Viral Load as a Predictor of Outcome in Crimean-Congo Hemorrhagic Fever

Çevik, Mustafa Aydın; Erbay, Ayşe; Bodur, H.; Eren, Selim Sırrı; Akinci, E.; Şener, Kenan; Öngürü, Pınar; Kubar, Ayhan

doi:10.1086/521244

Cited by 97 publications

(72 citation statements)

References 17 publications

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“…For example, a study of 36 patients in Turkey found that 8 of 9 fatal cases had peak serum virus levels >10 9 viral genome copies/mL, whereas the peak levels of 25 of 26 survivors were below that level (Cevik et al, 2007). Similar observations have been made in Kosovo and Albania (Duh et al, 2007;Papa et al, 2006).…”

Section: Predictors Of Survival or Deathmentioning

confidence: 57%

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

et al. 2013

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Bente, Dennis A.; Forrester, Naomi L.; Watts, Douglas M.; McAuley, Alexander J.; Whitehouse, Chris A.; and Bray, Mike, "CrimeanCongo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity" (2013 b s t r a c tCrimean-Congo hemorrhagic fever (CCHF) is the most important tick-borne viral disease of humans, causing sporadic cases or outbreaks of severe illness across a huge geographic area, from western China to the Middle East and southeastern Europe and throughout most of Africa. CCHFV is maintained in vertical and horizontal transmission cycles involving ixodid ticks and a variety of wild and domestic vertebrates, which do not show signs of illness. The virus circulates in a number of tick genera, but Hyalomma ticks are the principal source of human infection, probably because both immature and adult forms actively seek hosts for the blood meals required at each stage of maturation. CCHF occurs most frequently among agricultural workers following the bite of an infected tick, and to a lesser extent among slaughterhouse workers exposed to the blood and tissues of infected livestock and medical personnel through contact with the body fluids of infected patients. CCHFV is the most genetically diverse of the arboviruses, with nucleotide sequence differences among isolates ranging from 20% for the viral S segment to 31% for the M segment. Viruses with diverse sequences can be found within the same geographic area, while closely related viruses have been isolated in far distant regions, suggesting that widespread dispersion of CCHFV has occurred at times in the past, possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during co-infection of ticks or vertebrates appears to have played an important role in generating diversity, and represents a potential future source of novel viruses. In this article, we first review current knowledge of CCHFV, summarizing its molecular biology, maintenance and transmission, epidemiology and geographic range. We also include an extensive discussion of CCHFV genetic diversity, including maps of the range of the virus with superimposed phylogenetic trees. We then review the features of CCHF, including the clinical syndrome, diagnosis, treatment, pathogenesis, vaccine development and laboratory animal models of CCHF. The paper ends with a discussion of the possible future geographic range of the virus. For the benefit of researchers, we include a Supplementary Table listing all published reports of CCHF cases and outbreaks in the English-language literature, plus some principal articles in other languages, with total case numbers, case fatality rates and all CCHFV strains on GenBank.

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Section: Predictors Of Survival or Deathmentioning

confidence: 57%

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

et al. 2013

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“…A direct correlation between the severity of disease for CCHF and a high viral load had already been observed in several patient studies (9,14,33), although the molecular mechanisms underlying this observation were not further elucidated. We tentatively speculate that the mechanism underlying the correlation between high viral load and disease severity in patients could be caused in part by the virus-enhanced endothelial cell activation, followed by excessive inflammatory reactions and leukocyte recruitment.…”

Section: Fig 2 Activation Of Endothelial Cells Is Virus Dose Dependmentioning

confidence: 94%

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Connolly‐Andersen

Moll

Andersson

et al. 2011

J Virol

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Crimean-Congo hemorrhagic fever virus (CCHFV) causes viral hemorrhagic fever with high case-fatality rates and is geographically widely distributed. Due to the requirement for a biosafety level 4 (BSL-4) laboratory and the lack of an animal model, knowledge of the viral pathogenesis is limited. Crimean-Congo hemorrhagic fever (CCHF) is characterized by hemorrhage and vascular permeability, indicating the involvement of endothelial cells (ECs). The interplay between ECs and CCHFV is therefore important for understanding the pathogenesis of CCHF. In a previous study, we found that CCHFV-infected monocyte-derived dendritic cells (moDCs) activated ECs; however, the direct effect of CCHFV on ECs was not investigated. Here, we report that ECs are activated upon infection, as demonstrated by upregulation of mRNA levels for E-selectin, vascular cell adhesion molecule 1 (VCAM1), and intercellular adhesion molecule 1 (ICAM1). Protein levels and cell surface expression of ICAM1 responded in a dose-dependent manner to increasing CCHFV titers with concomitant increase in leukocyte adhesion. Furthermore, we examined vascular endothelial (VE) cadherin in CCHFVinfected ECs by different approaches. Infected ECs released higher levels of interleukin 6 (IL-6) and IL-8; however, stimulation of resting ECs with supernatants derived from infected ECs did not result in increased ICAM1 expression. Interestingly, the moDC-mediated activation of ECs was abrogated by addition of neutralizing tumor necrosis factor alpha (TNF-␣) antibody to moDC supernatants, thereby identifying this soluble mediator as the key cytokine causing EC activation. We conclude that CCHFV can exert both direct and indirect effects on ECs.

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“…Another study designed to evaluate criteria predicting the disease severity reported the lab parameters indicating disease severity: platelet count<20000/mm 3 , and decrease of levels of hematocrit and fibrinogen, elevation of creatine phosphokinase titer and lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, prothrombin time (PT) and partial thromboplastin time (PTT) , developing melena and loss of consciousness [10]. Other studies have shown that the presence of risk factors including plt<90,000/mm 3 , increased levels of AST, ALT and PTT, are associated with significantly disease severity in these patients [11] and also high viremia predicted higher mortality rate [13,14]. Patients with severe lethal CCHF disease have been reported to have significantly higher serum levels of IL-6 and TNF-α and lower levels of IL-10 [8].…”

Section: Introductionmentioning

confidence: 99%

Can Serum Ferritin Level Predict Disease Severity in Patients with Crimean-Congo Hemorrhagic Fever?

Metanat

Sharifi-Mood

Tabatabaei

et al. 2013

EAJM

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Objective: Crimean-Congo hemorrhagic fever (CCHF) is an acute viral disease. Several factors have already been suggested to explain the pathogenesis as well as predict the disease severity. In our study we aim to investigate the role of serum ferritin level as a possible predicting factor of disease severity in these patients. Materials and Methods:We evaluated all patients with laboratory confirmed diagnosis of CCHF who were admitted to Boo-Ali Hospital of Zahedan from May 2011 to June 2012. Confirmation of the disease determined using the presence of anti-CCHFV IgM in the serum by enzyme-linked immunosorbent assay (ELISA) or by polymerase chain reaction(PCR). After ethical approval, patients were categorized into two groups of mild and severe disease according to disseminated intravascular coagulation (DIC) severity using the scoring system of International Society on Thrombosis and Hemostasis (ISTH) . Serum ferritin levels were evaluated and compared between these two groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the optimal cutoff value of serum ferritin for predicting the disease severity.Results: A total of 42 patients (36 men, 6 women, age range: 17-78 years) were included in this study, of whom 38% had Persian and 62% had Baloch ethnicity. According to DIC severity score, 54.7% of the patients had severe disease and 45.3% had mild disease. The area under the ROC curve was 0.896 and 95% CI was 0.801-0.991 (p<0.0001). A cut-off point of 1060 ng/dL, had a sensitivity of 78.9%, a specificity of 87%, a positive predictive value of 6% and a negative predictive value of 100%. Positive and negative likelihood ratios for this serum ferritin level were 6.05 and 0.24, respectively. Conclusion:Increased serum ferritin level has a significant positive correlation with disease severity in patients with CCHF and can evaluate the prognosis of these patients with a high sensitivity and specificity.Key Words: Crimean-Congo hemorrhagic fever, disease severity, ferritin Bulgular:Toplam 42 hasta (36 erkek, 6 kadın, yaş aralığı: 17-78 yıl olmak üzere) bu çalışmaya dahil edilmiştir, hastaların %38 Pers ve %62 Baloch etnik grubuna dahildir. DIC şiddet skoruna göre, hastaların %54.7 ciddi ve %45.3 'ü hafif olarak sınıflandırılmıştır. ROC eğrisi altında kalan alan 0.896 ve %95 CI 0.801-0.991 (p değeri <0.05) bulunmuştur. 1.060 ng/dL bir kesim noktası %78.9 bir duyarlılık, %87 özgüllük, %6 bir pozitif prediktif değer ve %100 bir negatif prediktif değer tespit edilmiştir. Bu serum ferritin düzeyi için pozitif ve negative olabilirlik oranları sırasıyla 6.05 ve 0.24 olarak bulunmuştur.Sonuç: Artmış serum ferritin düzeyi KKKA hastalarında hastalık şid-deti ile anlamlı pozitif korelasyona sahiptir ve bu hastalarda prognozu yüksek bir duyarlılık ve özgüllük ile gösterebilir.

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Viral Load as a Predictor of Outcome in Crimean-Congo Hemorrhagic Fever

Cited by 97 publications

References 17 publications

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

Crimean-Congo hemorrhagic fever: History, epidemiology, pathogenesis, clinical syndrome and genetic diversity

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Can Serum Ferritin Level Predict Disease Severity in Patients with Crimean-Congo Hemorrhagic Fever?

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