The frequency of typhoid carriage in patients undergoing cholecystectomy for gallbladder disease in Pakistan: A cross-sectional study
Authors: Qureshi Sonia , Maria Noshi , Chawla Tabish , Iqbal Junaid , Kazi Abdul Momin , Adnan Mehreen , Hotwani Aneeta , Rahman Najeeb , Sadiq Muhammed Wahhaab , Charles Richelle , Baker Stephen , Qamar Farah Naz 
Published: November 2023

Background

Enteric fever is caused bySalmonellaenterica serovars Typhi (S. Typhi) and Paratyphi A, B, and C. It continues to be a significant cause of morbidity and mortality worldwide. In highly endemic areas, children are disproportionately affected, and antimicrobial resistance reduces therapeutic options. It is estimated that 2–5% of enteric fever patients develop chronic asymptomatic infection. These carriers may act as reservoirs of infection; therefore, the prospective identification and treatment of carriers are critical for long-term disease control. We aimed to find the frequency ofSalmonellaTyphi carriers in patients undergoing cholecystectomy. We also compared the detection limit of culturing versus qPCR in detectingS.Typhi, performed a geospatial analysis of the carriers identified using this study, and evaluated the accuracy of anti-Vi and anti-YncE in identifying chronic typhoid carriage.

Methods

We performed a cross-sectional study in two centers in Pakistan. Gallbladder specimens were subjected to quantitative PCR (qPCR) and serum samples were analyzed for IgG against YncE and Vi by ELISA. We also mapped the residential location of those with a positive qPCR result.

Findings

Out of 988 participants, 3.4% had qPCR-positive gallbladder samples (23S.Typhi and 11S.Paratyphi). Gallstones were more likely to be qPCR positive than bile and gallbladder tissue. Anti-Vi and YncE were significantly correlated (r=0.78 p<0.0001) and elevated among carriers as compared to qPCR negative controls, except for anti-Vi response in Paratyphi A. But the discriminatory values of these antigens in identifying carriers from qPCR negative controls were low.

Conclusion

The high prevalence of typhoid carriers observed in this study suggests that further studies are required to gain information that will help in controlling future typhoid outbreaks in a superior manner than they are currently being managed.

Author Summary

Enteric fever, caused by bacteriaSalmonellaTyphi or Paratyphi, is a serious global illness particularly affecting children in areas with inadequate hygiene and sanitation facilities. It is transmitted through the oral-fecal route. In Pakistan, prevalence of extensively drug resistantS.Typhi resistant strain further complicates its treatment. Some infected individuals develop chronic infections and become carriers of these pathogens. These asymptomatic carriers may potentially spread the disease by shedding the bacteria in urine or stool. To assess the frequency of the carrier state, we examined gallbladder specimens (bile, stones, and tissue) from patients who underwent gallbladder removal surgeries at Aga Khan University and Jinnah Post-graduate Medical Centre. We demonstrated that PCR had a higher sensitivity in detectingSalmonellacarriage with a detection limit of 102CFU/ml and identified 3.4% of typhoid carriers. Additionally, we investigated whether specific antibodies could identify these carriers using various serological tests. The results underscore the need for further research to promptly detect and appropriately treat this disease, thereby enhancing control and preventing future outbreaks.