Cuamba I, Santano R, Grau-Pujol B, Vidal M, Aguilar R, et al.
BMC medicine •
Clearance of Plasmodium falciparum infection requires a T1 immune response with production of pro-inflammatory cytokines, IgG1, and IgG3 responses. In contrast, infections with helminths are dominated by T2/T immune responses characterized by production of anti-inflammatory cytokines, IgE, and IgG4, which could potentially interfere with malaria outcomes and immune responses. We recruited 441 malaria-symptomatic children aged 2-10 years attending two hospitals in the Manhiça District (Mozambique) and assessed infection by rapid antigen diagnostic test, microscopy, and/or quantitative PCR. Using Luminex, we measured concentrations of 30 cytokines and IgA, IgM, IgE, IgG, and IgG1-4 levels against 12 P. falciparum antigens and total IgE. Among 74 children diagnosed with malaria, 22% (16) were coinfected with STH, and 78% (58) had only P. falciparum. Soil-transmitted helminths (STH) coinfection associated with lower P. falciparum density (P = 0.005) and fever (P = 0.047). Coinfected children also had lower concentrations of plasma pro-inflammatory (IL-8, TNF, IFNα, IP-10, MCP1, MIG, MIP1β, and GM-CSF) and anti-inflammatory cytokines (IL-5, IL-10) (P < 0.05). Furthermore, antibody responses to a set of P. falciparum antigens, including SSP2 (IgG1, IgG4, IgG), PTRAMP (IgG3), MSP3 (IgG), RH5 (IgG1), and α-gal (IgG1), as well as total IgE, were elevated in STH coinfected children (P < 0.05). STH infections were associated with decreased P. falciparum parasitemia, downregulation of inflammatory cytokines, and enhanced antibody responses, potentially resulting in milder malaria episodes, suggesting enhanced protective immunity.
Shaker M, Wang J, Chu D, Anagnostou A, Greenhawt M
The journal of allergy and clinical immunology. In practice •
Sensitization to galactose-α-1,3-galactose (alpha-gal) can present with variable signs and symptoms. Although sensitization may be asymptomatic in a large proportion of individuals, in some it may present as alpha-gal syndrome (AGS) with risks for potentially fatal anaphylaxis if not managed appropriately. We conducted a health-economic evaluation of population screening to decrease the risk of fatal anaphylaxis from asymptomatic unrecognized alpha-gal sensitization. Markov models evaluated patients with asymptomatic sensitization comparing outcomes in patients identified to have sensitization through screening with those who did not undergo screening. Those with detected alpha-gal sIgE received prescriptions for self-administered epinephrine and were assumed to have a 10-fold decrease in the risk of anaphylaxis fatality. The model incorporated the associated disutility of food allergy diagnosis and allergic reactions, as well as costs of screening, emergency department evaluations, and hospitalizations. Probabilities and costs were derived from the medical literature. Population-level microsimulation evaluated 1% of the US population with outcomes considered over a 5-year treatment course. In the population microsimulation (n = 3,431,477 per arm), costs were greater in the population receiving screening ($2,683,565,074 [standard deviation, SD, $2150] vs $1,711,493,170 [SD $1976]) with lower quality-adjusted life years (QALYs) in the screened population (15,355,262 QALYs [SD 0.35] vs 15,795,107 [SD 0.27]). A no-screening approach was associated with $972,071,904 in savings, while improving health quality by 439,845 QALYs. Extrapolated to the entire US population, not screening (compared with screening) would result in savings that could exceed $90 billion and preserve over 40 million QALYs during the 5-year horizon. Screening could be cost-effective if the annual anaphylaxis risk exceeded 50% for high-risk populations in whom identification of sensitization decreased the frequency of anaphylaxis. General screening of asymptomatic populations to prevent fatal AGS would be a low-value practice, though in patients at very high risk for severe anaphylaxis, screening could be considered.
Essani NA, Fisher MA, Farhood A, Manning AM, Smith CW, et al.
Hepatology (Baltimore, Md.) •
Neutrophil-induced liver injury during endotoxemia is dependent on the adhesion molecule Mac-1 (CD11b/CD18) on neutrophils. The potential involvement of its counterreceptor, intercellular adhesion molecule-1 (ICAM-1), in the pathogenesis was investigated after administration of 100 micrograms/kg Salmonella abortus equi endotoxin (ET) in galactosamine-sensitized mice (Gal). In ET-sensitive mice (C3Heb/FeJ), which generated large amounts of tumor necrosis factor-alpha (TNF-alpha), massive neutrophil infiltration and severe liver injury were observed. In an ET-resistant strain (C3H/HeJ), which did not generate TNF-alpha Gal/ET failed to cause neutrophil accumulation or injury. ICAM-1 messenger RNA (mRNA), negligible in control livers, was selectively induced by Gal/ET in ET-sensitive mice. Intravenous injection of murine TNF-alpha, interleukin-1 alpha (IL-1 alpha) or IL-I beta (13 to 23 micrograms/kg) strongly induced the ICAM-1 message in both strains, showing a comparable capacity for ICAM-1 mRNA synthesis. All cytokines caused similar neutrophil accumulation in the liver; however, only Gal/TNF-alpha also caused upregulation of Mac-1 on circulating neutrophils and liver injury. The anti-murine ICAM-1 monoclonal antibody YN.1 (3 mg/kg) attenuated liver injury in ET-sensitive mice by 67% to 90% compared with isotype-matched control antibody-treated animals but did not reduce neutrophil accumulation in hepatic sinusoids. Our data suggest that the cytokines TNF-alpha and IL-1 are the main mediators responsible for upregulation of ICAM-1 mRNA in the liver during endotoxemia. The upregulation of both adhesion molecules, ICAM-1 and Mac-1, is necessary for a neutrophil-induced liver injury to occur. (ABSTRACT TRUNCATED AT 250 WORDS)