Management of listeriosis.

Determination of the MIC in vitro is often used as the basis for predicting the clinical efficacy of antibiotics. Listeriae are uniformly susceptible in vitro to most common antibiotics except cephalosporins and fosfomycin. However, the clinical outcome is poor. This is partially because listeriae are refractory to the bactericidal mechanisms of many antibiotics, especially to ampicillin-amoxicillin, which still is regarded as the drug of choice. A true synergism can be achieved by adding gentamicin. Another point is that listeriae are able to reside and multiply within host cells, e.g., macrophages, hepatocytes, and neurons, where they are protected from antibiotics in the extracellular fluid. Only a few agents penetrate, accumulate, and reach the cytosol of host cells, where the listeriae are found. Furthermore, certain host cells may exclude antibiotics from any intracellular compartment. Thus, determination of the antibacterial efficacy of a drug against listeriae in cell cultures may be a better approximation of potential therapeutic value. Certain host cells may have acquired the property of excluding certain antibiotics, for example macrolides, from intracellular spaces, which might explain therapeutic failures of antibiotic therapy in spite of low MICs. Animal models do not completely imitate human listeriosis, which is characterized by meningitis, encephalitis, soft tissue and parenchymal infections, and bacteremia. Meningitis produced in rabbits is a hyperacute disease, whereby most listeriae lie extracellularly, fairly accessible to antibiotics that can cross the blood-cerebrospinal fluid barrier. In the murine model of systemic infection, Listeria monocytogenes is located mainly within macrophages and parenchymal cells of the spleen and liver, hardly accessible to certain drugs, such as ampicillin and gentimicin. The therapeutic efficacy of drugs clearly depends on the model used. Thus, for example, the combination of ampicillin with gentamicin acts synergistically in the rabbit meningitis model but not in the mouse model. Since conventional antimicrobial therapy with antibiotics is not satisfactory, particularly in the immunocompromised host (about 30% of patients with listeriosis die in spite of a rational choice of antibiotics), other possibilities must be considered for therapy as well as prevention. Indeed, listeriae are highly susceptible to several endogenous antibiotics, such as defensins. Bacteriocins produced by related bacterial species, e.g., lactobacilli and enterococci, are rapidly bactericidal. However, unfortunately, the use of such alternative measures along with immunization and immunmodulation is not yet feasible.     

Colony-stimulating factor 1 in the human response to neonatal listeriosis.

Immunity to Listeria monocytogenes, an important pathogen in human neonatal sepsis, is mediated by mononuclear phagocytes, which are regulated by the hematopoietic growth factor colony-stimulating factor 1. Neonates with listeriosis had higher circulating colony-stimulating factor 1 levels and subsequent monocyte counts than those of both noninfected newborns and newborns infected with nonlisterial organisms.     

Epidemiology of human reproduction

This study on the epidemiology of human fertility emphasizesthe study and analysis of several parameters. These include:(a) the measure and distribution of fertility. The incidenceof sterility is low (3–5% of couples) and the fecundabilityof fertile couples is {small tilde}30% per cycle. Approximately7% of newly-formed couples per year will undergo complex treatmentfor infertility. (b) The results of clinical and diagnosticexplorations. Among infertile couples, the woman is responsiblein {small tilde}60% of cases, and the man in {small tilde}25%of cases, and both of these factors may be associated. Clinicaland diagnostic explorations are negative in {small tilde}18%of couples and the infertility is termed idiopathic. (c) ‘Normal’sperm characteristics vary according to age, seasonal or environmentalfactors, (d) Female factors varying as a function of age, menstrualcycle, ovulation and functional status of the genital organs.(e) Infertility in both partners leads to specific difficultiesfor epidemiological analyses, where the base unit is not anindividual.     

Epidemiology of human metapneumovirus

Since the discovery of human metapneumovirus (hMPV) in 2001, the virus has been identified worldwide. hMPV is a common respiratory pathogen, particularly in infants and young children. The virus is associated with both upper and lower respiratory tract infections and may be a trigger for asthma. At least two major genotypes of hMPV circulate during community outbreaks. Whether these genotypes represent distinct serotypes remains controversial. The major challenges faced by the medical and scientific communities are the understanding of the pathogenesis of hMPV disease and the development of a safe and effective vaccine to protect against infection and disease caused by this newly recognized respiratory virus.     

An unusual case of cutaneous listeriosis.

Listeria monocytogenes was identified as the etiological agent in the cutaneous and febrile illness of a 64-year-old male who acquired the organism as a result of contact with the genital tract of a cow while assisting in the delivery of a stillborn calf.     

Nitric oxide produced during murine listeriosis is protective.

Nitric oxide (NO) has been shown to be important for intracellular microbiostasis in vitro. To determine the role of NO in immune function in vivo, groups of C57BL/6 mice were given a sublethal intravenous inoculum of Listeria monocytogenes EGD, and their urine was monitored daily for nitrate, the mammalian end product of NO metabolism. Urinary nitrate levels peaked at 5 to 10 times the basal level on days 5 to 6, when spleen and liver Listeria counts declined most steeply, and decreased thereafter, when spleens and livers were nearly sterile. Peritoneal macrophages explanted from Listeria-infected mice produced nitrite spontaneously, whereas macrophages from uninfected mice did not. The inducible NO synthase mRNA was detectable in the spleens of infected mice on days 1 to 4 of infection. When Listeria-infected mice were treated orally throughout the infection with NG-monomethyl-L-arginine (NMMA), a specific NO synthase inhibitor they showed no detectable rise in urinary nitrate excretion. Mean Listeria counts in the livers and spleens NMMA-treated mice were 1 to 3 orders of magnitude greater than counts in control mice on days 4 through 8 of infection. Compared with control mice, NMMA-treated mice also showed worse clinical signs of infection, namely, weight loss, hypothermia, decreased food and water intake, and decreased urine output. Histologically NMMA-treated mice had many more inflammatory foci in their livers and spleens than control mice. The histologic observation that mononuclear cells are present at sites of infection suggests that inhibiting NO production did not block the flux of macrophages into infected viscera. As controls for possible drug toxicity, a group of uninfected mice given NMMA orally showed no detrimental effects on weight, temperature, and food and water intake. These experiments demonstrate that inhibition of NO production in Listeria-infected mice results in an exacerbated infection and thus that NO synthesis is important for immune defense against Listeria infection in mice.     

Interleukin-4 and listeriosis

Summary: Experimental infection of mice with Listeria monocytogenes (L. monocytogenes) has served as an appropriate model for analyzing Thl nil driven immune responses. Generally, Th2 responses are absent and IL-4 is not detectable. Here, we describe experimental settings under which IL-4 is detectable in listeriosis. Our data suggest that IL-4 is rapidly produced after infection. This prompt IL-4 burst seems to stimulate chemokine responses and, therefore, may participate in the regulation of the early antilisterial host response. Soon thereafter, lL-4 production wanes. At least partially this seems to be caused by downregulation of IL-4–producing CD4+ NK1+ TCRαβ^int lymphocytes by IL-12. In the absence of IFN-γ responsiveness, IL-4 production is demonstrable during acquired immunity against L. monocytogenes, and this elevated IL-4 production apparently contributes to disease exacerbation. In conclusion, the data are consistent with a detrimental role of IL-4 in listeriosis and active control of IL-4 synthesis by the antilisterial immune response. The rapid, but transient, IL-4 burst in listeriosis probably contributes to host defense without impairing development of the acquired T-cell response because of its shortness.     

Immunohistologic diagnosis of avian listeriosis

Listeriosis in a chicken from a small farm was diagnosed by the per-oxidase-antiperoxidase (PAP) method. The animal had diffuse myocarditis and necrotic foci in the liver and in the spleen. PAP technique performed on formalin-fixed tissues confirmed the presumptive diagnosis. Serological and microbiological studies were also done. It is concluded that PAP method is useful for the diagnosis of avian listeriosis allowing retrospective studies with formalin-fixed, paraffin-embedded tissues, avoiding cumbersome microbiological culture.     

Epidemic perinatal listeriosis at autopsy

Seven cases of listeriosis identified at perinatal autopsy are described. The cases occurred during the time of a 1985 Los Angeles, California, epidemic of listeriosis from suspected food contamination by Listeria monocytogenes. In only one of seven cases were gross pathologic lesions encountered. Microscopic lesions in six cases consisted of rare, localized microabscesses or granuloma-like lesions in multiple organs and contained histiocytes, monocytes, lymphocytes, and polymorphonuclear leukocytes with variable necrosis. One case had no gross or microscopic findings. Organomegaly was uncommon. The diagnosis was confirmed in three cases by postmortem blood culture. Complete perinatal autopsy is important for confirmation of listeriosis when microbiologic, gross, or microscopic findings alone may not yield characteristic features.     

Morphology and time course of experimental listeriosis in nude mice.

Experimental listeriosis in phenotypically normal (nu/+) euthymic NMRI mice has a characteristic morphology and short-term course. In contrast, listeric infection in congenitally dysthymic nude (nu/nu) mice does not proceed in clear-cut phases, develops more slowly, displays a chronic tendency from the beginning, and shows a considerably different morphology. The inability of nude mice to effectively control and terminate infection by Listeria monocytogenes obviously results from the lack of T lymphocytes.