Changing patterns in the burden of paediatric injuries during the COVID-19 pandemic: a study in Mozambique's central hospitals.

INTRODUCTION: There is a substantial body of knowledge on the effects of the COVID-19 pandemic on injuries showing frequent but inconsistent reductions in both volume and pattern. Yet, studies specifically addressing children are less common, not least from low- and middle-income countries. This study investigated whether changes in the pattern and outcome of paediatric injury admissions to Mozambique's four regional referral hospitals during 2020. METHODS: Clinical charts of paediatric patients presenting to the targeted hospitals with acute injuries were reviewed using a set of child, injury, and outcome characteristics during each of two consecutive restriction periods in 2020 using as a comparator the same periods in 2019, the year before the pandemic. Differences between 2020 and 2019 proportions for any characteristic were examined using the t-test (significance level 0.05). RESULTS: During both restriction periods, compared with the previous year, reductions in the number of injuries were noticed in nearly all aspects investigated, albeit more remarkably during the first restriction period, in particular, greater proportions of injuries in the home setting and from burns (7.2% and 11.5% respectively) and a reduced one of discharged patients (by 2.5%). CONCLUSION: During the restrictions implemented to contend the pandemic in Mozambique in 2020, although each restriction period saw a drop in the volume of injury admissions at central hospitals, the pattern of child, injury and outcome characteristics did not change much, except for an excess of home and burn injuries in the first, more restrictive period. Whether this reflects the nature of the restrictions only or, rather, other mechanisms that came into play, individual or health systems related, remains to be determined.

Differential Outcomes following Optimization of Simian-Human Immunodeficiency Viruses from Clades AE, B, and C.

Simian-human immunodeficiency virus (SHIV) infection of rhesus monkeys is an important preclinical model for human immunodeficiency virus type 1 (HIV-1) vaccines, therapeutics, and cure strategies. SHIVs have been optimized by incorporating HIV-1 Env residue 375 mutations that mimic the bulky or hydrophobic residues typically found in simian immunodeficiency virus (SIV) Env to improve rhesus CD4 binding. We applied this strategy to three SHIV challenge stocks (SHIV-SF162p3, SHIV-AE16, and SHIV-325c) and observed three distinct outcomes. We constructed six Env375 variants (M, H, W, Y, F, and S) for each SHIV, and we performed a pool competition study in rhesus monkeys to define the optimal variant for each SHIV prior to generating large-scale challenge stocks. We identified SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH as the optimal variants. SHIV-SF162p3S could not be improved, as it already contained the optimal Env375 residue. SHIV-AE16W exhibited a similar replicative capacity to the parental SHIV-AE16 stock. In contrast, SHIV-325cH demonstrated a 2.6-log higher peak and 1.6-log higher setpoint viral loads than the parental SHIV-325c stock. These data demonstrate the diversity of potential outcomes following Env375 modification in SHIVs. Moreover, the clade C SHIV-325cH challenge stock may prove useful for evaluating prophylactic or therapeutic interventions against clade C HIV-1.IMPORTANCE We sought to enhance the infectivity of three SHIV stocks by optimization of a key residue in human immunodeficiency virus type 1 (HIV-1) Env (Env375). We developed the following three new simian-human immunodeficiency virus (SHIV) stocks: SHIV-SF162p3S/wild type, SHIV-AE16W, and SHIV-325cH. SHIV-SF162p3S could not be optimized, SHIV-AE16W proved comparable to the parental virus, and SHIV-325cH demonstrated markedly enhanced replicative capacity compared with the parental virus.

Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo.

Adenoviral vectors have shown significant promise as vaccine delivery vectors due to their ability to elicit both innate and adaptive immune responses. α-defensins are effector molecules of the innate immune response and have been shown to modulate natural infection with adenoviruses, but the majority of α-defensin-adenovirus interactions studied to date have only been analyzed in vitro. In this study, we evaluated the role of α-defensin 5 (HD5) in modulating adenovirus vaccine immunogenicity using various serotype adenovirus vectors in mice. We screened a panel of human adenoviruses including Ad5 (species C), Ad26 (species D), Ad35 (species B), Ad48 (species D) and a chimeric Ad5HVR48 for HD5 sensitivity. HD5 inhibited transgene expression from Ad5 and Ad35 but augmented transgene expression from Ad26, Ad48, and Ad5HVR48. HD5 similarly suppressed antigen-specific IgG and CD8+ T cell responses elicited by Ad5 vectors in mice, but augmented IgG and CD8+ T cell responses and innate cytokine responses elicited by Ad26 vectors in mice. Moreover, HD5 suppressed the protective efficacy of Ad5 vectors but enhanced the protective efficacy of Ad26 vectors expressing SIINFEKL against a surrogate Listeria-OVA challenge in mice. These data demonstrate that HD5 differentially modulates adenovirus vaccine delivery vectors in a species-specific manner in vivo.

An introduction to the microbiome and MS.

The human microbiota is composed of diverse forms of microorganisms that live on or in us and plays a crucial role in the health and development. Commensal species that reside in the intestine particularly influence host physiology at local and systemic levels. Multiple sclerosis (MS) is a debilitating autoimmune disorder of the central nervous system for which there is currently no cure. While the cause of MS is unknown, there is a growing body of evidence suggesting that the microbiota can play both pathogenic and protective roles in disease progression. In this review, we provide a brief overview, based on both animal and clinical studies, of the current understanding by which the microbiota may influence MS and discuss opportunities for therapeutic intervention that may alleviate the symptoms associated with this debilitating neuroimmunological disease.