To see all articles in this section, click on "browse by Title".

Recent Submissions

  • Adherence and population pharmacokinetic properties of amodiaquine when used for seasonal malaria chemoprevention in African children

    Ding, J; Coldiron, ME; Assao, B; Guindo, O; Blessborn, D; Winterberg, M; Grais, RF; Koscalova, A; Langendorf, C; Tarning, J (American Society for Clinical Pharmacology and Therapeutics, 2019-10-25)
    Poor adherence to seasonal malaria chemoprevention (SMC) might affect the protective effectiveness of SMC. Here, we evaluated the population pharmacokinetic properties of amodiaquine and its active metabolite, desethylamodiaquine, in children receiving SMC under directly‐observed ideal conditions (n=136), and the adherence of SMC at an implementation phase in children participating in a case‐control study to evaluate SMC effectiveness (n=869). Amodiaquine and desethylamodiaquine concentration‐time profiles were described simultaneously by two‐compartment and three‐compartment disposition models, respectively. The developed methodology to evaluate adherence showed a sensitivity of 65‐71% when the first dose of SMC was directly observed and 71‐73% when no doses were observed in a routine programmatic setting. Adherence simulations and measured desethylamodiaquine concentrations in the case‐control children showed complete adherence (all doses taken) in less than 20% of children. This result suggests that more efforts are needed urgently to improve the adherence to SMC among children in this area.
  • Competing risk events in antimalarial drug trials in uncomplicated Plasmodium falciparum malaria: a WorldWide Antimalarial Resistance Network individual participant data meta-analysis.

    Dahal, P; Simpson, JA; Abdulla, S; Achan, J; Adam, I; Agarwal, A; Allan, R; Anvikar, AR; Arinaitwe, E; Ashley, EA; et al. (BioMed Central, 2019-07-05)
    BACKGROUND: Therapeutic efficacy studies in uncomplicated Plasmodium falciparum malaria are confounded by new infections, which constitute competing risk events since they can potentially preclude/pre-empt the detection of subsequent recrudescence of persistent, sub-microscopic primary infections. METHODS: Antimalarial studies typically report the risk of recrudescence derived using the Kaplan-Meier (K-M) method, which considers new infections acquired during the follow-up period as censored. Cumulative Incidence Function (CIF) provides an alternative approach for handling new infections, which accounts for them as a competing risk event. The complement of the estimate derived using the K-M method (1 minus K-M), and the CIF were used to derive the risk of recrudescence at the end of the follow-up period using data from studies collated in the WorldWide Antimalarial Resistance Network data repository. Absolute differences in the failure estimates derived using these two methods were quantified. In comparative studies, the equality of two K-M curves was assessed using the log-rank test, and the equality of CIFs using Gray's k-sample test (both at 5% level of significance). Two different regression modelling strategies for recrudescence were considered: cause-specific Cox model and Fine and Gray's sub-distributional hazard model. RESULTS: Data were available from 92 studies (233 treatment arms, 31,379 patients) conducted between 1996 and 2014. At the end of follow-up, the median absolute overestimation in the estimated risk of cumulative recrudescence by using 1 minus K-M approach was 0.04% (interquartile range (IQR): 0.00-0.27%, Range: 0.00-3.60%). The overestimation was correlated positively with the proportion of patients with recrudescence [Pearson's correlation coefficient (ρ): 0.38, 95% Confidence Interval (CI) 0.30-0.46] or new infection [ρ: 0.43; 95% CI 0.35-0.54]. In three study arms, the point estimates of failure were greater than 10% (the WHO threshold for withdrawing antimalarials) when the K-M method was used, but remained below 10% when using the CIF approach, but the 95% confidence interval included this threshold. CONCLUSIONS: The 1 minus K-M method resulted in a marginal overestimation of recrudescence that became increasingly pronounced as antimalarial efficacy declined, particularly when the observed proportion of new infection was high. The CIF approach provides an alternative approach for derivation of failure estimates in antimalarial trials, particularly in high transmission settings.
  • Severe acute malnutrition results in lower lumefantrine exposure in children treated with artemether-lumefantrine for uncomplicated malaria

    Chotsiri, P; Denoeud-Ndam, L; Baudin, E; Guindo, O; Diawara, H; Attaher, O; Smit, M; Guerin, PJ; Duombo, OK; Weisner, L; et al. (American Society for Clinical Pharmacology and Therapeutics, 2019-06-01)
    Severe acute malnutrition (SAM) has been reported to be associated with increased malaria morbidity in Sub‐Saharan African children and may affect the pharmacology of antimalarial drugs. This population pharmacokinetic‐pharmacodynamic study included 131 SAM and 266 non‐SAM children administered artemether‐lumefantrine twice daily for 3 days. Lumefantrine capillary plasma concentrations were adequately described by two transit‐absorption compartments followed by two distribution compartments. Allometrically scaled body weight and an enzymatic maturation effect were included in the pharmacokinetic model. Mid‐upper arm circumference (MUAC) was associated with decreased absorption of lumefantrine (25.4% decrease per 1 cm reduction). Risk of recurrent malaria episodes (i.e. reinfection) were characterised by an interval‐censored time‐to‐event model with a sigmoid EMAX‐model describing the effect of lumefantrine. SAM children were at risk of under‐exposure to lumefantrine and an increased risk of malaria reinfection compared to well‐nourished children. Research on optimised regimens should be considered for malaria treatment in malnourished children.
  • Novel Approaches to Control Malaria in Forested Areas of Southeast Asia.

    von Seidlein, L; Peto, TJ; Tripura, R; Pell, C; Yeung, S; Kindermans, JM; Dondorp, A; Maude, R (Elsevier, 2019-05-07)
    The emergence and spread of drug resistance in the Greater Mekong Subregion (GMS) have added urgency to accelerate malaria elimination while reducing the treatment options. The remaining foci of malaria transmission are often in forests, where vectors tend to bite during daytime and outdoors, thus reducing the effectiveness of insecticide-treated bed nets. Limited periods of exposure suggest that chemoprophylaxis could be a promising strategy to protect forest workers against malaria. Here we discuss three major questions in optimizing malaria chemoprophylaxis for forest workers: which antimalarial drug regimens are most appropriate, how frequently the chemoprophylaxis should be delivered, and how to motivate forest workers to use, and adhere to, malaria prophylaxis.
  • Complex interactions between malaria and malnutrition: a systematic literature review

    Das, D; Grais, R F; Okiro, E A; Stepniewska, K; Mansoor, R; van der Kam, S; Terlouw, D J; Tarning, J; Barnes, K I; Guerin, P J (BMC, 2018-10-29)
    Despite substantial improvement in the control of malaria and decreased prevalence of malnutrition over the past two decades, both conditions remain heavy burdens that cause hundreds of thousands of deaths in children in resource-poor countries every year. Better understanding of the complex interactions between malaria and malnutrition is crucial for optimally targeting interventions where both conditions co-exist. This systematic review aimed to assess the evidence of the interplay between malaria and malnutrition.
  • Using ante-natal clinic prevalence data to monitor temporal changes in malaria incidence in a humanitarian setting in the Democratic Republic of Congo.

    Hellewell, J; Walker, P; Ghani, A; Rao, B; Churcher, TS (BMC, 2018-08-29)
    The number of clinical cases of malaria is often recorded in resource constrained or conflict settings as a proxy for disease burden. Interpreting case count data in areas of humanitarian need is challenging due to uncertainties in population size caused by security concerns, resource constraints and population movement. Malaria prevalence in women visiting ante-natal care (ANC) clinics has the potential to be an easier and more accurate metric for malaria surveillance that is unbiased by population size if malaria testing is routinely conducted irrespective of symptoms.
  • Malaria in pregnancy: a call for a safe, efficient, and patient-centred approach to first-trimester treatment.

    Rao, VB; Jensen, TO; Jimenez, BC; Robays, J; Lasry, E; Sterk, E; de Smet, M (Elsevier, 2018-06-06)
  • Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis

    Kloprogge, F; Workman, L; Borrmann, S; Tékété, M; Lefèvre, G; Hamed, K; Piola, P; Ursing, J; Kofoed, PE; Mårtensson, A; et al. (Public Library of Science, 2018-06)
    The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations.
  • 'I could not join because I had to work for pay.': A qualitative evaluation of falciparum malaria pro-active case detection in three rural Cambodian villages

    Taffon, P; Rossi, G; Kindermans, JM; Van den Bergh, R; Nguon, C; Debackere, M; Vernaeve, L; De Smet, M; Venables, E (Public Library of Science, 2018-04-12)
    Pro-active case detection (Pro-ACD), in the form of voluntary screening and treatment (VSAT) following community mobilisation about 'asymptomatic malaria', is currently being evaluated as a tool for Plasmodium falciparum elimination in Preah Vihear Province, Cambodia.
  • Molecular markers of resistance to amodiaquine plus sulfadoxine-pyrimethamine in an area with seasonal malaria chemoprevention in south central Niger

    Grais, RF; Laminou, IM; Woi-Messe, L; Makarimi, R; Bouriema, SH; Langendorf, C; Amambua-Ngwa, A; D'Alessandro, U; Guérin, PJ; Fandeur, T; et al. (BioMed Central, 2018-02-27)
    In Niger, malaria transmission is markedly seasonal with most of the disease burden occurring in children during the rainy season. Seasonal malaria chemoprevention (SMC) with amodiaquine plus sulfadoxine-pyrimethamine (AQ + SP) is recommended in the country to be administered monthly just before and during the rainy season. Moreover, clinical decisions on use of SP for intermittent preventive treatment in pregnancy (IPTp) now depend upon the validated molecular markers for SP resistance in Plasmodium falciparum observed in the local parasite population. However, little is known about molecular markers of resistance for either SP or AQ in the south of Niger. To address this question, clinical samples which met clinical and biological criteria, were collected in Gabi, Madarounfa district, Maradi region, Niger in 2011-2012 (before SMC implementation). Molecular markers of resistance to pyrimethamine (pfdhfr), sulfadoxine (pfdhps) and amodiaquine (pfmdr1) were assessed by DNA sequencing.
  • Community participation during two mass anti-malarial administrations in Cambodia: lessons from a joint workshop

    Peto, TJ; Debackere, M; Etienne, W; Vernaeve, L; Tripura, R; Falq, G; Davoeung, C; Nguon, C; Rekol, H; von Seidlein, L; et al. (BioMed Central, 2018-01-27)
    Two mass drug administrations (MDA) against falciparum malaria were conducted in 2015-16, one as operational research in northern Cambodia, and the other as a clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh the field teams from Médecins Sans Frontières and the Mahidol-Oxford Tropical Medicine Research Unit discussed lessons for future MDAs.
  • Efficacy of artesunate-amodiaquine, dihydroartemisinin-piperaquine and artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Maradi, Niger

    Grandesso, F; Guindo, O; Woi Messe, L; Makarimi, R; Traore, A; Dama, S; Laminou, IM; Rigal, J; de Smet, M; Ouwe Missi Oukem-Boyer, O; et al. (BioMed Central, 2018-01-25)
    Malaria endemic countries need to assess efficacy of anti-malarial treatments on a regular basis. Moreover, resistance to artemisinin that is established across mainland South-East Asia represents today a major threat to global health. Monitoring the efficacy of artemisinin-based combination therapies is of paramount importance to detect as early as possible the emergence of resistance in African countries that toll the highest burden of malaria morbidity and mortality.
  • Single low-dose primaquine for blocking transmission of Plasmodium falciparum malaria - a proposed model-derived age-based regimen for sub-Saharan Africa

    Taylor, WR; Naw, HK; Maitland, K; Williams, TN; Kapulu, M; D'Alessandro, U; Berkley, JA; Bejon, P; Okebe, J; Achan, J; et al. (BioMed Central, 2018-01-18)
    In 2012, the World Health Organization recommended blocking the transmission of Plasmodium falciparum with single low-dose primaquine (SLDPQ, target dose 0.25 mg base/kg body weight), without testing for glucose-6-phosphate dehydrogenase deficiency (G6PDd), when treating patients with uncomplicated falciparum malaria. We sought to develop an age-based SLDPQ regimen that would be suitable for sub-Saharan Africa.
  • Closing in on the Reservoir: Proactive Case Detection in High-Risk Groups as a Strategy to Detect Plasmodium falciparum Asymptomatic Carriers in Cambodia

    Rossi, Gabriele; Vernaeve, Lieven; Van den Bergh, Rafael; Nguon, Chea; Debackere, Mark; Abello Peiri, Carme; Van, Vuthea; Khim, Nimol; Kim, Saorin; Eam, Rotha; et al. (Oxford University Press, 2018-01-18)
    In the frame of elimination strategies of Plasmodium falciparum (Pf), active case detection has been recommended as complementary approach to the existing passive case detection programs. We trialed a polymerase chain reaction (PCR)-based active detection strategy targeting asymptomatic individuals, named proactive case detection (PACD), with the aim of assessing its feasibility, the extra yield of Pf infections, and the at-risk population for Pf carriage status.
  • Adapting Reactive Case Detection Strategies for falciparum Malaria in a Low-Transmission Area in Cambodia.

    Rossi, G; Van den Bergh, R; Nguon, C; Debackere, M; Vernaeve, L; Khim, N; Kim, S; Menard, D; De Smet, M; Kindermans, JM (Oxford University Press, 2018-01-06)
    Reactive case detection around falciparum malaria cases in Cambodia presents a low output. We improved it by including individuals occupationally coexposed with index case patients and using polymerase chain reaction-based diagnosis. The positivity rate increased from 0.16% to 3.9%.
  • Emergence of Plasmodium falciparum triple mutant in Cambodia.

    Rossi, G; De Smet, M; Khim, N; Kindermans, JM; Menard, D (Elsevier, 2017-12)
  • Seasonal Malaria Chemoprevention: successes and missed opportunities

    Coldiron, ME; Von Seidlein, L; Grais, RF (BioMed Central, 2017-11-28)
    Seasonal malaria chemoprevention (SMC) was recommended in 2012 for young children in the Sahel during the peak malaria transmission season. Children are given a single dose of sulfadoxine/pyrimethamine combined with a 3-day course of amodiaquine, once a month for up to 4 months. Roll-out and scale-up of SMC has been impressive, with 12 million children receiving the intervention in 2016. There is evidence of its overall benefit in routine implementation settings, and a meta-analysis of clinical trial data showed a 75% decrease in clinical malaria compared to placebo. SMC is not free of shortcomings. Its target zone includes many hard-to-reach areas, both because of poor infrastructure and because of political instability. Treatment adherence to a 3-day course of preventive treatment has not been fully documented, and could prove challenging. As SMC is scaled up, integration into a broader, community-based paradigm which includes other preventive and curative activities may prove beneficial, both for health systems and for recipients.
  • Evaluation of the Deki Reader™, an automated RDT reader and data management device, in a household survey setting in low malaria endemic southwestern Uganda

    Oyet, C; Roh, ME; Kiwanuka, GN; Orikiriza, P; Wade, M; Parikh, S; Mwanga-Amumpaire, J; Boum, Y (BioMed Central, 2017-11-07)
    Early diagnosis of suspected malaria cases with a rapid diagnostic test (RDT) has been shown to be an effective malaria control tool used in many resource-constrained settings. However, poor quality control and quality assurance hinder the accurate reporting of malaria diagnoses. Recent use of a portable, battery operated RDT reader (Deki Reader™, Fio Corporation) has shown to have high agreement with visual inspection across diverse health centre settings, however evidence of its feasibility and usability during cross sectional surveys are limited. This study aimed to evaluate the performance of the Deki Reader™ in a cross-sectional survey of children from southwestern Uganda.
  • Malaria in an Internally Displaced Persons Camp in the Democratic Republic of the Congo

    Brooks, H; Jean Paul, M; Claude, K; Houston, S; Hawkes, M (Oxford University Press, 2017-08-01)

View more