TY - JOUR
T1 - An age-stratified serosurvey against purified Salmonella enterica serovar Typhi antigens in the Lao People´s Democratic Republic
AU - Hefele, Lisa
AU - Black, Antony P.
AU - Tan, Trinh Van
AU - Minh, Nguyen Tri
AU - Hoang, Nguyen Duc
AU - Virachith, Siriphone
AU - Muller, Claude P.
AU - Hübschen, Judith M.
AU - Russell, Paula
AU - Scott, Josefin Bartholdson
AU - Minh, Chau Nguyen Ngoc
AU - Nga, Tran Vu Thieu
AU - Baker, Stephen
N1 - Funding Information:
This work was supported by the Ministry of Foreign and European Affairs, Luxembourg and the Luxembourg Institute of Health (project ?Luxembourg-Laos Partnership for Research and Capacity Building in Infectious Disease Surveillance II?) to LH and APB and a Wellcome senior research fellowship to SB (215515/Z/19/Z). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Publisher Copyright:
© 2021 Hefele et al.
PY - 2021/12
Y1 - 2021/12
N2 - 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 dif-ferences 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). Con-versely, 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 ele-vated 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.
AB - 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 dif-ferences 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). Con-versely, 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 ele-vated 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.
UR - http://www.scopus.com/inward/record.url?scp=85122250714&partnerID=8YFLogxK
UR - https://www.ncbi.nlm.nih.gov/pubmed/34898620
U2 - 10.1371/journal.pntd.0010017
DO - 10.1371/journal.pntd.0010017
M3 - Article
C2 - 34898620
AN - SCOPUS:85122250714
SN - 1935-2727
VL - 15
JO - PLoS Neglected Tropical Diseases
JF - PLoS Neglected Tropical Diseases
IS - 12
M1 - e0010017
ER -