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Emerging and Rare Viral Infections in Transplantation

  • Staci A. FischerEmail author
Chapter
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Abstract

Immunocompromised patients such as those undergoing solid organ or hematopoietic stem cell transplantation are at substantial risk for infection with numerous pathogens. Infections with cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein–Barr virus (EBV), and human herpesvirus-6 (HHV-6) are well-described complications of transplantation. As viruses previously believed to be quiescent through widespread vaccination (e.g., measles and mumps) reemerge and molecular diagnostic techniques are refined, rare and emerging viral infections are increasingly diagnosed in transplant recipients. This chapter will review the clinical manifestations, diagnosis, and potential antiviral therapies for these viruses in the transplant population.

Keywords

Bocavirus Coronavirus Hepatitis E Norovirus Parvovirus Metapneumovirus 

Viral infections are common following solid organ and hematopoietic stem cell transplantation, as detailed in other chapters. While cytomegalovirus (CMV) remains the most prominent virus in transplantation, and the clinical manifestations and complications of infection with other herpesviruses (e.g., herpes simplex virus, Epstein–Barr virus, and human herpesviruses 6 and 8) are well described, improvements in diagnostic techniques have led to the recognition of a number of additional viruses with potential pathogenicity in the immunocompromised host. Outbreaks of emerging viruses, the resurgence of vaccine-preventable viral infections, and the identification of viruses which cause self-limited infection in immunocompetent children but significant disease in transplant recipients have highlighted the breadth of pathogens in this patient population. Some of these emerging and unusual viral pathogens are discussed in alphabetical order below.

49.1 Astrovirus

Astrovirus is a common cause of viral gastroenteritis throughout the world and has been a cause of outbreaks of diarrheal disease in schools, hospitals, nursing homes, and military bases [1, 2, 3]. Several recent reports have highlighted the impact of this RNA virus on immunocompromised hosts. In addition to its role in gastroenteritis in these patients, one astrovirus subgroup (VA1/HMO-C) has been reported to cause encephalitis in allogeneic hematopoietic stem cell transplant (HSCT) recipients and children with X-linked agammaglobulinemia [4, 5]. Molecular techniques including reverse-transcription polymerase chain reaction (RT-PCR), RNA sequencing, and next-generation sequencing have demonstrated the presence of this subgroup in the cerebrospinal fluid (CSF) and brain tissue of infected patients. Immunohistochemical staining on biopsy tissue has confirmed the presence of invasive infection. There are no known antiviral treatments available, and central nervous system (CNS) infection has been fatal in the cases reported to date. Additional study is needed to determine the prevalence of astrovirus infection in transplanted patients.

49.2 Bocavirus

Bocavirus is a human parvovirus that causes upper and lower respiratory tract infection, gastroenteritis, and encephalitis in children [6, 7]. Infection is most common in the late fall and winter, and most commonly presents with rhinorrhea, fever, cough, wheezing, or diarrhea. Thirty percent of children develop hypoxia, and a variety of radiographic findings have been reported, including peribronchial cuffing, lobar infiltrates, and pleural effusions. Nosocomial infection has occurred [8]. Bocavirus infection has been reported in the first few weeks following hematopoietic stem cell transplantation, presenting with fever, rhinorrhea, cough, diarrhea, and hypoxia [9]. Virus has been detected in high quantities in plasma, nasopharyngeal aspirates, and stool. Fecal shedding occurs for several weeks to months after clinical resolution of infection [10]. Severe and prolonged diarrhea has been described in liver transplant and hematopoietic stem cell recipients [11]. It has been suggested that bocavirus, like respiratory syncytial virus (RSV) and parainfluenza, may play a role in the development of bronchiolitis obliterans, a manifestation of chronic rejection in lung transplantation [12, 13, 14]. To date, there are no data on antiviral efficacy against bocavirus.

49.3 Chikungunya Virus

Chikungunya virus, a mosquito-borne alphavirus transmitted by Aedes aegypti and Aedes albopictus, is a tropical infection which has caused epidemic disease in India, Thailand, Malaysia, Madagascar, and Reunion Island [15, 16]. It is endemic in eastern, central, and southern Africa. In 2013, chikungunya was reported in St. Martin, with epidemic spread throughout the Caribbean, Central America, South America, and Florida, where infection spread locally via A. aegypti [17].

After an incubation period of 2–4 days, infection presents with high fever, headache, myalgias, and arthralgias, and can resemble dengue. Arthralgias are typically symmetric and involve large joints, particularly in the legs and arms. Frank arthritis may also occur in the interphalangeal joints, wrists, and ankles. Half of patients also develop a rash, which can be maculopapular, petechial, or bullous and is most commonly located on the trunk, with occasional involvement of the face, extremities, palms, and soles. Ocular pain has also been reported. Rarely, meningoencephalitis, myocarditis, or hepatitis can occur. Symptoms resolve in 7–10 days, although arthralgias and joint stiffness may persist for weeks to months after fever resolves. Severe manifestations of infection with fatal outcomes have been reported in patients with underlying diabetes, lung disease, or chronic neurologic conditions.

Laboratory findings include lymphopenia, thrombocytopenia, elevated transaminases, and hypocalcemia. Diagnosis may be made serologically or by RT-PCR. IgM antibodies develop as fever resolves, typically 1 week after symptom onset. There is currently no known effective antiviral therapy for chikungunya.

During a widespread outbreak of infection on Reunion Island in the Indian Ocean, organ and tissue donors were screened for the presence of chikungunya infection [18]. Corneal donors were found to have serologic and PCR evidence of infection in serum and corneal tissue. Transmission of infection with corneal transplantation is presumed to occur. There have been no reports of transmission of chikungunya in solid organ or stem cell transplantation to date although with reports of infection in Asia, Europe, and North America in travelers from endemic areas, the risk of transmission and the clinical course of infection in these patients require further study.

49.4 Coronavirus

In February 2003 a worldwide outbreak of severe respiratory infection occurred, infecting more than 8000 patients over several months in 29 countries, most severely affecting southern China, Hong Kong, and Canada, with well-described healthcare-associated outbreaks [19, 20, 21, 22, 23, 24, 25, 26]. Eighty percent of those affected were previously healthy, with no comorbid conditions. The outbreak began in Guangdong Province, China, in November 2002 and with global travel spread rapidly to multiple continents. The infection of numerous health care workers and the rapidly fatal course of infection, even in healthy hosts, were remarkable. Named Severe Acute Respiratory Syndrome (SARS), this infection was quickly determined to be due to a new strain of coronavirus, a group of viruses known to cause human disease since the 1960s [27].

Patients initially noted high fever, myalgias, headache, and cough, and subsequently became dyspneic [19, 20, 25, 28]. A productive cough was seen in nearly one third of patients, while rash and lymphadenopathy were absent. Lymphopenia, thrombocytopenia, mild elevation of transaminases, prolonged prothrombin time with elevated D-dimers, elevated lactate dehydrogenase (LDH) and creatine kinase (CK), and hyponatremia were common lab findings [25]. Chest radiographs revealed focal airspace consolidation or ground glass opacities, initially without the interstitial infiltrates most characteristic of viral pneumonitis, with lower lung field predominance [22, 25]. Pleural effusions and mediastinal lymphadenopathy were generally absent. Histopathologic findings in lung biopsies and at autopsy included diffuse alveolar damage consistent with adult respiratory distress syndrome (ARDS), with significant alveolar edema, minimal inflammation, and no viral inclusions.

Treatment included corticosteroids and intravenous or oral ribavirin. Although published data are not yet available in humans, animal models suggest that monoclonal antibody to SARS coronavirus (SARS-CoV) is effective in decreasing viral replication and improving outcomes [26]. The overall case fatality rate during the SARS epidemic was nearly 10% [19]. A novel coronavirus was rapidly isolated and identified as the cause of SARS and sequenced, allowing for RT-PCR and serologic testing to be developed [29, 30].

During the SARS outbreak in Toronto, a liver transplant recipient was fatally infected while visiting a medical center for an outpatient clinic visit nearly 10 years posttransplant [31]. Disseminated infection was described in a lung transplant recipient in whom virus was detected in lungs, bowel, lymph nodes, liver, kidney, skeletal muscle, and brain at autopsy [32, 33]. Tissue viral loads were significantly higher in transplant recipients than in their immunocompetent counterparts [34]. The last of the nearly 8000 reported cases of SARS-CoV was reported in May 2004, after which no additional cases have been reported, for unclear reasons.

In September 2012, initial reports of infection with another novel human coronavirus began in Saudi Arabia, with rapid spread to neighboring Egypt, Iran, Jordan, Kuwait, Lebanon, Qatar, Oman, Yemen, and the United Arab Emirates, then to other continents with airline travel [35]. Middle East Respiratory Syndrome Coronavirus (MERS CoV) has been reported to cause severe respiratory tract infection in adult patients, with a mortality rate as high as 60%, most commonly in those with diabetes mellitus and end stage renal disease [36]. After a median incubation period of 5 days (range, 2–14 days), patients often present with fever, cough, dyspnea, and diarrhea after close contact with an infected case and/or travel from an area where infection is active. Coryza, headache, nausea, vomiting, and abdominal pain have also been reported [37]. Laboratory findings include thrombocytopenia, leukopenia, lymphopenia, and elevated transaminases and LDH. Coinfection with other respiratory viruses has been reported [38]. As with SARS-CoV, health care workers are at risk for infection [39, 40]. Dromedary camels have been reported to harbor infection in the Arabian Peninsula, although the mode of transmission of infection has not yet been elucidated [41].

Several cases of MERS CoV infection have been reported in hematopoietic stem cell and solid organ transplant recipients, who have developed bilateral pulmonary infiltrates with respiratory failure, acute renal failure, leukopenia, thrombocytopenia, and elevated transaminases, at times without fever [36, 42].

While difficult to grow in cell culture, MERS CoV may be diagnosed by RT-PCR on respiratory secretions. Virus has been detected with these techniques in urine and stool as well. To increase the yield of testing, it is recommended that multiple specimens from different sites (e.g., nasopharyngeal swab, sputum, BAL fluid, serum, and stool) be tested using RT-PCR, which is available from the CDC and local health departments in the USA [37]. Due to the risk of transmission of infection to health care workers, contact and airborne precautions are recommended in caring for the suspected MERS-CoV infected patient [39, 40].

While there have been no randomized, controlled clinical trials of antivirals against MERS-CoV, ribavirin and mycophenolate mofetil (an immunosuppressive agent used commonly in transplantation) have in vitro activity against the virus [43]. Ribavirin (in combination with interferon α-2b) has demonstrated promise in decreasing lung injury and viral replication in rhesus macaques infected with MERS-CoV [44]. A retrospective cohort study describing the use of ribavirin and interferon α-2a in twenty patients with severe infection demonstrated an early survival benefit [45].

Whereas coronaviruses made world headlines with the SARS epidemic in 2002–2004 and the MERS-CoV emergence in 2012, coronaviruses OC43 (group 1) and 229E (group 2) have been known for decades to cause upper respiratory tract infections during the fall and winter months. Coronavirus NL63 (group 1) has been reported to cause upper and lower respiratory tract infections in immunocompetent hosts in the Netherlands, and coronavirus HKU1 (group 2) has been reported to cause pneumonia in Hong Kong and France [21]. Non-SARS coronaviruses have recently been associated with severe lower respiratory tract infections in hospitalized patients, including lung and liver transplant recipients [46]. Coronavirus 229E has been isolated from hematopoietic stem cell transplantation recipients with fever and cough associated with interstitial and alveolar pulmonary infiltrates [46]. Pancytopenia may be present. Radiographic infiltrates are most commonly interstitial, although 28% are alveolar. Pleural effusions may be present, and pneumothorax has been noted in a minority of patients. Diagnosis may be made by culture in human hepatoma HUH7 cell line, or by RT-PCR [46, 47].

49.5 Hepatitis E

Hepatitis E is endemic in developing countries and has been reported to cause epidemic disease in Asia, Africa, and Latin America via fecal–oral transmission [48]. Travel-related infection has been reported in those returning from endemic areas with poor sanitation. Recent reports have highlighted the important role of this infection in transplant recipients.

Hepatitis E virus (HEV) is an RNA virus with four major genotypes with presumed reservoirs in pigs, wild boars, deer, and mollusks [49, 50]. Seroprevalence surveys indicate that infection in blood donors, even in France and the USA, is significant; in some areas, hepatitis E is more prevalent than hepatitis A [51, 52]. Epidemics of infection have been described from ingestion of contaminated water, mollusks, and undercooked deer, boar, or pig meat [53, 54, 55]. Blood transfusion-transmitted infection has also been described [56, 57, 58, 59]. After an incubation period of two to nine weeks, patients develop jaundice, abdominal pain, anorexia, and nausea. Fever and chills may occur as well, although rash is unusual. Diagnosis can be made by RT-PCR detection of HEV RNA, which is present between 2 and 6 weeks after infection, as symptoms occur [60]. IgM antibodies develop as symptoms resolve, approximately 4 weeks after infection. Elevated transaminases occur, peaking approximately 6 weeks after infection. While viremia resolves within 6 weeks of infection, virus remains detectable in stool for several weeks after viremia resolves and IgG appears. Serum IgG antibodies persist for years after acute infection.

Approximately 10% of patients with acute HEV infection develop fulminant hepatitis with acute hepatic failure; the presence of pregnancy or underlying chronic liver disease (e.g., chronic hepatitis C infection or cirrhosis) increases the risk for severe infection [61, 62]. Histopathologic findings on liver biopsy include lymphocytic infiltration of portal triads. Chronic hepatitis appears to be rare in immunocompetent hosts.

Disease in organ transplant recipients has been characterized by a high incidence of chronic infection (in up to 60% of acutely infected patients) with progressive fibrosis and eventual cirrhosis [63, 64, 65, 66]. Reactivation of infection has been described in liver and allogeneic HSCT recipients, in whom nearly half of infections became chronic [67, 68, 69]. Liver transplant recipients appear to be at increased risk for chronic infection resulting from reactivation of HEV after transplantation, as well as acute graft hepatitis from reactivation or primary infection [70]. Extrahepatic manifestations of infection in transplant recipients have included glomerulonephritis and neurologic involvement [69, 71].

There are no FDA-approved therapies for HEV infection, although decreasing immunosuppression appears to have helped control viremia in some chronically infected transplant recipients. In small studies, interferon alpha and ribavirin have been reported to decrease viremia in these patient populations [72, 73].

49.6 Lymphocytic Choriomeningitis Virus

Lymphocytic choriomeningitis virus (LCMV) gained notoriety as a pathogen in solid organ transplantation in 2005, when the first two outbreaks of donor-transmitted infection were described [74, 75, 76]. Additional donor-transmitted outbreaks have recently occurred in the USA and Australia [77, 78, 79, 80]. Four clusters of donor-derived infection have occurred in the USA to date.

LCMV is a rodent-borne Old World arenavirus that causes asymptomatic or mild, self-limited illness in the immunocompetent host. Rodents, especially common house mice, laboratory mice, and hamsters, often acquire infection congenitally, resulting in lifelong, asymptomatic excretion of virus in urine, saliva, and feces [81, 82, 83, 84]. Human infection occurs via direct contact with infected rodents or aerosolized infected excreta (e.g., with cleaning soiled cage bedding). Symptoms described in immunocompetent humans include fever, headache, and myalgias, with CSF findings consistent with aseptic meningitis (e.g., lymphocytic pleocytosis). In the normal host, infection is self-limited and carries a mortality rate of less than 1% [85].

In the transplant clusters, infection with LCMV has been fatal in more than 80% of cases [74, 78, 80]. Patients have presented within the first month posttransplant with fever, diarrhea, abdominal pain, and dyspnea. Rash, headache, lethargy, hypotension, and the presence of pulmonary infiltrates are variable. Thrombocytopenia and anemia have been present, with variable peripheral leukocyte and lymphocyte counts. Acute hepatitis with elevated transaminases has been noted, as well as coagulopathy with prolonged protimes. Patients have developed rapidly progressive multisystem failure with encephalopathy prior to death. In one cluster, while the donor had no evidence of infection in multiple tissues tested, a pet hamster present in the donor’s home for several weeks prior to donation was found to have LCMV in multiple tissues [74]. Virus isolated from the hamster was identical to that isolated from the infected transplant recipients. The survivor in that cluster, a kidney recipient, was treated with discontinuation of all immune suppression except corticosteroids and with intravenous ribavirin. Similar approaches have been used in more recent cases [80].

With four donor-derived infection outbreaks in the USA alone, LCMV infection is likely more common than previously recognized in transplant recipients. Detailed workup of potential organ donors with aseptic meningitis or meningoencephalitis may prevent transmission in some cases. Whether LCMV infection occurs posttransplant in recipients with exposure to pet hamsters or house mice is unknown.

49.7 Metapneumovirus

Human metapneumovirus is a single-stranded RNA paramyxovirus of worldwide endemicity that causes respiratory tract infection in children, the elderly, and immunocompromised adults, with outbreaks reported in long-term care facilities [86, 87, 88, 89, 90]. Infection occurs in the late winter and early spring (January through April), similar to the seasonality of respiratory syncytial virus (RSV). Upper and lower respiratory tract symptoms, including rhinorrhea, sore throat, cough, dyspnea, and fever, have been described.

Infection has been described following lung and heart–lung transplantation, resulting in acute pneumonia with diffuse alveolar damage and hyaline membrane formation [91, 92]. Lung transplant recipients with metapneumovirus pneumonia have a 14% mortality rate and are at higher risk for acute and chronic rejection [92, 93]. In renal transplant recipients, pneumonitis due to metapneumovirus has been reported 3 years posttransplant [94]. In one study of HSCT recipients, human metapneumovirus was isolated via RT-PCR in 26% of symptomatic patients undergoing bronchoscopy and carried a mortality rate of 80% [95]. Infection occurred within the first few weeks following transplant, and was characterized by fever, nasal congestion, and cough, with rapid development of hypoxia, hypotension, and progressive pneumonia, with diffuse alveolar hemorrhage in three of five patients [94, 95, 96]. Pleural effusions and nodular infiltrates may be seen, which may help differentiate infection from RSV. Coinfection with RSV, rhinovirus, and CMV has been described following lung transplantation [97].

Ribavirin has been demonstrated to decrease human metapneumovirus replication in the lungs in a mouse model [98], and intravenous ribavirin has been effective in the treatment of several lung transplant recipients with metapneumovirus infection [99].

49.8 Measles

Measles outbreaks have occurred in multiple states in recent years, with an attack rate of greater than 90% among susceptible patients, including unvaccinated children and adults [100, 101, 102, 103, 104, 105, 106, 107, 108]. Affected patients develop fever, cough, and coryza, associated with a characteristic rash. Infection may be complicated by pneumonia, encephalitis, or dissemination, with significant mortality noted in solid organ and HSCT recipients [109]. Infection has been associated with waning immunity and is diagnosed serologically. There are no data on antivirals for treatment of measles.

49.9 Mumps

Mumps has been increasingly reported in the USA, with more than 10,000 cases reported in a large multistate outbreak in 2005–2006 [110, 111, 112, 113, 114, 115, 116]. Patients present with acute onset of unilateral or bilateral parotitis; infection may be complicated by orchitis, oophoritis, pancreatitis, mastitis, meningitis, and encephalitis [117]. Infection may be diagnosed serologically or via PCR [118, 119]. No antivirals have been investigated in the treatment of mumps. Enhanced efforts at immunization against measles and mumps pretransplant as well as active surveillance posttransplant are warranted.

As a result of the re-emergence of these vaccine-preventable viruses, recent guidelines suggest vaccination with the measles, mumps, and rubella (MMR) vaccine 2 years following hematopoietic stem cell transplantation in patients without evidence of graft-versus-host disease [120, 121]. If at all possible, patients undergoing solid organ transplantation who do not have evidence of protection against measles and mumps (e.g., positive IgG antibody to each) should be vaccinated prior to the initiation of immunosuppressive therapy.

49.10 Norovirus

Noroviruses are caliciviruses that cause over 20 million cases of gastroenteritis annually in the USA and over half of all epidemics of gastroenteritis worldwide [122, 123, 124, 125, 126, 127, 128, 129]. Infection is acquired via consumption of contaminated foods (including raw oysters, fruit, and vegetables) or via ingestion of or swimming in contaminated water, with spread via fomites and from person to person [130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145]. Infection is extremely contagious and often spreads rapidly as a result of prolonged fecal shedding in affected patients after resolution of symptoms. Outbreaks of infection have been described in multiple settings including military barracks, restaurants, hospitals, long-term care facilities, schools, and cruise ships [122].

Infection may be asymptomatic or present with the sudden onset of nausea, vomiting, and diarrhea after an incubation period of less than 48 h. Some studies have suggested that vomiting is more common in children, with diarrheal symptoms predominating in infants and adults [138, 148]. Infection is most common in the winter months, with symptoms lasting 1–7 days [122, 142, 148]. Attack rates in some outbreaks have been 50–90%, with health care workers at substantial risk for infection [127, 130, 137, 138, 139, 144, 145, 146, 147].

Noroviruses cannot be cultured in vitro, but RT-PCR and enzyme immunoassay (EIA) assays are available for diagnosis in stool specimens [148, 149, 150].

Norovirus infection in solid organ transplant recipients is common, and marked by risk for chronic and relapsing infection [150]. Infection presents with watery diarrhea, which can cause volume depletion and acute renal failure in renal transplant recipients [126, 142, 149, 151]. Patients may be symptomatic for months and may shed virus in stool for years. Hematopoietic stem cell transplant recipients have been reported to develop acute and chronic diarrheal disease from norovirus infection, which has been associated with the subsequent development of chronic GVHD [151, 152]. Receipt of cord blood, induction with fludarabine, and receipt of alemtuzumab have been reported to be risk factors for norovirus infection in this setting. Nosocomial outbreaks of infection in HSCT units have resulted in infection of staff and patients, with sepsis from bacterial translocation complicating several cases [152, 153].

Treatment of norovirus infection in transplant recipients has not been investigated in randomized, controlled trials to date. Reduction of immunosuppression resulted in clearance of infection in one intestinal transplant recipient with norovirus infection [154]. There are no available antiviral therapies to date. Noroviruses are highly resistant to disinfectants, propagating prolonged transmission in many environments.

49.11 Parvovirus B19

Parvovirus B19 infection is common, with 60–90% of adults having serologic evidence of prior infection [155]. In children, parvovirus infection causes erythema infectiosum, a febrile illness with a characteristic “slapped cheek” rash. Adults with acute parvovirus infection develop a flu-like illness, sometimes with resultant arthropathy. A pathogen of erythroid progenitor cells, parvovirus B19 causes severe anemia in patients with underlying hemolytic disorders and hydrops fetalis in pregnancy. In recent years, neurologic involvement including meningoencephalitis has been described, which may be more common in immunocompromised hosts [156, 157].

In transplant recipients, anemia is the most common presentation of infection. Fever occurs in 25% of patients and arthralgia or rash occurs in less than 10% of those affected [158]. Pancytopenia may be present. Other manifestations described in the transplant population include hepatitis, myocarditis, pneumonitis, encephalitis, meningitis, peripheral neuritis, and collapsing glomerulopathy [155, 157, 158, 159, 160]. Those with CNS infection may develop sequelae including seizures, cognitive deficits, stroke, and muscle wasting [157]. Donor-transmitted infection has been described, presenting with allograft dysfunction, fever, arthralgia, and pancytopenia, often without a rash [161, 162, 163, 164]. Chronic or recurrent anemia may be seen posttransplant, as well as pure red cell aplasia [165, 166]. Parvovirus B19 infection has also been associated with the subsequent development of thrombotic microangiopathy in kidney transplant recipients, including a cluster of cases in Iran; hemophagocytic lymphohistiocytosis has also been described in this population [167, 168]. The significance of the frequent finding of parvovirus DNA in renal allografts pre- and posttransplant is under investigation [169]. In other transplant populations, parvovirus may be associated with chronic cellular allograft rejection [170].

Diagnosis of parvovirus B19 infection may be made by serology, PCR, or bone marrow examination in immunocompetent hosts. The yield of serologic testing (especially IgM) is limited in transplant recipients who may not mount an adequate antibody response to infection, so that RT-PCR on blood, bone marrow, or other involved tissues is necessary to detect infection in many cases [155].

Infection may respond to intravenous immunoglobulin (IVIg), with relapses occurring in up to 25% of immunosuppressed hosts [155]. There are no published data on the use of antivirals in parvovirus infection.

49.12 Polyoma Viruses (KI, WU, and Merkel Cell Carcinoma Polyomaviruses)

Human polyoma viruses such as BK virus and JC virus are well known pathogens in transplantation and are discussed elsewhere. In recent years three additional polyoma viruses have been described as potential pathogens in immunocompromised hosts. Like BK and JC, these viruses frequently cause asymptomatic primary infection in healthy patients and are capable of establishing latent infection which can be reactivated in the setting of immune suppression. KI and WU viruses (named for the institutions in which they were discovered, Karolinska Institutet and Washington University) have been isolated in children with acute respiratory symptoms including wheezing as well as in the setting of pneumonia [171, 172]. Respiratory infection has also been described in HIV-infected patients, in whom higher viral loads have been demonstrated in those with lower CD4 counts [173].

KI and WU polyomaviruses have been isolated in nasopharyngeal, sputum, and bronchoalveolar lavage specimens in hematopoietic stem cell and solid organ transplant recipients [174, 175]. These viruses have also been detected in transbronchial biopsy specimens in lung transplant recipients, who in many cases were asymptomatic. Coinfection with other viral and bacterial pathogens has been reported. RT-PCR results should be interpreted with caution in transplant recipients, in whom severe infection has not been described to date. There are no available data on the role of decreasing immunosuppressive therapy or the use of antiviral agents in the development or treatment of infection with KI and WU polyomaviruses.

Merkel cell carcinoma is a neuroendocrine malignancy of the skin which is most common in immunocompromised hosts including transplant recipients [173, 176]. Over 80% of these tumors contain a polyoma virus named Merkel Cell polyomavirus (MCPyV); virus has also been found in respiratory secretions in asymptomatic transplant recipients. Further study of each of these polyomaviruses is ongoing in the transplant population.

49.13 Rotavirus

Rotavirus, the most common cause of enteritis worldwide and a common pathogen in healthy children under the age of 3, has become increasingly recognized as a pathogen in pediatric and adult recipients of solid organ transplants [177]. Epidemics have occurred through fecal–oral transmission, primarily in the winter and spring. Affected patients present with watery diarrhea, nausea, vomiting, abdominal pain, and, in some cases, gastrointestinal bleeding from colonic ulcers. Infection may be diagnosed by antigen detection in stool specimens using ELISA, latex agglutination, or quantitative PCR. Infection is generally self-limited with weaning immunosuppression during the acute phase of illness. There are no published data on antiviral activity against rotavirus; treatment remains symptomatic.

Rotavirus has been associated with a high risk of acute cell-mediated rejection in intestinal transplant recipients, which has been proposed to be related to poor absorption of immunosuppressive agents in the setting of vomiting and diarrhea, as well as immune reactivation of gastrointestinal tract-associated lymphocytes in the setting of infection [178]. In HSCT recipients, rotavirus infection may be difficult to differentiate clinically and histopathologically from GVHD.

In 1998, a live, oral, tetravalent rhesus–human reassortment rotavirus vaccine (RotaShield, Wyeth-Ayerst Laboratories, St. David, PA) was licensed and recommended for routine immunization of infants in the USA; it was voluntarily withdrawn from the market in 1999 due to its association with intestinal intussusception noted in postmarketing surveillance [179, 180, 181]. Two additional Rotavirus vaccines have been studied (RotaTeq, Merck & Company, Whitehouse Station, NJ; Rotarix, GlaxoSmithKline Biologicals, Rixensart, Belgium). Both vaccines are oral and contain live virus, and are thus contraindicated in highly immunocompromised patients. Fecal virus shedding has been noted with both vaccines, with transmission of vaccine-associated virus to household members noted with Rotarix [181].

Current vaccination guidelines in immunocompromised hosts recommend that HSCT and solid organ transplant recipients not receive this live virus vaccine. Household contacts of patients with immune deficiency may be vaccinated, but the transplant recipient should not change diapers for 4 weeks after vaccination, the usual duration of viral shedding in stool [182].

49.14 West Nile Virus

West Nile virus (WNV) was initially isolated from a febrile patient in the West Nile Province in Uganda in the 1930s and has been enzootic in Africa, Asia, the Middle East, and parts of the Mediterranean and Europe, causing asymptomatic disease or a self-limited febrile flu-like illness [183]. This flavivirus was first detected in the northeastern USA in 1999 and has caused outbreaks of infection in the late summer and early fall throughout the USA since then [184, 185]. Birds are the primary reservoir of infection. Mosquitoes acquire lifelong infection after biting viremic birds, spreading infection from their salivary glands to other species, including humans, with a subsequent bite. In human infection, the incubation period is 2–14 days [186]. While approximately 80% of infections are asymptomatic, 20% of patients develop West Nile fever, characterized by fever, malaise, anorexia, nausea, myalgias, headache, and occasionally lymphadenopathy [187]. One in 150 symptomatic patients develops meningitis and/or encephalitis [188]. Meningitis presents with photophobia, phonophobia, meningismus, and hyperreflexia; CSF analysis reveals a lymphocytic pleocytosis (<500 leukocytes/mm3, glucose usually normal). Patients with encephalitis develop altered mental status, cranial nerve palsies, seizures, and movement disorders. A minority of patients develop rapid asymmetric weakness that may progress to flaccid paralysis mimicking poliomyelitis, associated with hyporeflexia or areflexia [184, 189, 190]. Acute neuromuscular respiratory failure may develop, which carries a mortality rate of more than 50% [188]. Hemorrhagic fever characteristic of other flaviviruses has also been described [191]. The presence of severe weakness and hyporeflexia in a patient with meningoencephalitis should raise the suspicion of WNV infection. MRI may demonstrate meningeal or periventricular enhancement, sometimes mimicking ischemic changes [186].

Transmission of WNV via dialysis has been suggested [192], and transmission via blood transfusion and organ transplantation has been well documented [193, 194, 195, 196, 197]. In immunocompromised hosts, central nervous system involvement is common, although CSF pleocytosis may be minimal [198, 199, 200]. Community-acquired infection has been reported following solid organ transplantation, occurring 2 months to 10 years posttransplant [185, 199, 200, 201, 202]. A study of WNV infection during an outbreak in Toronto noted that liver, kidney, and heart transplant recipients had 40 times the risk of symptomatic infection as normal hosts [203]. In all cases, the recipients had participated in outdoor activities without the use of insect repellant or other personal protective measures. Fever often preceded neurologic symptoms. A delayed serologic response was noted in the transplanted cohort in which infection carried a mortality rate of 25%, versus 9% in the general population. In a Colorado outbreak in 2003, 11 transplant recipients (4 kidney, 2 liver, 2 kidney/pancreas, 1 lung, and 2 HSCT) developed infection requiring hospitalization [204]. Ten (91%) developed meningoencephalitis, one developed acute flaccid paralysis without encephalitis, and three patients had meningoencephalitis and paralysis. Two patients died (18% mortality), and three suffered significant neurologic sequelae. It appears that transplant recipients are more likely to develop meningoencephalitis in the setting of acute West Nile virus infection than immunocompetent hosts, perhaps with a higher mortality rate. Prolonged infection can also occur [205].

Several cases of WNV infection have been reported in HSCT recipients [206, 207]. Infection occurred 3–5 months posttransplant in the most well-described cases, after engraftment but while on calcineurin inhibitor-based prophylaxis or treatment of chronic graft-versus-host disease. Fever, lethargy, progressive bilateral extremity weakness, and hyporeflexia or areflexia were present. CSF contained 0–6 white blood cells/μL; IgG and IgM were negative in CSF and blood in most cases. Diagnosis of WNV infection was made by PCR performed on serum and CSF. All of the described patients died.

Diagnosis of WNV infection in immunocompetent hosts may be made serologically or via RT-PCR. An IgM antibody capture assay is available and becomes positive in CSF 3–5 days after onset of symptoms in nonimmunosuppressed hosts [202, 207], before serum antibody develops; CSF IgG appears approximately 5 days later. Antibody presence may be confirmed with viral neutralization studies. IgM antibodies may persist in serum for up to 12 months after infection resolution, and IgG may persist for years. As in the hematopoietic stem cell recipients noted above, immunocompromised patients demonstrate delayed seroconversion, making diagnosis of acute infection difficult at times. Nucleic acid testing in plasma and/or CSF is the most useful diagnostic test in this setting [208].

There are no antiviral agents that have proven efficacy in the treatment of WNV infection. Ribavirin possesses in vitro activity but demonstrates poor clinical efficacy [186, 209]. IVIg with high titers of anti-WNV antibodies (e.g., from Israel, where infection is endemic) has demonstrated significant clinical benefits in animal models, although antibody titers are low in immune globulin derived from the US donors, which have proven ineffective in treating acute infection [184, 210, 211]. A report of successful treatment of donor-transmitted WNV infection in a liver transplant recipient by reducing immunosuppression and administering plasma from seropositive blood donors has been published [212]. Overall case fatality rates of infection with WNV are 4–20% [189, 192], with significantly higher rates in transplant recipients.

Unlike the case in other neuroinvasive viral infections, the severity of initial clinical presentation does not predict the prognosis of WNV infection [187, 190, 213]. Survivors frequently suffer from prolonged fatigue, myalgias, cognitive deficits, memory loss, and tremors. Parkinsonism, excessive somnolence, and postural instability are reported. Phase I trials of a vaccine have been promising [214]. Transplant recipients should be educated about the transmission of West Nile virus and urged to remove any stagnant water collections and to use insect repellant when outdoors at dusk during the later summer and fall in order to prevent infection.

49.15 Conclusion

Viruses remain the most significant and elusive pathogens infecting patients following solid organ and hematopoietic stem cell transplantation. The days of “it’s just a virus” are clearly behind us, as immunosuppression has changed, posttransplant longevity is increasing, and molecular diagnostic methods have dramatically improved [215]. Serology may be of limited value in immunocompromised hosts in the diagnosis of acute infection as well as in detecting reactivation of latent infections. Multiplex, quantitative real-time PCR assays are now available to detect multiple viruses, including panels of PCRs for detection of respiratory viruses and CNS pathogens [216, 217]. These sensitive techniques are being evaluated carefully in transplant populations for their specificity and for their potential utility as markers of early infection with surveillance monitoring. The impact of community-acquired respiratory viral infections on the development of acute rejection and bronchiolitis obliterans in lung transplantation appears to be significant and warrants further study [218, 219]. Continued vigilance in detecting emerging viral infections and continued study of potential antiviral therapies in the transplant population will likely improve patient survival.

References

  1. 1.
    Palombo EA, Bishop RF. Annual incidence, serotype distribution, and genetic diversity of human astrovirus isolates from hospitalized children in Melbourne, Australia. J Clin Microbiol. 1996;34:1750–3.PubMedPubMedCentralGoogle Scholar
  2. 2.
    Lewis DC, Lightfoot NF, Cubitt WD, Wilson SA. Outbreaks of astrovirus type 1 and rotavirus gastroenteritis in a geriatric in-patient population. J Hosp Infect. 1989;14:9–14.PubMedCrossRefGoogle Scholar
  3. 3.
    Lopes-Joao A, Costa I, Mesquita JR, et al. Multiple enteropathogenic viruses in a gastroenteritis outbreak in a military exercise of the Portuguese army. J Clin Virol. 2015;68:73–5.PubMedCrossRefGoogle Scholar
  4. 4.
    Naccache SN, Peggs KS, Mattes FM, et al. Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing. Clin Infect Dis. 2015;60:919–23.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    Brown JR, Morfopoulou S, Hubb J, et al. Astrovirus VA1/HMO-C: an increasingly recognized neurotropic pathogen in immunocompromised patients. Clin Infect Dis. 2015;60:881–8.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Kesebir D, Vazquez M, Weibel C, et al. Human bocavirus infection in young children in the United States: molecular epidemiological profile and clinical characteristics of a newly emerging respiratory virus. J Infect Dis. 2006;194:1276–82.PubMedCrossRefGoogle Scholar
  7. 7.
    Cheung W-X, Jin Y, Duan Z-J, et al. Human bocavirus in children hospitalized for acute gastroenteritis: a case–control study. Clin Infect Dis. 2008;47:161–7.CrossRefGoogle Scholar
  8. 8.
    Campe H, Hartberger C, Sing A. Role of human bocavirus infections in outbreaks. J Clin Virol. 2008;43:340–2.PubMedCrossRefGoogle Scholar
  9. 9.
    Mitui MT, Bin Tabib SMS, Matsumoto T, et al. Detection of human bocavirus in the cerebrospinal fluid of children with encephalitis. Clin Infect Dis. 2012;54:964–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Manning A, Russell V, Eastick K, et al. Epidemiological profile and clinical associations of human bocavirus and other human parvoviruses. J Infect Dis. 2006;194:1283–90.PubMedCrossRefGoogle Scholar
  11. 11.
    Schenk T, Strahm B, Kontny U, et al. Disseminated bocavirus infection after stem cell transplant. Emerg Infect Dis. 2007;13:1425–7.PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Schenk T, Maier B, Hufnage M, et al. Persistence of human bocavirus DNA in immunocompromised children. Pediatr Infect Dis J. 2011;30:82–4.PubMedCrossRefGoogle Scholar
  13. 13.
    Miyakis S, van Hal SJ, Barratt J, et al. Absence of human Bocavirus in bronchoalveolar lavage fluid of lung transplant patients. J Clin Virol. 2009;44:179–80.PubMedCrossRefGoogle Scholar
  14. 14.
    Soccal PM, Aubert J-D, Bridevaux P-O, et al. Upper and lower respiratory tract viral infection and acute graft rejection in lung transplant recipients. Clin Infect Dis. 2010;51:163–70.PubMedCrossRefGoogle Scholar
  15. 15.
    Pialoux G, Gauzere B-A, Jaureguiberry S, Strobel M. Chikungunya, an epidemic arbovirus. Lancet Infect Dis. 2007;7:319–27.PubMedCrossRefGoogle Scholar
  16. 16.
    Weaver SC, Lecuit M. Chikungunya virus and the global spread of a mosquito-borne disease. N Engl J Med. 2015;372:1231–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Leparc-Goffart I, Nougairede A, Cassadou S, et al. Chikungunya in the Americas. Lancet. 2014;383:514.PubMedCrossRefGoogle Scholar
  18. 18.
    Couderc T, Gangneux N, Chretien F, et al. Chikungunya virus infection of corneal grafts. J Infect Dis. 2012;206:851–9.PubMedCrossRefGoogle Scholar
  19. 19.
    Centers for Disease Control and Prevention (CDC). Revised U.S. surveillance case definition for severe acute respiratory syndrome (SARS) and update on SARS cases—United States and worldwide, December 2003. MMWR Morb Mortal Wkly Rep. 2003;52:1202–6.Google Scholar
  20. 20.
    Leung GM, Hedley AJ, Ho LM, et al. The epidemiology of severe acute respiratory syndrome in the 2003 Hong Kong epidemic: an analysis of all 1755 patients. Ann Intern Med. 2004;141:662–73.PubMedCrossRefGoogle Scholar
  21. 21.
    Vabret A, Dina J, Gouarin S, et al. Detection of the new human coronavirus HKU1: a report of 6 cases. Clin Infect Dis. 2006;42:634–9.PubMedCrossRefGoogle Scholar
  22. 22.
    Tsang KW, Ho PL, Ooi GC, et al. A cluster of cases of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348:1977–85.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee N, Hui D, Wu A, et al. A major outbreak of severe acute respiratory syndrome in Hong Kong. N Engl J Med. 2003;348:1986–94.PubMedCrossRefGoogle Scholar
  24. 24.
    Poutanen SM, Low DE, Henry B, et al. Identification of severe acute respiratory syndrome in Canada. N Engl J Med. 2003;348:1995–2005.PubMedCrossRefGoogle Scholar
  25. 25.
    Muller MP, Richardson SE, McGeer A, et al. Early diagnosis of SARS: lessons from the Toronto SARS outbreak. Eur J Clin Microbiol Infect Dis. 2006;25:230–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Roberts A, Thomas WD, Guarner J, et al. Therapy with a severe acute respiratory syndrome-associated coronavirus-neutralizing human monoclonal antibody reduces disease severity and viral burden in golden Syrian hamsters. J Infect Dis. 2006;193:685–92.PubMedCrossRefGoogle Scholar
  27. 27.
    Drosten C, Gunther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med. 2003;348:1967–76.PubMedCrossRefGoogle Scholar
  28. 28.
    Ksiazek TG, Erdman D, Goldsmith CS, et al. A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med. 2003;348:1953–66.PubMedCrossRefGoogle Scholar
  29. 29.
    Booth TF, Kournikakis B, Bastien N, et al. Detection of airborne severe acute respiratory syndrome (SARS) coronavirus and environmental contamination in SARS outbreak units. J Infect Dis. 2005;191:1472–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Adachi D, Johnson G, Draker R, et al. Comprehensive detection and identification of human coronaviruses, including the SARS associated coronavirus, with a single RT-PCR assay. J Virol Methods. 2004;122:29–36.PubMedCrossRefGoogle Scholar
  31. 31.
    Kumar D, Tellier R, Draker R, et al. Severe acute respiratory syndrome (SARS) in a liver transplant recipient and guidelines for donor SARS screening. Am J Transplant. 2003;3:977–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Farcas GA, Poutanen SM, Mazzulli T, et al. Fatal severe acute respiratory syndrome is associated with multiorgan involvement by coronavirus. J Infect Dis. 2005;191:193–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Xu J, Zhing S, Liu J, et al. Detection of severe acute respiratory syndrome coronavirus in the rain: potential role of the chemokine Mig in pathogenesis. Clin Infect Dis. 2005;41:1089–96.PubMedCrossRefGoogle Scholar
  34. 34.
    Svoboda T, Henry B, Shulman L, et al. Public health measures to control the spread of the severe acute respiratory syndrome during the outbreak in Toronto. N Engl J Med. 2004;350:2352–61.PubMedCrossRefGoogle Scholar
  35. 35.
    Gautret P, Gray GC, Charrel RN, et al. Emerging viral respiratory tract infections – environmental risk factors and transmission. Lancet Infect Dis. 2014;14:1113–22.PubMedCrossRefGoogle Scholar
  36. 36.
    Drosten C, Seilmaier M, Corman VM, et al. Clinical features and virological analysis of a case of Middle East respiratory syndrome coronavirus infection. Lancet. 2013;13:745–51.PubMedCrossRefGoogle Scholar
  37. 37.
    Rasmussen SA, Gerber SI, Swerdlow DL. Middle East Respiratory Syndrome Coronavirus: update for clinicians. Clin Infect Dis. 2015;60(11):1686–9.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Arabi YM, Arifi AA, Balkhy HH, et al. Clinical course and outcomes of critically ill patients with Middle East respiratory syndrome coronavirus infection. Ann Intern Med. 2014;160:389–97.PubMedCrossRefGoogle Scholar
  39. 39.
    Memish ZA, Zumla AI, Assiri A. Middle East respiratory syndrome coronavirus infections in health care workers. N Engl J Med. 2013;369:884–6.PubMedCrossRefGoogle Scholar
  40. 40.
    Al-Abdallat MM, Payne DC, Alqasrawi S, et al. Hospital associated outbreak of Middle East respiratory syndrome coronavirus: a serologic, epidemiologic, and clinical description. Clin Infect Dis. 2014;59:1225–33.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Memish ZA, Cotton M, Meyer B, et al. Human infection with MERS coronavirus after exposure to infected camels, Saudi Arabia, 2013. Emerg Infect Dis. 2014;20(6):1012–5.PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    AlGhamdi M, Mushtaq F, Awn N, Shalhoub S. MERS CoV infection in two renal transplant recipients: case report. Am J Transplant. 2015;15:1101–4.PubMedCrossRefGoogle Scholar
  43. 43.
    Chan JFW, Chan K-H, Kao RYT, et al. Broad-spectrum antivirals for the emerging Middle East respiratory syndrome coronavirus. J Infect. 2013;67:606–16.PubMedCrossRefGoogle Scholar
  44. 44.
    Falzarano D, de Wit E, Rasmussen AL, et al. Treatment with interferon –alpha2b and ribavirin improves outcome in MERS-CoV-infected rhesus macaques. Nat Med. 2013;19:1313–7.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Omrani AS, Saad MM, Baig K, et al. Ribavirin and interferon alfa-2a for severe Middle East respiratory syndrome coronavirus infection: a retrospective cohort study. Lancet Infect Dis. 2014;14:1090–5.PubMedCrossRefGoogle Scholar
  46. 46.
    Garbino J, Crespo S, Aubert JD, et al. A prospective hospital based study of the clinical impact of non-severe acute respiratory syndrome (non-SARS)-related human coronavirus infection. Clin Infect Dis. 2006;43:1009–15.PubMedCrossRefGoogle Scholar
  47. 47.
    Pene F, Merlat A, Vabret A. Coronavirus 229E-related pneumonia in immunocompromised patients. Clin Infect Dis. 2003;37:929–32.PubMedCrossRefGoogle Scholar
  48. 48.
    Dalton HR, Bendall R, Ijaz S, Banks M. Hepatitis E: an emerging infection in developed countries. Lancet Infect Dis. 2008;8:698–709.PubMedCrossRefGoogle Scholar
  49. 49.
    Banks M, Heath GS, Grierson SS, et al. Evidence for the presence of hepatitis E virus in pigs in the United Kingdom. Vet Rec. 2004;154:223–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Wang YC, Zhang HY, Xia NS, et al. Prevalence, isolation and partial sequence analysis of hepatitis E virus from domestic animals in China. J Med Virol. 2002;67:516–21.PubMedCrossRefGoogle Scholar
  51. 51.
    Mansuy JM, Legrand-Abravanel F, Calot JP, et al. High prevalence of anti-hepatitis E virus antibodies in blood donors from south west France. J Med Virol. 2008;80:289–93.PubMedCrossRefGoogle Scholar
  52. 52.
    Thomas DL, Yarbough PO, Vlahov D, et al. Seroreactivity to hepatitis E virus in areas where the disease is not endemic. J Clin Microbiol. 1997;35:1244–7.PubMedPubMedCentralGoogle Scholar
  53. 53.
    Matsuda H, Okada K, Takahashi K, Mishiro S. Severe hepatitis E virus infection after ingestion of uncooked liver from a wild boar. J Infect Dis. 2003;188:944.PubMedCrossRefGoogle Scholar
  54. 54.
    Tei S, Kitajima N, Takahashi K, Mishiro S. Zoonotic transmission of hepatitis E virus from deer to human beings. Lancet. 2003;362:371–3.PubMedCrossRefGoogle Scholar
  55. 55.
    Feagins AR, Opriessnig T, Guenette DK, et al. Detection and characterization of infectious hepatitis E virus from commercial pig livers sold in local grocery stores in the USA. J Gen Virol. 2007;88:912–7.PubMedCrossRefGoogle Scholar
  56. 56.
    Mitsui T, Tsukamoto Y, Yamazaki C, et al. Prevalence of hepatitis E virus infection among hemodialysis patients in Japan: evidence for infection with a genotype 3 HEV by blood transfusion. J Med Virol. 2004;74:563–72.PubMedCrossRefGoogle Scholar
  57. 57.
    Boxall E, Herborn A, Kochethu G, et al. Transfusion-transmitted hepatitis E in a “nonhyperendemic” country. Transfus Med. 2006;16:79–83.PubMedCrossRefGoogle Scholar
  58. 58.
    Khuroo MS, Kamili S, Yattoo GN. Hepatitis E infection may be transmitted through blood transfusions in an endemic area. J Gastroenterol Hepatol. 2004;19:778–84.PubMedCrossRefGoogle Scholar
  59. 59.
    Matsubayashi K, Nagaoka Y, Sakata H, et al. Transfusion-transmitted hepatitis E caused by apparently indigenous hepatitis E virus strain in Hokkaido, Japan. Transfusion. 2004;44:934–40.PubMedCrossRefGoogle Scholar
  60. 60.
    Clayson ET, Myint KS, Snitbhan R, et al. Viremia, fecal shedding and IgM and IgG responses in patients with hepatitis E. J Infect Dis. 1995;172:927–33.PubMedCrossRefGoogle Scholar
  61. 61.
    Khuroo MS, Kamili S. Aetiology, clinical course and outcome of sporadic acute viral hepatitis in pregnancy. J Viral Hepat. 2003;10:61–9.PubMedCrossRefGoogle Scholar
  62. 62.
    Bhatia V, Singhal A, Panda SK, Acharya SK. A 20-year single center experience with acute liver failure during pregnancy: is the prognosis really worse? Hepatology. 2008;48:1577–85.PubMedCrossRefGoogle Scholar
  63. 63.
    Halac U, Beland K, Lapierre P, et al. Chronic hepatitis E in children with liver transplantation. Gut. 2012;61:597–603.PubMedCrossRefGoogle Scholar
  64. 64.
    Legrand-Abravanel F, Kamar N, Sandres-Saune K, et al. Hepatitis E virus infection without reactivation in solid organ transplant recipients, France. Emerg Infect Dis. 2011;17:30–7.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Kamar N, Selves J, Mansuy J-M, et al. Hepatitis E virus and chronic hepatitis in solid organ transplant recipients. N Engl J Med. 2008;358:811–7.PubMedCrossRefGoogle Scholar
  66. 66.
    leCoutre P, Meisel H, Hoffman J, et al. Reactivation of hepatitis E infection in a patient with acute lymphoblastic leukemia after allogeneic stem cell transplantation. Gut. 2009;58:699–702.CrossRefGoogle Scholar
  67. 67.
    Haagsma EB, Niesters HGM, van den Berg AP, et al. Prevalence of hepatitis E virus infection in liver transplant recipients. Liver Transpl. 2009;15:1225–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Versluis J, Pas SD, Agteresch HJ, et al. Hepatitis E virus: an underestimated opportunistic pathogen in recipients of allogeneic hematopoietic stem cell transplantation. Blood. 2013;122:1079–86.PubMedCrossRefGoogle Scholar
  69. 69.
    Kamar N, Weclawiak H, Guilbeau-Frugier C, et al. Hepatitis E virus and the kidney in solid organ transplant patients. Transplantation. 2012;93:617–23.PubMedGoogle Scholar
  70. 70.
    Pischke S, Suneetha PV, Baechlein C, et al. Hepatitis E virus infection as a cause of graft hepatitis in liver transplant recipients. Liver Transpl. 2010;16:74–82.PubMedCrossRefGoogle Scholar
  71. 71.
    Kamar N, Izopet J, Cintas P, et al. Hepatitis E virus-induced neurological symptoms in a kidney-transplant patient with chronic hepatitis. Am J Transplant. 2010;10:1321–4.PubMedCrossRefGoogle Scholar
  72. 72.
    Kamar N, Rostaing L, Abravanel F, et al. Pegylated interferon-alpha for treating chronic hepatitis E virus infection after liver transplantation. Clin Infect Dis. 2010;50:e30–3.PubMedCrossRefGoogle Scholar
  73. 73.
    Kamar N, Rostaing L, Abravanel F, et al. Ribavirin therapy inhibits viral replication on patients with chronic hepatitis E virus infection. Gastroenterology. 2010;139:1612–8.PubMedCrossRefGoogle Scholar
  74. 74.
    Fischer SA, Graham MB, Kuehnert MJ, et al. Transmission of lymphocytic choriomeningitis virus by organ transplantation. N Engl J Med. 2006;354:2235–49.PubMedCrossRefGoogle Scholar
  75. 75.
    Centers for Disease Control and Prevention (CDC). Lymphocytic choriomeningitis virus infection in organ transplant recipients – Massachusetts, Rhode Island, 2005. MMWR Morb Mortal Wkly Rep. 2005;54:537–9.Google Scholar
  76. 76.
    Paddock C, Ksiazek T, Comer JA, et al. Pathology of fatal lymphocytic choriomeningitis virus infection in multiple organ transplant recipients from a common donor. Mod Pathol. 2005;18 Suppl 1:263A.Google Scholar
  77. 77.
    Palacios G, Druce J, Du L, et al. A new arenavirus in a cluster of fatal transplant-associated diseases. N Engl J Med. 2008;358:991–8.PubMedCrossRefGoogle Scholar
  78. 78.
    Simmonds P. A new arenavirus in transplantation. N Engl J Med. 2008;358:2638–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Gregg MB. Recent outbreaks of lymphocytic choriomeningitis in the United States of America. Bull World Health Organ. 1975;52:549–53.PubMedGoogle Scholar
  80. 80.
    MacNeil A, Stoher U, Farnon E, et al. Solid organ transplant-associated lymphocytic choriomeningitis virus, United States, 2011. Emerg Infect Dis. 2012;18:1256–62.PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Hirsch MS, Moellering Jr RC, Pope HG, et al. Lymphocytic choriomeningitis virus infection traced to a pet hamster. N Engl J Med. 1974;291:610–2.PubMedCrossRefGoogle Scholar
  82. 82.
    Skinner HH, Knight EH. The potential role of Syrian hamsters and other small animals as reservoirs of lymphocytic choriomeningitis virus. J Small Anim Pract. 1979;20:145–61.PubMedCrossRefGoogle Scholar
  83. 83.
    Childs JE, Glass GE, Ksiazek TG, et al. Human-rodent contact and infection with lymphocytic choriomeningitis and Seoul viruses in an inner city population. Am J Trop Med Hyg. 1991;44:117–21.PubMedCrossRefGoogle Scholar
  84. 84.
    Amman BR, Pavlin BI, Albarino CG, et al. Pet rodents and fatal lymphocytic choriomeningitis in transplant patients. Emerg Infect Dis. 2007;13:719–25.PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Warkel RL, Rinaldi CF, Bancroft WH, et al. Fatal acute meningoencephalitis due to lymphocytic choriomeningitis virus. Neurology. 1973;23:198–203.PubMedCrossRefGoogle Scholar
  86. 86.
    Dare R, Sanghavi S, Bullotta A, et al. Diagnosis of human metapneumovirus infection in immunocompromised lung transplant recipients and children evaluated for pertussis. J Clin Microbiol. 2007;45:548–52.PubMedCrossRefGoogle Scholar
  87. 87.
    Esper F, Boucher D, Weibel C, et al. Human metapneumovirus infection in the United States: clinical manifestations associated with a newly emerging respiratory infection in children. Pediatrics. 2003;111:1407–10.PubMedCrossRefGoogle Scholar
  88. 88.
    Bastien N, Ward D, Van Caeseele P, et al. Human metapneumovirus infection in the Canadian population. J Clin Microbiol. 2003;41:4642–6.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Esper F, Martinello RA, Boucher D, et al. A 1-year experience with human metapneumovirus in children aged <5 years. J Infect Dis. 2004;189:1388–96.PubMedCrossRefGoogle Scholar
  90. 90.
    Boivin G, De Serres G, Hamelin ME, et al. An outbreak of severe respiratory tract infection due to human metapneumovirus in a long-term care facility. Clin Infect Dis. 2007;44:1152–8.PubMedCrossRefGoogle Scholar
  91. 91.
    Sumino KC, Agapov E, Pierce RA, et al. Detection of severe human metapneumovirus infection by real-time polymerase chain reaction and histopathological assessment. J Infect Dis. 2005;192:1052–60.PubMedCrossRefGoogle Scholar
  92. 92.
    Larcher C, Geltner C, Fischer H, et al. Human metapneumovirus infection in lung transplant recipients: clinical presentation and epidemiology. J Heart Lung Transplant. 2005;24:1891–901.PubMedCrossRefGoogle Scholar
  93. 93.
    Dosanjh A. Respiratory metapneumovirus infection without co-infection in association with acute and chronic lung allograft dysfunction. J Inflamm Res. 2015;8:79–82.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Richards A, Chuen JN, Taylor C, et al. Acute respiratory infection in a renal transplant recipient. Nephrol Dial Transplant. 2005;20:2848–50.PubMedCrossRefGoogle Scholar
  95. 95.
    Englund JA, Boeckh M, Kuypers J, et al. Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients. Ann Intern Med. 2006;144:344–9.PubMedCrossRefGoogle Scholar
  96. 96.
    Debiaggi M, Canducci F, Sampaolo M, et al. Persistent symptomless human metapneumovirus infection in hematopoietic stem cell transplant recipients. J Infect Dis. 2006;194:474–8.PubMedCrossRefGoogle Scholar
  97. 97.
    Gerna G, Vitulo P, Rovida F, et al. Impact of human metapneumovirus and human cytomegalovirus versus other respiratory viruses on the lower respiratory tract infections of lung transplant recipients. J Med Virol. 2006;78:408–16.PubMedCrossRefGoogle Scholar
  98. 98.
    Hamlin ME, Prince GA, Boivin G. Effect of ribavirin and glucocorticoid treatment in a mouse model of human metapneumovirus infection. Antimicrob Agents Chemother. 2006;50:774–7.CrossRefGoogle Scholar
  99. 99.
    Raza K, Ismailjee SB, Crespo M, et al. Successful outcome of human metapneumovirus (hMPV) pneumonia in a lung transplant recipient treated with intravenous ribavirin. J Heart Lung Transplant. 2007;26:862–4.PubMedCrossRefGoogle Scholar
  100. 100.
    Centers for Disease Control and Prevention (CDC). Import associated measles outbreak-Indiana, May–June 2005. MMWR Morb Mortal Wkly Rep. 2005;54:1073–75.Google Scholar
  101. 101.
    Centers for Disease Control and Prevention (CDC). Measles among adults associated with adoption of children in China—California, Missouri, and Washington, July–August 2006. MMWR Morb Mortal Wkly Rep. 2007;56:144–6.Google Scholar
  102. 102.
    Centers for Disease Control and Prevention (CDC). Multistate measles outbreak associated with an international youth sporting event—Pennsylvania, Michigan and Texas, August–September 2007. MMWR Morb Mortal Wkly Rep. 2008;57:169–73.Google Scholar
  103. 103.
    Centers for Disease Control and Prevention (CDC). Outbreak of measles – San Diego, California, January–February 2008. MMWR Morb Mortal Wkly Rep. 2008;57:203–6.Google Scholar
  104. 104.
    Centers for Disease Control and Prevention (CDC). Measles—United States, January 1–April 25, 2008. MMWR Morb Mortal Wkly Rep. 2008;57:1–4.Google Scholar
  105. 105.
    Kennedy AM, Gust DA. Measles outbreak associated with a church congregation: a study of immunization attitudes of congregation members. Public Health Rep. 2008;123:126–34.PubMedPubMedCentralCrossRefGoogle Scholar
  106. 106.
    Sugarman DE, Barskey AE, Delea MG, et al. Measles outbreak in a highly vaccinated population, San Diego, 2008: role of the intentionally undervaccinated. Pediatrics. 2010;125:747–55.CrossRefGoogle Scholar
  107. 107.
    Centers for Disease Control and Prevention (CDC). Notes from the field: measles outbreak among members of a religious community – Brooklyn, New York, March – June 2013. MMWR Morb Mortal Wkly Rep. 2013;62:752–3.Google Scholar
  108. 108.
    Zipprich J, Winter K, Hacker J, et al. Measles outbreak-California, December 2014-February 2015. MMWR Morb Mortal Wkly Rep. 2015;64:153–4.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Wong RD, Goetz MB. Clinical and laboratory features of measles in hospitalized adults. Am J Med. 1993;95:377–83.PubMedCrossRefGoogle Scholar
  110. 110.
    Peltola H, Kulkarni PS, Kapre SV, et al. Mumps outbreak in Canada and the United States: time for new thinking on mumps vaccines. Clin Infect Dis. 2007;45:459–66.PubMedCrossRefGoogle Scholar
  111. 111.
    Centers for Disease Control and Prevention (CDC). Update: multistate outbreak of mumps-United States, January 1–May 2, 2006. MMWR Morb Mortal Wkly Rep. 2006;55:1.Google Scholar
  112. 112.
    Centers for Disease Control and Prevention (CDC). Update: multistate outbreak of mumps-United States, January 1–May 2, 2006. MMWR Morb Mortal Wkly Rep. 2006;55:559.Google Scholar
  113. 113.
    Centers for Disease Control and Prevention (CDC). Update: mumps activity—United States, January 1–October 7, 2006. MMWR Morb Mortal Wkly Rep. 2006;55:1152.Google Scholar
  114. 114.
    Dayan GH, Quinlisk P, Parker AA, et al. Recent resurgence of mumps in the United States. N Engl J Med. 2008;358:1580–9.PubMedCrossRefGoogle Scholar
  115. 115.
    Park DW, Nam M-H, Kim JY, et al. Mumps outbreak in a highly vaccinated school population: assessment of secondary vaccine failure using IgG avidity measurements. Vaccine. 2007;25:4665–70.PubMedCrossRefGoogle Scholar
  116. 116.
    Reid F, Hassan J, Irwin F, et al. Epidemiologic and diagnostic evaluation of a recent mumps outbreak using oral fluid samples. J Clin Virol. 2008;41:134–7.PubMedCrossRefGoogle Scholar
  117. 117.
    Shanley JD. The resurgence of mumps in young adults and adolescents. Cleve Clin J Med. 2007;74(42–44):47–8.Google Scholar
  118. 118.
    Bitsko RH, Cortese MM, Dayan GH, et al. Detection of RNA of mumps virus during an outbreak in a population with a high level of measles, mumps, and rubella vaccine coverage. J Clin Microbiol. 2008;46:1101–3.PubMedPubMedCentralCrossRefGoogle Scholar
  119. 119.
    Jin L, Feng Y, Parry R, et al. Real-time PCR and its application to mumps rapid diagnosis. J Med Virol. 2007;79:1761–7.PubMedCrossRefGoogle Scholar
  120. 120.
    Patel SR, Ortin M, Cohen BJ, et al. Revaccination with measles, tetanus, poliovirus, Haemophilus influenzae b, meningococcus C, and pneumococcus vaccines in children after hematopoietic stem cell transplantation. Clin Infect Dis. 2007;44:625–34.PubMedCrossRefGoogle Scholar
  121. 121.
    Centers for Disease Control and Prevention (CDC). Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients: recommendations of CDC, the Infectious Diseases Society of America, and the American Society of Blood and Marrow Transplantation. MMWR Morb Mortal Wkly Rep. 2000;49(RR10):1–125.Google Scholar
  122. 122.
    Centers for Disease Control and Prevention (CDC). Updated norovirus outbreak management and disease prevention guidelines. MMWR Morb Mort Wkly Rep. 2011;60(RR03):1–15.Google Scholar
  123. 123.
    Mead PS, Slutsker L, Dietz V, et al. Food-related illness and death in the United States. Emerg Infect Dis. 1999;5:607–25.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Marshall JA, Hellard ME, Sinclair MI, et al. Incidence and characteristics of endemic Norwalk-like virus-associated gastroenteritis. J Med Virol. 2003;69:568–78.PubMedCrossRefGoogle Scholar
  125. 125.
    Lopman BA, Adak GK, Reacher MH, et al. Two epidemiologic patterns of norovirus outbreaks: surveillance in England and Wales, 1992–2000. Emerg Infect Dis. 2003;9:71–7.PubMedPubMedCentralCrossRefGoogle Scholar
  126. 126.
    Tu ET-V, Bull RA, Kim M-J, et al. Norovirus excretion in an aged-care setting. J Clin Microbiol. 2008;46:2119–21.PubMedPubMedCentralCrossRefGoogle Scholar
  127. 127.
    Makary P, Maunula L, Niskanen T, et al. Multiple norovirus outbreaks among workplace canteen users in Finland, July 2006. Epidemiol Infect. 2009;137:402–7.PubMedCrossRefGoogle Scholar
  128. 128.
    Chen S-Y, Tsai C-N, Lai M-W, et al. Norovirus infection as a cause of diarrhea-associated benign infantile seizures. Clin Infect Dis. 2009;48:849–55.PubMedCrossRefGoogle Scholar
  129. 129.
    Patel MM, Hall AJ, Vinje J, et al. Noroviruses: a comprehensive review. J Clin Virol. 2009;44:1–8.PubMedCrossRefGoogle Scholar
  130. 130.
    Berg DE, Kohn MA, Farley TA, et al. Multistate outbreaks of acute gastroenteritis traced to fecal-contaminated oysters harvested in Louisiana. J Infect Dis. 2000;181 Suppl 2:S381–6.PubMedCrossRefGoogle Scholar
  131. 131.
    Anderson AD, Garrett VD, Sobel J, et al. Multistate outbreak of Norwalk-like virus gastroenteritis associated with a common caterer. Am J Epidemiol. 2001;154:1013–9.PubMedCrossRefGoogle Scholar
  132. 132.
    Centers for Disease Control and Prevention. Norwalk-like virus associated gastroenteritis in a large, high-density encampment—Virginia, July 2001. JAMA. 2001;288:1711–3.Google Scholar
  133. 133.
    Becker KM, Moe CL, Southwick KL, et al. Transmission of Norwalk virus during a football game. N Engl J Med. 2000;343:1223–7.PubMedCrossRefGoogle Scholar
  134. 134.
    Kuritsky JN, Osterholm MT, Greenberg HB, et al. Norwalk gastroenteritis: a community outbreak associated with bakery product consumption. Ann Intern Med. 1984;100:519–21.PubMedCrossRefGoogle Scholar
  135. 135.
    Long SM, Adak GK, O’Brien SJ, et al. General outbreaks of infectious intestinal disease linked with salad vegetables and fruit, England and Wales, 1992–2000. Commun Dis Public Health. 2002;5:101–5.PubMedGoogle Scholar
  136. 136.
    Lawson HW, Braun MM, Glass RI, et al. Waterborne outbreak of Norwalk virus gastroenteritis at a southwest US resort: role of geological formations in contamination of well water. Lancet. 1991;337:1200–4.PubMedCrossRefGoogle Scholar
  137. 137.
    Baron RC, Murphy FD, Greenberg HB, et al. Norwalk gastrointestinal illness: an outbreak associated with swimming in a recreational lake and secondary person-to-person transmission. Am J Epidemiol. 1982;115:163–72.PubMedCrossRefGoogle Scholar
  138. 138.
    Gotz H, Ekdahl K, Lindback J, et al. Clinical spectrum and transmission characteristics of infection with Norwalk-like virus: findings from a large community outbreak in Sweden. Clin Infect Dis. 2001;33:622–8.PubMedCrossRefGoogle Scholar
  139. 139.
    Hewitt J, Bell D, Simmons GC, et al. Gastroenteritis outbreak caused by waterborne norovirus at a New Zealand ski resort. Appl Environ Microbiol. 2007;73:7853–7.PubMedPubMedCentralCrossRefGoogle Scholar
  140. 140.
    Green KY, Belliot G, Taylor JL, et al. A predominant role for Norwalk-like viruses as agents of epidemic gastroenteritis in Maryland nursing homes for the elderly. Clin Infect Dis. 2001;33:622–8.CrossRefGoogle Scholar
  141. 141.
    Ahmad K. Norwalk-like virus attacks troops in Afghanistan. Lancet Infect Dis. 2002;2:391.PubMedCrossRefGoogle Scholar
  142. 142.
    Mattner F, Sohr D, Heim A, et al. Risk groups for clinical complications of norovirus infections: an outbreak investigation. Clin Microbiol Infect. 2006;12:69–74.PubMedCrossRefGoogle Scholar
  143. 143.
    Said MA, Perl TM, Sears CL. Gastrointestinal flu: norovirus in health care and long-term care facilities. Clin Infect Dis. 2008;47:1202–8.PubMedCrossRefGoogle Scholar
  144. 144.
    Cunha BA, Thekkel V, Eisenstein L. Community-acquired norovirus diarrhoea outbreak mimicking a community-acquired C. difficile diarrhoea outbreak. J Hosp Infect. 2008;70:98–100.PubMedCrossRefGoogle Scholar
  145. 145.
    Centers for Disease Control and Prevention (CDC). Norovirus outbreak associated with a natural lake used for recreation – Oregon, 2014. MMWR Morb Mortal Wkly Rep. 2015;64:485–90.Google Scholar
  146. 146.
    Harris JP, Edmunds J, Pebody R, et al. Deaths from norovirus among the elderly, England and Wales. Emerg Infect Dis. 2008;14:1546–52.PubMedPubMedCentralCrossRefGoogle Scholar
  147. 147.
    Verhoef LPB, Kroneman A, van Duynhoven Y, et al. Selection tool for foodborne norovirus outbreaks. Emerg Infect Dis. 2009;15:31–8.PubMedPubMedCentralCrossRefGoogle Scholar
  148. 148.
    Patel MM, Widdowson M-A, Glass RI, et al. Systematic literature review of role of noroviruses in sporadic gastroenteritis. Emerg Infect Dis. 2008;14:1224–31.PubMedPubMedCentralCrossRefGoogle Scholar
  149. 149.
    Ludwig A, Adams O, Laws H-J, et al. Quantitative detection of norovirus excretion in pediatric patients with cancer and prolonged gastroenteritis and shedding of norovirus. J Med Virol. 2008;80:1461–7.PubMedCrossRefGoogle Scholar
  150. 150.
    Roos-Weil D, Ambert-Balay K, Lanternier F, et al. Impact of norovirus/sapovirus-related diarrhea in renal transplant recipients hospitalized for diarrhea. Transplantation. 2011;92:61–9.PubMedCrossRefGoogle Scholar
  151. 151.
    Robles JDR, Cheuk DKL, Ha SY, et al. Norovirus infection in pediatric hematopoietic stem cell transplantation recipients: incidence, risk factors, and outcome. Biol Blood Marrow Transplant. 2012;18:1883–9.PubMedCrossRefGoogle Scholar
  152. 152.
    Schwartz S, Vergoulidou M, Schreier E, et al. Norovirus gastroenteritis causes severe and lethal complications after chemotherapy and hematopoietic stem cell transplantation. Blood. 2011;117:5850–6.PubMedCrossRefGoogle Scholar
  153. 153.
    Schreier E, Doring F, Kunkel U. Molecular epidemiology of outbreaks of gastroenteritis associated with small round structured viruses in Germany in 1997/98. Arch Virol. 2000;145:443–53.PubMedCrossRefGoogle Scholar
  154. 154.
    Kauffman SS, Cahtterjee NK, Fuschino ME, et al. Calicivirus enteritis in an intestinal transplant recipient. Am J Transplant. 2003;3:764–8.CrossRefGoogle Scholar
  155. 155.
    Eid AJ. Posfay-Barbe KM and the AST Infectious Diseases Community of Practice. Am J Transplant. 2009;9 Suppl 4:S147–50.PubMedCrossRefGoogle Scholar
  156. 156.
    Bonvicini F, Marinacci G, Pajno MC, et al. Meningoencephalitis with persistent parvovirus B19 infection in an apparently healthy woman. Clin Infect Dis. 2008;47:384–7.CrossRefGoogle Scholar
  157. 157.
    Douvoyiannis M, Litman N, Goldman DL. Neurologic manifestations associated with parvovirus B19 infection. Clin Infect Dis. 2009;48:1713–23.PubMedCrossRefGoogle Scholar
  158. 158.
    Klumpen H-J, Petersen EJ, Verdonck LF. Severe multiorgan failure after parvovirus B19 infection in an allogeneic stem cell transplant recipient. Bone Marrow Transplant. 2004;34:469–70.PubMedCrossRefGoogle Scholar
  159. 159.
    Laurenz M, Winkelmann B, Roigas J, et al. Severe parvovirus B19 encephalitis after renal transplantation. Pediatr Transplant. 2006;10:978–81.PubMedCrossRefGoogle Scholar
  160. 160.
    Park JB, Kim D-J, Woo S-Y, et al. Clinical implications of quantitative real time-polymerase chain reaction of parvovirus B19 in kidney transplant recipients – a prospective study. Transpl Int. 2009;22:455–62.PubMedCrossRefGoogle Scholar
  161. 161.
    Yango A, Morrissey P, Gohh R, et al. Donor-transmitted parvovirus infection in a kidney transplant recipient presenting as pancytopenia and allograft dysfunction. Transpl Infect Dis. 2002;4:163–6.PubMedCrossRefGoogle Scholar
  162. 162.
    Wasak-Szullkowska E, Grabarczyk P, Rzepecki P. Pure red cell aplasia due to parvovirus B19 infection transmitted probably through hematopoietic stem cell transplantation. Transpl Infect Dis. 2008;10:201–5.CrossRefGoogle Scholar
  163. 163.
    Muetherig A, Christopeit M, Muller LP, et al. Human parvovirus B19 infection with GvHD-like erythema in two allogeneic stem cell transplant recipients. Bone Marrow Transplant. 2007;39:315–6.PubMedCrossRefGoogle Scholar
  164. 164.
    Plentz A, Hahn J, Holler E, et al. Long-term parvovirus B19 viraemia associated with pure red cell aplasia after allogeneic bone marrow transplantation. J Clin Virol. 2004;31:16–9.PubMedCrossRefGoogle Scholar
  165. 165.
    Renoult E, Bachelet C, Krier-Coudert M-J, et al. Recurrent anemia in kidney transplant recipients with parvovirus B19 infection. Transplant Proc. 2006;38:2321–3.PubMedCrossRefGoogle Scholar
  166. 166.
    Beckhoff A, Steffen I, Sandoz P, et al. Relapsing severe anaemia due to primary parvovirus B19 infection after renal transplantation: a case report and review of the literature. Nephrol Dial Transplant. 2007;22:3660–3.PubMedCrossRefGoogle Scholar
  167. 167.
    Ardalan MR, Shoja MM, Tubbs RS, Jayne D. Parvovirus B19 microepidemic in renal transplant recipients with thrombotic microangiopathy and allograft vasculitis. Exp Clin Transplant. 2008;6:137–43.PubMedGoogle Scholar
  168. 168.
    Ardalan MR, Shoja MM, Tubbs RS, et al. Postrenal transplant hemophagocytic lymphohistiocytosis and thrombotic microangiopathy associated with parvovirus B19 infection. Am J Transplant. 2008;8:1340–4.PubMedCrossRefGoogle Scholar
  169. 169.
    Barzon L, Murer L, Pacenti M, et al. Investigation of intrarenal infections in kidney transplant recipients unveils an association between parvovirus B19 and chronic allograft injury. J Infect Dis. 2009;199:372–80.PubMedCrossRefGoogle Scholar
  170. 170.
    Breinholt JP, Moulik M, Dreyer WJ, et al. Viral epidemiologic shift in inflammatory heart disease: the increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients. J Heart Lung Transplant. 2010;29:739–46.PubMedPubMedCentralCrossRefGoogle Scholar
  171. 171.
    Allander T, Andreasson K, Gupta S, et al. Identification of a third human polyomavirus. J Virol. 2007;81:4130–6.PubMedPubMedCentralCrossRefGoogle Scholar
  172. 172.
    Gaynor AM, Missen MD, Whiley DM, et al. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog. 2007;3:595–604.CrossRefGoogle Scholar
  173. 173.
    Sharp CP, Norja P, Anthony I, Bell JE, Simmonds P. Reactivation and mutation of newly discovered WU, KI and Merkel Cell carcinoma polyomaviruses in immunosuppressed individuals. J Infect Dis. 2009;199:398–404.PubMedCrossRefGoogle Scholar
  174. 174.
    Mourez T, Bergeron A, Ribaud P, et al. Polyomaviruses KI and WU in immunocompromised patients with respiratory disease. Emerg Infect Dis. 2009;15:107–9.PubMedPubMedCentralCrossRefGoogle Scholar
  175. 175.
    Dibiaggi M, Canducci F, Brerra R, et al. Molecular epidemiology of KI and WU polyomaviruses in infants with acute respiratory disease and in adult hematopoietic stem cell transplant recipients. J Med Virol. 2010;82:153–6.CrossRefGoogle Scholar
  176. 176.
    Penn I, First MR. Merkel’s cell carcinoma in organ recipients: report of 41 cases. Transplantation. 1999;68:1717–21.PubMedCrossRefGoogle Scholar
  177. 177.
    Stelzmueller I, Wiesmayr S, Swenson BR, et al. Rotavirus enteritis in solid organ transplant recipients: an underestimated problem? Transpl Infect Dis. 2007;9:281–5.PubMedCrossRefGoogle Scholar
  178. 178.
    Yin Y, Metselaar HJ, Sprengers D, et al. Rotavirus in organ transplantation: drug-virus-host interactions. Am J Transplant. 2015;15:585–93.PubMedCrossRefGoogle Scholar
  179. 179.
    Haber P, Patel M, Izurieta HS, et al. Postlicensure monitoring of intussusception after RotaTeq vaccination in the United States, February 1, 2006 to September 25, 2007. Pediatrics. 2008;121:1206–12.PubMedCrossRefGoogle Scholar
  180. 180.
    Heyse JF, Kuter BJ, Dallas MJ, et al. Evaluating the safety of a rotavirus vaccine: the REST of the story. Clin Trials. 2008;5:131–9.PubMedPubMedCentralCrossRefGoogle Scholar
  181. 181.
    Reisinger KS, Block SL. Characteristics of an ideal rotavirus vaccine. Clin Pediatr. 2008;47:555–63.CrossRefGoogle Scholar
  182. 182.
    Rubin LG, Levin MJ, Davies EG, et al. 2013 IDSA clinical guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58:309–18.PubMedCrossRefGoogle Scholar
  183. 183.
    Gubler DJ. The continuing spread of West Nile virus in the western hemisphere. Clin Infect Dis. 2007;45:1039–46.PubMedCrossRefGoogle Scholar
  184. 184.
    Planitzer CB, Modrof J, Kreil TR. West Nile virus neutralization by US plasma-derived immunoglobulin products. J Infect Dis. 2007;196:435–40.PubMedCrossRefGoogle Scholar
  185. 185.
    Nash D, Mostashari F, Fine A, et al. The outbreak of West Nile virus infection in the New York City area in 1999. N Engl J Med. 2001;344:1807–14.PubMedCrossRefGoogle Scholar
  186. 186.
    Gea-Banacloche J, Johnson RT, Bagic A, et al. West Nile virus: pathogenesis and therapeutic options. Ann Intern Med. 2004;140:545–53.PubMedCrossRefGoogle Scholar
  187. 187.
    Ferguson DD, Gershman K, LeBailly A, et al. Characteristics of the rash associated with West Nile virus fever. Clin Infect Dis. 2005;41:1204–7.PubMedCrossRefGoogle Scholar
  188. 188.
    Sejvar JJ. The long-tern outcomes of human West Nile virus infection. Clin Infect Dis. 2007;44:1617–24.PubMedCrossRefGoogle Scholar
  189. 189.
    Bode AV, Sejvar JJ, Pape J, et al. West Nile virus disease: a descriptive study of 228 patents hospitalized in a 4-county region of Colorado in 2003. Clin Infect Dis. 2006;42:1234–40.PubMedCrossRefGoogle Scholar
  190. 190.
    Sejvar JJ, Haddad MB, Tierney BC, et al. Neurologic manifestations and outcome of West Nile virus infection. JAMA. 2003;290:511–5.PubMedCrossRefGoogle Scholar
  191. 191.
    Paddock CD, Nicholson WL, Bhatnager J, et al. Fatal hemorrhagic fever caused by West Nile virus in the United States. Clin Infect Dis. 2006;42:1527–35.PubMedCrossRefGoogle Scholar
  192. 192.
    Centers for Disease Control and Prevention (CDC). Possible dialysis-related West Nile virus transmission-Georgia, 2003. MMWR Morb Mortal Wkly Rep. 2004;53:738–9.Google Scholar
  193. 193.
    Iwamoto M, Jernigan DB, Guasch A, et al. Transmission of West Nile virus from an organ donor to four transplant recipients. N Engl J Med. 2003;348:2196–203.PubMedCrossRefGoogle Scholar
  194. 194.
    Centers for Disease Control and Prevention (CDC). Public health dispatch: West Nile virus infection in organ donor and transplant recipients-Georgia and Florida, 2002. MMWR Morb Mortal Wkly Rep. 2002;51:790.Google Scholar
  195. 195.
    Centers for Disease Control and Prevention (CDC). Update: investigations of West Nile virus infections in recipients of organ transplantation and blood transfusion. MMWR Morb Mortal Wkly Rep. 2002;51:833–6.Google Scholar
  196. 196.
    Centers for Disease Control and Prevention (CDC). Public health dispatch: investigations of West Nile virus infections in recipients of blood transfusions. MMWR Morb Mortal Wkly Rep. 2002;51:973–4.Google Scholar
  197. 197.
    Barshes NR, Agee EE, Zgabay T, et al. West Nile virus encephalopathy following pancreatic islet transplantation. Am J Transplant. 2006;6:3037.PubMedCrossRefGoogle Scholar
  198. 198.
    Shepard JC, Subramanian A, Montgomery RA, et al. West Nile virus encephalitis in a kidney transplant recipient. Am J Transplant. 2004;4:830–3.CrossRefGoogle Scholar
  199. 199.
    Armali Z, Ramadan R, Chlebowski A, et al. West Nile meningoencephalitis infection in a kidney transplant recipient. Transplant Proc. 2003;35:2935–6.PubMedCrossRefGoogle Scholar
  200. 200.
    DeSalvo D, Roy-Chaudhury P, Peddi R, et al. West Nile virus encephalitis in organ transplant recipients: another high-risk group for meningoencephalitis and death. Transplantation. 2004;77:466–9.PubMedCrossRefGoogle Scholar
  201. 201.
    Kumar D, Prasad GV, Zaltzman J, et al. Community-acquired West Nile virus infection in solid-organ transplant recipients. Transplantation. 2004;77:399–402.PubMedCrossRefGoogle Scholar
  202. 202.
    Kleinschmidt-DeMasters BK, Marder BA, Levi ME, et al. Naturally acquired West Nile virus encephalitis in transplant recipients: clinical, laboratory, diagnostic, and neuropathological features. Arch Neurol. 2004;61:1210–20.PubMedCrossRefGoogle Scholar
  203. 203.
    Penn RG, Guarner J, Sejvar JJ, et al. Persistent neuroinvasive West Nile virus infection in an immunocompromised patient. Clin Infect Dis. 2006;42:680–3.PubMedCrossRefGoogle Scholar
  204. 204.
    Hong DS, Jacobson KL, Raad II, et al. West Nile encephalitis in 2 hematopoietic stem cell transplant recipients: case series and literature review. Clin Infect Dis. 2003;37:1044–9.PubMedCrossRefGoogle Scholar
  205. 205.
    Hiatt B, Desjardin L, Carter T, et al. A fatal case of West Nile virus infection in a bone marrow transplant recipient. Clin Infect Dis. 2003;37:e129–31.PubMedCrossRefGoogle Scholar
  206. 206.
    Tilley PA, Fox JD, Jayaraman GC, et al. Nucleic acid testing for West Nile virus RNA in plasma enhances rapid diagnosis of acute infection in symptomatic patients. J Infect Dis. 2006;193:1361–4.PubMedCrossRefGoogle Scholar
  207. 207.
    Jordan I, Briese T, Fischer N, et al. Ribavirin inhibits West Nile virus replication and cytopathic effect in neural cells. J Infect Dis. 2000;182:1214–7.PubMedCrossRefGoogle Scholar
  208. 208.
    Hamden A, Green P, Mendelson E, et al. Possible benefit of intravenous immunoglobulin therapy in a lung transplant recipient with West Nile virus encephalitis. Transpl Infect Dis. 2002;4:160–2.CrossRefGoogle Scholar
  209. 209.
    Ben-Nathan D, Lustig S, Tam G, et al. Prophylactic and therapeutic efficacy of human intravenous immunoglobulin in treating West Nile virus infection in mice. J Infect Dis. 2003;188:5–12.PubMedCrossRefGoogle Scholar
  210. 210.
    Makhoul B, Braun E, Herskovitz M, et al. Hyperimmune gammaglobulin for the treatment of West Nile Virus encephalitis. Isr Med Assoc J. 2009;11:151–3.PubMedGoogle Scholar
  211. 211.
    Carson PJ, Konewko P, Wold KS, et al. Long-term clinical and neuropsychological outcomes of West Nile virus infection. Clin Infect Dis. 2006;43:723–30.PubMedCrossRefGoogle Scholar
  212. 212.
    Morelli MC, Sambri V, Grazi GL, et al. Absence of neuroinvasive disease in a liver transplant recipient who acquired West Nile Virus (WNV) infection from the organ donor and who received WNV antibodies prophylactically. Clin Infect Dis. 2010;51:e34–7.PubMedCrossRefGoogle Scholar
  213. 213.
    Martin JE, Pierson TC, Hubka S, et al. A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase I clinical trial. J Infect Dis. 2007;196:1732–40.PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Funk GA, Gosert R, Hirsch HH. Viral dynamics in transplant patients: implications for disease. Lancet Infect Dis. 2007;7:460–72.PubMedCrossRefGoogle Scholar
  215. 215.
    Wada K, Kubota N, Ito Y, et al. Simultaneous quantification of Epstein-Barr virus, cytomegalovirus, and human herpesvirus 6 DNA in samples from transplant recipients by multiplex real-time PCR assay. J Clin Microbiol. 2007;45:1426–32.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Smith TF, Espy MJ, Mandrekar J, et al. Quantitative real-time polymerase chain reaction for evaluating DNAemia due to cytomegalovirus, Epstein-Barr virus, and BK virus in solid-organ transplant recipients. Clin Infect Dis. 2007;45:1056–61.PubMedCrossRefGoogle Scholar
  217. 217.
    Weinberg A, Zamora MR, Li S, et al. The value of polymerase chain reaction for the diagnosis of viral respiratory tract infections on lung transplant recipients. J Clin Virol. 2002;25:171–5.PubMedCrossRefGoogle Scholar
  218. 218.
    Kumar D, Erdman D, Keshavjee S, et al. Clinical impact of community-acquired respiratory viruses on bronchiolitis obliterans after lung transplant. Am J Transplant. 2005;5:2031–6.PubMedCrossRefGoogle Scholar
  219. 219.
    Matar LD, McAdams HP, Palmer SM, et al. Respiratory viral infections in lung transplant recipients: radiologic findings with clinical correlation. Radiology. 1999;213:735–42.PubMedCrossRefGoogle Scholar

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© Springer International Publishing Switzerland 2016

Open Access This chapter is distributed under the terms of the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

Authors and Affiliations

  1. 1.Department of Infectious DiseasesThe Warren Alpert Medical School of Brown UniversityBristolUSA

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