Bacterial shedding and serologic responses following an outbreak of Salmonella Typhi in an endemic cohort

Abstract

Background: Salmonella enterica serovar Typhi (Salmonella Typhi) is the cause of typhoid fever. Salmonella Typhi may be transmitted through shedding in the stool, which can continue after recovery from acute illness. Shedding is detected by culturing stool, which is challenging to co-ordinate at scale. We hypothesised that sero-surveillance would direct us to those shedding Salmonella Typhi in stool following a typhoid outbreak.

Methods: In 2016 a typhoid outbreak affected one in four residents of a Nursing School in Malosa, Malawi. The Department of Health asked for assistance to identify nursing students that might spread the outbreak to other health facilities. We measured IgG antibody titres against Vi capsular polysaccharide (anti-Vi IgG) and IgM / IgG antibodies against H:d flagellin (anti-H:d) three and six months after the outbreak. We selected participants in the highest and lowest deciles for anti-Vi IgG titre (measured at visit one) and obtained stool for Salmonella culture and PCR. All participants reported whether they had experienced fever persisting for three days or more during the outbreak (in keeping with the WHO definitions of 'suspected typhoid'). We tested for salmonellae in the Nursing School environment.

Results: We obtained 320 paired serum samples from 407 residents. We cultured stool from 25 residents with high anti-Vi IgG titres and 24 residents with low titres. We did not recover Salmonella Typhi from stool; four stool samples yielded non-typhoidal salmonellae; one sample produced a positive PCR amplification for a Salmonella Typhi target. Median anti-Vi and anti-H:d IgG titres fell among participants who reported persistent fever. There was a smaller fall in anti-H:d IgG titres among participants who did not report persistent fever. Non-typhoidal salmonellae were identified in water sampled at source and from a kitchen tap.

Conclusion: High titres of anti-Vi IgG did not identify culture-confirmed shedding of Salmonella Typhi. There was a clear serologic signal of recent typhoid exposure in the cohort, represented by waning IgG antibody titres over time. The presence of non-typhoidal salmonellae in drinking water indicates sub-optimal sanitation. Developing methods to detect and treat shedding remains an important priority to complement typhoid conjugate vaccination in efforts to achieve typhoid elimination.

Keywords: Outbreak; Salmonella Typhi; Sero-surveillance; Shedding; Typhoid.

Fig. 1

A. Log anti-Vi IgG concentration at the three month visit among participants from whom Salmonella spp. was cultured (purple) compared to culture-negative participants(turquoise). B. log anti-H:d IgM concentration at the three month visit among participants from whom Salmonella spp. was cultured (green) compared to culture-negative participants(red). C. log anti-H:d IgG concentration at the three month visit among participants from whom Salmonella spp. was cultured (brown) compared to culture-negative participants (black)

Fig. 2

A. log anti-Vi IgG concentration amongst participants with persistent fever, comparing titres at 3 months (lilac) and 6 months (turquoise) post-outbreak. B. log anti-Vi IgG concentration amongst participants without persistent fever, comparing titres at 3 months (lilac) and 6 months (turquoise) post-outbreak. C. log anti-H:d IgM concentration amongst participants with persistent fever, comparing titres at 3 months (beige) and 6 months (yellow) post-outbreak. D. log anti-H:d IgM concentration amongst participants without persistent fever, comparing titres at 3 months (beige) and 6 months (yellow) post outbreak. E. log anti-H:d IgG concentration amongst participants without persistent fever, comparing titres at 3 months (green) and 6 months (purple) post-outbreak. F. log anti-H:d IgM concentration amongst participants without persistent fever, comparing titres at 3 months (green) and 6 months (purple) post-outbreak. All graphs: red crossbar shows median antibody concentration; brackets show p-values (Wilcoxon signed rank test)