Updates on clinical pharmacology of dengue.

Sir,

Dengue is an increasingly prevalent tropical arbovirus infection with significant morbidity and mortality.[1] The clinical presentation of dengue is the acute febrile illness with the classical triad of laboratory findings, hemoconcentration, atypical lymphocytosis and thrombocytopenia.[1] In severe cases, the most serious form of dengue, dengue shock syndrome is seen and can result in death. Treatment of dengue is mainly based on the fluid replacement therapy.[1] For prevention, the mosquito control is the key. The search for dengue vaccine is underway.[2]

Of the several new drugs being researched for dengue treatment, the natural product research is a widely studied field.[1] Indeed, there are many reports on natural products that have potential for treatment of dengue. However, only a few natural products are further evaluated in clinical pharmacology studies. The study on the potential use of neem (Azadirachta indica Juss) leaves for destroying dengue virus was published by Parida et al.[3] In this report, in vitro study showed that aqueous extract of neem could inhibit dengue virus; however the in vivo study in mice model revealed no inhibitory activity.[3] Another interesting report is published by Reis et al. In this report, immunomodulating and antiviral activities of Uncaria tomentosa on human monocytes infected with Dengue was presented.[4] In this work, alkaloidal fraction in Uncaria tomentosa was effective in reducing monocyte infection rates and cytokine levels.[4]

There are also some interesting publications on novel anti-dengue therapeutic agents. In the study by Lee et al, antiviral effects of three novel anti-dengue therapeutic agents, sulfated polysaccharides, suramin, pentosan polysulfate (PPS) and PI-88, were tested and it was shown that PI-88 was the only effect novel agent.[5] Indeed, there are also other reports on other novel agents. For example, Prestwood et al. reported on the efficacy of c-Src protein kinase inhibitors in blocking assembly and maturation of dengue virus.[6] Shigeta et al. also reported the good effectiveness of polyoxometalates in viral inhibition in mice model.[7] On the other hand, Tassniyom et al. reported the unsuccessful usage of carbazochrome sodium sulfonate or AC-17 to prevent vascular permeability or shock caused by dengue virus.[8] Focusing on the modern RNA technology, the use of mismatched double-stranded RNA was also trailed and reported for its good effectiveness as novel alternative anti-dengue therapeutic agent.[9]

There are many dengue vaccines which are presently on trials. Vaughn et al. firstly reported on testing of a dengue two live-attenuated vaccine, strain 16681 PDK 53. in volunteers and presented for high immunogenicitiy but some minor adverse effects such as fever, headache and myalgia.[10] Kanesa- thasan et al. reported another study of attenuated dengue virus vaccines developed by Aventis Pasteur that this vaccine alternative was safe and demonstrated immunogenicity.[11]

Many similar studies using animal models, a useful tool for research on dengue virus have been conducted.[12] However, there is no large study that confirms and leads to paradigm shift in treatment and prevention of dengue. More systematic researches on this area is still warranted.