patient was very similar to a virus recently isolated from rodents associated with HPS cases in Paraguay.

tion rate 6, and a C-reactive protein 2.8 mg/dl. He was sent home on clarithromycin 250 mg, twice a day. Three days later (March 31), he returned to the emergency room with persistent high fever, myalgia, and shortness of breath; distal cyanosis was noted. Vital signs were as follows: blood pressure 115/80, pulse 120, temperature 38.5°C, and respiratory rate 32. Physical examination found few petechiae on the forearms, diffuse bilateral rales, regular cardiac rhythm, no murmurs, and no hepatomegaly or splenomegaly. Chest X-rays showed diffuse bilateral alveolar infiltrates. Oxygen saturation was 90%. Laboratory values included white blood cells 11,700 with a left shift, platelets 150,000, hemoglobin 19.4, erythrocyte sedimentation rate 2, C-reactive protein 8.18, INR 1.6, activated partial thromboplastin 43s, blood urea nitrogen 38.9 mg/dl, and liver function tests normal limits.
The patient was transferred to the intensive care unit with a diagnosis of bilateral pneumonia of unknown etiology and secondary respiratory failure. In 3 to 4 hours, acute respiratory distress developed; arterial blood gases (on 50% oxygen) were PaO 2 61, PaCO 2 22.7, pH 7.49, and HCO 3 17.1. The patient was connected to a ventilator and was started on imipenen, erythromycin, amantadine, dopamine, dobutamine, fluids, and nitric oxide. Two 500-mg doses of methylprednisolone were administered, and a Swan-Ganz catheter was installed. The pulse wedge pressure was 7, and the cardiac output 6.1. During the first 24 hours, acute renal failure developed, and hemodialysis was started.
Hypotension was quite refractory to vasoactive drugs (mean BP 30 to 40), and critical

Hantavirus Pulmonary Syndrome in a Chilean Patient with Recent Travel in Bolivia
A case of hantavirus pulmonary syndrome (HPS) was serologically confirmed in a critically ill patient in Santiago, Chile. The patient's clinical course had many similarities to that of other HPS patients in North and South America but was complicated by acute severe renal failure. The patient's history included self-reported urban and probable rural rodent exposure during travel in Bolivia. Comparison of a viral sequence from an acute-phase serum sample with other known hantaviruses showed that the hantavirus nucleic acid sequence from the patient was very similar to a virus recently isolated from rodents associated with HPS cases in Paraguay. The patient's condition deteriorated progressively, with further bronchial bleeding and markedly unstable ventilatory function, and required constant administration of vasoactive drugs; he died of massive pulmonary hemorrhage and shock on April 28. A postmortem lung sample was taken with a needle. The patient's serum, collected on April 1, was tested for immunoglobulin G (IgG) and IgM antibodies to Sin Nombre virus at CDC. Both IgG and IgM antibodies were found, which suggested recent infection with a hantavirus associated with Sigmodontine rodents. Subsequent testing of sera collected on April 21 and April 25 confirmed the initial findings. Hematoxylin and eosin stained sections of the lung sample showed diffuse alveolar damage with extensive hyaline membrane formation, proliferation of type II pneumocytes, and fibroblastic and edematous thickening of alveolar walls. Abundant fibrin, necrotic debris, and acute inflammatory cellular infiltrates were also observed in the alveolar spaces. Rare endothelial cells and macrophages were hantavirus-antigen positive by previously described immunohistochemical procedures (9). The destructive changes seen by histopathology and a small amount of antigen found in the patient's tissues are compatible with the long course of the patient's illness (9). Viral RNA was extracted from the earliest serum sample, and reverse transcriptasepolymerase chain reaction amplification with primers designed specifically for hantaviruses associated with Sigmodontine rodents (8) yielded polymerase chain reaction fragments for the S and M segments. These cDNA fragments were sequenced and compared with those of other American hantaviruses. These comparisons show that the virus is closely related to other South American hantaviruses, and most closely related to Laguna Negra virus detected in patients and Calomys laucha rodents (vesper mice) in the Chaco region of Paraguay (7,8). The nucleotide sequence identity was 84% for the G1 protein encoding fragment and 87% for the N protein encoding fragment. However, the deduced amino acid sequences for both fragments were identical to Laguna Negra virus. This shows that the virus associated with this HPS case is a Laguna Negra virus variant and suggests that the virus is probably associated with the same or a very closely related species of rodent host.
C. laucha, the apparent primary rodent reservoir for Laguna Negra virus, is common in savanna and grassland areas as far north as southern Brazil and Bolivia, throughout much of Paraguay and Uruguay, and in Argentina as far south as Rio Negro province, but not in Chile (10). A number of the lowland rural locations that the patient visited in Bolivia are within the range of C. laucha.
The clinical course and travel history of the patient and the laboratory serology and molecular characterization of the viral RNA are compatible with infection in Bolivia with a Laguna Negra virus variant. This report and evolving information concerning hantaviruses associated with clinical HPS in Argentina and Paraguay strongly suggest that a diagnosis of HPS should be considered in patients with febrile respiratory distress syndrome throughout Latin America.