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

Diagnostic performance of a novel loop-mediated isothermal amplification (LAMP) assay targeting the apicoplast genome for malaria diagnosis in a field setting in sub-Saharan Africa.

BACKGROUND: New diagnostic tools to detect reliably and rapidly asymptomatic and low-density malaria infections are needed as their treatment could interrupt transmission. Isothermal amplification techniques are being explored for field diagnosis of malaria. In this study, a novel molecular tool (loop-mediated isothermal amplification-LAMP) targeting the apicoplast genome of Plasmodium falciparum was evaluated for the detection of asymptomatic malaria-infected individuals in a rural setting in The Gambia. METHODS: A blood was collected from 341 subjects (median age 9 years, range 1-68 years) screened for malaria. On site, a rapid diagnostic test (RDT, SD Bioline Malaria Antigen P.f) was performed, thick blood films (TBF) slides for microscopy were prepared and dry blood spots (DBS) were collected on Whatman(®) 903 Specimen collection paper. The TBF and DBS were transported to the field laboratory where microscopy and LAMP testing were performed. The latter was done on DNA extracted from the DBS using a crude (methanol/heating) extraction method. A laboratory-based PCR amplification was done on all the samples using DNA extracted with the Qiagen kit and its results were taken as reference for all the other tests. RESULTS: Plasmodium falciparum malaria prevalence was 37 % (127/341) as detected by LAMP, 30 % (104/341) by microscopy and 37 % (126/341) by RDT. Compared to the reference PCR method, sensitivity was 92 % for LAMP, 78 % for microscopy, and 76 % for RDT; specificity was 97 % for LAMP, 99 % for microscopy, and 88 % for RDT. Area under the receiver operating characteristic (ROC) curve in comparison with the reference standard was 0.94 for LAMP, 0.88 for microscopy and 0.81 for RDT. Turn-around time for the entire LAMP assay was approximately 3 h and 30 min for an average of 27 ± 9.5 samples collected per day, compared to a minimum of 10 samples an hour per operator by RDT and over 8 h by microscopy. CONCLUSION: The LAMP assay could produce reliable results the same day of the screening. It could detect a higher proportion of low density malaria infections than the other methods tested and may be used for large campaigns of systematic screening and treatment

Supporting registration of child-focused clinical trials in Africa: The Child Strategy Project

Editorial abstract not applicabl

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

School-based countrywide seroprevalence survey reveals spatial heterogeneity in malaria transmission in the Gambia.

BACKGROUND: As the geographical distribution of malaria transmission becomes progressively clustered, identifying residual pockets of transmission is important for research and for targeting interventions. Malarial antibody-based surveillance is increasingly recognised as a valuable complement to classic methods for the detection of infection foci especially at low transmission levels. The study presents serological evidence for transmission heterogeneity among school children in The Gambia measured during the dry, non-transmission season. METHODS: Healthy primary school children were randomly selected from 30 schools across the country and screened for malaria infection (microscopy) and antimalarial antibodies (MSP119). Antibody distribution was modelled using 2-component finite mixture model with cut-off for positivity from pooled sera set at 2-standard deviation from the mean of the first component. Factors associated with a positive serological status were identified in a univariate model and then combined in a multilevel mixed-effects logistic regression model, simultaneously adjusting for variations between individuals and school. RESULTS: A total of 4140 children, 1897 (46%) boys, were enrolled with mean age of 10.2 years (SD 2.6, range 4-20 years). Microscopy results available for 3640 (87.9%) children showed that 1.9% (69) were positive for Plasmodium falciparum infections, most of them (97.1%, 67/69) asymptomatic. The overall seroprevalence was 12.7% (527/4140) with values for the schools ranging from 0.6% to 43.8%. Age (OR 1.12, 95% CI 1.07-1.16,) and parasite carriage (OR 3.36, 95% CI 1.95-5.79) were strongly associated with seropositivity. CONCLUSION: Serological responses to malaria parasites could identify individuals who were or had been infected, and clusters of residual transmission. Field-adapted antibody tests able to guide mass screening and treatment campaigns would be extremely useful

Risk factors for delay in age-appropriate vaccinations among Gambian children.

BACKGROUND: Vaccination has been shown to reduce mortality and morbidity due to vaccine-preventable diseases. However, these diseases are still responsible for majority of childhood deaths worldwide especially in the developing countries. This may be due to low vaccine coverage or delay in receipt of age-appropriate vaccines. We studied the timeliness of routine vaccinations among children aged 12-59 months attending infant welfare clinics in semi-urban areas of The Gambia, a country with high vaccine coverage. METHODS: A cross-sectional survey was conducted in four health centres in the Western Region of the Gambia. Vaccination dates were obtained from health cards and timeliness assessed based on the recommended age ranges for BCG (birth-8 weeks), Diphtheria-Pertussis-Tetanus (6 weeks-4 months; 10 weeks-5 months; 14 weeks-6 months) and measles vaccines (38 weeks-12 months). Risk factors for delay in age-appropriate vaccinations were determined using logistic regression. Analysis was limited to BCG, third dose of Diphtheria-Pertussis -Tetanus (DPT3) and measles vaccines. RESULTS: Vaccination records of 1154 children were studied. Overall, 63.3% (95 % CI 60.6-66.1%) of the children had a delay in the recommended time to receiving at least one of the studied vaccines. The proportion of children with delayed vaccinations increased from BCG [5.8% (95 % CI 4.5-7.0%)] to DPT3 [60.4% (95 % CI 57.9%-63.0%)] but was comparatively low for the measles vaccine [10.8% (95 % CI 9.1%-12.5%)]. Mothers of affected children gave reasons for the delay, and their profile correlated with type of occupation, place of birth and mode of transportation to the health facilities. CONCLUSION: Despite high vaccination coverage reported in The Gambia, a significant proportion of the children's vaccines were delayed for reasons related to health services as well as profile of mothers. These findings are likely to obtain in several countries and should be addressed by programme managers in order to improve and optimize the impact of the immunization coverage rates

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

Tolerance of Gambian Plasmodium falciparum to Dihydroartemisinin and Lumefantrine Detected by Ex Vivo Parasite Survival Rate Assay.

Monitoring of Plasmodium falciparum sensitivity to antimalarial drugs in Africa is vital for malaria elimination. However, the commonly used ex vivo/in vitro 50% inhibitory concentration (IC50) test gives inconsistent results for several antimalarials, while the alternative ring-stage survival assay (RSA) for artemisinin derivatives has not been widely adopted. Here, we applied an alternative two-color flow cytometry-based parasite survival rate assay (PSRA) to detect ex vivo antimalarial tolerance in P. falciparum isolates from The Gambia. The PSRA infers parasite viability by quantifying reinvasion of uninfected cells following 3 consecutive days of drug exposure (10-fold the IC50 of drug for field isolates). The drug survival rate is obtained for each isolate from the slope of the growth/death curve. We obtained parasite survival rates of 41 isolates for dihydroartemisinin (DHA) and lumefantrine (LUM) out of 51 infections tested by ring-stage survival assay (RSA) against DHA. We also determined the genotypes for known drug resistance genetic loci in the P. falciparum genes Pfdhfr, Pfdhps, Pfmdr, Pfcrt, and Pfk13 The PSRA results determined for 41 Gambian isolates showed faster killing and lower variance after treatment with DHA than after treatment with LUM, despite a strong correlation between the two drugs. Four and three isolates were tolerant to DHA and LUM, respectively, with continuous growth during drug exposure. Isolates with the PfMDR1-Y184F mutant variant showed increased LUM survival, though the results were not statistically significant. Sulfadoxine/pyrimethamine (SP) resistance markers were fixed, while all other antimalarial variants were prevalent in more than 50% of the population. The PSRA detected ex vivo antimalarial tolerance in Gambian P. falciparum This calls for its wider application and for increased vigilance against resistance to artemisinin combination therapies (ACTs) in this population

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