Strengthening adult mosquito surveillance in Africa for disease control: Learning from the present

Mosquito surveillance is essential to successfully control and eliminate mosquito-borne diseases. Yet, it is often done by numerous organizations with little collaboration, incomplete understanding of existing gaps, and limited long-term vision. There is a clear disconnect between entomological and epidemiological indices, with entomological data informing control efforts inadequately. Here we discuss current mosquito surveillance practises across the heterogenous disease landscape in Africa. We advocate for the development of mosquito surveillance strategic plans to increase the impact and functionality of mosquito surveillance. We urge for a proactive approach to set up centralized mosquito data systems under custodian of national governments, focus on epidemiologically relevant mosquito data and increase robustness of mosquito surveillance using a more spatially explicit sampling design

Human Immunodeficiency Virus type 1 Endocytic Trafficking Through Macrophage Bridging Conduits Facilitates Spread of Infection

Bridging conduits (BC) sustain communication and homeostasis between distant tethered cells. These are also exploited commonly for direct cell-to-cell transfer of microbial agents. Conduits efficiently spread infection, effectively, at speeds faster than fluid phase exchange while shielding the microbe against otherwise effective humoral immunity. Our laboratory has sought to uncover the mechanism(s) for these events for human immunodeficiency virus type one (HIV-1) infection. Indeed, in our prior works HIV-1 Env and Gag antigen and fluorescent virus tracking were shown sequestered into endoplasmic reticulum-Golgi organelles but the outcomes for spreading viral infection remained poorly defined. Herein, we show that HIV-1 specifically traffics through endocytic compartments contained within BC and directing such macrophage-to-macrophage viral transfers. Following clathrin-dependent viral entry, HIV-1 constituents bypass degradation by differential sorting from early to Rab11+ recycling endosomes and multivesicular bodies. Virus-containing endocytic viral cargoes propelled by myosin II through BC spread to neighboring uninfected cells. Disruption of endosomal motility with cytochalasin D, nocodasole and blebbistatin diminish intercellular viral spread. These data lead us to propose that HIV-1 hijacks macrophage endocytic and cytoskeletal machineries for high-speed cell-to-cell spread

DAF-16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans

The DAF-16/FoxO transcription factor controls growth, metabolism and aging in Caenorhabditis elegans. The large number of genes that it regulates has been an obstacle to understanding its function. However, recent analysis of transcript and chromatin profiling implies that DAF-16 regulates relatively few genes directly, and that many of these encode other regulatory proteins. We have investigated the regulation by DAF-16 of genes encoding the AMP-activated protein kinase (AMPK), which has ?, ? and ? subunits. C. elegans has 5 genes encoding putative AMP-binding regulatory ? subunits, aakg-1-5. aakg-4 and aakg-5 are closely related, atypical isoforms, with orthologs throughout the Chromadorea class of nematodes. We report that ?75% of total ? subunit mRNA encodes these 2 divergent isoforms, which lack consensus AMP-binding residues, suggesting AMP-independent kinase activity. DAF-16 directly activates expression of aakg-4, reduction of which suppresses longevity in daf-2 insulin/IGF-1 receptor mutants. This implies that an increase in the activity of AMPK containing the AAKG-4 ? subunit caused by direct activation by DAF-16 slows aging in daf-2 mutants. Knock down of aakg-4 expression caused a transient decrease in activation of expression in multiple DAF-16 target genes. This, taken together with previous evidence that AMPK promotes DAF-16 activity, implies the action of these two metabolic regulators in a positive feedback loop that accelerates the induction of DAF-16 target gene expression. The AMPK ? subunit, aakb-1, also proved to be up-regulated by DAF-16, but had no effect on lifespan. These findings reveal key features of the architecture of the gene-regulatory network centered on DAF-16, and raise the possibility that activation of AMP-independent AMPK in nutritionally replete daf-2 mutant adults slows aging in C. elegans. Evidence of activation of AMPK subunits in mammals suggests that such FoxO-AMPK interactions may be evolutionarily conserved

Indoor residual spraying for malaria control in sub-Saharan Africa 1997 to 2017: an adjusted retrospective analysis

Background: Indoor residual spraying (IRS) is a key tool for controlling and eliminating malaria by targeting vectors.To support the development of efective intervention strategies it is important to understand the impact of vector control tools on malaria incidence and on the spread of insecticide resistance. In 2006, the World Health Organization (WHO) stated that countries should report on coverage and impact of IRS, yet IRS coverage data are still sparse and unspecifc. Here, the subnational coverage of IRS across sub-Saharan Africa for the four main insecticide classes from 1997 to 2017 were estimated. Methods: Data on IRS deployment were collated from a variety of sources, including the President’s Malaria Initiative spray reports and National Malaria Control Programme reports, for all 46 malaria-endemic countries in sub-Saharan Africa from 1997 to 2017. The data were mapped to the applicable administrative divisions and the proportion of households sprayed for each of the four main insecticide lasses; carbamates, organochlorines, organophosphates and pyrethroids was calculated. Results: The number of countries implementing IRS increased considerably over time, although the focal nature of deployment means the number of people protected remains low. From 1997 to 2010, DDT and pyrethroids were commonly used, then partly replaced by carbamates from 2011 and by organophosphates from 2013. IRS deployment since the publication of resistance management guidelines has typically avoided overlap between pyrethroid IRS and ITN use. However, annual rotations of insecticide classes with difering modes of action are not routinely used. Conclusion: This study highlights the gaps between policy and practice, emphasizing the continuing potential of IRS to drive resistance. The data presented here can improve studies on the impact of IRS on malaria incidence and help to guide future malaria control eforts.</p

Actin Dependence of Polarized Receptor Recycling in Madin-Darby Canine Kidney Cell Endosomes

Mammalian epithelial cell plasma membrane domains are separated by junctional complexes supported by actin. The extent to which actin acts elsewhere to maintain cell polarity remains poorly understood. Using latrunculin B (Lat B) to depolymerize actin filaments, several basolateral plasma membrane proteins were found to lose their polarized distribution. This loss of polarity did not reflect lateral diffusion through junctional complexes because a low-density lipoprotein receptor mutant lacking a functional endocytosis signal remained basolateral after Lat B treatment. Furthermore, Lat B treatment did not facilitate membrane diffusion across the tight junction as observed with ethylenediaminetetraacetic acid or dimethyl sulfoxide treatment. Detailed analysis of transferrin recycling confirmed Lat B depolarized recycling of transferrin from endosomes to the basolateral surface. Kinetic analysis suggested sorting was compromised at both basolateral early endosomes and perinuclear recycling endosomes. Despite loss of function, these two endosome populations remained distinct from each other and from early endosomes labeled by apically internalized ligand. Furthermore, apical and basolateral early endosomes were functionally distinct populations that directed traffic to a single common recycling endosomal compartment even after Lat B treatment. Thus, filamentous actin may help to guide receptor traffic from endosomes to the basolateral plasma membrane

Actin acting at the Golgi

The organization, assembly and remodeling of the actin cytoskeleton provide force and tracks for a variety of (endo)membrane-associated events such as membrane trafficking. This review illustrates in different cellular models how actin and many of its numerous binding and regulatory proteins (actin and co-workers) participate in the structural organization of the Golgi apparatus and in traf- ficking-associated processes such as sorting, biogenesis and motion of Golgi-derived transport carriers