Infectious Diseases

Hanta virus, California Encephalitis (CE)

OVERVIEW: What every clinician needs to know

Pathogen name and classification

California encephalitis (CE) and hanta virus cardiopulmonary syndrome (HCPS) are both caused by zoonotic viruses that belong to the Bunyaviridae family. La Crosse encephalitis virus (LACV), which belongs to genus orthobunyavirus, is the causative agent of CE. Sin Nombre virus (SNV), a member of the hantavirus genus, is the major cause of HCPS in North America. Both viruses are 90-100 nm in diameter, spherical negative-stranded, tri-segmented RNA viruses.

What is the best treatment?

No specific antiviral therapies are currently available for treating LACV and SNV infections. Treatment relies solely on hospitalization and supportive care until the virus is cleared by the immune system. Treatment of convulsions is necessary if they arise in CE. Ribavirin is a broad-spectrum antiviral drug that has been shown to inhibit hantavirus replication both in vitro and in vivo. However, clinical trial data are still lacking.

How do patients contract this infection, and how do I prevent spread to other patients?

CE: CE is an arboviral disease transmitted from intermediate rodent hosts (e.g., wild rabbits, chipmunks, and squirrels) by the bite of infected tree-hole mosquitoes (Aedes triseriatus). The rodent hosts show no clinical symptoms and act as amplifiers of the virus. The virus is maintained in the mosquito population through trans-ovarian transmission.

  • It is primarily a disease of children and rarely seen in adults.

  • Humans are accidental dead-end hosts, as they don't develop enough virus titers in their bloodstream to infect feeding mosquitoes. No person-to-person transmission has been recorded.

  • CE is a seasonal, summertime illness that occurs mainly during July-October, when the mosquito vector is most active.

  • According to the Centers for Disease Control and Prevention (CDC), 80-100 cases are reported every year. Most cases in the United States were reported in the rural areas of the upper Midwestern, mid-Atlantic, and southeastern states.

  • Forest workers and hikers are at the greatest risk of acquiring the infection.

  • HCPS: Unlike many other members of the Bunyaviridae family, hantaviruses are not transmitted by biting insects. Human infection occurs accidentally by inhalation of dust contaminated by droppings, urine, or saliva from infected rodents (deer mice in the case of SNV). Rodents are the main natural reservoir in which the virus can establish asymptomatic persistent infection. Within rodents, the disease is transmitted horizontally, mainly through aggressive behavior, such as biting and scratching.

  • It is mainly a rural disease associated with the risk factors of farming, hunting, and camping, because these activities bring humans into close contact with the rodent reservoirs.

  • Human-to-human transmission is very rare and was reported only in an outbreak that occurred in Argentina.

  • Approximately, 300 cases of HCPS are reported each year in North and South America.

What host factors protect against this infection?

  • Currently, no FDA-approved vaccine is available in the United States for immunization against LACV or SNV infections. Avoiding mosquito bites during occupational or recreational activities in wooded areas can reduce CE infections.

What are the clinical manifestations of infection with this organism?

  • CE: It is typically a disease of children, but all ages are susceptible. In adults, the infection is always asymptomatic or cause benign febrile illness that resolves within few days. The disease occurs mainly in children younger than 16 years of age. The clinical picture ranges from mild aseptic meningitis to severe encephalitis. The incubation period ranges from 5 to 15 days. Mild cases usually show non-specific symptoms with fever lasting 2-3 days, chills, headache, and lethargy. Gastrointestinal (GI) manifestations are common, including anorexia, nausea, and vomiting. The neuro-invasive disease is characterized by neurological symptoms, such as seizures, tremors, and convulsions. Meningitis, encephalitis, flaccid paralysis, and coma can also occur.

  • HCPS: The incubation period for HCPS ranges from 9 to 33 days. The prodromal phase of illness usually lasts 3-6 days and is characterized by flu-like symptoms, such as fever, headache, chills, and muscle pain. Abdominal pain, nausea, vomiting, and dizziness can also occur. This phase usually progresses rapidly to severe respiratory disease characterized by non-productive cough and dyspnea. This bilateral pulmonary edema is usually visible in chest X-rays. Thrombocytopenia, hemoconcentration, and leukocytosis are the most prominent hematologic findings.

What common complications are associated with infection with this pathogen?

  • CE: The total duration of illness rarely exceeds 10-14 days, and most patients with clinical symptoms recover completely. Approximately 10% of children may develop neurological sequelae after recovery with cognitive and behavioral abnormalities that may affect future school performance. Death can occur in less than 1% of severe cases because of brain herniation.

  • HCPS: Rapid deterioration, cardiac insufficiency, and respiratory failure caused by edema and hypotension, shock, and death can occur within 2-10 days after the onset of illness in almost 50% of cases. Patients who survive the acute phase recover within 5-7 days.

How should I identify the organism?

  • CE: Clinical and epidemiological history should be taken into consideration when diagnosis is made. IgM antibodies are detectable 2-8 days after the onset of illness. LACV IgM capture enzyme-linked immunosorbent assay (ELISA) is commercially available and is the most widely used diagnostic method. A positive IgM test from serum or cerebrospinal fluid (CSF) samples should be further confirmed by a four-fold or greater rise in neutralizing IgG antibody titers between serum samples collected during the acute and convalescent phases of illness. During the acute phase, viral nucleic acid can be detected by polymerase chain reaction (PCR) in blood or CSF samples.

  • HCPS: Diagnosis of hantavirus in the clinic relies on the establishment of a history of rodent exposure, symptoms suggestive of respiratory involvement, blood exams showing severe thrombocytopenia, and positive serological tests. High titers of IgM and IgG antibodies are detectable in the sera of patients during the acute phase of the disease. The most widely used serological tests for diagnosing HCPS are IgM capture and IgG indirect ELISAs. A prototype rapid immunoblot test for SNV is also available. PCR is useful for detecting viral RNA in blood samples collected during the acute phase of illness.

How does this organism cause disease?

  • Most of the neurological symptoms of CE are the direct result of the involvement of the meningitis, rather than the CNS itself. The hallmark of hantavirus pathogens is capillary leakage. Vascular endothelial cells show increased permeability, which is believed to result from the intense host immune response to infection.

WHAT’S THE EVIDENCE for specific management and treatment recommendations?

Hussein, IT, Haseeb, A, Haque, A, Mir, MA. "Recent advances in hantavirus molecular biology and disease". Adv Appl Microbiol. vol. 74. 2011. pp. 35-75.

Mir, MA. "Hantaviruses". Clin Lab Med. vol. 30. 2010. pp. 67-91.

Rust, RS, Thompson, WH, Matthews, CG, Beaty, BJ, Chun, RWM. "Topical review: La Crosse and other forms of California encephalitis". J Child Neurol. vol. 14. 1999. pp. 1-14.

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