Crimean-Congo Hemorrhagic Fever: An Emerging Zoonotic Disease

Crimean-Congo Hemorrhagic Fever: An Emerging Zoonotic Disease

PN Gandhale*, S. Sruthy, H.V.Murugkar and A. Sanyal

ICAR-National Institute of High Security Animal Diseases, Bhopal, Madhya Pradesh

Introduction: The global landscape is witnessing a concerning surge in emerging zoonotic diseases, presenting an intricate challenge at the intersection of human and animal health. Within this panorama, Crimean-Congo Haemorrhagic Fever (CCHF) is silently emerging as a formidable zoonotic threat. The causative agent of this disease is a tick-borne, biosafety level-4 pathogen, Crimean-Congo Haemorrhagic Fever virus (CCHFV), a member of the Orthonairovirus genus under the family Nairoviridae, The roots of this viral disease trace back to the Crimean Peninsula in 1944 when Soviet scientists identified it among soldiers and peasants, thus the diseases was initially termed “Crimean Hemorrhagic Fever”. Subsequently, in 1969, ‘Congo Haemorrhagic Fever’ virus that was isolated from a patient in the former Zaire (now Democratic Republic of the Congo) in 1956 was shown to be the same virus as the Russian strain. As a consequence, the names of both countries have been used in combination to describe the disease as Crimean- Congo Hemorrhagic Fever.

CCHF is recognized as a priority disease within the Global Early Warning and Response System (GLEWS). This joint initiative between the World Organization for Animal Health (WOAH), the Food and Agriculture Organization (FAO), and the World Health Organization (WHO), aims to enhance the detection of health threats and events at the human-animal-ecosystem interface. CCHF is also listed by the WHO as one of the seven highest-priority epidemic-prone diseases. Likewise, CCHF is also WOAH listed disease meaning it is one of international concern, for which member countries are obliged to submit information such as the outbreak and number of cases in the country to the WOAH every year. Moreover, the Center for Disease Control and Prevention (CDC) recognizes CCHFV as a significant biosecurity risk. This summary aims to provide information on CCHF from a public and animal health perspective for general awareness.

 CCHF Disease:

In Humans:

Humans act as dead-end hosts for the virus which causes severe hemorrhagic fever leading to fatality rate ranging from 5% to 80%. The length of the incubation period depends on the mode of infection. The incubation period is usually 1-3 days following infection by a tick bite that can extend upto a maximum of 9 days. Following contact with infected blood or tissues, the incubation period has been documented for 5-6 days and  maximum of 13 days. The disease in humans progresses through four distinct stages; the incubatory stage, marked by viral replication within the body; the pre-hemorrhagic stage; the hemorrhagic stage; and the convalescent stage.

In Animals:

The CCHFV may cause a transient and low-intensity viremia in animals and hence generally goes unnoticed. Animals readily become infected by the bite of infected ticks and persist in their bloodstream for up to one week after infection thus acting source of virus to other co-feeding ticks. Even though CCHFV does not cause any clinical symptoms in animals, they play a very crucial role in virus perpetuation, transmission, and amplification through the Tick-Animal-Tick cycle. Most experimentally infected livestock (cattle, sheep, goats, horses, donkeys) and wild species (e.g., hares, hedgehogs) remain asymptomatic, although a transient mild fever, lethargy, and reduced appetite are seen in a few animals.

CCHF presents a complex epidemiological scenario involving a plethora of domestic and wild animals such as cattle, goats, sheep, deer, hares, and hedgehogs, that serve as amplifying hosts for the virus. Although most birds (excluding ostriches) seem to be resistant to CCHF infection, they have the potential to serve as mechanical vectors. Migratory birds, along with ungulates and livestock, can carry attached ticks to great distances into new, previously unpopulated areas thus expanding the geographic range of the CCHFV.

Vectors:  

The principal vectors are Ixodid (hard) ticks of the genus Hyalomma including, but not limited to, Hyal. anatolicum, Hyal. marginatum, Hyal. nitidum & Hyal. truncatum, etc. These ticks act as reservoirs as well as amplifiers for the CCHFV.  CCHFV has also been reported from more than 25 tick species of the genera Rhipicephalus, Amblyomma, and Dermacantor, although their role in virus maintenance and transmission is unclear. The CCHFV is maintained in the tick population through horizontal transmission, vertical transmission (larvae to eggs), and  non-viremic transmission (between the infected & healthy ticks during co-feeding).

 Fig. 1a. Hyalomma rufipes (female & male)        1b. Hyalomma anatolicum (female & male)

(Photo: Daktaridudu/Wikimedia Commons)

 Transmission:

The primary modes of CCHF transmission to humans are through tick bites, exposure to blood or tissue of infected livestock, and direct contact with blood or body fluids of other infected persons. In animals CCHFV is mostly transmitted by infected ticks.

Epidemiology:

 World:

Geographical distribution of the disease aligns with the presence of Hyalomma ticks, the primary vectors of the virus. CCHFV is limited to areas below the 50^th parallel north where Hyalomma ticks are ubiquitous throughout Eurasia and Africa, excluding Sri Lanka, Indonesia, and Japan. The serological and/or virological evidence of CCHF has been reported across Asia, Eastern Europe, the Middle East, Central Africa, Western Africa, South Africa, and Madagascar. Besides antibodies against CCHFV have been detected in numerous vertebrate species including buffaloes, cattle, sheep, goats, camels, horses, chickens, ducks, dogs, donkeys, ostriches, and wild species including hares, buffalo, rhinoceroses, hedgehogs, and Chiroptera (Spengler et al., 2016; Dave et al., 2022).

 India:

India entered the narrative of CCHF in 2011 when the first confirmed case surfaced during a nosocomial outbreak in Ahmadabad, Gujarat. Since then several sporadic cases were reported from Gujarat and few from Rajasthan and Uttar Pradesh. Subsequently, various serosurveillance studies carried out in Gujarat, Rajasthan, Madhya Pradesh, and Kerala states have demonstrated the presence of CCHFV antibodies in domestic animals (Yadav, et al., 2014; Dave et al., 2022;  Bhawana, et al., 2023). Moreover, the cross-sectional serosurvey spanning 22 states and 01 Union Territory also revealed the widespread prevalence of antibodies against CCHFV in animals (Mourya, et al., 2015). Furthermore, livestock sera collected from the vicinity of human CCHF case/s, affected and adjoining villages have also shown anti-CCHFV antibodies (Gandhale, et a.l, 2020). Interestingly even though the vector ticks are present throughout the country, the incidence of CCHF in humans is restricted to only Gujarat so far.

 Diagnosis:

Owing to the risk of laboratory-acquired infections, diagnostic tests should be conducted in biosafety level 3 & 4 biocontainment facilities only. For rapid genomic detection of CCHFV in animal samples (serum, plasma) and ticks, several nucleic acid detection assays viz. conventional RT-PCR, real-time reverse transcription-PCR, and immunofluorescence are being used across world. For the detection of antibodies against CCHFV, host-specific and multispecies the Enzyme-linked Immunosorbent Assays are being used widely (WOAH, 2023).

 Diagnostic preparedness at ICAR-NIHSAD, Bhopal:

To have in-house diagnostic preparedness during outbreak situations, the diagnostic capacity using WOAH referred assay viz. nested RT-PCR, RT-PCR, and real-time reverse transcription-PCR, has been established for genomic detection. These assays are being used for testing animal samples as well as ticks thereof collected from the vicinity of index human cases during the outbreak.

Prevention and Control: Being a zoonotic disease, there are two aspects of prevention and control of this disease.

For Humans: Due to the limited treatment and the absence of an FDA-approved vaccine or specific antiviral, emphasizing prevention becomes paramount for this fatal disease.

• Those working with livestock in endemic areas may use tick repellents, such as DEET, and treat clothing with substances like permethrin.
• Wearing protective clothing is essential to minimize skin contact with infected tissues or blood in slaughterhouses.
• In the health care setting, safe disposal practices should be followed for needles, penetrating surgical instruments, body fluids, virus-infected material, etc.
• Regular awareness campaigns should be organised in the endemic areas.

For Animals/Ticks:

Interrupting the tick-animal-tick cycle is crucial in CCHFV prevention and control. Therefore, acaricides and other tick control measures are of paramount importance in controlling the disease. However, complete tick control may be difficult but regular tick control activities result in reduced disease incidence.

 Challenges:

India is vast country with large livestock population spread in rural areas. The farmers often rear small herds of 4-5 animals and houses them near own residence. In such animal husbandry settings, the risk of CCHFV transmission to farmers and their family members becomes very high. Furthermore, unorganised animal husbandry settings make it difficult for implementing the effective tick control programs. Uncontrolled animal movements between and within the state (for trade, exhibitions) are frequent, thereby increasing the chance of virus transmission to newer host/area.  Moreover ticks carried along with livestock plays an important role in establishing CCHFV ecology in newer areas.

Public health significance:

CCHFV can cause high case fatality rates and can be transmitted from human to human. Also, no vaccine prophylaxis and therapeutic interventions are available at present. Since 2011, regular sporadic outbreaks have been reported in Gujarat. It seems that the virus is spreading to neighbouring states as is evident from several serosurveys in animals. CCHF poses a considerable public health threat in India owing to ubiquitous presence of Hyalomma ticks and their host, favorable climate for ticks, animal husbandry practices involving close contact with animal-human, diagnostic insufficiency in rural areas, and lack of awareness. CCHF is an excellent example of a disease well-suited to the One Health approach as controlling it requires coordinated efforts by veterinary practitioners, medical professionals, public health experts, and parasitologist.

Conclusion:

As we navigate the intricacies of CCHF, it is imperative to take measures not only in understanding its origins and transmission but in charting a course toward vigilance and prevention. The absence of specific antivirals and vaccines underscores the critical need for robust preventive measures. Proactive tick control, stringent biosafety precautions in laboratories and hospitals, and swift reporting mechanisms by medical and veterinary professionals are imperative. The journey to control CCHF demands collaboration across borders, disciplines, and sectors. Only through collective efforts we can shield communities from the silent but potent threat of this public health adversary.

References:

1. Crimean-Congo Haemorrhagic Fever factsheet, WHO.  https://www.who.int/news-room/fact-sheets/detail/crimean-congo-haemorrhagic-fever. Retrieved on 30.4.2024.
2. Crimean–Congo Haemorrhagic Fever (2023). Chapter 3.1.5 in WOAH terrestrial manual 2023.
3. Centers for Disease Control and Prevention. https://www.cdc.gov/vhf/crimean-congo/index.html. Retrieved on 30.4.2024.
4. Spengler JR, Bergeron É, Rollin PE (2016). Seroepidemiological Studies of Crimean-Congo Hemorrhagic Fever Virus in Domestic and Wild Animals. PLoS Negl Trop Dis; 7;10(1).
5. Dave KM, Raval SK, Nayak JB, Kanani AN, Shah N, Dash PK, Shrivastava N, Yashavanth BS and Gandhale PN (2022). Influence of Herd structure on the prevalence of Crimean Congo Hemorrhagic Fever virus antibodies among Bovines in Gujarat. Ruminant Science; 11(1):1-5.
6. Yadav P, Raut C, Patil D, Majumdar TDand Mourya DT (2014). Crimean-congo hemorrhagic fever: Current scenario in India. Proceedings of the National Academy of Sciences, India, Section B: Biological Sciences; 84:9-18.
7. Bhawana Rani, Kashyap Yadav, BS Yashavanth, Aniket Sanyal, HV Murugkar and PN Gandhale (2023). Evaluation of general health status and deworming as determinants in the CCHFV seroprevalence in animals in Madhya Pradesh. Ruminant Science (Accepted).
8. Gandhale PN, Raut AA, Rajukumar K, Senthil kumar D, Kanani A, Shah N, Kachhiapatel AJ, Mishra A and Kulkarni DD (2020). Investigation of Crimean-Congo Hemorrhagic Fever Virus in the livestock & ticks samples collected from the Human CCHF outbreak area. In: International e-conference on “Paradigm shift in animal disease diagnostics; Veracious path in disease prevention and control” October, 7-9, 2020 at Veterinary College and Research Institute, Tirunelveli, TANUVAS, Chennai, India.
9. Mourya, D. T., Yadav, P. D., Shete, A. M., Sathe, P. S., Sarkale, P. C., Pattnaik, B., &Chaubal, G. Y. (2015). Cross-sectional serosurvey of Crimean-Congo hemorrhagic fever virus IgG in livestock, India, 2013–2014. Emerging Infectious Diseases; 21(10), 1837.

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