Prevalence and Determinants of Endothelial Dysfunction among Adults Living with HIV in Northwest Nigeria

Background: Endothelial dysfunction constitutes an early pathophysiological event in atherogenesis and cardiovascular disease. This study aimed to assess the prevalence, determinants, and degree of endothelial dysfunction in antiretroviral therapy (ART)–treated people living with HIV (PLWH) in northwestern Nigeria using brachial flow-mediated dilatation (FMD). Methods: This was a comparative, cross-sectional study. A total of 200 ART-treated adults living with HIV with no evidence of kidney disease were compared with 200 HIV-negative participants attending a tertiary hospital in Kano, Nigeria, between September 2020 and May 2021. Endothelial function was evaluated by measuring FMD with a high-resolution vascular ultrasound transducer. FMD was calculated as the ratio of the brachial artery diameter after reactive hyperemia to baseline diameter and expressed as a percentage of change. Blood and urine samples were obtained from participants in both arms. Urine albumin-to-creatinine ratio (uACR) was calculated using the 2021 CKD-EPI estimated glomerular filtration rate (eGFR) creatinine-cystatin C equation without the race variable, and low-density lipoprotein (LDL) cholesterol was measured using enzymatic method. Results: The overall mean age (± standard deviation) of the study participants was 42 ± 11 years. Participants in the comparison arm were younger than PLWH (38 ± 11 versus 46 ± 10 years, respectively). The median (interquartile range) uACR was 41.6 (23.2–162.9) mg/g for the ART-treated PLWH versus 14.5 (7.4–27.0) mg/g for healthy controls. PLWH had a significantly lower mean percent FMD when compared to HIV-negative participants (9.8% ± 5.4 versus 12.1% ± 9.2, respectively). Reduced FMD was independently associated with HIV infection (β = –2.83%, 95% CI, –4.44% to –1.21%, p = 0.001), estimated glomerular filtration rate (β = –0.04%, 95% CI, –0.07% to –0.01%, p = 0.004) and LDL cholesterol (β = –1.12%, 95% CI, –2.13% to –0.11%, p = 0.029). Conclusion: HIV-positive status, lower estimated GFR, and higher LDL cholesterol levels were independently associated with endothelial dysfunction. Future prospective studies with larger cohorts of persons living with HIV (and age- and sex-matched HIV-negative controls) are needed to gain further insight into these important findings. In the interim, aggressive management of modifiable risk factors is warranted

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Cours National de Paludologie du Niger : Bilan de cinq ans.

Le Cours National de Paludologie (CNP) est une formation organisée depuis 2011 par le Centre de Recherche Médicale et Sanitaire (CERMES) de Niamey en collaboration avec le Programme National de Lutte contre le Paludisme (PNLP) du Niger, la Faculté des Sciences de la Santé (FSS) de l’université Abdoul Moumouni et l’Hôpital National de Niamey.Objectif : L’objectif de ce cours est de renforcer l’aptitude des acteurs de la lutte contre le paludisme. Nous présentons le bilan de cinq ans d’animation du cours.Méthodologie et résultats : La méthodologie du cours est une approche interactive, basée sur le principe de l’andragogie et utilisant les nouvelles technologies de l’information et de la communication (NTIC). Cent quarante-six candidats ont postulé au CNP en 5 ans. Soixante-seize candidats ont été retenus par la commission de sélection des dossiers. 97,4% des candidats étaient de nationalité Nigérienne. Le taux de réussite était de 95,9% (N=74). Cinquante-trois conférences ont été animées par des chercheurs séniors venus de 7 pays différents. La moyenne générale au pré test était de 9,2/20 (D=6,2, [3 ; 16,5]) contre 14,9/20 (D=8,3 ; [7,5 ; 20]) au post test. L’analyse du questionnaire de satisfaction montre que 69,9% (N=44) des apprenants étaient satisfaits du cours.Conclusion : Le CNP s’est déroulé avec beaucoup de satisfaction durant ces cinq années consécutives. Les résultats d’évaluation de ce cours sont excellents. Le Réseau International des Instituts Pasteur (RIIP) auquel appartient le CERMES doit pérenniser ce cours en le transformant en un cours sous régional dénommé « Cours Ouest Africain de Paludologie (COAP) ».Mots clés : Formation, Paludisme, Bilan, Niger

Modulatory role of rutin on 2,5-hexanedione-induced chromosomal and DNA damage in rats: validation of computational predictions

<p>The aim of this study was to evaluate the potentials of rutin on 2,5-hexanedione-induced toxicities. Two successive phases were involved using <i>in silico</i> and <i>in vivo</i> approaches. The <i>in silico</i> was adopted for potential oral toxicity and docking. The <i>in vivo</i> was carried-out in two stages for two weeks; the ameliorative (stage 1, first week), preventive, and curative studies (stage 2, extended to second week). In stage 1, rats were divided into four groups of seven each (distilled water, 3% (v/v) 2,5-hexanedione, 10 mg/kg rutin, and co-administration). In stage 2, the experimental groups were given either rutin or 2,5-hexanedione and treated in reverse order. Lipid peroxidation, protein carbonyl, and DNA fragmentation in tissues and bone marrow cells micronucleus were determined. The predicted Median lethal dose (LD₅₀) of >5000 mg/kg and toxicity class of five (5) indicates the safety of rutin when orally administered. 2,5-Hexanedione comfortably docked in to the active sites of SOD (−22.857Kcal/mol; <i>KI</i> = 0.9621 µM), GPx (−11.2032Kcal/mol; <i>KI</i> = 0.9813 µM), and CAT (−16.446Kcal/mol; <i>KI</i> = 0.9726 µM) with strong hydrogen bond and hydrophobic interactions. However, only strong hydrophobic interaction was observed in the case of DNA (−3.3296Kcal/mol; <i>KI</i> = 0.9944). <i>In vivo</i> findings revealed deleterious effects of 2,5-hexanedione through induction of oxidative and chromosomal/DNA damage characterized by higher level of malondialdehyde, micronuclei formations, and DNA fragmentation. These have invariably, validates the findings from <i>in silico</i> experiments. Furthermore, rutin was able to ameliorate, protect, and reverse these effects, and was relatively non-toxic corroborating toxicity predictions. Rutin exhibited counteractive effects on 2,5-hexanedione-induced oxidative, chromosomal, and DNA damage.</p

A Systematic Review and Meta-Analysis of the Prevalence of Triplex Infections (Combined Human Immunodeficiency Virus, Hepatitis B Virus, and Hepatitis C Virus) among Pregnant Women in Nigeria

Objective. We systematically identified the prevalence of triplex infections (combined human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV)) in pregnancy. Methods. To gather information on the frequency of triplex infections, we searched the databases of PubMed, CINAHL, and Google Scholar. Without regard to language, we utilized search terms that covered HIV, HBV, HCV, and pregnancy. Pregnant women with triplex infections of HIV, HBV, and HCV were included in studies that also examined the prevalence of triplex infections. Review Manager 5.4.1 was employed to conduct the meta-analysis. Critical appraisal and bias tool risk data were provided as percentages with 95% confidence intervals (95% CIs), and I2 was used as the statistical measure of heterogeneity. The checklist was created by Hoy and colleagues. The study protocol was registered on PROSPERO, under the registration number CRD42020202583. Results. Eight studies involving 5314 women were included. We identified one ongoing study. Pooled prevalence of triplex infections was 0.03% (95% CI: 0.02–0.04%) according to meta-analysis. Subgroup analysis demonstrated a significantly high prevalence of 0.08% (95% CI: 0.06–0.10%; 3863 women) in HIV-positive population than 0.00% (95% CI:−0.00-0.00; 1451 women; P<0.001) in general obstetric population. Moreover, there was a significant difference in the pooled prevalence between studies published between 2001 and 2010 and between 2011 and 2021 (0.14% (95% CI: 0.12 to 0.16 versus 0.03% (95% CI: 0.02 to 0.04%; P<0.001))) and participants recruited in the period between 2001 and 2011 and between 2012 and 2021 (0.13% (95% CI: 0.05 to 0.21; p=0.002 versus 0.00% (95% CI: −0.00 to 0.00%; p=1.00))), respectively. Conclusion. The combined prevalence of prenatal triplex infections was 0.03%, with rates notably higher among the group of pregnant women who were HIV-positive and during the recruitment period that took place before 2012. This prevalence still necessitates screening for these infections as necessary