The cases described here are the first reported laboratory-confirmed cases of HPS in the Department of Santa Cruz, Bolivia. The sequence of the LANV from the physician was 99% identical to viruses obtained from a large vesper mouse (Calomys callosus
) caught on his ranch, clearly marking this area as endemic for LANV 
. This is further evidenced by the finding of other IgM-positive persons on the ranch, some of whom recently had syndromes consistent with mild HPS. Although the small vesper mouse (Calomys laucha
) is considered the primary reservoir of LANV, the virus has been found in large vesper mice in Argentina, suggesting that LANV is also adapted to this rodent species 
. Laguna Negra virus was also isolated from a Chilean traveler who developed HPS after traveling throughout Bolivia, including Santa Cruz Department 
. The precise location of his infection is unknown. Hantavirus pulmonary syndrome due to LANV or LANV-like viruses has also been confirmed in Paraguay 
, Brazil 
, and Argentina 
Unfortunately, no sample was available to identify the specific virus that infected the sugarcane worker. However, a virus with 90% nucleotide homology with the hantavirus Río Mamoré (RIOMV) was obtained from a small-eared pygmy rice rat (Oligoryzomys microtis
) trapped in the region where the man worked and was presumably infected 
. Although RIOMV has not been definitively linked to human disease, fatal HPS has been reported in eastern Brazil putatively linked to viruses (coined Anajatuba and Río Mearim) phylogenetically very similar (94–96% nucleotide homology) to RIOMV 
. Although RIOMV-infected small-eared pygmy rice rats have been found to date only in the Bolivian departments of Santa Cruz, La Paz, and Beni, and in neighboring Peru, the range of this species, and thus the potential area at risk for RIOMV transmission, is vast, including the Amazon Basin of Brazil and contiguous lowlands of Peru, Bolivia, and Paraguay 
Assuming that the episode of rodent urine falling on the physician's face was the infecting event, we can calculate a precise incubation period of 33–35 days for this case (still with a small range, since the physician did not recall which day during his weekend stay the exposure occurred). This is in keeping with other reported incubation periods for HPS 
Four different hantaviruses have now been confirmed in Bolivia: LANV 
, RIOMV 
, Bermejo 
, and Andes 
. Furthermore, two distinct hantaviruses circulate in the Department of Santa Cruz (LANV and RIOMV) and three in Tarija (LANV, Andes, and Bermejo)(). Cases of HPS have also been reported from Cochabamba Department, although no information is available on the specific hantavirus involved 
. The risk of infection should probably be considered particularly high in the Departments of Santa Cruz, Tarija, and Cochabamba, especially to agricultural workers and others with frequent exposure to rodents.
The prevalence of antibody to hantavirus in Santa Cruz Department was relatively high and consistent throughout the areas studied. Age stratification showed a steady increase in IgG antibody-prevalence with increasing age group, suggesting continuous exposure to hantaviruses over the course of the lives of the population (). It is notable that, despite the apparent consistently high rate of exposure to hantaviruses, confirmed cases of HPS have never before been reported from Santa Cruz Department. Possible explanations for this finding include frequent mild or asymptomatic infection not necessitating medical care (as we have documented here in the four IgM antibody-cases), inadequate surveillance or reporting, and misdiagnosis of HPS by clinicians, perhaps due to unfamiliarity with the condition compounded by lack of readily available diagnostic testing for HPS in most hospitals. Similar high antibody prevalence with infrequent reporting of HPS has been reported from Cochabamba Department in Bolivia, as well as from neighboring areas of Paraguay, Argentina, and Chile 
. In contrast, data do not suggest frequent mild or asymptomatic transmission of Sin Nombre or other hantaviruses in North America 
The occurrence of six human hantavirus infections (including both PCR- and IgM-positive cases) in two ecologically disparate areas of Santa Cruz Department within a few months may relate to region-wide climatic or ecological influences resulting in increased rodent populations 
. Deviations in precipitation or temperature, sometimes associated with effects on flowering and fruiting or seed-set of particular plants known to be significant sources of food for rodents, have been implicated in other hantavirus outbreaks, although the precise relationship remains ill-defined 
. Interestingly, precipitation in the city of Santa Cruz in the months prior to the outbreak appeared to be particularly heavy in comparison to other years (). The cases occurred at the end of the rainy season at a time of cooler temperatures.
Average monthly precipitation in Santa Cruz de la Sierra, the capital of Santa Cruz Department, comparing the year of the reported hantavirus outbreak (2002) with averages of the preceding and following four years.
The cases reported here occurred in areas of significant anthropogenic perturbation of the landscape (i.e., clearing forest for ranching and sugarcane farming), which is thought to increase the risk of rodent-borne virus infection to humans through the intrusion of opportunistic rodents as well as increased exposure to animal excreta 
. Interestingly, hantavirus antibody prevalence did not vary among the regions and communities we studied, despite the presumed lower risk in the groups not primarily involved in agriculture. Possible explanations for this finding include the non-random sample and that many of the non-agricultural workers still had significant rodent exposure in and around their homes. Furthermore, it is possible that the rate of exposure varies significantly between the populations, with the antibody prevalence in the more stable urban population representing life-time exposure while the largely immigrant agricultural population may have achieved a similar prevalence in the much shorter time since coming from other, perhaps non-endemic regions. The work reported here was part of an outbreak investigation. Larger and more comprehensive antibody prevalence surveys, including longitudinal studies, systematic rodent surveys with hantavirus testing, and aggressive case surveillance would help elucidate the epidemiology of HPS and the potential risk to humans in Santa Cruz Department.