Study Population

Thirteen HPS cases that occurred during the second half of 2002 in Argentina were analyzed in this study (Table 1). Cases were grouped in 4 clusters (C1–C4) according to their known epidemiologic relationships. Samples from 12 of the 13 case-patients were available: we collected serum and clot samples from almost all patients; from patient C4-a, clot samples could not be obtained; from patient C2-d1, a hemoculture was available after death. A sample from the son in cluster 2 (C2-s) was not available. Serologic confirmation was performed on 11 serum specimens and on the hemoculture samples as previously described (17).

Genetic Characterization

Ten clot samples and 1 serum sample were subjected to viral detection methods as described (7). For viral genetic characterization, a partial fragment of G2-encoding region from the M segment was analyzed: genomic positions 2717–2943 (G2). For cases sharing 100% nucleotide identity in G2 fragment, 1 or 2 additional regions were analyzed: positions 66–434 from G1-encoding region (G1); positions 1384–1795 for C4 and 1395–1809 for C1 from the S-noncoding region (S-NCR). All fragments were numbered in the antigenome-sense sequence relative to ANDV. The new sequences used in this manuscript have been submitted to GenBank (accession nos. DQ189092–DQ189095).

Epidemiologic Findings

Figure 1

Figure 1. Location of residences and possible sites of exposure of hantavirus pulmonary syndrome patients in the provinces of Buenos Aires and Neuquén and Andes virus (ANDV)–endemic regions, 2002.

Figure 2

Figure 2. Contact events and incubation period of hantavirus pulmonary syndrome patients, Argentina, 2002. One line was drawn per case for C1 and C4; dotted lines represent the incubation period since the established...

The cases were grouped into 4 clusters (Table 1), and the approximate geographic locations of the exposure sites are shown in Figure 1. Cluster 1 (C1) was a father-son pair (C1-f and C1-s). The first patient, C1-f, was a previously healthy veterinarian. He worked on a farm >65 km away from his home. He began working there 40 days before the onset of symptoms. He slept at the farm during the week and returned to his home on weekends. The first manifestation of his illness, abdominal pain and vomiting, began on a Wednesday. On the Friday of that week, he exhibited typical indistinguishable features of the prodromal phase. The following weekend, he remained in his house with his 2 sons. Although he was very ill, his younger son slept with him in the same bed; at that time, the prodromal phase was ending, since on the next Monday he began to experience progressive dyspnea. He sought medical attention but proceeded rapidly to pulmonary edema and shock. He died on Wednesday. His 2 sons had never visited his place of work, and they lived with their mother in another house in the city of Buenos Aires. Epidemiologist from Buenos Aires City reported that both houses were in urban areas, were in very good condition, and showed no evidence of rodents. Twenty-four days after the last contact with his sick father, fever developed in the younger son (C1-s) (Figure 2). Once immunoglobulin M antibodies to hantavirus was confirmed, he was hospitalized.

Cluster 2 (C2) was a rural cluster within a family of 5 that lived in a cabin. Rodent infestation of the house and surrounding areas was evident. The onset of symptoms of 3 of the 4 case-patients occurred during a 12-day period (Table 1). The mother in C2 (C2-m) began having symptoms when HPS was already confirmed in her 2 daughters (C2-d1 and C2-d2), but she did not seek medical consultation until 5 days later, when she was hospitalized and died.

Cluster 3 (C3), a rural cluster composed of 4 friends (cases C3-1 to C3-4), was similar to the previous cluster since all became ill during a period of 20 days (Table 1). They lived together in a cabin within the farm where they worked. Rodent infestation of the house and surrounding areas was also evident.

Cluster 4 (C4) involved a case-patient (C4-a) and a person he came into contact with (C4-b), and a third person who came into contact with C4-b. The index patient lived and worked in Neuquén City, where neither HPS cases nor rodent infestation had been registered. He traveled to Mar del Plata in the province of Buenos Aires, 1,005 km northeast of Neuquén City, where he remained for a few days while attending a meeting. His first symptoms (fever and myalgia) began before his return to Neuquén from Mar del Plata, 23 days after he returned from a vacation in Villa La Angostura, a small town surrounded by a wilderness area, 447 km southwest of Neuquén City (Figure 1). Two HPS cases were reported in 2002, and several infected rodents were captured previously. During the case-patient's 14-hour bus trip from Mar del Plata to Neuquén, he sat next a man he did not know (C4-b). During the trip, a nonproductive cough, dyspnea, tachypnea, and headache developed, and myalgia worsened. After their arrival in Neuquén, patient C4-b helped patient C4-a with his luggage and shared a taxicab with him. Patient C4-a was hospitalized 24 hours later. Patient C4-b spent 2 days in Neuquén (he never left the city). Fifteen days after the 14-hour bus trip to Neuquén City, patient C4-b became ill. He first experienced weakness and myalgia; vomiting and diarrhea developed 2 days later, and fever developed 6 days after the onset of the first symptoms. C4-b met a friend and co-worker (C4-c) 3 times during his prodromal phase; C4-c visited C4-b while he was hospitalized (Figure 2). Although C4-b did not have respiratory clinical symptoms, the chest radiograph showed interstitial infiltrates and Kurley B lines, and he had severe hypoxemia. The major clinical manifestations were weakness, gastrointestinal illness, and myalgia. An epidemiologic investigation led clinicians to suspect HPS. C4-c began to exhibit the first HPS symptoms 22 days after C4-b. C4-c had never left the province of Buenos Aires.

Viral Characterization

Nucleotide sequence comparisons of G2 fragment between sequences from the 11 cases, 5 nonlinked (NL) cases, and 5 previously published ANDV lineages are shown in Table 2. Comparisons in each of the 4 clusters showed 100% identity between cases in the same cluster. ANDV Cent BsAs lineage was characterized from C1, C2 (2/4 cases), and C3, while ANDV Sout was characterized from the 3 C4 cases, although C4-3 had never been to the southwestern part of the country. The 3 clusters from La Plata and NL-1 showed the highest similarity between them and showed significant differences with HPS cases from other places in Buenos Aires (Table 1).

Assessment of the Route of Transmission

Rodent transmission is the most common route of hantavirus infection. However, when a new HPS case is suspected, if rodent exposure was not evident, for interhuman transmission to be suspected, one must 1) find a epidemiologic link with a previous case-patient (index case-patient); 2) confirm 100% viral nucleotide identity with the index patient in the fragments analyzed; and 3) assuming that the secondary patient could have been exposed to infectious rodents in the same or a different place than the index patient, determine the probability that both viral strains have 100% nucleotide identity in the fragments analyzed.

In C1, only C1-f had an evident rodent exposure. The only risk for C1-s was the close contact with C1-f during his prodromal phase. In C4, only C4-a had an evident risk of rodent transmission because he had visited a disease-endemic area. The only risky activity of C4-b was close contact with C4-a during the 14-hour bus trip. C4-c was in contact with C4-b at several times after the latter returned from Neuquén. All nucleotide fragment comparisons showed 100% identity for G1, G2, and S-NCR for C1 and C4. We analyzed viral variability in the areas of circulation of AND Cent Bs As and ANDV Sout lineages by comparing viral nucleotide sequences from previous HPS cases and found a positive correlation between geographic distance and genetic distance for each ANDV lineage (data not shown). Each ANDV lineage showed a significant degree of variability between the supposed sites of exposure in C1 for C1-f and C1-s and in C4 for C4-a and C4-b. In summary, C1-s, C4-b, and C4-c were infected by interhuman transmission.