Paradigm shift in the diagnosis of peste des petits ruminants: scoping review

Peste des petits ruminants virus causes a highly contagious disease, which poses enormous economic losses in domestic animals and threatens the conservation of wild herbivores. Diagnosis remains a cornerstone to the Peste des petits ruminants Global Control and Eradication Strategy, an initiative of the World Organisation for Animal Health and the Food and Agriculture Organisation. The present review presents the peste des petits ruminants diagnostic landscape, including the practicality of commercially available diagnostic tools, prototype tests and opportunities for new technologies. The most common peste des petits ruminants diagnostic tools include; agar gel immunodiffusion, counter-immunoelectrophoresis, enzyme-linked immunosorbent assays, reverse transcription polymerase chain reaction either gel-based or real-time, reverse transcription loop-mediated isothermal amplification, reverse transcription recombinase polymerase amplification assays, immunochromatographic lateral flow devices, luciferase immunoprecipitation system and pseudotype-based assays. These tests vary in their technical demands, but all require a laboratory with exception of immunochromatographic lateral flow and possibly reverse transcription loop-mediated isothermal amplification and reverse transcription recombinase polymerase amplification assays. Thus, we are proposing an efficient integration of diagnostic tests for rapid and correct identification of peste des petits ruminants in endemic zones and to rapidly confirm outbreaks. Deployment of pen-side tests will improve diagnostic capacity in extremely remote settings and susceptible wildlife ecosystems, where transportation of clinical samples in the optimum cold chain is unreliable

FIGO postpartum intrauterine device initiative: Complication rates across six countries.

OBJECTIVE: To record and analyze complication rates following postpartum intrauterine device (PPIUD) insertion in 48 hospitals in six countries: Sri Lanka, India, Nepal, Bangladesh, Tanzania, and Kenya. METHODS: Healthcare providers were trained in counselling and insertion of PPIUD via a training-the-trainer model. Data were collected on methodology, timing, cadre of staff providing care, and number of insertions. Data on complications were collected at 6-week follow-up. Statistical analysis was performed to elucidate factors associated with increased expulsion and absence of threads. RESULTS: From May 2014 to September 2017, 36 766 PPIUDs were inserted: 53% vaginal and 47% at cesarean delivery; 74% were inserted by doctors. Follow-up was attended by 52%. Expulsion and removal rates were 2.5% and 3.6%, respectively. Threads were not visible in 29%. Expulsion was less likely after cesarean insertion (aOR 0.33; 95% CI, 0.26-0.41), following vaginal insertion at between 10 minutes and 48 hours (aOR 0.59; 95% CI, 0.42-0.83), and when insertion was performed by a nurse (aOR 0.33; 95% CI, 0.22-0.50). CONCLUSION: PPIUD has low complication rates and can be safely inserted by a variety of trained health staff. Given the immediate benefit of the one-stop approach, governments should urgently consider adopting this model

Induction of humoral immune response to multiple recombinant Rhipicephalus appendiculatus antigens and their effect on tick feeding success and pathogen transmission

BACKGROUND: Rhipicephalus appendiculatus is the primary vector of Theileria parva, the etiological agent of East Coast fever (ECF), a devastating disease of cattle in sub-Saharan Africa. We hypothesized that a vaccine targeting tick proteins that are involved in attachment and feeding might affect feeding success and possibly reduce tick-borne transmission of T. parva. Here we report the evaluation of a multivalent vaccine cocktail of tick antigens for their ability to reduce R. appendiculatus feeding success and possibly reduce tick-transmission of T. parva in a natural host-tick-parasite challenge model. METHODS: Cattle were inoculated with a multivalent antigen cocktail containing recombinant tick protective antigen subolesin as well as two additional R. appendiculatus saliva antigens: the cement protein TRP64, and three different histamine binding proteins. The cocktail also contained the T. parva sporozoite antigen p67C. The effect of vaccination on the feeding success of nymphal and adult R. appendiculatus ticks was evaluated together with the effect on transmission of T. parva using a tick challenge model. RESULTS: To our knowledge, this is the first evaluation of the anti-tick effects of these antigens in the natural host-tick-parasite combination. In spite of evidence of strong immune responses to all of the antigens in the cocktail, vaccination with this combination of tick and parasite antigens did not appear to effect tick feeding success or reduce transmission of T. parva. CONCLUSION: The results of this study highlight the importance of early evaluation of anti-tick vaccine candidates in biologically relevant challenge systems using the natural tick-host-parasite combination

Epigenetic Alteration of the Cancer-Related Gene TGFBI in B Cells Infected with Epstein–Barr Virus and Exposed to Aflatoxin B1: Potential Role in Burkitt Lymphoma Development

Burkitt lymphoma (BL) is a malignant B cell neoplasm that accounts for almost half of pediatric cancers in sub-Saharan African countries. Although the BL endemic prevalence is attributable to the combination of Epstein–Barr virus (EBV) infection with malaria and environmental carcinogens exposure, such as the food contaminant aflatoxin B1 (AFB1), the molecular determinants underlying the pathogenesis are not fully understood. Consistent with the role of epigenetic mechanisms at the interface between the genome and environment, AFB1 and EBV impact the methylome of respectively leukocytes and B cells specifically. Here, we conducted a thorough investigation of common epigenomic changes following EBV or AFB1 exposure in B cells. Genome-wide DNA methylation profiling identified an EBV–AFB1 common signature within the TGFBI locus, which encodes for a putative tumor suppressor often altered in cancer. Subsequent mechanistic analyses confirmed a DNA-methylation-dependent transcriptional silencing of TGFBI involving the recruitment of DNMT1 methyltransferase that is associated with an activation of the NF-κB pathway. Our results reveal a potential common mechanism of B cell transformation shared by the main risk factors of endemic BL (EBV and AFB1), suggesting a key determinant of disease that could allow the development of more efficient targeted therapeutic strategies

Genetic and antigenic variation of the bovine tick-borne pathogen Theileria parva in the Great Lakes region of Central Africa

BACKGROUND : Theileria parva causes East Coast fever (ECF), one of the most economically important tick-borne diseases of cattle in sub-Saharan Africa. A live immunisation approach using the infection and treatment method (ITM) provides a strong long-term strain-restricted immunity. However, it typically induces a tick-transmissible carrier state in cattle and may lead to spread of antigenically distinct parasites. Thus, understanding the genetic composition of T. parva is needed prior to the use of the ITM vaccine in new areas. This study examined the sequence diversity and the evolutionary and biogeographical dynamics of T. parva within the African Great Lakes region to better understand the epidemiology of ECF and to assure vaccine safety. Genetic analyses were performed using sequences of two antigencoding genes, Tp1 and Tp2, generated among 119 T. parva samples collected from cattle in four agro-ecological zones of DRC and Burundi. RESULTS : The results provided evidence of nucleotide and amino acid polymorphisms in both antigens, resulting in 11 and 10 distinct nucleotide alleles, that predicted 6 and 9 protein variants in Tp1 and Tp2, respectively. Theileria parva samples showed high variation within populations and a moderate biogeographical sub-structuring due to the widespread major genotypes. The diversity was greater in samples from lowlands and midlands areas compared to those from highlands and other African countries. The evolutionary dynamics modelling revealed a signal of selective evolution which was not preferentially detected within the epitope-coding regions, suggesting that the observed polymorphism could be more related to gene flow rather than recent host immune-based selection. Most alleles isolated in the Great Lakes region were closely related to the components of the trivalent Muguga vaccine. CONCLUSIONS : Our findings suggest that the extensive sequence diversity of T. parva and its biogeographical distribution mainly depend on host migration and agro-ecological conditions driving tick population dynamics. Such patterns are likely to contribute to the epidemic and unstable endemic situations of ECF in the region. However, the fact that ubiquitous alleles are genetically similar to the components of the Muguga vaccine together with the limited geographical clustering may justify testing the existing trivalent vaccine for cross-immunity in the region.Additional file 1: Table S1. Cattle blood sample distribution across agroecological zones.Additional file 2: Table S2. Nucleotide and amino acid sequences of Tp1 and Tp2 antigen epitopes from T. parva Muguga reference sequence.Additional file 3: Table S3. Characteristics of 119 T. parva samples obtained from cattle in different agro-ecological zones (AEZs) of The Democratic Republic of Congo and Burundi.Additional file 4: Figure S1. Multiple sequence alignment of the 11 Tp1 gene alleles obtained in this study.Additional file 5: Table S4. Estimates of evolutionary divergence between gene alleles for Tp1 and Tp2, using proportion nucleotide distance.Additional file 6: Table S5. Tp1 and Tp2 genes alleles with their corresponding antigen variants.Additional file 7: Table S6. Amino acid variants of Tp1 and Tp2 CD8+ T cell target epitopes of T. parva from DRC and Burundi.Additional file 8: Figure S2. Multiple sequence alignment of the 10 Tp2 gene alleles obtained in this study.Additional file 9: Table S7. Distribution of Tp1 gene alleles of T. parva from cattle and buffalo in the sub-Saharan region of Africa.Additional file 10: Table S8. Distribution of Tp2 gene alleles of T. parva from cattle and buffalo in the sub-Saharan region of Africa.Additional file 11: Figure S3. Neighbor-joining tree showing phylogenetic relationships among 48 Tp1 gene alleles described in Africa.Additional file 12: Figure S4. Phylogenetic tree showing the relationships among concatenated Tp1 and Tp2 nucleotide sequences of 93 T. parva samples from cattle in DRC and Burundi.This study is part of the PhD work supported by the University of Namur (UNamur, Belgium) through the UNamur-CERUNA institutional PhD grant awarded to GSA for bioinformatic analyses, interpretation of data and manuscript write up in Belgium. The laboratory aspects (molecular biology analysis) of the project were supported by the BecA-ILRI Hub through the Africa Biosciences Challenge Fund (ABCF) programme. The ABCF Programme is funded by the Australian Department for Foreign Affairs and Trade (DFAT) through the BecA-CSIRO partnership; the Syngenta Foundation for Sustainable Agriculture (SFSA); the Bill & Melinda Gates Foundation (BMGF); the UK Department for International Development (DFID); and the Swedish International Development Cooperation Agency (Sida). The ABCF Fellowship awarded to GAS was funded by BMGF grant (OPP1075938). Sample collection, field equipment and preliminary sample processing were supported through the “Theileria” project co-funded to the Université Evangélique en Afrique (UEA) by the Agence Universitaire de la Francophonie (AUF) and the Communauté Economique des Pays des Grands Lacs (CEPGL). The International Foundation for Science (IFS, Stockholm, Sweden) supported the individual scholarship awarded to GSA (grant no. IFS-92890CA3) for field work and part of field equipment to the “Theileria” project.http://www.parasitesandvectors.comam2020Veterinary Tropical Disease

Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

<p><b>Background:</b> Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.</p> <p><b>Methodology/Principal Findings:</b> Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (similar to 12%) in Tp1 and in 320 positions (similar to 61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.</p> <p><b>Conclusions/Significance:</b> The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.</p&gt

Two Theileria parva CD8 T Cell Antigen Genes Are More Variable in Buffalo than Cattle Parasites, but Differ in Pattern of Sequence Diversity

<p><b>Background:</b> Theileria parva causes an acute fatal disease in cattle, but infections are asymptomatic in the African buffalo (Syncerus caffer). Cattle can be immunized against the parasite by infection and treatment, but immunity is partially strain specific. Available data indicate that CD8(+) T lymphocyte responses mediate protection and, recently, several parasite antigens recognised by CD8(+) T cells have been identified. This study set out to determine the nature and extent of polymorphism in two of these antigens, Tp1 and Tp2, which contain defined CD8(+) T-cell epitopes, and to analyse the sequences for evidence of selection.</p> <p><b>Methodology/Principal Findings:</b> Partial sequencing of the Tp1 gene and the full-length Tp2 gene from 82 T. parva isolates revealed extensive polymorphism in both antigens, including the epitope-containing regions. Single nucleotide polymorphisms were detected at 51 positions (similar to 12%) in Tp1 and in 320 positions (similar to 61%) in Tp2. Together with two short indels in Tp1, these resulted in 30 and 42 protein variants of Tp1 and Tp2, respectively. Although evidence of positive selection was found for multiple amino acid residues, there was no preferential involvement of T cell epitope residues. Overall, the extent of diversity was much greater in T. parva isolates originating from buffalo than in isolates known to be transmissible among cattle.</p> <p><b>Conclusions/Significance:</b> The results indicate that T. parva parasites maintained in cattle represent a subset of the overall T. parva population, which has become adapted for tick transmission between cattle. The absence of obvious enrichment for positively selected amino acid residues within defined epitopes indicates either that diversity is not predominantly driven by selection exerted by host T cells, or that such selection is not detectable by the methods employed due to unidentified epitopes elsewhere in the antigens. Further functional studies are required to address this latter point.</p&gt

Potential impact of prickly pear cactus flour and Salix babylonica extract on cecal fermentation and methane production in horses

The cecal gas (GP) and methane (CH4) production and cecal fermentation kinetics when corn grain (CG) was replaced with prickly cactus (PC) in a horse’s diet at different levels of Salix babylonica (SB) extract was investigated. Three total mixed rations where CG was replaced with PC at three levels (/kg): 0 g (Control), 75 g (PC75) or 150 g (PC150) were prepared and SB extract added at four levels: 0, 0.6, 1.2 and 1.8 mL/g dry matter (DM) of substrates. No ration type 9 SB extract dose interaction was observed (P [0.05) for GP kinetics and CH4 production. Increasing the level of PC in the ration quadratically increased (P \0.01) the asymptotic GP and decreased (P\0.01) the rate and lag time of GP. Increasing the level of PC in the ration, increased GP values (P\0.05). Increasing the level of SB extract linearly decreased (P = 0.001) the lag time of GP of all diets without affecting the asymptotic GP or the rate of GP. Ration type and SB level had no effect (P [0.05) on CH4 production; however, at 36 h of incubation, SB extract decreased CH4 production. The rations PC75 and PC150 increased cecal pH compared with the control ration. The PC150 ration had the highest (P\0.05) DM degradability, short chain fatty acids production, and gas yield after 24 h of incubation, with no effect (P[0.05) of SB inclusion on all investigated fermentation kinetic parameters. It is concluded that increasing the level of PC in the diet of horse and replacing CG up to 60%, increased GP and improved cecal fermentation kinetics without affecting CH4 production. Inclusion of S. babylonica extract in the tested rations had weak effects on fermentation kinetics although it decreased the lag time of GP