NTS is increasingly recognized as an important pathogen associated with bacteraemia in both the immunosuppressed as well as the immunocompetent patients. In the present study, serogroup D had the highest blood invasiveness with 40 out of the 43 (93%) serogroup D isolates belonging to Salmonella enterica serovar Enteritidis. Salmonella enterica serovar Typhimurium , the most common serotype isolated in Malawi was not noted in any of our bacteraemic patients. Taiwan demonstrates a high prevalence of serogroup B and C  and Thailand has a higher proportion of serogroup C  amongst their bacteraemic patients. The knowledge about the prevalent serotypes with high invasive potential is of epidemiological and public health importance.
The extra-intestinal focus of infection (EFI) rate of 30.9% in our study was higher than that reported by Galofre J et al. . However, EFI rates of as high as 47% have been reported in Taiwan involving patients with Salmonella enterica serovar Choleraesuis bacteraemia . Contrary to previous studies which found higher percentage mycotic aneurysms amongst their NTS bacteraemic patients [12, 13], our study had significantly lower rates; an overall rate of 5.5% which increased to 17% amongst patients > 50 years (P = 0.031). The risk factors for vascular infection in NTS bacteraemic patients which includes age > 50 and underlying atherosclerosis [12, 14] were present in our patients and this serious complication should always be kept in mind when an elderly patient presents with NTS bacteraemia. The overall low rates of mycotic aneurysm in the present study could be partly attributed to very low prevalence of Salmonella enterica serovar Choleraesuis bacteraemia, which has a high predilection for causing bacteraemia and mycotic aneurysm [12, 13]. The presence of mycotic aneurysm and atherosclerotic conditions were significantly lower in the immunosuppressed patients in this study (p < 0.05). Although immunosuppression predisposes patients to bacteraemia, it has a contradictory role in the pathogenesis of endovascular infection , suggesting the possible role of immune system in the process of inflammation and destruction of aorta and heart valves.
In recent years, NTS bacteraemia has been increasingly reported as a cause of life-threatening infection in immunocompromised hosts. It is worth noting that, in our study, malignancy and HIV/AIDS were the two most common conditions associated with NTS bacteraemia. As suggested by several recent reports in Thailand and Malawi, NTS bacteraemia has become increasingly important amongst patients with HIV [2, 15]. Multiple series have identified malignancy as a risk factor for NTS bacteraemia . SLE was the predisposing disease in 10.9% of our cases. In a recent series involving SLE bacteraemic patients , NTS was the most common gram-negative bacteria isolated. In the present study, significantly lower proportion of patients >50 years had severe immunosuppressive conditions like HIV and malignancy, instead they presented with age-related conditions like atherosclerosis.
The findings in the present study showed that the presence of primary bacteraemia and absence of gastroenteritis was more common in patients with severe immunosuppression and this concurred with the findings of Ramos et al. . Underlying immunosuppression should be excluded in patients presenting with NTS bacteraemia in the absence of gastroenteritis [17, 18].
Although the overall mortality in the present study was 21.8% (12/55), 11 of the 12 deaths actually occurred in patients with severe immunosuppressive diseases. Therefore, in the present study the deaths were most likely attributable to the underlying conditions. Variations in mortality rates associated with NTS bacteraemia ranging from 12%  to 47%  has been reported in previous studies. These wide ranges may reflect the differences in the severity of underlying diseases, the serovars of NTS, the availability of antimicrobials and the antimicrobial resistance of NTS in various countries.
A predisposition to NTS bacteraemia in immunosuppressed patients and a trend towards higher mortality observed in patients with immunosuppressed conditions illustrate the importance of immune system in defense against Salmonella infection. Cell mediated immunity is vital for defense against intracellular bacteria like Salmonella and leukocytes especially lymphocytes are essential host defense. In the present study, severely immunosuppressed patients presented with significantly lower lymphocyte counts. Cytokine deficiencies such as interleukin IL-12/IL-23 and interferon gamma can predispose one to invasive NTS infections [4, 19]. Equally important is to determine the virulence of Salmonella strains which may favor systemic dissemination in the host. Direct inhibition of T lymphocyte activation, the interference of professional antigen presenting cells function to process and present Salmonella-expressed antigens to T cell are some of the immune evasion techniques to escape immune detection by virulent Salmonella. The elucidation of these virulent factors will allow for the design of new strategies to prevent the systemic diseases caused by this pathogen .
A major limitation of the present study was that it was based in a tertiary hospital and hence might be biased towards patients with invasive NTS diseases. Moreover, most patients attended local health clinics for diarrhoeal diseases. Therefore, our data on blood invasiveness ratio which is based on positive stool and blood isolates obtained from the microbiology laboratory may not be reflective of the true incidence. However, it provides a relative comparison between the different serovars. Secondly, owing to the retrospective nature of the study, the presence of an extra-intestinal focus of infection could not be verified for all patients. Thirdly, since our study was conducted in a tertiary hospital where a high proportion of patients are immunosupressed as a result of underlying disease or modern aggressive therapy, similar results may not be extrapolated to other institutions in Malaysia where the patient population might differ.