Elsevier

Antiviral Research

Volume 98, Issue 2, May 2013, Pages 248-260
Antiviral Research

Review
The impact of Crimean-Congo hemorrhagic fever virus on public health

https://doi.org/10.1016/j.antiviral.2013.02.007Get rights and content

Abstract

Climatic, environmental and economic changes, as well as the steadily increasing global trade and personal mobility provide ample opportunities for emerging pathogens with zoonotic potential to spread to previously unaffected countries. Crimean-Congo hemorrhagic fever virus (CCHFV) is considered to be one of the major emerging disease threats spreading to and within the European Union following an expanding distribution of its main vector, ticks of the genus Hyalomma. Every year more than 1000 human CCHF cases are reported from countries of southeastern Europe and Turkey. CCHFV can cause high case fatality rates and can be transmitted from human to human. There are no vaccine prophylaxis and therapeutic interventions available at present. Several EU-funded research projects focus currently on CCHFV which highlights the awareness for this problem at the European level. As public health deals with questions of prevention on a population level rather than healing and health on an individual level, the analysis of existing data plays a fundamental role to minimize its epidemic potential, by reducing infection risks, and to manage disease outbreaks. This review gives a summary of the current knowledge and data with focus at the interface between public health and CCHFV. Based on this knowledge, guidelines for the risk classification of a region and for outbreak prevention are given. This review will assist decision makers and public health authorities in understanding risk scenarios and in deciding on effective countermeasures, as well as human and veterinary scientists by highlighting existing gaps in knowledge.

Highlights

► Crimean-Congo hemorrhagic fever infections are a major public health threat in Europe. ► Ticks of the genus Hyalomma are the main vector for Crimean-Congo hemorrhagic fever virus. ► More than 1000 cases are reported from southeastern Europe and Turkey every year. ► There is an increasing concern that the virus could spread to new areas through the vectors’ distribution. ► The analysis of existing data is fundamental for devising control measures.

Introduction

Crimean-Congo hemorrhagic fever virus (CCHFV) is a member of the genus Nairovirus within the family Bunyaviridae. Since arthropods serve as transmission vectors, CCHFV is assigned to the group of Arboviruses (Arthropod-borne virus). Ticks of the genus Hyalomma are considered to be the main vector and also constitute the natural reservoir, as reviewed by Whitehouse (2004). Hyalomma spp. are present on the ground and infest small and large mammals (e.g. hedgehogs, hares, foxes, sheep, and cattle). Ticks therefore play a pivotal role in the CCHFV transmission cycle (tick-vertebrate-tick cycle) (Zeller et al., 1994). Although viremia in animals can last for up to two weeks, animals do not show clinical signs (Gunes et al., 2011).

CCHFV is an emerging virus with zoonotic potential. Tick bites constitute the main infection route for humans (Gunes et al., 2009). However, contact with body fluids, tissue or blood of viremic animals also represents infection risks for humans. Additionally, there are several reports about person-to-person transmission by unprotected handling of infected blood or material from CCHF patients, by accidental needle stick injuries, and by accident or inadequate protection measures during surgeries, which are the main reasons for nosocomial infections (Chinikar et al., 2010, Ergonul et al., 2007, Mourya et al., 2012).

CCHFV infections of humans can cause a severe hemorrhagic fever (CCHF) with lethality rates ranging from 5% to 80% (Yen et al., 1985, Yilmaz et al., 2008). Scientific data on the virulence of CCHFV and the morbidity rates following infections in humans are scarce. According to the literature 10–20% of infected humans develop clinical signs (Bodur et al., 2012, Goldfarb et al., 1980). There is no safe vaccine available and therapeutic interventions are restricted to supportive measures. Because of the classification of CCHFV as a Biosafety Level 4 pathogen by the World Health Organization (WHO) and the Centre for Disease Control and Prevention (CDC), high biocontainment facilities are required for work with infectious material or with the virus itself (Bronze et al., 2002, Keshtkar-Jahromi et al., 2011).

Section snippets

Vector distribution

Although CCHFV was isolated from 31 tick species, until now only a few species were shown to be competent as a vector. The spread of CCHFV primarily coincides with the distribution of Hyalomma ticks as its main vector. To date, these ticks have been found in regions of many countries in southeastern Europe (Fig. 1). Ticks are not only relevant as vectors but also play a role as natural reservoir, since the virus can be transmitted transstadially, transovarially or by venereal route within the

Tick-related infections

To date, only few reports of the prevalence of CCHFV in ticks have been published. A prevalence of 15% CCHFV-positive ticks was found in Kosovo in 2001 by quantitative RT-PCR (Duh et al., 2006), 3% in Albania in 2005 by nested RT-PCR (Papa et al., 2009) and up to 20% in Turkey in 2007 by antigen-capture ELISA (Vector-Best, Novosibirsk, Russia) (Gunes et al., 2011). Tick bites represent the most important route of infection for humans, although the frequency of tick bites in human cases seems to

Protection of the population at large

To protect the public, monitoring programs in ticks and animals should be implemented to define endemic or high-risk areas and to detect virus spread at an early stage (Vorou, 2009). The infection rate in ticks can be used as an indicator for defining the endemic status of a region (Gunes et al., 2011). If a human CCHF case is diagnosed, national authorities should be informed which will notify the case to the European Centre for Disease Prevention and Control (ECDC) and the WHO. After

Availability of diagnostic tools

There are a few IgG and IgM ELISAs, as well as IFA slides commercially available for the detection of CCHFV-specific human antibodies (Table 3). Additionally, there is one antigen-capture ELISA on the market. Unfortunately, some of these assays are difficult to order or not offered to international customers. In addition to these commercial assays, several in-house ELISAs, as well as IFA tests have been published for testing human sera. Unfortunately, most of these assays are only sparsely

Treatment and vaccination

Patients should be monitored closely, in terms of clinical parameters, and the blood indices should be analyzed regularly to allow adjusting the treatment. In general, treatment of CCHF is limited to supportive measures. In case of extensive blood loss transfusions and injections of blood substitutes and aminocaproic acid are indicated. To support the hematological treatment fresh frozen plasma, thrombocyte solutions and erythrocyte preparations can be given. In addition, respiratory support

Public health risk perception

Risk perception has to be regarded and evaluated separately for different groups, e.g. the European Commission, countries with and without endemic areas, the national ministries, the public health institutions, the health care systems, and the public. It becomes clear that health education and information on prevention and behavioral measures have a high priority to enhance the public risk perception. Risk perception of the public in turn has a high potential to decrease the probability of

Management and communication

The distribution of CCHFV in southeastern Europe and the risk of virus spread is a challenge for the European community. In general, for evaluation of the situation regarding any vector-transmitted pathogen and for the decision if additional measures should be implemented, a systematic approach for the analysis, assessment and governance of emerging health risks should be followed (Schmidt et al., 2013). It is the task for decision makers, public health authorities and also for scientists to

Conclusion

Addressing its potential impact on public health, this review summarizes the current understanding of CCHFV to provide a broad basis for the risk assessment and the development of prevention strategies. In respect to the wide distribution of CCHFV, the broad host range of its vectors, the good adaptation of the virus to the vector population together with its potential to be transmitted from human to human (e.g. by nosocomial infections), the high lethality rate, and the limited therapeutic

Acknowledgment

This study was funded by EU grant FP7-261504 EDENext and is catalogued by the EDENext Steering Committee as EDENext089 (http://www.edenext.eu). The contents of this publication are the sole responsibility of the authors and don’t necessarily reflect the views of the European Commission.

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