The provinces of Llanquihue and Palena are located in southern Chile, on the western edge of South America. Together they comprise 30,178 km² and 340,464 inhabitants. These 2 provinces are subdivided into 13 communes (Figure 1).

Our study comprised all HPS cases reported to HSR during 1995–2012. All were confirmed by serologic tests performed at the National Reference Centers at the Public Health Institute (Santiago) or Universidad Austral (Valdivia). These tests are ELISAs for IgM and IgG that use hantavirus Sin Nombre antigen provided by the US Centers for Disease Control and Prevention (Atlanta, GA, USA).

We obtained data from 3 sources. First, we used epidemiologic records from all cases reported during 1995–2012. Data included patient age, sex, occupation, residence, site of probable infection, contact with other HPS patients, dates of hospitalization, and outcome.

Second, we reviewed clinical records of all patients admitted to Hospital of Puerto Monttwith confirmed HPS during the same period. Data recorded were age, sex, probable mechanism of infection, incubation period (only for patients for whom precise information about the time of rodent exposure and onset of symptoms was available), and medical history. On admission, presence of dyspnea, fever, asthenia, headache, myalgias, chills, cough, abdominal pain, and cyanosis and blood pressure, pulse, temperature, and respiratory frequency were recorded. During hospital stay, the following data were collected: presence of bleeding, alterations in renal and hepatic functions, admissions to intensive care unit (ICU), oxygen support, arterial oxygen tension/inspiratory oxygen fraction (PAFI) index, steroid administration, mechanical ventilation (MV) (specifying timing of connection), and circulatory shock. Shock was defined as systolic blood pressure <90 mm Hg that did not improve with fluid administration or that required the use of vasoactive drugs and abnormalities in tissue perfusion manifested by alteration of consciousness, oliguria, and lactate acidosis (5). One of the authors (R.R.) analyzed chest radiographs and classified the infiltrates as alveolar, interstitial, or mixed pattern and unilateral or bilateral; number of compromised quadrants and presence of pleural effusion were recorded. Results of laboratory tests performed on admission and during illness were also recorded. Each case was classified into 1 of 3 groups: grade I (mild disease) when patients had only prodromal symptoms without pulmonary involvement; grade II (moderate disease) when patients had interstitial pulmonary infiltrates or required supplemental oxygen but were hemodynamically stable; and grade III (severe disease) when patients required MV or had hemodynamic instability (6). Final outcome (death or survival) was also recorded.

Finally, we reviewed reports of epidemiologic inspections to homes, workplaces, and probable sites of infection (dwellings and their surroundings) at the time of case report to HSR. A survey administered to each patient or to close relatives asked about HPS risk during the 6 weeks before symptom onset. Visited places were classified as urban, rural, or semirural. We stratified the infection risk in visited dwellings according to a 5-parameter scale, each with 1 point assigned to absence of foundations, presence of holes, poor ventilation and lighting, presence of trash without adequate container inside the dwelling, and grainstorage, flour, and other food packaging Risk was considered high for scores 4–5, moderate for 2–3, low for 1, and absent for 0. We similarly classified dwelling surroundings according to presence of droppings, rodent pathways, rubbing stains, gnawing signs, rodent nests or holes, or observation of rodents themselves.

We used the Student t test to compare parametric variables and χ² and Fisher exact tests to compare discrete variables when necessary. A p value <0.05 was considered statistically significant. Incidence rate of HPS per commune was calculated from information provided by Chilean Census 2002 (7).

We identified 52 rural locations as probable infection sites for 100 patients. For the remaining 3 patients, infection site could not be determined because of exposure to several risky sites.

Infection most likely was acquired through farming and forestry work for 44% of patients and was associated with recreational activities for 13%. For the remaining patients, infection-associated activity was not determined because of similar risk at home and at work.

HPS incidence per 100,000 inhabitants varied widely among communes. The highest rates occurred within Andean mountainous areas, mainly Palena and Cochamó communes (350 and 364 cases per 100,000 inhabitants, respectively). Incidence for the aforementioned communes was 8.5 times higher than that for the rest of the region (Table 1; Figure 1).

Yearly incidence varied widely during 1995–2012. Most cases occurred during 2005–2007 (Figure 2). In the region studied, incidence was highest during winter. By contrast, in the rest of the country, incidence was highest during summer and autumn (Figure 3).

For 23 patients, HPS occurred in related persons and made up a total of 8 clusters, 5 with 3 cases each and 4 with 2 cases each. All patients in each cluster shared both environmental risk factors and family relationship; included in the clusters were 6 cohabitating couples.

Epidemiologic reports on home or workplaces were available for 42 patients. Thirty-one percent of houses, 43% of housing environments, and 39% of working environments had high or moderate risk for rodent infestation.

The 80 HPS patients admitted to Hospital of Puerto Montt during 1995–2012 represented 78% of cases reported to HRS during that period. Seventy percent were men. Patients were 35.7 ± 16 years of age (range 4–73 years), and 90% were rural inhabitants. Their main occupational activities were farming or forestry (35%), housework (25%), student (15%), and fishery or marine harvesting (11%). Of these patients, 25 (31%) had a history of contact with rodents or rodent droppings. Infection was attributed to occupational exposure for 35 (44%) patients and traveling to a high incidence zone for 10 (12%).

Mean interval from appearance of symptoms to hospitalization was 5.7 ± 3 days (range 2–17 days). Incubation period, estimated from the analysis of 20 patients, was 10 ± 7 days (range 2–28 days).

For patients admitted during 1995–2004, HPS was considered 1of the admission diagnoses for only 7 (27%) of 26 case-patients. This presumptive diagnosis increased to 76% (37/49) during 2005–2012 (Tables 2, 3).

Duration of hospitalization for HPS patients was 5.2 ± 4.6 days (range 1–25 days). Sixty-three (79%) case-patients were admitted to the ICU; 72 (90%) required oxygen administration; and 40 (50%) were connected to MV for 4.2 ± 4.7 days (range 1–17 days).

Mean PAFI at admission was 216 ± 107 (range 40–508). Five (6%) patients had no pulmonary involvement. Shock occurred in 37 (46%) patients, all of whom received vasoactive drugs as prescribed. Hemorrhagic manifestations occurred in 31 (39%) patients: hematuria in 15 patients; cutaneous or puncture sites bleeding in 12 patients, hemoptysis in 5 patients, metrorrhagia in 4 patients; and epistaxis gingivorrhagia, rectorrhagia, and epidural hematoma after lumbar puncture in 1 patient each.

For 95% of patients, platelet counts were <100 × 10³/μL(reference range 140–44010³/μL) at a given time; for 34%, platelet counts were <35 × 10³/μL. The mean platelet count was 50 ± 39 (range 8–238) × 10³/μL. In 48% of hospitalized patients, creatinine increased >1.2 mg/dL (reference range 0.5–0.9 mg/dL); 4 (5%) of these patients required hemodialysis. Hepatic enzymes were elevated in 57 (71%) patients.

Thirty-one patients received steroids. Methylprednisolone was administered to 20 patients in accordance with a published protocol (8): 1 g intravenously per day for 3 days, followed by 16 mg orally per day for 3 days, 8 mg per day for 3 days, and 4 mg per day for 3 days. Eleven other patients were enrolled in a clinical trial and received methylprednisolone 1 g intravenously per day for 3 days (9). Nevertheless, we observed no difference in CFR between patients who did and did not receive methylprednisolone.

According to their clinical course, 5 (6%) patients were classified as having grade I HPS; 34 (42%) as having grade II HPS, and 41 (51%) as having grade III HPS. Twenty-four (30%) hospitalized patients died; for 21 (88%) of these, death was attributed directly to HPS. Shock was considered the cause of death for 18 (75%) patients, respiratory failure for 2 (8%), multiorgan failure for 2 (8%), and secondary sepsis for 2 (8%) (1 gram-negative sepsis and 1 Staphylococcus aureus sepsis).

Fifteen (63%) of 24 patients died during the first 24 hours after admission, and 22 (92%) died during the first 72 hours after admission. All deaths occurred among patients with grade III disease. Independent factors associated with death were respiratory frequency >30 breaths/minute and creatinine >1.3 mg/dL on admission (Table 4). CFR did not differ by sex, abnormal hepatic test results, or chest radiographic images progression >50% in 48 hours. Furthermore, we found no relation to CFR for patients with hematocrits >45% or >50%; platelet counts <100, <50 or <35 × 10³/μL at admission; or PAFI <250, <200, <150, or <120 at admission.