Crimean–Congo hemorrhagic fever

Crimean-Congo hemorrhagic fever
Classification and external resources
Isolated male patient diagnosed with Crimean-Congo hemorrhagic fever
ICD-10	A98.0
ICD-9	065.0
DiseasesDB	31969
MedlinePlus	article
eMedicine	830594/

Crimean–Congo hemorrhagic fever (CCHF) is a widespread tick-borne viral disease, a zoonosis of domestic animals and wild animals, that may affect humans. The pathogenic virus, especially common in East and West Africa, is a member of the Bunyaviridae family of RNA viruses. Clinical disease is rare in infected mammals, but commonly severe in infected humans, with a 30% mortality rate. Outbreaks of illness are usually attributable to handling infected animals or people.

Signs and symptoms

Typically, after a 1–3 day incubation period following a tick bite (5–6 days after exposure to infected blood or tissues), flu-like symptoms appear, which may resolve after one week. In up to 75% of cases, however, signs of hemorrhage appear within 3–5 days of the onset of illness in case of bad containment of the first symptoms: first mood instability, agitation, mental confusion and throat petechiae, then soon nosebleeds, bloody urine and vomiting, and black stools. The liver becomes swollen and painful. Disseminated intravascular coagulation may occur as well as acute kidney failure and shock, and sometimes acute respiratory distress syndrome. Patients usually begin to show signs of recovery after 9–10 days from when the symptoms appear, however 30% of the cases result in death on the second week of the illness.

Virology

Crimean–Congo hemorrhagic fever
Virus classification
Group:	Group V ((-)ssRNA)
Order:	Unassigned
Family:	Bunyaviridae
Genus:	Nairovirus
Species:	Crimean-Congo hemorrhagic fever virus

The virus is a member of the genus Nairovirus, family Bunyaviridae.

Molecular biology

The genome is circular, ambisense RNA in three parts - Small (S), Middle (M) and Large (L). The L segment is 11–14.4 kilobases in length while the M and S segments are 4.4–6.3 and 1.7–2.1 kilobases long respectively. The L segment encodes the RNA polymerase; the M segment encodes the envelope proteins (Gc and Gn); and the S segment encodes the nucleocapsid protein. The envelope protein is initially translated as a glycoprotein precursor which is then cleaved into two smaller proteins.

Population genetics

CCHFV is the most genetically diverse of the arboviruses: Its nucleotide sequences frequently differ between isolates with a range of 20% of the based being different (viral S segment) to 31% (viral segment M). Viruses with diverse sequences can be found within the same geographic area; closely related viruses have been isolated widely separated regions. This suggests that viral dispersion has occurred possibly by ticks carried on migratory birds or through the international livestock trade. Reassortment among genome segments during coinfection of ticks or vertebrates seems likely to have played a role in generating diversity in this virus.

Based on the sequence data seven genotypes have been recognised: Africa 1 (Senegal), Africa 2 (Democratic Republic of the Congo and South Africa), Africa 3 (southern and western Africa), Europe 1 (Albania, Bulgaria, Kosovo, Russia and Turkey), Europe 2 (Greece), Asia 1 (the Middle East, Iran and Pakistan) and Asia 2 (China, Kazakhstan, Tajikistan and Uzbekistan).

Morphology

The virons are 80–120 nanometers (nm) in diameter and are pleomorphic. There are no host ribosomes within the viron. Each viron contains three copies of the genome. The envelope is single layered and is formed from a lipid bilayer 5 nm thick. It has no protrusions. The envelope proteins form small projections ~5–10 nm long. The nucleocapsids are filamentous and circular with a length of 200–3000 nm.

Evolution

This virus appears to have evolved 3100–3500 years ago. The mutation rates for the three parts of the genome were estimated to be: 1.09×10⁻⁴, 1.52×10⁻⁴ and 0.58×10⁻⁴ substitutions/site/year for the S, M, and L segments respectively.

Vectors

Hyalomma tick

The virus has been isolated from at least 31 different species of ticks from the genera Haemaphysalis and Hyalomma. Sporadic infection of people is usually caused by Hyalomma tick bite. Clusters of illness typically appear after people treat, butcher or eat infected livestock, particularly ruminants and ostriches. Outbreaks have occurred in clinical facilities where health workers have been exposed to infected blood and fomites. The causative organism is found in Asia, Eastern Europe, the Middle East, a belt across central Africa and South Africa and Madagascar (see map ) The main environmental reservoir for the virus is small mammals (particularly European Hare, Middle-African hedgehogs and multimammate rats). Ticks carry the virus to domestic animal stock. Sheep, goats and cattle develop high titers of virus in blood, but tend not to fall ill. Birds are generally resistant with the exception of ostriches.

Tick species that have been identified as infected with this virus include Argas reflexus, Hyalomma anatolicum, Hyalomma detritum, Hyalomma marginatum marginatum and Rhipicephalus sanguineus.Both working with humans and animals infected from Congo–Crimean Hemorrhagic fever usually transmit the virus to other humans.

Receptors

The cell surface protein nucleolin has been identified as a putative receptor for this virus.

Prevention

Where mammalian tick infection is common, agricultural regulations require de-ticking farm animals before transportation or delivery for slaughter. Personal tick avoidance measures are recommended, such as use of insect repellents, adequate clothing and body inspection for adherent ticks.

When feverish patients with evidence of bleeding require resuscitation or intensive care, body substance isolation precautions should be taken.

The United States armed forces maintain special stocks of ribavirin to protect personnel deployed to Afghanistan and Iraq from CCHF.

Vaccine

Since the 1970s, several vaccine trials around the world against CCHF have been scrapped due to high toxicity.

In 2011, a Turkish research team led by Erciyes University has successfully developed the first non-toxic preventive vaccine, which passed clinical trials. The vaccine is pending approval by the FDA.

Treatment

Treatment is primarily symptomatic and supportive, as there is no established specific treatment. Ribavirin is effective in vitro and has been used during outbreaks, but there is no trial evidence to support its use.

A Turkish research team led by Refik Saydam Health Institute has developed treatment-serum derived from blood of several CCHF-patients, which have been proven to be 90% effective in CCHF-patients.

Epidemiology

Crimean–Congo hemorrhagic fever 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.

During the summers of 1944 and 1945 over 200 cases of an acute, hemorrhagic, febrile illness occurred in Soviet troops rescuing the harvest following the ethnic cleansing of the Crimean Tatars.

On July 28, 2005 authorities reported 41 cases of CCHF in Turkey's Yozgat Province, with one death. As of August 2008, a total of 50 people were reported to have lost their lives in various cities in Turkey due to CCHF. 3128 Crimean–Congo hemorrhagic fever cases with 5% of case-fatality rate have been reported by the Ministry of Health of Turkey between 2002–2008.

On May 27, 2010 Hospitals reported 70 cases of CCHF in Kosovo's Kosovo Polje, with 4 deaths reported so far. The Authorities are not able to deal with the disease because of the lack of advanced medication.

In September 2010 an outbreak has been reported in Pakistan's Khyber Pakhtunkhwa province. Poor diagnosis and record keeping has caused the extent of the outbreak to be uncertain, though some reports indicate over 100 cases, with a case-fatality rate above 10%.

In January 2011, the disease has been reported in Gujarat, India, with 4 reported deaths, which consisted of the patient along with the doctor and the nurse who treated the patient.

As of May 2012, 71 people are reported to have contracted the disease in Iran, resulting in 8 fatalities.

In October 2012, a British man died from the disease at the Royal Free Hospital in London. He had earlier been admitted to Gartnavel General Hospital in Glasgow after returning on a flight from Kabul in Afghanistan.

In July 2013, in Kariyana village in Babra Taluka, Amreli district, India the virology report of four persons who died last week tested positive for CCHF.

On August 16, 2013, a farmer from Agago, Uganda was treated at Kalongo Hospital for a confirmed CCHF infection. Additionally, the deaths of three other people in the northern region were suspected to have been caused by the virus. Six people who had come in contact with the Agago man were placed under observation, and released after showing no symptoms in two weeks. Another unrelated suspected CCHF patient as admitted to Mulago Hospital on the same day. The Ministry of Health announced on the 19th that the outbreak was under control, but the second patient, a 27-year old woman from Nansana, died on the 21st. She is believed to have contracted the virus from her husband, who returned to Kampala after being treated for CCHF in Juba, South Sudan.

History

A case reported in the 12th century of a hemorrhagic disease from what is now Tajikistan may have been the first known case of Crimean–Congo hemorrhagic fever. Soviet scientists first identified the disease they called Crimean hemorrhagic fever in 1944 and established its viral etiology by passage of the virus through human "volunteers" (fatality rate unreported), but were unable to isolate the agent at that time. In June 1967, Soviet virologist Mikhail Chumakov registered an isolate from a fatal case that occurred in Samarkand (on the ancient Silk Road in Central Asia, not the Crimea) in the Catalogue of Arthropod-borne Viruses.

Four months earlier, virologists Jack Woodall, D Simpson and others had published initial reports on a virus they called the Congo virus, first isolated in 1956 by physician Ghislaine Courtois, head of the Provincial Medical Laboratory, Stanleyville, Belgian Congo. Strain V3010, isolated by Courtois, was sent to the Rockefeller Foundation Virus Laboratory (RFVL) in New York City and found to be identical to another strain from Uganda, but to no other named virus at that time. Chumakov later sent his strain to the RFVL, where it was found to be identical to the Congo virus.

The International Committee on Taxonomy of Viruses proposed the name Congo–Crimean hemorrhagic fever virus, but the Soviets insisted on Crimean–Congo hemorrhagic fever virus. Against all principles of scientific nomenclature based on priority of publication, it was adopted as the official name in 1973 in possibly the first instance of a virus losing its name to politics and the Cold War.^{[citation needed]} However, since then Congo–Crimean or just Congo virus has been used in many reports, which would be missed in searches of medical databases using the official name. These reports include records of the occurrence of the virus or antibodies to the virus from Greece, Portugal, South Africa, Madagascar (the first isolation from there), the Maghreb, Dubai, Saudi Arabia, Kuwait and Iraq.

External links

• Ergönül O. (2006). "Crimean–Congo haemorrhagic fever". Lancet Infect Dis 6 (4): 203–214. doi:10.1016/S1473-3099(06)70435-2. PMID 16554245. 
• World Health Organization Fact Sheet