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Aims: To elucidate the diagnostic value of sarcoplasmic expression of myxovirus resistance protein A (MxA) for dermatomyositis (DM) specifically analysing different DM subforms, and to test the superiority of MxA to other markers. Methods: Immunohistochemistry for MxA and retinoic acid‐inducible gene I (RIG‐I) was performed on skeletal muscle samples and compared with the item presence of perifascicular atrophy (PFA) in 57 DM patients with anti‐Mi‐2 (n = 6), ‐transcription intermediary factor 1 gamma (n = 10), ‐nuclear matrix protein 2 (n = 13), ‐melanoma differentiation‐associated gene 5 (MDA5) (n = 10) or ‐small ubiquitin‐like modifier activating enzyme (n = 1) autoantibodies and with no detectable autoantibody (n = 17). Among the patients, nine suffered from cancer and 22 were juvenile‐onset type. Disease controls included antisynthetase syndrome (ASS)‐associated myositis (n = 30), immune‐mediated necrotizing myopathy (n = 9) and inclusion body myositis (n = 5). Results: Sarcoplasmic MxA expression featured 77% sensitivity and 100% specificity for overall DM patients, while RIG‐I staining and PFA reached respectively 14% and 59% sensitivity and 100% and 86% specificity. In any subset of DM, sarcoplasmic MxA expression showed higher sensitivity than RIG‐I and PFA. Some anti‐MDA5 antibody‐positive DM samples distinctively showed a scattered staining pattern of MxA. No ASS samples had sarcoplasmic MxA expression even though six patients had DM skin rash. Conclusions: Sarcoplasmic MxA expression is more sensitive than PFA and RIG‐I expression for a pathological diagnosis of DM, regardless of the autoantibody‐related subgroup. In light of its high sensitivity and specificity, it may be considered a pathological hallmark of DM per se. Also, lack of MxA expression in ASS supports the idea that ASS is a distinct entity from DM. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the effectiveness of magnetic resonance imaging (MRI) in the evaluation of muscle inflammation using a mouse model of myositis. Also cited are the use of MRI in assessing muscle damages like atrophy, fatty infiltration and their distribution, as well as the use of nonobese diabetic (NOD) mouse model invalidated for Inducible-CoStimulator (ICOS)/ICOS ligand (ICOSL) costimulation pathway in the study.

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A report on the Second H3Africa Ethics Consultation Meeting, which was held in Livingstone, Zambia on 11 May 2015. The meeting demonstrated considerable evolution by African Research Ethics Committees on thinking about broad consent as a consent option for genomics research and biobanking. The meeting concluded with a call for broader engagement with policy makers across the continent in order to help these recognise the need for guidance and regulation where these do not exist and to explore harmonisation where appropriate and possible. [ABSTRACT FROM AUTHOR]

Hepatitis C (HCV) molecular epidemiology is documented poorly in central African countries. In response to this, a population-based study of 319 consenting adults resident in a remote village of Gabon was undertaken (mean age: 38 years; age range: 13-85+; sex ratio: 0.74). Screening for anti-HCV antibodies was performed using ELISA and recombinant immunoblot assay. Seropositive samples were assessed further with viral load and genotyping techniques. Sixty-six (20.7%) individuals were HCV seropositive. Viral loads ranged from 600 to 24.9 million IU/ml (median: 372,500). Seroprevalence and viral loads increased significantly with age ( P < 10−5 and P < 0.003, respectively). HCV sequences of the 5′UTR genome region were obtained from 60 (90.9%) samples and NS5B region sequences were obtained from 22 (36.6%) samples. All strains belonged to subtypes of genotype 4: 4e (72.7%), 4c (13.6%), 4p (4.5%), 4r (4.5%) and one unclassified genotype 4 strain. Evolutionary analysis of the subtype 4e sequences indicates a period of raised transmission during the early twentieth century. J. Med. Virol. 80:1581-1587, 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Plasmodium falciparum infection can lead to a life threatening disease and the pathogenetic mechanisms of severe manifestations are not fully understood. Here, we investigated the capacity of P. falciparum -parasitized red blood cells (PRBC) from 45 children with clinical malaria to induce endothelial cell (EC) apoptosis. In all subjects, PRBC that cytoadhered to ECs could be found albeit to a variable degree. By contrast, PRBC that induce EC apoptosis were found only in nine (20%) subjects. Interestingly, children with neurological manifestations were significantly more likely to harbour apoptogenic strains. There was no quantitative relationship between the capacity of these isolates to cytoadhere and apoptosis induction. We hypothesize that P. falciparum -encoded molecules could be responsible for apoptosis induction and therefore suggest new insights in the pathogenesis of P. falciparum malaria. Further investigations are currently in progress to determine whether these results can be confirmed and to identify putative parasite apoptogenic factors. [ABSTRACT FROM AUTHOR]

A national population-based survey was carried out in Niger in 2002 to assess HIV prevalence in the population aged 15–49 years. A two-stage cluster sampling was used and the blood specimens were collected on filter paper and tested according to an algorithm involving up to three diagnostic tests whenever appropriate. Testing was unlinked and anonymous. The refusal rate was 1.1% and 6056 blood samples were available for analysis. The adjusted prevalence of HIV was 0.87% (95% CI, 0.5–1.3%) and the 95% CI of the estimated number of infected individuals was 22 864–59 640. HIV-1 and HIV-2 represented, respectively, 95.6% and 2.9% of infections while dual infections represented 1.5%. HIV positivity rate was 1.0% in women and 0.7% in men. It was significantly higher among urban populations than among rural ones (respectively, 2.1% and 0.6%,P < 10−6). Using logistic regression, the variables significantly related to the risk of being tested positive for HIV were urban housing, increasing age and being either widowed or divorced. The estimate from the national survey was lower than the prevalence assessed from antenatal clinic data (2.8% in 2001). In the future, the representativeness of sentinel sites should be improved by increasing the representation of rural areas accounting for more than 80% of the population. Compared with other sub-Saharan countries, the HIV prevalence in Niger is still moderate. This situation represents a strong argument for enhancing prevention programmes and makes realistic the projects promoting an access to potent antiretroviral therapies for the majority. [ABSTRACT FROM AUTHOR]

Aims: Guidelines regarding voiding cystourethrogram (VCUG) indications following a paediatric kidney abscess are lacking. This study evaluates vesicoureteral reflux (VUR) prevalence and outcome after a first kidney abscess., Methods: This retrospective study included all children presenting to a tertiary paediatric reference centre with de-novo kidney abscesses from 2011 to 2022, diagnosed through imaging (ultrasonography or computed tomography). VCUG's clinical utility was assessed by exploring outcomes related to interventions., Results: Among the 17 patients (median age 9 months, IQR; 6 months-6 years), VCUG identified VUR in 7 (41%; 95% CI: 18-65%), including two with grade IV-V. Median abscess size was 19 mm (IQR; 14-27). 7/8 (88%) children with DMSA scan presented scars, including 4 with hypofunctioning (20%-44%), and one with a non-functioning kidney. Scarring on the DMSA scan was similar regardless of identified VUR. Six children had subsequent pyelonephritis. Three of the remaining 11 had grade I-III and two IV-V VUR. Surgery was required in four children overall: three for recurrent pyelonephritis and one for high-grade VUR and scars., Conclusion: Among initial kidney abscess cases, 41% had VUR, similar to children experiencing their first uncomplicated pyelonephritis. VCUG results guided antibiotic prophylaxis but not surgical decisions. We suggest considering VCUG following recurrent pyelonephritis/kidney abscess and/or kidney scarring., (© 2024 The Author(s). Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Aims: Glucocorticoids are 1 of the primary treatments in paediatric kidney transplantation. The aims of this study were: (i) to build a population pharmacokinetics (PPK) model of free prednisolone, which is the active form of prednisone, in paediatric kidney transplant recipients; (ii) to identify covariates accounting for interindividual variability (IIV) of pharmacokinetics (PK) parameters; and (iii) to investigate drug exposure-safety relationships., Methods: Ninety-seven samples were obtained from 39 paediatric kidney transplant recipients (aged 3.4-17.2 years) in order to investigate prednisone PPK. We selected children receiving oral prednisone as part of their immunosuppressive regimen. A PPK analysis was performed using Monolix., Results: A 1-compartment model best described prednisolone concentrations. Large IIV was observed as prednisolone was undetectable at H12 in some patients but could still be detected at H24 in others. Both bodyweight and ciclosporin cotreatment influenced the PK. The clearance (CL U ) and volume of distribution of free prednisolone allometrically scaled to 70 kg were 27.6 L/h and 101 L. Ciclosporin cotreatment decreased CL U by 67%. High blood pressure and new onset diabetes after transplantation were associated with daily free prednisolone exposure., Conclusion: This study is the first analysis of prednisolone PPK in kidney-transplanted children. Some of the IIV in the PK parameters was explained by bodyweight and ciclosporin cotreatment. These data suggest that dose adjustment is required after identifying variability factors to optimize efficacy and limit side effects. The use of therapeutic drug monitoring in kidney-transplanted children may be useful, especially with respect to safety issues., (© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Objective: To investigate the influence of myoinjury on antigen presentation to T cells in draining lymph nodes (LNs)., Methods: Muscle crush was performed in mice injected with exogenous ovalbumin (OVA) and in transgenic SM-OVA mice expressing OVA as a muscle-specific self antigen. Antigen exposure and the resulting stimulation of T cell proliferation in draining LNs was assessed by transferring carboxyfluorescein succinimidyl ester (CFSE)-labeled OVA-specific CD8+ and CD4+ T cells from OT-I and OT-II mice and by measuring the dilution of CFSE, which directly reflects their proliferation. The role of monocyte-derived dendritic cells (DCs) in T cell priming was assessed using pharmacologic blockade of DC migration. Immunofluorescence was used to detect CD8+ T cells, inflammatory monocyte-derived DCs, and type I major histocompatibility complex (MHC)-expressing myofibers in crushed muscle, and to assess expression of perforin, interferon-γ (IFNγ), interleukin-2 (IL-2), IL-10, and transforming growth factor β1 (TGFβ1)., Results: OVA injection into intact muscle induced strong proliferation of CD4+ and CD8+ T cells, indicating efficient exposure of soluble antigens in draining LNs. OVA-specific CD8+ T cell proliferation in draining LNs of SM-OVA mice required myoinjury and was unaffected by pharmacologic inhibition of monocyte-derived DC migration. On day 7 postinjury, activated CD8+ T cells expressing perforin, IFNγ and IL-2 were transiently detected in crushed muscle, and these cells were in close contact with class I MHC-positive regenerating myofibers. Beginning on day 7, the immunosuppressive cytokines IL-10 and TGFβ1 were conspicuously expressed by CD11b+ cells, and CD8+ T cells rapidly disappeared from the healing muscle., Conclusion: Myofiber damage induces an episode of muscle antigen-specific CD8+ T cell proliferation in draining LNs. Activated CD8+ T cells transiently infiltrate the injured muscle, with prompt control by immunosuppressive cues. Inadequate control might favor sustained autoimmune myositis., (Copyright © 2012 by the American College of Rheumatology.)

Objective: Anti-signal recognition particle (anti-SRP) autoantibodies are associated with severe acquired necrotizing myopathies. The role of these autoantibodies remains elusive, and the evolution of anti-SRP levels over time is unknown. In this study, we developed an addressable laser bead immunoassay (ALBIA) technique to investigate a correlation between anti-SRP levels, serum creatine kinase (CK) levels, and muscle strength in patients with necrotizing myopathy., Methods: The diagnostic value of the ALBIA assay was determined by comparing serum levels of anti-SRP autoantibodies in 31 anti-SRP immunodot-positive patients to those in 190 healthy blood donors and 199 control patients with different inflammatory/autoimmune conditions or polyclonal hypergammaglobulinemia. Among the 31 anti-SRP-positive patients, serum samples from 8 patients were monitored over time for levels of anti-SRP autoantibodies and levels of CK (determined at least 3 times, consecutively, over a mean followup period of 783 days). The relationship between levels of anti-SRP autoantibodies and levels of CK was tested using a linear mixed model., Results: The assay yielded positive results for anti-SRP in all anti-SRP immunodot-positive serum samples tested, while all control sera tested negative. The 8 anti-SRP-positive patients who were followed up longitudinally were found to have normalized CK levels and improved muscle strength. There was a striking correlation between the degree of myolysis, as measured by CK levels, in patients receiving therapy and the anti-SRP54 autoantibody levels in these same patients (P = 0.002)., Conclusion: Anti-SRP-positive myositis appears to be one of the few autoimmune diseases in which specific autoantibody levels are correlated with surrogate disease activity markers. These results reveal the usefulness of monitoring anti-SRP autoantibody levels in patients receiving therapy, and may also suggest a possible pathogenic role for anti-SRP autoantibodies in the necrotizing myopathies., (Copyright © 2011 by the American College of Rheumatology.)