ABSTRACT

However, new diseases and threats are continually emerging. Acquired immune deficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) and influenza virus H1N1 are prime examples of infectious diseases that have had major impacts on the world in the last 20 years. Multi-drug resistance in many infectious agents such as tuberculosis and methicillin resistant Staphylococcus aureus (MRSA) is a real threat. Global warming is predicted to result in new diseases or the emergence of old scourges [38]. There is a real need for new preventive measures (e.g. vaccines), therapeutics (new classes of antibiotics) and diagnostics. In the latter category, the infectious disease has typically been diagnosed by the presence of the aetiological agent in clinical specimens directly by either microscopy, after culture or the presence of nucleic acids (DNA/ RNA), or antibodies or immune reactions that indicate a particular infection. Depending on the disease and infectious agent, there have been varying degrees of success. CD4 count and viral load is a good indicator of AIDS infection. However, in the case of paediatric tuberculosis diagnosis is very difficult primarily due to the low bacterial load of the causative agent Mycobacterium tuberculosis. With the availability of new technologies, there has been an increasing focus on identifying host biomarkers specific to a particular infection or a syndrome that is caused by a number of possible infectious agents. This is a natural extension to the extensive use of acute phase reactants such as C-reactive protein (CRP) that are indicative of infection but lack specificity. In addition, biomarkers are being sought that can indicate effectiveness of therapeutic regimens. This review will focus on a high throughput method to identify biomarkers for specific infectious diseases, syndromes caused by different microorganisms and/or monitoring therapy that is called surface-enhanced laser desorption/ionisation mass spectrometry (SELDI). It will focus on the technology, study design, sampling considerations and the advantages and disadvantages of its use. Emphasis will be given to papers published from January 2008 onwards, as the literature prior to this has been extensively reviewed [29, 34], and to examples of its use applied to infectious diseases that are particularly informative. Discussion has been restricted to clinical-based studies involving SELDI analysis of fluids or specific cell types from infected humans or animals. Such studies include those where there may have been sub-culture of cells from infected and/or controls. Only papers where samples are obtained from infected patients and controls, whether they be analysed directly or from cultured cells, will be considered. For the convenience of

readers, we have formulated a summary table of all of the studies discussed in this review in Section 13.9.