Under-diagnosis of rickettsial disease in clinical practice: A systematic review

Louise E. van Eekeren, Sophia G. de Vries, Jiri F. P. Wagenaar, René Spijker, Martin P. Grobusch, Abraham Goorhuis

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19 Citations (Scopus)


Rickettsial diseases present as acute febrile illnesses, sometimes with inoculation eschars. We performed a systematic review of studies published between 1997 and 2017 to assess the underestimation of non-eschar rickettsial disease (NERD) relative to eschar rickettsial disease (ERD), as a cause of acute fever in patients with rickettsial diseases that commonly present with eschar(s): scrub typhus (ST), Mediterranean spotted fever (MSF), and African tick-bite fever. We compared ERD/NERD ratios according to study design: 'complete approach' studies, with testing performed in all patients with 'unspecified febrile illness'; versus 'clinical judgement' studies, with testing performed if patients presented with specific symptoms. In 'complete approach' studies, ERD/NERD ratios were significantly lower, suggesting a considerable under-diagnosis of NERD in 'clinical judgement' studies. Based on these results, we estimate that the diagnosis of rickettsial disease was missed in 66.5% of patients with ST, and in 57.9% of patients with MSF. Study design influences the reported eschar rates in ST and MSF significantly. NERD is likely to be a vastly underdiagnosed entity, and clinicians should consider and test for the disease more often. CRD 42016053348
Original languageEnglish
Pages (from-to)7-15
JournalTravel Medicine and Infectious Disease
Publication statusPublished - 2018

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