The Wolbachia endosymbiont as an anti-filarial nematode target

Human disease caused by parasitic filarial nematodes is a major cause of global morbidity. The parasites are transmitted by arthropod intermediate hosts and are responsible for lymphatic filariasis (elephantiasis) or onchocerciasis (river blindness). Within these filarial parasites are intracellular alpha-proteobacteria, Wolbachia, that were first observed almost 30 years ago. The obligate endosymbiont has been recognized as a target for anti-filarial nematode chemotherapy as evidenced by the loss of worm fertility and viability upon antibiotic treatment in an extensive series of human trials. While current treatments with doxycycline and rifampicin are not practical for widespread use due to the length of required treatments and contraindications, anti-Wolbachia targeting nevertheless appears a promising alternative for filariasis control in situations where current programmatic strategies fail or are unable to be delivered and it provides a superior efficacy for individual therapy. The mechanisms that underlie the symbiotic relationship between Wolbachia and its nematode hosts remain elusive. Comparative genomics, bioinfomatic and experimental analyses have identified a number of potential interactions, which may be drug targets. One candidate is de novo heme biosynthesis, due to its absence in the genome sequence of the host nematode, Brugia malayi, but presence in Wolbachia and its potential roles in worm biology. We describe this and several additional candidate targets, as well as our approaches for understanding the nature of the host-symbiont relationship

Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use meta-genomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.Peer reviewe

Setting a baseline for global urban virome surveillance in sewage

The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Introducing the Ensemble-Based Dual Entropy and Multiobjective Optimization for Hydrometric Network Design Problems: EnDEMO

Entropy applications in hydrometric network design problems have been extensively studied in the most recent decade. Although many studies have successfully found the optimal networks, there have been assumptions which could not be logically integrated into their methodology. One of the major assumptions is the uncertainty that can arise from data processing, such as time series simulation for the potential stations, and the necessary data quantization in entropy calculations. This paper introduces a methodology called ensemble-based dual entropy and multiobjective optimization (EnDEMO), which considers uncertainty from the ensemble generation of the input data. The suggested methodology was applied to design hydrometric networks in the Nelson-Churchill River Basin in central Canada. First, the current network was evaluated by transinformation analysis. Then, the optimal networks were explored using the traditional deterministic network design method and the newly proposed ensemble-based method. Result comparison showed that the most frequently selected stations by EnDEMO were fewer and appeared more reliable for practical use. The maps of station selection frequency from both DEMO and EnDEMO allowed us to identify preferential locations for additional stations; however, EnDEMO provided a more robust outcome than the traditional approach

Organic manure availability, food security and poverty relationships at farm level in the old cotton basin of Mati

International audienc

Exploring the potential usefulness of U.S. maize expired Plant Variety Protection Act lines for maize breeding in sub‐Saharan Africa

Maize (Zea mays L.) inbred lines with expired Plant Variety Protection Act (ExPVP) certificates are publicly available and potentially represent a new germplasm resource for many public and private breeding programs. The use of these inbred lines for maize breeding in Sub-Saharan African (SSA) was little investigated. Hence, this study was conducted to explore their potential usefulness. Ninety-six (96) ExPVP lines, two (2) temperate public lines and fourteen (14) tropical lines were evaluated in five (5) different trials from 2016 to 2018 in Burkina Faso to determine their phenotypic characteristics, resistance to drought, heat and three diseases, and to identify elite ExPVP lines for local maize breeding programs. Cluster analysis based on phenotypic traits highlighted a clear distinction between the different groups (NS vs SS heterotic groups, temperate vs tropical germplasms). The screening showed that 3%, 28% and 68% of ExPVP lines were resistant, tolerant and susceptible to maize leaf blight disease, respectively. However, the lines were either tolerant or resistant to curvularia leaf spot and maize streak virus. About 30% of ExPVP lines presented a tolerance to the three maize diseases tested and, 8% of the lines were tolerant to drought. Heat stress was severe to both ExPVP and tropical lines. Yield potential of ExPVP lines varied from 1.68 to 2635.63 kg/ha compared to 798.76 - 1707.56 kg/ha for tropical lines. The ExPVP lines identified showing tolerance to stresses and or a high yield performance can be integrated in inbred-hybrid development program