The impact of approaches in improving male partner involvement in the prevention of mother-to-child transmission of HIV on the uptake of safe infant feeding practices by HIV positive women in sub-Saharan Africa. A systematic review and meta-analysis.

BACKGROUND: The low level of male partner involvement in Prevention of Mother to Child Transmission of HIV services such as safe infant feeding practices poses a serious challenge to the implementation of guidelines on safe infant feeding and may undermine efforts towards elimination of mother to child transmission of HIV in sub Saharan Africa(SSA). We conducted a systematic review and meta-analysis to identify the approaches that have been utilized to improve male partner involvement in PMTCT services as well as their impact on the uptake of safe infant feeding practices by HIV positive mothers in SSA. METHODS: In this systematic review and meta-analysis, Ovid Medline, Embase, PsycINFO, Cochrane library, ClinicalTrials.gov, Web of Science and Current Controlled Trials were searched. Only studies performed in SSA that reported an approach that specifically involved male partners and its impact on the uptake of safe infant feeding practices (irrespective of the language and date of publication) were included. Odds ratios were extracted or calculated from studies and combined in a meta-analysis using the statistical package Stata version 11.0. Forest plots were generated using the random effect model. RESULTS: From an initial 2416 non-duplicate articles, 06 articles were included in the systematic review and meta-analysis. The overall pooled unadjusted OR was 3.08[95%CI: 2.58-3.68], while the effect sizes for interventions aimed at promoting male partner involvement such as verbal encouragement, complex community intervention and enhanced psychosocial interventions were 1.93[95%CI: 1.34-2.79], 3.45[95%CI: 2.79-4.25] and 5.14[95%CI: 2.42-10.90] respectively. Using only adjusted odd ratios, the pooled adjusted OR = 1.78[95%CI: 1.35-2.34]. The I2 = 60.1% p = 0.057 using adjusted ORs. CONCLUSION: Interventions aimed at promoting male partner involvement such as enhanced psychosocial interventions, verbal encouragement and complex community interventions increase the uptake of safe infant feeding options. The heterogeneity was moderate among studies. More studies including randomised trials that will recruit larger, representative samples of patients are needed in the future. Prospero registration number: 42016032673

Orthohantaviruses, Emerging Zoonotic Pathogens

Orthohantaviruses give rise to the emerging infections such as of hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in Eurasia and the Americas, respectively. In this review we will provide a comprehensive analysis of orthohantaviruses distribution and circulation in Eurasia and address the genetic diversity and evolution of Puumala orthohantavirus (PUUV), which causes HFRS in this region. Current data indicate that the geographical location and migration of the natural hosts can lead to the orthohantaviruses genetic diversity as the rodents adapt to the new environmental conditions. The data shows that a high level of diversity characterizes the genome of orthohantaviruses, and the PUUV genome is the most divergent. The reasons for the high genome diversity are mainly caused by point mutations and reassortment, which occur in the genome segments. However, it still remains unclear whether this diversity is linked to the disease’s severity. We anticipate that the information provided in this review will be useful for optimizing and developing preventive strategies of HFRS, an emerging zoonosis with potentially very high mortality rates

DEFINING A STRUCTURAL BASIS FOR ANTIBODY FC REGIONS IN INFLUENZA VIRUS NEUTRALIZATION

Ph.DDOCTOR OF PHILOSOPHY (SOM

Male partner involvement in the utilization of hospital delivery services by pregnant women living with HIV in Sub Saharan Africa: a systematic review and meta-analysis

Objective The level of male partner involvement in hospital delivery by pregnant women living with HIV in sub Saharan Africa (SSA) is low. We conducted a systematic review and meta-analysis to identify the approaches that are used in improving male partner involvement and their impact on the utilization of hospital delivery services by pregnant women living with HIV in SSA. Methods Ovid Medline, Embase, PsycINFO, Cochrane library, ClinicalTrials.gov, Web of Science and Current Controlled Trials were searched. Only studies carried out in SSA that reported an approach used in involving male partners and the impact on the uptake of hospital delivery services irrespective of the language and date of publication were included. Odds ratios were extracted or calculated from studies and combined in a meta-analysis using the statistical package Stata version 11.0. A forest plot was used to show the impact of various male involvement approaches. A funnel plot was used to report publication bias. Results From an initial 2316 non-duplicate articles, 08 articles were included in the systematic review and meta-analysis. The overall pooled OR was 1.56 (95% CI 1.45-1.68). After stratification, the odds ratios were: 1.51 (95% CI 1.38-1.65), 1.58 (95% CI 1.38-1.80), 3.47 (95% CI 2.16-5.58) for complex community interventions without community health workers (CHWs), complex community interventions with community health workers, and verbal encouragement respectively. The overall I-square was 91.0% but after stratification into the three different approaches, the I-squared within the complex community intervention without CHWs group was 0.0%. Conclusions for Practice Complex community interventions and verbal encouragement increase the utilization of hospital delivery services by pregnant women living with HIV in SSA. The overall heterogeneity was high but very low for studies that used complex community interventions without CHWs. More well conducted studies (including randomized controlled trials) are needed in future to add to the quality of evidence

SARS-CoV-2 Antibody Effectiveness Is Influenced by Non-Epitope Mutation/Binding-Induced Denaturation of the Epitope 3D Architecture

The public health threat from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to intensify with emerging variants of concern (VOC) aiming to render COVID-19 vaccines/infection-induced antibodies redundant. The SARS-CoV-2 spike protein is responsible for receptor binding and infection of host cells making it a legitimate antibody target. Antibodies mostly target epitopes in the receptor binding domain (RBD). Mutations occurring within epitopes influence antibody specificity and function by altering their 3D architecture. However, the mechanisms by which non-epitope mutations in the RBD influence antibody specificity and function remain a mystery. We used Protein Data Bank (PDB) deposited 3D structures for the original, Beta, Delta, BA.1, and BA.2 RBD proteins in complex with either neutralizing antibodies or Angiotensin-Converting Enzyme 2 (ACE2) to elucidate the structural and mechanistic basis for neutralizing antibody evasion driven by non-epitope amino acid substitutions in the RBD. Since the mechanism behind the extensively reported functional discrepancies between the same antibody when used individually and when used in an antibody cocktail is lacking, we explored the structural basis for this inconsistency. Finally, since SARS-CoV-2 antibodies are viral mutagens, we deciphered determinants for antibody-pressured amino acid substitutions. On the one hand, we show that non-epitope mutations in the RBD domain of SARS-CoV-2 VOC influence the formation of hydrogen bonds in the paratope-epitope interface by repositioning RBD amino-acid sidechains (AASCs). This increases the distance between complementary donor/acceptor atoms on paratope and epitope AASCs leading to weaker or the complete prevention of the formation of hydrogen bonds in the paratope-epitope interface. On the other hand, we show that SARS-CoV-2 VOC employ the same strategy to simultaneously search for complementary donor/acceptor atoms on ACE2 AASCs to form new interactions, potentially favoring increased viral transmission. Additionally, we illustrate that converting the spike protein to an RBD, a deletion mutation, also repositions epitope AASCs and that AASC interactions in the paratope-epitope interface vary when an antibody is used individually versus when utilized as a cocktail with other antibodies. Finally, we show that the process of substituting immunogenic RBD amino acids begins with the repositioning of their AASCs induced by immune/antibody pressure. We show that donor/acceptor atoms from any amino acid can determine cross-reactivity instead, provided they possess and present spatially pairing donor/acceptor atoms. By studying structural alignments for PDB deposited antibody-RBD 3D structures and relating them to published binding and neutralization profiles of the same antibodies, we demonstrate that minor structural alterations such as epitope AASC repositioning have a major impact on antibody effectiveness and, hence, should receive adequate attention given that protein structure dictates protein function

Male partner involvement in increasing the uptake of infant antiretroviral prophylaxis/treatment in sub Saharan Africa: A systematic review and meta-analysis

Infant antiretroviral prophylaxis plays an important role towards ensuring the reduction of HIV transmission from mother to child in the postpartum period. However in sub Saharan Africa (SSA), the low level of involvement of male partners may hinder the uptake of such services by HIV positive mothers. We conducted a systematic review and meta-analysis to determine the impact of male partner involvement approaches on the uptake of infant antiretroviral prophylaxis in SSA.In this systematic review and meta-analysis, Ovid Medline, Embase, PsycINFO, Cochrane library, ClinicalTrials.gov, Web of Science and Current Controlled Trials were searched from 1st December 2015 up until 30th March 2016. Only studies carried out in SSA that reported an approach used in involving male partners and the impact on the uptake of infant antiretroviral prophylaxis irrespective of the Language and date of publication were included. Odds ratios were extracted or calculated from studies and combined in a meta-analysis using the statistical package Stata version 11.0. Forest plots were generated using the random effect model.From an initial 2316 non-duplicate articles, 09 articles were included in the systematic review and meta-analysis. The pooled unadjusted odds ratio was 2.09(95% CI: 1.31 to 3.36) while the unadjusted odds ratios for enhanced psychosocial interventions (02 studies pooled), complex community interventions (02 studies pooled), verbal encouragement (02 studies pooled) and invitation letters(03 pooled studies) were 3.48(95% CI: 1.42 to 8.53), 1.85(95%CI: 0.85 to 4.03), 2.37(95%CI: 1.22 to 4.61) and 1.81(95%CI: 0.64 to 5.14) respectively. I squared was 89.5%, p

Switching Heavy Chain Constant Domains Denatures the Paratope 3D Architecture of Influenza Monoclonal Antibodies

Several human monoclonal Abs for treating Influenza have been evaluated in clinical trials with limited success despite demonstrating superiority in preclinical animal models including mice. To conduct efficacy studies in mice, human monoclonal Abs are genetically engineered to contain mouse heavy chain constant domain to facilitate the engagement of Fc-receptors on mouse immune effector cells. Although studies have consistently reported discrepancies in Ab effectiveness following genetic engineering, the structural and mechanistic basis for these inconsistencies remain uncharacterized. Here, we use homology modeling to predict variable region (VR) analogous monoclonal Abs possessing human IgG1, mouse IgG1, and mouse IgG2a heavy chain constant domains. We then examine predicted 3D structures for variations in the spatial location and orientation of corresponding paratope amino acid residues. By structurally aligning crystal structures of Fabs in complex with hemagglutinin (HA), we show that corresponding paratope amino acid residues for VR-analogous human IgG1, mouse IgG1, and mouse IgG2a monoclonal Abs interact differentially with HA suggesting that their epitopes might not be identical. To demonstrate that variations in the paratope 3D fine architecture have implications for Ab specificity and effectiveness, we genetically engineered VR-analogous human IgG1, human IgG4, mouse IgG1, and mouse IgG2a monoclonal Abs and explored their specificity and effectiveness in protecting MDCK cells from infection by pandemic H1N1 and H3N2 Influenza viruses. We found that VR-analogous monoclonal Abs placed on mouse heavy chain constant domains were more efficacious at protecting MDCK cells from Influenza virus infection relative to those on human heavy chain constant domains. Interestingly, mouse but not human heavy chain constant domains increased target breadth in some monoclonal Abs. These data suggest that heavy chain constant domain sequences play a role in shaping Ab repertoires that go beyond class or sub-class differences in immune effector recruitment. This represents a facet of Ab biology that can potentially be exploited to improve the scope and utilization of current therapeutic or prophylactic candidates for influenza