Developing a PmSLP3-based vaccine formulation that provides robust long-lasting protection against hemorrhagic septicemia–causing serogroup B and E strains of Pasteurella multocida in cattle

BackgroundPasteurella multocida is a bacterial pathogen that causes a variety of infections across diverse animal species, with one of the most devastating associated diseases being hemorrhagic septicemia. Outbreaks of hemorrhagic septicemia in cattle and buffaloes are marked by rapid progression and high mortality. These infections have particularly harmful socio-economic impacts on small holder farmers in Africa and Asia who are heavily reliant on a small number of animals kept as a means of subsistence for milk and draft power purposes. A novel vaccine target, PmSLP-3, has been identified on the surface of hemorrhagic septicemia–associated strains of P. multocida and was previously shown to elicit robust protection in cattle against lethal challenge with a serogroup B strain.MethodsHere, we further investigate the protective efficacy of this surface lipoprotein, including evaluating the immunogenicity and protection upon formulation with a variety of adjuvants in both mice and cattle.ResultsPmSLP-3 formulated with Montanide ISA 61 elicited the highest level of serum and mucosal IgG, elicited long-lasting serum antibodies, and was fully protective against serogroup B challenge. Studies were then performed to identify the minimum number of doses required and the needed protein quantity to maintain protection. Duration studies were performed in cattle, demonstrating sustained serum IgG titres for 3 years after two doses of vaccine and full protection against lethal serogroup B challenge at 7 months after a single vaccine dose. Finally, a serogroup E challenge study was performed, demonstrating that PmSLP-3 vaccine can provide protection against challenge by the two serogroups responsible for hemorrhagic septicemia.ConclusionTogether, these data indicate that PmSLP-3 formulated with Montanide ISA 61 is an immunogenic and protective vaccine against hemorrhagic septicemia-causing P. multocida strains in cattle

Magnitude and causes of first-line antiretroviral therapy regimen changes among HIV patients in Ethiopia: a systematic review and meta-analysis

Background: Antiretroviral therapy (ART) has markedly decreased the morbidity and mortality due to HIV/AIDS. ART regimen change is a major challenge for the sustainability of human immunodeficiency virus (HIV) treatment program. This is found to be a major concern among HIV/AIDS patients in a resource-limited setting, where treatment options are limited. Objectives: The aim of this review is to generate the best available evidence regarding the magnitude of first-line antiretroviral therapy regimen change and the causes for regimen change among HIV patients on ART in Ethiopia. Methods: The reviewed studies were accessed through electronic web-based search strategy from PubMed Medline, EMBASE, Hinari, Springer link and Google Scholar. Data were extracted using Microsoft Excel and exported to Stata software version 13 for analyses. The overall pooled estimation of outcomes was calculated using a random-effect model of DerSimonian-Laird method at 95% confidence level. Heterogeneity of studies was determined using I2 statistics. For the magnitude of regimen change, the presence of publication bias was evaluated using the Begg's and Egger's tests. The protocol of this systematic review and meta-analysis was registered in the Prospero database with reference number ID: CRD42018099742. The published methodology is available from: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=99742. Results: A total of 22 studies published between the years 2012 and 2018 were included. Out of 22 articles, 14 articles reported the magnitude of regimen change and consisted of 13,668 HIV patients. The estimated national pooled magnitude of regimen change was 37% (95% CI: 34, 44%; Range: 15.1-63.8%) with degree of heterogeneity (I2), 98.7%; p-value < 0.001. Seventeen articles were used to identify the causes for first-line antiretroviral therapy regimen change. The major causes identified were toxicity, 58% (95% CI: 46, 69%; Range: 14.4-88.5%); TB co-morbidity, 12% (95% CI: 8, 16%; Range: 0.8-31.7%); treatment failure, 7% (95% CI: 5, 9%; Range: 0.4-24.4%); and pregnancy, 5% (95% CI: 4, 7%; Range: 0.6-11.9%). Conclusions: The original first-line regimen was changed in one-third of HIV patients on ART in Ethiopia. Toxicity of the drugs, TB co-morbidity, treatment failure, and pregnancy were the main causes for the change of the first-line regimen among HIV patients on antiretroviral therapy

Data from: Ecology and genomics of an important crop wild relative as a prelude to agricultural innovation

Domesticated species are impacted in unintended ways during domestication and breeding. Changes in the nature and intensity of selection impart genetic drift, reduce diversity, and increase the frequency of deleterious alleles. Such outcomes constrain our ability to expand the cultivation of crops into environments that differ from those under which domestication occurred. We address this need in chickpea, an important pulse legume, by harnessing the diversity of wild crop relatives. We document an extreme domestication-related genetic bottleneck and decipher the genetic history of wild populations. We provide evidence of ancestral adaptations for seed coat color crypsis, estimate the impact of environment on genetic structure and trait values, and demonstrate variation between wild and cultivated accessions for agronomic properties. A resource of genotyped, association mapping progeny functionally links the wild and cultivated gene pools and is an essential resource chickpea for improvement, while our methods inform collection of other wild crop progenitor species