High-dimensional supervised classification in a context of non-independence of observations to identify the determining SNPs in a phenotype.

This work addresses the problem of supervised classification for highly correlated high-dimensional data describing non-independent observations to identify SNPs related to a phenotype. We use a general penalized linear mixed model with a single random effect that performs simultaneous SNP selection and population structure adjustment in high-dimensional prediction models. Specifically, the model simultaneously selects variables and estimates their effects, taking into account correlations between individuals. Single nucleotide polymorphisms (SNPs) are a type of genetic variation and each SNP represents a difference in a single DNA building block, namely a nucleotide. Previous research has shown that SNPs can be used to identify the correct source population of an individual and can act in isolation or simultaneously to impact a phenotype. In this regard, the study of the contribution of genetics in infectious disease phenotypes is of great importance. In this study, we used uncorrelated variables from the construction of blocks of correlated variables done in a previous work to describe the most related observations of the dataset. The model was trained with 90% of the observations and tested with the remaining 10%. The best model obtained with the generalized information criterion (GIC) identified the SNP named rs2493311 located on the first chromosome of the gene called PRDM16 ((PR/SET domain 16)) as the most decisive factor in malaria attacks.

Establishing National Multisectoral Coordination and collaboration mechanisms to prevent, detect, and respond to public health threats in Guinea, Liberia, and Sierra Leone 2016-2018.

BACKGROUND: The governments of Guinea, Liberia, and Sierra Leone have acknowledged that weak health systems and poor coordination of efforts hampered effectiveness of the 2014-2016 Ebola outbreak response. The bitter experience of the Ebola outbreak response served as an important catalyst for increased efforts to comply with World Health Organization (WHO) International Health Regulations (IHR 2005), Performance of Veterinary Services (PVS) Pathway capacities, and Global Health Security Agenda (GHSA) goals. In November 2016, an interministerial meeting held in Dakar, Senegal, resulted in formalized commitments from the three nations to strengthen resilience to health threats by establishing a Regional Strategic Roadmap to institutionalize the One Health approach. Since then, each country has made significant progress towards establishing National One Health Platforms to coordinate health security interventions, in collaboration with international partners. This paper outlines the methodology and results of these efforts for the period June 2016-January 2019, with a specific focus on activities supported by the US Agency for International Development (USAID)-funded Preparedness & Response (P&R) project. OBJECTIVES: In support of the West African Health Organization's November 2016 Regional Strategic Roadmap for institutionalization of the One Health approach, the Preparedness & Response (P&R) project worked in coordination with national partners in Guinea, Liberia, and Sierra Leone to establish multisectoral, One Health coordinating mechanisms. METHODOLOGY: The global USAID-funded P&R project was launched in 2014 to support the achievement of this objective, and began coordinating with partners in Guinea, Liberia, and Sierra Leone in 2016 to tailor its multi-step conceptual framework to fit the priorities and operating constraints of national stakeholders. Organized in phases of Collaboration (building key relationships), Formalization (defining and establishing a coordination structure), and Implementation (using newfound coordination to produce better health security outcomes), the framework features steps such as One Health sensitizations for multisectoral national stakeholders, development of One Health platform terms of reference and other operating guidelines, and application of these tools to coordination of technical assistance during outbreaks. RESULTS: In Guinea, Liberia, and Sierra Leone, in less than 3 yrs there has been a marked improvement in cross-sectoral coordination on health security actions. All three countries have passed legislation establishing permanent multisectoral coordination mechanisms referred to in this document as National One Health Platforms, or simply Platforms; instituted an annual mechanism for assessing capacity and performance of these platforms to lead health security actions; and have undertaken key steps towards developing and updating National Preparedness & Response Plans which truly reflect the multisectoral nature of emerging disease threats. However, multisectoral coordination is a work in progress: government stakeholders and their international partners continue to work together to further strengthen national ownership and investment in the newly established Platforms. CONCLUSION AND NEXT STEPS: Newly established Platforms in Guinea, Liberia, and Sierra Leone offer a long-term structure for coordinating health security actions. However, given the short period of time since their formalization, they depend on continued national, regional, and international resources to build from recent progress and further improve capacity and performance. Regional programs such as the World Bank Regional Disease Surveillance Systems Enhancement (REDISSE) project are of critical importance in keeping the momentum going. The highlighted progress and outputs to date provide reasons and motivation for continued, longer-term investment in the Platforms.

Efficacy of praziquantel against urinary schistosomiasis and reinfection in Senegalese school children where there is a single well-defined transmission period.

BACKGROUND: Human schistosomiasis is a significant health problem in Sub-Saharan Africa. In Niakhar, West central Senegal, the transmission of S. haematobium occurs seasonally between July and November. No control measures have been implemented despite high prevalence reported in previous studies. This aim of this study was to i) determine the current prevalence of S. haematobium in children at Niakhar, ii) assess the efficacy of one dose of PZQ (40 mg/kg) against S. haematobium and iii) monitor reinfection. METHODS: The current study was carried out in a cohort of 329 children aged five to 15 years enrolled from six villages in Niakhar to determine the efficacy of one dose of PZQ, as well as reinfection. Parasitological screening was performed in June 2011 to determine the baseline prevalence of S. haematobium, and then a single dose of PZQ was administered to all selected subjects in the transmission season in August 2011. The efficacy of PZQ treatment and reinfection were monitored respectively five weeks after in September 2011 and from February to March 2012. RESULTS: At baseline, the overall prevalence and the heavy intensity of infection were 73.2% and 356.1 eggs/10 ml of urine. Significant differences in the prevalence and intensity of S. haematobium infection were noted between villages. A single dose of PZQ significantly reduced the prevalence of S. haematobium infection from 73.2% to 4.6% and the geometric mean intensity of infection from 356.1 to 43.3 eggs/10 ml of urine. The cure rates ranged from 89.4% to 100%. The egg reduction rates also ranged from 77.6% to 100%. Two to three months after the period of transmission, the overall rate of reinfection was 12.6% and was significantly higher in male children than in female children. The overall prevalence at this period was 13.8%, which was significantly lower than the prevalence at baseline (73.2%). CONCLUSION: The Niakhar study area remains a hot spot of urinary schistosomiasis in Senegal with differences in transmission between villages. This study suggests that when transmission is strictly seasonal, Praziquantel shows the expected efficacy in reducing the prevalence and intensity of infection, but also a significant effect on the occurrence of reinfection.

Seroprevalence investigation of bovine brucellosis in Macenta and Yomou, Guinea.

Brucellosis is one of the world's major zoonotic diseases associated with reproductive disorders and a potential infection of human. Brucellosis leads to serious economic losses due to late-term abortion, stillbirth, weak calves, and sterility. In Guinea, the data on brucellosis was only detected as far back as 10 years ago. The purpose of this study was to estimate the prevalence of bovine brucellosis in the provinces of Macenta and Yomou of Guinea. A structured questionnaire was used in the clinical study, and 345 cattle were clinically examined. Three hundred serum samples were initially subjected to the Rose Bengal test (RBT); the positive results of which were confirmed by the complement fixation test (CFT). The investigation indicated that farmers had little information on brucellosis. Hygroma, abortion, sterility, and placental retention were the observed symptoms. Of the 29 RBT-positive samples, 26 were confirmed by CFT. The prevalence of brucellosis in Macenta and Yomou was 12 and 5.33 %, respectively. In both provinces, the prevalence mean was 8.67 %. This study highlighted the immediate necessity to carry out a strengthened surveillance of human and animal brucellosis to obtain as many data as possible in order to establish strategies for prevention and management of brucellosis in Guinea.

Protective immunity conferred by porcine circovirus 2 ORF2-based DNA vaccine in mice.

Post-weaning multisystemic wasting syndrome (PMWS) associated with porcine circovirus type 2 (PCV2) has caused the swine industry significant health challenges and economic damage. Although inactivated and subunit vaccines against PMWS have been used widely, so far no DNA vaccine is available. In this study, with the aim of exploring a new route for developing a vaccine against PCV2, the immunogenicity of a DNA vaccine was evaluated in mice. The pEGFP-N1 vector was used to construct a PCV2 Cap gene recombinant vaccine. To assess the immunogenicity of pEGFP-Cap, 80 BALB/c mice were immunized three times at 2 weekly intervals with pEGFP-Cap, LG-strain vaccine, pEGFP-N1 vector or PBS and then challenged with PCV2. IgG and cytokines were assessed by indirect ELISA and ELISA, respectively. Specimens stained with hematoxylin and eosin (HE) and immunohistochemistry (IHC) techniques were examined histopathologically. It was found that vaccination of the mice with the pEGFP-Cap induced solid protection against PCV2 infection through induction of highly specific serum IgG antibodies and cytokines (IFN-γ and IL-10), and a small PCV2 viral load. The mice treated with the pEGFP-Cap and LG-strain developed no histopathologically detectable lesions (HE stain) and IHC techniques revealed only a few positive cells. Thus, this study demonstrated that recombinant pEGFP-Cap substantially alleviates PCV2 infection in mice and provides evidence that a DNA vaccine could be an alternative to PCV2 vaccines against PMWS.

RNA interference targeting nucleocapsid protein inhibits porcine reproductive and respiratory syndrome virus replication in Marc-145 cells.

Porcine reproductive and respiratory syndrome (PRRS) is an important disease, which leads to severe economic losses in swine-producing areas of the world. However, current antiviral strategies cannot provide highly effective protection. In this study, three theoretically effective interference target sites (71-91, 144-164, 218-238) targeting the nucleocapsid (N) gene of PRRSV were designed and selected, and then three siRNA-expressing plasmids were constructed, respectively named p2.1-N71, p2.1-N144, and p2.1-N218. The recombinant siRNA-expressing plasmids were transfected into Marc-145 cells; then the cells were infected with PRRSV (JL07SW strain); finally, after incubation for 48 h, the antiviral activity of those siRNA-expressing plasmids in Marc-145 cells was assessed by cytopathic effects, virus titers, indirect immunofluorescence, and quantitative real-time PCR. Experimental results demonstrated that these three siRNA-expressing plasmids could effectively and significantly inhibit the replication of PRRSV by 93.2%, 83.6%, and 89.2% in Marc-145 cells, respectively. Among these three siRNA-expressing plasmids, p2.1-N71 was found to be most effective, while p2.1-N144 and p2.1-N218 displayed relatively weak inhibition of virus replication. The results indicated that siRNA-expressing plasmids targeting the N gene of PRRSV could significantly inhibit PRRSV replication in Marc-145 cells. Based on our experimental results and previous reports, the 71-91, 179-197, and 234-252 sites of the N gene are good choices to effectively inhibit the replication of PRRSV, and this RNA interference technique can be a potential anti-PRRSV strategy.

Prevalence and intensity of urinary schistosomiasis among school children in the district of Niakhar, region of Fatick, Senegal.

BACKGROUND: Urinary schistosomiasis is a parasitic disease that exists in all regions of Senegal. It is a major public health issue in this country. This study was carried out to determine the prevalence and intensity of this parasitosis in 12 villages of Niakhar (Fatick, Senegal). METHODS: A total of 210 schoolchildren, aged 7 to 15 years, were enrolled in this study, and urine samples were examined for Schistosoma haematobium eggs using a standard urine filtration technique. RESULTS: Of these children, 121 (57.6%) were found to be infected with a mean geometric count of 185 eggs per 10 ml of urine. The disease was present in all surveyed villages, and the prevalence ranged from 14.3% to 92.8%. The prevalence of infection was significantly correlated with increasing age and was higher in boys. Infection intensity was significantly higher in boys but did not significantly differ with age. Significant relationships between i) water contact or access to running water and ii) the prevalence or intensity of urinary schistosomiasis were also noted. CONCLUSIONS: The district of Niakhar is endemic for urinary schistosomiasis, with a high intensity of infection. A control program to decrease the prevalence and intensity should be implemented in this area to improve community health.