Informed consent comprehension in African research settings

ObjectivePrevious reviews on participants' comprehension of informed consent information have focused on developed countries. Experience has shown that ethical standards developed on Western values may not be appropriate for African settings where research concepts are unfamiliar. We undertook this review to describe how informed consent comprehension is defined and measured in African research settings.MethodsWe conducted a comprehensive search involving five electronic databases: Medline, Embase, Global Health, EthxWeb and Bioethics Literature Database (BELIT). We also examined African Index Medicus and Google Scholar for relevant publications on informed consent comprehension in clinical studies conducted in sub-Saharan Africa. 29 studies satisfied the inclusion criteria; meta-analysis was possible in 21 studies. We further conducted a direct comparison of participants' comprehension on domains of informed consent in all eligible studies.ResultsComprehension of key concepts of informed consent varies considerably from country to country and depends on the nature and complexity of the study. Meta-analysis showed that 47% of a total of 1633 participants across four studies demonstrated comprehension about randomisation (95% CI 13.9–80.9%). Similarly, 48% of 3946 participants in six studies had understanding about placebo (95% CI 19.0–77.5%), while only 30% of 753 participants in five studies understood the concept of therapeutic misconception (95% CI 4.6–66.7%). Measurement tools for informed consent comprehension were developed with little or no validation. Assessment of comprehension was carried out at variable times after disclosure of study information. No uniform definition of informed consent comprehension exists to form the basis for development of an appropriate tool to measure comprehension in African participants.ConclusionsComprehension of key concepts of informed consent is poor among study participants across Africa. There is a vital need to develop a uniform definition for informed consent comprehension in low literacy research settings in Africa. This will be an essential step towards developing appropriate tools that can adequately measure informed consent comprehension. This may consequently suggest adequate measures to improve the informed consent procedure.ObjectifLes normes éthiques élaborées selon les valeurs occidentales ne sont peut-être pas appropriées au contexte africain où les concepts de recherche ne sont pas familiers. Cette revue décrit comment la compréhension du consentement éclairé est définie et mesurée dans les cadres de recherche africains.MéthodesDes recherches ont été effectuées sur Medline, Embase, Global Health, EthxWeb, base de données de la Bioéthique Littérature, Index Medicus African et Google Scholar pour des publications pertinentes sur la compréhension du consentement éclairé dans les études cliniques menées en Afrique sub-saharienne. 29 études répondaient aux critères d'inclusion; une méta-analyse a été possible pour 21 études. La compréhension des participants sur les domaines du consentement éclairé dans toutes les études admissibles a été comparée directement.RésultatsLa compréhension des concepts clés du consentement éclairé varie considérablement selon les pays et dépend de la nature et de la complexité de l’étude. La méta-analyse a montré que 47% des participants ont compris la randomisation (IC95%: 13,9 - 80,9%), 48% ont compris le placebo (IC95%: 19,0 - 77,5%), 30% ont compris le concept de méprise thérapeutique (IC95%: 4,6 - 66,7%). Les outils de mesure de la compréhension du consentement éclairé étaient développés avec peu ou pas de validation.ConclusionsLa compréhension des concepts clés du consentement éclairé est faible en Afrique. Il y a une nécessité vitale d’élaborer une définition uniforme pour la compréhension du consentement éclairé dans les cadres de recherche avec un faible niveau d'alphabétisation en Afrique.ObjetivoLos estándares éticos desarrollados basándose en valores occidentales podrían no ser apropiados para emplazamientos Africanos en donde los conceptos de investigación no son familiares. En esta revisión se describe como la comprensión del consentimiento informado se define y mide en un centro de investigación Africano.MétodosSe buscaron publicaciones relevantes sobre la comprensión del consentimiento informado en estudios clínicos en África subsahariana en Medline, Embase, Global Health, EthxWeb, Bioethics Literature Database, African Index Medicus y Google Scholar. 29 estudios satisfacían los criterios de inclusión y el metaanálisis era posible para 21. La comprensión del consentimiento informado por parte de los participantes se comparó directamente en todos los estudios elegibles.ResultadosLa comprensión de conceptos claves del consentimiento informado varió de forma considerable entre países, y dependía de la naturaleza y de la complejidad del estudio. El meta-análisis mostró que un 47% entendía la aleatorización (IC 95% 13.9-80.9%); un 48% entendía el placebo (IC 95% 19.0-77.5%); y un 30% entendió el concepto terapéutico errado (IC 95% 4.6-66.7%). Las herramientas para medir la comprensión del consentimiento informado se desarrollaron con poca o ninguna validación.ConclusionesEn África, la comprensión de conceptos claves del consentimiento informado es pobre. Existe una necesidad vital de desarrollar una definición uniforme para la comprensión del consentimiento informado en lugares con bajos niveles de alfabetización en África

Involving community health workers in disease-specific interventions: perspectives from The Gambia on the impact of this approach

Background The Community Health Worker (CHW) programme is recognised as key for providing healthcare to communities, particularly in remote locations. CHWs are usually volunteers, nominated by their communities and trained to provide basic care and prevention for common illnesses. However, differences in disease-specific programmes aimed at meeting national agenda and perceived health needs of the community raises questions about the best approach to maximise the potential of this workforce. Methods This was an explorative qualitative study, ancillary to a larger trial on a malaria control intervention. In July 2017, 40 semi-structured interviews were conducted with 17 village health workers (VHWs), four community health nurses who supervise VHWs, and 19 key informants from the community. Analysis was concurrent to data collection and carried out using a deductive process for thematic analysis, with the aid of NVivo 11 Qualitative Analysis Software. Results There were three key aspects of the VHW role identified in this setting; (1) to give health advice; (2) to treat and refer patients; and (3) to support environmental cleaning. The VHWs’ involvement in the clinical trial impacted their role in several ways. Overall, this was perceived very positively by the community and the VHWs since it improved access to medication and training on how to treat malaria. However, involvement was also perceived to increase VHWs’ workload, and placed more emphasis on malaria over other common illnesses, creating a shift in the balance of their role between disease prevention and treatment. Conclusions VHWs are essential for the successful delivery of disease-specific activities at the community level. However, involving them in these activities has important implications for their everyday role. If carefully managed, it has the potential to improve their capacity to screen and treat specific diseases such as malaria

Implementing integrated care clinics for HIV-infection, diabetes and hypertension in Uganda (INTE-AFRICA): process evaluation of a cluster randomised controlled trial

BACKGROUND: Sub-Saharan Africa is experiencing a dual burden of chronic human immunodeficiency virus and non-communicable diseases. A pragmatic parallel arm cluster randomised trial (INTE-AFRICA) scaled up ‘one-stop’ integrated care clinics for HIV-infection, diabetes and hypertension at selected facilities in Uganda. These clinics operated integrated health education and concurrent management of HIV, hypertension and diabetes. A process evaluation (PE) aimed to explore the experiences, attitudes and practices of a wide variety of stakeholders during implementation and to develop an understanding of the impact of broader structural and contextual factors on the process of service integration. METHODS: The PE was conducted in one integrated care clinic, and consisted of 48 in-depth interviews with stakeholders (patients, healthcare providers, policy-makers, international organisation, and clinical researchers); three focus group discussions with community leaders and members (n = 15); and 8 h of clinic-based observation. An inductive analytical approach collected and analysed the data using the Empirical Phenomenological Psychological five-step method. Bronfenbrenner’s ecological framework was subsequently used to conceptualise integrated care across multiple contextual levels (macro, meso, micro). RESULTS: Four main themes emerged; Implementing the integrated care model within healthcare facilities enhances detection of NCDs and comprehensive co-morbid care; Challenges of NCD drug supply chains; HIV stigma reduction over time, and Health education talks as a mechanism for change. Positive aspects of integrated care centred on the avoidance of duplication of care processes; increased capacity for screening, diagnosis and treatment of previously undiagnosed comorbid conditions; and broadening of skills of health workers to manage multiple conditions. Patients were motivated to continue receiving integrated care, despite frequent NCD drug stock-outs; and development of peer initiatives to purchase NCD drugs. Initial concerns about potential disruption of HIV care were overcome, leading to staff motivation to continue delivering integrated care. CONCLUSIONS: Implementing integrated care has the potential to sustainably reduce duplication of services, improve retention in care and treatment adherence for co/multi-morbid patients, encourage knowledge-sharing between patients and providers, and reduce HIV stigma. TRIAL REGISTRATION NUMBER: ISRCTN43896688

Strengthening integration of chronic care in Africa: protocol for the qualitative process evaluation of integrated HIV, diabetes and hypertension care in a cluster randomised controlled trial in Tanzania and Uganda.

INTRODUCTION: In sub-Saharan Africa, the burden of non-communicable diseases (NCDs), particularly diabetes mellitus (DM) and hypertension, has increased rapidly in recent years, although HIV infection remains a leading cause of death among young-middle-aged adults. Health service coverage for NCDs remains very low in contrast to HIV, despite the increasing prevalence of comorbidity of NCDs with HIV. There is an urgent need to expand healthcare capacity to provide integrated services to address these chronic conditions. METHODS AND ANALYSIS: This protocol describes procedures for a qualitative process evaluation of INTE-AFRICA, a cluster randomised trial comparing integrated health service provision for HIV infection, DM and hypertension, to the current stand-alone vertical care. Interviews, focus group discussions and observations of consultations and other care processes in two clinics (in Tanzania, Uganda) will be used to explore the experiences of stakeholders. These stakeholders will include health service users, policy-makers, healthcare providers, community leaders and members, researchers, non-governmental and international organisations. The exploration will be carried out during the implementation of the project, alongside an understanding of the impact of broader structural and contextual factors. ETHICS AND DISSEMINATION: Ethical approval was granted by the Liverpool School of Tropical Medicine (UK), the National Institute of Medical Research (Tanzania) and TASO Research Ethics Committee (Uganda) in 2020. The evaluation will provide the opportunity to document the implementation of integration over several timepoints (6, 12 and 18 months) and refine integrated service provision prior to scale up. This synergistic approach to evaluate, understand and respond will support service integration and inform monitoring, policy and practice development efforts to involve and educate communities in Tanzania and Uganda. It will create a model of care and a platform of good practices and lessons learnt for other countries implementing integrated and decentralised community health services. TRIAL REGISTRATION NUMBER: ISRCTN43896688; Pre-results

Booster Dose of Bacille Calmette-Guérin Vaccine for Tuberculosis in Low and Middle-Income Countries: A Systematic Review

Background: The Bacille Calmette-Guérin (BCG) vaccine, given as a single dose, offers variable protection against Tuberculosis (TB). It is plausible that repeat doses could improve the effectiveness of the BCG vaccine in settings where the population remain at risk of the disease. Objective: To assess the effectiveness of BCG revaccination as a booster dose in preventing TB in Low- and Middle- Income Countries (LMICs). Methods: We searched the electronic databases without language or publication restrictions and followed the procedures for preparing systematic reviews, including assessing the risk of bias as outlined in the Cochrane handbook. We included randomised controlled trials (RCTs) conducted in LMICs involving children and adults receiving one or more BCG vaccine doses after the primary BCG vaccination. The incidence of severe forms of TB, active TB and adverse events were the primary outcomes. Results: Five RCTs were included in this systematic review. Revaccination with BCG probably makes little or no difference to the risk of active TB measured after five years (Relative risk (RR) 1.16, 95% CI 0.88 to 1.51; 348,083 participants; one study, moderate certainty evidence) or nine years post-revaccination (RR 0.96, 95% CI 0.82 to 1.12; 348,083 participants; one study, moderate certainty evidence). In populations with HIV co-infection, revaccination probably increases the risk of pulmonary tuberculosis compared to placebo (RR 1.74, 95% CI 1.00 to 3.01; 46,764 participants; one study, moderate certainty evidence). Conclusion: The available evidence suggests that BCG revaccination probably makes little or no difference in preventing tuberculosis disease in LMICs

Community perspectives on treating asymptomatic infections for malaria elimination in The Gambia

BACKGROUND: Innovative and cost-effective strategies that clear asymptomatic malaria infections are required to reach malaria elimination goals, but remain a challenge. This mixed methods study explored people's attitudes towards the reactive treatment of compound contacts of malaria cases with a 3-day course of dihydroartemisinin-piperaquine (DHAP), the socio-cultural representations of asymptomatic infections, and more specifically their treatment. METHODS: Prior to the start of the intervention, a sequential mixed method study was carried out. Qualitative data collection involved in-depth interviews and participant observations (including informal conversations) with key informants from the trial communities and the trial staff. Quantitative data were derived from a pre-trial cross-sectional survey on health literacy and health-seeking behaviour among randomly selected members of the study communities. RESULTS: In the pre-trial cross-sectional survey, 73% of respondents reported that malaria could be hidden in the body without symptoms. Whilst this may be interpreted as people's comprehension of asymptomatic malaria, qualitative data indicated that informants had different interpretations of asymptomatic disease than the biomedical model. It was described as: (i) a minor illness that does not prevent people carrying out daily activities; (ii) an illness that oscillates between symptomatic and asymptomatic phases; and, (iii) a condition where disease agents are present in the body but remain hidden, without signs and symptoms, until something triggers their manifestation. Furthermore, this form of hidden malaria was reported to be most present in those living in the same compound with a malaria case (71%). CONCLUSION: Treating asymptomatic malaria with pharmaceuticals was considered acceptable. However, people felt uncertain to take treatment without screening for malaria first, largely due to the lack of symptoms. Knowledge of asymptomatic malaria was not a strong re-inforcement for treatment adherence. In this study, the pre-intervention active engagement of communities existed of having people co-design accurate information messages about their personal risk of malaria, which increased their trust in expert knowledge and thus proved essential for the successful implementation of the community-based intervention

Distinct roles for FOXP3(+) and FOXP3(-) CD4(+) T cells in regulating cellular immunity to uncomplicated and severe plasmodium falciparum Malaria

Failure to establish an appropriate balance between pro- and anti-inflammatory immune responses is believed to contribute to pathogenesis of severe malaria. To determine whether this balance is maintained by classical regulatory T cells (CD4+ FOXP3+ CD127−/low; Tregs) we compared cellular responses between Gambian children (n = 124) with severe Plasmodium falciparum malaria or uncomplicated malaria infections. Although no significant differences in Treg numbers or function were observed between the groups, Treg activity during acute disease was inversely correlated with malaria-specific memory responses detectable 28 days later. Thus, while Tregs may not regulate acute malarial inflammation, they may limit memory responses to levels that subsequently facilitate parasite clearance without causing immunopathology. Importantly, we identified a population of FOXP3−, CD45RO+ CD4+ T cells which coproduce IL-10 and IFN-γ. These cells are more prevalent in children with uncomplicated malaria than in those with severe disease, suggesting that they may be the regulators of acute malarial inflammation

Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis.

Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesi