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{{Encephalitis}}
{{Viral encephalitis}}
{{CMG}}; {{AE}} [[Priyamvada Singh|Priyamvada Singh, MBBS]] [mailto:psingh13579@gmail.com]; {{JS}}; {{AG}}
{{CMG}}; {{AE}} [[Priyamvada Singh|Priyamvada Singh, MBBS]] [mailto:psingh13579@gmail.com]; {{JS}}; {{AG}}


Revision as of 15:43, 4 February 2016

Viral encephalitis Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Priyamvada Singh, MBBS [2]; João André Alves Silva, M.D. [3]; Anthony Gallo, B.S. [4]

Overview

Empiric therapy for encephalitis includes Acyclovir and it should be administered to all patients with suspected encephalitis as early as possible to reduce the risk of neurologic sequelae. Doxycycline should be added to the empirical regimen if epidemiological or clinical clues suggest rickettsial or ehrlichial infection.[1] Despite the wide range of viruses that cause encephalitis, specific antiviral agents are generally limited to infections caused by the herpesviridae and human immunodeficiency virus (HIV). Treatment for other viral encephalitis is largely supportive.

Medical Therapy

General Considerations

  • Reliably tested specific antiviral agents are available only for a few viral agents (e.g. acyclovir or ganciclovir for herpes simplex virus and varicella-zoster encephalitis). Administer the first dose of acyclovir as soon as possible (in the emergency department itself). Acyclovir can be initiated with or without antibiotics or steroids.The advantages of an early antiviral drug administration are:
    • Decreases disease duration
    • Decreases development of latency
    • Decreases development of complications
    • Decreases recurrence
    • Decreases transmission from infected person
  • Treatment for Toxoplasma gondii and cytomegalovirus encephalitis are available but are used with limited success
  • Treatment is usually symptomatic. In patients who are very sick, supportive treatment, such as mechanical ventilation, is equally important.
  • Systemic complications like hypotension, shock, hypoxemia, electrolyte imbalances (hyponatremia, SIADH should be treated promptly.
  • Neuroimaging with MRI or CT scan should be done before lumbar puncture especially if raised intracranial pressure is suspected.
  • Lab tests like blood samples should be taken before initiation of therapy.
  • Bed rest, plenty of fluids and anti-inflammatory drugs to relieve headache and fever should be used.

Treatment for Increased Intracranial Pressure

General

  • Elevation of head end of the bed
  • Hyperventilation may be used to decrease intra-cranial pressure on emergency basis
  • Constant monitoring of neurological status
  • Avoid increase in intra cranial pressure i.e. control of straining and coughing
  • Antipyretics and analgesic for fever and pain.
  • Monitoring and preventing seizures and hypotension.

Drug Therapy

  • Furosemide 20 mg iv and mannitol 1 gm/kg intravenously for diuresis (blood pressure and CVP should be monitored while administrating these drugs)
  • Dexamethasone 10mg intravenously 6 hourly to decrease cerebral edema.

Encephalitis Drug Summary

Acyclovir

  • It is effective for HSV1, HSV2 and varicella zoster.
  • It is selectively taken up by the body cells infected with HSV and varicella zoster
  • Prompt treatment with acyclovir is useful in decreasing complications, latency and communicability
  • Side effects may include nausea, vomiting, diarrhea, loss of appetite, and muscle or joint pain. Rarely, serious adverse effects may include renal and liver functions abnormalities or suppression of bone marrow activity.

Foscarnet

  • It is effective against HSV 1, HSV 2 and CMV
  • It is useful in patients who have developed resistance or are non-responders against acyclovir for e.g. HIV positive patients
  • Drug dosage depends on the renal function of the patient as Foscarnet is excreted through kidneys.

Dexamethasone

  • It is used in post-infectious and disseminated encephalitis.
  • It may be used as an adjunct with the antiviral agents

Furosemide

  • It is used to in encephalitis associated with increased intracranial pressure. The mechanism of action is:
    • It decreases the production of CSF by inhibiting carbonic anhydrase enzymes
    • Decreases cerebral sodium uptake
    • Inhibits cellular membrane chloride pumps
  • The dose should be individualized for patients

Mannitol

  • Used only on short term basis.
  • The doses should be individualized based on renal function.

Lorazepam

  • It is used for treatment of seizures associated with encephalitis.

Antimicrobial Regimen

  • 1. Empiric antimicrobial therapy[2]
  • Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
  • Note (1): Acyclovir should be initiated in all patients with suspected encephalitis, pending results of diagnostic studies.
  • Note (2): Other empiric antimicrobial agents should be administered on the basis of specific epidemiologic or clinical clues.
  • 2. Specific epidemiologic considerations[2]
  • 2.1 Agammaglobulinemia — Enteroviruses, Mycoplasma pneumoniae
  • 2.2 Age
  • 2.2.1 Neonates — Herpes simplex virus type 2, cytomegalovirus, rubella virus, Listeria monocytogenes, Treponema pallidum, Toxoplasma gondii
  • 2.2.2 Infants and children — Eastern equine encephalitis virus, Japanese encephalitis virus, Murray Valley encephalitis virus, influenza virus, La Crosse virus
  • 2.2.3 Elderly persons — Eastern equine encephalitis virus, St. Louis encephalitis virus, West Nile virus, sporadic CJD, L. monocytogenes
  • 2.3 Animal contact
  • 2.3.1 Bats — Rabies virus, Nipah virus
  • 2.3.2 Birds — West Nile virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, Cryptococcus neoformans (bird droppings)
  • 2.3.3 Cats — Rabies virus, Coxiella burnetii, Bartonella henselae, T. gondii
  • 2.3.4 Dogs — Rabies virus
  • 2.3.5 Horses — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, Hendra virus
  • 2.3.6 Old World primates — B virus
  • 2.3.7 Raccoons — Rabies virus, Baylisascaris procyonis
  • 2.3.8 Rodents — Eastern equine encephalitis virus (South America), Venezuelan equine encephalitis virus, tickborne encephalitis virus, Powassan virus (woodchucks), La Crosse virus (chipmunks and squirrels), Bartonella quintana
  • 2.3.9 Sheep and goats — C. burnetii
  • 2.3.10 Skunks — Rabies virus
  • 2.3.11 Swine — Japanese encephalitis virus, Nipah virus
  • 2.3.12 White-tailed deer — Borrelia burgdorferi
  • 2.4 Immunocompromised persons — Varicella zoster virus, cytomegalovirus, human herpesvirus 6, West Nile virus, HIV, JC virus, L. monocytogenes, Mycobacterium tuberculosis, C. neoformans, Coccidioides species, Histoplasma capsulatum, T. gondii
  • 2.5 Ingestion
  • 2.5.1 Raw or partially cooked meat — T. gondii
  • 2.5.2 Raw meat, fish, or reptiles — Gnanthostoma species
  • 2.5.3 Unpasteurized milk — Tickborne encephalitis virus, L. monocytogenes, C. burnetii
  • 2.6 Insect contact
  • 2.6.1 Mosquitoes — Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, Murray Valley encephalitis virus, Japanese encephalitis virus, West Nile virus, La Crosse virus, Plasmodium falciparum
  • 2.6.2 Sandflies — Bartonella bacilliformis
  • 2.6.3 Ticks — Tickborne encephalitis virus, Powassan virus, Rickettsia rickettsii, Ehrlichia chaffeensis, Anaplasma phagocytophilum, C. burnetii (rare), B. burgdorferi
  • 2.6.4 Tsetse flies — Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense
  • 2.7 Occupation
  • 2.7.1 Exposure to animals — Rabies virus, C. burnetii, Bartonella species
  • 2.7.2 Exposure to horses — Hendra virus
  • 2.7.3 Exposure to Old World primates — B virus
  • 2.7.4 Laboratory workers — West Nile virus, HIV, C. burnetii, Coccidioides species
  • 2.7.5 Physicians and health care workers — Varicella zoster virus, HIV, influenza virus, measles virus, M. tuberculosis
  • 2.7.6 Veterinarians — Rabies virus, Bartonella species, C. burnetii
  • 2.8 Person-to-person transmission — Herpes simplex virus (neonatal), varicella zoster virus, Venezuelan equine encephalitis virus (rare), poliovirus, nonpolio enteroviruses, measles virus, Nipah virus, mumps virus, rubella virus, Epstein-Barr virus, human herpesvirus 6, B virus, West Nile virus (transfusion, transplantation, breast feeding), HIV, rabies virus (transplantation), influenza virus, M. pneumoniae, M. tuberculosis, T. pallidum
  • 2.9 Recent vaccination — Acute disseminated encephalomyelitis
  • 2.10 Recreational activities
  • 2.10.1 Camping/hunting — Agents transmitted by mosquitoes and ticks
  • 2.10.2 Sexual contact — HIV, T. pallidum
  • 2.10.3 Spelunking — Rabies virus, H. capsulatum
  • 2.10.4 Swimming — Enteroviruses, Naegleria fowleri
  • 2.11 Season
  • 2.11.1 Late summer/early fall — Agents transmitted by mosquitoes and ticks, enteroviruses
  • 2.11.2 Winter — Influenza virus
  • 2.12 Transfusion and transplantation — Cytomegalovirus, Epstein-Barr virus, West Nile virus, HIV, tickborne encephalitis virus, rabies virus, iatrogenic CJD, T. pallidum, A. phagocytophilum, R. rickettsii, C. neoformans, Coccidioides species, H. capsulatum, T. gondii
  • 2.13 Travel
  • 2.13.1 Africa — Rabies virus, West Nile virus, P. falciparum, T. brucei gambiense, T. brucei rhodesiense
  • 2.13.2 Australia — Murray Valley encephalitis virus, Japanese encephalitis virus, Hendra virus
  • 2.13.3 Central America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, P. falciparum, Taenia solium
  • 2.13.4 Europe — West Nile virus, tickborne encephalitis virus, A. phagocytophilum, B. burgdorferi
  • 2.13.5 India, Nepal — Rabies virus, Japanese encephalitis virus, P. falciparum
  • 2.13.6 Middle East — West Nile virus, P. falciparum
  • 2.13.7 Russia — Tickborne encephalitis virus
  • 2.13.8 South America — Rabies virus, Eastern equine encephalitis virus, Western equine encephalitis virus, Venezuelan equine encephalitis virus, St. Louis encephalitis virus, R. rickettsii, B. bacilliformis (Andes mountains), P. falciparum, T. solium
  • 2.13.9 Southeast Asia, China, Pacific Rim — Japanese encephalitis virus, tickborne encephalitis virus, Nipah virus, P. falciparum, Gnanthostoma species, T. solium
  • 2.13.10 Unvaccinated status — Varicella zoster virus, Japanese encephalitis virus, poliovirus, measles virus, mumps virus, rubella virus
  • 3. Specific clinical considerations[2]
  • 3.1 General findings
  • 3.1.1 Hepatitis — Coxiella burnetii
  • 3.1.2 Lymphadenopathy — HIV, Epstein-Barr virus, cytomegalovirus, measles virus, rubella virus, West Nile virus, Treponema pallidum, Bartonella henselae and other Bartonella species, Mycobacterium tuberculosis, Toxoplasma gondii, Trypanosoma brucei gambiense
  • 3.1.3 Parotitis — Mumps virus
  • 3.1.4 Rash — Varicella zoster virus, B virus, human herpesvirus 6, West Nile virus, rubella virus, some enteroviruses, HIV, Rickettsia rickettsii, Mycoplasma pneumoniae, Borrelia burgdorferi, T. pallidum, Ehrlichia chaffeensis, Anaplasma phagocytophilum
  • 3.1.5 Respiratory tract findings — Venezuelan equine encephalitis virus, Nipah virus, Hendra virus, influenza virus, adenovirus, M. pneumoniae, C. burnetii, M. tuberculosis, Histoplasma capsulatum
  • 3.1.6 Retinitis — Cytomegalovirus, West Nile virus, B. henselae, T. pallidum
  • 3.1.7 Urinary symptoms — St. Louis encephalitis virus
  • 3.2 Neurologic findings
  • 3.2.1 Cerebellar ataxia — Varicella zoster virus (children), Epstein-Barr virus, mumps virus, St. Louis encephalitis virus, Tropheryma whipplei, T. brucei gambiense
  • 3.2.2 Cranial nerve abnormalities — Herpes simplex virus, Epstein-Barr virus, Listeria monocytogenes, M. tuberculosis, T. pallidum, B. burgdorferi, T. whipplei, Cryptococcus neoformans, Coccidioides species, H. capsulatum
  • 3.2.3 Dementia — HIV, human transmissible spongiform encephalopathies (sCJD and vCJD), measles virus (SSPE), T. pallidum, T. whipplei
  • 3.2.4 Myorhythmia — T. whipplei (oculomasticatory)
  • 3.2.5 Parkinsonism — Japanese encephalitis virus, St. Louis encephalitis virus, West Nile virus, Nipah virus, T. gondii, T. brucei gambiense
  • 3.2.6 Poliomyelitis-like flaccid paralysis — Japanese encephalitis virus, West Nile virus, tickborne encephalitis virus; enteroviruses (enterovirus-71, coxsackieviruses), poliovirus
  • 3.2.7 Rhombencephalitis — Herpes simplex virus, West Nile virus, enterovirus 71, L. monocytogenes
  • 4. Pathogen-directed antimicrobial therapy[2]
  • 4.1 Viruses
  • 4.1.1 Adenovirus
  • Preferred regimen: supportive
  • 4.1.2 B virus (herpes B virus)
  • 4.1.2.1 Established disease
  • Preferred regimen: Valacyclovir 1,000 mg PO tid OR Ganciclovir 5 mg/kg IV q12h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily indefinitely OR Valacyclovir 1 g PO tid indefinitely
  • Alternative regimen: Acyclovir 15 mg/kg IV q8h for ≥ 14 days until resolution of neurologic symptoms, then Acyclovir 800 mg PO 5 times daily OR Valacyclovir 1 g PO tid indefinitely
  • 4.1.2.2 Prophylaxis after bite or scratch
  • 4.1.3 Cytomegalovirus (CMV)
  • Preferred regimen: Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance AND Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance
  • 4.1.4 Chikungunya virus
  • Preferred regimen: supportive
  • 4.1.5 Eastern equine encephalitis virus
  • Preferred regimen: supportive
  • 4.1.6 Epstein-Barr virus (EBV)
  • Preferred regimen: supportive ± Corticosteroids
  • Note: Acyclovir is not recommended.
  • 4.1.7 Hendra virus
  • Preferred regimen: supportive
  • 4.1.8 HSV-1 and HSV-2
  • Preferred regimen: Acyclovir 10 mg/kg IV q8h for 14–21 days
  • Preferred regimen (neonates): Acyclovir 20 mg/kg IV q8h for 21 days
  • 4.1.9 Human herpesvirus 6 (HHV-6)
  • Preferred regimen (1): Ganciclovir 5 mg/kg IV q12h for 14–21 days, followed by 5 mg/kg IV qd for maintenance
  • Preferred regimen (2): Foscarnet 90 mg/kg IV q12h for 14–21 days, followed by 90-120 mg/kg IV qd for maintenance
  • 4.1.10 Human immunodeficiency virus (HIV)
  • 4.1.11 Influenza virus
  • 4.1.12 Japanese encephalitis virus
  • Preferred regimen: supportive
  • Note: Interferon alpha is not recommended.
  • 4.1.13 JC virus
  • Preferred regimen: Reversal or control of immunosuppression OR HAART in patients with AIDS
  • 4.1.14 La Crosse virus
  • Preferred regimen: supportive
  • 4.1.15 Louping ill virus
  • Preferred regimen: supportive
  • 4.1.16 Lymphocytic choriomeningitis virus (LCMV)
  • Preferred regimen: supportive
  • 4.1.17 Me Tri virus
  • Preferred regimen: supportive
  • 4.1.18 Measles virus
  • Preferred regimen: supportive
  • Note: Ribavirin is not approved by the US Food and Drug Administration (FDA) for this indication, and such use should be considered experimental.
  • 4.1.19 Monkeypox virus
  • Preferred regimen: supportive
  • Alternative regimen: Cidofovir OR vaccinia immune globulin
  • 4.1.20 Mumps virus
  • Preferred regimen: supportive
  • 4.1.21 Murray Valley encephalitis virus
  • Preferred regimen: supportive
  • 4.1.22 Nipah virus
  • Preferred regimen: supportive
  • Alternative regimen: Ribavirin
  • 4.1.23 Nonpolio enteroviruses
  • Preferred regimen: supportive
  • Note: Consider intraventricular γ-globulin for chronic and/or severe disease.
  • 4.1.24 Poliovirus
  • Preferred regimen: supportive
  • 4.1.25 Powassan virus
  • Preferred regimen: supportive
  • 4.1.26 Rabies virus[3]
  • 4.1.26.1 Not previously vaccinated
  • Preferred regimen (1): Wound cleansing with soap and water followed by povidine-iodine solution irrigation if available.
  • Preferred regimen (2): Human rabies immune globulin (HRIG) 20 IU/kg
  • Preferred regimen (3): Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1.0 mL, IM (deltoid area), 1 each on days 0, 3, 7, and 14
  • 4.1.26.2 Previously vaccinated
  • Preferred regimen (1): Wound cleansing with soap and water followed by povidine-iodine solution irrigation if available.
  • Preferred regimen (2): Human diploid cell vaccine (HDCV) or purified chick embryo cell vaccine (PCECV) 1.0 mL, IM (deltoid area), 1 each on days 0 and 3
  • Note: If anatomically feasible, the full dose of HRIG should be infiltrated around and into the wounds, and any remaining volume should be administered at an anatomical site intramuscularly distant from vaccine administration. In addition, HRIG should not be administered in the same syringe as vaccine. Because RIG might partially suppress active production of rabies virus antibody, no more than the recommended dose should be administered.
  • 4.1.27 Rocio virus
  • Preferred regimen: supportive
  • 4.1.28 Rubella virus
  • Preferred regimen: supportive
  • 4.1.29 Snowshoe hare virus
  • Preferred regimen: supportive
  • 4.1.30 St. Louis encephalitis virus
  • Preferred regimen: supportive
  • Alternative regimen: IFN-α-2b
  • 4.1.31 Tickborne encephalitis virus
  • Preferred regimen: supportive
  • 4.1.32 Toscana virus
  • Preferred regimen: supportive
  • 4.1.33 Vaccinia
  • Preferred regimen: supportive ± Corticosteroids (if suggestive of post-immunization)
  • 4.1.34 Venezuelan equine encephalitis virus
  • Preferred regimen: supportive
  • 4.1.35 Varicella zoster virus (VZV)
  • 4.1.36 West Nile virus
  • Preferred regimen: supportive
  • 4.1.37 Western equine encephalitis virus
  • Preferred regimen: supportive
  • 4.2 Bacteria
  • 4.2.1 Anaplasma phagocytophilum (human granulocytotrophic ehrlichiosis)
  • Preferred regimen: Doxycycline 100 mg PO/IV bid for 8 weeks
  • 4.2.2 Bartonella bacilliformis (Oroya fever, Carrion's disease)
  • 4.2.3 Bartonella henselae (cat scratch disease)
  • 4.2.4 Borrelia burgdorferi (Lyme disease)
  • 4.2.5 Coxiella burnetii (Q fever)
  • 4.2.6 Ehrlichia chaffeensis (human monocytotrophic ehrlichiosis)
  • Preferred regimen: Doxycycline 100 mg IV/PO bid for 8 weeks
  • 4.2.7 Listeria monocytogenes
  • 4.2.8 Mycobacterium tuberculosis
  • 4.2.9 Mycoplasma pneumoniae
  • 4.2.10 Rickettsia rickettsii (Rocky Mountain spotted fever)
  • Preferred regimen: Doxycycline 100 mg PO/IV bid for 8 weeks
  • Alternative regimen, pregnant patient: Chloramphenicol 25 mg/kg q6h for 14 days
  • 4.2.11 Treponema pallidum (syphilis)
  • Preferred regimen: Penicillin G 20MU IV q4hr in divided doses for 2-4 weeks
  • Alternative regimen: Ceftriaxone 2g IV q24h for 2-4 weeks
  • 4.2.12 Tropheryma whipplei (Whipple's disease)
  • 4.3 Fungi
  • 4.3.1 Coccidioides
  • 4.3.2 Cryptococcus neoformans
  • 4.3.3 Histoplasma capsulatum
  • Preferred regimen: Amphotericin B liposomal for 4–6 weeks, followed by Itraconazole for at least 1 year and until resolution of CSF abnormalities
  • 4.4 Protozoa
  • 4.4.1 Acanthamoeba
  • 4.4.2 Balamuthia mandrillaris
  • 4.4.3 Naegleria fowleri
  • 4.4.4 Plasmodium falciparum
  • 4.4.5 Toxoplasma gondii
  • 4.4.6 Trypanosoma brucei gambiense (West African trypanosomiasis)
  • Preferred regimen: Eflornithine OR Melarsoprol 2-3.6 mg/kg IV q24h for 3 days THEN repeat the same regimen after 7 days THEN repeat the same regimen again (total of 3 regimens after 7 days of the 2nd regimen
  • 4.4.7 Trypanosoma brucei rhodesiense (East African trypanosomiasis)
  • 4.5 Helminths
  • 4.5.1 Baylisascaris procyonis
  • 4.5.2 Gnathostoma
  • 4.5.3 Taenia solium (cysticercosis)
  • 4.6 Prion
  • 4.6.1 Human transmissible spongiform encephalopathy
  • Preferred regimen: supportive

References

  1. ↑ Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
  2. ↑ 2.0 2.1 2.2 2.3 Tunkel, Allan R.; Glaser, Carol A.; Bloch, Karen C.; Sejvar, James J.; Marra, Christina M.; Roos, Karen L.; Hartman, Barry J.; Kaplan, Sheldon L.; Scheld, W. Michael; Whitley, Richard J.; Infectious Diseases Society of America (2008-08-01). "The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America". Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America. 47 (3): 303–327. doi:10.1086/589747. ISSN 1537-6591. PMID 18582201.
  3. ↑ Rupprecht, Charles E.; Briggs, Deborah; Brown, Catherine M.; Franka, Richard; Katz, Samuel L.; Kerr, Harry D.; Lett, Susan M.; Levis, Robin; Meltzer, Martin I.; Schaffner, William; Cieslak, Paul R.; Centers for Disease Control and Prevention (CDC) (2010-03-19). "Use of a reduced (4-dose) vaccine schedule for postexposure prophylaxis to prevent human rabies: recommendations of the advisory committee on immunization practices". MMWR. Recommendations and reports: Morbidity and mortality weekly report. Recommendations and reports / Centers for Disease Control. 59 (RR-2): 1–9. ISSN 1545-8601. PMID 20300058.
  4. ↑ Thwaites G, Fisher M, Hemingway C, Scott G, Solomon T, Innes J; et al. (2009). "British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children". J Infect. 59 (3): 167–87. doi:10.1016/j.jinf.2009.06.011. PMID 19643501.

References

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