Browsing by Author "Allen, Elizabeth"
Now showing 1 - 14 of 14
Results Per Page
Sort Options
- ItemOpen AccessA mixed method study of the factors influencing the validity of medical and medication histories obtained from potential healthy adult clinical trial participants(2019) Ltayef, Hanan; Allen, Elizabeth; Annemie, StewartBackground: The medical histories of patients are data picked up by a doctor by making inquiries of the patient and of other individuals who know the individual and can give a reasonable response. In clinical trials, obtaining an accurate medical and treatment history is also an important factor in establishing whether or not a person is an eligible participant, and thereafter supports the assessment of any change in health during the trial, for example, the assessment of adverse events (AEs). Study objectives: To understand discrepancies between the medical histories from online self-reports, electronic medical records, and in-depth interviews of those applying to be part of an adult volunteer database for clinical trials; explore ways of engaging with potential volunteers, such that self-reported medical histories are as comprehensive as possible; explore the feasibility of accessing electronic records for those responding to advertisements. Methodology: This study was designed as mixed methods, with sequential explanatory design collecting quantitative and qualitative data and nested in an existing adult volunteer database. people from the Cape Town community were invited to join the database, in response to an advertisement and through a link to the database website; particularly those who were potentially eligible for a typical healthy volunteer trial, and who reported different information to that obtained from the electronic records. Results: 38 people responded to the online questionnaire, the majority being female. According to the online self-report questionnaire, ten people (10/38; 26.3%) had chronic medical conditions; mostly HIV (7/10; 70%). We accessed the Western Cape electronic medical records for only 8/38 (21%). Comparing the online questionnaire with the medical records, it was found that 25% of respondents had no difference in information. 10/38 people (26.3%) agreed to participate and were available for an in-depth interview. The main findings were: 1) a very low response rate to the advertisement, 2) people in this community are willing to consider taking part in clinical research, but have different understandings of what that means, 3) there were discrepancies between online self-reported health and medication data and what was found in a pilot database of electronic public health records and during a face-to-face interview, 4) the reason for these differences, as perceived by participants, included forgetting some information, feeling it was not relevant or important to report because of the attributes of the online questionnaire and 5) these participants had no concerns about us accessing their electronic medical records. Conclusion: Our study provides some evidence for optimal places to advertise for an adult volunteer database, and the appropriate wording and format of both the advertisements and the online questionnaire. More efforts are needed to educate the general public on understand the meaning of clinical trials. Electronic medical records may be accessed to help understand potential participants’ eligibility for trials, but the feasibility of accessing such data timeously may need further negotiation.
- ItemOpen AccessComparison of three levels of ascertainment of antenatal medication use at Gugulethu Midwife Obstetric Unit(2022) van Der Hoven, Jani; Kalk, Emma; Allen, ElizabethBackground The use of medicines and/or remedies among pregnant women is common. Pregnant women are generally excluded from clinical trials due to ethical reasons. There are therefore minimal data available about the safety of most drugs during pregnancy by the time they come to the market, and post-marketing evaluation of medicine use during pregnancy is required. In South-Africa, with mass treatment campaigns for Tuberculosis (TB) and Human Immunodeficiency Virus (HIV), the introduction of new therapeutic agents and frequent self-medication, it is important for reliable methods to determine medicine exposures, including the frequency and timing of use, to support such evaluations. Databases about medication exposures are promising resources for pharmaco-epidemiological investigations, however the optimal method of ascertainment of medicine use during pregnancy is uncertain. Different data sources could also be better for different types of medication. To improve the quality of data, a combination of data sources may be ideal but time-consuming and expensive. By looking at and comparing three data sources: 1) self-report, 2) clinician records and 3) electronic dispensing systems, we aimed to identify the optimal method of ascertainment of antenatal medicine use for multiple medication types. Methods The aim of this investigation was to provide a more comprehensive reflection of the drug exposures during pregnancy and to make recommendations to strengthen routine clinical data capturing to improve maternity case reporting. The data of 988 pregnant women seeking antenatal care at Gugulethu Midwife Obstetric Unit (GMOU) in Cape Town between 2016 and 2018 were used. The three data sources consisted of self-reports gathered by an interviewer administered questionnaire at up to three antenatal visits to the GMOU; clinical records as recorded in the Pregnancy Exposure Registry (PER); and linked electronic dispensing data obtained from the Provincial Health Data Centre (PHDC) of the Western Cape Department of Health. Medication exposure data were coded using the Anatomical Therapeutic Chemical (ATC) Classification system, an internationally acknowledged system to classify medicine maintained by the WHO. ATC codes were assigned to active ingredients, depending on the therapeutic indication. The three data sources were then assessed in terms of missing or overlapping information and evaluated on the level of agreement between sources using Spearman's rank coefficient and Cohen's Kappa. Results According to the Spearman rank test, the PER and PHDC datasets as a whole showed the highest correlation both at 1st and 5th ATC level. The overlaps between the datasets were poor and the Kappa agreement between the sources was low for most therapeutic classes, except for HIV treatments. An “almost perfect” Kappa agreement existed between anti-diabetic medication (ATC A10) reported in the self-report and PHDC datasets. Traditional, herbal, complementary and home remedies were only reported in the self-report dataset. Conclusion We found an overall poor agreement between data sources, with one alone not able to effectively capture all data. The datasets should thus be used in conjunction to ensure accurate and reliable record of exposure. Self-report was the best data source for traditional, home, herbal and complementary medicine exposures while the PER provided a better and more complete reflection of influenza vaccines and vitamins. The best method of ascertaining antenatal medicine exposure therefore depends on the type of medicine being investigated, and choice of data source depends on the objectives of the investigation. This study suggests that PER, PHDC and self-report should ideally be used together since each is critical to ensure accurate, reliable and effective exposure data, although this will have resource and cost implications.
- ItemOpen AccessDevelopment of harmonised approaches for detecting and recording participant-reported anti-malarial drug safety data: The Delphi process(2017) Mandimika, Nyaradzo; Allen, Elizabeth; Barnes, Karen IEliciting adverse event (AE) and non-study medication reports from clinical research participants is integral for evaluating drug safety. However, using different methods to question participants yields inconsistent results, compromising the interpretation, comparison and pooling of data across studies. This is particularly important given the widespread use of antimalarials in vulnerable populations, and their increasing use in healthy but at-risk individuals as preventive treatment or to reduce malaria transmission. Experienced, qualified antimalarial drug clinical researchers were invited to participate in a Delphi process, to facilitate consensus on what panellists consider to be optimal (relevant, important and feasible) methods, tools, and approaches for detecting participant-reported AE and non-study medication data in uncomplicated malaria treatment studies. This Delphi built on a previous survey conducted among malaria clinical researchers about different elicitation methods they used. The findings thereof, and a summary of relevant literature, were presented to Delphi panellists in round one after which they were asked to suggest further questioning methods or approaches that they considered as important and feasible for asking participants (or their caregivers) about their health to collect adverse events, and use of non-study medications to collect previous or concomitant medication data. In round two, the panellists were presented with the collated suggestions from round one to rate each type of question in terms of its relevance, importance and feasibility. Here, panellists would rate methods or approaches as either optimal or not optimal for inclusion in a 'menu' of harmonized or standard types of core questions to be used in a variety of uncomplicated antimalarial treatment studies. In round three, panellists were presented with a summary of items which had achieved consensus in round two and, for items that had not achieved consensus they were asked whether or not they wished to change their response in view of the group's overall response. Of the 72 invited, 25; 16 and 10 panellists responded to the first, second and third rounds of the Delphi process respectively. Overall, 68% of all questioning items presented for rating achieved consensus. When asking general questions about health, panellists agreed to include a question/concept about any change in health, taking care to ensure that such questions/concepts do not imply causality. Eighty-nine percent (39/44) of structured items about specific signs and symptoms, were rated as optimal. For non-study medications, a general question and most structured questioning items were considered an optimal approach. The use of mobile phones, patient diaries, rating scales as well as openly engaging with participants to discuss concerns were also considered optimal complementary data-elicitation tools. This study succeeded in reaching consensus within a section of the antimalarial drug clinical research community about using a general question concept, and some structured questions for eliciting data about AEs and non-study medication reports. The findings suggest that one method of questioning may not be superior to another, or sufficient to fulfil its purpose on its own and that the use of a combination of methods may be optimal. As malaria clinical research is often conducted in children (and other vulnerable groups), this becomes an important consideration in the design of appropriate elicitation methods cognisant of any particular factors that may impede accurate reporting in these groups. The concepts and items found in this Delphi survey to be relevant, important and feasible should be further investigated for potential inclusion in a harmonised approach to collect participant-elicited antimalarial drug safety data. This, in turn, should improve understanding of antimalarial drug safety.
- ItemOpen AccessEffect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa(Public Library of Science, 2005) Barnes, Karen I; Durrheim, David N; Little, Francesca; Jackson, Amanda; Mehta, Ushma; Allen, Elizabeth; Dlamini, Sicelo S; Tsoka, Joyce; Bredenkamp, Barry; Mthembu, D JothamIn KwaZulu-Natal strengthening of vector control and a change in antimalarial treatment policy to use of artemether-lumefantrine has been associated with a decrease in malaria cases, admissions, and deaths.
- ItemOpen AccessEffect of artemether-lumefantrine policy and improved vector control on malaria burden in KwaZulu-Natal, South Africa(2005) Barnes, Karen I; Durrheim, David N; Little, Francesca; Jackson, Amanda; Mehta, Ushma; Allen, Elizabeth; Dlamini, Sicelo S; Tsoka, Joyce; Bredekamp, Barry; Mthembu, D Jotham; White, Nicholas J; Sharp, Brian LBetween 1995 and 2000, KwaZulu–Natal province, South Africa, experienced a marked increase in Plasmodium falciparum malaria, fuelled by pyrethroid and sulfadoxine-pyrimethamine resistance. In response, vector control was strengthened and artemether-lumefantrine (AL) was deployed in the first Ministry of Health artemisinin-based combination treatment policy in Africa. In South Africa, effective vector and parasite control had historically ensured low-intensity malaria transmission. Malaria is diagnosed definitively and treatment is provided free of charge in reasonably accessible public-sector health-care facilities.
- ItemOpen AccessEfficacy of sulfadoxine-pyrimethamine with and without artesunate for the treatment of uncomplicated malaria in Mozambique : a randomised controlled trial(2008) Allen, Elizabeth; Boulle, Andrew; Little, Francesca[Background and rationale] Malaria accounts for a large public health burden in Mozambique and a treatment policy with effective anti-malarials is a key component of their malaria control programme. Artemisinin-based combination therapies (ACTs) are now generally considered as the best treatment for uncomplicated falciparum malaria; the use of artesunate (AS) in combination with sulfadoxine-pyrimethamine (SP) is recommended by the World Health Organisation (WHO). Mozambique policy-makers recommended that an ACT be implemented and studied in 2003. Therefore this RCT was conducted to compare SP monotherapy with AS, plus SP in order to provide further evidence of available treatment options in the region. [Trial design and methods] A prospective multi-centre, open-label, parallel-group randomised clinical trial (RCT) was conducted at 4 public health facilities in Maputo Province, Mozambique during the malaria seasons of 2003 - 2004 and 2004 - 2005. Eligible patients were aged over 1 year with body weight over 10kg and uncomplicated Plasmodium falciparum malaria (parasitaemia less than 500 000 asexual parasites/ml blood with axillary temperature less than or equal to 37.5oC or a history of fever). Patients were excluded if they took other anti- malarials or folate within 7 days, had moderately severe/severe malaria, history of G6PD deficiency or allergy to study drugs, or serious underlying disease. Patients were randomly assigned to sulfadoxine-pyrimethamine (SP): a single oral 25/1.25mg per kg dose on Day 0, with a maximum of 3 tablets), or artesunate (AS) plus SP: SP as above, plus single oral doses of 4mg/kg AS on Days 0, 1 and 2 with a maximum daily dose of 4 tablets). The study aimed to compare the efficacy of SP monotherapy to SP in combination with AS as first line treatment of uncomplicated falciparum malaria. The primary objective was the comparison of the time to treatment failure (the relative hazard of treatment failure) between groups using standard WHO response to treatment definitions for low to moderate malaria transmission areas, modified to a 42 day follow up. Randomisation was computer-generated with sequential allocation concealed in opaque sealed envelopes. Treatments were open-label, however laboratory staff responsible for parasite density measurements (in order to determine the primary efficacy end point) were blinded to treatment allocation.
- ItemOpen AccessEliciting harms data from trial participants: how perceptions of illness and treatment mediate recognition of relevant information to report(BioMed Central Ltd, 2011) Allen, Elizabeth; Barnes, Karen; Mushi, Adiel; Massawe, Isolide; Staedke, Sarah; Mehta, Ushma; Vestergaard, Lasse; Lemnge, Martha; Chandler, ClareBackground: There is no consensus on the ideal methodology for eliciting participant-reported harms, but question methods influence the extent and nature of data detected. This gives potential for measurement error and undermines meta-analyses of adverse effects. We undertook to identify barriers to accurate and complete reporting of harms data, by qualitatively exploring participants’ experiences of illness and treatment, and reporting behaviours; and compared the number and nature of data detected by three enquiry methods. Methods: Participants within antiretroviral/antimalarial interaction trials in South Africa and Tanzania were asked about medical history, treatments and/or adverse events by general enquiries followed by checklists. Those reporting differently between these two question methods were invited to an in-depth interview and focus group discussion. Health narratives were analysed to investigate accuracy and completeness of case record form data and to understand reasons for differential reporting between question methods. Outcomes were the number and nature of data by question method, themes from qualitative analyses and a theoretical interpretation of participants’ experiences. Results: We observed a cumulative increase in sensitivity of detection of all types of reports while progressing from general enquiry, through checklist, to in-depth interview. Questioning detail and terminology influenced participants’ recognition of health issues and treatments. Reporting patterns and vocabulary suggest influence from the relative importance that illnesses and treatments have for participants. Perceptions were often dichotomised (e.g. ‘street’ versus clinic treatments, symptoms experienced versus tests and examinations performed, chronic versus acute illness, persistent versus intermittent symptoms, activity- versus malaria-related symptoms) and this differentiation extended to ideas of relevance to report. South African participants displayed a ‘trial citizenship’, taking responsibility for the impact of their reporting on trial results, and even reaching reporting decisions by consensus. In contrast, Tanzanians perceived their role more as patients than participants; the locus of responsibility for knowing information relevant to the trial fell with trial staff as doctors rather than with themselves. Conclusions: Our observations of how reporting relates to participant perceptions inside and outside trials could help optimise how harms data are elicited. Questions reflecting the different ways that biomedically defined illness and treatment data are perceived by participants may help them understand relevance for reporting. We will theorise how these two disparate trial environments may have influenced how participants understood their role, as this could help researchers achieve empowered participation in similar trials.
- ItemOpen AccessEvaluating harm associated with anti-malarial drugs: a survey of methods used by clinical researchers to elicit, assess and record participant-reported adverse events and related data(BioMed Central Ltd, 2013) Allen, Elizabeth; Chandler, Clare; Mandimika, Nyaradzo; Pace, Cheryl; Mehta, Ushma; Barnes, KarenBACKGROUND:Participant reports of medical histories, adverse events (AE) and non-study drugs are integral to evaluating harm in clinical research. However, interpreting or synthesizing results is complicated if studies use different methods for ascertaining and assessing these data. To explore how these data are obtained in malaria drug studies, a descriptive online survey of clinical researchers was conducted during 2012 and 2013. METHODS: The survey was advertised through e-mails, collaborators and at conferences. Questions aimed to capture the detail, rationale and application of methods used to obtain relevant data within various study designs and populations. Closed responses were analysed using proportions, open responses through identifying repeating ideas and underlying concepts. RESULTS: Of fifty-two respondents from 25 counties, 87% worked at an investigational site and 75% reported about an interventional study. Studies employed a range of methods to elicit, assess and record participant-reported AEs and related data. Questioning about AEs in 31% of interventional studies was a combination of general (open questions about health) and structured (reference to specific health-related items), 26% used structured only and 18% general only. No observational studies used general questioning alone. A minority incorporated pictorial tools. Rationales for the questioning approach included: standardization of assessment or data capture, specificity or comprehensiveness of data sought, avoidance of suggestion, feasibility, and understanding participants' perceptions. Most respondents considered the approach they reported was optimal, though several reconsidered this. Four AE grading, and three causality assessment approaches were reported. Combining general and structured questions about non-study drug use were considered useful for revealing and identifying specific medicines, while pictures could enhance reports, particularly in areas of low literacy. CONCLUSIONS: It is critical to evaluate the safety of anti-malarial drugs being deployed in large, diverse populations. Many studies would be suitable for contributing to a larger body of evidence for answering questions on harm. However this survey showed that various methods are used to obtain relevant data, which could influence study results. As the best practices for obtaining such data are unclear, anti-malarial clinical researchers should work towards consensus about the selection and/or design of optimal methods.
- ItemOpen AccessHow experiences become data: the process of eliciting adverse event, medical history and concomitant medication reports in antimalarial and antiretroviral interaction trials(BioMed Central Ltd, 2013) Allen, Elizabeth; Mushi, Adiel; Massawe, Isolide; Vestergaard, Lasse; Lemnge, Martha; Staedke, Sarah; Mehta, Ushma; Barnes, Karen; Chandler, ClareBACKGROUND:Accurately characterizing a drug's safety profile is essential. Trial harm and tolerability assessments rely, in part, on participants' reports of medical histories, adverse events (AEs), and concomitant medications. Optimal methods for questioning participants are unclear, but different methods giving different results can undermine meta-analyses. This study compared methods for eliciting such data and explored reasons for dissimilar participant responses. METHODS: Participants from open-label antimalarial and antiretroviral interaction trials in two distinct sites (South Africa, n=18 [all HIV positive]; Tanzania, n=80 [86% HIV positive]) were asked about ill health and treatment use by sequential use of (1) general enquiries without reference to particular conditions, body systems or treatments, (2) checklists of potential health issues and treatments, (3) in-depth interviews. Participants' experiences of illness and treatment and their reporting behaviour were explored qualitatively, as were trial clinicians' experiences with obtaining participant reports. Outcomes were the number and nature of data by questioning method, themes from qualitative analyses and a theoretical interpretation of participants' experiences. RESULTS: There was an overall cumulative increase in the number of reports from general enquiry through checklists to in-depth interview; in South Africa, an additional 12 medical histories, 21 AEs and 27 medications; in Tanzania an additional 260 medical histories, 1 AE and 11 medications. Checklists and interviews facilitated recognition of health issues and treatments, and consideration of what to report. Information was sometimes not reported because participants forgot, it was considered irrelevant or insignificant, or they feared reporting. Some medicine names were not known and answers to questions were considered inferior to blood tests for detecting ill health. South African inpatient volunteers exhibited a "trial citizenship", working to achieve researchers' goals, while Tanzanian outpatients sometimes deferred responsibility for identifying items to report to trial clinicians. CONCLUSIONS: Questioning methods and trial contexts influence the detection of adverse events, medical histories and concomitant medications. There should be further methodological work to investigate these influences and find appropriate questioning methods.
- ItemOpen AccessOptimising methodology for the elicitation of participant-reported data relating to drug safety in resource poor settings(2015) Allen, Elizabeth; Barnes, Karen I; Chandler, Clare I R; Atuyambe, Lynn MIn addition to treating symptomatic patients, malaria prevention and elimination requires giving antimalarial drugs to asymptomatic or uninfected individuals. This shifts the harm-benefit balance and heightens the importance of accurately defining drug safety. Large data sets, including those pooled from multiple sources, are needed to understand uncommon adverse drug reactions. Interpreting individual studies , comparisons between studies and pooled datasets can be compromised, however, by inadequate or varied methods of safety data collection. Specifically, questioning methods may influence participants' reports of medical history, adverse events (AEs) and non-study medications. A Cochrane systematic review synthesised literature on research comparing methods for eliciting AEs from trial participants . A global online survey investigated how antimalarial researchers collect these data, and mixed-methods were used to identify barriers to accurate and complete reporting in South African and Tanzanian antimalarial-antiretroviral drug interaction trials. Focus group discussions were conducted in Ghana, Kenya and Uganda with women in a drugs exposure pregnancy registry to examine barriers to reporting at antenatal clinics, and how they might be overcome. The review included thirty-three studies in various therapeutic areas showing that more specific questioning increases the number of AEs reported by trial participants. Survey responses of 52 antimalarial researchers in 25 countries evidenced a range of methods to obtain AEs, medical histories and non-study drug reports. Qualitative data revealed that the trial context is influential and that detailed questioning facilitated participants' recognition and consideration of what to report. Non-reporting is due to forgetting, not knowing drug names, considering which information is relevant or significant to themselves or trial/healthcare workers, the potential consequences of reporting, and perceiving verbal responses inferior to what blood test results can show. Pregnant women's improved relationship with antenatal staff facilitated information-sharing and registry tools helped overcome problems with recall and naming of medicines. This project provides evidence of the substantial impact of different questioning methods on safety assessments . The results should contribute to developing a framework for researchers when planning globally-relevant, yet context-specific, antimalarial drug safety data collection strategies, and enhance efforts to pool data from multiple sources.
- ItemOpen AccessProtocol for a drugs exposure pregnancy registry for implementation in resource-limited settings(BioMed Central Ltd, 2012) Mehta, Ushma; Clerk, Christine; Allen, Elizabeth; Yore, Mackensie; Sevene, Esperanca; Singlovic, Jan; Petzold, Max; Mangiaterra, Viviana; Elefant, Elizabeth; Sullivan, Frank; Holmes, Lewis; Gomes, MelbaBACKGROUND: The absence of robust evidence of safety of medicines in pregnancy, particularly those for major diseases provided by public health programmes in developing countries, has resulted in cautious recommendations on their use. We describe a protocol for a Pregnancy Registry adapted to resource-limited settings aimed at providing evidence on the safety of medicines in pregnancy.METHODS/DESIGN:Sentinel health facilities are chosen where women come for prenatal care and are likely to come for delivery. Staff capacity is improved to provide better care during the pregnancy, to identify visible birth defects at delivery and refer infants with major anomalies for surgical or clinical evaluation and treatment. Consenting women are enrolled at their first antenatal visit and careful medical, obstetric and drug-exposure histories taken; medical record linkage is encouraged. Enrolled women are followed up prospectively and their histories are updated at each subsequent visit. The enrolled woman is encouraged to deliver at the facility, where she and her baby can be assessed.DISCUSSION:In addition to data pooling into a common WHO database, the WHO Pregnancy Registry has three important features: First is the inclusion of pregnant women coming for antenatal care, enabling comparison of birth outcomes of women who have been exposed to a medicine with those who have not. Second is its applicability to resource-poor settings regardless of drug or disease. Third is improvement of reproductive health care during pregnancies and at delivery. Facility delivery enables better health outcomes, timely evaluation and management of the newborn, and the collection of reliable clinical data. The Registry aims to improve maternal and neonatal care and also provide much needed information on the safety of medicines in pregnancy.
- ItemOpen AccessQuality assurance of qualitative research: a review of the discourse(BioMed Central Ltd, 2011) Reynolds, Joanna; Kizito, James; Ezumah, Nkoli; Mangesho, Peter; Allen, Elizabeth; Chandler, ClareBACKGROUND:Increasing demand for qualitative research within global health has emerged alongside increasing demand for demonstration of quality of research, in line with the evidence-based model of medicine. In quantitative health sciences research, in particular clinical trials, there exist clear and widely-recognised guidelines for conducting quality assurance of research. However, no comparable guidelines exist for qualitative research and although there are long-standing debates on what constitutes 'quality' in qualitative research, the concept of 'quality assurance' has not been explored widely. In acknowledgement of this gap, we sought to review discourses around quality assurance of qualitative research, as a first step towards developing guidance. METHODS: A range of databases, journals and grey literature sources were searched, and papers were included if they explicitly addressed quality assurance within a qualitative paradigm. A meta-narrative approach was used to review and synthesise the literature. RESULTS: Among the 37 papers included in the review, two dominant narratives were interpreted from the literature, reflecting contrasting approaches to quality assurance. The first focuses on demonstrating quality within research outputs; the second focuses on principles for quality practice throughout the research process. The second narrative appears to offer an approach to quality assurance that befits the values of qualitative research, emphasising the need to consider quality throughout the research process. CONCLUSIONS: The paper identifies the strengths of the approaches represented in each narrative and recommend these are brought together in the development of a flexible framework to help qualitative researchers to define, apply and demonstrate principles of quality in their research.
- ItemOpen AccessSafety and tolerability of single low-dose primaquine in a low-intensity transmission area in South Africa: an open-label, randomized controlled trial(2019-06-24) Raman, Jaishree; Allen, Elizabeth; Workman, Lesley; Mabuza, Aaron; Swanepoel, Hendrik; Malatje, Gillian; Frean, John; Wiesner, Lubbe; Barnes, Karen IAbstract Background To reduce onward falciparum malaria transmission, the World Health Organization recommends adding single low-dose (SLD) primaquine to artemisinin-based combination treatment in low transmission areas. However, uptake of this recommendation has been relatively slow given concerns about whether individual risks justify potential community benefit. This study was undertaken to generate comprehensive local data on the risk–benefit profile of SLD primaquine deployment in a pre-elimination area in South Africa. Methods This randomized, controlled open-label trial investigated adding a single low primaquine dose on day 3 to standard artemether–lumefantrine treatment for uncomplicated falciparum malaria. Efficacy, safety and tolerability of artemether–lumefantrine and primaquine treatment were assessed on days 3, 7, 14, 28 and 42. Lumefantrine concentrations were assayed from dried blood spot samples collected on day 7. Results Of 217 patients screened, 166 were enrolled with 140 randomized on day 3, 70 to each study arm (primaquine and no primaquine). No gametocytes were detected by either microscopy or PCR in any of the follow-up samples collected after randomization on day 3, precluding assessment of primaquine efficacy. Prevalence of the CYP2D6*4, CYP2D6*10 and CYP2D6*17 mutant alleles was low with allelic frequencies of 0.02, 0.11 and 0.16, respectively; none had the CYP2D6*4/*4 variant associated with null activity. Among 172 RDT-positive patients G6PD-genotyped, 24 (14%) carried the G6PD deficient (A−) variant. Median haemoglobin concentrations were similar between treatment arms throughout follow-up. A third of participants had a haemoglobin drop > 2 g/dL; this was not associated with primaquine treatment but may be associated with G6PD genotype [52.9% (9/17) with A− genotype vs. 31% (36/116) with other genotypes (p = 0.075)]. Day 7 lumefantrine concentrations and the number and nature of adverse events were similar between study arms; only one serious adverse event occurred (renal impairment in the no primaquine arm). The artemether–lumefantrine PCR-corrected adequate clinical and parasitological response rate was 100%, with only one re-infection found among the 128 patients who completed 42-day follow-up. Conclusions Safety, tolerability, CYP2D6 and G6PD variant data from this study support the deployment of the WHO-recommended SLD primaquine without G6PD testing to advance malaria elimination in South African districts with low-intensity residual transmission. Trial registration Pan African Clinical Trial Registry, PACTR201611001859416. Registered 11 November 2016, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=1859
- ItemOpen AccessTherapeutic efficacy of sulfadoxine-pyrimethamine for plasmodium falciparum malaria(2005) Mabuza, Aaron; Govere, John; La Grange, Kobus; Mngomezulu, Nicros; Allen, Elizabeth; Zitha, Alpheus; Mbokazi, Frans; Durrheim, David; Barnes, KarenObjectives. To assess the therapeutic efficacy of sulfadoxinepyrimethamine (SP) after 5 years of use as first-line treatment of uncomplicated Plasmodium falciparum malaria, and thus guide the selection of artemisinin-based combination therapy in Mpumalanga, South Africa. Design. An open-label, in vivo therapeutic efficacy study of patients with uncomplicated P. falciparum malaria treated with a single oral dose of SP, with response to treatment monitored clinically and parasitologically on days 1, 2, 3, 7, 14, 21, 28 and 42. Setting. Mangweni and Naas public health care clinics, Tonga district in rural Mpumalanga. Subjects, outcome measures and results. Of 152 patients recruited sequentially, 149 (98%) were successfully followed up for 42 days. One hundred and thirty-four patients (90%) demonstrated adequate clinical and parasitological response. Of the 15 patients (10%) who failed treatment, 2 (1.3%) had an early treatment failure, and polymerase chain reaction confirmed recrudescent infection in all 13 patients (8.7%) who had late parasitological (N = 11) or clinical (N = 2) failure. Gametocyte carriage was prevalent following SP treatment (84/152) and this has increased significantly since implementation in 1998 (relative risk 2.77 (confidence interval 1.65 - 4.66); p = 0.00004). Conclusion. Asexual P. falciparum parasites in Mpumalanga remain sensitive to SP, with no significant difference between the baseline cure rate (94.5%) at introduction in 1998, and the present 90% cure rate (p = 0.14). However, since gametocyte carriage has increased significantly we recommend that SP be combined with artesunate in Mpumalanga to reduce gametocyte carriage and thus decrease malaria transmission and potentially delay antimalarial resistance. S Afr Med J 2005; 95: 346-349.