African histoplasmosis during HIV infection is rare.

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Optimal staging and evaluation of residual lesions of invasive fungal infections (IFIs) are major challenges in the immunocompromised host. Preliminary data have suggested that [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake may be observed in the course of active invasive fungal infections. The aim of this study was to assess the role of positron emission tomography with [¹⁸F]FDG ([¹⁸F]FDG-PET) in the diagnosis and staging of IFI. A prospective monocentric study evaluating [¹⁸F]FDG-PET in 30 consecutive adults and children with European Organization for Research and Treatment of Cancer/Mycoses Study Group probable or proven IFI was performed. Twenty males and ten females (median age, 45 years (range 6-7 years)) were enrolled. Twenty-six were immunocompromised, as follows: haematological malignancy (18) with allogeneic stem cell transplantation (16/18), solid tumour (three), solid organ transplantation (two), diabetes mellitus (two) and cystic fibrosis (one). IFIs were acute invasive aspergillosis (ten), chronic disseminated candidiasis (ten), zygomycosis (two), black grains eumycetoma (two), pulmonary Histoplasma capsulatum var. capsulatum histoplasmosis (two), and Phomopsis sp. osteoarthritis, Scedosporium apiospermum and Candida krusei spondylodiscitis, and acute pulmonary coccidioidomycosis in one case each. An increased uptake of [¹⁸F]FDG was observed in all areas previously identified by computed tomography and/or magnetic resonance imaging to be involved by IFI. In 4/10 chronic disseminated candidiasis cases, [¹⁸F]FDG-PET revealed small splenic abscesses that were unapparent on the corresponding computed tomography scan. [¹⁸F]FDG uptake disappeared after 6 months of antifungal therapy in three patients with chronic disseminated candidiasis for whom the [¹⁸F]FDG-PET was performed to assess the evolution of the disease. [¹⁸F]FDG-PET could potentially be useful for the initial diagnosis and staging of IFI. Whether or not [¹⁸F]FDG-PET might be useful for assessing the optimal duration of IFI therapy should now be assessed in a specific prospective study.

SummaryBackgroundApproximately 164,000 deaths yearly are due to shigellosis, primarily in developing countries. Thus, a safe and affordable Shigella vaccine is an important public health priority. The GSK Vaccines Institute for Global Health (GVGH) developed a candidate Shigella sonnei vaccine (1790GAHB) using the Generalized Modules for Membrane Antigens (GMMA) technology. The paper reports results of 1790GAHB Phase 1 studies in healthy European adults.MethodsTo evaluate the safety and immunogenicity profiles of 1790GAHB, we performed two parallel, phase 1, observer-blind, randomized, placebo-controlled, dose escalation studies in France (“study 1”) and the United Kingdom (“study 2”) between February 2014 and April 2015 (ClinicalTrials.gov, number NCT02017899 and NCT02034500, respectively) in 18–45 years old subjects (50 in study 1, 52 in study 2). Increasing doses of Alhydrogel adsorbed 1790, expressed by both O Antigen (OAg) and protein quantity, or placebo were given either by intramuscular route (0.059/1, 0.29/5, 1.5/25, 2.9/50, 5.9/100 μg of OAg/μg of protein; study 1) or by intradermal (ID), intranasal (IN) or intramuscular (IM) route of immunization (0.0059/0.1, 0.059/1, 0.59/10 μg ID, 0.29/5, 1.2/20, 4.8/80 μg IN and 0.29/5 μg IM, respectively; study 2). In absence of serologic correlates of protection for Shigella sonnei, vaccine induced immunogenicity was compared to anti-LPS antibody in a population naturally exposed to S. sonnei.FindingsVaccines were well tolerated in both studies and no death or vaccine related serious adverse events were reported. In study 1, doses ≥ 1.5/25 μg elicited serum IgG median antibody greater than median level in convalescent subjects after the first dose. No vaccine group in study 2 achieved median antibody greater than the median convalescent antibody.InterpretationIntramuscularly administered Shigella sonnei GMMA vaccine is well tolerated, up to and including 5.9/100 μg and induces antibody to the OAg of at least the same magnitude of those observed following natural exposure to the pathogen. Vaccine administered by ID or IN, although well tolerated, is poorly immunogenic at the doses delivered. The data support the use of the GMMA technology for the development of intramuscular multivalent Shigella vaccines.

HIV infects activated CD4 ؉ T cells and induces their depletion. Progressive HIV infection leading to AIDS is fueled by chronic immune hyperactivation, mediated by inflammatory cytokines like TNF␣. This has been related to intestinal epithelial damage and microbial LPS translocation into the circulation. Using 11-color flow cytometry, cell sorting, and cell culture, we investigated the numbers and TNF␣ production of fully defined circulating dendritic cell and monocyte populations during HIV-1 infection. In 15 viremic, untreated patients, compared with 8 treated, virologically suppressed patients or to 13 healthy blood donors, circulating CD141 (BDCA-3) ؉ and CD1c (BDCA-1) ؉ dendritic cell counts were reduced. Conversely, CD14 ؉ CD16 ؉؉ monocyte counts were increased, particularly those expressing M-DC8, while classical CD14 ؉؉ CD16 ؊ M-DC8 ؊ monocyte numbers were unchanged. Blood mononuclear cells from viremic patients produced more TNF␣ in response to LPS than those from virologically suppressed patients. M-DC8 ؉ monocytes were mostly responsible for this overproduction. Moreover, M-DC8 ؉ monocytes differentiated in vitro from classical monocytes using M-CSF and GM-CSF, which is increased in viremic patient's plasma. This M-DC8 ؉ monocyte population, which is involved in the pathogenesis of chronic inflammatory diseases like Crohn disease, might thus be considered as a major actor in the immune hyperactivation fueling HIV infection progression. (Blood. 2012;120(11): 2259-2268) IntroductionHIV-1 infection induces the depletion of CD4 ϩ T lymphocytes in blood and lymphoid organs, particularly in the gut-associated lymphoid tissue. [1][2][3] The absence of immune activation during the chronic phase of the infection distinguishes nonprogressive from progressive infections in patients as well as in nonhuman primate models of HIV infection. [4][5][6] Systemic immune activation is correlated to the increased translocation of gut luminal microbial products such as the Gram-negative bacterial lipopolysaccharide (LPS). 7 LPS stimulates the production of proinflammatory cytokines, particularly TNF␣. In HIV-1-infected patients, TNF␣ serum levels increase in correlation with disease progression and drop to normal levels after treatment only in patients with good virologic and immunologic responses. 3,8 By activating the NF-B pathway, TNF␣ induces viral replication in HIV-infected CD4 ϩ T lymphocytes. 3,9 In chronic inflammatory bowel diseases, TNF␣ affects mucosal integrity, leading to microbial product systemic translocation. 10 Granulocyte/macrophage colony-stimulating factor (GM-CSF) and LPS also induce HIV replication in infected myeloid cells. 11,12 GM-CSF and TNF␣ are produced by monocytes and dendritic cells (DCs) after LPS stimulation.During chronic HIV infection, circulating plasmacytoid and myeloid DC (pDC and mDC) numbers are reduced. [13][14][15] Myeloid DCs were mostly studied in HIV-infected patients using CD11c as a marker. Now, they are further subdivided into BDCA-1 ϩ and BDCA-3 ϩ mDC subsets, the latter r...

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