Special Attention for Eid-Al-Azha Sacrificial Animals!!!

FOOD BORNE ZOONOSIS SERIES- PART-II

“Crimean Congo Hemorrhagic Fever (CCHF)”

BY Dr. Iqra Zaheer* and

Tean Zaheer**

*PhD (Pathology) Scholar

**Assistant Editor, the Veterinary News and Views, DVM Student, FVS, UAF.

Crimean Congo Hemorrhagic fever (CCHF) is a zoonotic, tick-borne and hemorrhagic viral disease. It is mostly acquired by contact with infected blood or other tissues of livestock or human patients or from tick bite. CCHF is endemic in Africa, the Balkans, the Middle East and Asia. The case fatality up to 40% has been reported in Pakistan area [who.int/factsheets].

Brief History:

A hemorrhagic disease with symptoms suggestive of CCHF infection was described in Eastern Europe and Asia as far back as the 12th century (Hoogstraal 1979).

CCHF was first reported in Pakistan in 1976 but the number of cases has shown a dramatic rise since 2000 with 50-60 cases being reported annually. The incidence of CCHF peaks in June to October but cases occur throughout the year [nih.org.pk]. In 2002, two cases were reported from contact with an Afghan patient. Recently, in 2015, the doctors announced the risk of Peshawar locals to be possibly affected by the Afghan patients, where the disease is endemic [dawn.com]. According to the NIH survey September 2013, 11 people had been killed from the fever in the country. Five people had succumbed to the disease in Khyber Pakhtunkhwa while six fatalities have been recorded in Balochistan. It said that 137 people have been suffering from Congo fever in Balochistan and Khyber Pakhtunkhwa [samaa.pk]. Around Eid Al Azha and the seasonal change, the outbreaks of CCHF are anticipated, for which the preventive measures like use of acaricidal agents on animals, purchase of animals from a well-ventilated area of the market, use of sterilized equipment and utensils and proper cooking of the meat at consumer level should be adopted.

Epidemiology:

CHF is endemic in many countries in Africa, the Middle East, Eastern Europe and Asia.

Outbreaks have been recorded in Russia, Turkey, Iran, Kazakhstan, Mauritania, Kosovo, Albania, Pakistan, and Southern Africa in recent years. On epidemiological analysis of Pakistan, the exposure of bulk of cases was traced back to animals from Quetta, Zhob, Killa Saifullah, Killa Abdullah, Pishin, Loralai and Musa Khel districts of Balochistan. Similarly a number of patients diagnosed in Karachi, Rawalpindi, Multan, D. I. Khan, Mansehra, Peshawar, Landi Kotal and recently from Abbottabad also possessed history of contact and slaughtering animals.

Transmission of CCHF: The Causative Agent:

The causative agent, CCHF virus (genus Nairovirus, family Bunyaviridae), is an enveloped negative-sense, tri-segmented, single-stranded RNA virus. The CCHFV’s are classified into 7 genotypes (Asia-1, Asia-2, Euro-1, Euro-2, Africa-1, Africa-2, and Africa-3) on the basis of genetic variation.

Vector:

Infected Ixodid tickks spread the virus. The most efficient and common vectors appear to be members of the Hyalomma genus. Virus in ticks can be transmitted from the infected to uninfected ticks via Trans ovarian or through Trans venereal route. Immature ticks acquire the virus by feeding on infected small animals. Ticks are lifelong carriers of CCHF agent.

Hosts:

Livestock and human infested by the vector tick. Numerous wild and domestic animals, such as cattle, goats, sheep and hares, serve as amplifying hosts for the virus. Most birds are thought to be relatively resistant to infection with CCHF virus. Many bird species carry Hyalomma ticks, and human infections have occurred in people consuming the infected animal’s meat.

Transmission:

Human transmission occurs by the consumption of infected meat and through contact with infected ticks or animal blood. CCHF can be transmitted from one infected human to another by contact with

infectious blood or body fluids. Documented spread of CCHF has also occurred in hospitals due to improper sterilization of medical equipment, reuse of injection needles, and contamination of medical supplies.

Pathogenesis/Clinical Pathology of CCHF:

The pathogenesis of Crimean Congo Hemorrhagic Fever is incompletely known, the main reason being the high level zoonotic threat of the causative agent. As a standard biosafety recommendation for autopsies or necropsies or handling of the causative virus, a Bio Safety Level 4 (BSL-4) laboratory and protocol is a requirement. The course of CCHF can be divided into four distinct phases, the duration and severity of which may differ greatly:

1. Incubation phase 2. Pre-hemorrhagic phase3. Hemorrhagic phase4. Convalescent phase

Following a tick bite, incubation period ranges from 1 - 5 days. Factors contributing to a fatal outcome include cerebral hemorrhage, severe anemia, severe dehydration, and shock associated with prolonged diarrhea, myocardial infarction, lung edema, and pleural effusion. Patients who die develop terminal multiple organ failure, including cerebral, liver, and kidney failure and cardiac and pulmonary insufficiency. Capillary fragility is a common finding of CCHF. Thrombocytopenia is an important feature of CCHF. Appearance of characteristic rashes on the body are an outcome of progressive endothelial damage which in turn contributes to the hemostatic failure. The endothelial damage may follow a pathway initiated by the direct contact of virus with the host or it may be triggered by some host-induced mechanisms, induction of pro-inflammatory cytokines, and the dysregulation of coagulation cascade leading to DIC eventually.

Coagulation abnormalities develop with progressive hepatic involvement resulting in increased levels of liver-associated enzymes and BUN levels along with the creatinine levels indicate the renal in sufficiency.

Signs and Symptoms:

Patients show a sudden onset of fever, accompanied by weakness, sore throat, headache, muscular pain, vomiting, and photo-phobia. Patients rapidly develop myalgia and malaise with severe leg and back pain may be observed. Like most other Viral Hemorrhagic Fevers (including E-bola, Marburg, Lassa fever and

Yellow fever) CCHF’s early symptoms are not dramatically distinguished. In advanced cases symptoms like:

Marked hyperemia of the face and oropharynx, Hemorrhagic rash with development of ecchymosis, Bleeding from the nasopharynx, gastrointestinal tract and other sites may appear.

The case fatality of people infected with CCHF is 10-40%, after the appearance of advanced symptoms.

Prophylaxis:

The risk factors for the spread of Crimean Congo Hemorrhagic Fever have been attributed already, which must be overcome by observing strict biosecurity and quarantine measures (in case of suspected cases)to prevent the spread of the disease. The ways to control the vectors must be communicated from farmer up to consumer level in order to minimize this fatal zoonotic disease. Following methods may be employed as a prophylactic measure:

Possible ways to control the Vectors: Complete Eradication (not feasible) Administration of acaricidal agents Genetically resistant animals Movement control of infected animals Anti-tick vaccines Pheromone-based tick control Integrated control of ticks Vaccine development against CCHF:

An inactivated, mouse-brain derived vaccine against CCHF has been developed and is used on a small scale in Eastern Europe. However, there is no safe and effective vaccine currently available for human use.

A lot of work on the preparation of commercial CCHF vaccine is being carried out, the efforts need to be further fortified in order to prevent this endemic outbreak at the consumer level.

Diagnosis:

Laboratory diagnosis of a patient with a clinical history compatible with CCHF can be made during the acute phase of the disease by using the combination of detection of the viral antigen (ELISA antigen capture), viral RNA sequence (RT-PCR) in the blood or in tissues collected from a fatal case and virus isolation. Laboratory tests that are used to diagnose CCHF include:

Antigen-capture enzyme-linked immunosorbent assay (ELISA) Real time polymerase chain reaction (RT-PCR) Serum neutralization Virus isolation attempts Detection of antibody by ELISA (IgG and IgM).

Immunohistochemical staining can also show evidence of viral antigen in formalin-fixed tissues. Later in the course of the disease, in people surviving, antibodies can be found in the blood. But antigen, viral RNA and virus are no more present and detectable.

Treatment: The Anti-viral therapy employing high dose Ribavirin via oral route may be effective. The injection of commercially available specific hyper immunoglobulins for both

suspected and as a prophylactic measure. Interferons and interferon-stimulated antiviral proteins may be administered. Supportive therapy

The use of Antibodies to CCHF i.e. Gamma-globulin obtained from immunization of horses and the development of monoclonal antibodies would allow better control of CCHF.

Conclusion:

The outbreaks of CCHF can be associated with the change in persisting situations such as animal movements from infected area for sale purposes e.g. for Eid Al Azha , seasonal migrations, war, human population explosion, and climatic or vegetation changes which provide more ground cover for small mammals which act as hosts for ticks. These conditions can lead to explosions in tick populations, and allow increased tick and human contact. Being a potential candidate of bioterrorism, the prophylactic measures against CCHF must be strictly followed, so as to prevent this food-borne zoonotic havoc at its best.