Toxoplasma gondii in the cerebrospinal fluid of a hematopoietic stem cell recipient

Abstract

A 59-year-old woman with a history of refractory acute myelomonocytic leukemia with normal karyotype showing NPM1 mutation (FAB classification M4) experienced fever, progressive weakness, fatigue, and fluctuating levels of consciousness about 1.5 months after haplomatched NK cell infusion, followed by peripheral blood stem cell transplant. The patient was originally from Russia, but had been living in the United States for almost 30 years and had recently undertaken a trip to China. Pretransplant serologies included positive IgG titers for CMV, HSV, VZV, and EBV. Serologies for HIV, hepatitis B, and C virus, Treponema pallidum and Trypanosoma cruzi were negative. Pretransplant serologies for Toxoplasma gondii were not performed.The patient's post hematopoietic stem cell transplant (HSCT) course was complicated by neutropenia, profound immunosuppression, and multiple systemic infections including positive blood cultures for vancomycin-resistant Enterococcus faecium, Escherichia coli, and HHV6 viremia. The patient was treated prophylactically or preemptively with antiviral agents (Acyclovir), multiple antifungals (caspofungin, voriconazole), and antibacterial agents (meropenem, levofloxacin, quinupristin/dalfopristin). Pentamidine was given by nebulizer once monthly for Pneumocystis prophylaxis.On post transplant day 48, the patient developed highgrade fevers and an acute decline in mental status. Brain MRI demonstrated new confluent punctate areas of T2 signal change involving the periventricular white matter of both cerebral hemispheres, predominantly in a subarachnoid location, and white matter changes in both cerebellar hemispheres. Lumbar puncture demonstrated a CSF white blood cell count of 36/ll (reference range 0-5), with 100% neutrophils, a red blood cell count of 3/ll (reference range 0-2), glucose of 49 mg/dl (reference range 40-70), and total CSF protein 107 (reference range 15-60 mg/dl) with increased IgG and albumin levels. No blasts were identified cytologically or by flow cytometry. CSF cultures for bacteria and fungi were negative. CSF PCR tests for HHV6, HSV1, HSV2, and VDRL testing were negative. Gram stain demonstrated neutrophils with multiple ovoid intracytoplasmic inclusions. Chemiluminescent immunoassay showed the presence of T. gondii IgG antibodies (14 IU/ml, reference range 6 IU/ml or less) but not of T. gondii IgM antibodies (0.27 IV, reference range 0.89 IV or less). Cytologic examination of Wright-stained cytospin preparations and Papanicolaou-stained Surepath 1 preparations of the CSF demonstrated intracellular and extracellular ovoid to crescent or banana-shaped organisms measuring 2-3 by 6 micron [ Fig. C-1], with an illdefined eccentric nucleus, best seen in the Wright-stained preparation [ Fig. C-2]. Extracellular organisms were best defined in the Papanicolaou-stained preparation and were frequently seen in close contact with the cytoplasmic membrane or within invaginations of neutrophils. Intracellular organisms were sometimes surrounded by a thin halo and were more rounded, mea...

Toxoplasma Encephalitis following Tandem Autologous Hematopoietic Stem Cell Transplantation: A Case Report and Review of the Literature

“…PCR is the most valuable test and can be performed on blood, CSF [ 17 , 18 ], or bronchoalveolar lavage samples, especially in untreated patients. Our patient was diagnosed by positive PCR, performed on serum and cerebrospinal fluid.…”

Cerebrospinal fluid cytology in nonmalignant aseptic meningeal disorders

“…Tachyzoites can be reliably identified in CSF ( Figure 5). 41 In patients with obstructive hydrocephalus, tachyzoites are more likely to be found in ventricular rather than lumbar CSF samples. 40 There may be intracellular and/or extracellular forms present, the latter are characterized as ovoid to crescent or bananashaped organisms measuring 2-3 mm by 6 mm, with an ill-defined eccentric nucleus.…”

“…40 There may be intracellular and/or extracellular forms present, the latter are characterized as ovoid to crescent or bananashaped organisms measuring 2-3 mm by 6 mm, with an ill-defined eccentric nucleus. 41 In patients with obstructive hydrocephalus, tachyzoites are more likely to be found in ventricular rather than lumbar CSF samples. 42 Cysticercosis in humans is caused by infection of the larval stage (cysticercus) of Taenia solium (the pork tapeworm) and usually occurs in areas where human fecal sanitation is poor.…”

Toxoplasma in crush preparation of the brain biopsy from a cord blood hematopoietic stem cell transplant recipient

“…Currently, the diagnosis of CNS toxoplasmosis is usually made clinically based on symptoms, imaging findings, CSF analysis, including cytology, serologic investigations, and response to empirical therapy. When a diagnosis cannot be achieved by other methods, a stereotactic or surgical brain biopsy is still necessary.…”