Letter: chronic Salmonella typhi carrier status and gall‐bladder cancer – authors’ reply

Abstract

We thank Dr Arya and colleagues for their interest in our article1, 2 and highlighting the relationship between HLA and susceptibility to typhoid fever. The momentum for the implementation of personalised medicine in clinical practice is gaining. Recently, HLA genetic screening has been used to prevent carbamazepine-induced toxic effects among persons of Han Chinese descent3 and hypersensitivity to abacavir.4 Similarly, Ivacaftor, an orally available CFTR modulator that is specific for the G551D mutation has come up as a potential treatment for cystic fibrosis,5 thiopurine methyltransferase enzyme activity is predictive of azathioprine related life-threatening myelotoxicity in inflammatory bowel disease6 and reduced-function of CYP2C19 genotype has been related to adverse clinical outcomes among patients treated with clopidogrel.7 Imperial College of Science investigated the association between class II and class III major histocompatibility complex and typhoid fever in Vietnam. It is interesting to see that HLADRB1* 0301/6/8, HLA-DQB1*0201-3 and TNFA*2 (-308)) were associated with susceptibility to typhoid fever and HLA-DRB1*04, HLA-DQB1*0401/2 and TNFA*1 (-308) were linked with disease resistance.8 It would be a good strategy to utilize this characteristic to help prevent typhoid in this cohort of patients, especially in South East Asia. The endemic regions for typhoid can implement more stringent vaccination policies to reduce the health care burden of chronic Salmonella typhi carrier status-related gall-bladder cancer with the help of HLA screening. Another strategy would be to identify the HLA association between chronic Salmonella typhi carriage and gall-bladder cancer. However, whether this will be a cost-effective strategy is a question for the future. We suggest further research in this area to determine this association with the help of genome-wide association studies and animal studies. The authors’ declarations of personal and financial interests are unchanged from those in the original article.2