A comparative, randomized clinical trial of artemisinin/naphtoquine twice daily one day versus artemether/lumefantrine six doses regimen in children and adults with uncomplicated falciparum malaria in Côte d'Ivoire

<p>Abstract</p> <p>Background</p> <p>Drug resistance in <it>Plasmodium falciparum </it>poses a major threat to malaria control. Combination anti-malarial therapy, including artemisinins, has been advocated to improve efficacy and limit the spread of resistance. The fixed combination of oral artemether-lumefantrine (AL) is highly effective and well-tolerated. Artemisinin/naphtoquine (AN) is a fixed-dose ACT that has recently become available in Africa.</p> <p>The objectives of the study were to compare the efficacy and safety of AN and AL for the treatment of uncomplicated <it>falciparum </it>malaria in a high transmission-intensity site in Ivory Coast.</p> <p>Methods</p> <p>We enrolled 122 participants aged 6 months or more with uncomplicated <it>falciparum </it>malaria. Participants were randomized to receive either artemisinin/naphtoquine or artemether/lumefantrine with variable dose according to their weight. Primary endpoints were the risks of treatment failure within 28 days, either unadjusted or adjusted by genotyping to distinguish recrudescence from new infection.</p> <p>Results</p> <p>Among 125 participants enrolled, 123 (98.4%) completed follow-up. Clinical evaluation of the 123 participants showed that cumulative PCR-uncorrected cure rate on day 28 was 100% for artemisinin/naphtoquine and 98.4% for artemether/lumefantrine. Both artemisinin-based combinations effected rapid fever and parasite clearance.</p> <p>Interpretation</p> <p>These data suggest that Arco^®could prove to be suitable for use as combination antimalarial therapy. Meanwhile, pharmacokinetic studies and further efficacy assessment should be conducted before its widespread use can be supported.</p

Haematological consequences of acute uncomplicated falciparum malaria: a WorldWide Antimalarial Resistance Network pooled analysis of individual patient data

Background: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. Methods: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. Results: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0–19.7 g/dL) in Africa, 11.6 g/dL (range 5.0–20.0 g/dL) in Asia and 12.3 g/dL (range 6.9–17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39–3.05], p < 0.001). Conclusions: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery

Genotyping of S and C Mutated Beta Globin Gene: Development of a Set of Primers for Use with DfV'VnG PCR Systems

International audienceSickle cell disease is a genetic disorder that affects nearly 5% of world population. In ivory coast, SCD is a real problem of health and screening is not systematic after born. Here, we designed a set of primers to detect abnormal hemoglobin S and C which can be used both in conventional and quantitative PCR (by curves combinations analysed). A total of 60 blood samples including 13 AA, 23 AS, 9 SS, 12 SC and 3 CC hemoglobin type were screened using hemoglobin electrophoresis and PCR. The universal control primer HBU/R4 was successfully amplified for all of 60 samples. In conventional PCR, for typing of allele S sensibility and specificity of primers were respectively 86.36% and 87.50%. For allele C, sensibility and specificity of this pair were respectively 53.33% and 91.11%. In qPCR, specificity and sensitivity of primers were greater than 85% for allele S and C specific primers

Artemisinin derivative-containing therapies and abnormal hemoglobin: Do we need to adapt the treatment?

International audienceBackground: Artemisinin-based treatment in malaria patients with abnormal hemoglobin may be ineffective because of their genetic particularity, which could lead to resistance. The main purpose of this study was to assess the effect of artemisinin derivatives on in vivo parasite clearance according to erythrocyte variants. In vivo response was investigated through retrospective data obtained over a 42-day artemether-lumefantrine/artesunate amodiaquine efficacy protocol conducted from 2012 to 2016. Results: A total of 770 patients in Côte d’Ivoire attending the hospitals of Anonkoua-koute (Abidjan), Petit Paris (Korhogo), Libreville (Man), Dar es salam (Bouaké), Ayamé and Yamoussoukro with acute uncomplicated falciparum malaria were selected for successful hemoglobin typing. HbAS, HbSS, HbAC, and HbSC genotypes were found. Parasite clearance time was obtained for 414 patients. In the population with abnormal hemoglobin, parasite densities on admission and parasite clearance rates were significantly lower in the HbSC group compared to HbAA (p = 0.02 and p = 0.007, respectively). After PCR correction on day 42, the acute treatment rate was 100% for each group. Parasite half-life and time for initial parasitaemia to decline by 50 and 99% were longer for the HbSC group (p < 0.05). The study also investigated the prevalence of K13-propeller polymorphisms across different hemoglobin genotype groups. A total of 185 and 63 samples were sequenced in the HbAA group and patients with abnormal Hb, respectively. Only two nonsynonymous mutations D559N and V510M were found in the HbAA group. Conclusion: Although this study proved good efficacy of artemether-lumefantrine and artesunate amodiaquine in the treatment of uncomplicated Plasmodium falciparum malaria in patients with abnormal hemoglobin, the increased delay of parasite clearance may represent a threat to health in these patients in relation with sickle cell crisis, which could support selection of parasites resistant to artemisinin

Influence of Host-Related Factors and Exposure to Mosquito Bites on the Dynamics of Antibody Response to Plasmodium falciparum Antigens

Humoral immunity to Plasmodium falciparum is acquired after repeated infections, and can lead to clinical protection. This study aimed to evaluate how human-, parasite-, and environment-related determinants can modulate the dynamics of IgG responses to Plasmodium falciparum after an infection. Individuals (n = 68, average age = 8.2 years) with uncomplicated malaria were treated with ACT and followed up for 42 days. IgG responses to P. falciparum merozoite antigens (PfMSP1, PfMSP3, PfAMA1, PfGLURP-R0), to whole schizont extract (PfSchz), and to Anopheles gSG6-P1 and Aedes Nterm–34 kDa salivary peptides were measured. Regression analyses were used to identify factors that influence the dynamics of IgG response to P. falciparum antigen between D0 and D42, including demographic and biological factors and the level of exposure to mosquito bites. The dynamics of IgG response to P. falciparum differed according to the antigen. According to multivariate analysis, IgG responses to PfSchz and to PfGLURP-R0 appear to be affected by exposure to Aedes saliva and are associated with age, parasite density, and anti-Plasmodium pre-existing immune response at study inclusion. The present work shows that human exposure to Aedes saliva may contribute, in addition to other factors, to the regulation of anti-Plasmodium immune responses during a natural infection