Abstract
The epidemiology of typhoid fever in Lao People`s Democratic Republic is poorly defined. Estimating the burden of typhoid fever in endemic countries is complex due to the cost and limitations of population-based surveillance; serological approaches may be a more cost-effective alternative. ELISAs were performed on 937 serum samples (317 children and 620 adults) from across Lao PDR to measure IgG antibody titers against Vi polysaccharide and the experimental protein antigens, CdtB and HlyE. We measured the significance of the differences between antibody titers in adults and children and fitted models to assess the relationship between age and antibody titers. The median IgG titres of both anti-HylE and CdtB were significantly higher in children compared to adults (anti-HylE; 351.7 ELISA Units (EU) vs 198.1 EU, respectively; p<0.0001 and anti-CdtB; 52.6 vs 12.9 EU; p<0.0001). Conversely, the median anti-Vi IgG titer was significantly higher in adults than children (11.3 vs 3.0 U/ml; p<0.0001). A non-linear trend line fitted to the anti-CdtB and anti-HlyE IgG data identified a peak in antibody concentration in children <5 years of age. We identified elevated titers of anti-HlyE and anti-CdtB IgG in the serum of children residing in Lao PDR in comparison to adults. These antigens are associated with seroconversion after typhoid fever and may be a superior measure of disease burden than anti-Vi IgG. This approach is scalable and may be developed to assess the burden of typhoid fever in countries where the disease may be endemic, and evidence is required for the introduction of typhoid vaccines.
Highlights
Typhoid fever is a systemic disease caused by Salmonella enterica subspecies enterica serovar Typhi
Typhoid fever is a serious bloodstream infection caused by the bacterium Salmonella Typhi
We measured the significance of the differences between antibody titers in adults and children and fitted models to assess the relationship between age and antibody titers
Summary
Typhoid fever is a systemic disease caused by Salmonella enterica subspecies enterica serovar Typhi Typhi), a bacterium transmitted via contaminated food or water. An estimated 128,000–161,000 people per year die as a consequence of this infection [1]. Typhoid fever is typically diagnosed clinically, with blood culture as confirmatory gold standard [2,3,4,5]. Despite its limited performance, the serological Widal test is still commonly used [3,6]. All current diagnostic tests for typhoid fever have limitations and new technologies are constantly being evaluated [7,8]
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