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 ≥ 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.

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.

Post-operative fever is common following emergency surgery. Investigation and management of post-operative fever can be challenging when a clear source of sepsis is not evident or the underlying source of infection is not recognised. We herein report a case of secondary pulmonary tuberculosis presenting as post-operative fever following emergency laparotomy for a perforated duodenal ulcer. This case of tuberculosis was diagnosed on day 41 post-operatively and prior inconclusive results meant that we relied mainly on re-visiting history and examination in order to identify 3 targeted investigations: plain chest X-ray, sputum sample and blood test. Accordingly, the co-management of this complex patient achieved a good outcome.