Research: Malaria and Parasitic Diseases

Listed in Issue 244



MAWSON, Health Policy and Management, School of Health Sciences, College of Public Service, Jackson State University, Jackson, MS 39213, United States. reviews the literature regarding the pathogenesis and possible future treatments of Dengue hemorrhagic fever (DHF).


Dengue hemorrhagic fever (DHF) is the most significant mosquito-borne viral disease worldwide in terms of illness, mortality and economic cost, but the pathogenesis of DHF is not well understood and there is no specific treatment or vaccine.


Based on evidence of liver involvement, it is proposed that dengue virus and retinoids interact to cause cholestatic liver damage, resulting in the spillage of stored retinoids into the circulation and in an endogenous form of hypervitaminosisis A manifested by the signs and symptoms of the disease, including: fever, severe joint and bone pain, capillary leakage, thrombocytopenia, headache, and gastrointestinal symptoms.


While retinoids in low concentration are essential for numerous biological functions, they are prooxidant, cytotoxic, mutagenic and teratogenic in higher concentration, especially when unbound to protein, and an endogenous form of vitamin A intoxication is recognized in cholestasis. The model tentatively explains the observations that 1) repeat infections are more severe than initial dengue virus infections; 2) the incidence of dengue has increased dramatically worldwide in recent decades; 3) DHF is less prevalent in people of African ancestry than those of other racial backgrounds; and 4) infants are protected from dengue. The retinoid toxicity hypothesis of DHF predicts the co-existence of low serum concentrations of retinol coupled with high concentrations of retinoic acid and an increased percentage of retinyl esters to total vitamin A.


Subject to such tests, it may be possible to treat DHF effectively using drugs that target the metabolism and expression of retinoids.


Mawson AR.  Retinoids, race and the pathogenesis of dengue hemorrhagic fever. Med Hypotheses. 81(6):1069-74. Dec 2013. doi: 10.1016/j.mehy.2013.08.004. Epub Aug 13 2013.

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