Human Biomarkers of Outcome Following Rift Valley Fever Virus Infection

McElroy, Anita K.; Harmon, Jessica R.; Flietstra, Timothy D.; Nichol, Stuart T.; Spiropoulou, Christina F.

doi:10.1093/infdis/jiy393

Cited by 12 publications

(14 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Haemorrhage is also caused by direct viral invasion and damage to the endothelial cells and thrombocytopenia. The elevation in hepatic transaminases has previously been associated with a fatal outcome [ 82 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In all host species, innate immunity is a key component of early RVFV detection and activation of further effector cells, e.g., macrophages, via release of cellular mediators including IFNs [24,27,34,45,70]. The B6-IFNAR tmAgt mice lack the IFN type I receptor (IFNAR) and showed severe RVF characterized by severe clinical signs, necrotizing hepatitis and virus spread to various organs as described previously [37,50].…”

Section: Discussionmentioning

confidence: 75%

“…Thus, they play a key role as pattern recognition receptors in many viral infections, e.g., the RVFV-related Punta Toro virus for which was shown that TLR 3 could even induce detrimental effects due to overstimulation [30][31][32]. Furthermore, it has been shown that genetic polymorphisms of TLR 7 correlate with RVF severity in humans; thus, it can be assumed that TLR 3 and 7 are relevant elements of RVFV recognition [33,34]. The interferon response is counteracted by RVFV via its major pathogenicity factors, the non-structural proteins s (NSs) and m (NSm) [24,[35][36][37][38][39][40][41][42].…”

Section: Introductionmentioning

confidence: 99%

NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection

Michaely

Rissmann

Keller

et al. 2022

Viruses

View full text Add to dashboard Cite

Rift Valley fever (RVF) is a zoonotic disease caused by RVF Phlebovirus (RVFV). The RVFV MP-12 vaccine strain is known to exhibit residual virulence in the case of a deficient interferon type 1 response. The hypothesis of this study is that virus replication and severity of lesions induced by the MP-12 strain in immunocompromised mice depend on the specific function of the disturbed pathway. Therefore, 10 strains of mice with deficient innate immunity (B6-IFNARtmAgt, C.129S7(B6)-Ifngtm1Ts/J, B6-TLR3tm1Flv, B6-TLR7tm1Aki, NOD/ShiLtJ), helper T-cell- (CD4tm1Mak), cytotoxic T-cell- (CD8atm1Mak), B-cell- (Igh-Jtm1DhuN?+N2), combined T- and B-cell- (NU/J) and combined T-, B-, natural killer (NK) cell- and macrophage-mediated immunity (NOD.Cg-PrkdcscidIl2rgtm1WjI/SzJ (NSG) mice) were subcutaneously infected with RVFV MP-12. B6-IFNARtmAgt mice were the only strain to develop fatal disease due to RVFV-induced severe hepatocellular necrosis and apoptosis. Notably, no clinical disease and only mild multifocal hepatocellular necrosis and apoptosis were observed in NSG mice, while immunohistochemistry detected the RVFV antigen in the liver and the brain. No or low virus expression and no lesions were observed in the other mouse strains. Conclusively, the interferon type 1 response is essential for early control of RVFV replication and disease, whereas functional NK cells, macrophages and lymphocytes are essential for virus clearance.

show abstract

“…Lymphopenia (measured by both methods) occurred by 1 dpi through 5 dpi in both groups, but the SC-infected rats returned to baseline levels quicker while AERO-infected rats only partially recovered. Lymphopenia and granulocytosis are documented findings during lethal RVF infection, in both animal models and human clinical samples [8, 19–22]. These data provide a direct comparison of changes in the peripheral blood between SC vs AERO infection routes and also serve to validate both the CBC analysis and flow cytometry as complementary methods for blood cell typing in rats.…”

Section: Resultsmentioning

confidence: 87%

Neutrophil and macrophage influx into the central nervous system are inflammatory components of lethal Rift Valley fever encephalitis in rats

et al. 2019

View full text Add to dashboard Cite

Rift Valley fever virus (RVFV) causes severe disease in livestock concurrent with zoonotic transmission to humans. A subset of people infected with RVFV develop encephalitis, and significant gaps remain in our knowledge of how RVFV causes pathology in the brain. We previously found that, in Lewis rats, subcutaneous inoculation with RVFV resulted in subclinical disease while inhalation of RVFV in a small particle aerosol caused fatal encephalitis. Here, we compared the disease course of RVFV in Lewis rats after each different route of inoculation in order to understand more about pathogenic mechanisms of fatal RVFV encephalitis. In aerosol-infected rats with lethal encephalitis, neutrophils and macrophages were the major cell types infiltrating the CNS, and this was concomitant with microglia activation and extensive cytokine inflammation. Despite this, prevention of neutrophil infiltration into the brain did not ameliorate disease. Unexpectedly, in subcutaneously-inoculated rats with subclinical disease, detectable viral RNA was found in the brain along with T-cell infiltration. This study sheds new light on the pathogenic mechanisms of RVFV encephalitis.

show abstract

Human Biomarkers of Outcome Following Rift Valley Fever Virus Infection

Cited by 12 publications

References 15 publications

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

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

NSG-Mice Reveal the Importance of a Functional Innate and Adaptive Immune Response to Overcome RVFV Infection

Neutrophil and macrophage influx into the central nervous system are inflammatory components of lethal Rift Valley fever encephalitis in rats

Contact Info

Product

Resources

About