Clinical Manifestations of Rift Valley Fever in Humans: Systematic Review and Meta-Analysis

Background: Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral haemorrhagic zoonosis associated with severe morbidity, mortality and expanding geographical scope. Human symptoms have poor specificity and case definitions vary. We determined the clinical manifestations of RVF in humans. Methods: In this systematic review and meta-analysis we searched Medline, Embase, Global Health, and Web of Science databases from indexing inception to 15th October 2019. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animals studies, those among asymptomatic volunteers and single case reports for which a proportion could not be estimated were excluded. Quality assessment was done, data extracted, and pooled frequency estimates calculated using random effects meta-analysis. Results: Of the 3765 articles retrieved, 32 were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including general febrile, gastrointestinal, hepatic, renal, neurological, haemorrhagic, obstetric, visual, and cardio-pulmonary syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69-91), nausea (38%; 12-67), jaundice (26%; 16-36), renal failure (41%; 23-59), encephalitis (21%; 11-33), haemorrhagic disease (26%; 17-36), miscarriage (54%), partial blindness (24%; 7-45), and cough (4%; 0-17), respectively. Death occurred in 21% (95% CI 14-29) of cases. Interpretation: This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreaks control, increase public awareness about RVF, and subsequently inform ‘one-health’ policies. Study protocol registration number: CRD42019128928. Funding: (UK Department of Health and Social care) The work was conducted at the MRC/UVRI and LSHTM Uganda Research Unit which is jointly funded by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordant agreement and is also part of the EDCTP2 programme supported by the European Union. This project was funded by the UK Biotechnology and Biological Sciences Research Council (BBSRC) and the Medical Research Council (MRC)/Department of Health, through the UK Vaccines Network which is a Government Funding Stream (Grant no: 16/107/02). SL was supported by the PANDORA-ID-NET Consortium (EDCTP Reg/Grant RIA2016E-1609) funded by the European and Developing Countries Clinical Trials Partnership (EDCTP2) programme under the Horizon 2020, the European Union’s Framework Programme for Research and Innovation. GMW is supported by an Oak foundation fellowship and a Wellcome Trust grant (grant number 203077_Z_16_Z). Declaration of Interests: All authors declare no potential conflicts of interest.