Providing health care in sub-Saharan Africa is a complex problem. Recent reports call for more resources to assist in the prevention and treatment of infectious diseases that affect this population, but policy makers, clinicians, and the public frequently fail to understand that diagnosis is essential to the prevention and treatment of disease. Access to reliable diagnostic testing is severely limited in this region, and misdiagnosis commonly occurs. Understandably, allocation of resources to diagnostic laboratory testing has not been a priority for resource-limited health care systems, but unreliable and inaccurate laboratory diagnostic testing leads to unnecessary expenditures in a region already plagued by resource shortages, promotes the perception that laboratory testing is unhelpful, and compromises patient care. We explore the barriers to implementing consistent testing within this region and illustrate the need for a more comprehensive approach to the diagnosis of infectious diseases, with an emphasis on making laboratory testing a higher priority.

Neutrophils are highly specialized innate effector cells that have evolved for killing of pathogens. Human neonates have a common multifactorial syndrome of neutrophil dysfunction that is incompletely characterized and contributes to sepsis and other severe infectious complications. We identified a novel defect in the antibacterial defenses of neonates: inability to form neutrophil extracellular traps (NETs). NETs are lattices of extracellular DNA, chromatin, and antibacterial proteins that mediate extracellular killing of microorganisms and are thought to form via a unique death pathway signaled by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-generated reactive oxygen species (ROS). We found that neutrophils from term and preterm infants fail to form NETs when activated by inflammatory agonists-in contrast to leukocytes from healthy adults. IntroductionPolymorphonuclear leukocytes (PMNs, neutrophils) are highly specialized cellular effectors in host defense and immune surveillance. Mature human PMNs from healthy adults have a unique repertoire of activities, including phagocytosis, degranulation of antimicrobial enzymes and peptides, and generation of oxygen radicals with antimicrobial properties. 1-6 Synthesis of inflammatory and regulatory lipids and proteins complements these innate mechanisms. 1,4,5 PMNs have evolved for capture, containment, and destruction of bacteria and fungi and also have activity against intracellular pathogens and viruses. 2,3 PMNs have additional important roles in tissue repair and integration of innate and adaptive immune responses. 6 If, however, these specialized defensive mechanisms become dysregulated or unregulated, PMNs can paradoxically be mediators of inflammatory tissue injury. 1,6 Consistent with their requisite activities in host defense, defects in PMN functions cause immune deficiency syndromes. 2,7 Neutrophil defects can be hereditary, developmental, or acquired in nature. Specific genetic deficiencies in PMN function cause significant morbidity in subsets of children and adults and, in parallel, provide unique insights into molecular mechanisms that regulate leukocyte activities. 7,8 Nevertheless, these disorders are rare and arcane. In contrast, the developmental syndrome of neonatal neutrophil dysfunction, which is particularly important in premature infants, is common and contributes to infections in infants worldwide. As an example, neonatal PMN dysfunction is thought to be a pivotal feature of sepsis in the newborn. 9-11 The incidence of neonatal sepsis is estimated to be 1 to 5 cases per 1000 live births in the United States and to be even higher after very low birth weight premature deliveries (15-19/1000); in contrast, the incidence of sepsis is much lower in children older than 1 year of age and in young adults. 12-15 Furthermore, the incidence of neonatal sepsis is as high as 25% in some areas of the developing world. 16,17 Thus, neonatal PMN dysfunction is a contributor to a public health problem of significant proportions, and also may pr...

13The identification of fungal species and determination of their significance in the clinical laboratory are complex practices that help establish or exclude a fungal cause of disease. In the past, the clinical mycologist utilized a limited array of phenotypic measurements for categorizing isolates to the species level. This scenario is shifting in favor of molecular identification strategies largely due to a combination of several factors: (i) the changing landscape of epidemiology of medically important fungi, in which novel organisms never before implicated in human infection are being reported from clinical samples (10, 41); (ii) reports of species-specific differences in antifungal susceptibilities of these newly recognized fungi (4, 10, 41); (iii) numerous studies demonstrating that morphology alone may not be a sufficiently objective method for species determination (7,8,10,23,41); and (iv) a growing scarcity of bench scientists and microbiologists trained in traditional mycology. With the increasing incidence of fungal infections and reports of invasive fungal infections in nontraditional populations, such as patients with critical illnesses, the onus is on the clinical microbiologist/mycologist to return a timely and accurate identification. Molecular methods are rapid with a turnaround time of about 24 h from the time of DNA extraction, yield results that are objective with data portable between labs, and could be more economical in the long run.Few topics are more controversial or evoke such a passionate response as the term "species" to a mycologist. Molecular studies have demonstrated that a strategy where multiple genes (or portions thereof) are sequenced and the resultant data are analyzed by phylogenetic methods is a robust strategy for fungal species recognition. This concept, known as phylogenetic species recognition (PSR) (40), has been used successfully to define species in the genera Fusarium and Aspergillus (8,23,29,31,32). The advent of PSR has greatly clarified the taxonomy of these genera and as such is a powerful tool for fungal species delimitation. However, this methodology is expensive and requires phylogenetic expertise, which may be limiting factors in clinical microbiology laboratories. In reality, once a species has been delimited by PSR using several robust loci, sequence diversity within the species is known, and on the basis of this knowledge, comparative sequence analyses from a single locus can be used for rapid species identification. "Cutoff scores," which are dependent on genetic diversity within and between sibling species, can then be provided.Thus, it is important to clarify that our intent in this editorial is to address the practice of species "identification" as applied to a clinical setting and not species "classification" necessary for taxonomic categorization. Although the two terms can be overlapping, the purpose of an "identification" method in a clinical microbiology laboratory is the ability to provide a specific name or epithet to an organism rapidly and wi...

Laboratory diagnosis of influenza is critical to its treatment and surveillance. With the emergence of novel and highly pathogenic avian influenza viruses, the role of the laboratory has been further extended to include isolation and subtyping of the virus to monitor its appearance and facilitate appropriate vaccine development. Recent progress in enhancing testing for influenza promises to both improve the management of patients with influenza and decrease associated health care costs. The present review covers the technological characteristics and utilization features of currently available diagnostic tests, the factors that influence the selection of such tests, and the developments that are essential for pandemic preparedness.