Rationale:

• Once malaria symptoms resolve and a negative blood smear is documented during initial therapy, routine parasitologic monitoring is not indicated.
• Patients who are inadequately treated due to noncompliance or parasite drug resistance are at risk for recrudescence from surviving blood parasites.
• Although the time to recrudescence will depend on a number of factors (drug pharmacokinetics, malaria immune status), most will occur within the first 28 days from the start of antimalarial treatment with some occurring as late as 10 weeks.
• Malaria recrudescence will be accompanied by a return of symptoms compelling patients to seek medical attention (“clinical failure”).

Evidence:

• Drugs that are eliminated slowly, such as mefloquine, may suppress recrudescence of drug-resistant parasites up to 10 weeks after treatment. One prospective randomized trial compared the treatment efficacy of standard- and high-dose mefloquine for P. falciparum malaria on the Thai-Cambodian border, an area with mefloquine-resistant malaria. Treatment failure, defined by recrudescence of parasites, occurred in 7% (days 7 to 9), 40% (day 28) and 50% (day 42) of 71 patients (153).

Comments:

• Recurrent parasitemia (“parasitologic failure”) occasionally may not be accompanied by recurrent symptoms in patients with immunity from long-term residence in an endemic area. These patients will not seek medical attention and will likely clear their parasitemia on their own without further drug treatment.
• World Health Organization definitions of treatment failure are most useful in monitoring drug resistance in the research setting. They have recently been summarized in a review article (154).