A systematic review of antiviral therapies and immunomodulator treatments in avian influenza A (H5N1) infections

Abstract

Background Avian influenza A (H5N1) has been circulating around and remains to be one of the major threats to human beings since it first emerged in 1997. Besides vaccines, currently there are two major countermeasures to infection in clinical settings, which are antiviral therapies and immunomodulator treatments.

Objectives To summarize evidence on the effectiveness of current treatments against H5N1 infection and to explore the potential benefits of several immunomodulatory agents.

Design Systematic review of cross-sectional studies and case series.

Data sources Searches of PubMed for articles using the search term “(H5N1[Title]) AND antiviral[Title/Abstract]” and also manual search on PubMed for studies that are cited in some review papers in the first automatic search. Previous search results relating to human H5N1 infection studies are also included.

Study selection Included studies that were human H5N1 infection cross-sectional studies or case series in which clinical outcomes were reported, CFR and survival rate were specified or could be easily derived from original data.

Results 11 articles met the selection criteria and were included in our analysis. Sample size of the included studies ranged from 8 to 308 lab confirmed cases with median age varied from 10 to 29. Leukopenia, lymphopenia, thrombocytopenia and elevated ALT and AST at admission were strongly associated with worse clinical outcomes with different significance across studies. Oseltmivir treatment was generally initiated earlier among those who survived. Survival benefit of oseltamivir was the most significant if the patient received the treatment within the first two days after symptom onset, and it is still significantly effective when treatment was given up to eight days after symptom onset according to one study we included. Corticosteroid didnot show any beneficial effect or it is associated with a higher risk of death when it is given according to the current treatment protocol and a delayed initiation time.

Conclusion Oseltamivir treatment is associated with survival benefit especially when initiated within the first two days after symptom onset, while immunomodulator therapies haven’t shown such benefit so far in clinical setting but some experiments in vitro and in vivo support their use in a manner which is different from the current protocol.