Single Donor-Derived Strongyloidiasis in Three Solid Organ Transplant Recipients: Case Series and Review of the Literature

Introduction

An estimated 100 million cases of strongyloidiasis are reported worldwide; however, the true burden is unknown due to the parasite's ability to cause chronic asymptomatic infections and autoinfection 1. Immunocompromised patients are at high risk for hyperinfection and disseminated disease 2. Strongyloides infections have been previously reported in transplant patients. In most cases, dissemination of latent infection in the recipient following immunosuppression has been suspected. Although rare, donor-derived disease has been reported 3.

In July 2012, a 24-year-old Puerto Rico-born Hispanic man was hospitalized for multiple gunshot wounds. He required intubation, multiple vasopressors and packed red blood cell transfusion. He developed cerebral edema. Certification of brain death was performed. On hospital Day 10, his organs were procured and transplanted. He received 2 g of methylprednisolone and 1 g of methylprednisolone with cefazolin at 12 and 3 h prior to cross-clamp, respectively. He had no history of symptoms suggestive of Strongyloides infection but had traveled to Puerto Rico often.

Case 1

A 60-year-old Hispanic man with end-stage ischemic cardiomyopathy underwent orthotopic heart transplantation. He was born in the United States and lived in Puerto Rico as a teenager. Induction therapy consisted of methylprednisolone followed by maintenance immunosuppression with tacrolimus, mycophenolate mofetil (MMF) and prednisone. Posttransplant course was complicated by recurrent episodes of grade 3A(2R) rejection in the first month requiring two courses of methylprednisolone 1 g daily for 3 days and one course of prednisone 270 mg daily for 3 days.

On posttransplant Day 48, he presented with fatigue, sore throat and hemoptysis. An endomyocardial biopsy demonstrated grade 1A rejection and multifocal myocyte necrosis. Echocardiography and right heart catheterization revealed normal allograft function and hemodynamics. Respiratory distress and hypotension developed shortly after catheterization requiring intubation and vasopressor support. Empiric vancomycin, piperacillin–tazobactam, fluconazole and oseltamivir were initiated. Chest radiograph revealed diffuse bilateral interstitial infiltrates (Figure 1). The organ procurement organization (OPO) was contacted about the clinical course of the other transplant recipients; however, no problems were reported at this time. Over the next 72 h, septic shock developed secondary to Enterobacter cloacae. Continuous veno-venous hemodialysis (CVVH) was initiated due to deteriorating renal function and persistent metabolic acidosis. On posttransplant Day 55, Strongyloides stercoralis larvae were found on bronchoalveolar lavage. Ivermectin and albendazole were initiated. Immunosuppression was maintained with a lower dose of MMF and a continuous infusion of tacrolimus. Three vasopressors, mechanical ventilation and CVVH were continued. Meropenem and daptomycin were started for bacteremia due to E. cloacae, Klebsiella pneumoniae and vancomycin-resistant enterococci. Lumbar puncture revealed Strongyloides in the cerebrospinal fluid (CSF). CSF cultures became positive for vancomycin-resistant enterococcus. Linezolid was added. On posttransplant Day 70, the transplant center was contacted by the OPO with the diagnosis of Strongyloides in the kidney–pancreas recipient. Care was withdrawn 7 days later. On autopsy, adult Strongyloides and rhabditiform and filariform larvae were found within a perirectal peritoneal parasitoma and intestinal mucosa; larval forms were found in the lung parenchyma, lymph nodes and cardiac allograft.

Case 2

Two months after travel to Louisiana and Florida, a 64-year-old US-born Caucasian man with end-stage renal disease secondary to type I diabetes mellitus underwent simultaneous pancreas and kidney transplant. Induction therapy consisted of antithymocyte globulin and 500 mg methylprednisolone followed by maintenance immunosuppression with tacrolimus, MMF and prednisone. Posttransplant course was complicated by small bowel obstruction requiring multiple surgeries and multidrug-resistant E. cloacae sepsis. Pseudo-aneurysm hemorrhage necessitated allograft pancreatectomy on posttransplant Day 33. Pathology showed fat necrosis and acute hemorrhage without evidence of Strongyloides larvae.

On posttransplant Day 66, a 2-week history of nausea, anorexia and abdominal fullness precipitated an esophagogastroduodenoscopy (EGD), which demonstrated diffusely ulcerated duodenal mucosa and adult Strongyloides on biopsy. The patient also had a maculopapular, nonpuritic rash on his trunk, which showed nonspecific porokeratosis on biopsy without evidence of parasitic infection. The patient was subsequently admitted and treated with ivermectin and albendazole. Immunosuppression was transitioned to cyclosporine; MMF and prednisone were discontinued. Empiric therapy with vancomycin, cefepime and metronidazole was started. Stool and urine ova and parasite (O&P) exams were positive for rhabditiform larvae (Figure 2) and cleared after 3 days of treatment. The patient was discharged on posttransplant Day 85 with good renal function. Albendazole and ivermectin were continued for 1 and 3 weeks, respectively.

Case 3

A 14-year-old US-born Caucasian boy with end-stage renal disease secondary to single dysplastic kidney underwent a preemptive renal transplant. He was a life-long resident of central West Virginia with no travel history. Induction therapy consisted of basiliximab and 360 mg methylprednisolone followed by maintenance immunosuppression with tacrolimus, MMF and prednisone. On posttransplant Day 72, the patient was admitted to another hospital because of fever, vomiting and diarrhea. He was started on cefepime. Knowledge of Strongyloides infection in the heart and kidney–pancreas recipients prompted patient transfer to the transplant center. His examination was notable for a diffuse petechial rash over the lower abdomen, buttocks and thighs. Renal function was stable. Duodenal aspirates and biopsies obtained by EGD revealed Strongyloides rhabditiform larvae (Figure 3). On posttransplant Day 74, he was started on ivermectin and albendazole; cefepime was continued. Immunosuppression was transitioned to cyclosporine; MMF and prednisone were discontinued. Stool O&P exam was positive for Strongyloides while urine was negative. The gastrointestinal symptoms and rash resolved. Stool O&P became negative after 3 days of treatment. On posttransplant Day 79, he was discharged to home with good renal function. Albendazole and ivermectin were continued for 2 and 4 weeks, respectively.

On posttransplant Day 114, the patient was diagnosed with acute T cell–mediated rejection. He was treated with three doses of methylprednisolone at 10 mg/kg followed by a prednisone taper. Empiric ivermectin treatment was restarted and continued for 2 weeks following completion of the prednisone taper.

The fourth organ recipient underwent orthotopic liver transplant and expired posttransplant Day 4 of undetermined causes. No evidence of Strongyloides was found on autopsy.

Because reactivation was suspected in the heart and kidney–pancreas recipients due to travel history, strongyloidiasis was not immediately reported to the OPO. No additional testing was completed to differentiate between reactivation and donor transmission. Prompted by the kidney recipient's symptoms, the transplant coordinator contacted the OPO 5 days after the kidney–pancreas recipient's Strongyloides diagnosis to report infection and inquire about the other recipients. Two days later, the Organ Procurement and Transplantation Network (OPTN) notified the Centers for Disease Control and Prevention (CDC) of strongyloidiasis in the three transplant recipients. Serology testing was performed on stored recipient and donor serum. All recipients were negative; however, the donor tested positive at 13.68 U/µL (positive >1.7 U/µL) (Table 1). In addition, the donor had no eosinophilia and tested negative for human T cell lymphotrophic virus-1 (HTLV-1).

Discussion

These cases represent probable transmission of Strongyloides infection from a common donor. Pretransplant Strongyloides serology results imply that the donor had chronic Strongyloides infection, which reactivated and became disseminated prior to transplantation of his organs. Guidelines from the American Society of Transplantation (AST) recommend screening for Strongyloides in at-risk recipients, living donors and, where feasible, deceased donors 4. No recipients in this series were screened or received prophylaxis pretransplant despite history suggesting potential exposure.

OPTN policy 4.5 requires reporting of potential disease transmissions within 24 h of any substantial concern for donor derivation. Early diagnosis and treatment may have mitigated morbidity and mortality in these cases. Our series demonstrates the need for timely communication between transplant centers and OPOs as there was a significant delay in diagnosis between cases 5, 6. Furthermore, a high index of suspicion of potential donor-transmitted disease is essential.

Conclusions

This case series of suspected donor-derived strongyloidiasis, once thought to be a rare phenomenon, draws attention to diligent screening in all at-risk recipients and donors. Further research on treatment regimens for immunocompromised hosts is also needed to maintain the safety of transplant recipients. Timely notification of OPOs and transplant centers as well as high index of suspicion of possible donor-derived infections is paramount.

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.