Safety and efficacy of Toll-like receptor agonists as therapeutic agents and vaccine adjuvants for infectious diseases in animals: A systematic review

Introduction: Strengthening global health security relies on adequate protection against infectious diseases through vaccination and treatment. Toll-like receptor (TLR) agonists exhibit properties that can enhance immune responses, making them potential therapeutic agents or vaccine adjuvants.Methods: We conducted an extensive systematic review to assess the efficacy of TLR agonists as therapeutic agents or vaccine adjuvants for infectious diseases and their safety profile in animals, excluding rodents and cold-blooded animals. We collected qualitative and available quantitative data on the efficacy and safety outcomes of TLR agonists and employed descriptive analysis to summarize the outcomes. Results: Among 653 screened studies, 51 met the inclusion criteria. In this review, 82% (42/51) of the studies used TLR agonists as adjuvants, while 18% (9/51) applied TLR agonist as therapeutic agents. The predominant TLR agonists utilized in animals against infectious diseases was CpG ODN, acting as a TLR9 agonist in mammals, and TLR21 agonists in chickens. In 90% (46/51) of the studies, TLR agonists were found effective in stimulating specific and robust humoral and cellular immune responses, thereby enhancing the efficacy of vaccines or therapeutics against infectious diseases in animals. Safety outcomes were assessed in 8% (4/51) of the studies, with one reporting adverse effects. Discussion: Although TLR agonists are efficacious in enhancing immune responses and the protective efficacy of vaccines or therapeutic agents against infectious diseases in animals, a thorough evaluation of their safety is imperative to in-form future clinical applications in animal studies.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_ record.php?RecordID=323122

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

Influence of Cultivars and Nitrogen Fertilizer Rates and Application Mode on Yields and Quality Parameters of Ratoon Sugarcane in Western Kenya

Productivity of sugarcane in Kenya has declined despite use of recommended production practices including introduction of elite high yielding and early maturing sugarcane varieties. Farmers continue to use recommended agronomic inputs for the old low yielding and late maturing varieties on these elite varieties. Nitrogen fertilizer rates in single or split doses for old varieties are still in use yet their appropriateness on new varieties remains untested culminating to decline in sugarcane productivity in Kenya. Currently, cane payment is based on delivered milling cane weight. The industry plans to change payment to a combination of quality and yields. Influence of agronomic inputs and timing of harvesting period on proposed mode of payment is unknown. Harvesting age in western Kenya remains 18-20 months after ratooning (MAR). However, optimal age that combines quality and yields is not documented. Influence of these agronomic practices on quality, yields and optimal harvesting age of ratoon crop of new (D8484) and old (CO421) varieties were evaluated in a 2x4x3 split-split-plot design replicated three times. Four rates of nitrogen as urea, all applied at 3 MAR, split once (50-50%) and applied at 3 and 6 MAR or split three times (40-30-30%) and applied at 3, 6 and 9 MAR were evaluated. Yields and quality parameters were monitored from 10th-24th MAR. Variety D8484 out-yielded (p≤0.05) CO421 throughout demonstrating its superiority. Yields reached maximum at 20 and 19 MAR for CO421 and D8484, respectively. Maximum pol and brix were attained at 18 and 15 MAR for CO421 and D8484, respectively, while commercial cane sugar (CCS) was maximum at 18 and 17 MAR for CO421 and D8484, respectively. Results demonstrated that for high returns, D8484 should be harvested between 15-18 MAR while CO421 between 17-19 MAR. The 60 kg N/ha, that produced higher (p≤0.05) output in both varieties, from 16th MAR is recommended for both varieties. Split fertilizer application did not affect productivity

Synchrony in Leafing, Flowering, and Fruiting Phenology of Senegalia senegal within Lake Baringo Woodland, Kenya: Implication for Conservation and Tree Improvement

Leafing, flowering, and fruiting patterns of Senegalia senegal were studied over a period of 24 months from January 2014 to December 2015. The phenological events of the species are bimodal and follow the rainfall patterns. The leafing phase starts during the onset of rains and lasts for 18 weeks. New leaves continued to appear on the new shoots while old leaves persisted to the leaf fall period. Flowering event takes 12 weeks and is concentrated in the months of high relative humidity (April and October) with one-month peak flowering period. Fruiting phase starts at the peak of the rainy seasons (May and November) and peaks in June and December. This phase lasted for 14 weeks. The fruits mature towards the end of the rainy season (January/February and July/August). The fruits open for dispersal mainly in February/March and September during the peak dry season. High synchrony index (SI) was found in leafing (SI: 0.87), flowering (SI: 0.75), and fruiting (SI: 0.85) events among the populations. Temperature, precipitation, and soil moisture content were significantly correlated with the phenological events. Significant variations in floral morphology and fruits traits were also evident. Seed collections should be undertaken in the months of January/February and July/August

Using poaching levels and elephant distribution to assess the conservation efficacy of private, communal and goverment land in northern Kenya

Efforts to curb elephant poaching have focused on reducing demand, confiscating ivory and boosting security patrols in elephant range. Where land is under multiple uses and ownership, determining the local poaching dynamics is important for identifying successful conservation models. Using 2,403 verified elephant, Loxodonta africana, mortality records collected from 2002 to 2012 and the results of aerial total counts of elephants conducted in 2002, 2008 and 2012 for the Laikipia-Samburu ecosystem of northern Kenya, we sought to determine the influence of land ownership and use on diurnal elephant distribution and on poaching levels. We show that the annual proportions of illegally killed (i.e., poached) elephants increased over the 11 years of the study, peaking at 70% of all recorded deaths in 2012. The type of land use was more strongly related to levels of poaching than was the type of ownership. Private ranches, comprising only 13% of land area, hosted almost half of the elephant population and had significantly lower levels of poaching than other land use types except for the officially designated national reserves (covering only 1.6% of elephant range in the ecosystem). Communal grazing lands hosted significantly fewer elephants than expected, but community areas set aside for wildlife demonstrated significantly higher numbers of elephants and lower illegal killing levels relative to non-designated community lands. While private lands had lower illegal killing levels than community conservancies, the success of the latter relative to other community-held lands shows the importance of this model of land use for conservation. This work highlights the relationship between illegal killing and various land ownership and use models, which can help focus anti-poaching activities

Livestock Presence Influences the Seroprevalence of Crimean Congo Hemorrhagic Fever Virus on Sympatric Wildlife in Kenya

Crimean Congo Hemorrhagic Fever (CCHF) is an emerging tick-borne zoonotic viral disease with the potential of causing public health emergencies. However, less is known about the role of wildlife and livestock in spreading the virus. Therefore, we aimed to assess how the interactions between African buffalo (Syncerus caffer) and cattle may influence the seroprevalence of CCHF across livestock-wildlife management systems in Kenya. The study included archived sera samples from buffalo and cattle from wildlife only habitats (Lake Nakuru National Park and Solio conservancy), open wildlife-livestock integrated habitats (Maasai Mara ecosystem and Meru National Park), and closed wildlife-livestock habitats (Ol Pejeta Conservancy) in Kenya. We analyzed 191 buffalo and 139 cattle sera using IDvet multispecies, double-antigen IgG enzyme-linked immunosorbent assay (ELISA). The seroprevalence toward Crimean Congo hemorrhagic fever virus (CCHFV) was significantly higher for buffalo compared to cattle (75.3% and 28.1%, respectively, p < 0.001). We obtained the highest seroprevalence among buffalo of 92.1% in closed wildlife only systems compared to 28.8% and 46.1% prevalence in closed-integrated and open-integrated systems, respectively. The regression coefficients were all negative for cattle compared to buffalo in both closed-integrated and open-integrated compared to wildlife only system. Our results show that CCHFV circulates among the diverse animal community in Kenya in spatially disconnected foci. The habitat overlap between cattle and buffalo makes cattle a "bridge species" or superspreader host for CCHFV and increases transmission risks to humans. The effect of animal management system on prevalence is depended on tick control on the cattle and not the animal per se. We conclude that buffalo, a host with a longer life span than livestock, is a reservoir and may serve as a sentinel population for longitudinal surveillance of CCHFV

Viral Population Diversity during Co-Infection of Foot-And-Mouth Disease Virus Serotypes SAT1 and SAT2 in African Buffalo in Kenya

African buffalo are the natural reservoirs of the SAT serotypes of foot-and-mouth disease virus (FMDV) in sub-Saharan Africa. Most buffalo are exposed to multiple FMDV serotypes early in life, and a proportion of them become persistently infected carriers. Understanding the genetic diversity and evolution of FMDV in carrier animals is critical to elucidate how FMDV persists in buffalo populations. In this study, we obtained oropharyngeal (OPF) fluid from naturally infected African buffalo, and characterized the genetic diversity of FMDV. Out of 54 FMDV-positive OPF, 5 were co-infected with SAT1 and SAT2 serotypes. From the five co-infected buffalo, we obtained eighty-nine plaque-purified isolates. Isolates obtained directly from OPF and plaque purification were sequenced using next-generation sequencing (NGS). Phylogenetic analyses of the sequences obtained from recombination-free protein-coding regions revealed a discrepancy in the topology of capsid proteins and non-structural proteins. Despite the high divergence in the capsid phylogeny between SAT1 and SAT2 serotypes, viruses from different serotypes that were collected from the same host had a high genetic similarity in non-structural protein-coding regions P2 and P3, suggesting interserotypic recombination. In two of the SAT1 and SAT2 co-infected buffalo identified at the first passage of viral isolation, the plaque-derived SAT2 genomes were distinctly grouped in two different genotypes. These genotypes were not initially detected with the NGS from the first passage (non-purified) virus isolation sample. In one animal with two SAT2 haplotypes, one plaque-derived chimeric sequence was found. These findings demonstrate within-host evolution through recombination and point mutation contributing to broad viral diversity in the wildlife reservoir. These mechanisms may be critical to FMDV persistence at the individual animal and population levels, and may contribute to the emergence of new viruses that have the ability to spill-over to livestock and other wildlife species