While exact estimates of incidence are not yet available, IRIS in patients initiating ART has been firmly established as a significant problem in both high and low income countries. Because of wide variation in clinical presentation and the still increasing spectrum of symptoms and etiologies reported, diagnosis remains problematic. Fur-thermore, no test is currently available to establish an IRIS diagnosis. Standardized disease-specific clinical criteria for common infectious manifestations of the disease should be developed to: 1) identify risk factors for developing the syndrome and 2) optimize the prevention, management of opportunistic infections. Results of trials addressing the optimal timing and duration of treatment of opportunistic infections will assist in developing guidelines for the prevention and management of IRIS. Treatment of IRIS will remain a clinical challenge due to the variety of clinical presentations and the presence of multiple pathogens capable of causing the syndrome. Until a greater understanding of the syndrome is achieved in different regions of the world, clinicians need to remain vigilant when initiating ART and individualize therapy according to known treatment options for the specific infectious agent.  Global Surveillance of Emerging Influenza Virus Genotypes by Mass Spectrometry BACKGROUND: Effective influenza surveillance requires new methods capable of rapid and inexpensive genomic analysis of evolving viral species for pandemic preparedness, to understand the evolution of circulating viral species, and for vaccine strain selection. We have developed one such approach based on previously described broad-range reverse transcription PCR/electrospray ionization mass spectrometry (RT-PCR/ESI-MS) technology. METHODS AND PRINCIPAL FINDINGS: Analysis of base compositions of RT-PCR amplicons from influenza core gene segments (PB1, PB2, PA, M, NS, NP) are used to provide sub-species identification and infer influenza virus H and N subtypes. Using this approach, we detected and correctly identified 92 mammalian and avian influenza isolates, representing 30 different H and N types, including 29 avian H5N1 isolates. Further, direct analysis of 656 human clinical respiratory specimens collected over a seven-year period (1999–2006) showed correct identification of the viral species and subtypes with >97% sensitivity and specificity. Base composition derived clusters inferred from this analysis showed 100% concordance to previously established clades. Ongoing surveillance of samples from the recent influenza virus seasons (2005–2006) showed evidence for emergence and establishment of new genotypes of circulating H3N2 strains worldwide. Mixed viral quasispecies were found in approximately 1% of these recent samples providing a view into viral evolution. CONCLUSION/SIGNIFICANCE: Thus, rapid RT-PCR/ESI-MS analysis can be used to simultaneously identify all species of influenza viruses with clade-level resolution, identify mixed viral populations and monitor global spread and emergence of novel viral genotypes. This high-throughput method promises to become an integral component of influenza surveillance. Influenza viruses cause serious global economic and public health burdens. Annual influenza epidemics resulted in more than 30,000 deaths a year in the United States during 1990-1999 [1, 2] . Periodic pandemics result in significantly higher death tolls. Emergence of new influenza A virus strains can be caused by ''antigenic shift,'' resulting from reassortment of gene segments, including H and/or N types [3, 4] , ''antigenic drift'' resulting from the continuing accumulation of mutations in the H and N genes [5] , or a pathogenic virus jumping species and acquiring the ability to infect and be transmitted among humans, as in the 1918 pandemic [6] . The recent outbreak of highly pathogenic H5N1 avian influenza virus (HPAI), which originated in Southeast Asia and has since spread globally, has resulted in 166 deaths (272 confirmed human cases) as of February 6, 2007 (http://www.who. int/en/). The global emergence of this virus has brought renewed urgency to the effort to track the spread and the evolution of influenza viruses.