Different patterns of resistance to drug therapy are seen in Plasmodium falciparum. The World Health Organization (WHO) used a grading scheme based on clinical symptoms and clearance of intra-erythrocytic forms in peripheral blood smears.


Original WHO Classification of In Vivo Response


Sensitive (S):

(1) reduction to < 25% of initial parasitemia on day 2 (numbers decrease by > 75%)

(2) smears negative for malaria from day 7 to end of follow-up (28 days or longer)

Parasitemia at Day 7 of Therapy


Pattern of Resistance to Therapy


recrudescence by day 28


markedly reduced

parasitemia not completely cleared


no reduction




Modified WHO Classification from 1996


The original classification is appropriate for areas with no or low malarial transmission. However, in areas with intensive transmission re-infection may be confused with drug resistance.




Pattern of Resistance to Therapy

present during first 3 days of followup

aggravation or persistence of clinical features

early treatment failure (ETR)

present on day 4-14 of followup

re-appearance of symptoms

late treatment failure (LTR)

absent on day 14

may or may not have fever

adequate clinical response (ACR)

may or may not be present

absence of clinical symptoms

adequate clinical response (ACR)



• The pattern of drug resistance does not assess the control of clinical symptoms. In non-immune patients, symptoms tend to parallel parasitemia, while in semi-immune patients the symptoms may improve without reduction in circulating parasitemia.

• Gametocytes may circulate for up to 2 weeks after successful therapy and their presence does not indicate drug resistance.


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