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Background: Dengue is the most important arthropod-borne viral infection of humans. In general, dengue fever is a disease with a benign course
and low fatality rate. However, some of patients progress to a more severe disease characterized by bleeding, hematological abnormalities and plasma
leakage. This more severe disease, previously known as dengue hemorrhagic fever (DHF), can lead to circulatory system collapse and death in 2.5-
20% of patients. Unfortunately, there is no specific treatment for dengue or its complications. However, treatment by modulation of the cytokine
response through use of drugs or antibodies has attracted considerable attention. While various antibiotics have been shown to possess immune
modulating activities, those belonging to the tetracycline family appear to have the most promise.
Aim: Aim of this study is to assess the effect of doxycycline on lowering IL-6 and TNF among patients with dengue hemorrhagic fever.
Methods: A systematic review of articles using PubMed was done. Search terms included tetracycline, doxycycline and dengue. RCTs that evaluated
the effects of doxycycline on cytokine levels of dengue hemorrhagic fever patients were included. Data extraction was performed by the primary
author and reviewed by the co-authors. Studies were assessed for risk of bias using the Cochrane Collaboration tool. Statistical analysis was performed
using Review Manager 5.3.
Results: Data was collected from two RCTs. In the pooled analysis using standardized (STD) paired difference in mean, doxycycline was favored in
lowering the serum IL-6 and serum TNF, both in day three and day seven post-treatment with p value of < 0.00001.
Conclusions: Our study showed that doxycycline lowered the levels of serum IL-6 and TNF; cytokines were directly implicated in the severe type
of dengue. This might translate to better clinical outcome for severely ill dengue patients. Further studies should focus on the overall effect of
doxycycline in lowering the mortality rate among dengue hemorrhagic fever patients.