In medical research, the ethical principle of respect for persons is operationalized into the process of informed consent. The consent tools should be contextualized and adapted to the different socio-cultural environment, especially when research crosses the traditional boundaries and reaches poor communities. We look at the challenges experienced in the malaria Quinact trial, conducted in the Democratic Republic of Congo, and describe some lessons learned, related to the definition of acceptable representative, the role of independent witness and the impact of socio-economic vulnerability. To ensure children's protection, consent is required by the parents or, in their absence, by a legally mandated representative. In our setting, children's responsibility is often entrusted permanently or temporarily to relatives or friends without a tribunal mandate. Hence, a notion of 'culturally acceptable representative' under supervision of the local Ethics Committee may be more suitable. To ensure protection of illiterate subjects, an independent witness is required to confirm that the consent was freely given. However, in low-literacy contexts, potential witnesses often don't have any previous relationship with patient and there may be power-unbalance in their relationship, rather than genuine dialogue. In poor communities, trial participation may be seen as an opportunity to secure access to healthcare. Poverty may also lead to 'competition' to access the research-related benefits, with a risk of disturbance at societal or household level. Adjusting consent procedures to sociocultural and socioeconomic realities is essential for fulfilling the underlying ethical principles. This requires a collaborative dialogue between researchers, regulators and ethics committees.

BackgroundIn the Democratic Republic of Congo, artesunate-amodiaquine (ASAQ) is the first-line medication recommended for uncomplicated malaria treatment. We conducted a study in Kinshasa to describe the clinical features of the disease and assess the efficacy of ASAQ and its impact on the multiplicity of infection in children with uncomplicated malaria.MethodsChildren aged 12 to 59 months with uncomplicated P. falciparum malaria were treated with ASAQ and followed up passively for 42 days. To distinguish new infections from recrudescent parasites, samples were genotyped using a stepwise strategy with three molecular markers (GLURP, MSP2 and MSP1). We then assessed PCR-corrected and -uncorrected day-42 cure rates and multiplicity of infection (MOI).ResultsIn total, 2,796 patients were screened and 865 enrolled in the study. Clinical features were characterized by history of fever (100%), coryza (59.9%) and weakness (59.4%). The crude and PCR-corrected efficacies of ASAQ were 55.3% (95%CI: 51.8–58.8) and 92.8% (95%CI: 91.0–94.6) respectively, as 83.6% (95%CI: 79.1–87.2) of the recurrences were new infections. Compared to monoclonal infections, polyclonal infections were more frequent at enrollment (88.1%) and in recurrences (80.1%; p = 0.005; OR: 1.8, 95%CI: 1.20–2.8). The median MOI at enrollment (MOI = 3.7; IQR: 0.7–6.7) decreased to 3 (IQR: 1–5) in the recurrent samples (p<0.001). Patients infected with a single haplotype on day 0 had no recrudescence; the risk of recrudescence increased by 28% with each additional haplotype (HR: 1.3, 95%CI: 1.24–1.44).ConclusionThe PCR-corrected efficacy of ASAQ at day 42 was 92.8%, but crude efficacy was relatively poor due to high reinfection rates. Treatment outcomes were positively correlated with MOI. Continued monitoring of the efficacy of ACTs—ASAQ, in this case—is paramount.Trial RegistrationClinicalTrials.gov NCT01374581

IntroductionArtemisinin-based combination therapy is currently the best option for the treatment of uncomplicated malaria. Quinine is recommended as a rescue treatment. Safety information during repeated treatment with the same drug is scarce. We report safety data from the Quinact randomized clinical trial (RCT) that was designed to assess efficacy and safety of artesunate-amodiaquine (ASAQ), artemether-lumefantrine (AL) and quinine+clindamycin (QnC).MethodologyMales and females aged 12 to 59 months with uncomplicated malaria were treated with ASAQ and followed up during 42 days (preRCT). Clinical failures were randomized to one of the 3 treatments and followed up for 28 days (RCT). Subsequent failures were repeatedly treated with ASAQ several times as needed (postRCT1, postRCT2 and so on) until a 28-days follow up period without parasitaemia.ResultsEight hundred and sixty-five, 242 and 64 patients were recruited respectively in preRCT, RCT and postRCTs. In preRCT, 433 (50.0%) patients experienced at least one drug-related adverse event (AE). The most reported AEs were anorexia (22.9%), asthenia (19.4%), and abnormal behavior (14.6%). Twenty-nine AEs (3.5%) were reported to be severe. In RCT, at least one drug-related AE was reported in 54.7%, 21.5% and 40.0% of patient randomized respectively to ASAQ, AL and QnC (p<0.001). During postRCT1 (n = 64), postRCT 2 (n = 17) and postRCT3 (n = 7), respectively 32.8%, 35.3% and 71.4% of patients experienced at least one drug-related AE. Three serious adverse events occurred but not judged related to study medication.ConclusionThe proportion of AEs did not increase over the treatment courses with ASAQ. However, continuous monitoring is important.

Background: Fever is a key symptom that motivates medical consultation mainly in tropical areas. This study aimed to assess non-malaria cases among those attending a primary health care facility with acute fever in Kinshasa suburb. Methods:Participants were screened independently with rapid diagnostic test (RDT) and microscopy. Dried blood spots were analyzed by polymerase chain reaction (PCR), which was considered as the golden standard for malaria diagnosis. A subpopulation benefited from blood culture to screen nonspecific bacterial infections.Results: A total of 296 patients were enrolled. Malaria was detected in 44.6%, 38.5%, and 37.2%, respectively, by RDT, microscopy, and PCR. Blood culture was positive for 5/151 patients (3.3%), essentially those aged under 5 years (4/5). Sleeping under mosquito net was protective against malaria (P = 0.026). In the subgroup assessed for blood culture, 94/151 patients (62.3%) had neither unspecific bacterial infection nor malaria. Conclusion:Neither malaria nor unspecific bacterial infection was responsible of the acute fever in more than half of the patients. These findings suggest that DTs (including viral agents) and diagnostic algorithms are paramount for the management of non-malaria acute fever.

Background: Fever is a key symptom that motivates medical consultation mainly in tropical areas. This study aimed to assess non-malaria cases among those attending a primary health care facility with acute fever in Kinshasa suburb. Methods:Participants were screened independently with rapid diagnostic test (RDT) and microscopy. Dried blood spots were analyzed by polymerase chain reaction (PCR), which was considered as the golden standard for malaria diagnosis. A subpopulation benefited from blood culture to screen nonspecific bacterial infections.Results: A total of 296 patients were enrolled. Malaria was detected in 44.6%, 38.5%, and 37.2%, respectively, by RDT, microscopy, and PCR. Blood culture was positive for 5/151 patients (3.3%), essentially those aged under 5 years (4/5). Sleeping under mosquito net was protective against malaria (P = 0.026). In the subgroup assessed for blood culture, 94/151 patients (62.3%) had neither unspecific bacterial infection nor malaria. Conclusion:Neither malaria nor unspecific bacterial infection was responsible of the acute fever in more than half of the patients. These findings suggest that DTs (including viral agents) and diagnostic algorithms are paramount for the management of non-malaria acute fever.