The clinical and microbiological characteristics of enteric fever in Cambodia, 2008-2015

Background: Enteric fever remains a major public health problem in low resource settings and antibiotic resistance is increasing. In Asia, an increasing proportion of infections is caused by Salmonella enterica serovar Paratyphi A, which until recently was assumed to cause a milder clinical syndrome compared to Salmonella enterica serovar Typhi. Methodology: A retrospective study was conducted of 354 unique cases of enteric fever (blood culture confirmed) that presented at a referral hospital for adults in Phnom Penh, Cambodia between 2008 and 2015. Demographic, clinical and laboratory data were collected from clinical charts and antibiotic susceptibility testing was performed. Whole genome sequencing was performed on a subset of isolates. Results: One-hundred-and-ninety unique patients were diagnosed with Salmonella Paratyphi A and 64 with Salmonella Typhi. In the period 2008-2012, Salmonella Paratyphi A comprised 25,5% of 47 enteric fever cases compared to 86,0% of 207 cases during 2013-2015. Presenting symptoms were identical for both serovars but higher median leukocyte counts (6.8 x 109/L vs. 6.3 x 109/L; p = 0.030) and C-reactive protein (CRP) values (47.0 mg/L vs. 36 mg/L; p = 0.034) were observed for Salmonella Typhi infections. All but one of the Salmonella Typhi isolates belonged to haplotype H58 associated with multidrug resistance (MDR) (i.e. resistance to ampicillin, chloramphenicol and co-trimoxazole) but only 40.3% actually showed MDR; none of the Salmonella Paratyphi A isolates did. Decreased ciprofloxacin susceptibility (DCS) was observed in 96.7% (59/61) of Salmonella Typhi isolates versus 10.3% (19/185) of Salmonella Paratyphi A isolates (all but one from 2015). All isolates were susceptible to azithromycin and ceftriaxone. Conclusions: In Phnom Penh, Cambodia, Salmonella Paratyphi A now causes the majority of enteric fever cases and decreased susceptibility against ciprofloxacin is increasing. Presenting symptoms of Salmonella Paratyphi A and Salmonella Typhi infections are identical with minor differences in laboratory parameters.