Pathogenesis of Crimean-Congo Hemorrhagic Fever

Abstract

Although Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne disease, little is known about its pathogenesis. The interaction of the virus with host cells is most likely responsible for the pathogenesis of CCHF. The main contributors are endothelial cells (ECs) and immune cells. There are 2 theories underlying the CCHF pathogenesis: One is that the virus interacts with the ECs directly and the other that it interacts indirectly via immune cells with subsequent release of soluble mediators. ECs are activated upon infection by the upregulation of soluble molecules and proinflammatory cytokines. Probably, in severe cases, deregulation and excessive release of the cytokines accompanied by endothelial activation have toxic effects, leading to increased vascular permeability, vasodilatation, and subsequently hypotension, multiple organ failure, shock, and death. Studies indicate that CCHF virus (CCHFV) also can impair the innate immune system and cause a delay in adaptive immune response, which is critical for the clearance of CCHFV. The virus has many different ways to block the immune response, leading to uncontrolled viral replication followed by systemic spread of the virus throughout the body. Partial activation of dendritic cells and macrophages, delayed induction of interferons, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. However, there are many points waiting for clarification about the pathogenesis of CCHF. Although the high risk of contagiousness limits research, we need more studies to understand the CCHF pathogenesis better. Here we review the main characteristics of the pathogenesis of CCHF.

Cutaneous Findings of Crimean-Congo Hemorrhagic Fever: a Study of 269 Cases

“…Despite these data, it remains unclear how tick-induced changes at the tick-dermal interface permeability, resulting in hypotension, shock, multiple organ failure and death (22)(23)(24)(25). The proinflammatory cytokines may be the reason for the CCHF dermatological signs (morbilliform eruptions, petechial lesions, purpura, ecchymosis and oral erythema-petechiae), and they are secreted after endothelial injury.…”

Crimean-Congo Hemorrhagic Fever

“…Kene ısırdıktan sonra KKKA virüsü, epiteli geçer, endotel hücrelerine ulaşır ve hücrelerde hasar oluşturur (5,17) . Endotel hücrelerinde oluşan bu hasar ya doğru-dan virüsün etkisi ile ya da dolaylı olarak immünolo-jik ve inflamatuar yolların aktivasyonu sonucu oluşur (5,18,19) .…”

“…Sitokinler, kemokinler ve diğer proinflamatuvar mediatörler salınır, gelişen endotel hücre aktivasyonu ve endotel hasarı sonucunda vasküler permeabilite artar, intrensek koagülasyon sistemi aktive olur ve dissemine intravaskuler koagulasyon (DİK) gelişir. DİK gelişmesi sonucunda kanamaya kadar giden tablolar oluşur (17,20,21) . Çalışmalar, patogenezde proinflamatuar sitokinlerin etkin rol oynadığını göstermiştir.…”

“…KKKA virüsünün hepatositleri yaygın olarak infekte etmesi sonucunda karaciğer enzimlerinde artış, hücrelerde ödem ve nekroz oluşmaktadır. Sonuçta, hemofagositoz ve karaciğer disfonksiyonu sonucunda kanamalar ortaya çıkmaktadır (5,17,20,21) .…”

Crimean-Congo Hemorrhagic Fever

“…Partial activation of dendritic cells and macrophages, delayed induction of IFNs, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. 32 The endothelial injury both leads to platelet aggregation and activation of the intrinsic coagulation pathway. The tissue factor releasing from the infected cells leads to developing of disseminated intravascular coagulation (DIC) by stimulating the extrinsic coagulation.…”