Provider and User Acceptability of Integrated Treatment for the Control of Malaria and Helminths in Saraya, South-Eastern Senegal.

Integration of vertical programs for the control of malaria, schistosomiasis, and soil-transmitted helminthiasis has been recommended to achieve elimination of malaria and neglected tropical diseases (NTD) by 2030. This qualitative study was conducted within the context of a randomized controlled trial to explore the perceptions and views of parents/caregivers of at-risk children and healthcare providers to determine their acceptability of the integrated malaria-helminth treatment approach. Randomly selected parents/caregivers of children enrolled in the trial, healthcare providers, trial staff, malaria, and NTD program managers were interviewed using purpose-designed topic guides. Transcripts obtained from the interviews were coded and common themes identified using content analysis were triangulated. Fifty-seven study participants comprising 26 parents/caregivers, 10 study children aged ≥ 10 years, 15 trial staff, four healthcare providers, and two managers from the Senegal Ministry of Health were interviewed. Thirty-eight of the participants (66.7%) were males, and their ages ranged from 10 to 65 years. Overall, the integrated malaria-helminth treatment approach was considered acceptable, but the study participants expressed concerns about the taste, smell, and side effects associated with amodiaquine and praziquantel in the combination package. Reluctance to accept the medications was also observed among children aged 10 to 14 years due to peer influence and gender-sensitive cultural beliefs. Addressing concerns about the taste and smell of amodiaquine and praziquantel is needed to optimize the uptake of the integrated treatment program. Also, culturally appropriate strategies need to be put in place to cater for the inclusion of children aged 10 to 14 years in this approach

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258

Role of EBV and HIV in the Generation of Burkitt Lymphoma’s t(8; 14) Chromosomal Translocation

Le Lymphome de Burkitt est un lymphome non hodgkinien de type B caractérisé dans 80% des cas par une translocation chromosomique impliquant l’oncogène MYC sur le chromosome 8 et le gène des chaines lourdes d’immunoglobuline IGH sur le chromosome 14. Le développement de ce lymphome est étroitement lié au virus EBV, systématiquement présent dans les formes endémiques et au VIH qui lui définit une entité clinique à part. Cependant, le rôle joué par ces virus dans la formation de la translocation est peu connu. Des cassures double brins simultanées, une réparation non-homologue de ces cassures et une proximité spatiale sont les conditions nécessaires pour que deux loci forment une translocation. Nous avons ainsi investigué l’effet des virus EBV sur ces trois conditions dans les lymphocytes B. Nos résultats montrent que la réactivation du virus EBV dans les lymphocytes B infectées de façon latente augmente la proximité spatiale entre MYC et IGH, normalement situés dans des compartiments différents. Cette relocalisation semble être secondaire à l’induction de dommages d’ADN spécifiques sur MYC et serait médiée par la protéine de réparation de l’ADN MRE11. Nous montrons aussi que la protéine Tat du VIH-1 peut pénétrer dans les cellules B et y induire une expression aberrante du gène AICDA qui peut secondairement introduire des cassures doubles brins simultanées sur MYC et IGH. Ce travail fournit une preuve de l’implication directe du cycle lytique d’EBV dans la formation de la t(8;14) et renforce les données existantes sur le rôle de Tat dans cette translocation.Abstract: Burkitt's lymphoma is a B cell non-Hodgkin's lymphoma characterized in 80% of cases by a chromosomal translocation involving the MYC oncogene on chromosome 8 and the immunoglobulin heavy chain gene IGH on chromosome 14. The development of this lymphoma is intricately linked to the EBV virus, almost always present in endemic forms, and to HIV, which defines a clinical entity. However, little is known about the role played by these viruses in translocation formation. Simultaneous double-strand breaks, non-homologous repair of these breaks, and spatial proximity are the conditions necessary for two loci to form a translocation. We thus investigated the effect of EBV viruses on these three conditions in B lymphocytes. Our results show that EBV reactivation in latently infected B lymphocytes increases the spatial proximity between MYC and IGH, normally located in different compartments. Specific DNA damage on MYC locus seems to induce this relocation of MYC next to IGH in a MRE11-dependant mechanism. We also show that the HIV1-Tat protein can enter B cells and induce an aberrant expression of the AICDA gene increasing the risk of simultaneous DNA double strand breaks on MYC and IGH loci. This work provides evidence for the direct involvement of the EBV lytic cycle in t (8; 14) formation and strengthens previously described data on of HIV1-Tat’s role in this translocation

Rôle des virus EBV et VIH dans la formation de la translocation chromosomique t(8;14) du Lymphome de Burkitt

Abstract: Burkitt's lymphoma is a B cell non-Hodgkin's lymphoma characterized in 80% of cases by a chromosomal translocation involving the MYC oncogene on chromosome 8 and the immunoglobulin heavy chain gene IGH on chromosome 14. The development of this lymphoma is intricately linked to the EBV virus, almost always present in endemic forms, and to HIV, which defines a clinical entity. However, little is known about the role played by these viruses in translocation formation. Simultaneous double-strand breaks, non-homologous repair of these breaks, and spatial proximity are the conditions necessary for two loci to form a translocation. We thus investigated the effect of EBV viruses on these three conditions in B lymphocytes. Our results show that EBV reactivation in latently infected B lymphocytes increases the spatial proximity between MYC and IGH, normally located in different compartments. Specific DNA damage on MYC locus seems to induce this relocation of MYC next to IGH in a MRE11-dependant mechanism. We also show that the HIV1-Tat protein can enter B cells and induce an aberrant expression of the AICDA gene increasing the risk of simultaneous DNA double strand breaks on MYC and IGH loci. This work provides evidence for the direct involvement of the EBV lytic cycle in t (8; 14) formation and strengthens previously described data on of HIV1-Tat’s role in this translocation.Le Lymphome de Burkitt est un lymphome non hodgkinien de type B caractérisé dans 80% des cas par une translocation chromosomique impliquant l’oncogène MYC sur le chromosome 8 et le gène des chaines lourdes d’immunoglobuline IGH sur le chromosome 14. Le développement de ce lymphome est étroitement lié au virus EBV, systématiquement présent dans les formes endémiques et au VIH qui lui définit une entité clinique à part. Cependant, le rôle joué par ces virus dans la formation de la translocation est peu connu. Des cassures double brins simultanées, une réparation non-homologue de ces cassures et une proximité spatiale sont les conditions nécessaires pour que deux loci forment une translocation. Nous avons ainsi investigué l’effet des virus EBV sur ces trois conditions dans les lymphocytes B. Nos résultats montrent que la réactivation du virus EBV dans les lymphocytes B infectées de façon latente augmente la proximité spatiale entre MYC et IGH, normalement situés dans des compartiments différents. Cette relocalisation semble être secondaire à l’induction de dommages d’ADN spécifiques sur MYC et serait médiée par la protéine de réparation de l’ADN MRE11. Nous montrons aussi que la protéine Tat du VIH-1 peut pénétrer dans les cellules B et y induire une expression aberrante du gène AICDA qui peut secondairement introduire des cassures doubles brins simultanées sur MYC et IGH. Ce travail fournit une preuve de l’implication directe du cycle lytique d’EBV dans la formation de la t(8;14) et renforce les données existantes sur le rôle de Tat dans cette translocation

Rôle des facteurs infectieux et environnementaux dans l'oncogenèse du Lymphome de Burkitt endémique

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HIV‐1 Tat protein induces aberrant activation of AICDA in human B‐lymphocytes from peripheral blood

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