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
Other
Pattern of Resistance to Therapy
cleared
recrudescence by day 28
RI
markedly reduced
parasitemia not completely cleared
RII
no reduction
RIII
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.
Parasitemia
Clinical
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)
Interpretation:
• 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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