Louise E van Eekeren1, Sophia G de Vries1, Jiri F P Wagenaar2, René Spijker3, Martin P Grobusch1, Abraham Goorhuis4. 1. Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands. 2. Leptospirosis Reference Center, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 3. Medical Library, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Cochrane Netherlands, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. 4. Center of Tropical Medicine and Travel Medicine, Department of Infectious Diseases, Division of Internal Medicine, Academic Medical Center (AMC), University of Amsterdam (UvA), Amsterdam, The Netherlands. Electronic address: a.goorhuis@amc.uva.nl.
Abstract
BACKGROUND: Rickettsial diseases present as acute febrile illnesses, sometimes with inoculation eschars. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. PROSPERO REGISTRATION NUMBER: CRD 42016053348.
BACKGROUND:Rickettsial diseases present as acute febrile illnesses, sometimes with inoculation eschars. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. PROSPERO REGISTRATION NUMBER: CRD 42016053348.
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