Clinical manifestations of Rift Valley fever in humans: Systematic review and meta-analysis

Abstract

Background Rift Valley fever (RVF) is an emerging, neglected, mosquito-borne viral zoonosis associated with significant morbidity, mortality and expanding geographical scope. The clinical signs and symptoms in humans are non-specific and case definitions vary. We reviewed and analysed the clinical manifestations of RVF in humans. Methods In this systematic review and meta-analysis we searched on different dates, the Embase (from 1947 to 13th October 2019), Medline (1946 to 14th October 2019), Global Health (1910 to 15th October 2019), and Web of Science (1970 to 15th October 2019) databases. Studies published in English, reporting frequency of symptoms in humans, and laboratory confirmed RVF were included. Animal studies, studies among asymptomatic volunteers, and single case reports for which a proportion could not be estimated, were excluded. Quality assessment was done using a modified Hoy and Brooks et al tool, data was extracted, and pooled frequency estimates calculated using random effects meta-analysis. Results Of the 3765 articles retrieved, less than 1% (32 articles) were included in the systematic review and meta-analysis. Nine RVF clinical syndromes were reported including the general febrile, renal, gastrointestinal, hepatic, haemorrhagic, visual, neurological, cardio-pulmonary, and obstetric syndromes. The most common clinical manifestations included fever (81%; 95% Confidence Interval (CI) 69–91; [26 studies, 1286 patients]), renal failure (41%; 23–59; [4, 327]), nausea (38%; 12–67; [6, 325]), jaundice (26%; 16–36; [15, 393]), haemorrhagic disease (26%; 17–36; [16, 277]), partial blindness (24%; 7–45; [11, 225]), encephalitis (21%; 11–33; [4, 327]), cough (4%; 0–17; [4, 11]), and miscarriage (54%) respectively. Death occurred in 21% (95% CI 14–29; [16 studies, 328 patients]) of cases, most of whom were hospitalised. Discussion This study delineates the complex symptomatology of human RVF disease into syndromes. This approach is likely to improve case definitions and detection rates, impact outbreak control, increase public awareness about RVF, and subsequently inform ‘one-health’ policies. This study provides a pooled estimate of the proportion of RVF clinical manifestations alongside a narrative description of clinical syndromes. However, most studies reviewed were case series with small sample sizes and enrolled mostly in-patients and out-patients, and captured symptoms either sparsely or using broad category terms.

Contemporary epidemiological data of Rift Valley fever virus in humans, mosquitoes and other animal species in Africa: A systematic review and meta‐analysis

“…This finding was consistent with another report based on pathological evaluation of post-mortem and necropsy tissue samples from animals and humans clinically suspected of having RVFV infection during the 2006-2007 outbreak in Eastern Africa (Breiman et al, 2010). In this review, relatively high estimates of the RVF CFR in humans (27.5%) during outbreak periods were consistent with previous study among confirmed cases (Anywaine et al, 2022). This high RVF CFR could be explained by the fact that during outbreaks, epidemiological investigations focus primarily on the identification of severe cases in epidemiological settings where all RVF cases are hard to trace.…”

Rift Valley fever and malaria co‐infection: A case report

“…24,[33][34][35] Alternatively, this difference in the clinical manifestation of RVF infection could be attributed to variation in the virus strains of some clades of viruses are more associated with severe clinical presentations of the disease. [36][37][38] A similar situation has been observed during the currently ongoing Mpox outbreak of global concern. 39 Clade IIb of the Mpox virus that diverged from the West African lineage is associated with globally expanded transmission outside the endemic areas with none severe clinical presentation.…”

“…Recently, there is growing evidence about disease emergence and unusual presentation of endemic diseases 24,33–35 . Alternatively, this difference in the clinical manifestation of RVF infection could be attributed to variation in the virus strains of some clades of viruses are more associated with severe clinical presentations of the disease 36–38 . A similar situation has been observed during the currently ongoing Mpox outbreak of global concern 39 .…”

Ophthalmic consequences of viral hemorrhagic fevers: Insights from the clinic and laboratory

“…Transmission occurs via contact with blood or organs of infected animals (typically cattle) or via mosquito bite. Following an incubation period of 2-6 days, a diverse array of systemic presentations of RVF can occur (65). The classical presentation is that of a generalized febrile/flu-like illness with hepatic syndrome (elevated liver enzymes, hepatosplenomegaly, liver failure).…”