Critical Care Medicine

Viral infections

Viral pneumonia

Viral meningitis/encephalitis

Skin manifestations of viral diseases

Viral hepatitis

Also known as: Viral pneumonitis, viral meningoencephalitis

Related conditions

Influenza

Respiratory syncytial virus (RSV)

Adenovirus

Cytomegalovirus

Metapneumovirus

Herpes simplex virus

Varicella zoster virus (VZV)

West Nile virus

Eastern equine encephalitis

Meningoencephalitis

Shingles

1. Description of the problem

Viral pneumonia

Viruses can cause both community-acquired and hospital-acquired pneumonia and are under-recognized as causes of pneumonia in critically ill patients. While the most common viral causes of pneumonia are influenza and parainfluenza, it is more common for pneumonia to develop as a result of bacterial superinfection in the setting of viral respiratory infection than due to the virus itself. Adenovirus and respiratory syncytial virus are less common causes of pneumonia.

Human metapneumovirus, and the severe acute respiratory syndrome (SARS), and Middle East Respiratory Syndrome (MERS) coronaviruses were identified in the early 21st century as causes of serious and sometimes fatal viral pneumonia. Healthy adults, especially women who are pregnant, who develop acute varicella infection are at risk for severe pneumonia with a high case fatality rate.

Viral meningitis/encephalitis

Most viral etiologies of meningitis do not cause critical illness. The most common notable exception is herpes simplex virus (HSV). Whereas HSV meningitis is generally caused by HSV 2 (which produces most genital herpes) and has a benign course, HSV encephalitis is most often due to HSV1 (which produces most cold cores) and is associated with a high risk of morbidity and mortality.

Regionally, West Nile virus (WNV), the Eastern and Western equine encephalitis viruses (EEEV and WEEV), St Louis virus, Colorado tick fever virus, Powassan virus, and others may be important to consider.

Outside the United States, Japanese encephalitis virus, Murray Valley virus and Chandipura virus should be considered in patients with severe encephalitis from the right regions.

Measles, mumps, varicella, influenza and rubella can cause both a viral encephalitis and an immune-mediated postinfectious encephalitis. The two entities can be difficult to distinguish clinically. In postinfectious encephalitis, magnetic resonance imaging (MRI) often shows multifocal white matter lesions.

Skin manifestations of viral diseases

While not in and of themselves thought to lead to critical illness, HSV and VZV skin manifestations may be seen in critically ill patients. These two viruses lie dormant in nerve roots from the time of infection, which is usually in childhood, until immunosuppression or stress cause reactivation.

Viral hepatitis

Viruses are the most common causative agents of infectious hepatitis. Though rare, fulminant hepatitis can be caused by the hepatitis A, B, C or E virus, and by HSV. Epstein Barr virus (EBV) and cytomegalovirus (CMV) generally cause a milder hepatitis.

Clinical features

Viral pneumonia

A chest x-ray or computerized tomography (CT) scan with diffuse infiltrates in a patient with clinical signs and symptoms consistent with infection should raise suspicion for viral pneumonia. Typical signs and symptoms include fever, shortness of breath and cough. More severe disease is suggested by tachypnea, hypoxia, and hemodynamic instability. Routine culture of respiratory specimens will be negative unless the patient is superinfected with bacteria, usually Staphylococcus aureus, Streptococcus pneumoniae or other streptococci.

Gram stain in viral pneumonia without superinfection may reveal polymorphonuclear cells, but few if any bacteria.

Viral meningitis/encephalitis

Patients with viral meningitis generally present with fever and a headache. Photophobia, stiff neck and lethargy may also be present. Cerebral spinal fluid (CSF) analysis reveals pleocytosis with white blood cell (WBC) count generally less than 250 cells/microliter, mildly elevated protein usually less than 150 mg/dL, and normal glucose. Early in the disease, neutrophilic predominance may be seen, which might lead the clinician to suspect bacterial meningitis. If repeated 8 hours later, a shift to lymphocytic predominance will be seen.

The distinction between meningitis and encephalitis is based on cerebral function. In meningitis, while lethargy may be present, cognitive function remains normal. In encephalitis, changes in mental status, motor or sensory function, speech or movement, or behavior and personality may be seen. Seizure can occur in either meningitis or encephalitis.

While a pure encephalitis is not accompanied by signs of meningeal irritation (photophobia and neck stiffness), often patients have meningoencephalitis, with elements of both meningeal and cerebral involvement. Focal neurologic signs associated with encephalitis may include paresis, cranial nerve palsies, and pathologic reflexes.

Skin manifestations of viral disease

Orofacial herpes lesions, generally caused by HSV1, are commonly seen in critically ill patients when the virus reactivates due to stress or immunosuppression, traveling from the nerve cell body along the axon to the skin. The typical appearance of orofacial HSV1 reactivation is that of multiple fluid-filled blisters, which later break and evolve into scabs. These lesions are most often seen on the lips but may be seen anywhere on the face and are often missed when they are attributed to pressure ulceration caused by gastric or endotracheal tubes.

Genital herpes lesions also reactivate under stress and are most often found on the genitals or in the perianal region. HSV1 and 2 lesions contain active virus, and strict hand hygiene should be employed to prevent transmission of the organism to oneself or one's other patients.

VZV reactivation, also known as shingles, occurs as a result of stress or immunosuppression. Like HSV, the virus remains latent in the nerve cell body and travels down the axon to the skin during reactivation. In varicella reactivation, the pain may precede the visible signs of infection.

VZV is the agent that causes chicken pox. Healthcare providers without immunity to chicken pox, particularly those who are or may be pregnant, because of the risk of fetal anomaly or loss in pregnant women with acute chicken pox, should avoid caring for patients with varicella zoster reactivation.

The typical skin appearance of shingles is a grouping of blisters, usually confined to one dermatome, often oriented in a stripe. Blisters are initially filled with clear fluid, and eventually fill with blood, then dry out and crust over. Once the lesions are fully crusted they are no longer considered infectious.

In immunosuppressed patients, the virus may spread along nerve cells and affect multiple dermatomes. This is referred to as disseminated zoster. The lesions will not cross the midline of the body. The rash of varicella zoster most often occurs on the trunk but can involve other parts of the body including eyes and ears, often with serious sequelae to vision and hearing.

Viral hepatitis

Liver enzyme abnormalities and abnormal liver function tests are common in critically ill patients and are caused by a wide variety of factors. Chronic hepatitis B or C can be underlying such abnormalities.

Fulminant acute viral hepatitis can result in critical illness. Typical initial presentation includes nausea/vomiting, anorexia, fever, abdominal pain, jaundice and evidence of coagulopathy.

Hepatitis A rarely causes fulminant hepatic failure, except when it occurs in the setting of pre-existing liver disease, particularly chronic hepatitis C. Case fatality rates are generally under 1% but somewhat higher in patients over 40 years of age.

Fulminant hepatic failure is very rare with acute hepatitis C and when seen is usually in the setting of chronic hepatitis B. Fulminant hepatic failure is very rare with hepatitis B as well except when coinfection with hepatitis D occurs. Fulminant hepatic failure in hepatitis E virus (HEV) has a case fatality rate of up to 3%, rising to nearly 25% in pregnant women, usually in their third trimester. Mortality is also higher in patients with pre-existing liver disease or malnutrition.

Both HSV 1 and HSV 2 have been implicated in fulminant hepatitis. Patients at risk include newborns, those with immunosuppression by disease or drugs, and pregnant women. Concomitant involvement of the lungs, lymph nodes or spleen may be seen, and oral or genital ulcers may be present. Case fatality rate is high.

CMV hepatitis is generally characterized by mild elevations of transaminases.

Key management points

Viral pneumonia

It is important to have a low index of suspicion for viral pneumonia, especially during the respiratory virus season, typically the winter months. Quick identification of a treatable virus such as influenza, RSV or CMV can reduce morbidity and mortality if therapy is initiated promptly. Supportive care, including mechanical ventilation if necessary, may be the only available therapy for many respiratory viruses. Patients with influenza pneumonia should be placed on droplet precautions. Obtaining appropriate specimens is essential to making the diagnosis.

Viral meningitis/encephalitis

Management for most central nervous system (CNS) viruses is supportive. Because HSV is responsive to antiviral medication, it is important to initiate empiric therapy for this common cause of encephalitis while awaiting results of CSF polymerase chain reaction (PCR) testing. CMV and VZV are also treatable CNS viruses and should be included in the panel of tests in susceptible individuals.

Skin manifestations of viral disease

Viral skin infections are rarely life threatening, but can be very painful. Antiviral medications are used for significant reactivated HSV skin manifestations and for VZV. Modified contact isolation precautions should be implemented in patients with VZV reactivation, so that healthcare workers and visitors who are susceptible to chicken pox do not become exposed via contact with the patient.

Patients with disseminated VZV reactivation (more than one dermatome) should be placed on airborne isolation precautions in addition to contact precautions. Some hospitals place all immunocompromised patients with VZV reactivation on airborne precautions while waiting to see whether the infection will disseminate. Precautions can be discontinued when lesions crust over.

Viral hepatitis

Treatment for acute viral hepatitis is supportive with the exception of HSV hepatitis, which should be treated with high-dose parenteral acyclovir. The role of therapy for CMV in immunocompetent patients is unclear. Immunocompromised patients with CMV disease should be treated with oral valganciclovir or, if unable to take oral medication, intravenous ganciclovir.

2. Emergency Management

Patients with viral infections in the intensive care unit (ICU) should be given the supportive care appropriate for any infection. Respiratory support may be needed for hypoxia or airway, and pressors may be required to maintain blood pressure. Expedient diagnosis is important to differentiate between treatable and untreatable infection. Prompt implementation of appropriate isolation precautions is important to control the spread of infectious viruses such as influenza and RSV to healthcare providers and other patients and their visitors.

3. Diagnosis

Viral pneumonia

The fastest and most efficient means to diagnose viral pneumonia is by use of a viral respiratory PCR panel. Nasal washing, nasopharyngeal swab, or bronchoalveolar lavage fluid can be sent and processed for the common viruses within a few hours. Caution should be exercised when interpreting results, because many people carry common respiratory viruses, especially during the winter months. Viral culture, enzyme immunoassay, immunofluorescence, and serology can also be used to identify the etiology of a suspected viral pneumonia. A history of influenza vaccination does not preclude the diagnosis of influenza.

Several studies suggest that serum levels of procalcitonin, a peptide precursor of calcitonin released by parenchymal cells in response to bacterial toxins, can be used as an indicator of the likelihood of bacterial versus viral pneumonia. Procalcitonin levels less than 0.1mcg/L are considered highly unlikely to be associated with bacterial pneumonia, and studies have demonstrated successful avoidance of antibiotics in those cases.

In patients in whom pneumonia is suspected, a rapid influenza antigen test should be performed right away provided the influenza season has begun (when rates of influenza infection in the community are low, the negative predictive value of the test falls and the test is not recommended). Antiviral therapy should not be withheld while awaiting test results in patients sick enough to be hospitalized. The test is highly specific, so positive results are usually indicative of infection, while negative results should be confirmed with a more sensitive identification technique such as culture, immunofluorescence, or reverse-transcriptase PCR. Note that recent receipt of the live attenuated influenza vaccine will result in a false-positive rapid influenza antigen test.

Most patients with influenza do not have lower respiratory tract involvement. The presence of viral pneumonia should be suspected in patients with progressive worsening of fever, dyspnea, and eventually hypoxia. High-resolution CT shows multifocal peribronchovascular consolidation or diffuse ground glass opacities. Bacterial pneumonia secondary to influenza is the cause of approximately 25% of influenza-related deaths. Its presence is suggested by recurrence of fever or worsening of cough after a period of improvement.

These findings should prompt immediate consideration of antibacterial therapy. Other more rare complications associated with influenza are myositis, encephalitis, transverse myelitis, meningitis, Guillain-Barre syndrome, myocarditis, and pericarditis.

Viral meningitis/encephalitis

Several clinical clues can suggest specific etiologies of viral CNS infection:

- evidence of or history of mosquito bites is suggestive of mosquito-borne virus, e.g., WNV or St Louis encephalitis virus depending on geography

-bat or dog bite should raise concern for rabies, as should hydrophobia and pharyngeal spasms

-profound weakness, especially flaccid paralysis, is suggestive of WNV

-exposure to rodents means lymphocytic choriomeningitis virus should be considered

-parotitis suggests mumps in an unvaccinated patient

-a vesicular rash in a dermatomal pattern is suggestive of VZV

-lesions predominating in the temporal lobes on MRI are often seen with HSV

-Red blood cells (RBCs) in the CSF in a nontraumatic tap are consistent with HSV

In most cases of aseptic meningitis/encephalitis, a diagnosis is not made. PCR tests are available for most viruses and have largely replaced viral culture. When a viral etiology of encephalitis is suspected, it is important to promptly rule out HSV, since therapy is available and the disease is nearly always fatal if left untreated.

When HSV encephalitis is suspected, empiric treatment with intravenous (IV) acyclovir should be initiated immediately. Serology can be used to aid in diagnosis when PCR testing is unrevealing. The presence of IgM in serum or CSF is diagnostic of WNV, and antibody tests can be useful for the other arthropod-borne encephalitis viruses as well.

Skin manifestations of viral disease

Skin lesions can often be attributed to HSV or VZV by clinical appearance alone. When in doubt as to the cause, a lesion can be unroofed and swabbed for PCR or direct fluorescent antibody testing.

Viral hepatitis

The diagnosis of hepatitis A, B, C, D and E can be made by serology. The presence of hepatitis B virus DNA in serum indicates active viral replication. The diagnosis of HSV hepatitis may require a liver biopsy, unless HSV viremia can be detected on a blood specimen. CMV hepatitis is suggested by liver test abnormalities in the absence of other causes in the setting of CMV viremia.

What else could it be?

Viral pneumonia

Pneumonitis (due to aspiration of gastric contents, drugs, chemicals, hypersensitivity, etc)

Pulmonary edema

Pulmonary infarction

Bacterial pneumonia (especially atypical organisms)

Fungal pneumonia

Adult respiratory distress syndrome

Diffuse alveolar haemorrhage

Eosinophilic pneumonia

Acute interstitial pneumonia

Cryptogenic organizing pneumonia

Meningitis/encephalitis

Intracranial tumor

Drug-induced meningitis (most commonly caused by NSAIDs, sulfa drugs, antithymocyte globulin and intravenous immune globulin)

CNS vasculitis

Cerebral malaria

Bacterial meningitis

Bacterial brain abscess

Tuberculous meningitis

Fungal meningitis

Skin manifestations of viral disease

Contact dermatitis

Irritant dermatitis

Candida dermatitis

Viral hepatitis

Hepatitis due to hypotension ("shock liver")

Drug-induced hepatitis

Toxin-induced hepatitis

Leptospirosis

Dengue fever

Malaria

Typhoid

Confirmatory tests

Viral pneumonia

Nasal washing, nasopharyngeal swab or bronchoalveolar lavage (send for culture, immunofluorescent antibody staining, or reverse-transcriptase PCR for viral respiratory pathogens)

Rapid influenza antigen test (during influenza season) of nasal washing, nasopharyngeal swab or bronchoalveolar lavage fluid

Viral meningitis/encephalitis

CSF PCR for HSV, VZV, CMV, enterovirus, WNV, other viruses according to region

Serum antibody for human immunodeficiency virus (HIV), lymphocytic choriomeningitis virus (LCMV), mumps, measles

Serum for HIV viral load

Skin manifestation of viral disease

PCR or Direct Fluorescent Antibody of skin scraping for HSV, VZV

Viral hepatitis

Serum hepatitis A IgM

Serum hepatitis B surface antigen and anti-hepatitis B core IgM

Serum hepatitis C immunoglobulin G (IgG) and qualitative RNA (viral load)

Serum hepatitis E IgM and qualitative RNA (viral load)

Serum total anti-HDV (hepatitis D virus)

Liver biopsy for HSV culture or immunohistochemistry

Serum CMV DNA

4. Specific Treatment

Viral pneumonia

Most etiologies of viral pneumonia have no effective treatment. The most notable common exception is influenza. For this reason, it is important to start empiric therapy for influenza in patients with signs and symptoms consistent with this infection during influenza season and to promptly send the appropriate diagnostic tests.

There are two classes of drugs active against influenza. The adamantanes, amantadine and rimantadine, which are only active against influenza A, and the neuraminidase inhibitors, zanamivir, oseltamivir, and peramivir, which are active against influenza A and B. Recent circulating strains have been resistant to one or the other class, so it is imperative to follow the guidance of public health officials when choosing an empiric antiviral drug in a given influenza season.

Oseltamivir is available in enteral formulation only. Administered orally or by orogastric or nasogastric tube, it is well absorbed even in critically ill patients. Zanamivir is readily available only as an orally inhaled agent and should not be administered to mechanically ventilated patients, because it has been known to clog ventilator tubing. It is also contraindicated in patients with asthma or other chronic respiratory disease due to its propensity to cause bronchospasm. Critically ill patients who cannot tolerate enteral medications due to gastrointestinal issues should be considered candidates for IV peramivir which was approved by the FDA in 2014. Phase III studies of IV zanamivir commenced in January 2011.

It should be noted that antiviral agents for influenza are not expected to result in disease cure. Antiviral therapy shortens the duration of influenza symptoms by 1 to 3 days. Their benefits are greatest when initiated within the first 24-48 hours of symptom onset. A number of retrospective studies, many conducted using data from the novel H1N1 influenza epidemic, suggest that the use of antivirals in hospitalized patients helps to decrease complications, shorten hospitalization and reduce ICU admission and mortality. Therefore, treatment should not be delayed while awaiting results of influenza testing. Some studies suggest that antivirals may have some benefit in hospitalized patients with influenza even after 4 or 5 days of symptoms.

Ribavirin has activity against RSV and human metapneumovirus. In adult stem cell transplant recipients with RSV infection, early use of inhaled ribavirin has been shown to reduce morbidity and mortality. Case reports have described the use of combinations of ribavirin with IVIG and/or palivizumab (a monoclonal antibody against RSV) with varying success.

Meningitis/encephalitis

Of all the viral causes of meningitis and encephalitis, only HSV and VZV clearly respond to therapy. The effects of influenza virus infection have been shown to be attenuated by administration of neuraminidase inhibitors and adamantanes but have not been specifically studied in CNS infection and would not be expected to be of use in postinfectious encephalitis.

Skin manifestations of viral disease

To maximize the potential benefits of treatment, antiviral therapy should be initiated within the first 72 hours of symptoms. Treatment of oral or genital HSV lesions or of zoster with acyclovir, famciclovir or valacyclovir hastens resolution and should be considered if such lesions are causing pain. Patients with herpes zoster who are over 50 years of age are at increased risk of developing post-herpetic neuralgia and should be treated if possible.

Patients with disseminated disease, ophthalmic involvement, and immunosuppression should be treated with intravenous acyclovir initially, then stepped down to an oral antiviral. All three of these agents may be associated with nephrotoxicity due to drug crystallization in the tubules. Patients should be hydrated during therapy. Analgesia for pain due to skin lesions should be provided. Several trials have failed to demonstrate efficacy of glucocorticoids in preventing post-herpetic neuralgia.

Viral hepatitis

With the exception of HSV hepatitis which is treated with high-dose parenteral acyclovir, treatment of viral hepatitis is supportive. The role of antivirals for CMV infection in immunocompetent patients is unclear, but immunocompromised patients with CMV disease should be treated with oral valganciclovir if possible, or intravenous ganciclovir.

For patients with fulminant hepatic failure due to hepatitis B, experts recommend antiviral therapy to reduce the risk of hepatitis B recurrence after liver transplantation.

Monotherapy with lamivudine, telbivudine, or entecavir are all acceptable options. Adefovir and tenofivir are not recommended due to risk of nephrotoxicity. Therapy with interferon is not recommended in the acute setting due to risk of hepatotoxicity.

Drugs and dosages

For influenza

Oseltamivir: 75 mg PO Q12 x 5 days (longer durations can be considered for critically ill or immunosuppressed patients, in whom viral replication in the respiratory tract is often prolonged)

Zanamivir (WARNING: should not be used in severely ill or ventilated patients): 2 inhalations (10 mg total) BID x 5 days

Peramivir: 600 mg IV (FDA approved as single-dose therapy for uncomplicated influenza, recommended by CDC to be given for 5 days in critically ill patients)

Amantidine:100 mg PO BID until 24 to 48 hours after symptom resolution

Rimantadine: 100 mg PO BID until 24 to 48 hours after symptom resolution

For herpes viruses:

Acyclovir

For encephalitis, herpes zoster and other serious infections (pneumonia, hepatitis): 10 mg/kg IV Q8 hours

For severe genital or mucocutaneous herpes: 5mg/kg IV Q8 hours

For mild to moderate genital herpes recurrence:

200 mg PO 5x/day for 5 days or 400 mg 3x/day for 5 days or 800 mg 3x/day for 2 days

Valacyclovir

For herpes zoster: 1g PO 3x/day for 3 days

For genital herpes recurrence: 500 mg PO BID for 3 days

For cold sores: 2g PO BID for 1 day

Famciclovir

For herpes zoster: 500 mg PO Q8 hours for 7 days

For recurrent genital herpes in immunocompetent patient: 1g PO BID for 1 day

For cold sores: 1500 mg PO x one dose

Mucocutaneous/genital herpes reactivation in immunocompromised patient: 500 mg PO BID x 7 days

For CMV:

Valganciclovir: 900 mg PO Q12 or

Ganciclovir: 5 mg/kg IV Q12

For Hepatitis B virus:

Lamivudine: 100 mg PO daily

Telbivudine: 600 mg PO daily

Entecavir: 1 mg PO daily

What do I do about particularly refractory cases?

There has been some reported success using extracorporeal membrane oxygenation (ECMO) for refractory cases of pneumonia caused by the novel H1N1 influenza virus.

Patients who do not recover from fulminant hepatic failure due to viral hepatitis should be referred for liver transplantation.

5. Disease monitoring, follow-up and disposition

Patients with viral infections in the ICU should be followed clinically for resolution of signs and symptoms of infection.

Pathophysiology

The influenza virus invades the columnar epithelial cells of the respiratory tract leading to necrosis, edema and inflammation.

HSV and VZV infect nerve endings and travel along sensory axons, becoming latent in ganglia. During reactivation, the virus spreads within the ganglion and involves sensory neurons and skin and/or mucous membranes.

Viral hepatitis can be characterized by a cholestatic picture with bile stasis, or by hepatocyte necrosis. Most of the injury is due to the host immune response.

Epidemiology

Pneumonia

Viruses cause 10% to 30% of community-acquired pneumonia in adults. Influenza and parainfluenza are the most common causes of viral pneumonia, while rhinovirus and coronavirus were identified most frequently in one study of patients with pulmonary infiltrates on chest x-ray, but in almost all instances were associated with the presence of another pathogen. Human metapneumovirus and respiratory syncytial virus are also becoming increasingly recognized as important causes of viral pneumonia. Influenza pneumonia typically occurs in high-risk patients.

In 2009, the emergence of the novel H1N1 (formerly referred to as swine flu) virus resulted in a worldwide pandemic. The pandemic virus differed from previously circulating strains in that the highest rate of infection was seen in individuals under the age of 24 with high rates of morbidity and mortality in young patients. Known risk factors for influenza pneumonia include diabetes, heart disease, lung disease, immunosuppression, renal disease, and age over 65. Obesity and pregnancy were additionally found to be independent risk factors for severe infection with novel H1N1 influenza.

The SARS virus outbreak lasted from February to July of 2003 and involved over 8000 cases in 29 countries. No cases of SARS have been identified since 2004.

MERS was first identified in 2012 in Saudi Arabia. At this writing, MERS has been identified in 9 Middle Eastern countries and has been imported into 11 other countries, including 2 cases in the United States.

Meningitis/encephalitis

The most common cause of viral meningitis is the enteroviruses (Coxsackie, echovirus, and others). These are particularly likely to be the cause of aseptic meningitis during the summer and early fall. A number of arthropod-borne viruses have been increasing in prevalence over the past decade, including WNV, EEEV, and Powassan virus.

A 2006 seroprevalence study demonstrated that 17% to 21% of participants ages 14 to 49 years of age were seropositive for HSV2 and 58% to 62% of participants were seropositive for HSV1. Asymptomatic seropositivity is extremely common. HSV encephalitis can occur during primary infection or as a reactivation of latent infection. The case-fatality rate with treatment can be as high as 30%, and up to 70% without treatment.

The CDC estimates that approximately 30% of Individuals in the United States will develop zoster. The risk increases with age. It has been estimated that 50% of persons to live to age 85 will develop zoster.

Viral hepatitis

Hepatitis B is a global problem, with the highest incidences occurring in southeast Asia, China and sub-Saharan Africa. Transmission occurs perinatally, via sexual contact, via close contact including sharing of toothbrushes and razors within households, through percutaneous inoculation, and as a result of blood transfusion or organ transplantation. Hepatitis D is endemic to the Mediterranean region. There is also high prevalence in certain Asian countries. It is rare in western countries. Transmission is thought to be similar to hepatitis B.

Hepatitis E is more common in Asia, Africa, the Middle East and Central America, and occurs only sporadically in western countries. Transmission is via fecally contaminated water. HEV can also be transmitted via blood transfusion or organ transplantation.

Transmission of herpes simplex is person to person as a result of contact with infected lesions, whereas CMV is transmitted person to person through blood, urine, respiratory secretions, cervical fluid and semen, and transmitted vertically. Both viruses remain latent in the body for life, and reactivate in response to immunosuppression or stress.

Prognosis

Viral pneumonia

The prognosis of viral pneumonia depends on the organism and underlying comorbidities of the patient. It can be hard to distinguish between pure viral pneumonia and viral pneumonia with concomitant ARDS, which is associated with a poor prognosis. Mortality due to influenza varies from year to year depending on the strain of the virus. Pandemic strains carry a higher risk of mortality and affect younger people to a greater extent than non-pandemic strains.

During the pandemic, the novel H1N1 strain was associated with higher death rates among children, pregnant women, and obese patients. In general, patients at highest risk for severe influenza are those with immunosuppression, lung disease, cardiac disease, diseases causing muscle weakness, pregnancy and diabetes. The case-fatality rate of SARS was over 9% and that of MERS is 30%.

Meningitis/Encephalitis

HSV encephalitis is associated with significant morbidity and mortality, even with prompt initiation of antiviral therapy. In one study in Sweden, 1-year mortality was 14%, 24% of patients went on to develop epilepsy, and 22% had long-term neuropsychiatric sequelae.

EEE is one of the most severe arthropod-borne viruses in the Unites States. Its case-fatality rate is over 30% and most survivors go on to suffer long-term brain damage.

Skin manifestations of viral disease

When HSV and VZV are confined to skin alone, there is no risk of mortality. Postherpetic neuralgia develops in 5-20% of patients with zoster, increasing with age. Ocular complications can occur with both HSV and VZV, and should be considered a sight-threatening emergency. Concern for zoster ophthalmicus should arise when zoster involves the face, particularly the nose. Vesicles in the ear, particularly with ipsilateral facial paralysis, should raise concern for Ramsay Hunt syndrome which is VZV, or less commonly HSV, infection of the trigeminal ganglion, and can result in vertigo and disturbances of taste, hearing, and lacrimation. Other rare neurological complications of zoster include aseptic meningitis, myelitis, peripheral motor neuropathy and encephalitis.

Viral hepatitis

The case fatality rates for viral hepatitides are low. The one notable exception is hepatitis E in pregnant females, in whom case fatality rates as high as 25% have been reported. It is important to transfer patients in fulminant hepatic failure to a liver transplant center.

What's the evidence?

Viral pneumonia

http://www.cdc.gov/flu/.

This website provides updated information on influenza activity throughout the country, recommendations on whom to vaccinate, and what empiric antiviral treatment to give and to whom depending on a given influenza season.

Peret, TC, Boivin, G, Li, Y. "Characterization of human metapneumoviruses isolated from patients in North America". J Infect Dis. vol. 185. 2002. pp. 1660-3.

(Genetic analysis from 10 patients with acute respiratory tract illness that provides additional support that this virus is a pathogen in humans.)

Boivin, G, Abed, Y, Pelletier, G. "Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infection in all age groups". J Infect Dis. vol. 186. 2002. pp. 1330-4.

(Two early reports identifying the significance of the HMP virus as a cause of respiratory infection.)

Hall, CB.. "The spread of influenza and other respiratory viruses: complexities and conjectures". Clin Infect Dis. vol. 45. 2007. pp. 353-9.

(Describes how respiratory viruses are spread from person to person and the infection control measures required to control this spread.)

Noah, MA. "Referral to an extracorporeal membrane oxygenation center and mortality among patients with severe influenza A(H1N1)". JAMA. vol. 306. 2011. pp. 1659-68.

(Matched cohort study demonstrating reduced mortality with use of ECMO in patients with H1N1-related ARDS.)

Schuetz, P, Müller, B, Christ-Crain, M.. "Procalcitonin to initiate or discontinue antibiotics in acute respiratory tract infections". Cochrane Database Syst Rev.. vol. 9. 2012. pp. CD007498.

(A systematic review demonstrating that use of procalcitonin as a marker of bacterial rather than viral infection to guide initiation and duration of antibiotic treatment in patients with acute respiratory infection was not associated with higher mortality rates or treatment failure.)

Viral hepatitis

Lok, AS, McMahon, BJ.. "Chronic hepatitis B: update 2009". Hepatology. vol. 50. 2009. pp. 661.

(This guideline gives recommendations for treatment of acute hepatitis B.)

HSV

Xu, F, Sternberg, MR, Kottiri, BJ. "Trends in herpes simplex virus type 1 and type 2 seroprevalence in the United States". JAMA. vol. 296. 2006. pp. 964.

(Seroprevalence study of HSV1 and HSV2.)

VZV

Hales, CM, Harpaz, R, Ortega-Sanchez, I, Bialek, SR.. "Update on recommendations for use of Herpes Zoster vaccine". MMWR. vol. 63. 2014. pp. 729-731.

(CDC recommendations for vaccination to prevent zoster reactivation and its sequelae.)

Meningitis/encephalitis

Tyler, KL.. "Emerging viral infections of the central nervous system: part 1". Arch Neurol.. vol. 66. 2009. pp. 939.

Tyler, KL.. "Emerging viral infections of the central nervous system: part 1". Arch Neurol.. vol. 66. 2009. pp. 1064-74.

(In these two reviews, emerging viral causes of CNS infections are discussed, including WNV, Japanese encephalitis virus, Toscana virus, monkeypox virus and chikungunya virus.)
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