Summaryobjectives Hypoglycaemia (glucose <2.2 mmol ⁄ l) is a defining feature of severe malaria, but the significance of other levels of blood glucose has not previously been studied in children with severe malaria.methods A prospective study of 437 consecutive children with presumed severe malaria was conducted in Mali. We defined hypoglycaemia as <2.2 mmol ⁄ l, low glycaemia as 2.2-4.4 mmol ⁄ l and hyperglycaemia as >8.3 mmol ⁄ l. Associations between glycaemia and case fatality were analysed for 418 children using logistic regression models and a receiver operator curve (ROC).results There was a significant difference between blood glucose levels in children who died (median 4.6 mmol ⁄ l) and survivors (median 7.6 mmol ⁄ l, P < 0.001). Case fatality declined from 61.5% of the hypoglycaemic children to 46.2% of those with low glycaemia, 13.4% of those with normal glycaemia and 7.6% of those with hyperglycaemia (P < 0.001). Logistic regression showed an adjusted odds ratio (AOR) of 0.75 (0.64-0.88) for case fatality per 1 mmol ⁄ l increase in baseline blood glucose. Compared to a normal blood glucose, hypoglycaemia and low glycaemia both significantly increased the odds of death (AOR 11.87, 2.10-67.00; and 5.21, 1.86-14.63, respectively), whereas hyperglycaemia reduced the odds of death (AOR 0.34, 0.13-0.91). The ROC [area under the curve at 0.753 (95% CI 0.684-0.820)] indicated that glycaemia had a moderate predictive value for death and identified an optimal threshold at glycaemia <6.1 mmol ⁄ l, (sensitivity 64.5% and specificity 75.1%).conclusions If there is a threshold of blood glucose which defines a worse prognosis, it is at a higher level than the current definition of 2.2 mmol ⁄ l.

A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.

Recent WHO guidelines recommend a universal "test and treat" strategy for malaria, mainly by use of rapid diagnostic test (RDT) in all areas. The evidence for this approach is questioned here as there is a risk of over-reliance on parasitological diagnosis in high transmission situations, which still exist. In such areas, when a patient has fever or other malaria symptoms, the presence of Plasmodium spp neither reliably confirms malaria as the cause of the fever, nor excludes the possibility of other diseases. This is because the patient may be an asymptomatic carrier of malaria parasites and suffer from another disease.To allow clinicians to perform their work adequately, local epidemiologic data are necessary. One size does not fit all. If parasite prevalence in the population is low, a diagnostic test is relevant; if the prevalence is high, the test does not provide information of any clinical usefulness, as happens with any test in medicine when the prevalence of the tested characteristic is high in the healthy population. It should also be remembered that, if in some cases anti-malarials are prescribed to parasite-negative patients, this will not increase selection pressure for drug resistance, because the parasite is not there.In high transmission situations at least, other diagnoses should be sought in all patients, irrespective of the presence of malaria parasites. For this, clinical skills (but not necessarily physicians) are irreplaceable, in order to differentiate malaria from other causes of acute fever, such as benign viral infection or potentially dangerous conditions, which can all be present with the parasite co-existing only as a "commensal" or silent undesirable guest.

Summary A prospective, dose-escalating, quasi-experimental clinical trial was conducted with a traditional healer using a decoction of Argemone mexicana for the treatment of malaria in Mali. The remedy was prescribed in three regimens: once daily for 3 days (Group A; n = 23); twice daily for 7 days (Group B; n = 40); and four times daily for the first 4 days followed by twice daily for 3 days (Group C; n = 17). Thus, 80 patients were included, of whom 80% were aged <5 years and 25% were aged <1 year. All presented to the traditional healer with symptoms of malaria and had a Plasmodium falciparum parasitaemia >2000/l but no signs of severe malaria. The proportions of adequate clinical response (ACR) at Day 14 were 35%, 73% and 65% in Groups A, B and C, respectively (P = 0.011). At Day 14, overall proportions of ACR were lower in children aged <1 year (45%) and higher in patients aged >5 years (81%) (P = 0.027). Very few patients had complete parasite clearance, but at Day 14, 67% of patients with ACR had a parasitaemia <2000/l. No patient needed referral for severe disease. Only minor side effects were observed. Further research should determine whether this local resource could represent a first-aid home treatment in remote areas.