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Background: European travellers to endemic countries are at risk of malaria and may be affected by a different range of co-morbidities than natives of endemic regions. The safety profile, especially cardiac issues, of artenimol (previously dihydroartemisinin)–piperaquine (APQ) Eurartesim® during treatment of uncomplicated imported falciparum malaria is not adequately described due to the lack of longitudinal studies in this population. The present study was conducted to partially fill this gap. Methods: Participants were recruited through Health Care Provider’s safety registry in 15 centres across 6 European countries in the period 2013–2016. Adverse events (AE) were collected, with a special focus on cardiovascular safety by including electrocardiogram QT intervals evaluated after correction with either Bazett’s (QTcB) or Fridericia’s (QTcF) methods, at baseline and after treatment. QTcB and/or QTcF prolongation were defined by a value > 450 ms for males and children and > 470 ms for females. Results: Among 294 participants, 30.3% were women, 13.7% of Caucasian origin, 13.5% were current smoker, 13.6% current alcohol consumer and 42.2% declared at least one illness history. The mean (SD) age and body mass index were 39.8 years old (13.2) and 25.9 kg/m2 (4.7). Among them, 75 reported a total of 129 AE (27 serious), 46 being suspected to be related to APQ (11 serious) and mostly labelled as due to haematological, gastrointestinal, or infection. Women and Non-African participants had significantly (p < 0.05) more AEs. Among AEs, 21 were due to cardiotoxicity (7.1%), mostly QT prolongation, while 6 were due to neurotoxicity (2.0%), mostly dizziness. Using QTcF correction, QT prolongation was observed in 17/143 participants (11.9%), only 2 of them reporting QTcF > 500 ms (milliseconds) but no clinical symptoms. Using QTcB correction increases of > 60 ms were present in 9 participants (6.3%). A trend towards increased prolongation was observed in those over 65 years of age but only a few subjects were in this group. No new safety signal was reported. The overall efficacy rate was 255/257 (99.2%). Conclusions: APQ appears as an effective and well-tolerated drug for treatment of malaria in patients recruited in European countries. AEs and QT prolongation were in the range of those obtained in larger cohorts from endemic countries. Trial registration This study has been registered in EU Post-Authorization Studies Register as EUPAS6942, SCOPUS: ar.j, info:eu-repo/semantics/published

Rosacea is a common facial dermatosis but its definition and classification are still unclear, especially in terms of its links with demodicosis. Triggers of rosacea (ultraviolet light, heat, spicy foods, alcohol, stress, microbes) are currently considered to induce a cascading innate and then adaptive immune response that gets out of control. Recent histological and biochemical studies support the concept that this inflammatory response is a continuum, already present from the onset of the disease, even when no clinical signs of inflammation are visible. The Demodex mite is beginning to be accepted as one of the triggers of this inflammatory cascade, and its proliferation as a marker of rosacea; moreover, the papulopustules of rosacea can be effectively treated with topical acaricidal agents. Demodex proliferation appears to be a continuum process in rosacea, and may not be clinically visible at the onset of the disease. Molecular studies suggest that Demodex may induce tolerogenic dendritic cells and collaborate with vascular endothelial growth factor (VEGF) to induce T cell exhaustion and favor its own proliferation. These interactions among VEGF, Demodex, and immunity need to be explored further and the nosology of rosacea adapted accordingly. However, treating early rosacea, with only clinically visible vascular symptoms, with an acaricide may decrease early inflammation, limit potential flare-ups following laser treatment, and prevent the ultimate development of the papulopustules of rosacea. The effectiveness of this approach needs to be confirmed by prospective controlled clinical trials with long-term follow-up. Currently, the evidence suggests that patients with only vascular symptoms of rosacea should be carefully examined for the presence of follicular scales as signs of Demodex overgrowth or pityriasis folliculorum so that these patients, at least, can be treated early with an acaricidal cream.

The 11th Congress of the African Society of Human Genetics (AfSHG) was held from September 16, 2018 to September 21, 2018, in conjunction with the 12th Human Heredity and Health in Africa (H3Africa) Consortium meeting in Kigali, Rwanda. The event was organized by the AfSHG in partnership with the Rwanda Society of Human Genetics and the University of Rwanda. A 2-day workshop on the application of next-generation sequencing technologies for analyzing monogenic disease in African populations was organized as part of the conference (September 22, 2018-September 23, 2018, Kigali, Rwanda). The theme of the conference was "Building skills and resources for genomics, epigenetics and bioinformatics research for Africa."The conference served as a platform to bring together members from country-specific Societies of Human Genetics, including Rwanda, Cameroon, Democratic Republic of Congo, Egypt, Mali, Senegal, and South Africa, and included 435 delegates from 38 countries, including 29 African countries that attended the conference. A major topic of discussion was how to bridge the gap between the emerging knowledge on genomics and Omics in African populations. The importance of understanding the role of genetic variation in disease causation and susceptibility among Africans was a constant theme during the meeting, as was the need to develop research infrastructure and resources to enhance healthcare systems, so that they are not left behind in the genomic revolution. It was concluded that there is a need to inspire more African scientists to train and work as investigators, clinicians, and genetic counselors in the field of human genetics in Africa. Local investments, and South-South and South-North collaboration were identified as the key drivers for the successful implementation of research and development on the continent., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Artemisinin-based combination therapy (ACT) is recommended to improve malaria treatment efficacy and limit drug-resistant parasites selection in malaria endemic areas. 5 years after they were adopted, the efficacy and safety of artemether-lumefantrine (AL) and artesunate-amodiaquine (ASAQ), the first-line treatments for uncomplicated malaria were assessed in Burkina Faso. Methods: In total, 440 children with uncomplicated Plasmodium falciparum malaria were randomized to receive either AL or ASAQ for 3 days and were followed up weekly for 42 days. Blood samples were collected to investigate the ex vivo susceptibility of P. falciparum isolates to lumefantrine, dihydroartemisinin (the active metabolite of artemisinin derivatives) and monodesethylamodiaquine (the active metabolite of amodiaquine). The modified isotopic micro test technique was used to determine the 50% inhibitory concentration (IC50) values. Primary endpoints were the risks of treatment failure at days 42. Results: Out of the 440 patients enrolled, 420 (95.5%) completed the 42 days follow up. The results showed a significantly higher PCR unadjusted cure rate in ASAQ arm (71.0%) than that in the AL arm (49.8%) on day 42, and this trend was similar after correction by PCR, with ASAQ performing better (98.1%) than AL (91.1%). Overall adverse events incidence was low and not significantly different between the two treatment arms. Ex vivo results showed that 6.4% P. falciparum isolates were resistant to monodesthylamodiaquine. The coupled in vivo/ex vivo analysis showed increased IC50 values for lumefantrine and monodesethylamodiaquine at day of recurrent parasitaemia compared to baseline values while for artesunate, IC50 values remained stable at baseline and after treatment failure (p > 0.05). Conclusion: These findings provide substantial evidence that AL and ASAQ are highly efficacious for the treatment of uncomplicated malaria in children in Burkina Faso. However, the result of P. falciparum susceptibility to the partner drugs advocates the need to regularly replicate such surveillance studies. This would be particularly indicated when amodiaquine is associated in seasonal malaria chemoprophylaxis (SMC) mass drug administration in children under 5 years in Burkina Faso. Trial registration clinicaltrials, NCT00808951. Registered 05 December 2008,https://clinicaltrials.gov/ct2/show/NCT00808951?cond=NCT00808951&rank=1., SCOPUS: ar.j, info:eu-repo/semantics/published

The scientific interest in Hemosporidia is currently being reawakened, following, amongst others, the damages they have caused on wildlife, as well as the expanding role of wildlife hospitals in matters of avifauna rehabilitation. This study’s objectives were twofold: firstly, to compile a global overview of the epidemiological situation concerning hemoparastism in the raptors and corvids fostered in a wildlife hospital in Île-de-France; secondly, to identify potential key factors in the haemosporidian infestation and its transmission in those species, in order to propose relevant risk mitigation measures. Between May 2018 and May 2019, a transversal and monocentric study was conducted on birds sheltered at the wildlife hospital of the national veterinary school of Alfort, which included 37 raptors (6 species), mainly of peri-urban origins, and 150 corvids (4 species), mainly of urban origins. The analysis of the resulting blood smears allowed for the morphological identification of Hemosporodia and gave an estimate for the parasitemia. This study highlighted the presence of three genera of hemosporidia (Haemoproteus, Leucocytozoon and Plasmodium). The close release rates between infested and non-infested birds (72% of raptors, 35% of corvids) shows the weak clinical impact of hemoparasitism. Statistical analysis of the results demonstrated a positive association between juvenile corvids and Plasmodium sp. infection. Plasmodium infestation was particularly predominant in corvids, and was also more frequently implicated in cases of co-infestations. Though it was not statistically proven, Leucocytozoon seems to be infecting raptors more often than any other genera of hemosporidia. Results suggest that hemoparasitism in raptors and corvids in wildlife hospitals is a largely sub- clinical infestation, and has very little impact of the potential release of the birds. It is therefore crucial to determine the existence of vectors in wildlife hospitals, and to limit the risk of transmission during the rehabilitation period. Thus, it will allow for the implementation of risk management measures concerning vector control and will reduce the risk of dissemination of hemosporidies via released birds.; Les hémosporidies bénéficient d'un regain d'intérêt à l'heure actuelle suite, entre autres, aux dommages qu'elles ont pu causer sur la faune sauvage et à l'importance croissante des centres de soin dans la réhabilitation de l'avifaune. Les objectifs de cette étude étaient de réaliser un état des lieux de la situation épidémiologique de l'hémoparasitisme touchant les rapaces et corvidés accueillis dans un centre de soins de la faune sauvage en Île-de-France, d'identifier de potentiels facteurs influençant l'infestation et sa transmission, afin de proposer des mesures adaptées de gestion du risque représenté par l'hémoparasitisme sur les rapaces et corvidés. Une étude transversale monocentrique était réalisée sur 37 rapaces (6 espèces) principalement d'origine péri-urbaine et 150 corvidés majoritairement d'origine urbaine (4 espèces) arrivés au Chuv- FS de l'EnvA entre mai 2018 et mai 2019. L'analyse des frottis a permit l'identification morphologique des hémosporodies et l'estimation de la parasitémie. Cette étude a mis en évidence trois genres d'hémosporidies (Haemoproteus, Leucocytozoon et Plasmodium). Le taux de relâché très proche parmi les infestés et non infestés (72% des rapaces, 35% des corvidés) montre la faible incidence clinique liée à l'hémoparasitisme. L'analyse statistique des résultats a montré une association positive entre les corvidés juvéniles et l'infection par Plasmodium sp., L'infestation à Plasmodium en particulier était prédominante chez les corvidés et était aussi plus fréquemment impliquée dans les cas de co-infestations. Bien que non démontré statistiquement, Leucocytozoon semblait infester plus fréquemment les rapaces que les autres genres d'hémosporidies. Les résultats suggèrent que l'hémoparasitisme chez les rapaces et corvidés en centre de soins est une infestation majoritairement subclinique influençant probablement peu le potentiel relâché des oiseaux. Il est donc important de déterminer la présence des vecteurs dans les centres de soin et le risque de transmission pendant la période de réhabilitation. Ceci permettra d'établir les mesures de gestion de ce risque sur la lutte antivectorielle et permettra de réduire le risque de dissémination des hémosporidies lors des relachés.

Les antiparasitaires externes en application cutanée pour animaux de compagnie font partie des médicaments vétérinaires les plus vendus en pharmacie. Comme tous les médicaments, leur utilisation est susceptible d’induire des effets indésirables qui peuvent être limités en respectant certaines précautions d’emploi.

La gestion de Varroa destructor est un impératif sanitaire pour la filière apicole. La disponibilité du médicament vétérinaire en apiculture a considérablement évolué au cours des 10 dernières années. Néanmoins, la gestion de l ’infestation reste complexe et une bonne connaissance des modalités d ’utilisation de ces médicaments est nécessaire pour élaborer un protocole de traitement adapté à chaque situation sur le terrain. Un certain nombre de paramètres comme la rapidité d ’action, les conditions de diffusion, le risque de résistance et l ’adéquation par rapport au parcours de production des colonies doivent être pris en compte pour le choix du traitement. Enfin, ces traitements doivent être associés à des méthodes de luttes zootechniques, et à un suivi régulier de l ’infestation tout au long de l ’année pour permettre une bonne maîtrise du parasite.

Background: To overcome the limitations of conventional malaria rapid diagnostic tests (cRDTs) in diagnosing malaria in patients with low parasitaemia, ultrasensitive malaria rapid diagnostic tests (uRDTs) have recently been developed, with promising results under laboratory conditions. The current study is the first meta-analysis comparing the overall sensitivity, and specificity of newly developed ultrasensitive Plasmodium falciparum malaria RDT (Alere™ Ultra-sensitive Malaria Ag P. falciparum RDT) with the cRDT conducted in the same field conditions. Methods: PubMed, EMBASE, Cochrane infectious diseases group specialized register, and African Journals Online (AJOL) were searched up to 20th April 2021. Studies with enough data to compute sensitivity and specificity of uRDT and cRDT were retrieved. A random-effect model for meta-analysis was used to obtain the pooled sensitivity and specificity. Results: Overall, 15 data sets from 14 studies were included in the meta-analysis. The overall sensitivity of the Alere™ ultra-sensitive Malaria Ag P. falciparum RDT regardless of the reference test and the clinical presentation of participants, was 55.5% (95% confidence interval [CI]: 45.5; 65.0), while the sensitivity regardless of the reference test and the clinical presentation of participants, was 42.9% (95% CI: 31.5; 55.2) for the cRDT performed in the same field conditions. When PCR was used as reference test, the sensitivity of uRDT was 60.4% (95% CI: 50.8; 69.2), while the sensitivity was 49.4% (95% CI: 38.2; 60.6) for the cRDT. The pooled specificity of uRDT regardless of the reference test and the clinical presentation of participants was 98.6% (95% CI: 97.1; 99.4), and the pooled specificity of cRDT regardless of the reference test and the clinical presentation of participants was 99.3% (95% CI: 98.1; 99.7). When PCR was used as reference test the specificity of uRDT and cRDT was 97.5% (95% CI: 94.1; 98.9) and 98.2% (95% CI: 95.5; 99.3). Regardless of the reference test used, the sensitivity of Alere™ Ultra-sensitive Malaria Ag P. falciparum RDT in symptomatic patients was 72.1% (95%CI: 67.4; 76.4), while sensitivity of cRDT was 67.4% (95%CI: 57.6; 75.9). Conclusion: Findings of the meta-analysis show that Alere™ Ultra-sensitive Malaria Ag P. falciparum RDT compared to cRDT performed in the same field conditions has higher sensitivity but lower specificity although the difference is not statistically significant., SCOPUS: ar.j, info:eu-repo/semantics/published

Onchocerciasis and lymphatic filariasis are both parasitic diseases that are targeted for elimination by control programs in Central Africa. These programs are based on massive drug administration to the entire population living in endemic areas. The choice of drugs used is based on the endemicity of onchocerciasis and lymphatic filariasis. Thus, ivermectin is used in areas where only onchocerciasis is endemic, while the combination of ivermectin and albendazole is used in areas where lymphatic filariasis and onchocerciasis are coendemic.These treatments must be repeated because they kill the larval stage of the parasite, the microfilariae, but not the adult worms. These control programs are undoubtedly successful, but the fight continues. A current issue is the use of ivermectin in areas where another filariasis, loaisis, is also endemic. Indeed, subjects with a high microfilarial density of Loa loa in the blood are at risk of serious post-ivermectin adverse effects. Although the benefit/risk ratio of mass ivermectin treatment remains acceptable in these areas when onchocerciasis or lymphatic filariasis are meso-hyperendemic, it is not acceptable when they are hypoendemic.In order to interrupt the transmission of lymphatic filariasis and onchocerciasis, it is essential to develop effective and safe alternative strategies to control these filariasis in areas where they are hypoendemic and coendemic for loaisis, and to accelerate the control of these filariasis in areas where they are meso- or hyperendemic and coendemic for loaisis. Finally, in order to treat these areas, it seems important to better understand loaisis, which has been ignored by public health programs.This work provides new evidence for the evaluation of an existing alternative strategy: the semi-annual administration of albendazole against lymphatic filariasis in areas where loaisis is endemic. The added value of maintaining good compliance with mass albendazole administration programs has been evaluated.This work also reports the results of a clinical trial investigating the use of levamisole to decrease Loa loa microfilaremia below the threshold for the occurrence of severe post-ivermectin adverse effects, and thus would allow the safe administration of ivermectin to the general population in control programs.New approaches have also been investigated: the prophylactic effect of ivermectin which could be of interest in accelerating control through more frequent mass treatments and as chemoprophylaxis for travelers and expatriates.The use of levamisole in the management of loaisis or of ivermectin as chemoprophylaxis for onchocerciasis requires a precise evaluation of the safety of these molecules. We have thus conducted two pharmacovigilance studies using the WHO global pharmacovigilance database.Finally, concerning loaisis, we have studied and modeled the daily periodicity, the short- and long-term variability as well as the diagnostic variability of blood microfilaremia allowing to improve our understanding of the parasite and thus to bring new elements that will be useful in interventions seeking to evaluate new alternative strategies to manage endemic areas for loaisis; L'onchocercose et la filariose lymphatique sont toutes les deux des parasitoses faisant l'objet de programmes de lutte visant leurs éliminations en Afrique centrale. Ces programmes reposent sur l'administration massive de médicaments à toute la population vivant en zone d'endémie. Le choix des médicaments utilisés repose sur l’endémicité de l’onchocercose et de la filariose lymphatique. Ainsi, l'ivermectine est utilisée dans les zones où seule l'onchocercose est endémique tandis que l'association ivermectine et albendazole est utilisée dans les zones où la filariose lymphatique et l’onchocercose sont coendémiques.Ces traitements doivent être répétés car ils tuent le stade larvaire du parasite, les microfilaires, mais pas les vers adultes. Ces programmes de lutte sont, sans aucun doute, une réussite mais la lutte continue. Une problématique qui se pose actuellement est l’utilisation d'ivermectine dans les zones où une autre filariose, la loase, est également endémique. En effet, les sujets ayant une forte densité microfilarienne à Loa loa dans le sang sont à risque d'effet secondaire grave post-ivermectine. Bien que le rapport bénéfice/risque des traitements de masse par ivermectine reste acceptable dans ces zones lorsque l’onchocercose ou la filariose lymphatique sont méso-hyperendémiques, il ne l'est pas en lorsqu’elles sont hypoendémiques. Afin d’interrompre la transmission de la filariose lymphatique et de l’onchocercose, il est primordial de mettre en place des stratégies alternatives efficaces et sûres permettant de lutter contre ces filarioses dans les régions où elles sont hypoendémiques et coendémiques pour la loase et d’accélérer la lutte contre ces filarioses dans les régions où elles sont méso- ou hyperendémiques et coendémiques pour la loase. Enfin, pour parvenir à traiter ces zones, il semble important de mieux comprendre la loase, jusque-là ignoré par les programmes de santé publique.Ces travaux apportent de nouveaux éléments concernant l’évaluation d’une stratégie alternative déjà existante : l’administration semi-annuel d’albendazole contre la filariose lymphatique dans les zones où la loase est endémique. La valeur ajoutée du maintien d’une bonne observance thérapeutique aux programmes d’administration de masse d’albendazole a été évaluée.Ces travaux rapportent également les résultats d’un essai clinique portant sur l’utilisation du lévamisole pour diminuer la microfilarémie à Loa loa en dessous du seuil d’apparition des effets secondaires graves post-ivermectine, et ainsi permettrait l’administration sûre d’ivermectine à l’ensemble de la population dans le cadre des programmes de lutte.De nouvelles pistes de recherche ont également été étudiées : l’effet prophylactique de l’ivermectine qui pourrait avoir un intérêt dans le cadre de l’accélération de la lutte par mise en place de traitements de masse plus fréquents et en tant que chimioprophylaxie préexposition à destination des voyageurs et des expatriés.L’utilisation de lévamisole dans la prise en charge de la loase ou de l’ivermectine en chimioprophylaxie pour l’onchocercose nécessite d’évaluer précisément la sécurité d’emploi de ces molécules. Nous avons ainsi conduit deux études de pharmacovigilance à partir de la base mondiale de pharmacovigilance de l’OMS.Enfin, concernant la loase, nous avons étudié et modélisé la périodicité journalière, la variabilité à court terme et à long terme ainsi que la variabilité diagnostique de la microfilarémie sanguine permettant de mieux comprendre le parasite et donc d’apporter des éléments qui seront utiles dans les interventions cherchant à évaluer de nouvelles stratégies alternatives pour prendre en charge les zones d’endémie pour la loase.

Onchocerciasis and lymphatic filariasis are both parasitic diseases that are targeted for elimination by control programs in Central Africa. These programs are based on massive drug administration to the entire population living in endemic areas. The choice of drugs used is based on the endemicity of onchocerciasis and lymphatic filariasis. Thus, ivermectin is used in areas where only onchocerciasis is endemic, while the combination of ivermectin and albendazole is used in areas where lymphatic filariasis and onchocerciasis are coendemic.These treatments must be repeated because they kill the larval stage of the parasite, the microfilariae, but not the adult worms. These control programs are undoubtedly successful, but the fight continues. A current issue is the use of ivermectin in areas where another filariasis, loaisis, is also endemic. Indeed, subjects with a high microfilarial density of Loa loa in the blood are at risk of serious post-ivermectin adverse effects. Although the benefit/risk ratio of mass ivermectin treatment remains acceptable in these areas when onchocerciasis or lymphatic filariasis are meso-hyperendemic, it is not acceptable when they are hypoendemic.In order to interrupt the transmission of lymphatic filariasis and onchocerciasis, it is essential to develop effective and safe alternative strategies to control these filariasis in areas where they are hypoendemic and coendemic for loaisis, and to accelerate the control of these filariasis in areas where they are meso- or hyperendemic and coendemic for loaisis. Finally, in order to treat these areas, it seems important to better understand loaisis, which has been ignored by public health programs.This work provides new evidence for the evaluation of an existing alternative strategy: the semi-annual administration of albendazole against lymphatic filariasis in areas where loaisis is endemic. The added value of maintaining good compliance with mass albendazole administration programs has been evaluated.This work also reports the results of a clinical trial investigating the use of levamisole to decrease Loa loa microfilaremia below the threshold for the occurrence of severe post-ivermectin adverse effects, and thus would allow the safe administration of ivermectin to the general population in control programs.New approaches have also been investigated: the prophylactic effect of ivermectin which could be of interest in accelerating control through more frequent mass treatments and as chemoprophylaxis for travelers and expatriates.The use of levamisole in the management of loaisis or of ivermectin as chemoprophylaxis for onchocerciasis requires a precise evaluation of the safety of these molecules. We have thus conducted two pharmacovigilance studies using the WHO global pharmacovigilance database.Finally, concerning loaisis, we have studied and modeled the daily periodicity, the short- and long-term variability as well as the diagnostic variability of blood microfilaremia allowing to improve our understanding of the parasite and thus to bring new elements that will be useful in interventions seeking to evaluate new alternative strategies to manage endemic areas for loaisis, L'onchocercose et la filariose lymphatique sont toutes les deux des parasitoses faisant l'objet de programmes de lutte visant leurs éliminations en Afrique centrale. Ces programmes reposent sur l'administration massive de médicaments à toute la population vivant en zone d'endémie. Le choix des médicaments utilisés repose sur l’endémicité de l’onchocercose et de la filariose lymphatique. Ainsi, l'ivermectine est utilisée dans les zones où seule l'onchocercose est endémique tandis que l'association ivermectine et albendazole est utilisée dans les zones où la filariose lymphatique et l’onchocercose sont coendémiques.Ces traitements doivent être répétés car ils tuent le stade larvaire du parasite, les microfilaires, mais pas les vers adultes. Ces programmes de lutte sont, sans aucun doute, une réussite mais la lutte continue. Une problématique qui se pose actuellement est l’utilisation d'ivermectine dans les zones où une autre filariose, la loase, est également endémique. En effet, les sujets ayant une forte densité microfilarienne à Loa loa dans le sang sont à risque d'effet secondaire grave post-ivermectine. Bien que le rapport bénéfice/risque des traitements de masse par ivermectine reste acceptable dans ces zones lorsque l’onchocercose ou la filariose lymphatique sont méso-hyperendémiques, il ne l'est pas en lorsqu’elles sont hypoendémiques. Afin d’interrompre la transmission de la filariose lymphatique et de l’onchocercose, il est primordial de mettre en place des stratégies alternatives efficaces et sûres permettant de lutter contre ces filarioses dans les régions où elles sont hypoendémiques et coendémiques pour la loase et d’accélérer la lutte contre ces filarioses dans les régions où elles sont méso- ou hyperendémiques et coendémiques pour la loase. Enfin, pour parvenir à traiter ces zones, il semble important de mieux comprendre la loase, jusque-là ignoré par les programmes de santé publique.Ces travaux apportent de nouveaux éléments concernant l’évaluation d’une stratégie alternative déjà existante : l’administration semi-annuel d’albendazole contre la filariose lymphatique dans les zones où la loase est endémique. La valeur ajoutée du maintien d’une bonne observance thérapeutique aux programmes d’administration de masse d’albendazole a été évaluée.Ces travaux rapportent également les résultats d’un essai clinique portant sur l’utilisation du lévamisole pour diminuer la microfilarémie à Loa loa en dessous du seuil d’apparition des effets secondaires graves post-ivermectine, et ainsi permettrait l’administration sûre d’ivermectine à l’ensemble de la population dans le cadre des programmes de lutte.De nouvelles pistes de recherche ont également été étudiées : l’effet prophylactique de l’ivermectine qui pourrait avoir un intérêt dans le cadre de l’accélération de la lutte par mise en place de traitements de masse plus fréquents et en tant que chimioprophylaxie préexposition à destination des voyageurs et des expatriés.L’utilisation de lévamisole dans la prise en charge de la loase ou de l’ivermectine en chimioprophylaxie pour l’onchocercose nécessite d’évaluer précisément la sécurité d’emploi de ces molécules. Nous avons ainsi conduit deux études de pharmacovigilance à partir de la base mondiale de pharmacovigilance de l’OMS.Enfin, concernant la loase, nous avons étudié et modélisé la périodicité journalière, la variabilité à court terme et à long terme ainsi que la variabilité diagnostique de la microfilarémie sanguine permettant de mieux comprendre le parasite et donc d’apporter des éléments qui seront utiles dans les interventions cherchant à évaluer de nouvelles stratégies alternatives pour prendre en charge les zones d’endémie pour la loase.

Human African trypanosomiasis (HAT) also known as sleeping sickness is targeted for elimination as a public health problem by 2020 and elimination of infection by 2030. Although the number of reported cases is decreasing globally, integration of HAT control activities into primary healthcare services is endorsed to expand surveillance and control. However, this integration process faces several challenges in the field. This literature review analyzes what is known about integrated HAT control to guide the integration process in an era of HAT elimination. We carried out a scoping review by searching PubMed and Google Scholar data bases as well as gray literature documents resulting in 25 documents included for analysis. The main reasons in favor to integrate HAT control were related to coverage, cost, quality of service, or sustainability. There were three categories of factors influencing the integration process: 1) the clinical evolution of HAT, 2) the organization of health services, and 3) the diagnostic and therapeutic tools. There is a consensus that both active and passive approaches to HAT case detection and surveillance need to be combined, in a context-sensitive way. However, apart from some documentation about the constraints faced by local health services, there is little evidence on how this synergy is best achieved., SCOPUS: ar.j, info:eu-repo/semantics/published

My research topics concern the evolution of parasites and their adaptations to their hosts. To do so, I study two models: one terrestrial model, the nematode Trichostrongylina in vertebrates, and an aquatic model, the cirriped Rhizocephala in crabs. The nematode / vertebrate model allowed me to highlight the relay role of lagomorph hosts in the evolution of Trichostrongylina through a detailed study of life cycles, morphogenesis, and adult morphology. At Pierre and Marie Curie University, in the Computer and Systematic Laboratory (LIS) directed by Prof. Régine Vignes-Lebbe in 2004, I became interested in the morphological characters and taxonomy of Trichostrongylina. I proposed and constructed a database for the digital identification of these nematode parasites of lagomorphs using the Xper software developed by the team, while continuing to work on life cycles. In 2014, I made a thematic shift when I joined the BOREA laboratory, in a team led by Prof. Philippe Keith, in which I started the study of the marine model, Sacculina in crabs. It is on this subject that I co-supervised the PhD thesis of Fabien Trédez with Dr Nicolas Rabet (HDR) from 2012 to 2015. We worked on the larval development of Sacculina carcini, a parasite of the green crab Carcinus maenas, which allowed us to identify a new nauplius larval stage, thanks to very precise monitoring of the life cycle. We also demonstrated synchronism in egg-laying, a phenomenon explained by synchronous cell division. At the same time, I remain interested in the systematics and phylogeny of Trichostrongylina and Rhizocephala. This led me to describe new nematode species in particular and to research phylogenetic relationships, particularly from molecular data. Molecular data in Rhizocephala are often the only means to discriminate between species and this work allows us to test the true host specificity in Sacculins. In the future, I wish to develop my research on the Sacculin model, in particular on the chemical communication between the parasite and its host, and I wish to study the coevolution between the host and the parasite on Sacculins but also with new aquatic models like Monogens or Myxosporea and fish.; Mon sujet de recherche porte sur l'évolution des parasites et de leur adaptation chez l’hôte. Pour ce faire, j’étudie deux modèles : l’un terrestre, le modèle nématode Trichostrongylina / Vertébré, l’autre aquatique le modèle cirripède Rhizocephala / crabe. L’étude du modèle nématode / vertébré m’a permis de mettre en évidence le rôle relais des hôtes lagomorphes dans l’évolution des Trichostrongylina à travers une étude détaillée des cycles de vie et de la morphogénèse, mais aussi de la morphologie des adultes. Recrutée à l’université Pierre et Marie Curie, au Laboratoire Informatique et Systématique (LIS) dirigé par le Pr Régine Vignes-Lebbe en 2004, je me suis intéressée aux caractères morphologiques et à la taxinomie des Trichostrongylina. J’ai ainsi proposé une base d’identification numérique de ces nématodes, parasites de lagomorphes, à l’aide du logiciel Xper, développé par l’équipe, tout en continuant à travailler sur les cycles de vie. En 2014, j’ai fait une reconversion thématique à mon arrivée dans l’UMR BOREA, équipe dirigée par le Pr Philippe Keith, dans laquelle j’ai débuté une étude sur un second modèle aquatique marin : la sacculine et le crabe. C'est dans cette thématique que j'ai co-encadré avec le Dr Nicolas Rabet (HDR) de 2012 à 2015, la thèse de Fabien Trédez. Nous avons travaillé sur le développement larvaire de la sacculine Sacculina carcini, parasite du crabe vert Carcinus maenas ce qui nous a permis d’identifier un nouveau stade nauplius, grâce à un suivi très précis du cycle de vie, mais aussi de montrer un synchronisme dans les pontes, phénomène expliqué par une division cellulaire synchrone. Parallèlement, je m'intéresse à la systématique et la phylogénie des Trichostrongylina et des Rhizocephala. J’ai ainsi décrit plusieurs nouvelles espèces chez les nématodes en particulier et chercher à résoudre les relations phylogénétiques entre elles, à partir de données moléculaires. Chez les rhizocéphales, les données moléculaires, sont parfois les seules données permettant de discriminer des espèces entre elles en effet les caractères morphologiques sont souvent peu discriminants. Dans un futur proche, je souhaite continuer à développer mes recherches sur le modèle sacculine, en particulier sur la communication chimique entre le parasite et son hôte. Je vise aussi à continuer d’étudier la coévolution entre l’hôte et le parasite sur le modèle sacculine mais également avec de nouveaux modèles aquatiques comme les Monogènes ou les Myxosporea et les poissons.

Chagas disease is a vector-borne parasitic disease caused by the flagellated protozoan Trypanosoma cruzi and transmitted to humans by a large group of bloodsucking triatomine bugs. Triatomine insects, such as Rhodnius prolixus, ingest a huge amount of blood in a single meal. Their midgut represents an important interface for triatomine–trypanosome interactions. Furthermore, the development of parasites and their vectorial transmission are closely linked to the blood feeding and digestion; thus, an understanding of their physiology is essential for the development of new strategies to control triatomines. In this study, we used label-free quantitative proteomics to identify and analyze the early effect of blood feeding on protein expression in the midgut of Rhodnius prolixus. We both identified and quantified 124 proteins in the anterior midgut (AM) and 40 in the posterior midgut (PM), which vary significantly 6 h after feeding. The detailed analysis of these proteins revealed their predominant involvement in the primary function of hematophagy, including proteases, proteases inhibitors, amino acids metabolism, primary metabolites processing, and protein folding. Interestingly, our proteomics data show a potential role of the AM in protein digestion. Moreover, proteins related to detoxification processes and innate immunity, which are largely accepted to be triggered by blood ingestion, were mildly modulated. Surprisingly, one third of blood-regulated proteins in the AM have unknown function. This work contributes to the improvement of knowledge on the digestive physiology of triatomines in the early hours post-feeding. It provides key information for selecting new putative targets for the development of triatomine control tools and their potential role in the vector competence, which could be applied to other vector species., SCOPUS: ar.j, info:eu-repo/semantics/published

Background: Despite the huge and in parts very successfull global effort to eradicate malaria, it still is one of the most deadly infectious diseases. Therefore Plasmodium falciparum the disease causing parasite is a major target of medical research. Post-translational modifications (PTMs) constitute a huge group of chemical modifications that increase the complexity of the proteomes of living beings. PTMs have been discussed as potential anti-malarial drug targets due to their involvement in many cell processes. O-GlcNAcylation is a widespread PTM found in different organisms including P.falciparum. The aim of this study was to identify O-GlcNAcylated proteins of P. falciparum, to learn more about such modification process and to predict its possible funcional role in the Apicomplexans. Methods: The P. falciparum strain 3D7 was cultivated in erythrocytes, purified and the proteome checked for the O-GlcNAc-modification by using different methods. The level of UDP-GlcNAc, the donor of the sugar moiety for O-GlcNAcylation processes, was measured using high performance anion exchange chromatography (HPAEC). O-GlcNAcylated proteins were enriched and purified utilizing either click chemistry labelling or adsorption on succinyl-wheat germ agglutinin beads. Proteins were then identified by mass-spectrometry (nano-LC MS/MS). Results: While low, when compared to MRC-5 control cells, P. falciparum possesses its own pool of UDP-GlcNAc. By using proteomics methods, 13 O-GlcNAcylated proteins were unambiguously identified in late trophozoites (11 by click-chemistry and 6 by sWGA-beads enrichment; 4 being identified by the two approaches). These proteins are all part of pathways, functions and structures important for the parasite survival. By probing ���clicked��� proteins using specific antibodies the heat shock protein (Hsp)70 and alpha-tubulin were identified as P. falciparum O-GlcNAc-bearing proteins. Cultivation of P. falciparum in presence of an inhibitor for the O-GlcNAc catalysis reduced the parasite growth. However the interaction effect was not significant. Conclusion: This is the first study exploring the O-GlcNAcylated proteins in P.falciparum. While the parasite O-GlcNAcome seems to be close to those of other species, the structural differences exhibited by the proteomes provides a glimpse of innovative therapeutic paths to fight malaria. Blocking biosynthesis of UDP-GlcNAc or inhibiting the O-GlcNAc catalysis could be other promising options to inhibit the life cycle of Plasmodium. The existence of O-GlcNAcylation in P. falciparum and therefore in Apicomplexa in general could help to unravel the phylum���s difficult taxonomic classification., Hintergrund: Malaria tropica ist global gesehen eine der t��dlichsten Infektionskrankheiten. In einem historischen Kraftakt gelang es, die durch den Parasiten Plasmodium falciparum ausgel��ste und ��ber Mosquitos ��bertratgene Krankheit einzud��mmen und in vielen L��ndern vollst��ndig zu eradizieren. Dieses Ziel global zu erreichen, scheint jedoch noch in weiter Ferne. Vor allen in den tropischen Regionen Afrikas versterben j��hrlich weiterhin mehrere hunderttausend Menschen, vor allem S��uglinge und Kinder, an der Krankheit. Posttranslationale Modifikationen (PTMs) bilden eine gro��e Gruppe biochemischer Ver��nderungen, welche die Komplexit��t von Proteomen aller Lebewesen erh��hen. PTMs wurden aufgrund ihrer Beteiligung an verschiedensten Zellprozessen bereits mehrfach als Ziel potentieller Malaria-Therapeutika diskutiert. O-GlcNAcylierung ist eine bei vielen Organismen verbreitete PTM. Diese spezielle Form der Glykosylierung ist aufgrund der Beteiligung an verschiedenen Pathologien wie neurodegenerativen Erkrankungen und Neoplasien in den Fokus ger��ckt. Sie spielt jedoch auch eine wichtige regulative Rolle im zellul��ren Energiestoffwechsel. Auch bei P. falciparum ist ihr allgemeines Vorkommen bereits bekannt. Ziel dieser Arbeit war es zu identifizieren, welche Proteine im Proteom des Parasiten O-GlcNAc modifiziert sind, mehr ��ber den Prozess dieser Modifikation herauszufinden und eventuelle Funktionen bei Apikomplexa generell nachvollziehen zu k��nnen. Methoden: Der P. falciparum Stamm 3D7 wurde in Erythrozytenkulturen angez��chtet und vermehrt. Das Proteom wurde auf O-GlcNAcylierung untersucht, hierbei wurden unterschiedliche Nachweismethoden angewandt. Das Niveau der UDP-GlcNAc-Konzentration, dem Donor der O-GlcNAc-Modifikation, wurde in der high performance Anion Exchange Chromatography] (HPAEC) gemessen. O-GlcNAcylierte Proteine wurden nach click-chemistry-Biotinmarkierung und mit Weizenkeimlektin-Agaroseperlen angereichert. Die Identifizierung der modifizierten Proteine erfolgte in der Massenspektometrie (nano-LC MS/MS). Ergebnisse: P. falciparum verf��gt ��ber einen eigenen, wenn auch im Vergleich zu MRC-5 Kontrollzellen sehr niedrigen, UDP-GlcNAc-Vorrat. In der Immundetektion stellen sich Unterschiede der O-GlcNAcylierung der verschiedenen Parasitenstadien dar. Durch verschiedene proteomischeTechniken konnten im Proteom von reifen Trophozoiten 14 O-GlcNAcylierte Proteine eindeutig identifiziert werden (11 ��ber click-chemistry, 6 ��ber sWGA-Perlen Anreicherung und eine durch spezifische Antik��rper). Diese Proteine sind an f��r das ��berleben des Parasiten wichtigen, Funktionen, Strukturen und Stoffwechselwegen beteiligt. Vier der identifizierten Proteine sind Enzyme der Glykolyse. Diese ist von gro��er Bedeutung f��r den Energiestoffwechsel des Parasiten. Durch Inkubation click-chemistry-modifizierter Proteine mit spezifischen Antik��rpern konnte die O-GlcNAcyirung der Proteine Hsp70 und ��-Tubulin zus��tzlich zur Massenspektroskopie immunbiochemisch gezeigt werden. Die Inkubation von P. falciparum-Kulturen mit einem Inhibitor der O-GlcNAc-Abspaltung f��hrte zu einer nicht signifikanten Abnahme der Wachstumsrate Schlussfolgerungen: In dieser Studie konnten zum ersten Mal O-GlcNAcylierte Proteine im Proteom von P. falciparum nachgewiesen und benannt werden. Auch wenn einige Parallelen zum O-GlcNAcom anderer Organismen bestehen, lassen strukturelle Unterschiede doch die M��glichkeit erscheinen, diese Strukturen als m��gliche Ziele einer Malariatherapie in Angriff zu nehmen. Die Blockierung der UDP-GlcNAc Biosynthese oder der Abspaltung von O-GlcNAc von bereits modifizierten Proteinen k��nnten andere vielversprechende Ans��tze darstellen, um den Lebenszyklus von P. falciparum zu hemmen. Zudem k��nnen das Auftreten der posttranslationalen Modifikation bei P. falciparum sowie die Unterschiede im Vergleich zu anderen Spezies Hinweise bez��glich der taxonomischen Einordnung der Apicomplexa bieten.

Animal trypanosomoses due to trypanosomes of African origin (ATAO), mainly caused by Trypanosoma congolense type Savannah (TCS), T. brucei brucei (TBB), T. vivax (TV), and T. evansi, are widespread diseases that affect domestic and wild mammals and have a huge economic impact. ATAO clinical suspicions are usually confirmed by parasitological and molecular methods, while sero-epidemiological surveys are generally carried out using the OIE-recommended ELISA method based on whole cell lysate soluble antigens (WCLSA) from purified trypanosomes; this reagent is usually stored frozen. With a view to expanding this ELISA test, we assessed, standardized, and validated the use of dehydrated rather than frozen WCLSA and serum samples. For the three ELISA assays (TV, TCS & TBB), a repeatability study revealed no significant difference between repeats. The results obtained using frozen rather than freeze-dried antigen and serum strongly correlated for Pearson’s correlation values (>0.93) and Lin’s measure (“very good” to “excellent”). Reproducibility was robust, with Pearson’s correlation values >0.97 for inter technician effects, and 0.87 (TV) to 0.97 (TBB & TCS) for inter-laboratory tests; their combination was “very satisfactory” to “excellent” according to Lin’s measure and there was no impact on qualitative test results. Dehydrated reagents offer the advantage of shipment at room temperature, allowing the secured provision of reagents to regional laboratories. Together with a compendium of standard diagnostic protocols for ATAO (/OIE), dehydrated reagents will enable the serological diagnosis of ATAO at regional level in endemic countries. This very welcome improvement in the context of the Progressive Control Pathway for trypanosomes, recently launched by African countries, will possibly be extended to Latin America in the near future.

São Paulo, a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in São Paulo, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in São Paulo, we generated and analysed virus genomic data and epizootic case data from NHPs in São Paulo. We report the occurrence of three spatiotemporally distinct phases of the outbreak in São Paulo prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in São Paulo, mostly sampled from NHPs between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in São Paulo at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern São Paulo subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of São Paulo state. Our results shed light on the sylvatic transmission of YFV in highly fragmented forested regions in São Paulo state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species., SCOPUS: ar.j, info:eu-repo/semantics/published