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

BackgroundSalmonella enterica serovar Typhi (S. Typhi), the causative agent of Typhoid fever, is transmitted faecal-orally. Some typhoid sufferers shed S. Typhi beyond convalescence, but culturing stool following every case is impractical. Here we hypothesised that serology might direct testing and identify shedding after a typhoid outbreak. Methodology/Principle FindingsIn 2016 there was a typhoid outbreak in a Nursing School in Malosa, Malawi. We collected serum three and six-months post-outbreak. We measured IgG antibody titres against Vi capsular polysaccharide (anti-Vi IgG) and IgM / IgG antibodies against H:d flagellin (anti-H:d). We screened faecal samples from participants with high and low anti-Vi IgG (measured at visit one) by culture and PCR. Participants reported whether they had persistent fever for [&ge;] three days (in keeping with World Health Organization definitions for typhoid) during the outbreak. We tested for environmental S. Typhi. 368 people provided serum at 3-months, of whom 320 provided serum at 6-months; 49 participants provided a faecal sample (25 from the highest and 24 from the lowest deciles for anti-Vi IgG titre). We did not grow S. Typhi from faeces, but one sample produced a positive PCR amplification for S. Typhi. Median anti-Vi IgG titre fell amongst participants with persistent fever (8.08 to 3.7 EU/ml, <0.000001, Wilcoxon signed rank). Median anti-H:d IgG titres fell in those with and without persistent fever (87.8 to 77.4 EU/, p = <0.000001 and 82.4 to 79.2 EU/ml, p = 0.0002, Wilcoxon signed rank, respectively). Anti-H:d IgM titres did not change significantly. Non-Typhoidal Salmonellae were identified in water sampled at source and a kitchen tap. Conclusions / SignificanceWe did not identify culture-confirmed shedding through sero-surveillance. Serologic trends signify a fall from an outbreak-associated peak. Despite effective vaccines, identifying ways to detect and treat shedding remain vital to break transmission and eliminate typhoid. Author SummaryTyphoid fever spreads by the faecal-oral route. Some people continue to shed the bacterium that causes typhoid (Salmonella enterica serovar Typhi, or S. Typhi) after recovering from the illness. To stop onward spread it is important that these people are identified and treated. Shedders are detected when S. Typhi grows from faeces, but it is not practical to obtain stool samples from large populations. Following a typhoid outbreak we tested whether a subset of participants with high antibodies to S. Typhi proteins contained more shedders than a subset with low antibody responses. We tested whether antibody levels changed in the months after the outbreak, to inform whether they are useful markers of exposure in a population. We did not grow S. Typhi. This may be because our population had few risk factors for S. Typhi carriage, or because exposure to other endemic bacteria influence antibody levels. We saw a decline in antibody levels over time, most marked in those who reported fever during the outbreak. We think that this reflects a response to recent infection. It is important to continue to evaluate ways of finding carriers so that, combined with vaccines and improved sanitation, we can one day eliminate typhoid.