Abstract
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 registrationName of the registry: Clinical Trials Registry—India (CTRI)Registration No.: CTRI-REF/2017/02/013314
Highlights
Dengue is a mosquito borne flaviviral infection endemic to the tropics and sub-tropics
In some instances, it can progress to severe disease characterized by thrombocytopenia, excessive bleeding and plasma leakage, which eventually leads to shock and death
We investigated the safety and efficacy of Carica papaya leaf extract (CPLE) in improving platelet counts and reducing the need for platelet transfusions in the management of dengue patients with severe thrombocytopenia
Summary
Dengue is a mosquito borne flaviviral infection endemic to the tropics and sub-tropics. With a case fatality rate (CFR) of 2.5% and 1,300 disability-adjusted life years (DALYs) per million, dengue infections cause significant economic burden to public health systems in the endemic countries [1, 2]. According to the National Vector Borne Disease Control Program (NVBDCP), the number of dengue cases reported in India in 2017 was 153656 with 226 deaths [3]. Dengue infections usually present as mild fever that resolves rapidly. In some instances, it can progress to severe disease characterized by thrombocytopenia, excessive bleeding and plasma leakage, which eventually leads to shock and death. There are four distinct serotypes of dengue virus that can cause infection viz. DEN-1, DEN-2, DEN-3 and DEN-4
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