Treatment of uncomplicated malaria in Guinea-Bissau

Abstract: Treatment of malaria has become increasingly difficult due to high levels of resistance to the cheap and commonly used antimalarials. In Guinea-Bissau, the first line drug is chloroquine (CQ), the second line drug is sulfadoxine-pyrimethamine (S/P), and the third line therapy is quinine (QU). During the last ten years we have studied these drugs in the Bandim area at the outskirt of the capital Bissau, to a large extent with the same methodology and the same staff. Chloroquine given in the standard total dose of 25 mg/kg proved to be less efficient with an adequate clinical and parasitological response (ACPR) rate on day 28 of 68% in 1996/1997 and 76% in 2001/2004. A higher total dose of 50 mg given in two daily doses over three days showed an ACPR rate of 86% and 90%. No severe adverse effects were found. Artemisinin derivatives reduce the parasite load and improve thereby in theory the efficacy of the partner drug. However, treatment with artesunate and CQ was no better than with CQ alone. Artesunate monotherapy for three days gave high treatment failure rates of 50% on day 35. S/P was efficient both as first and second line treatment with 35 day cure rates of 86% and 90%, respectively. No decrease in efficacy was seen from 1996 till 2004. However, as a high rate of mutations associated with resistance to S/P has been found in Guinea-Bissau its use should be restricted in order to prolong its period of usefulness. Quinine has traditionally been used during three days for treatment of uncomplicated malaria in Guinea-Bissau. However, treatment for 3 days gave high treatment failure rates. QU for three days followed by a standard dose of CQ did not add to the cure rate of CQ monotherapy and should therefore be abandoned and replaced by quinine for the full seven days. Amodiaquine (AQ) has been proposed as first line treatment when CQ 25 mg/kg has to be abandoned due to the level of resistance. We compared treatment with AQ and CQ. High rates of ACPR on day 35 were found treating with AQ 15 and 30 mg/kg (88% and 92%, respectively) but this was not better than following treatment with CQ 50 mg/kg (88%). AQ can thus be saved as a future partner drug for a combination therapy with artemisinin. To know whether a treatment benefits the child, effectiveness studies have to be performed. We compared supervised and unsupervised treatment with CQ. No differences were found, neither in the ACPR-rate nor in the drug concentrations on day 7. When good information is provided, mothers give the correct treatment to their children at home. Conclusion: 1) A total dose of 50 mg CQ/kg is effective and safe and much cheaper than the new combination therapies. As an interim strategy, a change of the recommended first line treatment for uncomplicated malaria to 50 mg/kg bodyweight of CQ could be implemented easily and without delay. 2) The use of S/P should be limited, but it can be used as second line therapy. 3) AQ could be reserved as the partner drug in a future combination therapy.