A 44-year-old African woman presented to the ED complaining of productive cough, headache, fever, chills and nausea for 5 days. PMH was significant for HIV (CD4 557 cells/ mm3, HIV RNA 20 copies/mL) and non-Hodgkin lymphoma (in remission since 2009). Medications included darunavir, ritonavir, abacavir/lamivudine and valacyclovir. She denied travel, drug and alcohol use. Physical examination was unrevealing except for genital herpes. Pertinent lab data was as follows: WBC count 3.8×109/L, hemoglobin 8.35mmol/L, platelets147x109/L, AST 49U/L, ALT 53U/L. Chest x-ray and brain CT were negative.
On day 2, platelets dropped to 47×109/L, hemoglobin to 6.83mmol/L, bicarbonate to 20mEq/L and bilirubin increased to 51.3μmol/L with elevated LDH, but normal haptoglobin. CT of chest was suggestive of RLL infiltrate. Despite empiric vancomycin, cefepime and moxifloxacin, her condition worsened and she became encephalopathic. Brain MRI was unremarkable. On day 3, platelets dropped to 21×109/L. Microscopy demonstrated trophozoites consistent with malaria with 7.5% parasitemia. Quinidine and doxycycline were initiated and her family admitted she returned from Cameroon 2 weeks prior to presentation. Plasmodium falciparum was confirmed by PCR. Her course was complicated by MRSA pneumonia requiring mechanical ventilation, ESBL K. pneumoniaUTI, prolonged hypotension, and AKI requiring renal replacement therapy. Encephalopathy and weakness slowly improved and at discharge, hemoglobin was 5.9mmol/L with parasitemia <1%.
Discussion:
Immunosuppressed patients and those without previous exposure to malaria are at very high risk for severe disease if infected with P. falciparum. Cerebral malaria is the most severe and rare neurologic complication and presents with impaired consciousness, delirium, and/or seizures. If untreated, cerebral malaria is universally fatal. With treatment, mortality is 15-20% and surviving patients are often left with neuro-cognitive deficits.
There are two major classes of drugs available for parenteral treatment of severe malaria. Artemisinin derivatives (artesunate and artemether) clear parasitemia faster than cinchona alkaloids (quinine and quinidine), are associated with lower mortality rates for severe malaria and can be obtained from the CDC. The only approved therapy in the USA is IV quinidine, which must be complemented by doxycycline, tetracycline or clindamycin. IV quinine was withdrawn by the CDC in 1990s. Quinidine can lead to QT prolongation, hypoglycemia, tinnitus, vomiting, dizziness and visual disturbances. Parasite density should be monitored every 12 hours, and once <1%, IV therapy may be transitioned to oral. Exchange transfusions are no longer recommended.
Conclusions:
History is crucial to a complete differential diagnosis and it is not always accurate or complete as demonstrated in our case. Cerebral malaria is rare in the US, requires prompt recognition and treatment, as it has high morbidity and mortality.