Panmicrobial oligonucleotide array for diagnosis of infectious diseases

Emerging Infectious Diseases, Jan, 2007 by Gustavo Palacios, Phenix-Lan Quan, Omar J. Jabado, sean Conlan, David L. Hirschberg, Yang Liu, Junhui Zhai, Neil Renwick, Jeffrey Hui, Hedi Hegyi, Allen Grolla, James E. Strong, Jonathan S. Towner, Thomas W. Geisbert, Peter B. Jahrling, Cornelia Buchen-Osmond, Heinz Ellerbrok, Maria Paz Sanchez-Seco, Yves Lussier, Pierre Formenty, Stuart T. Nichol, Heinz Feldmann, Thomas Briese, W. Ian Lipkin

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Discussion

Differential diagnosis of hemorrhagic fevers poses challenges for clinical medicine and public health. Syndromes associated with agents are not distinctive, particularly early in the course of disease. In some instances, including the case presented here, more than 1 agent may be endemic in the region of the outbreak. Outbreaks caused by different agents may also overlap in time and geography. Examples of such coincident outbreaks include monkeypox and varicella-zoster viruses in the Democratic Republic of Congo in 1996 and 2001 (19,20) and measles and Ebola viruses in Sudan in 2004 (21). Furthermore, implicit in globalization is the risk of known or new agents that appear in novel contexts. In 1996, a presumptive diagnosis of Ebola VHF in 2 children who had recently returned to New York City from West Africa resulted in closing a hospital emergency room (22). One of the children died of cardiac failure caused by P. falciparum parasitemia and hemolysis (23). Therapeutic options for treatment of VHF are limited; however, rapid isolation of infected persons is critical to curb contagion. In contrast, whereas human-to-human transmission is not a primary concern with malaria, early specific therapy can have a profound effect on illness and death (24).

To address the challenges of emerging infectious diseases and biodefense, public health practitioners and diagnosticians need a comprehensive set of tools for pathogen surveillance and isolation. PCR methods have advantages with respect to sensitivity, throughput, and simplicity, but are limited in potential for multiplexing. Although mieroarrays have potential to allow highly multiplexed, unbiased surveillance, their use has been limited because of low sensitivity and unwieldy analytical programs. The GreeneChip system introduces sample preparation and labeling methods that enhance sensitivity, as well as userfriendly analytical software that we anticipate will facilitate clinical application. The advent of validated highly multiplexed microbiologic assays will afford unprecedented opportunities for unbiased pathogen surveillance and discovery and reduction of illness and death caused by infectious disease.

Acknowledgments

We thank Mady Homig for helpful comments and providing host immune response probes and David Smith, David Boyle, Phyllis Della-Latta, Adolfo Garcia-Sastre, Gerry Hamett, Phillipa Jack, Cheryl Johansen, Anthony Mazzuli, John Mackenzie, Hendrik Nollens, Pilar Perez-Brena, and David Williams for specimens used in assay development and validation. We dedicate this paper to Allan Rosenfield, a humanitarian and visionary in global health.

The study was supported by National Institutes of Health grants AI51292, AI056118, AI55466, U54AI57158 (Northeast Biodefense Center-Lipkin), and U01AI070411, and the Ellison Medical Foundation.

References

(1.)Briese T, Palacios G, Kokoris M, Jabado O, Liu Z, Renwick N, et al. Diagnostic system for rapid and sensitive differential detection of pathogens. Emerg Infect Dis. 2005; 11:310-3.