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Reply to Farmakiotis et al:Typhoid fever in an inner city hospital: a 5-year retrospective review.

This paper comments on the difficulty diagnosing typhoid and other infections causing severe diarrhoea, especially in regions where it is a common problem...

Authors:
Waddington CS, Darton TC, Angus B, Pollard AJ

Authors notes:
Clin Infect Dis.

Keywords:
pathological changes,typhoid fever, hematological parameters, hemoglobin, total white cell counts (WCCs), neutrophil, eosinophil, diagnosis, Salmonella

Abstract:
Our recent development of a human Salmonella Typhi challenge model provided a detailed description of the clinical profile and associated pathological changes seen during typhoid fever.

Alterations in hematological parameters included decreases in hemoglobin and hematocrit in all participants, and, in those diagnosed with typhoid, decreases in both platelet and total white cell counts (WCCs).

The reduction in WCC manifested as falls in neutrophil and eosinophil count, with the eosinophil count declining from 6 days prior to diagnosis.

As Farmakiotis et al note, the finding of eosinopenia has previously been reported in typhoid, although not universally. These data call into question the diagnostic value of the eosinophil count in isolation, and highlight the need to assess the clinical picture in its entirety.

Clinical diagnosis of typhoid fever is challenging, particularly in endemic settings where the presentation can be indistinguishable from other common febrile diseases including malaria and dengue fever.

These uncertainties highlight the significant gaps remaining in our understanding of both typhoid and other enteric infections as well as more global mechanisms of the mucosal immune response.

Both need to be addressed to meaningfully impact the clinical management of patients and vaccination strategies.

Both our report and those of Farmakiotis and colleagues further highlight the lack of accurate diagnostic tests for typhoid and other Salmonella serovars, especially in endemic regions where resources are frequently limited.

Prompt diagnosis and treatment of typhoid decreases complications and limits the opportunity for onward transmission.

New, reliable diagnostic tests are needed to prevent treatment delays, minimize morbidity and mortality, prevent inappropriate use of antimicrobials, and provide reliable epidemiological data.