刚果民主共和国单纯性临床疟疾的特征、青蒿琥酯-阿莫地喹的疗效及其与感染多样性的关系
Uncomplicated Clinical Malaria Features, the Efficacy of Artesunate-Amodiaquine and Their Relation with Multiplicity of Infection in the Democratic Republic of Congo.
作者信息
Muhindo Mavoko Hypolite, Kalabuanga Marion, Delgado-Ratto Christopher, Maketa Vivi, Mukele Rodin, Fungula Blaise, Inocêncio da Luz Raquel, Rosanas-Urgell Anna, Lutumba Pascal, Van Geertruyden Jean-Pierre
机构信息
Tropical Medicine Department, Faculty of Medicine, University of Kinshasa, Kinshasa, Democratic Republic of Congo.
Global Health Institute, University of Antwerp, Antwerp, Belgium.
出版信息
PLoS One. 2016 Jun 9;11(6):e0157074. doi: 10.1371/journal.pone.0157074. eCollection 2016.
BACKGROUND
In 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.
METHODS
Children 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).
RESULTS
In 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).
CONCLUSION
The 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 REGISTRATION
ClinicalTrials.gov NCT01374581.
背景
在刚果民主共和国，青蒿琥酯-阿莫地喹（ASAQ）是推荐用于治疗非复杂性疟疾的一线药物。我们在金沙萨开展了一项研究，以描述该疾病的临床特征，并评估ASAQ的疗效及其对非复杂性疟疾患儿感染多样性的影响。
方法
对年龄在12至59个月的非复杂性恶性疟原虫疟疾患儿采用ASAQ进行治疗，并被动随访42天。为了区分新感染与复发寄生虫，使用具有三个分子标记（谷氨酸脱氢酶、MSP2和MSP1）的逐步策略对样本进行基因分型。然后，我们评估了第42天经PCR校正和未经校正的治愈率以及感染多样性（MOI）。
结果
总共筛查了2796例患者，865例纳入研究。临床特征表现为发热史（100%）、鼻炎（59.9%）和虚弱（59.4%）。ASAQ的粗治愈率和经PCR校正的治愈率分别为55.3%（95%CI：51.8 - 58.8）和92.8%（95%CI：91.0 - 94.6），因为83.6%（95%CI：79.1 - 87.2）的复发为新感染。与单克隆感染相比，多克隆感染在入组时（88.1%）和复发时（80.1%；p = 0.005；OR：1.8，95%CI：1.20 - 2.8）更为常见。入组时的MOI中位数（MOI = 3.7；IQR：0.7 - 6.7）在复发样本中降至3（IQR：1 - 5）（p<0.001）。第0天感染单一单倍型的患者无复发；每增加一个单倍型，复发风险增加28%（HR：1.3，95%CI：1.24 - 1.44）。
结论
第42天ASAQ经PCR校正的疗效为92.8%，但由于再感染率高，粗疗效相对较差。治疗结果与MOI呈正相关。在这种情况下，持续监测ACTs - ASAQ的疗效至关重要。
试验注册
ClinicalTrials.gov NCT01374581。
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