Sapovirus as an Emerging Pathogen Implicated in Chronic Diarrhea in Post-Solid Organ Transplant Setting: A Brief Report

Abstract

Background

Diarrhea is common in the post-solid organ transplant setting and can be infectious or noninfectious in origin. Among infectious causes of diarrhea norovirus and Clostridioides difficle have been implicated commonly while mycophenolate mofetil is one of the common noninfectious causes. There have been anecdotal reports of sapovirus as cause of chronic diarrhea in post-solid organ transplant recipients.

Methods

We report two such cases with sapovirus-associated chronic diarrhea presenting following renal transplant who were diagnosed on stool multiplex polymerase chain reaction (PCR) testing done at our center.

Results

A 74-year-old lady, post-renal transplant in 2013, presented with chronic diarrhea and weight loss for 9 months and was diagnosed to have sapovirus and norovirus coinfection on stool multiplex PCR testing. She was successfully treated with nitazoxanide and change in immunosuppression to azathioprine. Another 48-year-old lady with renal transplantation in 2014 presented with 6-month chronic diarrhea with acute worsening and acute kidney injury. Her stool multiplex PCR was also positive for sapovirus. She was also successfully managed with fluid repletion, antidiarrheal, nitazoxanide, and change in immunosuppression to enteric-coated mycophenolic acid.

Conclusion

Sapovirus is an emerging cause of post-renal transplant chronic diarrhea. Early recognition is crucial for appropriate management.

Keywords

multiplex PCR - post-transplant diarrhea - sapovirus

Introduction

Diarrhea is common in post-solid transplant individuals and adds to the morbidity and mortality in such individuals.[1] While most diarrheal episodes occur early in the posttransplant period as acute self-limiting gastroenteritis, rarely it can be recurrent or chronic in presentation. The etiologies of diarrhea in post-solid transplant individuals can be broadly classified into infectious and noninfectious causes.[1] Among the infectious causes a plethora of organisms including bacteria, viruses, and protozoan parasites have been implicated. While drug-induced and posttransplant lymphoproliferative disorder are notable etiologies in the noninfectious group. Guidelines suggest an initial empirical treatment of diarrhea with appropriate fluid and electrolyte management and an algorithmic evaluation if recurrent or chronic diarrhea occurs.[1]

Sapovirus, a single-stranded ribonucleic acid, nonenveloped virus belonging to the genus Sapovirus within the Caliciviridae family, is commonly and increasingly being implicated in self-limiting acute diarrhea in the community setting.[2] This increased recognition is due to improvement in molecular diagnostics, which have enabled its differentiation from norovirus, another common virus implicated in acute gastroenteritis belonging to the Caliciviridae family.[3] It is now also increasingly being recognized as emerging pathogen causing persistent diarrhea in immunocompromised individuals, particularly in the post-renal transplant setting.[4] [5] In this report, we present two cases who presented with chronic diarrhea in the post-renal transplant setting and were diagnosed as having sapovirus-associated diarrhea.

Case 1

A 74-year-old lady with deceased donor renal transplant 12 years back presented with chronic diarrhea for 9 months and significant weight loss of 10 kg in the outpatient clinic in March 2025 ([Table 1]). She denied any fever, vomiting, or blood in stools. She was on prednisolone 5 mg, mycophenolate mofetil (MMF) 500 mg twice a day, and tacrolimus 1.5 mg a day. Her diarrhea was evaluated with stool routine microscopy, stool for Clostridioides difficle toxin A and B assay, stool for opportunistic organisms with acid-fast staining, and upper gastrointestinal endoscopy and duodenal biopsy. The tests were unrevealing and negative. Her colonoscopy was also normal but her colonic biopsy was positive for cytomegalovirus (CMV) polymerase chain reaction (PCR) (3000 copies CMV deoxyribonucleic acid [DNA]/25 mg) but the histopathological specimen did not show any evidence of colitis or inclusions. She underwent a stool multiplex PCR (QIAstat-Dx GIP 2, Qiagen, Germany), which turned out to be positive for both sapovirus and norovirus GI/GII. She was treated with a course of nitazoxanide for 1 week and change in immunosuppression from MMF to azathioprine with resolution in her symptoms. In addition, due to the presence of high load of CMV DNA in the colonic biopsy she was treated with intravenous ganciclovir followed by oral valganciclovir.

Case 2

A 48-year-old lady with live unrelated renal transplant in 2014 on triple immunosuppression with tacrolimus 1.5 mg twice a day, MMF 500 mg twice a day, and prednisolone 5 mg once daily presented with chronic diarrhea for 6 months and weight loss of 6 kg in May 2025. She denied any blood in stools or fever. Her stool routine microscopy, stool for modified acid-fast stain for opportunistic organisms, and stool for C. difficle toxin assay were negative. Her endoscopy revealed some scalloping of duodenal folds but the biopsy was normal. Her colonoscopy was normal but PCR from biopsy specimen for CMV DNA showed 400 copies/25 mg and no evidence of colitis or inclusion bodies on biopsy. Her blood CMV PCR was also negative. Her presenting serum creatinine was 1.99 mg/dL suggestive of acute kidney injury. She was treated conservatively with intravenous fluid, loperamide, and nitazoxanide along with change in immunosuppression to enteric-coated mycophenolic acid 360 mg twice a day with improvement in symptoms and return of serum creatinine to 1.3 mg/dL. She was discharged after improvement in her symptoms. She was not administered ganciclovir as her CMV DNA load was low and biopsy or colonoscopy was not suggestive of any evidence of colitis.

Discussion

Diarrhea in post-solid organ transplant recipients is common with the prevalence ranging from 20 to 50%.[6] Apart from causing distressing symptoms, post-transplant diarrhea is associated with a risk of causing renal failure, potential medicine toxicity, rejection, and even mortality.[6] Although infectious causes are more common in the tropics, noninfectious diarrhea particularly due to immunosuppressive medications is fairly common as well.[1] [6]

Sapovirus infection is a rare cause of diarrhea in the posttransplant setting.[4] In a large Indian series evaluating 188 samples in posttransplant setting, sapovirus was isolated in stool PCR in only one patient.[7] In the same series norovirus was the most common cause of posttransplant diarrhea incriminated in one-fifth of the cases.[7] In our case one of the patients had both norovirus and sapovirus infection, this dual infection is not uncommon. In fact, in the Indian series evaluating the role of stool PCR in posttransplant diarrhea, 68% had coinfections.[7]

Norovirus/sapovirus diarrhea is not innocuous and is associated with a greater weight loss, greater duration of symptoms, and need for immunosuppressive dosage reduction as compared to bacterial and parasitic causes.[8] It can be associated with acute kidney injury in 80% of the post-renal transplant cases as in one of our cases.[8] In another large Indian series of 198 post-renal transplant patients, 85 (42.5%) had diarrhea and majority of these were infective in nature.[9] Among the microbiologically proven infective cases, sapovirus infection was present in just one case.[9] The same series showed that majority of patients with diarrhea were on MMF and MMF withdrawal was needed in 48% of these patients in view of persistent or chronic symptoms. Both of our patients were on MMF, which is a risk factor for developing chronic diarrhea in the posttransplant setting.[9] In another large prospective multicenter study (DIDACT) evaluating severe diarrhea in the post-transplant setting, close to 50% of the patients had an infective cause or nonimmunosuppressive drug-induced diarrhea causing medication as the etiologic agent.[10] Among the infective causes, bacterial causes including Campylobacter, Salmonella, and C. difficle outnumbered viral causes.[10] However, with the advent of stool multiplex PCR, viral etiologies are being increasingly recognized.[11]

There is no specific antiviral therapy for sapovirus. Treatment of sapovirus diarrhea entails fluid repletion and antidiarrheal agents like loperamide to reduce stool frequency.[5] Commonly, a reduction or a change in immunosuppression is required.[5] There have been anecdotal reports of use of nitazoxanide, a well-known anti-protozoal drug for its use in sapovirus diarrhea due to its purported action of suppression of intracellular viral replication.[4] [5] Nitazoxanide is a thiazolide broad-spectrum antiinfective drug against a range of extracellular and intracellular protozoa, helminths, and bacteria, in addition to viruses. Nitazoxanide acts by inhibiting pyruvate-ferredoxin oxidoreductase enzyme-dependent reactions necessary for anaerobic energy metabolism.[12] We used nitazoxanide for 1 week for both of our patients. Since MMF is commonly incriminated in posttransplant diarrhea, it has been suggested to either use enteric-coated mycophenolic acid or change immunosuppression to azathioprine to decrease the frequency of diarrhea as we did for our patients.[5] [6]

Although both the patients tested positive on the colonic biopsy specimen PCR testing, none of them demonstrated any evidence of colitis either clinically, on colonoscopy or histopathology. Demonstration of inclusion bodies is highly specific and immunohistochemistry remains the gold standard to diagnose CMV colitis.[13] The use of tissue PCR alone for the diagnosis of CMV colitis is controversial since it does not always connote active infection since CMV DNA can be detected even in latently infected leukocytes leading to a low positive predictive value of the test.[13] None of our patients had any other evidence of CMV colitis in form of fever, blood in stools, ulceration on colonoscopy, colitis on biopsy specimen, or presence of classical intranuclear inclusions. Hence, we cannot firmly incriminate CMV as the cause of diarrhea in our patients.

Our report indicates that sapovirus is an emerging cause of post-solid organ transplant diarrhea. (Unpublished data from our center suggest sapovirus infection in 10% post-transplant patients.) Stool multiplex PCR to detect sapovirus infection is crucial for the appropriate diagnosis and management of the condition. Future studies should further find out the prevalence of sapovirus, risk factors, and predictors of successful treatment among post-renal transplantation patients with chronic diarrhea.

Table 1 Summary of the post-renal transplant patients presenting with sapovirus-induced chronic diarrhea

Details	Patient 1	Patient 2
Year of transplant	2013	2014
Immunosuppressive medications	Tacrolimus (1.5 mg) MMF (1000 mg) Prednisolone 5 mg	Tacrolimus (3 mg) MMF (1000 mg) Prednisolone 5 mg
Duration of symptoms	9 mo	6 mo
Stool routine microscopy	Negative	Negative
Stool opportunistic organisms (modified acid-fast staining)	Negative	Negative
Stool C. difficle toxin assay	Negative	Negative
Stool multiplex PCR	Norovirus GI/GII Sapovirus	Sapovirus
Treatment offered	Nitazoxanide, loperamide, and change in immunosuppression to azathioprine	Fluids, loperamide, nitazoxanide, and change in immunosuppression to enteric-coated MPA
Response to treatment	Improvement	Improvement

Abbreviations: C. difficle, Clostridioides difficle; MMF, mycophenolate mofetil; MPA, mycophenolic acid; PCR, polymerase chain reaction.

Conflict of Interest

None declared.

Acknowledgments

None.

Ethical Statement

None.

Authors' Contributions

All authors contributed equally to the article.

Data Availability Statement

There is no data associated with this work.

• References

• 1 Mohta S, Sridharan S, Gopalakrishnan R, Prasad N, Bansal SB, Makharia GK. Diarrhea in solid organ transplant recipients in the South Asian region - expert group opinion for diagnosis and management. Indian J Transplant 2022; 16 (Suppl. 01) S23
• 2 Rippl M, Burkhard-Meier A, Schönermarck U, Fischereder M. Sapovirus: an emerging pathogen in kidney transplant recipients?. Infection 2024; 52 (05) 1831-1838
• 3 Rubio-Mora E, Carrascoso GR, Rodríguez JG. Sapovirus infection as another cause of persistent viral diarrhea: case series and review of the literature. Eur J Clin Microbiol Infect Dis 2024; 43 (01) 55-59
• 4 Andrews R, Samad MSA, Chimtalapudi T, Ramesh V, Ali MA. Sapovirus-associated diarrhea in renal transplant patient treated without altering immunosuppression. Indian J Nephrol 2025; 35 (01) 101-103
• 5 Amin K, Choksi V, Farouk SS, Sparks MA. Diarrhea in a patient with combined kidney-pancreas transplant. Am J Kidney Dis 2021; 78 (02) A13-A16
• 6 Angarone M, Snydman DR. AST ID Community of Practice. Diagnosis and management of diarrhea in solid-organ transplant recipients: guidelines from the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant 2019; 33 (09) e13550
• 7 Tiwari V, Anand Y, Gupta A. et al. Etiological spectrum of infective diarrhea in renal transplant patient by stool PCR: an Indian perspective. Indian J Nephrol 2021; 31 (03) 245-253
• 8 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 (01) 61-69
• 9 Patil AD, Saxena NG, Thakare SB, Pajai AE, Bajpai D, Jamale TE. Diarrhea after kidney transplantation: a study of risk factors and outcomes. J Postgrad Med 2023; 69 (04) 205-214
• 10 Maes B, Hadaya K, de Moor B. et al. Severe diarrhea in renal transplant patients: results of the DIDACT study. Am J Transplant 2006; 6 (06) 1466-1472
• 11 Atamna A, Rahamimov R, Levit A. et al. Enteric pathogen detection using multiplex PCR assay in kidney transplant recipients with diarrhea-retrospective before-after study. Infect Dis Ther 2024; 13 (11) 2415-2422
• 12 Treatment Of Sapovirus Infection In A Renal Transplant Patient With Nitazoxanide. Accessed June 27, 2025 at: Https://Anzsnevents.Com/11215/
• 13 Yerushalmy-Feler A, Padlipsky J, Cohen S. Diagnosis and management of CMV colitis. Curr Infect Dis Rep 2019; 21 (02) 5

Publikationsverlauf

Eingereicht: 01. Juli 2025

Angenommen: 16. August 2025

Artikel online veröffentlicht:
19. November 2025