Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). METHODS: This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as "definite," "probable," or "possible" using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. DISCUSSION: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT04145258. Registered on October 30, 2019

Les Sourds : une population particulièrement vulnérable aux pratiques sexuelles à risque en Afrique de l'Ouest

International audienceLes personnes sourdes constituent en Afrique subsaharienne une minorité importante fortement exposée aux pratiques sexuelles à risques. Peu de travaux prennent pourtant en compte leur situation. La méconnaissance de cette population et de leurs langues des signes en fait un groupe d’exclus parce que difficile à atteindre.Cette étude qualitative menée à Ouagadougou, Burkina Faso, s’intègre dans un programme de recherche plus large mené par Handicap International et l’Institut de Recherche pour le Développement sur la vulnérabilité des personnes handicapées face au VIH, au Cameroun et au Burkina Faso. Une centaine d’entretiens semi directifs ont été menés auprès : d’hommes et de femmes sourds communiquant en langue des signes, de membres de leurs familles, de personnels soignants et/ou associatifs. Le côté novateur de ce travail tient à la prise en compte des différents niveaux de langue des signes (très hétérogènes selon le niveau de scolarisation et socialisation), à l’étroite collaboration entre chercheur et assistant de recherche sourd et à l’utilisation de la caméra.La recherche met en avant :1/ Des modes de connaissances distinctifs : accès à l’information très limité, modes de transmission du VIH mal connus, déformation d’information et faibles moyens de protection, absence des Sourds au sein des structures de suivi VIH, remise en cause de la confidentialité des informations à communiquer au patient en présence d’un accompagnant entendant2/ Des modes de vie spécifiques : pratiques sexuelles marquées par la fréquence de multipartenariats (peu de relations stables, grossesses multiples et violences sexuelles), forte précarité, sentiment d’exclusion social et familial. Peu scolarisés et cantonnés aux tâches ménagères, les Sourds sont souvent contraints de se livrer à des activités génératrices de revenus pouvant les exposer à de gros risques. Des réseaux de « mendicité par les papiers » sont développés au Burkina Faso et dans les pays avoisinants, par des chefs sourds locaux et étrangers. Les filles sourdes recrutées (« pêchées ») et emmenées à l’étranger sont généralement soumises à une exploitation sexuelle. Invisibles et peu entendus, les Sourds sont très fortement exposés aux pratiques sexuelles à risques, dont la principale vulnérabilité est l’absence d’une prévention adaptée, en particulier par des professionnels sourds, et d’échanges avec les soignants. Il semble urgent de prendre en compte la langue des signes et de mettre en place une recherche action engagée au sein de structures de références. La question de la « mendicité par les papiers », connue et cachée par une grande partie de la communauté sourde, mérite d’être prise très au sérieux. Elle nous éclaire sur la situation des Sourds au Burkina Faso (et en Afrique de l’ouest) et devient un axe central dans la compréhension des pratiques sexuelles à risques

A review of screening strategies for cervical cancer in human immunodeficiency virus-positive women in sub-Saharan Africa

Cervical cancer (CC) is a leading cause of cancer-related death and a major public health issue in sub-Saharan Africa. This heavy burden parallels that of the human immunodeficiency virus (HIV) infection, which increases the risk of developing CC. Despite the progressive reduction of HIV prevalence in the past decade, the CC incidence and mortality rates in sub-Saharan Africa remain high. The heterogeneity of the distribution of the two diseases in the African continent, together with the different availability of human and material resources, stands in the way of finding an appropriate screening strategy. The lack of high-quality evidence on the prevention of CC for HIV-positive women, which is necessary for the implementation of efficient screening and treatment strategies, results in the absence of a clearly defined program, which is responsible for the low screening uptake and high mortality rates in sub-Saharan Africa. By taking advantage of the HIV-positive women's frequent access to health facilities, one way to increase the CC screening coverage rates would be by providing integrated HIV and screening services within the same infrastructure. With the increasing availability of cost-effective methods, screening is becoming more and more available to women who have limited access to health care. Moreover, the introduction of point-of-care technologies for human papillomavirus testing and the subsequent implementation of screen-and-treat strategies, by reducing the number of clinical appointments and, in the long term, the loss to follow-up rates, open up new opportunities for all women, regardless of their HIV status. The purpose of this review is to provide an insight into the different screening practices for CC in order to help define one that is adapted to the resources and necessities of HIV-positive women living in middle-to-low income countries

ACCÈS À LA PRÉVENTION ET AUX SOINS DU CANCER DU COL DE L'UTÉRUS À OUAGADOUGOU (BURKINA FASO): Etude socio-anthropologique

Le cancer du col de l’utérus (CCU) est une pathologie qui a un impact considérable en termes de santé publique, en particulier dans les pays du Sud. En Afrique de l’Ouest, cette pathologie féminine représente une des principales causes de mortalité par cancer. Alors qu’il est démontré que l’accès aux services de prévention et de prise en charge aide à réduire significativement l’incidence de la maladie, les pays ouest-africains font face à des défis techniques, logistiques, financiers et socioculturels qui limitent l’accès à la prévention, au dépistage et à la prise en charge du CCU.C’est dans cette optique que Médecins du Monde (MdM) a initié un projet pilote de prévention du CCU en 2018 dans le district sanitaire de Baskuy à Ouagadougou, en vue d’améliorer le dépistage et la prise en charge précoce du CCU répondant aux recommandations internationales dans le pays.La présente étude socio-anthropologique vise à identifier les facteurs qui favorisent ou qui constituent des obstacles au dépistage et à la prise en charge des lésions précancéreuses et du CCU. Il s’agit de documenter les systèmes de contraintes qui entravent l’accès aux services de dépistage et de prise en charge du CCU à Ouagadougou selon une perspective individuelle et institutionnelle

ACCÈS À LA PRÉVENTION ET AUX SOINS DU CANCER DU COL DE L'UTÉRUS À OUAGADOUGOU (BURKINA FASO): Etude socio-anthropologique

Le cancer du col de l’utérus (CCU) est une pathologie qui a un impact considérable en termes de santé publique, en particulier dans les pays du Sud. En Afrique de l’Ouest, cette pathologie féminine représente une des principales causes de mortalité par cancer. Alors qu’il est démontré que l’accès aux services de prévention et de prise en charge aide à réduire significativement l’incidence de la maladie, les pays ouest-africains font face à des défis techniques, logistiques, financiers et socioculturels qui limitent l’accès à la prévention, au dépistage et à la prise en charge du CCU.C’est dans cette optique que Médecins du Monde (MdM) a initié un projet pilote de prévention du CCU en 2018 dans le district sanitaire de Baskuy à Ouagadougou, en vue d’améliorer le dépistage et la prise en charge précoce du CCU répondant aux recommandations internationales dans le pays.La présente étude socio-anthropologique vise à identifier les facteurs qui favorisent ou qui constituent des obstacles au dépistage et à la prise en charge des lésions précancéreuses et du CCU. Il s’agit de documenter les systèmes de contraintes qui entravent l’accès aux services de dépistage et de prise en charge du CCU à Ouagadougou selon une perspective individuelle et institutionnelle

Implementation of HPV-based screening in Burkina Faso: lessons learned from the PARACAO hybrid-effectiveness study

International audienceBackground: Cervical cancer screening in sub-Saharan countries relies on primary visual inspection with acetic acid (VIA). Primary human papillomavirus (HPV)-based screening is considered a promising alternative. However, the implementation and real-life effectiveness of this strategy at the primary-care level in limited-resource contexts remain under explored. In Ouagadougou, Burkina Faso, free HPV-based screening was implemented in 2019 in two primary healthcare centers. We carried out a process and effectiveness evaluation of this intervention. Methods: Effectiveness outcomes and implementation indicators were assessed through a cohort study of screened women, observations in participating centers, individual interviews with women and healthcare providers and monitoring reports. Effectiveness outcomes were screening completeness and women's satisfaction. Logistic regression models and concurrent qualitative analysis explored how implementation variability, acceptability by women and the context affected effectiveness outcomes. Results: After a 3-month implementation period, of the 350 women included in the cohort, 94% completed the screening, although only 26% had their screening completed in a single visit as planned in the protocol. The proportion of highly satisfied women was higher after result disclosure (95%) than after sampling (65%). A good understanding of the screening results and recommendations increased screening completeness and women's satisfaction, while time to result disclosure decreased satisfaction. Adaptations were made to fit healthcare workers' workload. Conclusion: Free HPV-based screening was successfully integrated within primary care in Ouagadougou, Burkina Faso, leading to a high level of screening completeness despite the frequent use of multiple visits. Future implementation in primary healthcare centers needs to improve counseling and reduce wait times at the various steps of the screening sequence

Neurodevelopmental outcomes in HIV-infected and uninfected African children

International audienceOBJECTIVE:HIV infection is associated with cognitive impairments, but outcomes are poorly explored in children starting antiretroviral therapy (ART) early or in those exposed but uninfected.DESIGN:Nested cross-sectional evaluation of the neurocognitive and behavioural outcomes of HIV-infected, HIV-exposed uninfected (HEU) and HIV-unexposed (HUU) Cameroonian children at age 4-9 years prospectively followed.METHODS:Cognitive development was assessed in 127 HIV-infected, 101 HEU, 110 HUU children using the KABC-II, neurologic dysfunction using the Touwen examination and behavioural difficulties using the Strength and Difficulties Questionnaire (SDQ). Analyses were adjusted for children age, sex and primary language. Contextual factors were included in a second step to assess their effects on outcomes.RESULTS:All HIV-infected children were treated before 12 months. There was a negative linear gradient in KABC-II scores from HUU children to HEU and HIV-infected children [gradient: -6.0 (-7.7; -4.3) for nonverbal index, NVI, and -8.8 (-10.7; -6.8) for mental processing index, MPI]. After adjusting for contextual factors, scores of HEU children were not significantly different from those of HUU children (all P > 0.1) and differences between HIV-uninfected and HUU children reduced [NVI: from -11.9 (-15.3; -8.5) to -3.4 (-6.8; -0.01), MPI: from -17.6 (-21.3; -13.8) to -5.5 (-9.3; -1.7)]. Compared with uninfected children, HIV-infected children had more neurological dysfunctions and higher SDQ scores (P = 0.002).CONCLUSION:Despite early ART, perinatal-HIV infection is associated with poorer neurocognitive scores and increased behavioural difficulties during childhood. Contextual factors play an important role in this association, which emphasizes the need for early nutritional and developmental interventions targeting both HIV-affected infants and their relatives

Assessment of the impact of a personalised nutrition intervention in impaired glucose regulation over 26 weeks: a randomised controlled trial

International audienceAbstract Dietary interventions can reduce progression to type 2 diabetes mellitus (T2DM) in people with non-diabetic hyperglycaemia. In this study we aimed to determine the impact of a DNA-personalised nutrition intervention in people with non-diabetic hyperglycaemia over 26 weeks. ASPIRE-DNA was a pilot study. Participants were randomised into three arms to receive either (i) Control arm: standard care (NICE guidelines) (n = 51), (ii) Intervention arm: DNA-personalised dietary advice (n = 50), or (iii) Exploratory arm: DNA-personalised dietary advice via a self-guided app and wearable device (n = 46). The primary outcome was the difference in fasting plasma glucose (FPG) between the Control and Intervention arms after 6 weeks. 180 people were recruited, of whom 148 people were randomised, mean age of 59 years (SD = 11), 69% of whom were female. There was no significant difference in the FPG change between the Control and Intervention arms at 6 weeks (− 0.13 mmol/L (95% CI [− 0.37, 0.11]), p = 0.29), however, we found that a DNA-personalised dietary intervention led to a significant reduction of FPG at 26 weeks in the Intervention arm when compared to standard care (− 0.019 (SD = 0.008), p = 0.01), as did the Exploratory arm (− 0.021 (SD = 0.008), p = 0.006). HbA1c at 26 weeks was significantly reduced in the Intervention arm when compared to standard care (− 0.038 (SD = 0.018), p = 0.04). There was some evidence suggesting prevention of progression to T2DM across the groups that received a DNA-based intervention (p = 0.06). Personalisation of dietary advice based on DNA did not result in glucose changes within the first 6 weeks but was associated with significant reduction of FPG and HbA1c at 26 weeks when compared to standard care. The DNA-based diet was effective regardless of intervention type, though results should be interpreted with caution due to the low sample size. These findings suggest that DNA-based dietary guidance is an effective intervention compared to standard care, but there is still a minimum timeframe of adherence to the intervention before changes in clinical outcomes become apparent. Trial Registration: www.clinicaltrials.gov.uk Ref: NCT03702465