The role of T helper 17 cells in the Pathogenesis of Human Onchocerciasis

Onchocerciasis, also known as river blindness, is a tropical disease causing health and socioeconomic problems in endemic communities, especially sub-Saharan Africa. The disease is elicited by a filarial parasite called Onchocerca volvulus, which is transmitted by the bite of infected blackflies (Simulium). Characteristic disease symptoms include dermatological disorders and eye lesions that can lead to blindness. Two polar forms of clinical manifestations can occur: generalized onchocerciasis (GEO), presenting mild skin disease or the hyperreactive form (HO) which exhibits severe skin disorders and inflammation. Globally, 37 million individuals are estimated to be infected. The intensity of immune reactions against the parasite is believed to influence the clinical outcomes of the disease and the immune determinants that drive tolerance or pathology are still not fully characterized. Th17 cells are a distinct subpopulation of helper T cells with potent inflammatory properties and are characterized by their predominant production of interleukin (IL)-17 (IL-17A and IL-17F). These cells are implicated in several auto-immune and inflammatory diseases. Commitment into Th17 cells or regulatory T cells (Treg) required almost the same pathway since both need TGF-β. IL-6 is one of the innate cytokines that determine the balance Th17/Treg. The present study, investigated the role of Th17 cells and the way the balance of Th17/Treg influences the outcome of clinical manifestations during human onchocerciasis. Moreover, the mechanisms underlying the plasticity between a regulatory phenotype and an inflammatory Th17 response was studied. Using a flow cytometry approach, this study investigated the expression patterns of Th1, Th2, Th17, Treg markers and other immune cells such as B cells, monocytes, CD8 and NK cells in peripheral blood mononuclear cells (PBMCs) from HO and GEO patients to putative immune/endemic normals (EN). The findings indicated that HO individuals exhibit strong Th2 and Th17 responses, as reflected by higher expression of IL-4, GATA3, and IL-17A, RORC2 expressing CD4 T cells when compared to either GEO or EN. Based on the enhanced numbers of IL-10-expressing CD4+ T cells and CD4+CD25+Foxp3+ Treg, the work also showed that patients with GEO phenotype exhibited a regulatory milieu. EN individuals on the other hand showed prominent Th1 (CD4+IFN-γ+ T cells). Flow cytometry data was further confirmed using a Th17 based PCR array. Th17-related genes such as IL-17 cytokine family members as well as IL-6, IL-1β and IL-22, Th17 transcription factor and signalling pathway molecules (RORC2 and STAT3) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. Moreover, using in vitro cell cultures of PBMCs, this study further demonstrated that whereas Onchocerca volvulus-specific Th1 responses were increased in cultures from EN, a strong Th2 phenotype was observed in cultures from HO individuals due to elevated levels of filarial-specific IL-5 and IL-13. To further investigate the mechanism underlying the differences between GEO and HO, an in vitro Th17 cell polarization model was performed and provided initial evidence that the commitment to a Th17 lineage could be modulated in PBMCs from GEO individuals by the addition of innate receptor triggering. Interestingly, it was demonstrated that products of innate stimulation, such us IL-6 and IL-1β, could also modify the GEO phenotype into one reflecting that from HO individuals. For the first time, this study provides evidence that elevated frequencies of Th2 and Th17 cells and the balance of Th17/Treg form part of the immune network instigating the development of severe pathology in human onchocerciasis. At the end a mechanism elucidating possible pathways that drive GEO and HO phenotype was proposed

Depistage De L’anemie En Urgence Au Chu Campus : Validation Du Degre De Concordance Entre Les Resultats De L’hemocue® Hb 301 Et Ceux Du Sysmex Xn-1000®

Introduction: Un dépistage fiable de l’anémié dans un contexte d’urgence grâce à un hémoglobinomètre de biologie délocalisée demeure un défis en Afrique. Le but de cette étude était d’évaluer le degré de concordance des résultats d’hémoglobinémie obtenus sur l’HemoCue® Hb 301 par rapport à ceux de l’analyseur Sysmex XN-1000®. Méthodes : Il s’est agi d’une étude rétrospective et transversale descriptive réalisée du 08 Mai 2017 au 23 Février 2018 au CHU Campus du Togo. La performance du Sysmex XN-1000®  a été confirmée grâce à l’évaluation de l’exactitude et de la fidélité de mesure. La performance de l’Hemocue® Hb 301 a été évaluée au moyen d’une régression linéaire et du diagramme de Bland et Altman vis-à-vis du Sysmex XN-1000®. Les critères de performances utilisés étaient ceux du Clinical Laboratory Improvement Amendments (CLIA) et de RICOS et al.  Résultats: Le niveau d’exactitude selon CLIA du Sysmex XN-1000® était de 100%. L’équation de la droite de régression était: Y (HemoCue® Hb 301) = 0,99x (Symex XN-1000®) + 0,54 g/dl. Les valeurs médianes des 100 échantillons sur le Sysmex et l’Hemocue étaient respectivement de 12,55 g/dl et 13,00 g/dl avec un biais médian de 3,58%, qui était inférieur au biais limite de ±7,0% (CLIA). Conclusion: Le Sysmex XN-1000® fournit des résultats d’hémoglobinémie interchangeables avec ceux de l’HemoCue® Hb 301, sans altération de la capacité diagnostique pour le patient. Il reste donc performant pour un quelconque dosage d’hémoglobinémie en urgence.  Introduction: Reliable anemia screening in an emergency setting, using a Point-of-care hemoglobinometer remains a challenge in Africa. The purpose of this study was to assess the degree of agreement between hemoglobin results obtained on the HemoCue® Hb 301 compared to those of the Sysmex XN-1000® Analyzer. Methods: This was a retrospective and cross-sectional descriptive study carried out from May 08 2017 to February 23, 2018 at the Campus teaching hospital of Togo. The performance of the Sysmex XN-1000® was confirmed by evaluating the measurement accuracy and precision. The performance of Hemocue® Hb 301 was assessed using linear regression and a Bland and Altman plot against Sysmex XN-1000®. The performance criteria used were those of Clinical Laboratory Improvement Amendments (CLIA) and RICOS et al. Results: The CLIA level of accuracy of the Sysmex XN-1000® was 100%. The equation for the regression line was: Y (HemoCue® Hb 301) = 0.99x (Symex XN-1000®) + 0.54 g / dl. The median values of the 100 samples on the Sysmex and Hemocue were 12.55 g / dl and 13.00 g / dl respectively, with a median bias of 3.58%, which was less than the borderline bias of ± 7.0 % of CLIA. Conclusion: The Sysmex XN-1000® provides interchangeable hemoglobin results with those of HemoCue® Hb 301, without altering the diagnostic ability for the patient. It therefore remains effective for any emergency dosage of hemoglobinemia

Ethnobotanical survey of medicinal plants used in the management of hypertension in the Maritime region of Togo

Background: Hypertension is one of the most common chronic diseases in modern societies and there is evidence that its incidence and severity are increasing. This survey was conducted to investigate the plants used by the Togolese traditional healers to treat the disease.Method: From January to June 2016, an ethnobotanical survey was conducted using a semi-structured questionnaire with traditional healers (TH) in the southern region of Togo. The importance of the plants was assessed by the calculation of the use value (UV).Results: In Total, 128 TH male and female were interviewed and 116 plants species belonging to 46 families were identified as treating hypertension. The most represented families were: Fabaceae with 16 species followed by Euphorbiaceae and Rutaceae contributing with 8 and 6 species respectively. Based on the calculated use values the most important species were Byrsocarpus coccineus Schum. Et thonn. (UV = 0.47); Crateva religiosae G.Forst. (UV = 0.47), Boerhavia diffusa Engelm. &A.Gray L. (UV = 0.47), Xylopia athiopica A. Rich. (UV = 0.42), Mangnifera indica L. (UV = 0.38). The leaves and the roots were the parts of plant predominantly used to prepare the recipes, mainly decoctions administrated by oral route. Clinical manifestations such as dizzy spells, swarming, loss of consciousness, severe headache, severe anxiety and shortness of breath, nosebleed, and fear of heights were used by TH to diagnose the disease.Conclusion: This study showed initial evidence of the use of plant materials by Togolese TH to treat hypertension. These results constitute a database for pharmacological screenings with the aim of developing new therapies.Key words: Hypertension, traditional medicine, ethnobotanical survey, medicinal plants, Togo

ETHNOBOTANICAL SURVEY OF MEDICINAL PLANTS USED IN THE MANAGEMENT OF HYPERTENSION IN THE MARITIME REGION OF TOGO

Background: Hypertension is one of the most common chronic diseases in modern societies and there is evidence that its incidence and severity are increasing. This survey was conducted to investigate the plants used by the Togolese traditional healers to treat the disease. Method: From January to June 2016, an ethnobotanical survey was conducted using a semi-structured questionnaire with traditional healers (TH) in the southern region of Togo. The importance of the plants was assessed by the calculation of the use value (UV). Results: In Total, 128 TH male and female were interviewed and 116 plants species belonging to 46 families were identified as treating hypertension. The most represented families were: Fabaceae with 16 species followed by Euphorbiaceae and Rutaceae contributing with 8 and 6 species respectively. Based on the calculated use values the most important species were Byrsocarpus coccineus Schum. Et thonn. (UV = 0.47); Crateva religiosa G.Forst. (UV = 0.47), Boerhavia diffusa Engelm. &A.Gray L. (UV = 0.47), Xylopia aethiopica A. Rich. (UV = 0.42), Mangnifera indica L. (UV = 0.38). The leaves and the roots were the parts of plant predominantly used to prepare the recipes, mainly decoctions administrated by oral route. Clinical manifestations such as dizzy spells, swarming, loss of consciousness, severe headache, severe anxiety and shortness of breath, nosebleed, and fear of heights were used by TH to diagnose the disease. Conclusion: This study showed initial evidence of the use of plant materials by Togolese TH to treat hypertension. These results constitute a database for pharmacological screenings with the aim of developing new therapies

Impact of helminth infections on female reproductive health and associated diseases

A growing body of knowledge exists on the influence of helminth infections on allergies and unrelated infections in the lung and gastrointestinal (GI) mucosa. However, the bystander effects of helminth infections on the female genital mucosa and reproductive health is understudied but important considering the high prevalence of helminth exposure and sexually transmitted infections in low- and middle-income countries (LMICs). In this review, we explore current knowledge about the direct and systemic effects of helminth infections on unrelated diseases. We summarize host disease-controlling immunity of important sexually transmitted infections and introduce the limited knowledge of how helminths infections directly cause pathology to female reproductive tract (FRT), alter susceptibility to sexually transmitted infections and reproduction. We also review work by others on type 2 immunity in the FRT and hypothesize how these insights may guide future work to help understand how helminths alter FRT health

ETHNOBOTANICAL STUDY OF PLANTS USED TO TREAT ASTHMA IN THE MARITIME REGION IN TOGO

Background: Asthma is one of the most common chronic diseases in modern society and it is evident that its incidence and severity are increasing, however very little is known about the plants used in the management of the disease. This study therefore aimed to document the plants usage in the Togolese traditional medicine to treat asthma. Methodology: From January to June 2015, an ethnobotanical survey was conducted using a semi-structured questionnaire with traditional healers (THs) in the southern region of Togo. The importance of the plants species was assessed by the calculated use values. Results: In Total, 121 THs (92 males and 29 females) were interviewed and 98 plants species belonging to 54 families were identified as curing asthma. The most represented families were: Leguminosae with 7 species followed by Euphorbiaceae and Rutaceae contributing with 6 and 5 species respectively. Based on the calculated use values the most important species were Carcica papaya L., Cataranthus roseus L., Eucalyptus camaldulensis Dehnh., Piper guineense Thonn., Eucalyptus citriodora Hook., Eucalyptus globules Labill. and Euphorbia hirta L. The leaves and the root were the parts predominantly used to prepare the formulations, mainly decoctions, administrated by oral route. Clinical manifestations such as wheezing (91.74%), difficulty as speaking or coughing (73.55%), dyspnea (66.94%), dry cough (52.89%), sweating and increased heart rate (52.07%) were used by TH to diagnose the disease. Conclusion: This study showed initial evidence of the use of plant materials by Togolese TH to heal asthma. These results could be a starting point for laboratory screenings

Molecular characterization of high-risk humanpapillomavirus genotypes in women with or without cervical lesions at VIA/VILI in Kara, Togo

Background: Persistent infection with high-risk (HR) papillomavirus (HPV) genotypes plays a central role in the pathogenesis of invasive cervical cancer. Objectives: This study aimed to determine the prevalence and distribution of HR-HPV among women with or without cervical lesions at VIA/VILI in Togo. Methods: Cervical samples were collected from 238 women with or without cervical lesions at VIA / VILI and[c3] DNA [c4]was extracted and analyzed by real-time multiplex PCR. Logistic regression analysis was used to determined risk factors associated with HPV infection. inPietro Annigoni Biomolecular Research Center (CERBA / LABIOGENE) in Burkina Faso. Results: The age of the women ranged from 17 to 61 years old, and most were married (73.5%). The prevalence of HRHPV was 35.71% and this was higher in the age range 35-39 years. The six most common genotypes were HPV 31 (18.7%), HPV 52 (13.82%), HPV 68 (13.01%), HPV 66 (9.76%), HPV 58 (8.13%) and HPV 56 (8.13%). Genotypes HPV 18 (4.07%)and HPV 16 (0.81%) were less frequent.[c5] Married or living with a partner was associated with HPV infection ( OR=2,17, IC [1.20-3.91], p<0,009). Conclusion: This study allowed characterizing for the first time in Togo, HR-HPV genotypes. This will help mappingHR-HPV genotypes circulating in West Africa. Keywords: Human papillomavirus; High-risk; Genotyping; Kara; Togo

Is a mass drug administration deworming programme for school-aged children enough to reduce the prevalence of soil-transmitted helminths and Schistosoma mansoni in adults: a cross-sectional study from Togo

BackgroundThe world health organization (WHO) introduced the mass drug administration (MDA) strategy in order to reduce the prevalence of soil-transmitted helminths (STHs) and Schistosoma mansoni in endemic areas. However, this strategy is not implemented in adult population in Togo. Thus, the question arose if the present MDA strategy contributes to the reduction of transmission rates. The present study aimed to monitor the prevalence of STHs and S. mansoni among adult’s, between 2017 and 2022, in the central region of Togo.MethodsTwo cross-sectional studies were conducted in six villages in the central region of Togo in 2017 and 2022. Stool samples were collected from adults over the age of 18 years. To assess STHs and S. mansoni infections, real-time multiplex qPCR and Kato-Katz techniques were performed. Data were analysed using SPSS software version 21 and GraphPad PRISM version 9.2.0. A p-value less than 0.05 was considered statistically significant.ResultsA total of 210 and 289 individuals were recruited in 2017 and 2022, respectively. We detected significant increase in the prevalence of STHs and S. mansoni from 7.61% to 24.56% (p=0.0008) and from 27.62% to 46.36% (p=0.0014) by Kato-Katz and RT-qPCR, respectively. The prevalence of Ancylostoma duodenale infection was the highest with an increase from 7.14% to 23.53% by Kato-Katz and 9.09% to 40.0% by RT-qPCR.ConclusionThe prevalence of STHs and S. mansoni increased in the adult population in the central region of Togo from 2017 to 2022, despite the implementation of MDA in school-aged children. Hence, there is an urgent need to include adult individuals and adapt the MDA programme in the central region of Togo

Hyperreactive onchocerciasis is characterized by a combination of Th17-Th2 immune responses and reduced regulatory T cells

<div><p>Clinical manifestations in onchocerciasis range from generalized onchocerciasis (GEO) to the rare but severe hyperreactive (HO)/sowda form. Since disease pathogenesis is associated with host inflammatory reactions, we investigated whether Th17 responses could be related to aggravated pathology in HO. Using flow cytometry, filarial-specific cytokine responses and PCR arrays, we compared the immune cell profiles, including Th subsets, in individuals presenting the two polar forms of infection and endemic normals (EN). In addition to elevated frequencies of memory CD4⁺ T cells, individuals with HO showed accentuated Th17 and Th2 profiles but decreased CD4⁺CD25^hiFoxp3⁺ regulatory T cells. These profiles included increased IL-17A⁺, IL-4⁺, RORC2⁺ and GATA3⁺CD4⁺ T cell populations. Flow cytometry data was further confirmed using a PCR array since Th17-related genes (IL-17 family members, IL-6, IL-1β and IL-22) and Th2-related (IL-4, IL-13, STAT6) genes were all significantly up-regulated in HO individuals. In addition, stronger <i>Onchocerca volvulus</i>-specific Th2 responses, especially IL-13, were observed <i>in vitro</i> in hyperreactive individuals when compared to GEO or EN groups. This study provides initial evidence that elevated frequencies of Th17 and Th2 cells form part of the immune network instigating the development of severe onchocerciasis.</p></div