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Treatment of yellow fever

10 Jul 2008

Paul Chinnock

Source: Antiviral Research (see original article)

 

Citation: Monath TP (2008). Treatment of yellow fever. Antiviral Res; 78(1):116-24

© 2008

Yellow fever is a serious viral disease. For many years there has been an effective vaccine but, nevertheless, there are still an estimated 200,000 cases of the disease every year; there is no treatment and some 30,000 people die. Further information is available in a World Health Organization factsheet.

The search for an effective yellow fever treatment should therefore be a priority. This review summarizes the work that has been done so far, in particular the use of antiviral drugs which is still at the stage of animal experimentation.

Note: This article is published in a journal which is not open access. To see the full article a subscription to Antiviral Research is therefore required. In some developing countries, readers who are based in institutions may be able to access it through the HINARI programme.

Abstract

Yellow fever (YF) is a life-threatening mosquito-borne flaviviral hemorrhagic fever (VHF) characterized by severe hepatitis, renal failure, hemorrhage, and rapid terminal events with shock and multi-organ failure. A live, attenuated vaccine (YF 17D), in wide use for over 60 years, causes a disease identical to wild-type virus at an incidence of 2.5x10(-6). Our current understanding of the pathogenesis and treatment of YF (described in this brief review) is derived from studies of animal models (macaques, hamsters) that reproduce the features of human YF and from descriptive studies of human cases of naturally acquired and vaccine-associated VHF. The least understood, but potentially most important terminal events appear to be due to 'cytokine storm' and represent a potential target for therapeutic interventions. Areas for future study include dissection of cytokine-mediated events in animal models, the pathogenic role of the profound neutrophilia that occurs pre-terminally, the (pathological) role of adaptive immune clearance in pathogenesis, and treatments directed at cytokine storm. Antibody, interferon-alpha, polyICLC and other immune modulators are highly effective when administered before or within a narrow time window after infection, but are ineffective when given after the infection is established. A few antivirals have been evaluated (ribavirin, tiazofurin, carboxamide, pyrazoline compounds). Ribavirin has been used successfully to treat hamsters when the drug is given at high doses up to 2 days after virus infection (shortly before liver infection), but has not shown promise in nonhuman primate models. Future work should focus on evaluating higher doses of ribavirin alone or in combinations with potentially synergistic drugs, including interferons. Also specific inhibitors against other flaviviruses such as dengue virus should be investigated for potential pan-flavivirus activity since recent studies have shown that specific targets such as the flavivirus proteases and helicases are very similar in structure.

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