University of Alabama at Birmingham 2012 Case #8 Universidad Peruana Cayetano Heredia
The following patient was seen in the Intensive Care Unit of the 400-bed Cayetano National Hospital.

Image AB for 3/26/2012History:  38-year-old female presents with a-2-month history of daily fevers, chills and general malaise.  She noticed jaundice, nausea and vomiting one week before admission into a local hospital.  She was treated with intravenous antibiotics but due to continued deterioration and respiratory distress, after 5 days she was transferred to us in Lima.

Epidemiology:  Born and lives in Pucallpa in Ucayali Department in the jungle.  She is a food vendor in the city market.  No recent travel away from the city.

Physical Examination (on admission to Pucallpa):  Icteric [Image A].  Temp. 38.9, HR 98, respirations 32, BP 60/30; inspiratory rales in both lungs; hepato-splenomegaly.  Cardiovascular and neurological examinations were normal.

Laboratory Results:  Hemoglobin: 8.6 (26%), later went down to 6.3; WBC 3000 (59 neutrophils, no bands, 19 monocytes, 22 lymphs); platelets 22000.  Total bilirubin: 8.9, direct 1.4; ALT 106 (N<40); AST 54 (N<40); Alkaline phos. 133; BUN 33, creatinine: 0.4 (N).  Blood gases: pH: 7.56, PO2: 77, pCO2: 24, HCO3: 21, SatO2: 99, PFIO2: 154.  Abdominal ultrasound: liver and spleen enlargement.  Urine culture negative.  Chest x-ray: bilateral alveolar infiltrates, progressing to ARDS [Image B].





Diagnosis:  Plasmodium vivax.  Severe and complicated vivax malaria.
Images C for 3/26/2012 DiscussionDiscussion:  Three thick smears for malaria had been negative at the outside hospital.  Thick film on admission to our hospital showed Plasmodium vivax 2+; schizonts were easily seen throughout the smear [Image C], estimated parasitemia was 145,000 per µl.  Ongoing malaria surveillance in Perú is robust and ongoing, and P. falciparum does not occur in the Ucayali Department.  In areas where P. vivax and P. falciparum are co-endemic mixed infection must be ruled out by PCR, or less ideally RDT (rapid diagnostic test), before severe malaria is attributed to P. vivax.

Blood cultures were negative.  Widal O:1/40, H:1/100 (negative), Brucella: negative (both Rose Bengal and tube agglutination tests).  Serology sent to the INS (National reference lab) – ELISA IgM for dengue: negative; ELISA IgM yellow fever: negative; ELISA IgM leptospira: negative; IgM Hanta: negative.  Viral respiratory panel including influenza: negative.

Due to progressive hypoxia she was transferred to the ICU for mechanical ventilation.  Parenteral therapy for severe malaria with IV artesunate was begun and thick smears were negative after 24 hours of treatment.  Data on treatment of severe vivax malaria is only beginning to emerge.  WHO 2010 guidelines provide only brief guidance on severe vivax malaria stating, “prompt and effective treatment and case management should be the same as for severe and complicated falciparum malaria.”  Accordingly, when the patient is well enough to stop IV artesunate a recognized oral ACT (artemisinin combination therapy) regimen should be administered in its entirety.  She will receive primaquine on discharge.  Data on the use of oral ACTs for treatment of uncomplicated vivax malaria is now robust [Cochrane Database Syst Rev. 2011 Jul 6;(7):CD008492. and Lancet Infect Dis. 2010 Jun;10(6):405-16.], and programmatic consideration may now be given to use of the same ACT regimen without speciation in areas where P. falciparum and P. vivax co-exist.

Although P. vivax malaria is considered to be benign malaria, with a very low case-fatality ratio, it may still cause a severe and debilitating febrile illness.  Increasingly it is recognized that severe disease may result, as in P. falciparum malaria.  Severe P. vivax malaria manifestations that have been reported are severe anemia, severe thrombocytopenia, jaundice, splenic rupture, acute renal failure and notably acute respiratory distress syndrome.  Case series have come from India [Am J Trop Med Hyg. 2009 Feb;80(2):194-8.], Brazil [Malar J. 2012 Jan 9;11:12.], Indonesia [PLoS Med. 2008 Jun 17;5(6):e128.] and Papua New Guinea [PLoS Med. 2008 Jun 17;5(6):e127.].  Severe anemia and acute pulmonary edema are most common.  Coma and cerebral malaria are well described but with less frequency than in falciparum malaria [PLoS Negl Trop Dis. 2011 Jun;5(6):e1032.].  The underlying mechanisms of severe manifestations are not fully understood but a large component of increased capillary permeability appears to be present.

Acknowledgements:  We thank Gorgas Course Vistiting Professor David Warrell (Oxford University) for his advice on this case presentation.