Galleria mellonella: An invertebrate model to study pathogenicity in correctly defined fungal species.

The high mortality rates and economic burden associated with fungal infections, plus the emergence of fungal strains resistant to antifungal drugs, make it necessary to get a deeper understanding of fungal pathogenesis, as well as to identify new target structures for antifungal drug development. Still, murine models are considered as the gold standard for studying pathogenesis, quantifying virulence, and analysing the efficacy of antifungal drugs. However, invertebrates, such as the larvae of the greater wax moth Galleria mellonella, are promising alternative hosts to address some of these questions, especially when a large number of fungal strains need to be evaluated. The purpose of this review is to summarize the benefits and drawbacks, explain the utilization of the invertebrate model host G. mellonella, and compare the virulence potential of the most important human fungal pathogens, with the focus on different virulence potential of closely related species.

Noncongenital central nervous system infections in children: radiology review.

Infections of the central nervous system (CNS) are a very common worldwide health problem in childhood with significant morbidity and mortality. In children, viruses are the most common cause of CNS infections, followed by bacterial etiology, and less frequent due to mycosis and other causes. Noncomplicated meningitis is easier to recognize clinically; however, complications of meningitis such as abscesses, infarcts, venous thrombosis, or extra-axial empyemas are difficult to recognize clinically, and imaging plays a very important role on this setting. In addition, it is important to keep in mind that infectious process adjacent to the CNS such as mastoiditis can develop by contiguity in an infectious process within the CNS. We display the most common causes of meningitis and their complications.

Invasive mould infections in newborns and children.

Invasive mould infections represent important complications of different pediatric conditions. Epidemiology and clinical features vary according to the type of underlying conditions that determine the risk of invasive mycosis. No pediatric study has specifically evaluated the efficacy of prophylaxis or therapy invasive moulds infections, while pediatric dosages for the treatment of invasive aspergillosis are available for drugs that produced positive results in clinical trials undertaken in adults.

Antifungal prophylaxis in neonates.

Fungal-related morbidity and mortality is a major concern for most neonatal intensive care units (NICUs) worldwide. Incidence rates are increasing and might be higher than reported due to the challenges associated with diagnosing fungal infections. As preterm neonates display clinical characteristics that make them prone to Candida spp infections, and there is a high frequency of severe neurodevelopmental sequelae in those who survive neonatal fungal infections, specific prevention--rather than empiric or pre-emptive treatment--should be the optimal strategy. Besides stewardship of drug use and efforts to minimize invasive cares, pharmacological prevention with use of fluconazole has proved highly effective in decreasing the rates of fungal sepsis in very low birth weight (VLBW) neonates. Alternative options needing further and more conclusive assessments include use of nystatin, bovine lactoferrin or probiotics.

Role of echinocandins in the management of fungal infections in neonates.

As the incidence rates of neonatal systemic fungal infections (SFI) have been increasing over the last years, research efforts have been addressed towards identifying both effective preventative strategies, and efficacious and well-tolerated antifungal drugs. Historically, the first options in treatment of neonatal SFI have been – and currently are – fluconazole and amphotericin B. However, these two drugs carry limitations both in efficacy and in putative toxicity. Recently, new therapeutic alternatives have drawn the neonatologists' attention. Echinocandins are a new class of antifungal drugs with characteristics that might better meet the needs of this particular population of patients. Caspofungin (CSP), micafungin (MICA), and anidulafungin have inherent good activities both against biofilms, and against natively fluconazole-resistant strains of Candida spp, thus overcoming two of the major weaknesses of the commonly used antifungal drugs in nurseries. CSP and MICA have been recently studied in neonatal populations. The kinetics and appropriate dosing of this agent in premature and term infants have been described, but ongoing further studies are needed to better address this area. Case-report series show clinical efficacy and tolerability in critical neonatal patients given CSP and MICA. In addition, extrapolation of data from randomized trials conducted in pediatric and adult patients showed through a subgroup analysis that both CSP and MICA are effective and well tolerated also in neonates. Further studies properly designed for neonatal populations will better address long-term safety and ecological issues related to echinocandin use in neonates.

[The immune response to fungal infections]. / Odpowiedz immunologiczna na zarazenie grzybami.

In mycoses congenital--nonspecific innate as well as acquired immunity (involving neutrophiles, monocytes, macrophages, dendritic cells and lymphocytes) both play important roles in host defence. Th1 lymphocytes release cytokines (IL-2, IL-12, IFN gamma) and stimulate cytotoxic cells and neutrophiles to destroy fungal cells. Th2 lymphocytes, on the other hand, suppress cellular immunity by releasing the cytokines IL-4, IL-6 and IL-10 which counter regulate the secretion of IL-2, IL-12, IFN gamma and depress the activity of macrophages. Cellular mechanisms play essential roles in host responses to fungal infections. Dysfunction of T lymphocytes and a reduction in their number are typically observed in patients with mycotic diseases. There occurs a reduction of both T lymphocyte populations and the T-helper to T-suppressor cell number ratio, and these are of critical importance in explaining the diminished IgA production and enhanced adhesion of fungal cells to the surface of host cells as well as in facilitating the intrusion of fungi throughout the skin and mucous membranes. The specific immunological reaction, associated with the synthesis of antibodies against fungal cell wall or cytoplasmic antigens, is of little significance in protective immunity, but nevertheless has a rather important role to play in diagnosis as well as in supporting phagocytosis by inhibition of fungal cell adherence. In patients with mycoses, typically low blood serum level of the immunoglobulin class G and A and low sIgA in saliva are observed. A detailed understanding the nature and function of the immune system in mycoses is necessary to enable improvements in pharmacotherapy with antifungal antibiotics and chemotherapeutics, as well as to treatments based on immunotherapy and vaccination.

Systemic fungal infections in neonates.

Systemic fungal infections, previously considered to be a rare complication, are now frequently diagnosed in VLBW infants receiving intensive care. Confirming the diagnosis by laboratory tests is difficult and a high index of suspicion is required. Prompt and aggressive use of antifungal treatment is justified in a clinically septic neonate, especially those with a raised serum concentration of C reactive protein, who do not show a satisfactory response to antibiotics. The newer generation of liposomal amphotericin and azole antifungal drugs appear to be safe, effective, and well tolerated. With increasing awareness, prompt treatment, and better neonatal intensive care, the outcome of systemic fungal infection in preterm infants should improve.

[Acute bacterial and fungal neonatal meningitis]. / Méningites néonatales aiguës bactériennes et fongiques.

Neonatal meningitis has two closely related features: the mechanism of infection and the nature of the pathogen. When transmitted from mother to foetus, the infection is mainly caused by one of three microorganisms: Streptococcus group B, Escherichia coli or Listeria monocytogenes. It may occur before birth, in which case meningitis is of early onset and has a rather poor prognosis. When it occurs later, the infection is a pathological consequence of physiological bacterial colonization, and its symptoms and prognosis are those of post-natal meningitis. Post-natal infections are facilitated by a pre-existing pathology or by prematurity. The responsible organisms (Gram-positive or Gram-negative bacteria, or yeasts) are often multiresistant. Advances in biology provide increasingly clearer explanation of the cerebral complications that determine the medium- and long-term prognosis. The variety of organisms and their frequent resistance to antibacterials make it necessary to use antibiotics that possess an exceptionally broad spectrum.

Congenital Torulopsis glabrata infection in man.

A case of congenital infection by Torulopsis glabrata in a premature 0.52-kg female infant born at 23 weeks' gestation to a 37-year-old, gravida 7 mother is reported. The infant succumbed to an intrauterine pneumonia and fungemia. Acute chorioamnionitis was present. Budding yeasts were found in the lungs and amniotic membranes and in large numbers within the lumen of the gut. The role of a retained intrauterine contraceptive device in predisposing to the ascending infection is discussed.