Viral Pneumonia Clinical Presentation
- Author: Zab Mosenifar, MD; Chief Editor: Zab Mosenifar, MD more...
History
The clinical manifestations of viral pneumonia vary because of the number of diverse etiologic agents. Their presentations are described briefly below. Various viral pneumonias typically occur during specific times of the year, among close populations or in populations with underlying cardiopulmonary or immunocompromising disease.
The common constitutional symptoms of all viral pneumonias are fever, chills, nonproductive cough, rhinitis, myalgias, headaches, and fatigue. Symptoms of viral pneumonia are similar to that of bacterial pneumonia, although studies have shown a lower probability of having chest pain and rigors in viral pneumonias.[2] Most patients have cough, but in elderly persons, this may be only scant.
Ascertaining immunization status, travel history, and possible exposure is important. During outbreaks with the usual respiratory viruses, the signs and symptoms can suggest the correct diagnosis in most cases. In very elderly persons, the only complaint may be fever and change in mental status.
In immunocompromised patients, recognition of the clinical picture of viral pneumonia, risk factors, and new changes in clinical parameters is important. All of these findings can indicate the need for further imaging or other diagnostic procedures to make an etiologic diagnosis and to start early treatment.
The typical infection with influenza virus consists of a sudden onset of fever, chills, myalgia, arthralgia, cough, sore throat, and rhinorrhea. The incubation period is 1-2 days, and symptoms normally last 3-5 days. These symptoms are common to other respiratory viral infections but are highly suggestive of influenza virus infection when an outbreak is occurring in the community. Influenza is usually seen in epidemics and pandemics in late winter and early spring.
Peak attack rates for respiratory syncytial virus (RSV) occur in the winter in infants younger than 6 months. Parainfluenza (PIV) infection most often occurs in the late fall or winter, although PIV-3 pneumonia is especially common in the spring.
Physical Examination
The physical examination findings in viral pneumonia are similar to those of pyogenic pneumonia and are nonspecific. Physical examination demonstrates wheezing, crackles, increased fremitus, and bronchial breath sounds over the involved regions of the lungs.
Some patients have few, if any, physical findings other than mild fever, whereas other patients may have respiratory and/or multiorgan failure. Other findings include the following:
- Fever and/or chills
- Cough (with or without sputum production)
- Tachypnea and/or dyspnea
- Tachycardia or bradycardia
- Wheezing
- Rhonchi
- Rales
- Sternal or intercostal retractions
- Dullness to percussion
- Decreased breath sounds
- Pleurisy
- Friction rub
- Hypoxia
- Acute respiratory distress syndrome
Influenza virus
Influenza pneumonia especially affects the following groups of patients:
- Children with cystic fibrosis or transplants
- Adults with chronic cardiovascular or respiratory disease, diabetes mellitus, renal diseases, hemoglobinopathies, or immunosuppression
- Residents of nursing homes or chronic care facilities
- Healthy adults older than 65 years.
The 3 clinical forms of influenza pneumonia are primary influenza pneumonia, secondary bacterial pneumonia, and mixed viral and bacterial pneumonia.
Primary influenza pneumonia manifests with persistent symptoms of cough, sore throat, headache, myalgia, and malaise for more than 3-5 days. The symptoms worsen with time, and new respiratory symptoms, such as dyspnea and cyanosis, appear. This form is the least common but the most severe in terms of pulmonary complications.
Secondary bacterial pneumonia is characterized by the relapse of high fever, cough with purulent sputum after initial improvement, and radiographic evidence of new pulmonary infiltrates. The most common pathogen is Streptococcus pneumoniae (48%), followed by Staphylococcus aureus,[51] Haemophilus influenzae, and gram-negative pathogens.
Elderly persons may have a lower frequency of upper respiratory complaints; one study showed that the triad of cough, fever, and acute onset had only a 30% positive predictive value, in contrast to 78% in young adults. Fever and altered mental status may be the only signs of influenza pneumonia in an older patient with cognitive impairment. Gastrointestinal complaints and myalgia are more common in influenza than in RSV infection.[42, 52]
Avian influenza (H5N1) has an incubation period of 2-5 days, but it may be up to 7 days after exposure. The primary initial symptom is fever, and symptoms of cough, malaise, myalgia, headache, sore throat, abdominal pain, vomiting, and diarrhea are also common. The gastrointestinal complaints may initially suggest gastroenteritis. When pneumonia develops, cough, followed by dyspnea, tachypnea, and chest pain, are reported. In severe cases, encephalitis/encephalopathy, cardiac failure, renal failure, multiorgan failure, and disseminated intravascular coagulation can occur.[53]
H1N1 influenza presents similarly to seasonal influenza. Fever and cough are almost universal symptoms. Shortness of breath (54%), fatigue/weakness (40%), chills (37%), myalgias (36%), rhinorrhea (36%), sore throat (31%), headache (31%), vomiting (29%), wheezing (24%), and diarrhea (24%) are the most common other symptoms.
Mixed viral and bacterial pneumonia is common and can manifest as a gradual progression of disease or as a transiently improving condition followed by a worsening one. Both bacterial pathogens and an influenza virus are isolated.
Respiratory syncytial virus
Risk factors for RSV infection include age younger than 6 months, underlying lung disease (bronchopulmonary dysplasia or cystic fibrosis), and congenital heart disease in children with asthma. Institutionalized elderly and immunosuppressed patients (eg, those with severe combined immunodeficiency, leukemia, and/or transplant) are also at risk.
RSV infections in adults are poorly characterized and rarely diagnosed. They are accompanied by long-lasting upper respiratory tract infections and are more commonly associated with a prolonged productive or bronchitic cough and wheezing than with other features. The findings tend to mimic the decompensated underlying cardiopulmonary disease rather than the acute viral disease.
Various studies reported RSV pneumonia in recipients of solid organ transplants or HSCTs. The clinical manifestations are usually severe, and supplemental oxygen and mechanical ventilation are required.
Severe cases of RSV giant-cell pneumonia have been reported in 4-10% of cases and also during concurrent viral infections with EBV, CMV, or adenovirus.
In healthy hosts, RSV causes upper respiratory tract illness, tracheal bronchitis, bronchiolitis, and pneumonia. Upper respiratory tract symptoms, such as coryza and pharyngitis, precede lower respiratory tract involvement.
Patients with RSV pneumonia typically present with fever, nonproductive cough, otalgia, anorexia, and dyspnea. Wheezes, rales, and rhonchi are common physical findings.
Pneumonia and bronchiolitis often are difficult to differentiate, and both can be associated with wheezing, rales, and hypoxemia. Dyspnea and cough are seen in 60-80% of cases. Compared with influenza, RSV is more often associated with rhinorrhea, sputum production, and wheezing and less often associated with gastrointestinal complaints and fever.[54, 55]
Immunocompromised hosts may have a range of respiratory involvement. These patients develop fever, cough, rhinorrhea, sinus congestion, and respiratory difficulties; nearly half report wheezing. In these patients, the symptoms range from mild dyspnea to severe respiratory distress and respiratory failure.
While most patients with RSV infection, including infants, have only upper respiratory symptoms, as many as 25-40% develop bronchiolitis and/or pneumonia. Statistics show that as many as 20-25% of infants with pneumonia who require hospitalization are infected with RSV.
Lower respiratory disease in infants is preceded by a prodrome of rhinorrhea and, perhaps, poor appetite. Low-grade fever, cough, and wheezing usually occur. The chest examination reveals tachypnea, rales, and fine wheezes. Disease from RSV in young, healthy adults is usually mild, although one study of community-acquired pneumonia showed RSV to be the third most common pathogen,[54] after S pneumoniae and influenza viruses A and B.
During their first RSV infection, 25-40% of infants and young children have signs or symptoms of bronchiolitis of pneumonia, and 0.5-2% require hospitalization. Most pediatric patients hospitalized for RSV infection are younger than 6 months.
Parainfluenza virus
Clinical manifestations of PIV infection can range from mild upper respiratory tract infections (mainly in immunocompetent patients) to severe croup, bronchiolitis, or life-threatening pneumonia in the setting of immunosuppression. Incubation is 1-3 days. The classic croup symptoms of barking cough, hoarseness, and stridor commonly seen in children is less commonly seen in adults. In adults who are immunocompromised, cough is the hallmark.
PIV-1 and PIV-2 produce croup in children that initially manifests as an upper respiratory tract infection followed by a barking cough, dyspnea, stridor, and chest-wall retractions. PIV-2 infections tend to be milder than PIV-1 infections. PIV-4 causes mild upper respiratory tract infection in both adults and children.
PIV-3 is the main strain that causes pneumonia and bronchiolitis. The signs and symptoms are nonspecific, more prominent in children, and similar to, but milder than, those of RSV pneumonia. They include fever, cough, coryza, dyspnea with rales, and wheezing.
Immunosuppression promotes the development of PIV pneumonia. Situations leading to immunosuppression include the following: BMT, solid-organ transplantation (with mild forms), severe combined immunodeficiency in children, or therapy with etanercept.
PIV infection may appear as giant-cell pneumonia. This form is most frequent in immunocompromised patients (after BMT or umbilical-cord transfusion) and rarely associated with alveolar proteinosis. The mortality rate approaches 100% in children, with a better prognosis than this in adults.
PIV pneumonia may mimic other lung infections most commonly encountered in an immunocompromised host. Several clinical findings tend to distinguish PIV or RSV lung infection from CMV or other opportunistic forms of pneumonia: upper respiratory infection before lung infection, clinical and imaging evidence of sinusitis, and wheezing.
As many as one third of children with PIV infection can have bacterial superinfection. Even if long-term sequelae are uncommon, bronchiolitis obliterans organizing pneumonia is described after PIV infection.
Human metapneumovirus
Symptoms of human metapneumovirus (hMPV) infection are similar to those caused by other viruses: nasal congestion and cough are present in 82-100% of cases. Other symptoms include rhinorrhea (69-82%), dyspnea (69%), wheezing (62%), sputum production (55%), hoarseness (46-91%), and sore throat (23-45%). The incubation period is 5-6 days.
In one study, hoarseness was more common in hMPV than in RSV infection. Hoarseness, dyspnea, and wheezing were significantly more common among the elderly older than 65 years than among adults younger than 40 years.[15]
In different studies, cough was reported in 90% of patients; dyspnea, in 83%; coryza, in 88%; and fever, in 52-92%. Among the physical signs, rales, wheezing, or stridor were found in one half of infected children. In children, hMPV is an important cause of wheezing (9% in a 132 case series). Fever, cough, dyspnea, and sore throat are commonly described in adults. In HSCT recipients, hMPV pneumonia is reported and tends to cause respiratory failure.
Coronavirus
The incubation period is 2-5 days, with a mean of 3 days. Symptoms are similar to those from other respiratory viruses, including cough, rhinorrhea, sore throat, headache, and malaise, although fever was only seen in 21-23% of cases.
Varicella-zoster virus
The initial presenting symptoms of VZV infection are low-grade fever; malaise; and a rash that is typically vesicular, starts on the trunk and face, spreads centrifugally to other parts of the body, and usually is in various stages of evolution (from vesicles to crusted scabs) by the time of presentation. VZV pneumonia develops in 1 in 400 cases.
VZV pneumonia starts gradually within 1-6 days after the rash appears and manifests with fever, chest tightness, tachypnea, dyspnea, dry cough, cyanosis, and (in rare cases) pleuritic chest pain and hemoptysis. Physical examination reveals minimal findings, with rare rhonchi or wheezes. New chest symptoms are strongly associated with radiologic findings. VZV pneumonia can develop as a mild disease, or it can be severe and rapidly fatal, especially in immunocompromised individuals.
Some patients may be asymptomatic. One study in military personnel noted that only 25% of those with VZV pneumonitis experienced cough and 10% had tachypnea.[56]
Risk factors related to VZV pneumonia are smoking, pregnancy (third trimester), immunosuppression, and male sex. The presence of more than 100 spots during the skin eruption, prolonged fever, a history of contact with an index case, and chest symptoms at presentation are also reported risk factors.
Measles virus
The incubation period of measles is 10-14 days after exposure, after which a prodrome of fever, malaise, anorexia, conjunctivitis, cough, and coryza ensue. Toward the end of the prodrome, Koplik spots (small white punctate lesions) may appear on the buccal mucosa.
The rash is an erythematous, maculopapular eruption that may become confluent, beginning on the face, then progressing down the body to involve the extremities last, including palms and soles.
Atypical measles occurs in patients who were immunized from 1963-1967 with a killed vaccine and are exposed to measles virus or live measles virus vaccine. In these cases, the rash starts in the hands and feet rather than in a central distribution.
Duration of the rash is approximately 5 days, after which it may desquamate. Duration of symptoms is usually 10 days, and the cough may be the last symptom to disappear.
In adults, 3% of measles cases are complicated by significant pneumonia requiring hospitalization, with 17% of patients experiencing bronchospasm and 30%, bacterial superinfection. Bacterial superinfection most often occurs 5-10 days after the onset of the rash. The pulmonary findings parallel the cutaneous signs, and the severity of pneumonia correlates with worsening rash.
Persons at risk for measles-virus pneumonia are those with T-cell immunosuppression (eg, those taking steroids); BMT recipients; and those with HIV infection, lymphoma, leukemia, or Epstein-Barr virus infection. Others at risk are children and the elderly, pregnant women, those with vitamin A deficiency, and persons not vaccinated or those in whom primary vaccination failed.
Four types of measles-associated pneumonia are encountered. The first, measles-virus pneumonitis, usually appears within a few days after the onset of rash. High levels of KL6 (a glycoprotein secreted by pneumocyte-2) are markers for interstitial pneumonia and are associated with a poor prognosis.
The second form, bacterial superinfection, usually develops several days after rash appears. This type manifests with cough, fever, purulent expectoration, tachycardia, and pleural pain.
Third, giant cell pneumonia typically develops before or with the peak of viral exanthema. In rare cases, it develops after 5 months or longer. Rash may be absent. Cough may persist for 1-2 weeks during recovery. Lung biopsy may be needed for final diagnosis.
Fourth, pneumonia of atypical measles is described in adults. These patients developed a potentially fatal illness, with increased fever (7-14 d after exposure), minimal or absent rashes, headache, arthralgias, hepatitis, interstitial or nodular infiltrates, hilar lymphadenopathy, and occasional pleural effusions.
Cytomegalovirus
CMV pneumonia is usually mild in otherwise healthy individuals. It starts as a mononucleosis-like syndrome (eg, malaise, fever, myalgias) with mild hepatitis and no lymphadenopathy or splenomegaly.
In immunocompromised people, the clinical picture may vary. Most commonly, asymptomatic shedding affects pulmonary secretions, blood, and urine, with no clinical significance and low mortality rates.
CMV syndrome manifests with self-limited fever and constitutional symptoms (fever, malaise, anorexia, myalgias, arthralgias, fatigue). CMV syndrome precedes CMV pneumonitis by 1-2 weeks and usually has a sudden onset, with respiratory complaints (cough, dyspnea, tachypnea), fever, an increased A-a gradient, and radiologic infiltrates. The duration is less than 2 weeks.
In allogeneic HSCT recipients, CMV disease presents post engraftment (30-99 d after transplantation) and late (≥ 100 d) in those with graft versus host disease and/or on higher-dose immunosuppressive therapy. CMV pneumonia is seen in 10-30% of such patients, and the median time to occurrence is 44 days after transplantation.
Autologous HSCT recipients are at much lower risk for CMV pneumonia, seen in only 1-9% of cases, oftentimes with milder symptoms.
Among solid organ transplant recipients, CMV pneumonia is most common in lung transplantations, ranging from 15-55% of cases. Typically, this pneumonia develops between day 15-60 post transplantation and is characterized by fever, cough, and hypoxia. In CMV donor-positive/recipient-negative cases, the onset and progression can be rapid.
Other solid organ transplantations are associated with low rates of CMV pneumonia: liver, 9.2%; heart, 0.8-6.6%; and kidney less than 1%.
For BMT recipients, risk factors are pretreatment seropositivity, total-body irradiation, certain immunosuppressive treatment, severe acute or chronic graft-versus-host disease, underlying disease (acute lymphoblastic leukemia [ALL] or chronic lymphocytic leukemia [CLL]). Patients with primary CMV infection and allogeneic HSCT are at increased risk for severe disease.
In HIV patients, the pathogenic significance of CMV is considered low, even in the condition of common identification of viruses in bronchoalveolar lavage (BAL) and biopsy specimens. CMV pneumonia is found in HIV patients with a CD4 count of less than 200 cells/µL. CMV is thought to be a co-pathogen to Pneumocystis jiroveci and a cause of alveolar hemorrhage in HIV patients (due to thrombotic microangiopathy).
Clinical outcomes range from mild, self-limited illness to rapidly fatal infection with multiorgan involvement (retinitis, colitis, hepatitis). The mortality rate can be high.
CMV complicated by obstructive bronchiolitis in heart-lung and double-lung recipients affected 47% of 36 patients in a study in France. Risk factors were CMV seropositivity among donors and CMV pneumonia or CMV recurrence.
Herpes simplex virus
Herpes simplex virus causes pneumonia in only the most severely immunocompromised patients. HSV is not usually isolated from immunocompetent patients, or even from BAL fluid from HIV-infected patients. The rate of HSV pneumonia can be as high as 70-80% in HSCT recipients not receiving prophylaxis, and it can be decreased to 5% with acyclovir prophylaxis.
HSV pneumonia often is preceded by oral mucocutaneous lesions or esophagitis. The presence of mucocutaneous disease, esophagitis, or tracheitis, especially with endotracheal intubation, increases the likelihood of this pneumonia. The spectrum of respiratory diseases due to HSV infection ranges from oral pharyngitis to membranous tracheobronchitis and diffuse or localized pneumonia, which can proceed to ARDS.
In BMT recipients, the usual presentation of HSV pneumonitis consists of dyspnea, fever, cough, and hemoptysis with associated dysphagia, liver, and CNS involvement. HSV pneumonia in organ-transplant recipients is reported.
In ICU patients, HSV pneumonia manifests as an unexplained dyspnea or as a failure of weaning the patient from a ventilator. One study showed that most ICU patients had been intubated (95%) or had undergone thoracic surgery (73%) at the time of diagnosis. Blood transfusions, use of corticosteroids and other immunosuppressants, local trauma, smoking, and burns are risk factors.
Dyspnea, cough, fever, tachypnea, intractable wheezing, chest pain, and hemoptysis are common symptoms of HSV pneumonia.
Hantavirus
Hantavirus pulmonary syndrome (HPS) has an incubation period of 9-35 days.
HPS is characterized by 4 clinical phases, as follows:
- Prodrome
- Noncardiogenic pulmonary edema/adult respiratory distress syndrome and shock
- Diuresis
- Convalescence
Fever and myalgia are prominent in almost all phases and precede the onset of respiratory symptoms by 1-10 days. Cough and upper respiratory symptoms are uncommon, in contrast to many of the other viral prodromes to pneumonia. These patients often complain of severe back and hip pain, and they develop nausea, vomiting, abdominal pain, and diarrhea. Dry cough and shortness of breath herald the development of pulmonary edema.
Onset and rapid progression of cough, shortness of breath, fever, and hypotension herald the cardiopulmonary phase of the disease. Progressive pulmonary edema and respiratory failure can occur in 80-90% of patients within 2 days of hospitalization. The interval between the onset of dyspnea and respiratory failure requiring ventilatory support may be a few hours; the earliest indication is hypoxemia.
In addition to the rapidly progressive, fulminant, and often fatal form of HPS, there is also a limited, less severe form associated with mild interstitial edema and minimal airspace disease.
Adenovirus
Symptoms of adenovirus infection include fever, malaise, headache, sore throat, hoarseness, and cough. The incubation period is 4-5 days. Keratoconjunctivitis and diarrhea may or may not be seen, depending on the serotype (8, 19, 37 causing the former, and 2, 3, 5, 40, 41 causing the latter).
Serotype 14 pneumonia is associated most commonly with fever (89%) and cough (82%). Other common symptoms include shortness of breath (58%), vomiting (42%), diarrhea (34%), headache (29%), myalgias (29%), coryza (26%), chills (26%), sore throat (21%), and chest pain (16%).[11]
In adults who are immunocompromised, fever is predominant and gastrointestinal symptoms can be severe. Although adenovirus is almost always isolated from the respiratory tract, pulmonary symptoms may not be prominent and dissemination can occur without significant evidence of pneumonia (by symptoms or radiographs). Dissemination can lead to gastroenteritis, hepatitis, and hemorrhagic cystitis.[34]
Avian influenza
Avian influenza has a fulminant course and a high mortality rate. The clinical symptoms of avian influenza depend on the etiologic agent. Those infected with A/H7N7 have conjunctivitis and/or an influenzalike illness. In the 1997 outbreak of A/H5N5, 11 of 18 patients were younger than 14 years. Gastrointestinal symptoms of abdominal pain, diarrhea, and vomiting were prominent. Seven recovered, but 11 progressed to pneumonia and 6 died of ARDS or multiorgan failure.
In the 2004 outbreak, the young were affected more frequently, diarrhea was again prominent, fever was universally present, and the main presenting syndrome was community-acquired pneumonia. Lymphopenia and thrombocytopenia were common findings in all series of outbreaks and were prognostic indicators of ARDS and death. The case-fatality rate ranged from 64-80%. The incidence of asymptomatic or mild infection is unknown.
Epstein-Barr virus
Lung involvement secondary to EBV infection is rare and can occur as a complication of infectious mononucleosis. In healthy individuals, pulmonary manifestations, such as dyspnea and cough, are rare. Chronic interstitial lung disease is reported in immunocompetent patients.
In children with cystic fibrosis, EBV can cause deterioration in pulmonary function that lasts longer than 6 months after the infection is diagnosed.
In HIV patients, relatively few studies have been conducted to investigate EBV-related pulmonary disease. EBV seems to be related to the development of AIDS-associated non-Hodgkin lymphoma. BAL fluid samples from 72 European patients with AIDS were positive for EBV in 5. The patients had fever and low PaO2, with no radiographic infiltrates, and recovery was the rule.
In BMT recipients, EBV-related lung manifestations are among widespread extrarenal manifestations of posttransplant lymphatic disease. A fulminant presentation soon after transplantation is associated with a dire prognosis. Young age and primary infection are risk factors. Patients with EBV infection are at subsequent risk for other viral lung superinfection (eg, severe RSV or Mycoplasma pneumoniae infection).
Human herpesvirus
HHV 6 (A and B) and HHV 7 have a limited clinical significance and prevalence as lung pathogens. HHV 6 appears in healthy individuals or HIV-infected patients with a high CD4+ count, in whom it may result in further immunosuppression. HHV 8 is an important pathogen in HIV patients with a 200 CD4+ count of less than 200 cells/µL and has been associated with Kaposi sarcoma in the lungs, sometimes with alveolar hemorrhage.
Human immunodeficiency virus
HIV pneumonitis usually manifests as several months of mild cough and dyspnea and bilateral infiltrates on chest radiograph. Transbronchial biopsy is usually required for diagnosis. The differential diagnosis includes Pneumocystis pneumonia.
Human lymphotropic virus
HTLV-1–related lung inflammatory disorders (eg, bronchopneumopathy associated with HTLV-1) encountered in HTLV-1 carriers include lymphocytic interstitial pneumonia, diffuse panbronchiolitis, bronchiectasis, and bullous lung disease.
Rhinovirus
Rhinoviruses are a common cause of upper respiratory tract infection, but in rare cases they can trigger lower respiratory tract infections, too. Rhinoviruses commonly cause exacerbations of preexisting airway disease in those with asthma, chronic obstructive pulmonary disease (COPD),[57] or cystic fibrosis.
Rhinovirus-induced lower respiratory infections in children include bronchiolitis or bronchitis (25.6%), pneumonia (6.2%), and acute episodes of asthma (5.7%). Among 211 French children hospitalized with rhinovirus infection, 29% had ARDS. In addition, 9% of children had an associated bacterial infection, and 9% had a dual viral involvement.
Rhinoviral infection can be complicated by S pneumoniae superinfection. This might be explained by increased adherence of this virus to epithelial tracheal cells after rhinoviral infection.
Rotavirus
Rotavirus pneumonia is rare. In 1 study, rotaviruses were isolated in 27% of all tracheal aspirates from children with pneumonia. One case of fatal rotaviral pneumonitis occurred with myocarditis in a 2-year-old boy.
Two cases of fatal rotaviral pneumonitis were reported in adults. One patient was receiving long-term steroid therapy and developed rapidly progressive respiratory distress that evolved into severe respiratory failure not responsive to supportive measures. The other patient presented with massive pulmonary edema and pleural effusions.
Transplantation-related pneumonia
In recipients of thoracic organ transplants, chest complications, though rare, may manifest as tracheobronchitis, localized viral pneumonia, or diffuse and bilateral pneumonic infiltrates involving mainly the lower lobes. These findings may develop secondary to bacterial pneumonia, bronchiolitis obliterans syndrome, or acute allograft rejection. Mild clinical manifestations occur in 64% of lung transplant recipients with lung infection due to influenza virus or PIV.
Korppi M, Don M, Valent F, Canciani M. The value of clinical features in differentiating between viral, pneumococcal and atypical bacterial pneumonia in children. Acta Paediatr. Jul 2008;97(7):943-7. [Medline].
Jennings LC, Anderson TP, Beynon KA, Chua A, Laing RT, Werno AM, et al. Incidence and characteristics of viral community-acquired pneumonia in adults. Thorax. Jan 2008;63(1):42-8. [Medline].
Marcos MA, Camps M, Pumarola T, et al. The role of viruses in the aetiology of community-acquired pneumonia in adults. Antivir Ther. 2006;Vol. 11:351-359.
Templeton KE, Scheltinga SA, van den Eeden WC, Graffelman AW, van den Broek PJ, Claas EC. Improved diagnosis of the etiology of community-acquired pneumonia with real-time polymerase chain reaction. Clin Infect Dis. Aug 1 2005;41(3):345-51. [Medline].
Levy MM, Baylor MS, Bernard GR, Fowler R, Franks TJ, Hayden FG, et al. Clinical issues and research in respiratory failure from severe acute respiratory syndrome. Am J Respir Crit Care Med. Mar 1 2005;171(5):518-26. [Medline].
Legg JP, Hussain IR, Warner JA, Johnston SL, Warner JO. Type 1 and type 2 cytokine imbalance in acute respiratory syncytial virus bronchiolitis. Am J Respir Crit Care Med. Sep 15 2003;168(6):633-9. [Medline].
Falsey AR, Walsh EE. Viral pneumonia in older adults. Clin Infect Dis. Feb 15 2006;42(4):518-24. [Medline].
Shields AF, Hackman RC, Fife KH, Corey L, Meyers JD. Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med. Feb 28 1985;312(9):529-33. [Medline].
Metzgar D, Osuna M, Kajon AE, Hawksworth AW, Irvine M, Russell KL. Abrupt emergence of diverse species B adenoviruses at US military recruit training centers. J Infect Dis. Nov 15 2007;196(10):1465-73. [Medline].
Louie JK, Kajon AE, Holodniy M, Guardia-LaBar L, Lee B, Petru AM, et al. Severe pneumonia due to adenovirus serotype 14: a new respiratory threat?. Clin Infect Dis. Feb 1 2008;46(3):421-5. [Medline].
Tate JE, Bunning ML, Lott L, Lu X, Su J, Metzgar D, et al. Outbreak of severe respiratory disease associated with emergent human adenovirus serotype 14 at a US air force training facility in 2007. J Infect Dis. May 15 2009;199(10):1419-26. [Medline].
Lewis PF, Schmidt MA, Lu X, Erdman DD, Campbell M, Thomas A, et al. A community-based outbreak of severe respiratory illness caused by human adenovirus serotype 14. J Infect Dis. May 15 2009;199(10):1427-34. [Medline].
Lewis VA, Champlin R, Englund J, Couch R, Goodrich JM, Rolston K, et al. Respiratory disease due to parainfluenza virus in adult bone marrow transplant recipients. Clin Infect Dis. Nov 1996;23(5):1033-7. [Medline].
van den Hoogen BG, de Jong JC, Groen J, Kuiken T, de Groot R, Fouchier RA, et al. A newly discovered human pneumovirus isolated from young children with respiratory tract disease. Nat Med. Jun 2001;7(6):719-24. [Medline].
Falsey AR, Erdman D, Anderson LJ, Walsh EE. Human metapneumovirus infections in young and elderly adults. J Infect Dis. Mar 1 2003;187(5):785-90. [Medline].
Boivin G, Abed Y, Pelletier G, Ruel L, Moisan D, Côté S, et al. Virological features and clinical manifestations associated with human metapneumovirus: a new paramyxovirus responsible for acute respiratory-tract infections in all age groups. J Infect Dis. Nov 1 2002;186(9):1330-4. [Medline].
Cane PA, van den Hoogen BG, Chakrabarti S, Fegan CD, Osterhaus AD. Human metapneumovirus in a haematopoietic stem cell transplant recipient with fatal lower respiratory tract disease. Bone Marrow Transplant. Feb 2003;31(4):309-10. [Medline].
Gaunt ER, Hardie A, Claas EC, Simmonds P, Templeton KE. Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method. J Clin Microbiol. Aug 2010;48(8):2940-7. [Medline]. [Full Text].
Lau SK, Woo PC, Yip CC, Tse H, Tsoi HW, Cheng VC, et al. Coronavirus HKU1 and other coronavirus infections in Hong Kong. J Clin Microbiol. Jun 2006;44(6):2063-71. [Medline]. [Full Text].
Duchin JS, Koster FT, Peters CJ, Simpson GL, Tempest B, Zaki SR, et al. Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease. The Hantavirus Study Group. N Engl J Med. Apr 7 1994;330(14):949-55. [Medline].
Levy H, Simpson SQ. Hantavirus pulmonary syndrome. Am J Respir Crit Care Med. Jun 1994;149(6):1710-3. [Medline].
Centers for Disease Control and Prevention. Hantavirus Pulmonary Syndrome (HPS) Cases, by State. Available at http://www.cdc.gov/ncidod/diseases/hanta/hps/noframes/epislides/episls.htm. Accessed August 24, 2010.
World Health Organization. Cumulative Number of Confirmed Human Cases of Avian Influenza A/(H5N1) Reported to WHO. Available at http://www.who.int/csr/disease/avian_influenza/country/cases_table_2010_08_12/en/index.html. Accessed August 24, 2010.
Poon LL, Guan Y, Nicholls JM, Yuen KY, Peiris JS. The aetiology, origins, and diagnosis of severe acute respiratory syndrome. Lancet Infect Dis. Nov 2004;4(11):663-71. [Medline].
Beutel G, Wiesner O, Eder M, et al. Virus-associated hemophagocytic syndrome as a major contributor to death in patients with 2009 influenza A (H1N1) infection. Crit Care. Mar 2 2011;15(2):R80. [Medline].
Abughali N, Khiyami A, Birnkrant DJ, Kumar ML. Severe respiratory syncytial virus pneumonia associated with primary Epstein-Barr virus infection. Pediatr Pulmonol. May 2002;33(5):395-8. [Medline].
Johnstone J, Majumdar SR, Fox JD, Marrie TJ. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. Dec 2008;134(6):1141-8. [Medline].
Whitney CG, Harper SA. Lower respiratory tract infections: prevention using vaccines. Infect Dis Clin North Am. Dec 2004;18(4):899-917. [Medline].
Singh AM, Moore PE, Gern JE, Lemanske RF Jr, Hartert TV. Bronchiolitis to asthma: a review and call for studies of gene-virus interactions in asthma causation. Am J Respir Crit Care Med. Jan 15 2007;175(2):108-19. [Medline].
HILLEMAN MR. Epidemiology of adenovirus respiratory infections in military recruit populations. Ann N Y Acad Sci. Apr 19 1957;67(8):262-72. [Medline].
Anderson DJ, Jordan MC. Viral pneumonia in recipients of solid organ transplants. Semin Respir Infect. Mar 1990;5(1):38-49. [Medline].
Harrington RD, Hooton TM, Hackman RC, Storch GA, Osborne B, Gleaves CA, et al. An outbreak of respiratory syncytial virus in a bone marrow transplant center. J Infect Dis. Jun 1992;165(6):987-93. [Medline].
Kotloff RM, Ahya VN, Crawford SW. Pulmonary complications of solid organ and hematopoietic stem cell transplantation. Am J Respir Crit Care Med. Jul 1 2004;170(1):22-48. [Medline].
Barton TD, Blumberg EA. Viral pneumonias other than cytomegalovirus in transplant recipients. Clin Chest Med. Dec 2005;26(4):707-20, viii. [Medline].
Meyers JD, Flournoy N, Thomas ED. Nonbacterial pneumonia after allogeneic marrow transplantation: a review of ten years' experience. Rev Infect Dis. Nov-Dec 1982;4(6):1119-32. [Medline].
Maravi-Poma E, Martin-Loeches I, Regidor E, et al. Severe 2009 A/H1N1v influenza in pregnant women in Spain. Crit Care Med. May 2011;39(5):945-951. [Medline].
Chowell G, Bertozzi SM, Colchero MA, Lopez-Gatell H, Alpuche-Aranda C, Hernandez M, et al. Severe respiratory disease concurrent with the circulation of H1N1 influenza. N Engl J Med. Aug 13 2009;361(7):674-9. [Medline].
Thompson WW, Shay DK, Weintraub E, Brammer L, Bridges CB, Cox NJ, et al. Influenza-associated hospitalizations in the United States. JAMA. Sep 15 2004;292(11):1333-40. [Medline].
Centers for Disease Control and Prevention. Intensive-care patients with severe novel influenza A (H1N1) virus infection - Michigan, June 2009. MMWR Morb Mortal Wkly Rep. Jul 17 2009;58(27):749-52. [Medline].
Centers for Disease Control and Prevention. Updated CDC Estimates of 2009 H1N1 Influenza Cases, Hospitalizations and Deaths in the United States, April 2009 - April 10, 2010. Available at http://www.cdc.gov/h1n1flu/estimates_2009_h1n1.htm. Accessed August 24, 2010.
World Health Organization. Pandemic (H1N1) 2009 - update 89. Available at http://www.who.int/csr/don/2010_02_26/en/index.html. Accessed March 3, 2010.
Falsey AR, Walsh EE. Respiratory syncytial virus infection in adults. Clin Microbiol Rev. Jul 2000;13(3):371-84. [Medline]. [Full Text].
Pelletier G, Déry P, Abed Y, Boivin G. Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child. Emerg Infect Dis. Sep 2002;8(9):976-8. [Medline]. [Full Text].
Englund JA, Boeckh M, Kuypers J, Nichols WG, Hackman RC, Morrow RA, et al. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med. Mar 7 2006;144(5):344-9. [Medline].
Tu CC, Chen LK, Lee YS, Ko CF, Chen CM, Yang HH, et al. An outbreak of human metapneumovirus infection in hospitalized psychiatric adult patients in Taiwan. Scand J Infect Dis. 2009;41(5):363-7. [Medline].
Engelhardt SJ, Halsey NA, Eddins DL, Hinman AR. Measles mortality in the United States 1971-1975. Am J Public Health. Nov 1980;70(11):1166-9. [Medline]. [Full Text].
World Health Organization. Reported measles cases and incidence rates by WHO Member States, 2009, 2010, as of Reported measles cases and incidence rates by WHO Member States, 2009, 2010, as of 13 August 2010. Available at http://www.who.int/immunization.../diseases/measlesreportedcasesbycountry.pdf. Accessed 13 August 2010.
US Centers for Disease Control and Prevention. Epidemiologic notes and reports: measles in HIV-infected children, United States. Available at http://www.cdc.gov/mmwr/preview/mmwrhtml/00000002.htm. Accessed October 19, 2010.
Ison MG, Fishman JA. Cytomegalovirus pneumonia in transplant recipients. Clin Chest Med. Dec 2005;26(4):691-705, viii. [Medline].
Ramsey PG, Fife KH, Hackman RC, Meyers JD, Corey L. Herpes simplex virus pneumonia: clinical, virologic, and pathologic features in 20 patients. Ann Intern Med. Dec 1982;97(6):813-20. [Medline].
Kallen AJ, Brunkard J, Moore Z, Budge P, Arnold KE, Fosheim G, et al. Staphylococcus aureus community-acquired pneumonia during the 2006 to 2007 influenza season. Ann Emerg Med. Mar 2009;53(3):358-65. [Medline].
Govaert TM, Dinant GJ, Aretz K, Knottnerus JA. The predictive value of influenza symptomatology in elderly people. Fam Pract. Feb 1998;15(1):16-22. [Medline].
Uyeki TM. Human infection with highly pathogenic avian influenza A (H5N1) virus: review of clinical issues. Clin Infect Dis. Jul 15 2009;49(2):279-90. [Medline].
Dowell SF, Anderson LJ, Gary HE Jr, Erdman DD, Plouffe JF, File TM Jr, et al. Respiratory syncytial virus is an important cause of community-acquired lower respiratory infection among hospitalized adults. J Infect Dis. Sep 1996;174(3):456-62. [Medline].
Wald TG, Miller BA, Shult P, Drinka P, Langer L, Gravenstein S. Can respiratory syncytial virus and influenza A be distinguished clinically in institutionalized older persons?. J Am Geriatr Soc. Feb 1995;43(2):170-4. [Medline].
WEBER DM, PELLECCHIA JA. VARICELLA PNEUMONIA: STUDY OF PREVALENCE IN ADULT MEN. JAMA. May 10 1965;192:572-3. [Medline].
Ko FW, Ip M, Chan PK, Ng SS, Chau SS, Hui DS. A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia. Respir Med. Aug 2008;102(8):1109-16. [Medline].
Bonzel L, Tenenbaum T, Schroten H, Schildgen O, Schweitzer-Krantz S, Adams O. Frequent detection of viral coinfection in children hospitalized with acute respiratory tract infection using a real-time polymerase chain reaction. Pediatr Infect Dis J. Jul 2008;27(7):589-94. [Medline].
Falsey AR, McCann RM, Hall WJ, Criddle MM. Evaluation of four methods for the diagnosis of respiratory syncytial virus infection in older adults. J Am Geriatr Soc. Jan 1996;44(1):71-3. [Medline].
Osiowy C. Direct detection of respiratory syncytial virus, parainfluenza virus, and adenovirus in clinical respiratory specimens by a multiplex reverse transcription-PCR assay. J Clin Microbiol. Nov 1998;36(11):3149-54. [Medline]. [Full Text].
Luminex Corporation. Luminex Respiratory Viral Panel. Available at http://www.luminexcorp.com/rvp/overview.html.. Accessed August 28, 2009.
Pettila V, Webb SA, Bailey M, et al. Acute kidney injury in patients with influenza A (H1N1) 2009. Intensive Care Med. May 2011;37(5):763-7. [Medline].
Nin N, Lorente JA, Soto L, et al. Acute kidney injury in critically ill patients with 2009 influenza A (H1N1) viral pneumonia: an observational study. Intensive Care Med. May 2011;37(5):768-74. [Medline].
Erard V, Huang ML, Ferrenberg J, Nguy L, Stevens-Ayers TL, Hackman RC, et al. Quantitative real-time polymerase chain reaction for detection of adenovirus after T cell-replete hematopoietic cell transplantation: viral load as a marker for invasive disease. Clin Infect Dis. Oct 15 2007;45(8):958-65. [Medline].
Centers for Disease Control and Prevention. Acute respiratory disease associated with adenovirus serotype 14--four states, 2006-2007. MMWR Morb Mortal Wkly Rep. Nov 16 2007;56(45):1181-4. [Medline].
Kanne JP, Godwin JD, Franquet T, Escuissato DL, Müller NL. Viral pneumonia after hematopoietic stem cell transplantation: high-resolution CT findings. J Thorac Imaging. Aug 2007;22(3):292-9. [Medline].
Peters CJ, Khan AS. Hantavirus pulmonary syndrome: the new American hemorrhagic fever. Clin Infect Dis. May 1 2002;34(9):1224-31. [Medline].
Hayden FG, Osterhaus AD, Treanor JJ, Fleming DM, Aoki FY, Nicholson KG, et al. Efficacy and safety of the neuraminidase inhibitor zanamivir in the treatment of influenzavirus infections. GG167 Influenza Study Group. N Engl J Med. Sep 25 1997;337(13):874-80. [Medline].
Hayden FG, Treanor JJ, Fritz RS, Lobo M, Betts RF, Miller M, et al. Use of the oral neuraminidase inhibitor oseltamivir in experimental human influenza: randomized controlled trials for prevention and treatment. JAMA. Oct 6 1999;282(13):1240-6. [Medline].
Hayden FG, Atmar RL, Schilling M, Johnson C, Poretz D, Paar D, et al. Use of the selective oral neuraminidase inhibitor oseltamivir to prevent influenza. N Engl J Med. Oct 28 1999;341(18):1336-43. [Medline].
Hirji Z, O'Grady S, Bonham J, Mak M, Takata-Shewchuk J, Hawkins K, et al. Utility of zanamivir for chemoprophylaxis of concomitant influenza A and B in a complex continuing-care population. Can Commun Dis Rep. Feb 1 2001;27(3):21-4. [Medline].
Monto AS, Fleming DM, Henry D, de Groot R, Makela M, Klein T, et al. Efficacy and safety of the neuraminidase inhibitor zanamivirin the treatment of influenza A and B virus infections. J Infect Dis. Aug 1999;180(2):254-61. [Medline].
Treanor JJ, Hayden FG, Vrooman PS, Barbarash R, Bettis R, Riff D, et al. Efficacy and safety of the oral neuraminidase inhibitor oseltamivir in treating acute influenza: a randomized controlled trial. US Oral Neuraminidase Study Group. JAMA. Feb 23 2000;283(8):1016-24. [Medline].
Watanabe A, Chang SC, Kim MJ, Chu DW, Ohashi Y. Long-acting neuraminidase inhibitor laninamivir octanoate versus oseltamivir for treatment of influenza: A double-blind, randomized, noninferiority clinical trial. Clin Infect Dis. Nov 15 2010;51(10):1167-75. [Medline].
Martin-Loeches I, Lisboa T, Rhodes A, Moreno RP, Silva E, Sprung C, et al. Use of early corticosteroid therapy on ICU admission in patients affected by severe pandemic (H1N1)v influenza A infection. Intensive Care Med. Feb 2011;37(2):272-83. [Medline].
Moscona A. Management of respiratory syncytial virus infections in the immunocompromised child. Pediatr Infect Dis J. Mar 2000;19(3):253-4. [Medline].
Swedish Consensus Group. Management of infections caused by respiratory syncytial virus. Scand J Infect Dis. 2001;33(5):323-8. [Medline].
Bordigoni P, Carret AS, Venard V, Witz F, Le Faou A. Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. May 1 2001;32(9):1290-7. [Medline].
Morfin F, Dupuis-Girod S, Frobert E, Mundweiler S, Carrington D, Sedlacek P, et al. Differential susceptibility of adenovirus clinical isolates to cidofovir and ribavirin is not related to species alone. Antivir Ther. 2009;14(1):55-61. [Medline].
Kapelushnik J, Or R, Delukina M, Nagler A, Livni N, Engelhard D. Intravenous ribavirin therapy for adenovirus gastroenteritis after bone marrow transplantation. J Pediatr Gastroenterol Nutr. Jul 1995;21(1):110-2. [Medline].
McCarthy AJ, Bergin M, De Silva LM, Stevens M. Intravenous ribavirin therapy for disseminated adenovirus infection. Pediatr Infect Dis J. Nov 1995;14(11):1003-4. [Medline].
Adenovirus. Am J Transplant. Nov 2004;4 Suppl 10:101-4. [Medline].
Chakrabarti S, Collingham KE, Holder K, Fegan CD, Osman H, Milligan DW. Pre-emptive oral ribavirin therapy of paramyxovirus infections after haematopoietic stem cell transplantation: a pilot study. Bone Marrow Transplant. Oct 2001;28(8):759-63. [Medline].
Safdar A. Immune modulatory activity of ribavirin for serious human metapneumovirus disease: early i.v. therapy may improve outcomes in immunosuppressed SCT recipients. Bone Marrow Transplant. Apr 2008;41(8):707-8. [Medline].
Raza K, Ismailjee SB, Crespo M, Studer SM, Sanghavi S, Paterson DL, et al. Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin. J Heart Lung Transplant. Aug 2007;26(8):862-4. [Medline].
Bonney D, Razali H, Turner A, Will A. Successful treatment of human metapneumovirus pneumonia using combination therapy with intravenous ribavirin and immune globulin. Br J Haematol. Jun 2009;145(5):667-9. [Medline].
Chu CM, Cheng VC, Hung IF, Wong MM, Chan KH, Chan KS, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax. Mar 2004;59(3):252-6. [Medline]. [Full Text].
Chen F, Chan KH, Jiang Y, Kao RY, Lu HT, Fan KW, et al. In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds. J Clin Virol. Sep 2004;31(1):69-75. [Medline].
Forni AL, Schluger NW, Roberts RB. Severe measles pneumonitis in adults: evaluation of clinical characteristics and therapy with intravenous ribavirin. Clin Infect Dis. Sep 1994;19(3):454-62. [Medline].
Zamora MR. Cytomegalovirus and lung transplantation. Am J Transplant. Aug 2004;4(8):1219-26. [Medline].
Bacigalupo A, Bregante S, Tedone E, Isaza A, Van Lint MT, Moro F, et al. Combined foscarnet -ganciclovir treatment for cytomegalovirus infections after allogeneic hemopoietic stem cell transplantation (Hsct). Bone Marrow Transplant. Nov 1996;18 Suppl 2:110-4. [Medline].
Centers for Disease Control and Prevention. Seasonal Influenza (Flu). Recommendations of the Advisory Committee on Immunization Practices (ACIP). Available at http://www.cdc.gov/flu/professionals/acip/. Accessed August 22, 2010.
van der Hoek L. Human coronaviruses: what do they cause?. Antivir Ther. 2007;12(4 Pt B):651-8. [Medline].
Tang RS, Schickli JH, MacPhail M, et al. Effects of human metapneumovirus and respiratory syncytial virus antigen insertion in two 3' proximal genome positions of bovine/human parainfluenza virus type 3 on virus replication and immunogenicity. J Virol. Oct 2003;77(20):10819-28. [Medline]. [Full Text].
Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. Oct 2009;15(10):1143-238. [Medline]. [Full Text].
de Jong MD, Hien TT. Avian influenza A (H5N1). J Clin Virol. Jan 2006;35(1):2-13. [Medline].
Wong SS, Yuen KY. Avian influenza virus infections in humans. Chest. Jan 2006;129(1):156-68. [Medline].
| Virus | Viral Culture | Cytologic Evaluation | Rapid Antigen Detection | Gene Amplification |
| Influenza virus | HA*, SV† | IF‡, ELISA§ | RT-PCR# | |
| Adenovirus | CE, SV | Intranuclear inclusions | IF, ELISA | RT-PCR |
| Paramyxoviruses | ||||
| Respiratory syncytial virus | CE, SV | Eosinophilic cytoplasmic inclusions | IF, ELISA | RT-PCR |
| Parainfluenza virus | HA, SV | Eosinophilic intranuclear inclusions | IF, ELISA | RT-PCR |
| Measles virus | HA | |||
| Herpes viruses | ||||
| Herpes simplex virus | CE, SV | Cytoplasmic inclusions | IF, ELISA | PCR |
| Varicella-zoster virus | CE | Cytoplasmic inclusions | IF | RT-PCR |
| Cytomegalovirus | CE, SV | "Owl's eye" cells | IF, ELISA | RT-PCR |
| Hantavirus | Antibodies against FCV** | FVC RNA by RT-PCR | ||
| * HA - Hemaglutination † SV - Shell viral culture ‡ IF - Immunofluorescence § ELISA - Enzyme-linked immunosorbent assay CE - Cytopathogenic effects # RT-PCR - Reverse transcriptase polymerase chain reaction ** FCV - Four corners virus | ||||
| Virus | Treatment | Prevention |
| Influenza virus | Amantadine Rimantadine | Influenza vaccine Chemoprophylaxis with: Amantadine Rimantadine Zanamivir Oseltamivir |
| Respiratory syncytial virus | Ribavirin | RSV immunoglobulin Palivizumab |
| Parainfluenza virus | Ribavirin | |
| Herpes simplex virus | Acyclovir | |
| Varicella-zoster virus | Acyclovir | Varicella-zoster immunoglobulin |
| Adenovirus | Ribavirin | |
| Measles virus | Ribavirin | Intravenous immunoglobulin |
| Cytomegalovirus | Ganciclovir Foscarnet | Intravenous immunoglobulin |
| Amantadine (Symmetrel) | Rimantadine (Flumadine) | Zanamivir (Relenza) | Oseltamivir (Tamiflu) | |
| Mechanism of action | M2 ion channel blockade inhibits HA* cleavage beta block RNA encoding, which reduces early viral replication. | Viral NA† inhibition prevents sialic acid cleavage from HA beta virus gets trapped inside cells, and epithelial spread is blocked. | ||
| Spectrum | Influenza A only | Influenza A only | Influenza A and B | Influenza A and B |
| Oral bioavailability | Good | Good | Poor | Good |
| Protein binding, % | 67 | 40 | None | Minimal |
| Half-life, h | 12-18 | 24-36 | 2.5-5 | 1-3 |
| Excretion | Renal (not removed by hemodialysis) | Renal and gastrointestinal | Renal | |
| Drug interaction | Synergistic CNS toxicity with antihistamines, anticholinergics, CNS stimulants | Beta Plasma level: ASA§, acetaminophen | None | None |
| Renal clearance | TMP-SMZ¶, triamterene, hydrochlorothiazide, quinine sulfate, quinidine | Cimetidine | None | None |
| * HA - Hemagglutinin † NA - Neuraminidase § ASA - Acetylsalicylic acid ¶ TMP-SMZ - Trimethoprim and sulfamethoxazole | ||||
Print
