Salmonella enterica serovar Paratyphi A and S-enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal

Background. Enteric fever is a major global problem. Emergence of antibacterial resistance threatens to render current treatments ineffective. There is little research or public health effort directed toward Salmonella enterica serovar Paratyphi A, because it is assumed to cause less severe enteric fever than does S. enterica serovar Typhi. There are few data on which to base this assumption, little is known of the serovar's antibacterial susceptibilities, and there is no readily available tolerable vaccination. Methods. A prospective study was conducted of 609 consecutive cases of enteric fever ( confirmed by blood culture) to compare the clinical phenotypes and antibacterial susceptibilities in S. Typhi and S. Paratyphi A infections. Variables independently associated with either infection were identified to develop a diagnostic rule to distinguish the infections. All isolates were tested for susceptibility to antibacterials. Results. Six hundred nine patients ( 409 with S. Typhi infection and 200 with S. Paratyphi A infection) presented during the study period. The infections were clinically indistinguishable and had equal severity. Nalidixic acid resistance, which predicts a poor response to fluoroquinolone treatment, was extremely common ( 75.25% of S. Paratyphi A isolates and 50.5% of S. Typhi isolates;). S. Paratyphi A was more likely to be resistant to P < .001 ofloxacin ( 3.6% vs. 0.5%;) or to have intermediate susceptibility to ofloxacin ( 28.7% vs. 1.8%; P < .001) or ciprofloxacin ( 39.4% vs. 8.2%; P < .001). MICs for S. Paratyphi A were higher than for S. Typhi ( MIC .001) of ciprofloxacin, 0.75 vs. 0.38 mu g/mL [P < .001]; MIC of ofloxacin, 2.0 vs. 0.75 mg/ mL [p < .001]). Conclusions. The importance of S. Paratyphi A has been underestimated. Infection is common, the agent causes disease as severe as that caused by S. Typhi and is highly likely to be drug resistant. Drug resistance and lack of effective vaccination suggest that S. Paratyphi A infection may become a major world health problem.