153. Malaria

General

Protozoan infection by female Anopheles mosquito. Carried to liver where they reproduce (amplification stage), then rupture and infect RBCs (erythrocytic stage). 5 types: Plasmodium vivax, ovale, malariae, falciparum, knowlesi.

Regions: Central (Haiti, Honduras) / South America (Guyana, Brazil) , Caribbean, sub-Saharan Africa (MC area of transmission for US citizen coming home, think Nigeria, Ghana, Sierra Leone, Liberia), Indian subcontinent, Southeast Asia, Middle East, Oceania (Papua New Guinea). Top states for reports: New York, California, Maryland, Florida, Texas, New Jersey, Georgia, Virginia.

P. falciparum: most prevalent form in Africa; highest mortality 10-50%. Has resistance to chloroquine (central america and caribbean don’t have resistance), pyrimethamine-sulfadoxine, quinine, mefloquine, doxycycline.

P. vivax: more common in Indian and Central America. Both vivax and oval have dormant hepatic stage that can activate later and cause clinical relapse.

Clinical Features

Incubation period 8 days Р1 month.  Periodic fevers with flu-like symptoms: headache, chest pain, cough, arthralgias, diarrhea. After several hours of fever, fever goes down and then have diaphoresis and exhaustion. Usually every 48-72 hrs. Paroxysms absent with P.falciparum or partial chemoprophylaxis. Usually no lymphadenopathy. Can have hypoglycemia.

NNT – Malaria in Returning Travelers: Symptoms Likelihood Ratios

Complications include hemolysis, splenic enlargement or even rupture, glomerulonephritis. Cerebral malaria: coma, delirium, seizures – shows elevated opening pressure, elevated proteins, and some pleocytosis. Most organs can be affected by hypoxia. Blackwater fever (severe hemolysis with hemoglobinuria from P.falciparum = renal failure).

Testing

Visualization of parasites on Field or Giemsa-stained thick and thin blood smears (first smear 90% positive, thick smear puts many cells in one view so able to look for parasite in general, thin smears zooms on a few and hopefully able to differentiate the type of malaria). Repeat stain in 2-3 days if negative. Other tests available (PCR, etc) though smear still preferred. Smear able to show viral load as well as determine if from P.falciparum (small rings forms with double-chromatin knobs in RBCs, small amount of trophozoites and schizonts, crescent-shaped gametocyte, parasitemia > 4%). Check smears daily for treatment progress.

Nonspecific labs: anemia, mild neutropenia or thrombocytopenia, elevated LDH, mild liver/renal abnormalities, hyponatremia, hypoglycemia, false positive VDRL.

Treatment

Severe hospitalized cases (AMS, renal failure, severe anemia, shock, DIC, jaundice, parasitemia > 5%): In the US: IV quinidine (enhanced activity against P.falciparum than quinine). For severe malaria, add on IV artesunate (though recommends discussing with CDC Malaria Hotline). IV artesunate is limited and needs to be used with a second agent due to short half-life and increased resistance as single agent.  Quinine/Quinidine can cause hypoglycemia; also causes cinchonism (N/V, headache,tinnitus, dizziness, visual disturbances).

If suspecting P.falciparum with parasitemia > 3%, hospitalization recommended. Treat with quinine and doxycycline (C/I pregnancy, kids) or atovaquone-proguanil (Malarone) (though can treat with chloroquine if absolutely positive the geographic location of P.falciparum is not resistant). Clindamycin or tetracycline can be substituted for doxycycline.

Outpatient tx (though most US pts with malaria usually get admitted): Malarone (atovaquone-proguanil, SE: N/V, oral ulcers, headaches, dizziness, C/I pregnancy, kids <5kg, kidney dysfunction) is >90% effective. Don’t give if it was used as chemoprophylaxis. More effective than mefloquine. Coartem (1:6 fixed dose combo of artemether and lumefantrine, SE: headache, dizziness, severe skin rash rare, QT prolongation) over 3 days effective against P.falciparum. Mefloquine (SE: N/V, cramps, avoid in pregnancy/kids, if also taking quinidine) is effective against chloroquine-resistant P.falciparum. Don’t use if used as chemoprophylaxis or in area with resistance. More severe neuropsychiatric reactions. Chloroquine (SE: N/V, pruritus, hypotension with IV, can cause retinitis chronically) is tx for P.vivax, P.ovale, P.malariae. It does not tx dormant stage in liver with P.vivax or P.ovale so will need to add on primaquine (don’t give to G6PD pts – can cause massive hemolysis, SE: N/V, diarrhea, cramps, C/I pregnancy as well) so relapses don’t occur.

Prophylaxis

After dark, stay in well screened areas, use mosquito nets preferably with insecticides on them. Pyrethrum-containing insect sprays work well. Insect repellants: use DEET containing ones – only need to be at most 35%.

CDC Malaria Map Application – Shows countries that are susceptible and resistance patterns with prophylaxis recommendations.

Chloroquine-sensitive P.falciparum region: Chloroquine 300mg base qweekly + 4 weeks after exposure; Hydroxychloroquine 300mg base qweekly + 4 weeks after exposure. Second-line: Doxcycline 100mg daily + 4 weeks after exposure as well. Malarone 250mg/100mg qday + 1 week after exposure.

Chloroquine-resistance P.falciparum region: Malarone qday x 1 week after exposure; Mefloquine 228mg base qweek + 4 weeks, Doxycycline 100mg + 4 weeks. Second-line: Primaquine 30mg qd + 1 week.

Multiple-drug resistance P.falciparum region: Doxycycline or Malarone. Second-line: Primaquine.

Clinical Cases

EMRAP, January 2010, Swadron/Herbert, Malaria – A Case, Audio

The Poison Review, Was Sgt. Robert Bales on mefloquine when he alleged to have killed 17 Afghan civilians?

References/Resources

Tintinalli, Seventh Edition, Chapter 153: Malaria

Crashing Patient, Scott Weingart, Travel, Immigrant, Zoological Infections

CDC, Guidelines for Treatment of Malaria in the US, Reviewed 3/18/14

Life in the Fast Lane, Critical Care Compendium, Malaria

153. Malaria

Leave a Reply

Your email address will not be published. Required fields are marked *