Chapter 3Infectious Diseases Related To Travel
Viral Hemorrhagic Fevers
Pierre E. Rollin
Viral hemorrhagic fevers (VHFs) are caused by several families of enveloped RNA viruses: filoviruses (Ebola and Marburg viruses), arenaviruses (Lassa fever, Lujo, Guanarito, Machupo, Junin, Sabia, and Chapare viruses), bunyaviruses (Rift Valley fever [RVF], Crimean-Congo hemorrhagic fever [CCHF], and hantaviruses), and flaviviruses (dengue, yellow fever, Omsk hemorrhagic fever, Kyasanur Forest disease, and Alkhurma viruses) (see the Dengue Fever and Yellow Fever sections in this chapter).
MODE OF TRANSMISSION
Some VHFs are spread person to person through direct contact with symptomatic patients, body fluids, or cadavers or through inadequate infection control (filoviruses, arenaviruses, CCHF virus). Zoonotic spread includes the following:
- Livestock via slaughter or consumption of raw milk or meat from infected animals (CCHF, RVF, Alkhurma viruses)
- Bushmeat, likely via slaughter or consumption of infected animals (Ebola, Marburg viruses)
- Rodent (arenaviruses, hantaviruses) via inhalation of or contact with materials contaminated with rodent excreta
- Other reservoir species, such as bats (Ebola, Marburg viruses)
- Vectorborne transmission also occurs via mosquito (RVF virus) or tick (CCHF, Omsk, Kyasanur Forest disease, Alkhurma viruses) bites or by crushing ticks
The viruses that cause VHF are distributed over much of the globe. Each virus is associated with 1 or more nonhuman host or vector species, restricting the virus and the initial contamination to the areas inhabited by these species. The diseases caused by these viruses are seen in people living in or having visited these areas. Humans are incidental hosts for these enzootic diseases; however, person-to-person transmission of some viruses can result in large human outbreaks. Specific viruses are addressed below.
Ebola and Marburg: Filoviral Diseases
Ebola and Marburg viruses cause hemorrhagic fever in humans and nonhuman primates. Five species of Ebola virus have been identified: Côte d’Ivoire, Sudan, Zaire, Bundibugyo, and Reston. Ebola-Reston has not been shown to cause human disease. These diseases occur in tropical regions in Africa. Countries with confirmed human cases of Ebola hemorrhagic fever include Republic of the Congo, Côte d’Ivoire, Democratic Republic of the Congo, Gabon, Sudan, and Uganda. Countries with confirmed human cases of Marburg hemorrhagic fever include Uganda, Kenya, Democratic Republic of the Congo, Angola, and possibly Zimbabwe. Growing evidence indicates that fruit bats are the natural reservoir for filoviruses. Outbreaks occur when a person becomes infected after exposure to the reservoir species or an infected nonhuman primate and then transmits the virus to other people in the community.
Four cases of Marburg hemorrhagic fever have occurred in travelers visiting caves harboring bats, including Kitum cave in Kenya and Python cave in Maramagambo Forest, Uganda. Miners have also acquired Marburg infection from working in underground mines harboring bats in the Democratic Republic of the Congo and Uganda.
Lassa Fever and Other Arenaviral Diseases
Arenaviruses are transmitted from rodents to humans, except Tacaribe virus, which is found in bats. Most infections are mild, but some result in hemorrhagic fever with high death rates. Old World (Eastern Hemisphere) and New World (Western Hemisphere) viruses cause the following diseases:
- Old World viruses: Lassa virus (Lassa fever), Lymphocytic choriomeningitis virus (meningitis, encephalitis, and congenital fetal infection in normal hosts, hemorrhagic fever in organ transplant recipients). Lassa fever occurs in rural West Africa, with hyperendemic areas in Sierra Leone, Guinea, Liberia, and Nigeria. Lujo virus has been recently described in Zambia and the Republic of South Africa during a nosocomial outbreak.
- New World viruses: Junin (Argentine hemorrhagic fever), Machupo (Bolivian hemorrhagic fever), Guanarito (Venezuelan hemorrhagic fever), Sabia (Brazilian hemorrhagic fever), and the recently discovered Chapare virus (single case in Bolivia).
Reservoir host species are New World rats and mice (family Muridae, subfamily Sigmodontinae) and Old World rats and mice (family Muridae, subfamily Murinae). These rodent types are found worldwide, including Europe, Asia, Africa, and the Americas. Virus is transmitted through inhalation of aerosols from rodent urine, ingestion of rodent-contaminated food, or direct contact of broken skin with rodent excreta. Risk of Lassa virus infection is associated with peridomestic rodent exposure. Inappropriate food storage increases the risk for exposure. Nosocomial transmission of Lassa, Lujo, and Machupo viruses has occurred through droplet and contact. One anecdotal report of possible airborne transmission exists. Several cases of Lassa fever have been confirmed in international travelers living in traditional dwellings in the countryside.
Rift Valley Fever and Other Bunyaviral Diseases
RVF causes fever, hemorrhage, encephalitis, and retinitis in humans, but primarily affects livestock. RVF is endemic to sub-Saharan Africa. Sporadic outbreaks have occurred in humans in Egypt, Madagascar, and Mauritania. Large epidemics occurred in Kenya, Somalia, and Tanzania in 1997–1998 and 2006–2007, Saudi Arabia and Yemen in 2000, Madagascar in 2008, and South Africa in 2010. RVF virus is transmitted by mosquito, percutaneous inoculation, and slaughter or consumption of infected animals.
CCHF is endemic where ticks of the genus Hyalomma are found in Africa and Eurasia, including South Africa, the Balkans, the Middle East, Russia, and western China, and is highly endemic in Afghanistan, Iran, Pakistan, and Turkey. CCHF virus is transmitted to humans by infected ticks or direct handling and preparation of fresh carcasses of infected animals, usually domestic livestock. Nosocomial transmission often occurs.
Hantaviruses cause hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS). The viruses that cause HPS are present in the New World; those that cause HFRS occur worldwide. The viruses that cause both HPS and HFRS are transmitted to humans through contact with urine, feces, or saliva of infected rodents. Travelers staying in rodent-infested dwellings are at risk for HPS and HFRS. Human-to-human transmission has been reported only with Andes virus in Chile and Argentina.
Signs and symptoms vary by disease, but in general, patients with VHF present with abrupt onset of fever, myalgias, and prostration, followed in severe forms by coagulopathy with a petechial rash or ecchymoses and sometimes overt bleeding. Vascular endothelial damage leads to shock and pulmonary edema, and liver injury is common. Signs seen with specific viruses include renal failure (HFRS), ecchymoses (CCHF), hearing loss, anasarca and shock in newborns (Lassa fever), and spontaneous abortion (Lassa and lymphocytic choriomeningitis viruses). Because the incubation period may be as long as 21 days, patients may not develop illness until returning from travel; therefore, a thorough travel and exposure history is critical.
US-based clinicians should notify CDC’s Viral Special Pathogens Branch immediately of any suspected cases of VHF occurring in patients residing in or requiring evacuation to the United States: 404-639-1115 or the CDC Emergency Operations Center at 770-488-7100 after hours. CDC also provides consultation for international clinicians and health ministries. Whole blood or serum may be tested for virologic (RT-PCR, antigen detection, virus isolation) and immunologic (IgM, IgG) evidence of infection. Tissue may be tested by immunohistochemistry, RT-PCR, and virus isolation. Postmortem skin biopsies fixed in formalin and blood collected within a few hours after death by cardiac puncture can be used for diagnosis. Samples should be sent for testing to a reference laboratory with biosafety level 3 and 4 capability.
Ribavirin is effective for treating Lassa fever, New World arenaviruses, and likely CCHF, but it is not approved by the Food and Drug Administration (FDA) for these indications. Convalescent-phase plasma is effective in treating Argentine hemorrhagic fever. Intravenous ribavirin can be obtained for compassionate use through FDA from Valeant Pharmaceuticals (Aliso Viejo, California). Requests should be initiated by the provider through FDA (301-443-1240), with simultaneous notification to Valeant: 800-548-5100, extension 5 (domestic telephone) or 949-461- 6971 (international telephone). The process is explained on FDA’s website (http://www.fda.gov/ Drugs/DevelopmentApprovalProces...).
PREVENTIVE MEASURES FOR TRAVELERS
The risk of acquiring VHF is very low for international travelers. Travelers at increased risk for exposure include those engaging in animal research, health care workers, and others providing care for patients in the community, particularly where outbreaks of VHF are occurring.
Prevention should focus on avoiding contact with host or vector species. Travelers should not visit locations where an outbreak is occurring. Contact with rodents should be avoided. Travelers should avoid contact with livestock in RVF- and CCHF-endemic areas, and they should use insecticide-treated bed nets and insect repellent to prevent vectorborne disease.
Standard precautions and contact and droplet precautions for suspected VHF case-patients are recommended to avoid transmission. Direct contact should be avoided with corpses of patients suspected of having died of Ebola, Marburg, or Old World arenavirus infection. Contact with or consumption of primates, bats, and other bushmeat should be avoided. Bat-inhabited caves or mines should be avoided. Investigational vaccines exist for Argentine hemorrhagic fever and RVF; however, neither is approved by FDA or commonly available in the United States.
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