Patient-centred screening for primary immunodeficiency: a multi-stage diagnostic protocol designed for non-immunologists.

Efficient early identification of primary immunodeficiency disease (PID) is important for prognosis, but is not an easy task for non-immunologists. The Clinical Working Party of the European Society for Immunodeficiencies (ESID) has composed a multi-stage diagnostic protocol that is based on expert opinion, in order to increase the awareness of PID among doctors working in different fields. The protocol starts from the clinical presentation of the patient; immunological skills are not needed for its use. The multi-stage design allows cost-effective screening for PID within the large pool of potential cases in all hospitals in the early phases, while more expensive tests are reserved for definitive classification in collaboration with an immunologist at a later stage. Although many PIDs present in childhood, others may present at any age. The protocols presented here are therefore aimed at both adult physicians and paediatricians. While designed for use throughout Europe, there will be national differences which may make modification of this generic algorithm necessary.

How a different look at latency can help to develop novel diagnostics and vaccines against tuberculosis.

Mycobacterium tuberculosis is one of the most successful human pathogens. It kills every year approximately 1.5 - 2 million people, and at present a third of the human population is estimated to be infected. Fortunately, only a relatively small proportion of the infected individuals will progress to active disease, and most will maintain a latent infection. Although a latent infection is clinically silent and not contagious, it can reactivate to cause highly contagious pulmonary tuberculosis, the most prevalent form of the disease in adults. Therefore, a thorough understanding of latency and reactivation may help to develop novel control strategies against tuberculosis. The most widely held view is that the mycobacteria are imprisoned in granulomatous structures during latency, where they can survive in a non-replicating, dormant form until reactivation occurs. However, there is no hard data to sustain that the reactivating mycobacteria are indeed those that laid dormant within the granulomas. In this review an alternative model, based on evidence from early studies, as well as recent reports is presented, in which the latent mycobacteria reside outside granulomas, within non-macrophage cell types throughout the infected body. Potential implications for new diagnostic and vaccine design are discussed.