Early home treatment of childhood fevers with ineffective antimalarials is deleterious in the outcome of severe malaria

<p>Abstract</p> <p>Background</p> <p>Early diagnosis and prompt treatment including appropriate home-based treatment of malaria is a major strategy for malaria control. A major determinant of clinical outcome in case management is compliance and adherence to effective antimalarial regimen. Home-based malaria treatment with inappropriate medicines is ineffective and there is insufficient evidence on how this contributes to the outcome of severe malaria. This study evaluated the effects of pre-hospital antimalarial drugs use on the presentation and outcome of severe malaria in children in Ibadan, Nigeria.</p> <p>Methods</p> <p>Two hundred and sixty-eight children with a median age of 30 months comprising 114 children with cerebral malaria and 154 with severe malarial anaemia (as defined by WHO) were prospectively enrolled. Data on socio-demographic data, treatments given at home, clinical course and outcome of admission were collected and analysed.</p> <p>Results</p> <p>A total of 168 children had treatment with an antimalarial treatment at home before presenting at the hospital when there was no improvement. There were no significant differences in the haematocrit levels, parasite counts and nutritional status of the pre-hospital treated and untreated groups. The most commonly used antimalarial medicine was chloroquine. Treatment policy was revised to Artemesinin-based Combination Therapy (ACT) in 2005 as a response to unacceptable levels of therapeutic failures with chloroquine, however chloroquine use remains high. The risk of presenting as cerebral malaria was 1.63 times higher with pre-hospital use of chloroquine for treatment of malaria, with a four-fold increase in the risk of mortality. Controlling for other confounding factors including age and clinical severity, pre-hospital treatment with chloroquine was an independent predictor of mortality.</p> <p>Conclusion</p> <p>This study showed that, home treatment with chloroquine significantly impacts on the outcome of severe malaria. This finding underscores the need for wide-scale monitoring to withdraw chloroquine from circulation in Nigeria and efforts intensified at promoting prompt treatment with effective medicines in the community.</p

Sulfadoxine-pyrimethamine–based combinations for malaria : a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi

Background: In Malawi, there has been a return of Plasmodium falciparum sensitivity to chloroquine (CQ) since sulfadoxinepyrimethamine (SP) replaced CQ as first line treatment for uncomplicated malaria. When used for prophylaxis, Amodiaquine (AQ) was associated with agranulocytosis but is considered safe for treatment and is increasingly being used in Africa. Here we compare the efficacy, safety and selection of resistance using SP or CQ+SP or artesunate (ART)+SP or AQ+SP for the treatment of uncomplicated falciparum malaria. Methodology and Findings: 455 children aged 1–5 years were recruited into a double-blinded randomised trial comparing SP to the three combination therapies. Using intention to treat analysis with missing outcomes treated as successes, and without adjustment to distinguish recrudescence from new infections, the day 28 adequate clinical and parasitological response (ACPR) rate for SP was 25%, inferior to each of the three combination therapies (p,0.001). AQ+SP had an ACPR rate of 97%, higher than CQ+SP (81%) and ART+SP (70%), p,0.001. Nineteen children developed a neutropenia of #0.56103 cells/ml by day 14, more commonly after AQ+SP (p = 0.03). The mutation pfcrt 76T, associated with CQ resistance, was detected in none of the pre-treatment or post-treatment parasites. The prevalence of the pfmdr1 86Y mutation was higher after treatment with AQ+SP than after SP, p = 0.002. Conclusions: The combination AQ+SP was highly efficacious, despite the low efficacy of SP alone; however, we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment. This study confirms the return of CQ sensitivity in Malawi and importantly, shows no evidence of the re-emergence of pfcrt 76T after treatment with CQ or AQ. Given the safety record of AQ when used as a prophylaxis, our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny