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Mayor A.,Barcelona Institute for Global Health | Mayor A.,Manhica Health Research Center | Alano P.,Istituto Superiore di Sanita
Blood | Year: 2015

In this issue of Blood, Malleret and colleagues show the importance of the bone marrow in Plasmodium vivax biology by proving the preferential infection of young reticulocytes (generally restricted to the bone marrow), which then experience accelerated maturation postinvasion. © 2015 by The American Society of Hematology.

Djimde A.A.,University of Bamako | Tekete M.,University of Bamako | Tekete M.,University of Heidelberg | Abdulla S.,Ifakara Health Research and Development Center | And 8 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

The pharmacokinetic and pharmacodynamic properties of a new pediatric formulation of artemether-lumefantrine, dispersible tablet, were determined within the context of a multicenter, randomized, parallelgroup study. In an exploratory approach, we compared a new pediatric formulation with the tablet formulation administered crushed in the treatment of African children with uncomplicated Plasmodium falciparum malaria. Patients were randomized to 3 different dosing groups (weights of 5 to <15 kg, 15 and <25 kg, and 25 to <35 kg). Treatment was administered twice daily over 3 days. Plasma concentrations of artemether and its active metabolite, dihydroartemisinin (DHA), were determined at 1 and 2 h after the first dose of dispersible (n = 91) and crushed (n = 93) tablets. A full pharmacokinetic profile of lumefantrine was reconstituted on the basis of 310 (dispersible tablet) and 315 (crushed tablet) plasma samples, collected at 6 different time points (1 sample per patient). Dispersible and crushed tablets showed similar artemether and DHA maximum concentrations in plasma (Cmax) for the different body weight groups, with overall means of 175 ± 168 and 190 ± 168 ng/ml, respectively, for artemether and 64.7 ± 58.1 and 63.7 ± 65.0 ng/ml, respectively, for DHA. For lumefantrine, the population Cmax were 6.3 μg/ml (dispersible tablet) and 7.7 μg/ml (crushed tablet), whereas the areas under the concentration-time curves from time zero to the time of the last quantifiable plasma concentration measured were 574 and 636 μg · h/ml, respectively. For both formulations, descriptive quintile analyses showed no apparent association between artemether/DHA Cmax and parasite clearance time or between the lumefantrine Cmax and the occurrence of adverse events or corrected QT interval changes. The results suggest that the dispersible tablet provides adequate systemic exposure to artemether, DHA, and lumefantrine in African children with uncomplicated P. falciparum malaria. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Alonso P.L.,University of Barcelona | Alonso P.L.,Manhica Health Research Center | Tanner M.,Swiss Tropical and Public Health Institute | Tanner M.,University of Basel
Nature Medicine | Year: 2013

The past decade witnessed unprecedented efforts to control malaria, including renewed political and financial commitment and increased availability of both old and new strategies and tools. However, malaria still represents a major health burden, particularly in Africa. Important challenges such as the fragility of many health systems, the rise of insecticide and drug resistance, and particularly the expected decline both in funding and in the coverage of key interventions if they are not replaced as needed, urgently need to be addressed. Further research and development is also becoming increasingly crucial. Among other needs, common methodologies for estimating and tracking the malaria burden, new strategies to measure transmission, better understanding of immunity, and increased knowledge of the mechanisms and effects of resistance to drugs and insecticides stand out. The ongoing efforts in research and development for new antimalarial drugs, more sensitive point-of-care rapid diagnostic tests and new insecticides need further innovation and substantial strengthening. Clearly, efforts should focus not only on Plasmodium falciparum but also and increasingly on Plasmodium vivax, the neglected human malaria parasite. Addressing these challenges in a comprehensive and timely way will allow us to sustain the gains made so far and make further progress in control and progressive elimination. © 2013 Nature America, Inc. All rights reserved.

Gonzalez R.,Barcelona Center for International Heath Research | Gonzalez R.,Manhica Health Research Center | Hellgren U.,Karolinska University Hospital | Greenwood B.,London School of Hygiene and Tropical Medicine | And 2 more authors.
Malaria Journal | Year: 2014

Background: Control of malaria in pregnant women is still a major challenge as it constitutes an important cause of maternal and neonatal mortality. Mefloquine (MQ) has been used for malaria chemoprophylaxis in non-immune travellers for several decades and it constitutes a potential candidate for intermittent preventive treatment in pregnant women (IPTp). Methods. The safety of MQ, including its safety in pregnancy, is controversial and a continuing subject of debate. Published studies which evaluated the use of MQ for malaria prevention or treatment in pregnant women and which reported data on drug tolerability and/or pregnancy outcomes have been reviewed systematically. Results: Eighteen articles fitted the inclusion criteria, only one study was double-blind and placebo controlled. No differences were found in the risk of adverse pregnancy outcomes in women exposed to MQ compared to those exposed to other anti-malarials or to the general population. MQ combined with artesunate seems to be better tolerated than standard quinine therapy for treatment of non-severe falciparum malaria, but a MQ loading dose (10 mg/kg) is associated with more dizziness compared with placebo. When used for IPTp, MQ (15 mg/kg) may have more side effects than sulphadoxine- pyrimethamine. Conclusions: In the published literature there are no indications that MQ use during pregnancy carries an increased risk for the foetus. Ideally, the use of MQ to prevent malaria should be based on a risk-benefit analysis of adverse effects against the risk of acquiring the infection. For this purpose double-blinded randomized controlled trials in African pregnant women are much needed. © 2014 González et al.; licensee BioMed Central Ltd.

Moraleda C.,Manhica Health Research Center | Moraleda C.,University of Barcelona | De Deus N.,Manhica Health Research Center | De Deus N.,National Institute of Health | And 8 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2014

Background: Up to 30% of infants may be HIV-exposed noninfected (ENI) in countries with high HIV prevalence, but the impact of maternal HIV on the child's health remains unclear. Methods: One hundred fifty-eight HIV ENI and 160 unexposed (UE) Mozambican infants were evaluated at 1, 3, 9, and 12 months postdelivery. At each visit, a questionnaire was administered, and HIV DNA polymerase chain reaction and hematologic and CD4/ CD8 determinations were measured. Linear mixed models were used to evaluate differences in hematologic parameters and T-cell counts between the study groups. All outpatient visits and admissions were registered. ENI infants received cotrimoxazol prophylaxis (CTXP). Negative binomial regression models were estimated to compare incidence rates of outpatient visits and admissions. Results: Hematocrit was lower in ENI than in UE infants at 1, 3, and 9 months of age (P = 0.024, 0.025, and 0.012, respectively). Percentage of CD4 T cells was 3% lower (95% confidence interval: 0.86 to 5.15; P = 0.006) and percentage of CD8 T cells 1.15 times higher (95% confidence interval: 1.06 to 1.25; P = 0.001) in ENI vs. UE infants. ENI infants had a lower weight-for-age Z score (P = 0.049) but reduced incidence of outpatient visits, overall (P = 0.042), diarrhea (P = 0.001), and respiratory conditions (P = 0.042). Conclusions: ENI children were more frequently anemic, had poorer nutritional status, and alterations in some immunologic profiles compared with UE children. CTXP may explain their reduced mild morbidity. These findings may reinforce continuation of CTXP and the need to understand the consequences of maternal HIV exposure in this vulnerable group of children. Copyright © 2013 by Lippincott Williams and Wilkins.

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