Severe Plasmodium Falciparum Malaria: Utility of Exchange Transfusion

1
Severe Plasmodium Falciparum Malaria Utility
of Exchange Transfusion

• JC Hofmann, MD SJ Smith, RN RM Rohe, RN DD
  Kiprov, MD
• Division of Immunotherapy
• California Pacific Medical Center
• Bay Area Mobile Apheresis Program (BAMAP)
• San Francisco, California

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Background

• Infections due to malaria ? estimated 1.0-2.5
  million deaths/yr.
• Most malaria deaths due to plasmodium
  falciparum.
• Non-immune travelers and children lt 5 y.o.
  susceptible to severe
• infection.
• Case fatality rate of imported falciparum
  malaria 0.6-3.8.
• Progression from asymptomatic infection to
  death 36-48 hrs.
• Among U.S. civilians who die of malaria ? dx
  missed in 40.
• severe falciparum malaria ? altered
  consciousness, jaundice, severe normocytic
  anemia, oliguria, hypoglycemia, multiorgan
  failure, and parasitemia gt 5.

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Treatment

• Severe Falciparum Malaria
• ICU management for close monitoring.
• Blood smears Q 12 hrs. until parasitemia
  levels lt 1.
• Antimalarial drugs
• quinoline derivatives quinine, quinidine,
  chloroquine, mefloquine.
• antimicrobials clindamycin, doxycycline,
  tetracycline.
• antifolates sulfonamides, dapsone,
  pyrimethamine.
• artemisinin derivatives artemisinin,
  artemether.

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Adjunctive Treatment

• RBC exchange transfusion (ET) recommended in
  falciparum infection
• Parasitemia gt 10.
• In coma, renal failure, or ARDS, regardless of
  parasitemia level.
• ET removes parasitized RBCs, parasitic toxins,
  cytokines.
• ET should be combined with drug therapy ?
  parasitemia lt 5.
• Phillips et al (1990) ET not proven to
  enhance survival.
• Riddle et al (2002) meta-analysis no
  greater survival rate with using ET compared to
  antimalarials alone.
• No RCT has yet been performed.

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Patients

• 3 patients diagnosed with severe falciparum
  malaria in 11 months (referred for RBC exchange
  transfusion)
• 44-68 y.o. and non- or partially-immunized
  travelers.
• 67 patients were female.
• visited rural sub-Saharan Africa in prior 30
  days.
• experienced a 4-5 day h/o flu-like symptoms.
• 33 patients had prior h/o falciparum malaria.

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Patients

• 3 patients diagnosed with severe falciparum
  malaria
• presented with moderately severe hypotension,
  anemia, thrombocytopenia.
• 67 patients experienced mental status
  abnormalities, renal insufficiency, hematuria,
  and cholestasis (1 patient had mild DIC).
• 1 patient fulfilled criteria for cerebral
  malaria.

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Treatment

• IV quinidine (/- IV doxycycline) for 8-24 hrs.
  prior to receiving single RBC exchange
  transfusion (8-10 units of RBCs).
• Premedication acetaminophen, diphenylhydramine,
  hydrocortisone.
• Mean volume of RBCs exchanged 2777 ml
  (2500-3060 ml).
• Average FCR (fraction cells remaining) 33
  (27-42).

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Results

• Significant ? level of parasitemia
• Initial mean parasitemia 38 (10-90).
• Mean parasitemia (prior to RBC exchange
  transfusion) 8 (5-15).
• Mean parasitemia (6-12 hrs. after treatment)
  1.1 (0.3-2.0).
• Dramatic improvement in clinical status
• Significant resolution of fever, chills,
  hypotension, mental status abnormalities,
  nausea, and abdominal pain.
• 67 patients able to tolerate oral quinine and
  doxycycline after single RBC exchange
  transfusion.

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Table I Demographics Outcomes of Patients
with Severe Falciparum Malaria
Patient Demographics Clinical Progression Treatment Outcome
45 y.o. female ICU nurse PMH h/o severe RA on MTX infliximab. No prophylaxis 2 wks. in rural Mali, Africa. F/C, H/A, myalgias, LH ? exp. aphasia, seizures ? obtundation coma. hypotensive, ?plt, mild DIC hematuria, ecchymoses. received pRBC, FFP, plt. IV quinidine/IV doxycycline (48) (parasitemia ? 90 ? 5) 8U pRBC exch. transfusion (D3) (parasitemia 5 ? 0.3) FCR 30 D/c to home (d9) No neuro deficits. Back to work (d21)
44 y.o. African male PMH h/o prior f. malaria (2 yrs. ago) on prophylaxis. No prophylaxis 3 wks. in Cameron, Africa. fatigue, flu-like sxs X 5d ? somnolent, min. responsive hypotensive (on pressors). anemic ? received pRBC. PO quinine/PO doxycycline (6) ? IV quinine/IV doxycycline (6) (parasitemia 15 ? 10) 10U pRBC exch transfusion (D1) (parasitemia 10 ? lt 1.0) FCR 42 D/c to home (d7) No neuro deficits.
68 y.o. female scientist PMH h/o HTN, DM, hypothyroidism. Partial prophylaxis 4 days in rain forest (6 wk. in Nairobi, Kenya). F/C, flu-like sxs X 4d ? syncope X2, lethargic ? somnolent. anemic ? received pRBC. IV quinidine/IV doxycycline (24) (parasitemia 10 ? 9) 8U pRBC exch. transfusion (D2) (parasitemia 9 ? 2.0) FCR 27 D/c to home (d6) No neuro deficits.
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Summary

• In patients with severe plasmodium falciparum
  malaria, RBC exchange transfusion
• is useful in removing parasitized RBCs,
  toxins, and cytokines.
• should be instituted if parasitemia gt 10,
  and continued until parasitemia lt 5.0 .
• may be life saving.
• Adequate immunization is extremely important
  when traveling to endemic areas.

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Parasite Density

• 1) Calculate the of parasites per 200 WBC on a
  thick smear.
• 2) Divide the total WBC count by 200.
• 3) Multiply the parasites in 1) by the result
  in 2) parasites/uL.
• 4) parasitemia parasites/uL divided by the
  WBC.
• Ex thick smear 10 parasites/200 WBC and
  WBC8000/uL, 8000/200 40. 10 parasites X 40
  400 parasites/uL. Percent parasitemia 400/8000
  5.