Disseminated toxoplasmosis in a renal transplant patient.
Brief history of the Present Illness:
The patient was a 42-year-old man, 3 years status-post deceased-donor renal transplant for hypertensive nephropathy. His post-transplant course was complicated by grade 1B rejection 14 months after transplant and 2 years prior to presentation. This rejection was treated with corticosteroids and 7 doses of thymoglobulin, which was further complicated by CMV viremia, which responded to ganciclovir and was treated with valganciclovir for secondary prophylaxis. He had not been prescribed prophylactic TMP-SMX or valganciclovir for >18 months.
He was recently seen in clinic three weeks prior to presentation in routine follow-up, when he complained of tingling with urination (he reported a new sex partner three weeks prior) and three days of peri-umbilical abdominal pain and diarrhea. Laboratory testing was negative for Gonorrhea, Chlamydia, or Trichomonas, prior HIV testing was negative. Creatinine was elevated at 2.56 from baseline 1.5-1.7 and he was admitted for renal biopsy the following week, which showed eosinophilic interstitial nephritis but no evidence of rejection. He was treated with prednisone 75mg/day with plans to repeat biopsy in two weeks.
Three days prior to this planned repeat biopsy, he presented to an outside hospital complaining of weakness, anorexia, hematuria, urinary frequency, cough, and persistent diarrhea. His serum lipase was elevated, which raised concern for pancreatitis and he was transferred for further evaluation. The lipase was 177 (ref 11-82) when repeated. Blood, urine, stool cultures did not have significant growth. Stool testing for C. difficile and examination for ova & parasites was negative x2. Blood CMV quantitative PCR was detected at 2,200 IU. CT abdomen/pelvis showed non-specific distal esophageal, segmental small bowel, gastric, and cecal/ascending colonic wall thickening with pericolonic inflammation but no radiographic evidence of pancreatitis.
GI was consulted for upper and lower endoscopy. EGD showed hemorrhagic mucosa in the body of the stomach, cardia, and fundus, with areas of gastric erosion, which were all biopsied. Colonoscopy showed moderately congested and erythematous mucosa in the proximal transverse colon, hepatic flexure, ascending colon, and cecum that suggested ischemia, and granular/nodular mucosa in the hepatic flexure, which were all biopsied.
Past Medical History including allergies:
End-stage renal disease, status post deceased-donor renal transplant
CMV viremia in setting of thymoglobulin administration two years prior
Left upper extremity fistula creation 8 years prior
No known drug allergies
Belatacept(infusion every 4 weeks), MMF 1,000mg Q12H, Prednisone 5mg Q24H
Carvedilol, Clonidine, Hydralazine, Nifedipine
Brief course of 7 days of cephalexin 2 weeks prior to admission for urinary tingling (with negative urine culture and small leukocyte esterase on urinalysis)
Lives with mother in Southeast US. Does not smoke, has occasional red wine on weekends. Is not married, has four children. Completed high school. Previously incarcerated with last release 8 years prior to admission. No change in diet, travel, sick contacts. Recent new female sexual partner ~5 weeks prior to admission.
Physical Examination: General description, vital signs, and other relevant physical findings.
T: 37.3°C, BP: 108/69, HR: 107, RR: 18, O2 saturation: 97% on 2L.
Healthy appearing man, in no distress. No oral lesions, thrush, or lymphadenopathy. Lungs clear. Regular rhythm, tachycardic rate, systolic murmur referred from fistula. Abdomen soft, non-tender. Multiple tattoos. The examination was otherwise normal.
Studies: Relevant laboratory findings, radiology, etc.
WBC 10.2 (40%Eo). Hb 10.7. Plt 133. BUN 125, Cr 5.79.
AST 262, ALT 228, AP 52, TB 0.3. Lipase 177, Amylase 169.
UA: Pro 50 mg/dL, nitrite negative, small leukocyte esterase, 9 WBC on microscopy
Blood, Urine, Stool cultures negative. C. difficile & stool O&P negative. BK, EBV, HSV PCR negative. CMV quant PCR 2,200 IU.
CT abdomen/pelvis showed nonspecific distal esophageal, gastric, segmental small bowel, and cecal/ascending colonic wall thickening with pericolonic inflammation, and mild pelvocaliectasis with urothelial thickening of right lower quadrant allograft.
Clinical CoursePrior to Diagnosis:
He was more somnolent than expected after endoscopy, then became non-responsive overnight, prompting a stroke code. Stat CT head showed hypodensities in the right thalamus, right posterior limb internal capsule, and posterior right lentiform nucleus concerning for recent infarct. He further decompensated to hypoxic respiratory failure and shock with blood pressure of 75/52 mmHg. He was treated with vancomycin, meropenem, epinephrine, norepinephrine, and vasopressin, with evaluation for ECMO requested. With progressive and rapid decline, goals of care were discussed with his family, who transitioned him to DNR status, ECMO was deferred and he died <24 hours after endoscopy.
- Enterocytozoon bieneusi
- Cyclospora cayetanensis
- Cryptosporidium parvum
- Toxoplasma gondii
- Entamoeba histolytica
Diagnostic Procedure(s) and Result(s):
Biopsies from abnormal areas of stomach and colon showed tissue cysts and free bradyzoites with areas of acute inflammation and necrosis suggestive of Toxoplasma gondii. Tissue stains with Toxoplasma immunohistochemical stains were positive confirming toxoplasmosis.
Unfortunately, the patient’s decompensation was too rapid to allow specific treatment for toxoplasmosis.
Brief Discussion of Differential/Major Teaching points of case:
Toxoplasma gondii is a zoonotic parasite, which has a worldwide distribution and can infect virtually all warm-blooded animals.(1) Cats are the definitive host, which harbor the sexual parasitic life cycle, and spread oocysts through feces.(2) Oocysts sporulate in the environment, become infective and are ingested by intermediate hosts where oocysts transform into tachyzoites, which localize to neural and muscle tissue and form tissue cysts, which are also infectious if ingested. Toxoplasma seroprevalence varies widely between countries, from moderately high prevalence reported in Central and Southern Europe, Latin America and Southern Africa to lower prevalence in North America, Southeast Asia, Northern Europe, and Sahelian Africa.(1) Seroprevalence for Toxoplasma appears to be declining in the U.S. by sampling of NHANES participants, which could signal increasing risk of congenital toxoplasmosis as this is thought to occur with primary infection of a pregnant woman.(3)
The diagnosis of toxoplasmosis in transplant patients depends on identification of cysts in or positive Toxoplasma immunohistochemical stains of tissue biopsies, seroconversion from negative to positive, or PCR testing.(4)
Toxoplasmosis in solid-organ and hematopoietic cell transplant patients is rare in the era of universal prophylaxis with TMP-SMX but multiple infections have been recently reported in setting of prophylaxis with atovaquone (less effective) and inhaled pentamidine (ineffective) (personal communication, Dr. Aneesh Mehta).
In a multi-center study in France of 38 ICU patients with disseminated toxoplasmosis (22/38, 58% with HCT; 4/38, 10% SOT), 89% had respiratory failure, 53% had shock, 42% had encephalopathy.(5) The 60-day mortality observed in this study was 82%.(5)
In a multi-center study of toxoplasmosis in SOT recipients in Spain, the only significant risk factor by logistic regression was negative pre-transplant Toxoplasma IgG.(6) In contrast, the French series showed HCT patients are much more likely (22/22, 100%) to have positive pre-transplant Toxoplasma IgG and near-term infection after transplant, which suggests that reactivation is most important process of infection.(5) Disseminated toxoplasmosis should be considered in the differential diagnosis for transplant patients with acute respiratory failure, encephalopathy and shock.
Disseminated toxoplasmosis in a renal transplant patient.
- Robert-Gangneux F, Dardé M-L. Epidemiology of and diagnostic strategies for toxoplasmosis. Clin Microbiol Rev. 2012 Apr;25(2):264–96.
- Centers for Disease Control and Prevention. DPDx - Laboratory Identification of Parasites of Public Health Concern: Toxoplasmosis. [Internet]. 2017 [cited 2018 Apr 13]. Available from: https://www.cdc.gov/dpdx/toxoplasmosis/index.html
- Jones JL, Kruszon-moran D, Rivera HN, Price C, Wilkins PP. Toxoplasma gondii Seroprevalence in the United States 2009 – 2010 and Comparison with the Past Two Decades. 2014;90(6):1135–9.
- Schwartz BS, Mawhorter SD. Parasitic infections in solid organ transplantation. Am J Transplant. 2013;13(SUPPL.4):280–303.
- Schmidt M, Sonneville R, Schnell D, Bigé N, Hamidfar R, Mongardon N, et al. Clinical features and outcomes in patients with disseminated toxoplasmosis admitted to intensive care: A multicenter study. Clin Infect Dis. 2013 Dec 1;57(11):1535–41.
- Fernàndez-Sabé N, Cervera C, Fariñas MC, Bodro M, Muñoz P, Gurguí M, et al. Risk factors, clinical features, and outcomes of toxoplasmosis in solid-organ transplant recipients: A matched case-control study. Clin Infect Dis. 2012;54(3):355–61.
Figure 1: Selected images from CT abdomen/pelvis showing esophageal, gastric, wall thickening, and urothelial renal allograft thickening and pelvocaliectasis (slide 5 in ppt – most representative of this case).
Figure 2: Colon biopsy with H&E stain, 40x power showing Toxoplasmatissue cysts with free-form bradyzoites (slide 7 in ppt).
Figure 3: Colon biopsy with Toxoplasmaimmunohistochemical stain, 40x power (slide 9 in ppt).
Figure 4: Stomach biopsy with H&E stain, 20x power showing Toxoplasma tissue cysts and free bradyzoites (slide 10).
Figure 5: Colon biopsy with GMS stain, 40x power showing Toxoplasma tissue cysts (slide 14) in powerpoint.
G. M. Lyon III, None