Invasive Non-typhoidal Salmonella Infections in Asia: Clinical Observations, Disease Outcome and Dominant Serovars from an Infectious Disease Hospital in Vietnam

Abstract

Invasive non-typhoidal Salmonella (iNTS) infections are now a well-described cause of morbidity and mortality in children and HIV-infected adults in sub-Saharan Africa. In contrast, the epidemiology and clinical manifestations of iNTS disease in Asia are not well documented. We retrospectively identified >100 cases of iNTS infections in an infectious disease hospital in Southern Vietnam between 2008 and 2013. Clinical records were accessed to evaluate demographic and clinical factors associated with iNTS infection and to identify risk factors associated with death. Multi-locus sequence typing and antimicrobial susceptibility testing was performed on all organisms. Of 102 iNTS patients, 71% were HIV-infected, >90% were adults, 71% were male and 33% reported intravenous drug use. Twenty-six/92 (28%) patients with a known outcome died; HIV infection was significantly associated with death (p = 0.039). S. Enteritidis (Sequence Types (ST)11) (48%, 43/89) and S. Typhimurium (ST19, 34 and 1544) (26%, 23/89) were the most commonly identified serovars; S. Typhimurium was significantly more common in HIV-infected individuals (p = 0.003). Isolates from HIV-infected patients were more likely to exhibit reduced susceptibility against trimethoprim-sulfamethoxazole than HIV-negative patients (p = 0.037). We conclude that iNTS disease is a severe infection in Vietnam with a high mortality rate. As in sub-Saharan Africa, HIV infection was a risk factor for death, with the majority of the burden in this population found in HIV-infected adult men.

Fig 1. Identified Salmonella sequence types and serovars causing invasive disease and their antimicrobial susceptibility profiles.

a) Minimum spanning tree of 142 iNTS isolates created using seven allele MLST profiling. The sequence type (ST) of each allele profile is shown along with the inferred serovar. Clonal complexes (S. Typhimurium, S. Enteritidis, S. Cholerasuis and S. Paratyphi B [tartrate positive]) are highlighted. The size of each ST group corresponds with the number of isolates with the same ST profile (scale shown), and the branches are labeled by the number of variable alleles between STs. b) Bar graph showing the proportion of organisms (red, S. Typhimurium; blue, S. Enteritidis and grey, others) exhibiting resistance against ampicillin (AMP), amoxicillin/clavulanate (AMC), ceftazidime (CAZ), ceftriaxone (CRO), chloramphenicol (CHL), ciprofloxacin (CIP), gentamicin (GEN), nalidixic acid (NAL), ofloxacin (OFX) and trimethoprim-sulfamethoxazole (SXT). Asterisks signify statistically significant differences in the proportion of organisms exhibiting resistance to the individual antimicrobial (p<0.05, Fisher’s exact test).