Etiology of fever in returning travelers and migrants: a systematic review and meta-analysis

Abstract

Background

Numerous publications focus on fever in returning travelers, but there is no known systematic review considering all diseases, or all tropical diseases causing fever. Such a review is necessary in order to develop appropriate practice guidelines.

Objectives

Primary objectives of this review were i) to determine the etiology of fever in travelers/migrants returning from (sub) tropical countries as well as the proportion of patients with specific diagnoses, and ii) to assess the predictors for specific tropical diseases.

Method

Embase, MEDLINE and Cochrane Library were searched with terms combining fever AND travel/migrants. All studies focusing on causes of fever in returning travelers and/or clinical and laboratory predictors of tropical diseases were included. Meta-analyses were performed on frequencies of etiological diagnoses.

Results

10064 studies were identified; 541 underwent full-text review; 30 met criteria for data extraction. Tropical infections accounted for 33% of fever diagnoses, with malaria causing 22%, dengue 5% and enteric fever 2%. Non-tropical infections accounted for 36% of febrile cases, with acute gastroenteritis causing 14% and respiratory tract infections 13%. Positive likelihood ratios demonstrated that splenomegaly, thrombocytopenia and hyperbilirubinemia were respectively 5–14, 3–11 and 5–7 times more likely in malaria than non-malaria patients. High variability of results between studies reflects heterogeneity in study design, regions visited, participants’ characteristics, setting, laboratory investigations performed, and diseases included.

Conclusion

Malaria accounted for one fifth of febrile cases, highlighting the importance of rapid malaria testing in febrile returning travelers, followed by other rapid tests for common tropical diseases. High variability between studies highlights the need to harmonize study designs and to promote multi-center studies investigating predictors of diseases, including of lower incidence, which may help to develop evidence-based guidelines. The use of clinical decision support algorithms by health workers which incorporate clinical predictors, could help standardize studies as well as improve quality of recommendations.