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Trypanosoma cruzi, l'agent étiologique de la maladie de Chagas, est transmis aux humains par des insectes hématophages de la sous-famille des Triatominae. Son cycle de vie intravectoriel se déroule exclusivement dans le tractus digestif de ces insectes et est étroitement lié à sa physiologie. La compréhension de la physiologie digestive, ainsi que l'exploration des mécanismes régissant l'interaction entre le parasite et les triatomines, promettent de dévoiler de nouvelles cibles cruciales pour altérer le développement du parasite et réduire la compétence vectorielle. Ce travail de thèse s'est focalisé d'une part sur l'exploration de la physiologie digestive de Rhodnius prolixus, qui, malgré son statut comme organisme modèle en physiologie des insectes et vecteur majeur de la maladie de Chagas, présente plusieurs questions concernant sa biologie digestive encore méconnues. Cela a permis de disséquer la cascade multi-peptidases impliquée dans le catabolisme de l'hémoglobine et d'illuminer le rôle digestif joué par l'intestin moyen antérieur. D'autre part, ce travail a permis d'explorer l'impact de l'établissement du parasite sur le vecteur en dévoilant des perspectives fondamentales sur l'interaction moléculaire complexe entre les triatomines et le trypanosome. L'infection par T. cruzi module le protéome de l'intestin moyen de l'insecte en manipulant l'expression de protéines impliquées dans des processus cellulaires cruciaux. De plus, la présence du parasite déclenche une réponse immunitaire systémique, caractérisée par l'expression d'un ensemble de protéines immunitaires qui pourraient agir pour maîtriser la parasitémie dans le tube digestif, empêchant ainsi la propagation de l'infection dans l'hémocoele. Ce travail a mis en lumière diverses facettes de la biologie des triatomines, et présente des cibles prometteuses exploitables pour le contrôle de la transmission de la maladie de Chagas., Option Biologie moléculaire du Doctorat en Sciences, info:eu-repo/semantics/nonPublished

There are over 500 species of the genus Artemisia in the Asteraceae family distributed over the globe, with varying potentials to treat different ailments. Following the isolation of artemisinin (a potent anti-malarial compound with a sesquiterpene backbone) from Artemisia annua, the phytochemical composition of this species has been of interest over recent decades. Additionally, the number of phytochemical investigations of other species, including those of Artemisia afra in a search for new molecules with pharmacological potentials, has increased in recent years. This has led to the isolation of several compounds from both species, including a majority of monoterpenes, sesquiterpenes, and polyphenols with varying pharmacological activities. This review aims to discuss the most important compounds present in both plant species with anti-malarial properties, anti-inflammatory potentials, and immunomodulating properties, with an emphasis on their pharmacokinetics and pharmacodynamics properties. Additionally, the toxicity of both plants and their anti-malaria properties, including those of other species in the genus Artemisia, is discussed. As such, data were collected via a thorough literature search in web databases, such as ResearchGate, ScienceDirect, Google scholar, PubMed, Phytochemical and Ethnobotanical databases, up to 2022. A distinction was made between compounds involved in a direct anti-plasmodial activity and those expressing anti-inflammatory and immunomodulating activities or anti-fever properties. For pharmacokinetics activities, a distinction was made between compounds influencing bioavailability (CYP effect or P-Glycoprotein effect) and those affecting the stability of pharmacodynamic active components., SCOPUS: re.j, info:eu-repo/semantics/published

BACKGROUND: Adverse economic conditions often prevent the widespread implementation of modern surgical techniques in third world countries such as in Sub-Sahara Africa. AIM OF THE STUDY: To demonstrate that a modern technique (laparoscopic totally extraperitoneal inguinal hernioplasty [TEP]) can safely be performed at significantly lower cost using inexpensive mesh material. SETTINGS: Douala University Hospital Gynecology, Obstetrics and Pediatrics and two affiliated centers, Ayos Regional Hospital and Edéa Regional Hospital in Cameroon. PATIENTS AND METHODS: Prospective randomized controlled trial (RCT) of consecutive adult patients presenting with primary inguinal hernia treated by TEP, comparing implantation of sterilized mosquito mesh (MM) with conventional polypropylene mesh (CM). Primary endpoints were peroperative, early and midterm postoperative complications and hernia recurrence at 30 months. RESULTS: Sixty-two patients (48 males) were randomized to MM (n = 32) or CM (n = 30). Groups were similar in age distribution and occupational features. Peroperative and early outcomes differed in terms of conversion rate (2/32 MM) due to external (electrical power supply) factors and mesh removal for early obstruction (1/30 CM). No outcome differences, including no recurrences, were noted after a median follow-up of 21 months. CONCLUSION: In this RCT with medium-term follow-up, TEP performed with MM appears not inferior to CM.

The cuticle of C. elegans is impermeable to chemicals, toxins, and pathogens. However, increased permeability is a desirable phenotype because it facilitates chemical uptake. Surface lipids contribute to the permeability barrier. Here, we identify the lipid transfer protein GMAP-1 as a critical element setting the permeability of the C. elegans cuticle. A gmap-1 deletion mutant increases cuticular permeability to sodium azide, levamisole, Hoechst, and DiI. Expressing GMAP-1 in the hypodermis or transiently in the adults is sufficient to rescue this gmap-1 permeability phenotype. GMAP-1 protein is secreted from the hypodermis to the aqueous fluid filling the space between collagen fibers of the cuticle. In vitro, GMAP-1 protein binds phosphatidylserine and phosphatidylcholine while in vivo, GMAP-1 sets the surface lipid composition and organization. Altogether, our results suggest GMAP-1 secreted by hypodermis shuttles lipids to the surface to form the permeability barrier of C. elegans., SCOPUS: ar.j, info:eu-repo/semantics/published

Onchocerciasis is a Neglected Tropical Disease that has a significant socioeconomic im-pact, especially in Sub-Saharan Africa. Numerous reports indicate that the Expanded Special Project for the Elimination of Neglected Tropical Diseases needs novel diagnostic tools before achieving its goal of successful elimination of onchocerciasis in Africa. The current diagnostic tests are either invasive, insensitive, or not applicable in the field and about 25% of persons infected cannot mount immune responses against the single antigen used in the only approved Ov-16 serological test. In the quest to identify novel biomarkers that can be used to certify that a patient is free from the disease, evaluate the progress of elimination programmes, and conduct post elimination surveil-lances, mass spectrometric analysis of Onchocerca volvulus crude extract revealed that 1392 proteins are expressed in the adult and microfilariae stages of the parasite. Computational analysis predicted six of the proteins as O. volvulus potential diagnostic targets. Linear B-epitopes were predicted from the six proteins and used to construct a multiepitope antigen (OvMCBL02). Serological analysis revealed that the OvMCBL02 test significantly differentiated between serum samples of onchocer-ciasis patients from the Kombone Health Area in the South West Region of Cameroon (n = 63) and control serum samples from Rwanda (n = 29) and Europe (n = 26) as well as between serum samples from the onchocerciasis hyperendemic region of Kombone Health Area (n = 63) and the hypoen-demic region of Bandjoun Health District (n = 54). Interestingly, the test did not cross-react with serum samples from patients suffering from related nematode infections, thereby suggesting that further characterization of the OvMCBL02 multiepitope antigen will render it an additional mem-ber of the diagnostic toolbox for the elimination of onchocerciasis., SCOPUS: ar.j, info:eu-repo/semantics/published

Adverse economic conditions often prevent the widespread implementation of modern surgical techniques in third world countries such as in Sub-Sahara Africa., SCOPUS: ar.j, info:eu-repo/semantics/published

Onchocerciasis is a skin and eye disease that exerts a heavy socio-economic burden, particularly in sub-Saharan Africa, a region which harbours greater than 96% of either infected or at-risk populations. The elimination plan for the disease is currently challenged by many factors including amongst others; the potential emergence of resistance to the main chemotherapeutic agent, ivermectin (IVM). Novel tools, including preventative and therapeutic vaccines, could provide additional impetus to the disease elimination tool portfolio. Several observations in both humans and animals have provided evidence for the development of both natural and artificial acquired immunity. In this study, immuno-informatics tools were applied to design a filarial-conserved multi-epitope subunit vaccine candidate, (designated Ov-DKR-2) consisting of B-and T-lymphocyte epitopes of eight immunogenic antigens previously assessed in pre-clinical studies. The high-percentage conservation of the selected proteins and epitopes predicted in related nematode parasitic species hints that the generated chimera may be instrumental for cross-protection. Bioinformatics analyses were employed for the prediction, refinement, and validation of the 3D structure of the Ov-DKR-2 chimera. In-silico immune simulation projected significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-γ, and IL-2 responses. Preliminary immunological analyses revealed that the multi-epitope vaccine candidate reacted with antibodies in sera from both onchocerciasis-infected individuals, endemic normals as well as loiasis-infected persons but not with the control sera from European individuals. These results support the premise for further characterisation of the engineered protein as a vaccine candidate for onchocerciasis., info:eu-repo/semantics/published

Despite multiple public health interventions, the incidence of malaria in Cameroon among children U5 is not decreasing. Fine-scale analysis helps to better capture the incidence and determinant of disease at local level and therefore, may contribute to more contextualized public health interventions and better resource allocation. Based on the analysis of routinely collected data between 2012 and 2018 in U5, our findings indicate substantial variation in malaria trend, seasonality, and risk in U5 across health districts. Malaria incidence was correlated with maximum temperature and rainfall the month before. The East region has a disproportionately high malaria burden compared to other regions. This first spatiotemporal modelling of clinical data from the whole country provides one-month risk forecasts that can guide preventive action at the health district level in Cameroon. In the future, the optimisation of data should allow a finer analysis at the level of the health areas in Cameroon., (SP - Sciences de la santé publique) -- UCL, 2021

BACKGROUND: In Sub-Saharan Africa (SSA), economic conditions often do not always permit the use of modern surgical techniques, especially for hernia treatment. Aim of the study: To demonstrate that a modern technique such as Laparoscopic Total Extraperitoneal inguinal hernioplasty (TEP) can be performed at a significantly lower cost thanks to the use of a less expensive mesh material. SETTINGS: The study was performed in Douala at the Gynaecology-Obstetric and Paediatric University Hospital and at governmental Regional Hospitals of Ayos and Edéa in Cameroon. MATERIAL AND METHODS: Prospective, randomised, double-blind, controlled trial (RCT) including consecutive adult patients presenting with primary inguinal hernia treated by TEP, with implantation of either sterilised mosquito net mesh (MNM) or conventional polypropylene mesh (CPM). RESULTS: 62 patients were enrolled; randomization allocated 32 to MNM and 30 to CPM. Both groups were comparable for age and professional activities. Significant perioperative differences pertained to conversion rate (2/32 MNM), due to external (electrical power) factors and mesh removal for early obstruction (1/30 CPM). Hospital stay was less than 2 days in both groups. All patients resumed their activities after 3 weeks. Costs were significantly lower in the MNM group. No recurrences were noted with a follow-up of median 21(12-30) months. CONCLUSION: This RCT shows that TEP with MNM is feasible, cost-effective with good outcomes in SSA hospital setting.

BACKGROUND: During the last decade, many studies have assessed the performance of malaria tests on non-invasively collected specimens, but no systematic review has hitherto estimated the overall performance of these tests. We report here the first meta-analysis estimating the diagnostic performance of malaria diagnostic tests performed on saliva, urine, faeces, skin odour ('sniff and tell') and hair, using either microscopy or PCR on blood sample as reference test. METHODS: We searched on PubMed, EMBASE, African Journals Online and Cochrane Infectious Diseases from inception until 19 January 2021 for relevant primary studies. A random effects model was used to estimate the overall performance of various diagnostic methods on different types of specimen. RESULTS: Eighteen studies providing 30 data sets were included in the meta-analysis. The overall sensitivity, specificity and diagnostic OR (DOR) of PCR were 84.5% (95% CI 79.3% to 88.6%), 97.3% (95% CI 95.3% to 98.5%) and 184.9 (95% CI 95.8 to 356.9) in saliva, respectively; 57.4% (95% CI 41.4% to 72.1%), 98.6% (95% CI 97.3% to 99.3%) and 47.2 (95% CI 22.1 to 101.1) in urine, respectively. The overall sensitivity, specificity and DOR of rapid diagnostic test for malaria in urine was 59.8% (95% CI 40.0% to 76.9%), 96.9% (95% CI 91.0% to 99.0%) and 30.8 (95% CI:23.5 to 40.4). CONCLUSION: In settings where PCR is available, saliva and urine samples should be considered for PCR-based malaria diagnosis only if blood samples cannot be collected. The performance of rapid diagnostic testing in the urine is limited, especially its sensitivity. Malaria testing on non-invasively collected specimen still needs substantial improvement.

The current study aims to provide a fine-scale spatiotemporal estimate of malaria incidence among Cameroonian under-5, and to determine its associated environmental factors, to set up preventive interventions that are adapted to each health district of Cameroon. Routine data on symptomatic malaria in children under-5 collected in health facilities, between 2012 and 2018 were used. The trend of malaria cases was assessed by the Mann–Kendall (M–K) test. A time series decomposition was applied to malaria incidence to extract the seasonal component. Malaria risk was estimated by the standardised incidence ratio (SIR) and smoothed by a hierarchical Bayesian spatiotemporal model. In total, 4,052,216 cases of malaria were diagnosed between 2012 and 2018. There was a gradual increase per year, from 369,178 in 2012 to 652,661 in 2018. After adjusting the data for completeness, the national incidence ranged from 489‰ in 2012 to 603‰ in 2018, with an upward trend (M–K test p-value < 0.001). At the regional level, an upward trend was observed in Adamaoua, Centre without Yaoundé, East, and South regions. There was a positive spatial autocorrelation of the number of malaria incident-cases per district per year as suggested by the Moran’s I test (statistic range between 0.11 and 0.53). The crude SIR showed a heterogeneous malaria risk with values ranging from 0.00 to 8.90, meaning that some health districts have a risk 8.9 times higher than the national annual level. The incidence and risk of malaria among under-5 in Cameroon are heterogeneous and vary significantly across health districts and seasons. It is crucial to adapt malaria prevention measures to the specificities of each health district, in order to reduce its burden in health districts where the trend is upward.

info:eu-repo/semantics/published

In Fig. 2 of this Article, the Ct values for the orf1ab gene (shown in Fig. 2b) in samples B16121 and B16122 at 20×, 50× and 100× dilution were accidental duplications of those of the N gene (shown in Fig. 2a). The Ct values for orf1ab have been corrected in Fig. 2 of the original Article, and Fig. 1 of this Amendment shows the original and corrected Fig. 2b, for transparency. As B16121 and B16122 are both low-Ct samples, this change has no effect on our conclusion that typical samples are easily detected after 100-fold dilution. In Extended Data Table 2 of this Article, which presents the source data for Fig. 2, the orf1ab Ct values for sample B16121 were incorrectly given as 29, 29.74 and 30.54 for 20×, 50× and 100× dilution, respectively, instead of 31, 30.51 and 30.95, respectively. In addition, the orf1ab Ct values for sample B16122 were incorrectly given as 26.81, 27.75 and 29.07 for 20×, 50× and 100× dilution, respectively, instead of 28.5, 29.4 and 30.2, respectively. Extended Data Table 2 of the original Article has been corrected online. We thank T. Carey for drawing this error to our attention. The original Article has been corrected online. (Figure presented.)., SCOPUS: er.j, info:eu-repo/semantics/published

An efficient synthetic protocol was devised for the preparation of five cationic ruthenium-arene complexes bearing imidazol(in)ium-2-dithiocarboxylate ligands from the [RuCl2(p-cymene)]2 dimer and 2 equiv of an NHC·CS2 zwitterion. The reactions proceeded cleanly and swiftly in dichloromethane at room temperature to afford the expected [RuCl(p-cymene)(S2C·NHC)]Cl products in quantitative yields. When the [RuCl2(p-cymene)]2 dimer was reacted with only 1 equiv of a dithiolate betaine under the same experimental conditions, a set of five bimetallic compounds with the generic formula [RuCl(p-cymene)(S2C·NHC)][RuCl3(p-cymene)] was obtained in quantitative yields. These novel, dual anionic and cationic ruthenium-arene complexes were fully characterized by various analytical techniques. NMR titrations showed that the chelation of the dithiocarboxylate ligands to afford [RuCl(p-cymene)(S2C·NHC)]+ cations was quantitative and irreversible. Conversely, the formation of the [RuCl3(p-cymene)]- anion was limited by an equilibrium, and this species readily dissociated into Cl- anions and the [RuCl2(p-cymene)]2 dimer. The position of the equilibrium was strongly influenced by the nature of the solvent and was rather insensitive to the temperature. Two monometallic and two bimetallic complexes cocrystallized with water, and their molecular structures were solved by X-ray diffraction analysis. Crystallography revealed the existence of strong interactions between the azolium ring protons of the cationic complexes and neighboring donor groups from the anions or the solvent. The various compounds under investigation were highly soluble in water. They were all strongly cytotoxic against K562 cancer cells. Furthermore, with a selectivity index of 32.1, the [RuCl(p-cymene)(S2C·SIDip)]Cl complex remarkably targeted the erythroleukemic cells vs mouse splenocytes., SCOPUS: ar.j, info:eu-repo/semantics/published

SCOPUS: le.j, info:eu-repo/semantics/published

Inflammasomes are cytosolic protein platforms whose assembly/activation, in order to resolve various types of threats, can be triggered by a multitude of microbial and host derived stimuli. Their discovery was the key breakthrough in the understanding of inflammation initiation. Although beneficial in clearing microbes and restoring physiological or tissue homeostasis, aberrant or excessive stimulation of inflammasomes leads to various pathologies. The activation of NLRP3 inflammasome is associated with the physio-pathogenesis or the potentiation of the severity of so many diseases including respiratory diseases, such as asthma, COPD, COVID-19, malaria, diabetes, atherosclerosis, etc. Considering the extent of the NLRP3 inflammasome in diseases, therapies targeting the inhibition of its activation appear as a promising approach for the management of a wide range of diseases. The objective of this research work was to investigate the potential of Rwandan medicinal plants in the inhibition of the NLRP3 inflammasome. To this end, we first carried out a field survey to collect ethnobotanical information on plants used for the treatment of asthma in Rwanda. The present thesis is divided into two main parts:- The ethnobotanical study and screening of Rwandan medicinal plants with inhibitory activity on NLRP3 inflammasome activation;- The isolation and structure characterization of the active ingredients responsible for NLRP3 inflammasome inhibition, and the investigation of antiplasmodial activity of selected plants.In the first part, 19 herbal recipes were reconstituted from 61 medicinal plants based on an ethnobotanical survey. Most of these recipes exhibited significant inhibition of the NLRP3 inflammasome activation. The four recipe extracts named R03Cn and R07Kn aqueous extracts, and R10MK and R19Sz organic extracts significantly downregulated the activation of caspase-1 (more than 70% at 50 µg/ml). As R19Sz revealed the best NLRP3 inflammasome inhibitory activity an, Option Biologie moléculaire du Doctorat en Sciences, info:eu-repo/semantics/nonPublished

During the last decade, many studies have assessed the performance of malaria tests on non-invasively collected specimens, but no systematic review has hitherto estimated the overall performance of these tests. We report here the first meta-analysis estimating the diagnostic performance of malaria diagnostic tests performed on saliva, urine, faeces, skin odour ('sniff and tell') and hair, using either microscopy or PCR on blood sample as reference test., SCOPUS: re.j, info:eu-repo/semantics/published

Malaria remains one of the leading causes of death in sub-Saharan Africa, ranked in the top three infectious diseases in the world. Plants of the Eriosema genus have been reported to be used for the treatment of this disease, but scientific evidence is still missing for some of them. In the present study, the in vitro antiplasmodial activity of the crude extract and compounds from Eriosema montanum Baker f. roots were tested against the 3D7 strain of Plasmodium falciparum and revealed using the SYBR Green, a DNA intercalating compound. The cytotoxicity effect of the compounds on a human cancer cell line (THP-1) was assessed to determine their selectivity index. It was found that the crude extract of the plant displayed a significant antiplasmodial activity with an IC50 (µg/mL) = 17.68 ± 4.030 and a cytotoxic activity with a CC50 (µg/mL) = 101.5 ± 12.6, corresponding to a selective antiplasmodial activity of 5.7. Bioactivity-guided isolation of the major compounds of the roots' crude extract afforded seven compounds, including genistein, genistin and eucomic acid. Under our experimental conditions, using Artemisinin as a positive control, eucomic acid showed the best inhibitory activity against the P. falciparum 3D7, a well-known chloroquine-sensitive strain. The present results provide a referential basis to support the traditional use of Eriosema species in the treatment of malaria., SCOPUS: ar.j, info:eu-repo/semantics/published