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

Knowing who to trust: Exploring the role of 'ethical metadata' in mediating risk of harm in collaborative genomics research in Africa

Background: The practice of making datasets publicly available for use by the wider scientific community has become firmly integrated in genomic science. One significant gap in literature around data sharing concerns how it impacts on scientists’ ability to preserve values and ethical standards that form an essential component of scientific collaborations. We conducted a qualitative sociological study examining the potential for harm to ethnic groups, and implications of such ethical concerns for data sharing. We focused our empirical work on the MalariaGEN Consortium, one of the first international collaborative genomics research projects in Africa. Methods: We conducted a study in three MalariaGEN project sites in Kenya, the Gambia, and the United Kingdom. The study entailed analysis of project documents and 49 semi-structured interviews with fieldworkers, researchers and ethics committee members. Results: Concerns about how best to address the potential for harm to ethnic groups in MalariaGEN crystallised in discussions about the development of a data sharing policy. Particularly concerning for researchers was how best to manage the sharing of genomic data outside of the original collaboration. Within MalariaGEN, genomic data is accompanied by information about the locations of sample collection, the limitations of consent and ethics approval, and the values and relations that accompanied sample collection. For interviewees, this information and context were of important ethical value in safeguarding against harmful uses of data, but is not customarily shared with secondary data users. This challenged the ability of primary researchers to protect against harmful uses of ‘their’ data. Conclusion: We identified three protective mechanisms – trust, the existence of a shared morality, and detailed contextual understanding – which together might play an important role in preventing the use of genomic data in ways that could harm the ethnic groups included in the study. We suggest that the current practice of sharing of datasets as isolated objects rather than as embedded within a particular scientific culture, without regard for the normative context within which samples were collected, may cause ethical tensions to emerge that could have been prevented or addressed had the ‘ethical metadata’ that accompanies genomic data also been shared. </p

Establishing a National Shellfish Sanitation Program in The Gambia, West Africa

A successful national program to assure sanitary quality of molluscan shellfish requires a multi-disciplinary and multi-agency governmental training, data collection, policy development and management effort in collaboration with members of the shellfish industry. The Tanbi Wetlands and other estuaries of Gambia support shellfisheries for oysters, Crassostrea tulipa, and the senile ark, Senelia senilis, conducted by the TRY Oyster Women’s Association. With low shellfish prices and a small local market, a Gambian National Shellfish Sanitation Program (GNSSP) was begun as a means to boost consumer confidence and allow market access to Gambia’s robust seasonal international tourism trade. Gambian officials began training with a study tour to Rhode Island to work with counterpart officials engaged in administering the US-NSSP. Since August 2010, water was sampled bimonthly for total (TC) and fecal coliforms (FC) at stations near shellfish harvesting areas. Sanitary shoreline surveys began on 18 June 2011 to document sources of contamination and to establish priorities for remediation. Conclusions were 1) sanitary shoreline surveys identified numerous point contamination sources, 2) FC is a superior indicator of fecal contamination than TC, 3) FC values from most shellfish growing areas met or exceeded a FC standard of 14 MPN/100 ml most of the year, indicating clean growing waters, 4) highest average FC values corresponded to local rainfall maxima from July to October during the traditional off-season for shellfishing, 5) sanitary remediation (e.g. introduction of sanitary latrines at Old Jeshwang) resulted in localized water quality improvement and 6) there is enough data precision and repeatability to establish and map water quality classification zones. In areas without sanitation or near a dumpsite, FC values indicate a prohibited zone, but areas away from settlements could be certified year-around harvest sites. Postharvest shellfish sanitation and cold chain management from harvest to market remain as the key challenge of the GNSSP

Maternal colonization with Staphylococcus aureus and Group B streptococcus is associated with colonization in newborns.

OBJECTIVES: Although Staphylococcus aureus and Group B streptococcus (GBS) are major causes of neonatal sepsis in sub-Saharan Africa, it is unclear how these bacteria are transmitted to the neonate. METHODS: In a cohort of 377 Gambian women and their newborns, nasopharyngeal swabs were collected at delivery (day 0), and 3, 6, 14 and 28 days later. Breast milk samples and vaginal swabs were collected from the mother. Staphylococcus aureus and GBS were isolated using conventional microbiological methods. RESULTS: Most women were carriers of S. aureus (264 out of 361 with all samples collected, 73.1%) at some point during follow up and many were carriers of GBS (114 out of 361, 31.6%). Carriage of S. aureus was common in all three maternal sites and GBS was common in the vaginal tract and breast milk. Among newborns, carriage of S. aureus peaked at day 6 (238 out of 377, 63.1%) and GBS at day 3 (39 out of 377, 10.3%). Neonatal carriage of S. aureus at day 6 was associated with maternal carriage in the breast milk adjusted OR 2.54; 95% CI 1.45-4.45, vaginal tract (aOR 2.55; 95% CI 1.32-4.92) and nasopharynx (aOR 2.49; 95% CI 1.56-3.97). Neonatal carriage of GBS at day 6 was associated with maternal carriage in the breast milk (aOR 3.75; 95% CI 1.32-10.65) and vaginal tract (aOR 3.42; 95% CI 1.27-9.22). CONCLUSIONS: Maternal colonization with S. aureus or GBS is a risk factor for bacterial colonization in newborns

Risk factors for presentation to hospital with severe anaemia in Tanzanian children: a case-control study.

In malaria endemic areas anaemia is a usually silent condition that nevertheless places a considerable burden on health services. Cases of severe anaemia often require hospitalization and blood transfusions. The objective of this study was to assess risk factors for admission with anaemia to facilitate the design of anaemia control programmes. We conducted a prospective case-control study of children aged 2-59 months admitted to a district hospital in southern Tanzania. There were 216 cases of severe anaemia [packed cell volume (PCV) < 25%] and 234 age-matched controls (PCV > or = 25%). Most cases [55.6% (n = 120)] were < 1 year of age. Anaemia was significantly associated with the educational level of parents, type of accommodation, health-seeking behaviour, the child's nutritional status and recent and current medical history. Of these, the single most important factor was Plasmodium falciparum parasitaemia [OR 4.3, 95% confidence interval (CI) 2.9-6.5, P < 0.001]. Multivariate analysis showed that increased recent health expenditure [OR 2.2 (95% CI 1.3-3.9), P = 0.005], malnutrition [OR 2.4 (95%CI 1.3-4.3), P < 0.001], living > 10 km from the hospital [OR 3.0 (95% CI 1.9-4.9), P < 0.001], a history of previous blood transfusion [OR 3.8 (95% CI 1.7-9.1), P < 0.001] and P. falciparum parasitaemia [OR 9.5 (95% CI 4.3-21.3), P < 0.001] were independently related to risk of being admitted with anaemia. These findings are considered in terms of the pathophysiological pathway leading to anaemia. The concentration of anaemia in infants and problems of access to health services and adequate case management underline the need for targeted preventive strategies for anaemia control

Investigation of sequential outbreaks of Burkholderia cepacia and multidrug-resistant extended spectrum β-lactamase producing Klebsiella species in a West African tertiary hospital neonatal unit: a retrospective genomic analysis

Background Sick newborns admitted to neonatal units in low-resource settings are at an increased risk of developing hospital-acquired infections due to poor clinical care practices. Clusters of infection, due to the same species, with a consistent antibiotic resistance profile, and in the same ward over a short period of time might be indicative of an outbreak. We used whole-genome sequencing (WGS) to define the transmission pathways and characterise two distinct outbreaks of neonatal bacteraemia in a west African neonatal unit. Methods We studied two outbreaks of Burkholderia cepacia and multidrug-resistant extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae in a neonatal unit that provides non-intensive care on the neonatal ward in the Edward Francis Small Teaching Hospital, Banjul, The Gambia. We used WGS to validate and expand findings from the outbreak investigation. We retrospectively sequenced all clinical isolates associated with each outbreak, including isolates obtained from swabs of ward surfaces, environmental fluid cultures, intravenous fluids, and antibiotics administered to newborns. We also sequenced historical B cepacia isolates associated with neonatal sepsis in the same ward. Results Between March 1 and Dec 31, 2016, 321 blood cultures were done, of which 178 (55%) were positive with a clinically significant isolate. 49 episodes of neonatal B cepacia bacteraemia and 45 episodes of bacteraemia due to ESBL-producing K pneumoniae were reported. WGS revealed the suspected K pneumoniae outbreak to be contemporaneous outbreaks of K pneumoniae (ST39) and previously unreported Klebsiella quasipneumoniae subspecies similipneumoniae (ST1535). Genomic analysis showed near-identical strain clusters for each of the three outbreak pathogens, consistent with transmission within the neonatal ward from extrinsically contaminated in-use intravenous fluids and antibiotics. Time-dated phylogeny, including retrospective analysis of archived bacterial strains, suggest B cepacia has been endemic in the neonatal ward over several years, with the Klebsiella species a more recent introduction. Interpretation Our study highlights the emerging threat of previously unreported strains of multidrug-resistant Klebsiella species in this neonatal unit. Genome-based surveillance studies can improve identification of circulating pathogen strains, characterisation of antimicrobial resistance, and help understand probable infection acquisition routes during outbreaks in newborn units in low-resource settings. Our data provide evidence for the need to regularly monitor endemic transmission of bacteria within the hospital setting, identify the introduction of resistant strains from the community, and improve clinical practices to reduce or prevent the spread of infection and resistance

T-cell epitope polymorphisms of the Plasmodium falciparum circumsporozoite protein among field isolates from Sierra Leone: age-dependent haplotype distribution?

<p>Abstract</p> <p>Background</p> <p>In the context of the development of a successful malaria vaccine, understanding the polymorphisms exhibited by malaria antigens in natural parasite populations is crucial for proper vaccine design. Recent observations have indicated that sequence polymorphisms in the C-terminal T-cell epitopes of the <it>Plasmodium falciparum </it>circumsporozoite protein (Pf<it>csp</it>) are rather low and apparently stable in low endemic areas. This study sought to assess the pattern in a malaria endemic setting in Africa, using samples from Freetown, Sierra Leone.</p> <p>Methods</p> <p>Filter-paper blood samples were collected from subjects at a teaching hospital in Freetown during September–October 2006 and in April–May 2007. The C-terminal portion of the Pf<it>csp </it>gene spanning the Th2R and Th3R epitopes was amplified and directly sequenced; sequences were analysed with subject parameters and polymorphism patterns in Freetown were compared to that in other malaria endemic areas.</p> <p>Results and Discussion</p> <p>Overall, the genetic diversity in Freetown was high. From a total of 99 sequences, 42 haplotypes were identified with at least three accounting for 44.4% (44/99): the 3D7-type (19.2%), a novel type, P-01 (17.2%), and E12 (8.1%). Interestingly, all were unique to the African sub-region and there appeared to be predilection for certain haplotypes to distribute in certain age-groups: the 3D7 type was detected mainly in hospitalized children under 15 years of age, while the P-01 type was common in adult antenatal females (Pearson Chi-square = 48.750, degrees of freedom = 34, <it>P </it>= 0.049). In contrast, the single-haplotype predominance (proportion > 50%) pattern previously identified in Asia was not detected in Freetown.</p> <p>Conclusion</p> <p>Haplotype distribution of the T-cell epitopes of Pf<it>csp </it>in Freetown appeared to vary with age in the study population, and the polymorphism patterns were similar to that observed in neighbouring Gambia, but differed significantly at the sequence level from that observed in Asia. The findings further emphasize the role of local factors in generating polymorphisms in the T-cell epitopes of the <it>P. falciparum </it>circumsporozoite protein.</p

Long Term Outcome of Severe Anaemia in Malawian Children

Severe anaemia is a common, frequently fatal, condition in African children admitted to hospital, but its long term outcome is unknown. Early reports that survivors may be at risk of additional late morbidity and mortality may have significant implications for child survival in Africa. We assessed the short and long term outcome of severe anaemia in Malawian children and identified potential risk factors for death and further severe anaemia. For 18 months, we followed up children (6-60 months old) presenting to hospital with severe anaemia (haemoglobin <or=5 g/dl) and their hospital and community controls with the aim to compare all cause mortality and severe anaemia recurrence rates between the groups, and to identify risk factors for these adverse outcomes. A total of 377 cases, 377 hospital controls and 380 community controls were recruited. Among cases, the in-hospital mortality was 6.4% and post-discharge all cause mortality was 12.6%, which was significantly greater than in hospital controls (2.9%) or community controls (1.4%) (Log rank test, p <0.001). The incidence of recurrence of severe anaemia among the cases was 0.102 per child-year (95% Confidence Interval 0.075-0.138), and was significantly higher than the 0.007 per child-year (95% CI 0.003-0.015) in the combined controls (p <0.0001). HIV was the most important risk factor both for post-discharge mortality (Hazard Ratio 10.5, 95% CI 4.0-27.2) and for recurrence of severe anaemia (HR 5.6, 95% CI 1.6-20.1). Severe anaemia carries a high 'hidden' morbidity and mortality occurring in the months after initial diagnosis and treatment. Because severe anaemia is very common, this is likely to contribute importantly to overall under-five mortality. If not adequately addressed, severe anaemia may be an obstacle to achievement of the Millennium development goal No.4 on child survival. Strategies to diagnose and properly treat HIV infected children early most likely will reduce the high post-discharge mortality in severe anaemi