J-LSMS 2018 | Archive | Issues 1 to 4

JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY

Old World TBEVs

The Old World TBEVs remain common causes of permanent neurologic morbidity from Scandinavia to Eastern Japan, with more than 10,000 cases reported per year, a third of which result in permanent neurologic deficits. 2 In addition to tick bites, the OldWorldTBEVs may occasionally be transmitted by ingestion of unpasteurized milk products from viremic livestock (especially goats), breast-feeding, and slaughter of viremic animals. 2 Old World TBEV is typically biphasic in over 70% of cases, with an initial febrile flulike presentation followed by a 1-week (range, 1-21 days) asymptomatic interval. 2 This honeymoon or recovery period is followed by meningoencephalitis with CSF pleocytosis, with or without myelitis, and a poliomyelitis-like flaccid paralysis that targets the arms, neck, and shoulders. 2 Magnetic resonance imaging and electroencephalographic abnormalities are common, but very nonspecific. Other acute neurologic complications may include altered consciousness, seizure activity, cranial nerve palsies, and an often fatal bulbar syndrome with cardiorespiratory failure. Because no specific treatments other than supportive therapy exist, tick avoidance and immunization remain the best preventive measures. Effective vaccines have now been developed for the three subtypes of OldWorld TBEVs (TBEV-Sib in Russia and the Middle East, TBEV-FE in China and the Far East, and CCHF in Bulgaria), and some have been shown to even provide cross-protection among the subtypes in experimentally infected animals. 2 The tickborne hemorrhagic fever (TBHF) viruses are maintained in nature in extensive wild and domestic animal reservoirs and are transmitted by infected ixodid tick bites, squashing infected ticks, creating infective aerosols, direct contact with blood or tissues from infected animals or humans, or nosocomial spread by infective secretions among medical personnel (Table 2). 7 TBHFs are usually caused by either flaviviruses or bunyaviruses, which are distributed throughout Eastern Europe, Africa, and Asia. In 2014, a previously unidentified tickborne thogotovirus causing a TBHF syndrome (Family Orthomyxoviridae) was described in the U.S. in a healthy man in eastern Kansas with a history of fever, fatigue, and treatment with doxycycline for a presumed tickborne illness. 8 He later died from a critical illness characterized by high fever, thrombocytopenia, leukopenia, and multi-organ failure. 8 The thogogotovirus was phylogenetically distinct from Heartland virus (Family Bunyaviridae) and was named Bourbon virus after the patient’s county of residence in Kansas. 8 The tick vector was subsequently identified as the lone star tick, Amblyomma americanum (Figure 2). The TBHFs are characterized clinically by biphasic illnesses that present as febrile flulike symptoms and end as hepatomegaly with liver failure and hemorrhagic manifestations (petechiae, purpura, subconjunctival and pharyngeal hemorrhage, thrombocytopenia, cerebralhemorrhage, severe intrapulmonary hemorrhage, disseminated intravascular coagulation) separated by a few afebrile, nearly asymptomatic days. CFRs range from

Figure 2: Amblyomma americanum, the Lone Star tick, questing for a host. Shown is the dorsal view of a female Lone Star tick, the vector of southern tick-associated rash illness (STARI) caused by the spirochete Borrelia lonestari and the Bourbon virus caused by an unnamed thogotovirus. Note the “lone star” mark in the center of the dorsal surface. (From Centers for Disease Control and Prevention [CDC], Atlanta, GA. Public Health Image Library, image 8683.) 10% to over 50%, with most deaths occurring within 5-14 days of symptom onset during hemorrhagic stages. Diagnoses may be confirmed by immunologic techniques, such as antibody increases in paired sera and ELISA, and by molecular techniques, such as real-time reverse transcriptase polymerase chain reaction assay (r (RT)-PCR). Although ribavirin can inhibit Crimean-Congo hemorrhagic fever (CCHF) virus replication in animal models, it has not been tested in clinical trials in humans with CCHF. Nevertheless, if TBHF is suspected in the tropics, Eastern Europe, or the Middle East and laboratory confirmation is unavailable, intravenously administered ribavirin (30 mg/kg initially, followed by 16 mg/kg four times daily for four days, and then 8 mg/kg three times daily for six days) is recommended for severe cases, and oral ribavirin is recommended for high-risk contacts. 9,10 All patients with TBHFs should be placed in strict isolation, and strict universal precautions, including personal protective equipment, should be practiced by all medical personnel as fatal nosocomial transmission has been reported most likely by the generation of infectious aerosols during bag-valve-

50 J La State Med Soc VOL 170 MARCH/APRIL 2018

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