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On January 30, 2020, the WHO declared the COVID-19 outbreak a public health emergency of international concern and, in March 2020, began to characterize it as a pandemic in order to emphasize the gravity of the situation and urge all countries to take action in detecting infection and preventing spread. Unfortunately, there is no medication that has been approved by the FDA, gone through controlled studies and demonstrated an effect on the virus for this global pandemic. Although there are cures for illnesses and developments made by leaps and bounds in our day, the strongest and most effective weapon that society has against this virus is the prevention of its spread. The main points in preventing the spread in society are hand hygiene, social distancing, and quarantine. With increased testing capacity, detecting more COVID-19 positive patients in the community will also enable the reduction of secondary cases with stricter quarantine rules. Treatment with the use of plant extracts and vaccination are also control measures that are implemented in Cameroon. This review will focus on the prevention and control measures applied in Cameroon to combat the spread of the pandemic.

In low- and middle-income countries, undernutrition often co-exists with intestinal parasites, especially Soil Transmitted Helminth (STH) infections in children. The collective impact of both conditions result in undernutrition and can exacerbate the general poor health status of children. A cross-sectional survey of 422 mother-child (12-59 months old) pairs from 14 villages in the District of Ndelele, East Region of Cameroon, was carried out to assess the magnitude and correlates of undernutrition and intestinal parasites. Socio-demographic data were collected from mothers and anthropometric data were collected from children. Parasitological assessment was performed using a combination of direct microscopy flotation, sedimentation and centrifugation techniques. Correlates of undernutrition and intestinal parasites were identified using multinomial logistic regression at individual and household levels. 83.77% of the children assessed for undernutrition were undernourished and 66.82% were positive for one or more intestinal parasites. It was not uncommon for the study participants to be concurrently infected with two or more intestinal parasites. The most common intestinal parasitic infections detected in the study were A. lumbricoides, E. histolytica/dispar and Hookworm infection. Multinomial logistic regression using Nutritional status as outcome showed that, children who were not exclusively breastfed were 106% (RR = 2.06; C.I = 1.12-3.80) more likely to be underweight compared to those who were exclusively breastfed. The household size of 4 to 6 persons also significantly impacted wasting (p-value = 0.007) at 7% (RR = 1.07, C.I = 0.49-2.32). Analysis by a logistic regression model with STH infection as outcome revealed that, Fingernail cleanness (p-value = 0.044; AOR = 1.75; CI = 1.09-2.78) and household size (p-value = 0.038; AOR = 0.55; CI = 0.32-0.92) were positively associated with intestinal parasite infection at the 5% significant level. This study reveals that intestinal helminthic parasitic infections (STH) and undernutrition are serious health problems in children below five in the study area. To address this dire situation, concerted efforts are needed to improve sanitation, hygiene education access, community deworming programs, and improve diets. The authors thank the study participants, quarter heads, chiefs, data collectors and all staff of both the Ngotto and Banga health centers. We would also like to thank the University of Buea for support in materials and postgraduate funds. We are equally grateful to the Molecular and Cell Biology laboratory of the University of Buea for their support in the accomplishment of this study. We thank the field staff and data collectors for taking their precious time to collect the data and most especially our field coordinator Mr Caleb Yengo and our data analyst Ms Rahmah Mahdiyatur.

Additional file 1. Distribution of sampled water bodies within the study sites in Akonolinga health district.

Additional file 1. Although not significant GMPD decreased with an increase in age in the high lands as well as the higher values observed in males than females in the low (465) and high lands (385). However, the GMPD/ µL of blood in males (465) and females (434) was significantly higher (P < 0.001) in the lowland when compared with the other altitudinal sites.

Additional file 2. Distribution of MU-positivity per sampled locality and sample type.

Sapoviruses (SaVs) belong to the Sapovirus genus, in the family Caliciviridae. They have been associated with gastroenteritis in humans and in pigs but not in other animals. In addition, some strains from pigs, chimpanzees and rodents show close sequence identity with human SaVs thereby suggesting the possibility of interspecies transmissions. Bats are known to be a major reservoir of zoonotic viruses, however, very little is known about the genetic diversity of SaVs in bats. To explore the genetic diversity of bat SaVs, fecal samples of Eidolon helvum and Epomophorus gambianus were treated according to the NetoVIR protocol and sequenced by Illumina technology. Nearly complete genome sequences of six highly divergent SaVs and one partial SaV (only VP1 region) were identified in Eidolon helvum and based on sequence identities and phylogenetic analysis, they potentially represent two novel genogroups, only distantly related to known SaVs. Furthermore, comparing these sequences with currently used screening primers and probes indicated that the novel SaVs would not be detected in routine epidemiological screening studies in humans in case an interspecies transmission would occur. Therefore, we designed and validated new primers that can detect both human and bat SaVs. In this study, we identified multiple novel bat SaVs, however, further epidemiological studies in humans are needed to unravel their potential role in gastroenteritis. ispartof: Emerging Microbes & infections vol:6 issue:5 ispartof: location:United States status: published

THE STATE OF THE ART Cameroon being a lower income country with a population of 23.4million inhabitants in 2016 of which 43.5% live below the national poverty line (income less than 3.1 US dollars/day/capita). An estimated 24% of its population lives below the international poverty line (income of 1.9 dollars/day/capita). The agricultural sector contributes 20% of the Gross domestic product (GDP) of Cameroon with the livestock sector contributing 13% and employs 30% of the rural population. In Cameroon, one third of the households are involved in livestock production. 23.3% of these livestock rearing households farm pigs. Livestock provides these families with an income and nutrition. The current pig production is estimated to be 2.02kg/person and is substantially lower compared to the expected 5kg/person . Although Cameroon is the fourth largest pork producer in Africa, it does not reach its maximum capacity for reasons being that the sector is facing numerous livestock diseases of which African swine Fever (ASF) is of utmost important. The first ASF outbreak occurred in 1982 and affected over 80% of the 1.6 million pigs in Cameroon. Since 1982, there were numerous outbreaks, with the most recent one in 2017 in which the southwest and north part of the country were affected. The ASF virus (ASFV) is a double stranded DNA virus of the family Asfaviridae, genus Asfivirus. It causes lethal hemorrhagic fever in domestic pigs; while warthogs and bush pigs remain asymptomatic. ASFV is transmitted by arthropod vectors of the soft tick genus Ornithodoros amongst other modes of transmission. The virion has an icosahedral symmetry with an average diameter of 200nm. The virion consists of a nucleoprotin core surrounded by an inner envelope, an outer capsid layer and an outer envelope. The linear viral genomes encodes ~160 genes that are translated in more than 50 proteins. ASFV mainly targets immune cells of the myeloid lineage, especially monocytes and macrophages, which are thought to be crucial for viral persistence and dissemination. Bush pigs and warthogs are natural reservoir hosts of African swine fever virus, showing no clinical signs of disease when infected with the same highly virulent isolates of ASFV that induce rapid, hemorrhagic death in domestic pigs. To date there are no commercially available vaccines or antivirals for African swine fever (ASF). Although a number of experimental, live attenuated vaccines are promising, e.g. BA71ΔCD2. The current prospects for the development of a vaccine are good as pigs that survived from the disease can resist challenge by related virulent viruses. Unfortunately, inactivated ASF virions are not sufficient to induce a protective immune response, neither do they induce neutralizing antibodies. It is not surprising that with so many ASF outbreaks experienced in Cameroon since 1982, the genetic and serologic difference of ASF virus isolated is substantial. Hence, they are named per the year of isolation as CAM82, CAM 85, CAM 87, CAM87 and CAM88. The current circulating strain still remains to be characterized. Genetic heterogeneity and diversification are major challenges for disease prevention by vaccination because of the selection of mutants that are not significantly affected by the vaccine-induced immune response. An interesting approach for the treatment/prevention of ASFV could involve host-directed immunomodulatory therapies. This strategy aims to exploit natural mechanisms in the host to initiate or enhance protective antimicrobial immunity while limiting inflammation-induced tissue injury. With numerous outbreaks of ASFV in Africa and many other countries such as Poland, Russia Ukraine Moldova, and Czech republic in 2017, Cameroon might be at the verge of a new outbreak if nothing is done. Thus ASF remains a continuous threat to both Cameroon and the world at large. The epidemiological situation of ASF in the country is highly underestimated because of the multitude of factors that impact here-on. For example: (i) limited education and lack of training for livestock farmers, (ii) weak advisory services that hinders access to innovative techniques by farmers, (iii) low capacity for laboratories for diagnosis. Very limited research is being done at the level of Cameroon for the eradication of the ASF virus and the creation of prophylactic strategies in spite of the government's utmost effort to control the disease. GENERAL OBJECTIVES The aim of this project is to explore the epidemiology and molecular characterization of ASFV isolates and SLA class I diversity from ASFV susceptible and tolerant breeds of pigs in Cameroon. Generally, three main cycles for the spread of the ASFV in Africa are known, but in Cameroon, so far, it is proven that only a single cycle exists based on research conducted in 1985. Similarly, the indigenous pigs in Cameroon are tolerant to the ASFV but the exotic breeds are not. In this project, we aim to determine the main routes for the spread of the ASFV in Cameroon based on which appropriate control measures will be enacted by the authorities to help fight the disease. We will also molecularly characterize the isolates from Cameroon, which will help in the future in determining the origin of future outbreak strains if they are different from those already present in the country. Finally, we will compare the swine MHC within the tolerant (local and crosses between local and exotic) and susceptible (local and exotic) breeds with the aim of investigating for evidence of positive selection and heterogeneity. The results from this study will greatly help policy makers in the country and the ministry of livestock to develop and follow up with all stakeholders in the pig industry, aiming to reduce and eradicate the ASFV from Cameroon. status: published

Human Onchocerciasis is a neglected tropical disease of debilitating consequences caused by the nodule dwelling nematode Onchocerca volvulus. Excretory Secretory Products (ESPs) help the parasite to establishing infection in an immunocompetent host and thus make O. volvulus ESPs potential sources of diagnostic, therapeutic or immunomodulatory markers. Here, a blend of bioinformatics, biochemical, analytical and immunologic methods were employed to identify one such ESP as a GM2 activator protein orthologue. The cDNA of OvGM2AP was detected in most parasite stages and the protein was detected in ESPs of adult males, adult females and L3 stage. Recombinant OvGM2AP was expressed in Sf21 insect cells and was found to be glycosylated at Asn 173 by mass spectrometry analysis. The recombinant OvGM2AP could significantly differentiate infected from non-infected individuals on total IgG ELISA. No improvement in diagnostic indices was observed when IgG sub-classes were used to detect OvGM2AP by ELISA. A drop in IgG titre was observed to correlate with increased rounds of ivermectin administration. However, as observed from alignment of OvGM2AP sequences with other nematode species, recombinant OvGM2AP was found to cross react with sera from patients with other nematode infections such as Loa loa, Mansonella perstans and Brugia malayi. GM2 degradation to GM3 could not be mediated by OvGM2AP in the presence of human β-hexosaminidase A. However, when examined for competitive inhibition with artificial GM2 substrates such as MUG and MUGs, OvGM2AP was found to competitively inhibit the degradation of MUG by β-hexosaminidase A as opposed to the human GM2AP. Due to the genetic intractability of O. volvulus, Caenorhabditis elegans was used as a model to study the function of OvGM2AP. The C. elegans orthologous gene cpp-1 was found to be expressed predominantly in the hypoderm, with a paralogous form confined to specialized hypodermis such as seam cells. CRISPR-CAS9 mediated knock-out of a 1515 bp sequence on the cpp-1 locus generated mutant strains with altered permeability to chemicals including deionized water. The cpp-1(ulb13) mutant strains were also found to be significantly more permeable to Hoechst 33342 dye intake compared to WT worms and previously described strains with cuticle permeability. The cpp-1 phenotype was successfully rescued by cDNAs of cpp-1 and the human GM2AP (HsGM2AP) but not by the cDNA of OvGM2AP. Analysis of lipid binding abilities of baculovirus produced recombinant CPP-1 and OvGM2AP revealed a preferential lipid binding ability between the two proteins, with CPP-1 failing to recognize di and tri-phosphorylated phosphoinositides which are readily recognized by OvGM2AP on lipid overlay assays. Thus, with the information gathered so far, we conclude that OvGM2AP is an ESP of O. volvulus, is immunogenic and could assist in the diagnosis of onchocerciasis by determining ivermectin treatment endpoints. The C. elegans orthologous gene cpp-1 is essential for cuticle impermeability/integrity. Although the effects of OvGM2AP on immune cells is yet to be studied, we hypothesized based on the preferential lipid binding observed and the lack of rescue of the cpp-1 phenotype by OvGM2AP that OvGM2AP could utilize a preferential lipid binding mechanism to contribute in enabling parasite survival in the host., Doctorat en Sciences, info:eu-repo/semantics/nonPublished

Onchocerciasis is a severely debilitating yet neglected tropical disease (NTD) currently affecting approximately 15.5 million people, including 12.2 million people with skin disease and 1.025 million with vision loss. The disease causes social stigma, generates and perpetuates poverty, and leads ultimately to irreversible unilateral or bilateral blindness if untreated. Consequently, onchocerciasis is a major impediment to socioeconomic development in addition to being a major public health concern in some African countries. Many control programs have been launched against the disease with moderate successes achieved in Africa. These limited outcomes are partially due to the unavailability of reliable, non-invasive and easily applicable diagnostic tools for mapping endemic regions, monitoring control program successes, determining treatment endpoints and post-elimination surveillance. The current WHO recommendations for certification of elimination include the use of the Ov16 antibody detection ELISA which is flawed by an intrinsic systematic error as 15-25% of infected populations may not produce antibodies against this antigen due to genetic restrictions. With the recent shift in the global health goal of onchocerciasis from control to elimination, there is a need for the development of novel appropriate tools. These tools include amongst others, drugs, diagnostics, and vaccines. In this work, bioinformatics analyses combined with immunological assays were applied in a bid to develop potential tools for the current elimination programs. With regards to chemotherapy, Ivermectin which has been the sole drug for onchocerciasis treatment for over 30 years kills only the microfilariae (mf) leaving the adult worms intact which continue to produce the mf. Moreover, there is a recent problem of development of parasite resistance to this drug. In addition, moxidectin which was recently approved for treatment is contra-indicated in pregnant women and children under 12 who could continue to serve as reservoirs for infection. There is therefore a need to develop new treatment strategies, preferably for macrofilaricidal drugs. For a total eradication of onchocerciasis, diagnosis and treatment must be complemented with vaccine development. The aim of this work was therefore (i) to characterise an O. volvulus antigen, Ov58GPCR and (ii) to design an epitope-based chimeric antigen, which we designated, Ov-DKR-1, within the framework of the development of onchocerciasis control tools. In order to achieve the first goal, towards diagnosis, synthetic peptides representing linear B-epitopes and the recombinant extracellular domain of a G-protein coupled receptor (GPCR) with diagnostic potential were tested for their immune responses using serum from onchocerciasis-infected individuals and various controls. The results obtained indicate that (i) the O. volvulus antigen, Ov58GPCR is a G-protein coupled receptor (GPCR) conserved in related nematodes, (ii) synthetic peptides predicted to be in the extracellular domain (ECD) of Ov58GPCR are indeed immunogenic epitopes in onchocerciasis-infected individuals, (iii) synthetic peptide cocktails discriminate between actively-infected individuals, treated non-infected individuals and healthy African controls, (iv) polyclonal antibodies against one of the peptides or against the bacterially-expressed ECD reacted specifically with the native antigen in O. volvulus total and surface extracts, (v) Ov58GPCR is transcribed in both larvae and adult parasite stages, (vi) IgG and IgE responses to the recombinant ECD decline with Ivermectin treatment. All these findings suggest that the recombinant extracellular domain and synthetic peptides of Ov58GPCR, as well as the specific immune responses generated, could be harnessed in the context of disease diagnosis and surveillance. To assess the potential role of Ov58GPCR in drug or vaccine target development, preliminary examination on the essentiality of the Ov58GPCR for parasite survival was evaluated through RNA interference. A short-interfering RNA (siRNA) sequence targeting the gene designed and tested by soaking with O. volvulus male worms resulted in a reduction in motility. Results indicated that the gene may be involved primarily in motility. Further investigations are recommended in this light. With regards to the second goal, towards the development of a potential immune-protective tool, many indicators reveal the possibility of the development of protective tools against onchocerciasis. Consequently, an immuno-informatics approach was applied to design a filarial-conserved multi-epitope subunit vaccine candidate consisting of B-and T-cell epitopes of proteins reported to be potential novel vaccine candidates. Conservation of the selected proteins in other nematode parasitic species and predicted epitopes suggests that the generated chimera protein (Ov-DKR-1) could be vital in cross-protection. The 3D structure was predicted, refined and validated bioinformatically. Protein-protein docking of the chimeric vaccine candidate with the TLR4 receptor predicted efficient favourable binding. Immune simulation predicted significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses. Overall, the designed chimeric peptide demonstrated antigenicity superior to the current vaccine candidates., L’onchocercose est une maladie tropicale sévèrement débilitante mais négligée qui touche actuellement environ 15,5 millions de personnes, dont 12,2 millions de souffrant de maladies de la peau et 1,025 millions de souffrant de perte de vision. La maladie provoque une stigmatisation sociale, génère et perpétue la pauvreté et finit par conduire à une cécité unilatérale ou bilatérale irréversible si elle n'est pas traitée. En conséquence, l’onchocercose est un obstacle majeur au développement socioéconomique en plus d’être une préoccupation majeure pour la santé publique. De nombreux programmes de lutte ont été lancés contre la maladie, avec quelques succès en Afrique. Ces résultats sous-optimaux (limités) sont en partie dus à l’absence d’outils fiables, non invasifs et facilement applicables pour la cartographie des régions endémiques, le suivi des succès des programmes de contrôle, la détermination des paramètres de traitement et la surveillance post-élimination. Les recommandations actuelles de l’OMS pour la certification de l’élimination incluent l’utilisation du test ELISA de détection d’anticorps Ov16, entaché d’une erreur systématique intrinsèque puisque 15 à 25% des populations infectées peuvent ne pas produire d’anticorps contre cet antigène en raison de restrictions génétiques. Avec l’évolution récente de l’objectif de santé mondial de l’onchocercose de passé de la lutte à l’élimination, il est donc nécessaire de mettre au point de nouveaux outils appropriés. Ces outils nécessaires incluent, entre autres, des médicaments, des diagnostics et des vaccins. Dans ce travail, des analyses bio-informatiques combinées à des tests immunologiques ont été appliquées dans le but de développer des outils potentiels pour les programmes d'élimination actuels. En ce qui concerne la chimiothérapie, l’ivermectine, qui est le seul médicament utilisé depuis plus de 30 ans pour le traitement de l’onchocercose, ne tue que les microfilaires (mf) laissant intacts les vers adultes qui continuent à produire le mf. A ceci joint, il y a le problème récent du développement de la résistance des parasites à ce médicament. En outre, un traitement récemment approuvé, la moxidectine, est contre-indiquée chez les femmes enceintes et les enfants de moins de 12 ans qui pourraient continuer à servir de réservoirs d’infection. Il est donc absolument nécessaire d’élaborer de nouvelles stratégies de traitement, de préférence pour les médicaments macrofilaricides. Pour une éradication totale de l’onchocercose, le développement du vaccin doit être complété par le diagnostic et le traitement. Le but de ce travail est donc de caractériser un antigène d'O. volvulus, Ov58GPCR et de concevoir un antigène chimérique à base d'épitope, que nous avons appelé Ov-DKR-1, dans le cadre du développement d'outils de contrôle de l'onchocercose.Concernant le premier objectif, des peptides synthétiques représentant des épitopes B linéaires et le domaine extracellulaire (DEC) recombinant d'un récepteur couplé à la protéine G (GPCR) présentant un potentiel diagnostique ont été testés pour déterminer leur réponse immunitaire en utilisant du sérum d'individus infectés par l'onchocercose et divers témoins. Les résultats obtenus indiquent que (i) l'antigène d'O. volvulus, Ov58GPCR est un récepteur couplé à la protéine-G (GPCR) conservé dans les nématodes apparentés (ii) les peptides synthétiques prédits comme localisés dans le domaine extracellulaire de Ov58GPCR sont bien des epitopes immunogéniques chez les individus infectés par l’onchocercose, (iii) les cocktails de peptides synthétiques établissent une distinction entre les individus activement infectés avec l’onchocercose, les individus non-infectés traités et les témoins africains en bonne santé, (iv) les anticorps polyclonaux contre un des peptides ou le domaine extracellulaire exprimé au bactéries réagisent spécifiquement avec l'antigène natif dans les extraits total et de surface d'O. volvulus, (v) Ov58GPCR est transcrit aux stades larvaire et adulte, (vi) les niveaux détectés d’IgG et IgE grâce à le DEC recombinant diminuent au cours du traitement par l'ivermectine. Toutes ces découvertes suggèrent que le domaine extracellulaire recombinant et les peptides synthétiques de Ov58GPCR, ainsi que les réponses immunitaires spécifiques générées, pourraient être exploités dans le contexte du diagnostic et de la surveillance de la maladie. Pour évaluer le rôle potentiel d’Ov58GPCR dans le développement de médicaments ou de vaccins cible, un examen préliminaire de l’indispensabilité du gène Ov58GPCR pour la survie du parasite a été évalué par interférence d’ARN. Une séquence d'ARN interférant court (ARNic) ciblant le gène conçu et testé par trempage avec des vers mâles d'O. volvulus a entraîné une réduction de la motilité. Les résultats ont indiqué que le gène pourrait être impliqué principalement dans la motilité. Des investigations complémentaires sont recommandées dans cette optique.Concernant le deuxième objectif, de nombreux indicateurs révèlent la possibilité de développer des outils de protection contre l’onchocercose. En conséquence, une approche immuno-informatique a été appliquée pour concevoir un candidat-vaccin des sous-unités de multi-épitopes conservées-filarienne consistant des épitopes de cellules B et T de protéines qui seraient de nouveaux candidats vaccins. La conservation des protéines sélectionnées chez d'autres espèces parasitaires de nématodes et d'épitopes prédits suggère que la protéine chimère générée (Ov-DKR-1) pourrait être vitale pour la protection croisée. La structure 3D a été prédite, raffinée et validée bioinformatiquement. La fixation protéine-protéine du candidat vaccin chimère au récepteur TLR4 prédit une liaison favorable efficace. La simulation immunitaire prédit des niveaux significativement élevés d'IgG1, de réponses T-helper, de cellules T-cytotoxiques, de INF-γ et d'IL-2. Globalement, le peptide chimère conçu a démontré une antigénicité supérieure aux candidats vaccins actuels., Option Biologie moléculaire du Doctorat en Sciences, info:eu-repo/semantics/nonPublished