Persistent Submicroscopic Plasmodium falciparum Parasitemia 72 Hours after Treatment with Artemether-Lumefantrine Predicts 42-Day Treatment Failure in Mali and Burkina Faso.

A recent randomized controlled trial, the WANECAM (West African Network for Clinical Trials of Antimalarial Drugs) trial, conducted at seven centers in West Africa, found that artemether-lumefantrine, artesunate-amodiaquine, pyronaridine-artesunate, and dihydroartemisinin-piperaquine all displayed good efficacy. However, artemether-lumefantrine was associated with a shorter interval between clinical episodes than the other regimens. In a further comparison of these therapies, we identified cases of persisting submicroscopic parasitemia by quantitative PCR (qPCR) at 72 h posttreatment among WANECAM participants from 5 sites in Mali and Burkina Faso, and we compared treatment outcomes for this group to those with complete parasite clearance by 72 h. Among 552 evaluable patients, 17.7% had qPCR-detectable parasitemia at 72 h during their first treatment episode. This proportion varied among sites, reflecting differences in malaria transmission intensity, but did not differ among pooled drug treatment groups. However, patients who received artemether-lumefantrine and were qPCR positive at 72 h were significantly more likely to have microscopically detectable recurrent Plasmodium falciparum parasitemia by day 42 than those receiving other regimens and experienced, on average, a shorter interval before the next clinical episode. Haplotypes of pfcrt and pfmdr1 were also evaluated in persisting parasites. These data identify a possible threat to the parasitological efficacy of artemether-lumefantrine in West Africa, over a decade since it was first introduced on a large scale.

Bee venom: an unusual cause of acute kidney injury / Le venin d'abeille : une cause inhabituelle d'insuffisance rénale aiguë

Introduction: Bee sting venom is generally well tolerated. However, some rare cases of massive stings can lead to anaphylactic shock and even renal failure. This observation is the illustration of a case of acute kidney injury secondary to bee stings in a 64-year-old black african subject. Case presentation: A 64-year-old man without a known medical history was referred to the emergency department of the Fousseyni Daou hospital in Kayes (Mali) for disturbed consciousness 4 hours after massive stings from a bee swarm. Renal failure with serum creatinine level at 752,2 µmol/L was documented on day 3 in a context of total anuria. The patient was transferred to a nephrology unit and biology confirmed renal failure associated with intravascular haemolysis and rhabdomyolysis. The kidneys were of normal size and well differentiated. The diagnosis of severe acute kidney injury due to massive envenomation induced by bee venom was evoked. The evolution was favourable, with normalization of renal function at D26 after 5 sessions of haemodialysis in parallel with transfusions of packed red blood cells. Conclusion: A massive bee attack should be considered a medical emergency because of the organic damage it can inflict. The renal prognosis depends on the number of stings, and especially on the delay and the quality of the treatment. Early initiation of dialysis treatment reduces mortality.

Introduction: Le venin des piqûres d'abeilles est en général bien toléré. Cependant, quelques rares cas de piqûres massives peuvent entraîner un choc anaphylactique, voire une insuffisance rénale. Cette observation est l'illustration d'un cas d'insuffisance rénale aiguë par envenimation aux piqûres d'abeilles chez un sujet noir africain de 64 ans. Présentation du cas: Un homme de 64 ans sans antécédent médical connu, est adressé aux urgences de l'hôpital Fousseyni Daou de Kayes (Mali) pour trouble de la conscience 4 heures après des piqûres massives par un essaim d'abeilles. Une insuffisance rénale à 752,2 µmol/L de créatinine est découverte à J3 dans un contexte d'anurie totale. Le patient est transféré en unité de néphrologie où la biologie confirme l'insuffisance rénale associée à une hémolyse intravasculaire et une rhabdomyolyse. Les reins étaient de taille normale et bien différenciés à l'échographie. Le diagnostic d'une insuffisance rénale aiguë sévère par envenimation massive induite par le venin d'abeille a été évoqué. L'évolution était favorable, marquée par une normalisation de la fonction rénale à J26 après cinq séances d'hémodialyse en parallèle à des transfusions de culot globulaire. Conclusion: L'attaque massive d'abeilles doit être considérée comme une urgence médicale en raison des atteintes organiques qu'elle peut entraîner. Le pronostic rénal dépend du nombre de piqûres, et surtout du délai et de la qualité de prise en charge. L'instauration rapide de l'épuration extrarénale permet de réduire la mortalité.

AQ-13, an investigational antimalarial, versus artemether plus lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria: a randomised, phase 2, non-inferiority clinical trial.

BACKGROUND: Chloroquine was used for malaria treatment until resistant Plasmodium falciparum was identified. Because 4-aminoquinolines with modified side chains, such as AQ-13, are active against resistant parasites, we compared AQ-13 against artemether plus lumefantrine for treatment of uncomplicated P falciparum malaria. METHODS: We did a randomised, non-inferiority trial. We screened men (≥18 years) with uncomplicated malaria in Missira (northeast Mali) and Bamako (capital of Mali) for eligibility (≥2000 asexual P falciparum parasites per µL of blood). Eligible participants were randomly assigned to either the artemether plus lumefantrine group or AQ-13 group by permuting blocks of four with a random number generator. Physicians and others caring for the participants were masked, except for participants who received treatment and the research pharmacist who implemented the randomisation and provided treatment. Participants received either 80 mg of oral artemether and 480 mg of oral lumefantrine twice daily for 3 days or 638·50 mg of AQ-13 base (two oral capsules) on days 1 and 2, and 319·25 mg base (one oral capsule) on day 3. Participants were monitored for parasite clearance (50 µL blood samples twice daily at 12 h intervals until two consecutive negative samples were obtained) and interviewed for adverse events (once every day) as inpatients during week 1. During the 5-week outpatient follow-up, participants were examined for adverse events and recurrent infection twice per week. All participants were included in the intention-to-treat analysis and per-protocol analysis, except for those who dropped out in the per-protocol analysis. The composite primary outcome was clearance of asexual parasites and fever by day 7, and absence of recrudescent infection by parasites with the same molecular markers from days 8 to 42 (defined as cure). Non-inferiority was considered established if the proportion of patients who were cured was higher for artemether plus lumefantrine than for AQ-13 and the upper limit of the 95% CI was less than the non-inferiority margin of 15%. This trial is registered at ClinicalTrials.gov, number NCT01614964. FINDINGS: Between Aug 6 and Nov 18, 2013, and between Sept 18 and Nov 20, 2015, 66 Malian men with uncomplicated malaria were enrolled. 33 participants were randomly assigned to each group. There were no serious adverse events (grade 2-4) and asexual parasites were cleared by day 7 in both groups. 453 less-severe adverse events (≤grade 1) were reported: 214 in the combination group and 239 in the AQ-13 group. Two participants withdrew from the AQ-13 group after parasite clearance and three were lost to follow-up. In the artemether plus lumefantrine group, two participants had late treatment failures (same markers as original isolates). On the basis of the per-protocol analysis, the AQ-13 and artemether plus lumefantrine groups had similar proportions cured (28 [100%] of 28 vs 31 [93·9%] of 33; p=0·50) and AQ-13 was not inferior to artemether plus lumefantrine (difference -6·1%, 95% CI -14·7 to 2·4). Proportions cured were also similar between the groups in the intention-to-treat analysis (28 of 33, 84·8% for AQ-13 vs 31 of 33, 93·9% for artemether and lumefantrine; p=0·43) but the upper bound of the 95% CI exceeded the 15% non-inferiority margin (difference 9·1%, 95% CI -5·6 to 23·8). INTERPRETATION: The per-protocol analysis suggested non-inferiority of AQ-13 to artemether plus lumefantrine. By contrast, the intention-to-treat analysis, which included two participants who withdrew and three who were lost to follow-up from the AQ-13 group, did not meet the criterion for non-inferiority of AQ-13, although there were no AQ-13 treatment failures. Studies with more participants (and non-immune participants) are needed to decide whether widespread use of modified 4-aminoquinolones should be recommended. FUNDING: US Food and Drug Administration Orphan Product Development, National Institutes of Health, US Centers for Disease Control and Prevention, Burroughs-Wellcome Fund, US State Department, and WHO.