Current knowledge of vector-borne zoonotic pathogens in Zambia: A clarion call to scaling-up “One Health” research in the wake of emerging and re-emerging infectious diseases

BackgroundAlthough vector-borne zoonotic diseases are a major public health threat globally, they are usually neglected, especially among resource-constrained countries, including those in sub-Saharan Africa. This scoping review examined the current knowledge and identified research gaps of vector-borne zoonotic pathogens in Zambia.Methods and findingsMajor scientific databases (Web of Science, PubMed, Scopus, Google Scholar, CABI, Scientific Information Database (SID)) were searched for articles describing vector-borne (mosquitoes, ticks, fleas and tsetse flies) zoonotic pathogens in Zambia. Several mosquito-borne arboviruses have been reported including Yellow fever, Ntaya, Mayaro, Dengue, Zika, West Nile, Chikungunya, Sindbis, and Rift Valley fever viruses. Flea-borne zoonotic pathogens reported include Yersinia pestis and Rickettsia felis. Trypanosoma sp. was the only tsetse fly-borne pathogen identified. Further, tick-borne zoonotic pathogens reported included Crimean-Congo Haemorrhagic fever virus, Rickettsia sp., Anaplasma sp., Ehrlichia sp., Borrelia sp., and Coxiella burnetii.ConclusionsThis study revealed the presence of many vector-borne zoonotic pathogens circulating in vectors and animals in Zambia. Though reports of human clinical cases were limited, several serological studies provided considerable evidence of zoonotic transmission of vector-borne pathogens in humans. However, the disease burden in humans attributable to vector-borne zoonotic infections could not be ascertained from the available reports and this precludes the formulation of national policies that could help in the control and mitigation of the impact of these diseases in Zambia. Therefore, there is an urgent need to scale-up “One Health” research in emerging and re-emerging infectious diseases to enable the country to prepare for future epidemics, including pandemics.     

Discovery of novel benzo[b]thiophene tetrazoles as non-carboxylate GPR40 agonists

GPR40 partial agonism is a promising new mechanism for the treatment of type 2 diabetes mellitus with clinical proof of concept. Most of the GPR40 agonists in the literature have a carboxylic acid functional group, which may pose a risk for idiosyncratic drug toxicity. A novel series of GPR40 agonists containing a tetrazole as a carboxylic acid bioisostere was identified. This series of compounds features a benzo[b]thiophene as the center ring, which is prone to oxidation during phase 1 metabolism. Following SAR optimization targeting GPR40 agonist activity and intrinsic clearance in microsomes (human and rat), potent and metabolically stable compounds were selected for in vivo evaluation. The compounds are efficacious at lowering blood glucose in a SD rat oGTT model.     

Termite diversity along a land use intensification gradient in a semi-arid savanna

Disturbance, particularly agricultural expansion is one of the major threats to the biodiversity and ecological functions of tropical and sub-tropical ecosystems. In this regard, we examined changes in the species richness, abundance, and diversity of termites across different disturbance treatments in a sub-tropical semi-arid savanna in south eastern Zimbabwe. Nine transects (100?×?2 m) representing three habitat disturbance treatments (primary woodland; grazing area; agricultural field) were sampled for termites using a rapid biodiversity assessment protocol. Termites were more abundant and species-rich in primary woodland and grazing area than in the agricultural field. Twelve termite species from three sub-families were present, with Microtermes sp. constituting 35% of the identified termite species. Termite feeding group structure differed significantly among land-use types, and of all termites present, wood-feeding termites were the most abundant while soil-feeders were rare in the agricultural field. In conclusion the observed pattern in termite species richness and relative abundance indicates that termites are very resilient to natural disturbance and might actually benefit from some natural disturbances like they did in the grazing area of this study, but they are not resilient to extreme anthropogenic disturbance. Although there was no notable difference in termite species richness and relative abundance between agricultural field and primary woodland, the pattern observed across the three sites may be potential support for the IDH suggesting that intermediate levels of physical disturbance intensity influence the structure and functioning of termite assemblages in semi-arid savanna.     

Functional diversity of macroinvertebrates on abandoned cattle enclosures in a semi‐arid African savannah

Zimbabwe is experiencing a shift in land‐use, away from livestock farming and towards wildlife conservation. The abandonment of livestock farming may have unforeseen consequences on biodiversity and ecosystem functioning, as cattle kraals create valuable nutrient‐rich patches across the semi‐arid savannah. It is unclear how macroinvertebrates functionally respond to such nutrient‐rich patches in semi‐arid savannahs. We analysed functional diversity of both aboveground and belowground taxa on abandoned cattle kraals and savannah control plots in Save valley Conservancy (SVC). We used distance‐based multivariate techniques to estimate indices of functional diversity. Our results indicated that after two decades of abandonment, kraals had higher functional richness (FRic), functional divergence (FDiv) and functional dispersion (FDis) of macroinvertebrates when both aboveground and belowground species are combined. When aboveground macroinvertebrates were considered alone, no difference was observed for all the considered functional indices. However, only FRic was higher on kraals when belowground macroinvertebrates were separately considered. Our results suggest that two‐decade‐old abandoned kraals may have recovered enough for aboveground species to match the surrounding savannah plot and even surpassed the savannah control for belowground species functional diversity.     

Discovery of a novel potent GPR40 full agonist

Compound 12 is a GPR40 agonist that realizes the full magnitude of efficacy possible via GPR40 receptor agonism. In vitro and in vivo studies demonstrated superior glucose lowering by 12 compared to fasiglifam (TAK-875), in a glucose dependent manner. The enhanced efficacy observed with the full agonist 12 was associated with both direct and indirect stimulation of insulin secretion.     

Diversity and abundance of macro‐invertebrates on abandoned cattle kraals in a semi‐arid savanna

Abandoned cattle (Bos taurus) kraals are sources of habitat heterogeneity in dystrophic semi‐arid African savannas with a strong positive effect on soil nutrients and plant productivity. However, little is known regarding how macro‐invertebrate assemblages vary between abandoned kraals and the surrounding savanna matrix. We tested whether herbaceous biomass and basal and aerial covers and soil nutrients have an effect on aboveground and belowground macro‐invertebrate assemblages. Twelve abandoned kraals were contrasted with their paired control plots for soil characteristics, herbaceous productivity, and macro‐invertebrate assemblages in Save Valley Conservancy, Zimbabwe. Abandoned kraals had significantly higher concentrations of soil nitrogen (N), phosphorus (P), potassium (K), and calcium (Ca) as well as herbaceous biomass and basal and aerial covers than control plots. Both aboveground and belowground macro‐invertebrate species richness were higher on abandoned kraals. However, only belowground macro‐invertebrate diversity (Shannon H′ and Hill number 1) was significantly higher on abandoned kraals. Soil nutrients and herbaceous productivity had positive and significant correlations with the dominant taxa (Coleoptera, Hymenoptera, Hemiptera, Isoptera, and Myriapoda) on abandoned kraals. These results add to the growing body of evidence that abandoned kraals exert significant effects on savanna spatial heterogeneity years later, with implications on ecosystem processes and functioning.     

Spermatogenic cyst and organ culture in <Emphasis Type="Italic">Drosophila pseudoobscura</Emphasis>

Spermatogenesis is a complex series of processes that involves (1) the maintenance of a renewable pool of diploid stem cells within a niche, (2) the mitotic expansion of a subpopulation of stem cells committed to the spermatogenic pathway, and (3) the differentiation of diploid cells into highly specialized, haploid spermatozoa through meiotic and post-meiotic cellular transformations. Drosophila melanogaster is a desirable model for studying spermatogenesis, as similarities exist between mammalian and fly spermatogenesis. Like mammals, flies maintain a spermatogenic stem cell niche; the steps involved in mammalian spermatogenesis are mimicked in flies, with the main difference being that fly sperm develop within cysts rather than an epithelial cell layer. Here, we report a reliable robust system for culturing whole testes and individual spermatogenic cysts obtained from mid- to late-pupal stages of Drosophila pseudoobscura. D. pseudoobscura testes can be easily distinguished in later pupal stages because of their intense red pigmentation and are easily handled because of their simple ellipsoidal morphology. Cultured cysts are comparable in length to cysts obtained from adult flies, and motility is consistently achieved in vitro. This system not only offers a method for dissecting the mechanisms involved in meiotic and post-meiotic cellular transformations, but also can be used for the study of signaling during spermatogenesis.