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Guidelines for the treatment of malaria – 2 edition

may remain positive for weeks after the initial infection, even without recrudescence).
This may require referring the patient to a facility with microscopy. Referral may be
necessary anyway to obtain treatment.
In many cases, failures are missed because patients who present with malaria are not asked
whether they have received antimalarial treatment within the preceding 1–2 months. This
should be a routine question in patients who present with malaria.

7.4.1 Failure within 14 days
Treatment failure within 14 days of receiving an ACT is very unusual, with the majority
of treatment failures occurring after two weeks of initial treatment. Of 39 trials with
artemisinin or its derivatives, which together enrolled 6124 patients, 32 trials (4917
patients) reported no treatment failures by day 14. In the remaining 7 trials, failure rates
at day 14 ranged from 1–7%. Treatment failures within 14 days of initial treatment should
be treated with a second-line antimalarial (see Section 7.4.2).

7.4.2 Second-line antimalarial treatments

On the basis of the evidence from current practice and the consensus opinion of the
Guidelines Development Group, the following second-line treatments are recommended,
in order of preference:
■ an alternative ACT known to be effective in the region,
■ artesunate plus tetracycline or doxycycline or clindamycin (given for a total of 7 days),
■ quinine plus tetracycline or doxycycline or clindamycin (given for a total of 7 days).

The alternative ACT has the advantages of simplicity, and where available, a fixed-dose
combination formulation improves adherence. The 7-day regimes are not well tolerated,
and adherence is likely to be poor if treatment is not observed. It is essential that the
patient and the caregiver understand the importance of completing the full 7-day course
of treatment.
7.4.3 Failure after 14 days

Recurrence of fever and parasitaemia more than two weeks after treatment could result
either from recrudescence or new infection and this distinction can only be made through
parasite genotyping by PCR. Since PCR is not routinely used in patient management,
to simplify drug deployment, all presumed treatment failures after two weeks of initial
treatment should, from an operational standpoint, be considered as new infections,
especially in areas of high transmission, and be treated with the first-line ACT. This
simplifies operational management and drug deployment. If the failure is a recrudescence,
then the first-line treatment should still be effective in most cases. However, reuse of
mefloquine within 60 days of first treatment is associated with an increased risk of
neuropsychiatric reactions and, in cases where the initial treatment was AS+MQ, second-
line treatment not containing mefloquine should be given instead.
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