Efficacy and safety of the six-dose regimen of artemether-lumefantrine in pediatrics with uncomplicated Plasmodium falciparum malaria: A pooled analysis of individual patient data

Patient data from eight clinical trials were pooled and analyzed to study the efficacy and safety of the six-dose versus four-dose regimen of artemether-lumefantrine (coartemether; Coartem) in children weighing 5-25 kg. A total of 544 patients with uncomplicated P. falciparum malaria (six-dose: 343; four-dose: 201), matched for demographic and baseline characteristics and individual coartemether doses were included in the analysis. Analysis of day 28 cure rate based on the intention-to-treat and evaluable populations yielded corrected cure rates for the six-dose regimen of 93% and 96% compared with 61% and 76%, respectively, for the four-dose regimen (P \u3c 0.0001 for both comparisons). Similarly high cure rates were achieved with the six-dose regimen in non-immune infants weighing as little as 5 kg. The six- and four-dose regimens were equally well tolerated. The main finding of this analysis is that the six-dose regimen of coartemether is safe and more efficacious than the four-dose regimen in children. Copyright © 2006 by The American Society of Tropical Medicine and Hygiene

Artesunate-mefloquine combination therapy in acute Plasmodium falciparum malaria in young children: a field study regarding neurological and neuropsychiatric safety

BACKGROUND: Mefloquine-artesunate combination therapy for uncomplicated falciparum malaria is one of the treatments used in African children. Data concerning neurological safety in adults and children treated with mefloquine and artesunate combination therapy is well documented in Asia. Safety data for neurological and neuropsychiatric side effects of mefloquine and artesunate combination therapy in African children are scarce, although WHO recommends this therapy in Africa. METHODS: A phase IV, open label, single arm study was conducted among African children between 10 and 20 kg with acute uncomplicated falciparum malaria. They were treated over three consecutive days with a paediatric fixed-dose combination of artesunate (50 mg/d) and mefloquine (125 mg/d). Parasitological, clinical and neurological examinations and standardized questions about neuropsychiatric symptoms were carried out on days 0, 4, 7, 28 and 63. The primary objective was to assess the neurological and neuropsychiatric safety of artesunate-mefloquine combination therapy in young children. RESULTS: From December 2007 to March 2009, 220 children with uncomplicated Plasmodium falciparum malaria were treated with artesunate and mefloquine. 213 children were analysed according to study protocol. 50 neurological and neuropsychiatric adverse events occurred in 28 patients. Eleven drug-related neurological and neuropsychiatric adverse events occurred in eight patients. Sleeping disorders were present in 2.3%, neurological disorders in 1.4%, neuropsychiatric disorders in 1% and eating disorders in 0.5% of the patients. Adverse events were of mild to moderate intensity and resolved spontaneously. CONCLUSION: African children showed a low percentage of self-limited neurological and neuropsychiatric adverse events, confirming studies on neurological safety in Asian children treated with artesunate and mefloquine. Sleeping disorders were most frequently observed

Paracheck-Pf® accuracy and recently treated Plasmodium falciparum infections: is there a risk of over-diagnosis?

BACKGROUND: An assessment of the accuracy of Paracheck Pf, a malaria rapid diagnostic test (RDT) detecting histidine rich protein 2 was undertaken amongst children aged 6-59 months in eastern Democratic Republic of Congo. METHODS: This RDT assessment occurred in conjunction with an ACT efficacy trial. Febrile children were simultaneously screened with both RDT and high quality microscopy and those meeting inclusion criteria were followed for 35 days. RESULTS: 358 febrile children were screened with 180 children recruited for five weeks follow-up. On screening, the RDT accurately diagnosed all 235 true malaria cases, indicating 100% RDT sensitivity. Of the 123 negative slides, the RDT gave 59 false-positive results, indicating 52.0% (64/123) RDT specificity. During follow-up after treatment with an artemisinin-based combination therapy, 98.2% (110/112), 94.6% (106/112), 92.0% (103/112) and 73.5% (50/68) of effectively treated children were still false-positive by RDT at days 14, 21, 28 and 35, respectively. CONCLUSION: Results show that though the use of Paracheck-Pf is as sensitive as microscopy in detecting true malaria cases, a low specificity did present a high frequency of false-positive RDT results. What's more, a duration of RDT false-positivity was found that significantly surpassed the 'fortnight' after effective treatment reported by its manufacturer. Though further research is needed in assessing RDT accuracy, study results showing the presence of frequent false positivity should be taken into consideration to avoid clinicians inappropriately focusing on malaria, not identifying the true cause of illness, and providing unnecessary treatment

Plasmodium vivax Recurrence Following Falciparum and Mixed Species Malaria: Risk Factors and Effect of Antimalarial Kinetics

On the Thai-Myanmar border, Plasmodium vivax is the most common cause of parasitological failure following treatment for acute falciparum malaria. Slowly eliminated antimalarials significantly reduce the risk of early recurrence

Psychosis with paranoid delusions after a therapeutic dose of mefloquine: a case report

BACKGROUND: Convenient once-a-week dosing has made mefloquine a popular choice as malaria prophylaxis for travel to countries with chloroquine-resistant malaria. However, the increased use of mefloquine over the past decade has resulted in reports of rare, but severe, neuropsychiatric adverse reactions, such as anxiety, depression, hallucinations and psychosis. A direct causality between mefloquine and severe reactions among travelers has been partly confounded by factors associated with foreign travel and, in the case of therapeutic doses of mefloquine, the central nervous system manifestations of Plasmodium infection itself. The present case provides a unique natural history of mefloquine-induced neuropsychiatric toxicity and revisits its dose-dependent nature. CASE PRESENTATION: This report describes an acute exacerbation of neuropsychiatric symptoms after an unwarranted therapeutic dose (1250 mg) of mefloquine in a 37-year-old male previously on a once-a-week prophylactic regimen. Neuropsychiatric symptoms began as dizziness and insomnia of several days duration, which was followed by one week of escalating anxiety and subtle alterations in behaviour. The patient's anxiety culminated into a panic episode with profound sympathetic activation. One week later, he was hospitalized after developing frank psychosis with psychomotor agitation and paranoid delusions. His psychosis remitted with low-dose quetiapine. CONCLUSION: This report suggests that an overt mefloquine-induced psychosis can be preceded by a prodromal phase of moderate symptoms such as dizziness, insomnia, and generalized anxiety. It is important that physicians advise patients taking mefloquine prophylaxis and their relatives to recognize such symptoms, especially when they are accompanied by abrupt, but subtle, changes in behaviour. Patients with a history of psychiatric illness, however minor, may be at increased risk for a mefloquine-induced neuropsychiatric toxicity. Physicians must explicitly caution patients not to self-medicate with a therapeutic course of mefloquine when a malaria diagnosis has not been confirmed

Differences in anti-malarial activity of 4-aminoalcohol quinoline enantiomers and investigation of the presumed underlying mechanism of action

International audienc

An assessment of the usefulness of a rapid immuno-chromatographic test, "Determine™ malaria pf" in evaluation of intervention measures in forest villages of central India

BACKGROUND: Plasmodium falciparum malaria, is a major health problem in forested tribal belt of central India. Rapid and accurate methods are needed for the diagnosis of P. falciparum. We performed a blinded evaluation of the recently introduced Determine™ malaria pf test (Abbott, Laboratories, Japan) compared with microscopy and splenomegaly in children in epidemic prone areas of district Mandla to assess the impact of intervention measures. METHODS: Children aged 2–10 yrs with and without fever were examined for spleen enlargement by medical specialist by establishing a mobile field clinic. From these children thick blood smears were prepared from finger prick and read by a technician. Simultaneously, rapid tests were performed by a field lab attendant. The figures for specificity, sensitivity and predictive values were calculated using microscopy as gold standard. RESULTS: In all 349 children were examined. The sensitivity and specificity for Determine rapid diagnostic test were 91 and 80% respectively. The positive predictive values (PPV), negative predictive values (NPV) and accuracy of the test were respectively 79, 91 and 85%. On the contrary, the sensitivity and specificity of spleen in detecting malaria infection were 57 and 74 % respectively with PPV of 73%, NPV 59 % and an accuracy of 65%. CONCLUSIONS: Determine™ malaria rapid diagnostic test is easier and quicker to perform and has other advantages over microscopy in not requiring prior training of personnel or quality control. Thus, highlighting the usefulness of a rapid antigen test in assessing prevailing malaria situation in remote areas