NontyphoidalSalmonellaSerovars Cause Different Degrees of Invasive Disease Globally

To the Editor—In the 1 January 2008 issue of the Journal, Jones et al. [1] describe the various disease outcomes caused by different serovars of Salmonella enterica. Their large data set provides a detailed overview of the situation in the United States over a 10-year period and concludes that disease outcome is a function of the serovar and that understanding this may be key to a more general understanding of invasiveness. We support this conclusion but would like to refine it in light of data unavailable to the authors but now published as part of a book chapter that we updated in August 2008 [2]. We analyzed published data provided by public health statistics from a range of countries in Europe, Asia, Australasia, and North and South America, to see which nontyphoidal serovars (NTS) of Salmonella are able to cause invasive disease. We observed that different serovars are associated with different “invasive indexes”-defined as the ratio of the number of isolates recovered from blood to the total number of isolates recovered (table 1)-but that the results are not entirely consistent between different countries. Comparing these invasive indexes with the data published by Jones et al. [1] confirms this conclusion. Study enrollment of case patients with laboratory-confirmed reportable enteric infection caused by bacteria (REI-B). Numbers in parentheses are no. of participants. See Methods for details about exclusion criteria. The majority of serovars deemed to be invasive in the United States are also invasive globally; however, some that are presently invasive in the United States are not causing invasive disease elsewhere in the world, indicating geographic distribution plays a role in the percentage of invasive disease caused by a particular serovar. This finding is supported by other recent reports; for example, the invasive index of serovar Schwarzengrund is 15.4% in both the United States and Brazil [3] but is 25% in Taiwan [4]. Another, more worrying example comes from several sub- Saharan African countries, where NTS are now the most common cause of bacteremia. In these countries, cases of invasive disease have been attributed to serovars Typhimurium and Enteritidis, occurring in epidemics of disease caused by antibiotic- resistant strains associated with HIV status and age [5]. We believe that it is likely that the severity of salmonellosis caused by different serovars is related not only to humanhost factors [6] but also to bacterial phylogeny [7]. Twenty years ago, studies using multilocus enzyme electrophoresis showed that some serovars are single genetic entities (monomorphic), whereas others are clearly mixtures of strains [8]. These data are now supported by multilocus sequence typing (MLST), and certain groupings known by a single serovar name actually represent genetically distinct groups that may cause different disease outcomes in humans. For this reason, we propose that, where possible, descriptions of disease severity should be associated with sequence types obtained by MLST, as well as with serovars. An extensive open-access database (http://web.mpiib-berlin.mpg.de/mlst/) of sequence types of Salmonella enterica is available that will help to achieve this goal.