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.
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.
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).
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.
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.
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.
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.
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.
INTRODUCTIONLenalidomide is an immunomodulatory drug widely used in the treatment of multiple myeloma. Several cases of nephrotoxicity have been reported, but few have been documented histologically. ...CASE PRESENTATIONWe report a case of acute interstitial nephritis to lenalidomide in a 62-year-old patient with multiple myeloma after administration of the second course of chemotherapy according to the protocol combining bortezomib, lenalidomide and dexamethasone. The outcome was quickly favorable after stopping lenalidomide, with corticosteroid therapy. CONCLUSIONLenalidomide may be responsible for acute interstitial nephritis. When acute kidney injury occurs in myeloma, the nephrotoxicity of therapeutic agents should be considered in addition to the common causes of kidney failure. The chronology of events and the histological data are essential and guide the specific management.
The health-care needs and resources of disease-endemic regions such as west Africa have been a major focus during the recent Ebola outbreak. On the basis of that experience, we call attention to two ...priorities that have unfortunately been ignored thus far: 1) the development of clinical research facilities and 2) the training of host country investigators to ensure that the facilities and expertise necessary to evaluate candidate interventions are available on-site in endemic regions when and where they are needed. In their absence, as illustrated by the recent uncertainty about the use of antivirals and other interventions for Ebola virus disease, the only treatment available may be supportive care, case fatality rates may be unacceptably high and there may be long delays between the time potential interventions become available and it becomes clear whether those interventions are safe or effective. On the basis of our experience in Mali, we urge that the development of clinical research facilities and the training of host country investigators be prioritized in disease-endemic regions such as west Africa.
Le lénalidomide est un médicament immunomodulateur très souvent utilisé dans le traitement du myélome multiple. Plusieurs cas de néphrotoxicité ont été rapportés, mais peu ont été documentés ...histologiquement.
Nous rapportons un cas de néphrite interstitielle aiguë au lénalidomide chez un patient âgé de 62 ans atteint de myélome multiple, après l’administration de la seconde cure de chimiothérapie selon le protocole associant bortézomib, lénalidomide et déxaméthasone. L’évolution a été rapidement favorable après l’arrêt du lénalidomide et l’introduction d’une corticothérapie.
Le lénalidomide peut être responsable de néphrite interstitielle aiguë. Devant une insuffisance rénale aiguë au cours du traitement du myélome multiple, la néphrotoxicité des agents thérapeutiques doit également être évoquée en plus des causes d’atteintes rénales classiques. La chronologie des faits et les données histologiques sont essentielles et guident la prise en charge spécifique.
Lenalidomide is an immunomodulatory drug widely used in the treatment of multiple myeloma. Several cases of nephrotoxicity have been reported, but few have been documented histologically.
We report a case of acute interstitial nephritis to lenalidomide in a 62-year-old patient with multiple myeloma after administration of the second course of chemotherapy according to the protocol combining bortezomib, lenalidomide and dexamethasone. The outcome was quickly favorable after stopping lenalidomide, with corticosteroid therapy.
Lenalidomide may be responsible for acute interstitial nephritis. When acute kidney injury occurs in myeloma, the nephrotoxicity of therapeutic agents should be considered in addition to the common causes of kidney failure. The chronology of events and the histological data are essential and guide the specific management.
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.
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.
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: Multiple myeloma (MM) is a monoclonal proliferation of mature plasma cells. It usually occurs in people over 50 years of age with a peak in frequency at 65 years of age and less than 2% ...of patients are under 40 years of age. Case presentation: This case report is of a 38 year old black African woman with chronic kidney disease stage 5D. The IR was of glomerular origin (hypertension for 2 years, proteinuria at 4 g/24 hours, oedematous syndrome). Serum protein electrophoresis showed a beta peak at 29.7 g/l and urine protein immunoelectrophoresis showed a kappa/lambda ratio of 8.4. The myelogram showed a rich marrow with 51% plasma cells. Radiography showed multiple cystic images at the upper 1/3 of the left humeral shaft. Renal histology showed minimal glomerular damage. The diagnostic profile of IgG kappa light chain MM with CRAB criteria complicated by chronic glomerulonephritis with unorganised monoclonal immunoglobulin deposits was suggested. Management consisted of chemotherapy with bortezomib and dexamethasone for 4 cycles. The evolution under chronic dialysis was favourable after 1 year. Conclusion: MM in young adults (defined as 19-40 years of age) is rare, but it does exist. In young patients, this condition is initially not considered in the differential diagnosis and the occurrence of IR has a strong prognostic impact. Survival seems to be better in young adults than in elderly patients, which needs to be proven by a longer follow-up.
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