Department of General Medicine, Amrita Institute of Medical Sciences, Kochi, Kerala, India.
Clinical Virology Laboratory, Amrita Institute of Medical Sciences, Kochi, Kerala, India.
PLoS One. 2020 Feb 19;15(2):e0228699. doi: 10.1371/journal.pone.0228699. eCollection 2020.
Severe thrombocytopenia in dengue often prompts platelet transfusion primarily to reduce bleeding risk. In India, about 11-43% of dengue patients report receiving platelet transfusions which is considered scarce and expensive especially in resource limited settings. Herein, we evaluated the efficacy and safety of Carica papaya leaf extract (CPLE) in the management of severe thrombocytopenia (≤30,000/μL) in dengue infection. 51 laboratory confirmed adult dengue patients with platelet counts ≤30,000/μL were randomly assigned to either treatment (n = 26) or placebo (n = 24) group. By day 3, CPLE treated patients reported significantly (p = 0.007) increased platelet counts (482%± 284) compared to placebo (331%±370) group. In the treatment group, fewer patients received platelet transfusions (1/26 v/s 2/24) and their median time for platelets to recover to ≥ 50,000/μL was 2 days (IQR 2-3) compared to 3 days (IQR 2-4) in placebo. Overall, CPLE was safe and well tolerated with no significant decrease in mean hospitalization days. Plasma cytokine profiling revealed that by day 3, mean percent increase in TNFα and IFNγ levels in treatment group was less compared to that observed in placebos; (TNFα: 58.6% v/s 127.5%; p = 0.25 and IFNγ: 1.93% v/s 62.6% for; p = 0.12). While a mean percent increase in IL-6 levels occurred in placebos (15.92%±29.93%) by day 3, a decrease was noted in CPLE group (12.95%±21.75%; p = 0.0232). Inversely, CPLE treated patients reported a mean percent increase compared to placebo by day 3 (143% ±115.7% v/s 12.03%± 48.4%; p = 0.006). Further, by day 3, a faster clearance kinetics of viral NS1 antigenemia occurred-mean NS1 titers in treatment group decreased to 97.3% compared to 88% in placebos (p = 0.023). This study demonstrates safety and efficacy of CPLE in increasing platelet counts in severe thrombocytopenia in dengue infections. A possible immunomodulatory and antiviral activity may be attributed to CPLE treatment. These findings merit validation in larger prospective studies. Trial registration Name of the registry: Clinical Trials Registry-India (CTRI) Registration No.: CTRI-REF/2017/02/013314.
登革热患者常出现严重血小板减少症，这会导致出血风险增加，通常会进行血小板输注治疗。在印度，约有 11%-43%的登革热患者报告接受了血小板输注治疗，而在资源有限的情况下，血小板输注治疗被认为是稀缺和昂贵的。在此，我们评估了木瓜叶提取物（CPLE）在治疗登革热感染中严重血小板减少症（≤30,000/μL）的疗效和安全性。51 例经实验室确诊的成年登革热患者血小板计数≤30,000/μL，随机分为治疗组（n=26）或安慰剂组（n=24）。第 3 天，CPLE 治疗组的血小板计数显著增加（p=0.007）（482%±284），而安慰剂组（331%±370）血小板计数仅略有增加。在治疗组中，接受血小板输注的患者较少（1/26 例比 2/24 例），且血小板恢复到≥50,000/μL 的中位时间为 2 天（IQR 2-3），而安慰剂组为 3 天（IQR 2-4）。总体而言，CPLE 安全且耐受良好，平均住院天数无明显减少。血浆细胞因子谱分析显示，第 3 天，治疗组 TNFα和 IFNγ水平的平均百分比增加低于安慰剂组；（TNFα：58.6%比 127.5%；p=0.25 和 IFNγ：1.93%比 62.6%；p=0.12）。而在第 3 天，安慰剂组中 IL-6 水平出现了平均 15.92%±29.93%的百分比增加，而 CPLE 组则出现了下降（12.95%±21.75%；p=0.0232）。相反，CPLE 治疗组患者的血小板计数在第 3 天的平均百分比增加（143%±115.7%比 12.03%±48.4%；p=0.006）。此外，在第 3 天，病毒 NS1 抗原血症的清除动力学更快-治疗组的 NS1 滴度下降至 97.3%，而安慰剂组为 88%（p=0.023）。这项研究表明 CPLE 在增加登革热感染严重血小板减少症患者的血小板计数方面是安全有效的。CPLE 治疗可能具有免疫调节和抗病毒作用。这些发现值得在更大规模的前瞻性研究中进一步验证。试验注册 名称：临床试验注册印度（CTRI） 注册号：CTRI-REF/2017/02/013314。
