Crimean-Congo hemorrhagic fever

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Ilan Dock, B.S.

Overview

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 the majority of infected mammals, but commonly severe in infected humans, with a 30% mortality rate. Outbreaks of illness are usually attributed to handling the bodily fluids of infected animals or people.

Differentiating Crimean-Congo Hemorrhagic Fever from other Diseases

Crimean-Congo hemorrhagic fever should be differentiated from the following diseases:

Disease		Organism	Vector	Symptoms
Bacterial Infection
Borreliosis (Lyme Disease)		Borrelia burgdorferi sensu lato complex and B. mayonii	I. scapularis, I. pacificus, I. ricinus, and I. persulcatus	Erythema migrans, flu-like illness(fatigue, fever), Lyme arthritis, neuroborreliosis, and carditis.
Relapsing Fever	Tick-borne relapsing fever (TBRF):	Borrelia duttoni, Borrelia hermsii, and Borrelia parkerii	Ornithodoros species	Consistently documented high fevers, flu-like illness, headaches, muscular soreness or joint pain, altered mental status, painful urination, rash, and rigors.
	Louse-borne relapsing fever (LBRF) :	Borrelia recurrentis	Pediculus humanus
Typhus (Rickettsia)
Rocky Mountain Spotted Fever		Rickettsia rickettsii	Dermacentor variabilis, Dermacentor andersoni	Fever, altered mental status, myalgia, rash, and headaches.
Helvetica Spotted Fever		Rickettsia helvetica	Ixodes ricinus	Rash: spotted, red dots. Respiratory symptoms (dyspnea, cough), muscle pain, and headaches.
Ehrlichiosis (Anaplasmosis)		Ehrlichia chaffeensis, Ehrlichia ewingii	Amblyomma americanum, Ixodes scapularis	Fever, headache, chills, malaise, muscle pain, nausea, confusion, conjunctivitis, or rash (60% in children and 30% in adults).
Tularemia		Francisella tularensis	Dermacentor andersoni, Dermacentor variabilis	Ulceroglandular, glandular, oculoglandular, oroglandular, pneumonic, typhoidal.
Viral Infection
Tick-borne meningoencephalitis		TBEV virus	Ixodes scapularis, I. ricinus, I. persulcatus	Early Phase: Non-specific symptoms including fever, malaise, anorexia, muscle pains, headaches, nausea, and vomiting. Second Phase: Meningitis symptoms, headache, stiff neck, encephalitis, drowsiness, sensory disturbances, and potential paralysis.
Colorado Tick Fever		CTF virus	Dermacentor andersoni	Common symptoms include fever, chills, headache, body aches, and lethargy. Other symptoms associated with the disease include sore throat, abdominal pain, vomiting, and a skin rash. A biphasic fever is a hallmark of Colorado Tick Fever and presents in nearly 50% of infected patients.
Crimean-Congo Hemorrhagic Fever		CCHF virus	Hyalomma marginatum, Rhipicephalus bursa	Initially infected patients will likely feel a few of the following symptoms: headache, high fever, back and joint pain, stomach pain, vomiting, flushed face, red throat petechiae of the palate, and potentially changes in mood as well as sensory perception.
Protozoan Infection
Babesiosis		Babesia microti, Babesia divergens, Babesia equi	Ixodes scapularis, I. pacificus	Non-specific flu-like symptoms.

Epidemiology

• 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.
• On July 28, 2005 authorities reported 41 cases of CCHF in Turkey's Yozgat Province, with one death.

Endemic Regions

• Endemic areas include Asia, Eastern Europe, the Middle East, a belt across central Africa and South Africa and Madagascar.
• Main environmental reservoir for the virus are small mammals (particularly European hare, Middle-African hedgehogs and multimammate rats).

Notable outbreaks

• During the summers of 1944 and over 200 cases of an acute, hemorrhagic, febrile illness occurred in Soviet troops rescuing the harvest following the ethnic cleansing of the Crimean Tatars.
• Virus was discovered in blood samples of patients and in the tick Hyalomma marginatum marginatum.
• Researchers soon recognized that a similar disease had been occurring in the Central Asian Republics.

Causes

Life Cycle and Spread of Disease

General Tick Life Cycle

This image displays an example of the tick lifecycle, based on stages and the months that they are most likely to occur during.

• A tick's life cycle is composed of four stages: hatching (egg), nymph (six legged), nymph (eight legged), and an adult.
• Ticks require blood meal to survive through their life cycle.
• Hosts for tick blood meals include mammals, birds, reptiles, and amphibians. Ticks will most likely transfer between different hosts during the different stages of their life cycle.
• Humans are most often targeted during the nymph and adult stages of the life cycle.
• Life cycle is also dependent on seasonal variation.
• Ticks will go from eggs to larva during the summer months, infecting bird or rodent host during the larval stage.
• Larva will infect the host from the summer until the following spring, at which point they will progress into the nymph stage.
• During the nymph stage, a tick will most likely seek a mammal host (including humans).
• A nymph will remain with the selected host until the following fall at which point it will progress into an adult.
• As an adult, a tick will feed on a mammalian host. However unlike previous stages, ticks will prefer larger mammals over rodents.
• The average tick life cycle requires three years for completion.
  • Different species will undergo certain variations within their individual life cycles.

Spread of Tick-borne Disease

• Ticks require blood meals in order to progress through their life cycles.
• The average tick requires 10 minutes to 2 hours when preparing a blood meal.
• Once feeding, releases anesthetic properties into its host, via its saliva.
• A feeding tube enters the host followed by an adhesive-like substance, attaching the tick to the host during the blood meal.
• A tick will feed for several days, feeding on the host blood and ingesting the host's pathogens.
• Once feeding is completed, the tick will seek a new host and transfer any pathogens during the next feeding process.

Virology

• Nairovirus in the family of Bunyaviridae.

Transmission

• Ixodid ticks, of the Hyalomma genus, are the primary vector and reservoir of infection.
• Human transmission occurs through human contact with infected animal or human blood and body fluids.

History and Symptoms

Isolated male patient diagnosed with Crimean-Congo hemorrhagic fever

• 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: 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 recover after 9–10 days from symptom onset, but 30% die in the second week of illness.

Laboratory diagnostics

• ELISA, RT-PCR, antibody titers, immunohistochemical staining, and virus isolation attempts are all laboratory tests to assist in the diagnosis of a potential Crimean-Congo hemorrhagic fever.
• An ELISA may be used for diagnosis during the acute phase of infection.
• Polymerase Chain Reaction may be used to identify viral RNA sequences in the blood or tissues collected.

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.

Risk Factors

Endemic Areas

• Travelling through endemic areas increase the risk of infection.
• Endemic areas include Asia, Eastern Europe, the Middle East, a belt across central Africa and South Africa and Madagascar.

Livestock

• Sheep, goats and cattle develop high titers of virus in blood, but tend not to fall ill.
• Transmission may occur through unprotected contact with blood and other body fluids of an infected animal.

Occupational

• The following individuals are at a higher risk of infection in endemic areas:
• Livestock workers
• Animal herders
• Slaughterhouse workers

Prevention

Limiting tick exposure

Tuck pants into socks

It is unreasonable to assume that a person can completely eliminate activities that may result in tick exposure. Therefore, prevention measures should emphasize personal protection when exposed to natural areas where ticks are present:

• Wear light-colored clothing which allows you to see ticks that are crawling on your clothing.
• Tuck your pants legs into your socks so that ticks cannot crawl up the inside of your pants legs.
• Apply repellents to discourage tick attachment. Repellents containing permethrin can be sprayed on boots and clothing, and will last for several days. Repellents containing DEET (n, n-diethyl-m-toluamide) can be applied to the skin, but will last only a few hours before reapplication is necessary. Use DEET with caution on children. Application of large amounts of DEET on children has been associated with adverse reactions.
• Conduct a body check upon return from potentially tick-infested areas by searching your entire body for ticks. Use a hand-held or full-length mirror to view all parts of your body. Remove any tick you find on your body.
• Parents should check their children for ticks, especially in the hair, when returning from potentially tick-infested areas.
• Ticks may also be carried into the household on clothing and pets and only attach later, so both should be examined carefully to exclude ticks.

Public health measures

• Where mammal and 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.

External links

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

Gallery

• 
  Isolated male patient diagnosed with Crimean-Congo hemorrhagic fever (C-CHF). From Public Health Image Library (PHIL).
• 
  Cytoarchitectural changes found in a liver tissue specimen extracted from a Congo/Crimean hemorrhagic fever patient (280X mag). From Public Health Image Library (PHIL).
• 
  Cytoarchitectural changes found in a liver tissue specimen extracted from a Congo/Crimean hemorrhagic fever patient (400X mag). From Public Health Image Library (PHIL).