Infectious Gastroenteritis in Transplantation

Diarrhea is a major cause of morbidity and mortality in transplantation, both in hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. Nearly every HSCT recipient experiences at least one diarrheal episode, of which 40% is of infectious origin¹. Differentiation between infectious and non-infectious causes of diarrhea is challenging. A major clinical concern is that misdiagnosis of infectious gastroenteritis as graft versus host disease (GVHD) or graft rejection will lead to inappropriate augmented immunosuppression². It has been shown that increased immunosuppression in the presence of viral infection can significantly worsen symptoms and adversely affect outcome; conversely, a reduction in immunosuppression may be critical to resolving infection². Non-infectious causes of diarrhea include:

• HSCT conditioning regimen-associated mucositis
• Acute GVHD of the gut
• Antibiotic-associated diarrhea
• Immunosuppressive agent-associated diarrhea

Of the infectious causes of diarrhea, viruses are the most common and while no therapy has been shown to be effective, establishing an etiology has proven essential¹. Early identification enables effective clinical action to help reduce the prolonged and persistent course of diarrheal illness and associated hospital stays¹. Clinical measures include reduction in immunosuppression, administration of IVIG, and supportive care^3,4.

Of particular importance in establishing an etiology is the prevention of nosocomial outbreaks. Meticulous infection control practices are required due to the highly infectious nature of these pathogens coupled with prolonged excretion in the transplant setting¹.

Norovirus

Norovirus infection can cause severe disease with significant morbidity and mortality after transplantation, in both SOT and HSCT (before and after engraftment). Due to the similar and nonspecific features of norovirus gastroenteritis and gut GVHD, differentiation requires laboratory testing. Misdiagnosis of norovirus as GVHD may lead to inappropriate augmentation with immunosuppressants, which has been shown to significantly worsen symptoms and adversely affect outcome². Conversely, a reduction in immunosuppression may be critical to resolving infection². Thus, norovirus should always be considered in the differential diagnosis of gut GVHD or graft rejection⁵. This allows for early diagnosis in these vulnerable patients and prevents escalation of immunosuppression for wrongly suspected GVHD or graft rejection⁵.

Rotavirus

Rotavirus infection is an important cause of prolonged diarrhea post-transplantation, causing significant morbidity and frequently requiring hospitalization¹. The incidence of rotavirus in HSCT patients has been reported to be as high as 10% for both allogeneic and autologous transplants¹. One study showed the duration of symptoms ranged from 4 days to 4 months¹. Affected patients were lymphopenic and/or on immunosuppression for GVHD.

Adenovirus

Severe morbidity and mortality due to adenovirus infection has been observed in both HSCT and SOT recipients⁶. Early diagnosis and intervention provides the best chance of reducing the risk of illness and death among transplant recipients⁶. Molecular detection of adenovirus in stool specimens of allogeneic HSCT recipients has been shown to precede viremia, suggesting that intestinal infections may represent a common source of virus reactivation and dissemination⁷. A recent study reported a critical threshold of 1x10⁶ copies per gram stool preceded the onset of viremia by a week or more⁸. Intervention at this early stage may prevent or delay disseminated adenovirus disease⁸.

Viracor-IBT Gastroenteritis Testing

Viracor-IBT offers a full range of molecular diagnostic tests for viral gastroenteritis with the fastest turn-around times available, enabling clinicians to make prompt and effective treatment decisions. Due to increasing concern regarding the significant clinical and financial implications of nosocomial outbreaks, sensitive and rapid detection of these pathogens has never been more important. Implementation of effective infection control measures begins with reliable and rapid laboratory results.

Viracor-IBT Viral Gastroenteritis Menu

References

1. Liakopoulou E, Mutton K, Carrington D, Robinson S, Steward CG, Goulden NJ, et al. Rotavirus as a significant cause of prolonged diarrhoeal illness and morbidity following allogeneic bone marrow transplantation. Bone Marrow Transplantation. 2005;36:691–694.

2. Kaufman SS, Chatterjee NK, Fuschino ME, Magid MS, Gordon RE, Morse DL, et al. Calicivirus enteritis in an intestinal transplant recipient. Am J Transplant. 2003;3(6):764-768.

3. Thielman NM, Guerrant RL. Acute Infectious Diarrhea. N Engl J Med. 2004;350:38-47.

4. Guerrant RL, Van Gilder T, Steiner TS, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32:331-351.

5. Roddie C, Paul JP, Benjamin R, Gallimore CI, Xerry J, Gray JJ, et al. Allogeneic hematopoietic stem cell transplantation and norovirus gastroenteritis: a previously unrecognized cause of morbidity. Clin Infect Dis. 2009;49(7):1061-1068.

6. Echavarrı´a M. Adenoviruses in Immunocompromised Hosts. Clin Micro Rev. 2008;21(4):704–715.

7. Lion T, Baumgartinger R, Watzinger F, Matthes-Martin S, Suda M, Preuner S, et al. Molecular monitoring of adenovirus in peripheral blood after allogeneic bone marrow transplantation permits early diagnosis of disseminated disease. Blood. 2003;102:1114–1120.

8. Lion T, Kosulin K, Landlinger C, Rauch M, Preuner S, Jugovic D. Monitoring of adenovirus load in stool by real-time PCR permits early detection of impending invasive infection in patients after allogeneic stem cell transplantation. Leukemia. 2010:1–9.