Diagnostic Challenges and Treatment of Concurrent Toxoplasmosis and Disseminated Cryptococcus in an Immunocompromised Patient

<b>Background:</b> Co-infection with disseminated cryptococcosis and toxoplasma encephalitis is rare but presents significant diagnostic and therapeutic challenges, particularly in severely immunocompromised patients. This case study highlights the complexities involved in managing such dual infections. <b>Case Presentation:</b> We describe a 43-year-old Hispanic male with Stage IV EBV-positive diffuse large B-cell lymphoma and hemophagocytic lymphohistiocytosis who presented with progressive weakness and altered mental status. Initial brain MRI revealed multiple enhancing lesions. Diagnostic tests for cryptococcosis and toxoplasma were inconclusive; however, a positive cryptococcal antigen test, new lung nodules, and potential central nervous system involvement suggested possible disseminated cryptococcosis. Diagnosis of cryptococcal meningoencephalitis could not be confirmed due to negative CSF cultures. <b>Management and Outcome:</b> Despite initiating treatment with amphotericin B and flucytosine for suspected cryptococcosis, the patient's condition did not improve. Initial Karius and CSF PCR tests for Toxoplasma were negative. A subsequent brain biopsy, however, confirmed toxoplasmic encephalitis. Treatment was adjusted to intravenous Trimethoprim/Sulfamethoxazole for toxoplasmosis, with continued fluconazole for cryptococcosis. The patient exhibited significant clinical improvement with this revised therapy. <b>Conclusion:</b> Diagnosing concurrent cryptococcal and toxoplasma infections is challenging due to overlapping clinical symptoms and variability in test sensitivities. This case underscores the need for a comprehensive diagnostic approach and the critical role of brain biopsy when other diagnostic methods, such as Karius testing and CSF PCR, are inconclusive. Prompt empirical treatment based on clinical suspicion, with subsequent treatment adjustments guided by clinical response and follow-up assessments, is essential for effective management.