1. ID Case Conference Yvonne L. Carter, MD 11 June 2008

2. Headaches and Fever l 41yo female physician with a 3-day h/o headaches and fever l Began 3 days ago, fever and HA controlled with Tylenol…after which she feels better, but develops uncontrollable chills ~1 hour after dose l Denies neck stiffness, visual changes, or other neurological symptoms l HA currently 6/10. Pt also reports myalgias, but otherwise feels well, and would like to go home.

3. History l Pt is a Tropical Medicine Physician. l She works in the Rep. Of Congo, and had been there for four months l Had received travelers vaccinations –Typhoid, Rabies, Japanese Encephalitis, Yellow Fever

4. l PMH –Hepatitis A (remote) –Appendicitis, with Appendectomy –HIV negative l Meds –Prn Tylenol l Allergies –PCN - rash l SocHx –Married –Lives in Chapel Hill –No pets –Travel: recent travel to The Republic of Congo, Africa –Denies tobacco, Etoh, or illicits –No ill contacts

5. Physical Examination l VS: T 36.3, P 103, BP 115/76, R 20, Pox 100% on RA l Gen: WD, WN thin CF who appears uncomfortable, holding head, speaking softly l HEENT: NCAT, Perrla, Eomi, Sclera anicteric, conj pink, MMM, OP clear, Neck supple, No LAD. l CV: Tachycardic, II/VI SEM at apex w/o radiation l Pulm: CTA b/l, no w/r/r l Abd: Soft, ND, NT, no organomegaly l Ext: No c/c/e l Neuro: Normal exam, no focal deficits l Skin: No rashes

6. Laboratory Data 133 4.1 101 23 8 0.8 79 3.2 35.2 51 8.5 1.9 1.1 152 2.0252 151 2.2 4.4

8. Discussion

9. What I left out… l Mefloquine had caused dizziness in the past, therefore the pt did not take prophylaxis l Used bed nets and insect repellants throughout the trip, with success… l Until the last week of her trip, she was bitten on the Lower Exts, Abdomen, and Back l Developed a “tingling sensation” at the site of the bites on the trunk…locals suggested this was indicative of malaria transmission l Pt was given a dose of an “untraditional” treatment for malaria by local doctors

12. P. falciparum, 24%

17. Sub-Saharan Africa (Cases per 1000 patients with syndrome) l Systemic Febrile Illness = 718 –Malaria – 622 –Dengue – 7 –Mononucleosis (EBV/CMV) – 10 –Rickettsial infection – 56 –Salmonella typhi or S. paratyphi – 7 l No specific cause reported = 282 NEJM 354(2):119-130.

18. Copyright restrictions may apply. Griffith, K. S. et al. JAMA 2007;297:2264-2277. Plasmodium Life Cycle

19. Copyright restrictions may apply. Griffith, K. S. et al. JAMA 2007;297:2264-2277. Malaria Treatment Algorithm

20. Severe malaria Severe malaria if… l Parasitemia of >5% l Altered consciousness l Oliguria l Jaundice l Severe normocytic anemia l Hypoglycemia l Organ failure l Seizures l Acute renal failure l Fluid and electrolyte abnormalities l Metabolic acidosis l Acute respiratory distress syndrome l Circulatory collapse or shock l Hemoglobinuria l Bleeding

22. Exchange transfusion Rx l Recommended in P. falciparum infection when… –Parasitemia is greater than 10% –Patients with coma, renal failure or ARDS regardless of the level of parasitemia. l Should be combined with drug therapy l Should be continued until the level of parasitemia is <5% l Does not enhance survival

23. Exchange Transfusion (Meta-Analysis) l Meta-analysis l No greater survival rate among patients who received exchange transfusion compared to antimalarials alone l Patients who received exchange transfusions had higher degrees of parasitemia and more severe disease – not comparable to those receiving medications alone l No RCT has been performed Clin Infect Dis 2002;34(9):1192-8.

25. Hospital Course l Pt treated with IV Quinidine and Doxycycline, Exchange Transfusion via Right Subclavian l IV Quinidine initiated ~9:30pm, and bolused over four hours. Pt developed nausea, vomiting, and profuse watery diarrhea. l Exchange transfusion began at ~11pm, pt developed asymptomatic hypotension (SBP 80s), and exchange prematurely discontinued at 7/8 units complete.

26. Hospital Course, cont. l Pt became bradycardic, with a pulse in 60s. l QTc prolonged to 541ms, after IV Quinidine bolus finished. l 1am: Parasitemia 9% l 9am: Parasitemia 6%, QTc 510

27. Hospital Course, cont. 134 4.2 102 22 7 0.6 208 2.8 30.1 33 6.3 3.6 2.2

28. Discharge l Recommended switch to po Quinine and Doxycycline…Pt refused l Pt discharged on Malarone (Atovaquone/Plaguanil) to complete three day course. l Pt discharged on hospital day #2, with a parasitemia <1%

29. BUT… l Pt called UNC two days later, complaining of SOB, and was instructed to walk in to the ID Clinic l Orthopnea, Pleuritic CP, and facial swelling l Temp 37.0, BP 105/62, P 89, RR 16 Pox 85% l ABG: 7.49/34/54/89% on RA

30. 136 3.6 102 26 9 0.7 90 5.7 31.7 118 44 1.5152 2.7 LDH 774 Peripheral Smear: NO PARASITES Detected D-dimer 914 UA Neg

34. Diagnostic Studies l Cardiac enzymes negative l CTA negative for PE l TTE Normal l Bronchoscopy: –No gross abnormalities –Gram Stain Negative, Culture Negative

35. Bronchoscopy l BAL Fluid –Color: Pink –Appearance: Cloudy –TNC: 1100 Neut 2 Lymph 30 Mono 57 –RBC 6950 –Macrophages present l PCP DF : Neg l CMV PCR: Neg l Legionella: Neg l Cx: Negative l Viral Cx: Negative l Fungal Cx: Negative l C. pna Cx: Negative l Mycoplasma: Negative l AFBs: Negative

36. Differential Diagnosis – Pulmonary Edema l Drug-Induced Alveolitis l BOOP (Cryptogenic Organizing Pna) l Acute Lung Injury due to Malaria l ARDS l Atypical Pneumonia l Diffuse Aspiration

37. Discharge l Pt refused to stay longer, and was discharged on Levaquin, for a total course of 14 days.