Nonlethal Plasmodium yoelii Infection Drives Complex Patterns of Th2-Type Host Immunity and Mast Cell-Dependent Bacteremia.

Malaria strongly predisposes to bacteremia, which is associated with sequestration of parasitized red blood cells and increased gastrointestinal permeability. The mechanisms underlying this disruption are poorly understood. Here, we evaluated the expression of factors associated with mast cell activation and malaria-associated bacteremia in a rodent model. C57BL/6J mice were infected with Plasmodium yoeliiyoelli 17XNL, and blood and tissues were collected over time to assay for circulating levels of bacterial 16S DNA, IgE, mast cell protease 1 (Mcpt-1) and Mcpt-4, Th1 and Th2 cytokines, and patterns of ileal mastocytosis and intestinal permeability. The anti-inflammatory cytokines (interleukin-4 [IL-4], IL-6, and IL-10) and MCP-1/CCL2 were detected early after P. yoeliiyoelii 17XNL infection. This was followed by the appearance of IL-9 and IL-13, cytokines known for their roles in mast cell activation and growth-enhancing activity as well as IgE production. Later increases in circulating IgE, which can induce mast cell degranulation, as well as Mcpt-1 and Mcpt-4, were observed concurrently with bacteremia and increased intestinal permeability. These results suggest that P. yoeliiyoelii 17XNL infection induces the production of early cytokines that activate mast cells and drive IgE production, followed by elevated IgE, IL-9, and IL-13 that maintain and enhance mast cell activation while disrupting the protease/antiprotease balance in the intestine, contributing to epithelial damage and increased permeability.

Hookworm Infection in South American Fur Seal ( Arctocephalus australis) Pups.

Tissues of South American fur seal pups naturally infected with hookworms ( Uncinaria sp) were examined. Hookworm infection was found in nearly all pups examined (132/140, 94%), and hookworm enteritis with secondary bacteremia was considered the cause of death in 46 (35%) pups. Common findings in these pups included severe hemorrhagic enteritis and numerous (mean intensity = 761.8) hookworms in the jejunum. Hookworms were recovered from the abdominal cavity in 12 of 55 pups (22%) examined through peritoneal wash; these pups had an average of 1343.3 intestinal hookworms and marked fibrinohemorrhagic peritonitis. In all pups that died as a consequence of hookworm infection, the intestinal villi were short, blunt, and fused, and there were variable numbers of free and intrahistiocytic gram-negative bacteria in submucosal hookworm feeding tracks, mesenteric lymph nodes, spleen, blood vessels, and liver sinusoids. Pups that died of causes unrelated to the hookworm infection (trauma) had hookworm feeding tracks confined to the apical portions of the mucosa, and moderate to marked catarrhal eosinophilic enteritis. The number of hookworms was negatively correlated with intestinal villous length and number of leukocytes in the intestine. Pups with hookworm peritoneal penetration had nematodes with little or no blood in the hookworm intestine, suggesting that lack of food for the nematode could be associated with peritoneal penetration. Findings suggest that the initial burden of larval infection, the level of the host tissue response, or a combination determine the number of nematodes in the intestine, the severity of hookworm tissue damage, and pup mortality.

Reduced Parasite Burden in Children with Falciparum Malaria and Bacteremia Coinfections: Role of Mediators of Inflammation.

Bacteremia and malaria coinfection is a common and life-threatening condition in children residing in sub-Saharan Africa. We previously showed that coinfection with Gram negative (G[-]) enteric Bacilli and Plasmodium falciparum (Pf[+]) was associated with reduced high-density parasitemia (HDP, >10,000 parasites/µL), enhanced respiratory distress, and severe anemia. Since inflammatory mediators are largely unexplored in such coinfections, circulating cytokines were determined in four groups of children (n = 206, aged <3 yrs): healthy; Pf[+] alone; G[-] coinfected; and G[+] coinfected. Staphylococcus aureus and non-Typhi Salmonella were the most frequently isolated G[+] and G[-] organisms, respectively. Coinfected children, particularly those with G[-] pathogens, had lower parasite burden (peripheral and geometric mean parasitemia and HDP). In addition, both coinfected groups had increased IL-4, IL-5, IL-7, IL-12, IL-15, IL-17, IFN-γ, and IFN-α and decreased TNF-α relative to malaria alone. Children with G[-] coinfection had higher IL-1ß and IL-1Ra and lower IL-10 than the Pf[+] group and higher IFN-γ than the G[+] group. To determine how the immune response to malaria regulates parasitemia, cytokine production was investigated with a multiple mediation model. Cytokines with the greatest mediational impact on parasitemia were IL-4, IL-10, IL-12, and IFN-γ. Results here suggest that enhanced immune activation, especially in G[-] coinfected children, acts to reduce malaria parasite burden.

Systemic toxoplasmosis and Gram-negative sepsis in a southern chamois (Rupicapra pyrenaica) from the Pyrenees in northeast Spain.

A 6-year-old, male southern chamois (Rupicapra pyrenaica) had an absence of flight response and was captured by hand in the Catalan Pyrenees in northeast Spain. On clinical examination, the animal was in good body condition, and only atrophy of the right eye was observed. Blood samples were collected and hematologic analysis performed, but no alterations were observed. The animal was sent to a Wildlife Rescue Centre, where it developed chronic wasting and died after 32 days in captivity. At necropsy, the animal was cachectic and had edematous, mottled lungs. Histopathologic examination revealed systemic toxoplasmosis and acute Gram-negative septicemia. The protozoan organisms were identified as Toxoplasma gondii based on immunohistochemistry. An indirect fluorescent antibody test was performed, and the animal was positive with an antibody titer of 150.

Antimicrobial resistance predicts death in Tanzanian children with bloodstream infections: a prospective cohort study.

BACKGROUND: Bloodstream infection is a common cause of hospitalization, morbidity and death in children. The impact of antimicrobial resistance and HIV infection on outcome is not firmly established. METHODS: We assessed the incidence of bloodstream infection and risk factors for fatal outcome in a prospective cohort study of 1828 consecutive admissions of children aged zero to seven years with signs of systemic infection. Blood was obtained for culture, malaria microscopy, HIV antibody test and, when necessary, HIV PCR. We recorded data on clinical features, underlying diseases, antimicrobial drug use and patients' outcome. RESULTS: The incidence of laboratory-confirmed bloodstream infection was 13.9% (255/1828) of admissions, despite two thirds of the study population having received antimicrobial therapy prior to blood culture. The most frequent isolates were klebsiella, salmonellae, Escherichia coli, enterococci and Staphylococcus aureus. Furthermore, 21.6% had malaria and 16.8% HIV infection. One third (34.9%) of the children with laboratory-confirmed bloodstream infection died. The mortality rate from Gram-negative bloodstream infection (43.5%) was more than double that of malaria (20.2%) and Gram-positive bloodstream infection (16.7%). Significant risk factors for death by logistic regression modeling were inappropriate treatment due to antimicrobial resistance, HIV infection, other underlying infectious diseases, malnutrition and bloodstream infection caused by Enterobacteriaceae, other Gram-negatives and candida. CONCLUSION: Bloodstream infection was less common than malaria, but caused more deaths. The frequent use of antimicrobials prior to blood culture may have hampered the detection of organisms susceptible to commonly used antimicrobials, including pneumococci, and thus the study probably underestimates the incidence of bloodstream infection. The finding that antimicrobial resistance, HIV-infection and malnutrition predict fatal outcome calls for renewed efforts to curb the further emergence of resistance, improve HIV care and nutrition for children.

[Small bowel obstruction secondary to massive hookworm infestation complicated by fatal plurimicrobial bacteriemia]. / Occlusion iléale par infestation massive par des ankylostomes responsable d'une septicémie plurimicrobienne d'évolution fatale.

INTRODUCTION: Intestinal symptoms (cramping, flatulence) and iron deficient anemia are classical presenting manifestations of duodenal hookworm infestation in patients living in endemic area. CASE REPORT: We report a 45-year-old immunocompetent metropolitan man who presented with intestinal obstruction secondary to massive hookworm infestation complicated by fatal plurimicrobial bacteriemia with refractory septic shock. CONCLUSION: We report a case of acute surgical abdominal presentation with septicemia and refractory shock syndrome due to ileal translocation secondary to massive hookworm infestation. To the best of our knowledge, such a case has not yet been reported.

Bacteroides-associated pylephlebitis in a patient with strongyloidiasis.

Strongyloidiasis is associated with Gram-negative bacteremia. Septic portal vein thrombosis or pylephlebitis is a rare but serious complication of intra-abdominal infection, and it is often associated with Bacteroides bacteremia. We present the first report of pylephlebitis with Bacteroides bacteremia associated with underlying Strongyloides stercoralis infection and briefly review the management of septic portal vein thrombosis.

[Shrews as a Borrelia reservoir in northwestern Russia]. / Zemleroiki kak rezervuar borrelii na Severo-Zapade Rossii.

The borreliemia was discovered in 22 (44.9%) of 49 common shrews (Sorex araneus, Soricidae), which were captured in the end of July-August 1995 in the Novgorod Province. The borreliae were located near the capillaries of the true skin and in the veins of the subcutaneous layer.

[Borreliosis in laboratory rabbits]. / Borrelioz laboratornykh krolikov.

The borreliosis of laboratorian rabbits displays as a chronic infection with recurrences during a spring-autumn season. The clinical picture includes a skin-ulcerous lesion, arthritis accompanied by lymphocytosis and borreliemia.

MyD88 deficiency enhances acquisition and transmission of Borrelia burgdorferi by Ixodes scapularis ticks.

Borrelia burgdorferi strains exhibit various degrees of infectivity and pathogenicity in mammals, which may be due to their relative ability to evade initial host immunity. Innate immune cells recognize B. burgdorferi by Toll-like receptors (TLRs) that use the intracellular molecule MyD88 to mediate effector functions. To determine whether impaired TLR signaling enhances Ixodes scapularis acquisition of B. burgdorferi, we fed nymphs on wild-type (WT) and MyD88-/- mice previously infected with two clinical isolates of B. burgdorferi, BL206, a high-virulence strain, and B348, an attenuated strain. Seventy-three percent of the nymphs that fed on BL206-infected WT mice and 40% of the nymphs that fed on B348-infected WT mice acquired B. burgdorferi, whereas 100% of the nymphs that fed on MyD88-/- mice became infected, irrespective of B. burgdorferi strain. Ticks that acquired infection after feeding on MyD88-/- mice harbored more spirochetes than those that fed on WT mice, as assessed by quantitative PCR for B. burgdorferi DNA. Vector transmission of BL206 and B348 was also enhanced when MyD88-/- mice were the blood meal hosts, with the mean pathogen burden at the skin inoculation site significantly higher than levels in WT mice. These results show that the absence of MyD88 facilitates passage of both low- and high-infectivity B. burgdorferi strains between the tick vector and the mammal and enhances the infectivity of a low-infectivity B. burgdorferi strain.