Beware of Bat Caves! Marburg Hemorrhagic Fever in a Traveler

Abstract & Commentary

By John C. Christenson, MD, and Philip R. Fischer, MD, DTM&H

Dr. Christenson is Director, Ryan White Center for Pediatric Infectious Disease, Professor of Clinical Pediatrics, Indiana University School of Medicine, Director, Pediatric Travel Medicine Clinic, Riley Hospital for Children, Indianapolis. Dr. Fischer is Professor of Pediatrics, Department of Pediatric & Adolescent Medicine, Mayo Clinic, Rochester, MN.

Dr. Christenson and Dr. Fischer report no financial relationships relevant to this field of study.

Synopsis: Following a visit to a bat cave in Uganda, a woman developed Marburg hemorrhagic fever in Colorado. Exposures in and near bat caves have been linked to a variety of infections.

Source: CDC. Imported case of Marburg hemorrhagic fever — Colorado, 2008. MMWR 2009;58:1377-1381.

A 44-year-old Colorado woman developed severe headaches, chills, nausea, and diarrhea in January 2008, three days after returning from a two-week safari trip to Uganda. Self-medication for traveler's diarrhea with ciprofloxacin did not improve her symptoms. Two to three days into her illness, she had a low white blood cell count of 900/µL. Diarrhea persisted, accompanied by abdominal pain. Worsening fatigue, generalized weakness, paleness, and confusion ensued. Laboratory assays demonstrated evidence of hepatitis with an aspartate aminotransaminase of 9,660 U/dL and alanine aminotransferase of 4,823 U/dL. Renal dysfunction also was present with a creatinine of 2.3 mg/dL. Because of her continued illness and acute hepatitis, she was admitted to a local community hospital. She was afebrile on admission. She received IV fluid replacement as well as doxycycline for possible leptospirosis. Her clinical course was characterized by pancytopenia, coagulopathy, myositis, pancreatitis, and encephalitis. Testing for hepatitis viruses, malaria, leptospirosis, arboviruses, schistosomiasis, and rickettsial pathogens was unrevealing. Testing for viral hemorrhagic fever viruses including Marburg and Ebola also was negative. An early convalescent serum collected 10 days into her illness (January 14) and sent to the Centers for Disease Control and Prevention (CDC) failed to demonstrate evidence of Marburg virus (MARV) infection by virus isolation, antigen-detection, or anti-MARV immunoglobulin M and IgG. She was discharged 15 days into her illness. Her convalescence over the following year was characterized by persistent abdominal pain, fatigue, and confusion. No chronic hepatic or renal dysfunction was documented.

Six months after her initial presentation, the patient requested repeat testing for MARV after learning of a fatal case of Marburg hemorrhagic fever in a Dutch tourist who had visited Python Cave in Uganda as she did. She had visited the cave 10 days prior to the onset of symptoms. A serum specimen collected in July 2008 tested positive for anti-MARV IgG antibodies. An archived serum specimen obtained at day 10 of illness was retested using a nested reverse transcriptase polymerase chain reaction (RT-PCR), confirming the presence of MARV RNA fragments.

The traveler reported spending approximately 15-20 minutes in the cave and recalls seeing bats flying overhead. She denied any direct contact with bats or sustaining any injury inside the cave. However, she touched guano-covered rocks while climbing into the cave and she could not rule out the possibility of touching her mouth and nose once inside the cave. An investigation of the eight tour companions of the patient, and an additional 260 contacts, failed to detect any additional cases. Her spouse remained infection-free. Serum specimens from six out of eight tour companions were tested. None had evidence of prior MARV infection. The case represents the first imported filoviral hemorrhagic fever documented in the United States.

Commentary

Marburg hemorrhagic fever presents as an acute febrile illness that progresses to its severe hemorrhagic manifestations within one week. The incubation period varies between 2-21 days. Fever, chills, headaches, and myalgias are observed initially. On about the fifth day of the illness, a maculopapular exanthem may be observed and usually is followed by nausea, vomiting, chest pain, sore throat, abdominal pain, and diarrhea. Gradually it progresses to its more severe manifestations of jaundice, pancreatitis, delirium, shock, liver failure, and massive hemorrhaging or multi-organ dysfunction.1 Mortality rates have varied between 25% and 80%. In an outbreak in Angola in 2005, 117 of 124 identified cases were fatal.2 Seventy-five percent of these occurred in children younger than 5 years of age. At the time of this outbreak, an environmental reservoir for MARV was still unknown. However, human-to-human spread was suspected in most cases through direct contact with infected body fluids such as blood, saliva, and urine. The risk for person-to-person transmission of hemorrhagic fever viruses tends to be highest in the later stages of the illnesses, which are characterized by vomiting, diarrhea, shock, and hemorrhaging.

The earliest outbreak of MARV infection occurred in Marburg and Frankfurt in 1968, where laboratory workers were exposed to infected tissue from monkeys imported from Uganda.3 Years later, Egyptian fruit bats (Rousettus aegyptiacus) collected from caves in Uganda4 and Gabon5 were found to be a major natural reservoir for MARV. A large outbreak from 1998 to 2000 in a gold mine in Durba, located in the northeastern Demographic Republic of Congo, implicated bats as the source of the virus.6A general village cross-sectional antibody prevalence survey, performed in a location with confirmed transmission of MARV in that country, found that working in a mine was associated with a positive antibody result.7

In the past decade, bats have been identified as a natural reservoir host for multiple viruses such as coronavirus-SARS, Ebola, Hendra, and Nipah. Before these, they were well-recognized reservoirs for rabies and European and Australian bat lyssaviruses.8,9 In a recently published paper, Becquart and associates found that seroprevalance of Zaire ebolavirus was 15.3% among residents of rural communities in Gabon.10 The seroprevalence was highest in forested areas, suggesting that humans were exposed while handling and consuming fruit contaminated by bat saliva. Bat-associated histoplasmosis can be transmitted at cave entrances as well as within caves harboring bats.11

As previously mentioned, an additional case of MARV hemorrhagic fever occurred in a tourist from the Netherlands who visited the same cave as the traveler described above.12 During his visit, bats were flying around in the cave and bumping against the visitors. A large amount of droppings was on the ground. No reported bites or contact with any pre-existing wounds were reported. Python Cave is known for its colony of Egyptian fruit-eating bats. Travelers should be counseled about these risks. Recent international travel, especially to regions around the world such as Africa, South America, and Asia, clearly has the potential for importation of zoonotic pathogens such as hemorrhagic fever viruses including both Lassa fever and Ebola virus into the United States. In 2004, a businessman died of Lassa fever in New Jersey. He acquired his infection while traveling between Liberia and Sierra Leone.13 A large outbreak of Ebola virus infection among non-human primates was recognized in Virginia in 1989.14 From these experiences in the United States and other countries, the CDC issued guidelines for the prompt recognition and implementation of methods to prevent secondary cases in the US.15 Travelers should be advised to avoid high-risk activities such as visiting caves and contact with animals, especially non-human primates and bats.

While person-to-person transmission of viral hemorrhagic fevers is rare, clinicians must be attentive to manifestations of the diseases, especially in travelers returning from endemic countries. In most cases, the diagnoses of viral hemorrhagic fevers are accomplished late or in retrospect, resulting in the exposure of multiple medical staff and other individuals.

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