Pre-transplant Serologies in a Man from West Africa
By Neha Nanda, MD
Dr. Nanda is Assistant Professor of Medicine, Section of Infectious Diseases, Yale School of Medicine
Dr. Nanda reports no financial relationship to this field of study.
A 40-year-old Gambian male with end-stage renal disease secondary to focal segmental glomerulosclerosis (FSGS) was evaluated for a living unrelated kidney transplant. He had received immunosuppressive therapy for FSGS in the past, including long-term cyclosporine, prednisone, and recently, CellCept® (mycophenolate), with a poor therapeutic response, and was transitioned to hemodialysis 1 year prior to evaluation. He entered the United States 10 years ago, and made frequent trips to Gambia and the Ivory Coast to visit family. His last visit to Gambia was 16 months ago, and lasted for 1 month.
Prior to travel he was seen at a travel medicine clinic where he had received malaria prophylaxis and pre-travel vaccinations. On returning to the United States, he did not report any new constitutional symptoms. In preparation for an elective kidney transplant, serological tests for schistosomiasis, filariasis, and strongyloidiasis were obtained. Anti-schistosoma IgG and anti-filaria IgG4 antibody levels were elevated, and an anti-strongyloides IgG antibody level was high normal. His review of symptoms, including fevers, rashes, hematuria, increasing swelling in his lower extremities, and shortness of breath, was negative. The unrelated kidney donor was from the United States. The patient's physical examination was unremarkable except for a patent arterial-venous fistula in his left arm. White blood cell count was 6,000 cells/µL with a persistent mild eosinophilia varying from 8% to 12%. Anti-schistosoma IgG serology was positive at 0.6 optical density (OD; normal, 0-0.1). This was consistent with untreated active infection, or infection acquired in the past. Anti-filarial IgG4 was elevated at 0.9 (normal, < 0.8) and reported as "equivocal." Anti-strongyloides IgG was "high negative" at 1.47 (normal, < 1.49). A positive anti-strongyloides IgG antibody indicates current active, latent, or resolved previous infection. Multiple stool samples evaluated for ova and parasites were negative. Peripheral blood smears were unremarkable; specifically, no microfilaria were observed. Urinalysis did not show hematuria. Serological tests for HTLV-1 and HIV infections were negative.
How should one approach a potential renal transplant candidate who presents with such serological data? Could he still be at risk from these infections after his departure from an endemic setting? Will immunosuppressive agents potentially increase the morbidity associated with these infections?
Individuals traveling to West Africa are at risk of acquiring many classical tropical infections including malaria, dengue fever, schistosomiasis, filariasis, and strongyloidiasis. When evaluating individuals before solid organ transplantation, it is prudent to identify such infections and treat accordingly. After transplantation, patients receive potent immunosuppressive agents to prevent rejection. A latent infection may progress to an active, even fulminant, form of disease. Parasites posing the greatest risk can multiply within the host months or years after the patient has left an endemic area, if the pathogen can continue its life cycle by autoinfection or remain latent in the human host.
Schistosoma mansoni, S. haematobium, and S. intercalatum are endemic to West Africa. Schistosomiasis can manifest itself as an acute infection (Katayama fever syndrome) or as a chronic infection. Individuals being considered for transplantation should be evaluated for chronic schistosomiasis if they have an appropriate exposure history. In chronic schistosomiasis, adult worms can remain viable for years in the circulation surrounding the intestines, urinary bladder, or liver. The inflammatory response to ova normally results in granuloma formation within these organs. Symptomatic hepatic and gastric schistosomiasis have been reported in liver transplant recipients.1 The recipients had positive anti-schistosoma serology before transplant and ova were found in gastric and liver biopsies in the post-transplant period. Both these cases were potentially a result of accelerated ova production. The actual effects of immunosuppression on ova production or migration of adult worms are unknown. Although reactivation of schistosomiasis has not been reported in renal transplant recipients, they tend to have more urological complications in the post-transplant period. Therefore prior to transplant, obtaining serology for schistosomiasis in addition to stool and urine for ova is recommended. If the potential recipient does have a positive serology or has ova in the stool/urine sample, treatment with praziquantel should be initiated in the pre-transplant period.
Wucheria bancrofti is one common species implicated in filariasis. Inhabitants of West Africa may demonstrate either asymptomatic microfilaremia or symptomatic infection, i.e., lymphedema or tropical pulmonary eosinophilia. The adult worms can survive in the human lymphatic system or subcutaneous tissue for years, producing microfilariae that travel in the circulation to reach lungs, heart, or kidneys. Adult worms can live in the human body for up to 7 years.2 Filariasis can reactivate during the post-transplant period, and has been reported to cause graft dysfunction and lymphocele following renal transplantation.3 To prevent such complications, filarial antibody studies and peripheral blood smears for microfilariae should be obtained prior to a transplant if prior exposures have occurred. If either test is positive, the patient should receive appropriate treatment. Diethylcarbamazine citrate (DEC) is the drug of choice and can be obtained from the Centers for Disease Control and Prevention. Other effective regimens are combinations of ivermectin, albendazole, and doxycycline. Doxycycline causes sterility in the adult female worms.4
Strongyloides stercoralis is unique in its ability to perpetuate human infections by autoinfection. After transplantation it can cause a severe hyperinfection syndrome since the autoinfection cycle is up-regulated in the face of immunosuppression.2 Potential transplant recipients who have appropriate exposures should be evaluated for active infections. Stool samples should be examined for larvae and strongyloides serology (IgG) should be obtained, especially if there is unexplained eosinophilia. If either is positive, treatment with ivermectin should be initiated.
Since our patient was a renal transplant candidate, we treated him for presumptive schistosomiasis, filariasis, and strongyloidiasis on the basis of his serological findings. He received praziquantel for schistosomiasis and ivermectin for strongyloidiasis. For filariasis he received albendazole, doxycycline, and additional ivermectin. After treatment, his white blood cell count was 5,400 cells/µL and eosinophilia had resolved. He successfully underwent a living unrelated kidney transplant 1 week after therapy. After transplantation he was started on routine immunosuppressive regimen with excellent postoperative recovery. At the 2-month follow-up to his renal transplant, he was doing well.
- Hoare M, et al. Hepatic and intestinal schistosomiasis after orthotopic liver transplant. Liver Transpl 2005;11:1603-1607.
- Martin-Davila P, et al. Transmission of tropical and geographically restricted infections during solid-organ transplantation. Clin Microbiol Rev 2008;21:60-96.
- Derouiche A, et al. Post-kidney transplantation lymphocele due to a lymphatic filariasis. Transplant Proc 2010;42:2808-2812.
- Hoerauf A. Filariasis: New drugs and new opportunities for lymphatic filariasis and onchocerciasis. Curr Opin Infect Dis 2008;21:673-681.