Malaria Clinical Cases Presentation

1. Malaria Clinical Cases Presentation Gail Stennies, M.D., M.P.H. Medical Officer Malaria Epidemiology Branch DPD/ NCID/ CDC May, 2002

2. Information requested when evaluating a potential case of malaria Age Sex and pregnancy status Travel history, travel outside major or urban areas Visitors from endemic areas Exposure to mosquitoes Malaria prophylaxis used Receipt of blood transfusions or transplant Past history of malaria Drug allergies Clinical status of the patient, esp. neurological Lab results

3. Congenital malaria Previously healthy 10-week old female developed an fever and dark urine on September 7, 2000 Temp 103.7o F, WBC 24,600/µl, and Hb 8.7 g/dL She was admitted for possible sepsis Blood, urine, and cerebral spinal fluid cultures were done Treated with IV ampicillin and cefotaxime

4. Congenital malaria Past medical history Uncomplicated pregnancy and delivery Seen in ER on July 17 for abnormal breathing Normal exam and chest Xray, no diagnosis made or treatment given Parents from DR Congo- dad came in 1995, mom in 1996 Mom completed course of chloroquine prior to immigration for malaria (?self-diagnosis)

5. Congenital malaria Smears taken on September 8 showed P.m. Treatment with chloroquine was started She received 2 units of packed RBCs after Hgb dropped to 5.6 g/dL Responded well to treatment with negative smears 1 week post therapy

6. Congenital malaria Parents denied any episodes of malaria febrile illness foreign travel or blood transfusion since in US Lived in screened apartment, some mosquitoes seen indoors in August Friend from Kinshasha visited in August, he was well during visit

7. Congenital malaria Pretreatment labs on mother Blood smears were negative Positive IgG titers P.f. and P.m. 1:16,384 P.v. and P.o. 1:102 PCR - negative Mother was treated empirically with chloroquine

8. Transfusion-transmitted malaria 72 yo female with history of multiple medical problems admitted September 15, 1995 with neutropenic fever post chemotherapy Intracellular parasites found on peripheral smear – diagnosed with Babesia Improved after quinine and clindamycin were started on September 25

9. Transfusion-transmitted malaria Smears read as P.f. by CDC, same for smears from September 4 Risk factors No travel to endemic areas No IVDA, tattoos, acupuncture Yes recent recipient of blood April quantity unknown August 9 4 units September 3 2 units September 9 2 units September 24 2 units

10. Transfusion-transmitted malaria Which units are most suspect? American Red Cross centers were notified Identify donors – defer for future donation during investigation Put any unused blood products on hold Contact donors – reinterview about risk factors Obtain blood from donors – segments from units or new collection for smears and serology

11. Transfusion-transmitted malaria 1/6 donors was Nigerian national with remote history of malaria Thick & thin smears – too few parasites to identify species at CDC Species Index case Donor N P.v. < 16 64 P.f. 1:1024 > 1:4096 P.m. < 16 > 1:4096 P.o. < 16 1:256 IFA results on other 5 donors were negative for all species Donor N advised to seek treatment for P.f. and not donate

12. Unusual but possible case # 1 27 yo health care assistant with 3-day history of fever, sweats, rigors & frontal headache Past medical history was unremarkable Never had clinical malaria No recent foreign travel Left Sri Lanka 7.5 yrs earlier Visited France 3 yrs earlier

13. Unusual but possible case # 1 Exam – 38.5o, no other abnormal findings, no focal neurological signs Smears – P.f. , 0.001% parasitemia Started on oral quinine 600 mg 3x/day Initial increase in density to 0.005% but after 5 days of treatment parasites cleared 3 tabs of Fansidar were given prior to discharge

14. Unusual but possible case # 1 ? Exposure

15. Unusual but possible case # 1 10 days prior to admission, he had sustained a needlestick injury with a nonsterile needle while resuscitating a patient Patient was 16 yo Ghanaian boy with P.f., 1.7% parasitemia and febrile convulsion Haworth FLM, Cook CG. Needlestick malaria. Lancet 1995;346:1361.

16. Unusual but possible case # 2 28 yo English woman admitted to hospital on April 20 1997, had been unwell for 3 weeks with intermittent fever and diarrhea P. f. with 30% parasitemia was diagnosed Treated with IV quinine, blood transfusion, and prostacyclin and recovered fully Traveled to Sub-Saharan Africa previous month Used chloroquine + proguanil for prophylaxis

17. Unusual but possible case # 2 Flew to Italy on March 25, seen in Sicilian hospital on April 16 Given IV fluids and antibiotic, no specific diagnosis made, was not admitted Was still ill when returned to England on April 19

18. Unusual but possible case # 2 Patient’s story is not unusual HOWEVER Italian physician who treated her died 21 days later on May 6 Diagnosis of P.f was made on necropsy He had no travel history ?Risk

19. Unusual but possible case # 2 He had sustained a needlestick injury with the needle he used to start the woman’s IV drip Anonymous. Needlestick malaria with tragic consequences. Communicable Disease Report Weekly. 7(28)11 July 1997.

20. Unusual but possible case # 3 69 yo developed fever and chills on December 15, 1998 while at work Thick and thin smears showed rare intracellular rings consistent with P.v. or P.o. The diagnosis was confirmed at a reputable reference lab with PCR showing P.v. Patient did well with chloroquine and primaquine

21. Unusual but possible case # 3 Patient denied recent blood transfusion or international travel Last visit to a malarious area had been 10 yrs earlier Why is malaria on the differential diagnosis list, esp. during cold and flu season?

22. Unusual but possible case # 3 Occupational history?

23. Unusual but possible case # 3 Occupational history? Parasitologist Denies recent needlestick exposure Hmm?

24. Unusual but possible case # 3 During the 14 days prior to his illness, he had worked in the insectory with infective Anopheles mosquitoes carrying a Southeast Asian strain of P.v. and a West African strain of P.o. On December 8, a colleague had noticed a mosquito flying free in the work area but was unable to catch it

25. Things that keep risk management staff busy - Case 1 31 yo female returned home to South Florida on January 18, 1996 following a 16-day trip to Bolivia No antimalarial chemoprophylaxis taken; had significant rural exposure on trip Upon returning home she developed fever, chills, headache and malaise and was admitted that same day to Hospital A and evaluated for sepsis

26. Things that keep risk management staff busy - Case 1 Treated with IV antibiotics administered through a heparin lock Blood films obtained on January 23, 1996 were positive for P.v., later confirmed at CDC The patient was treated with oral chloroquine and primaquine, improved promptly, and was discharged on January 24, 1996

27. Things that keep risk management staff busy - Case 2 83 yo male with multiple medical problems including congestive heart failure and bradycardia Presented to another hospital in the same county as Hospital A on February 11, 1996 with a history of fever and chills P.v. parasites were identified on blood films obtained for a complete blood count at the time of admission. Diagnosis confirmed by CDC

28. Things that keep risk management staff busy - Case 2 Risk factors No history of travel outside the United States except for visiting the Bahamas more than 10 years previously No IVDA or malariotherapy No recent blood transfusions From January 22-24, 1996 he had been admitted to Hospital A for bradycardia Was in a room adjacent to that of Case 1

29. Things that keep risk management staff busy - Case 2 During that hospitalization he received intravenous medications through a heparin lock. The patient improved after treatment with chloroquine and was discharged.

30. Things that keep risk management staff busy - Déjà vu? 60 yo female patient with chronic obstructive pulmonary disease presented to the hospital A on February 12, 1996 with a similar history of fever and chills P.v. parasites were identified on her admission blood film, diagnosis confirmed at CDC Risk factors No travel outside the United States No IDVA or malariotherapy No recent transfusions of blood or blood products

31. Things that keep risk management staff busy– Case 3 However, she had also been hospitalized from January 20-26, 1996 in a room adjacent to Case 1 During that hospitalization, she had received IV medications through a heparin lock The patient improved after treatment with chloroquine and was discharged home.

32. Things that keep risk management staff busy – Discussion Investigation by the County Health Department and the hospital administration revealed All three patients had heparin locks at the same time All were cared for by the same health worker Deficient infection control practices In particular, nursing staff used 10 cc vials of sterile water to flush heparin locks Occasionally used the same vial for two or more patients

33. Things that keep risk management staff busy - Discussion Although this practice could not be retrospectively linked to the three cases, it seems the most plausible explanation for these three cases Following the investigation, the hospital routinely began to use single-dose vials for flushing intravenous devices

34. Management of induced or congenital cases No sporozoites are injected into the human by mosquito Therefore no exo-erythrocytic (hepatic) cycle No need for primaquine

36. The following will become knee-jerk questions Age Sex and pregnancy status Travel history, travel outside major or urban areas Visitors from endemic areas Exposure to mosquitoes Malaria prophylaxis used Receipt of blood transfusions or transplant Past history of malaria Drug allergies Clinical status of the patient, esp. neurological Labs

37. Don’t forget to ask Occupational history Healthcare workers Exposure to mosquitoes Needle exposure IV drug abuse Needlestick injuries Tattoos Acupuncture Other meds used with potential antimalarial effect Sulfa – Bactrim ® Tetra – or doxycycline Quinine Hydroxychloroquine – Plaquenil® Atovaquone Clindamycin Meds received abroad Artesunates Halofantrine

38. All “malaria” is not malaria Incubation periods unlikely Parasite density very high for nonfalciparum Species not likely given travel history Drug resistance? Misdiagnosis – species or parasite or negative Miscalculation of density Previously undetected mixed infection