Showing papers by "Philippe J Guerin published in 2023"
TL;DR: In this article , a scoping literature review was performed to evaluate how the eligibility criteria used in anti-malarial efficacy and safety trials translate into patient selection, and the proportion of trials with malaria-positive patients excluded was calculated and linked to the reported reason for exclusion.
Abstract: For the results of clinical trials to have external validity, the patients included in the study must be representative of the population presenting in the general clinical settings. A scoping literature review was performed to evaluate how the eligibility criteria used in anti-malarial efficacy and safety trials translate into patient selection.A search of the WorldWide Antimalarial Resistance Network (WWARN) Clinical Trials Publication Library, MEDLINE, The Cochrane Library, and clinicaltrials.gov was conducted to identify trials investigating anti-malarial efficacy and safety, published between 14th April 2001 and 31st December 2017. An updated search using the WWARN Clinical Trial Publication Library was undertaken to identify eligible publications from 1st January 2018 to 31st July 2021. The review included studies in patients of any age with uncomplicated malaria and any pharmaceutical therapeutic intervention administered. The proportion of trials with malaria-positive patients excluded was calculated and linked to the reported reason for exclusion. A subgroup analysis on eligibility criteria and trial baseline demographics was conducted to assess whether criteria are complied with when recruiting patients.Out of 847 studies, 176 (21%) trials were included in the final synthesis, screening a total of 157,516 malaria-positive patients, of whom 56,293 (36%) were enrolled and treated. Across the 176 studies included, 84 different inclusion and exclusion criteria were identified. The reason for exclusion of patients who tested positive for malaria was reported in 144 (82%) studies. Three criteria account for about 70% of malaria-positive patients excluded: mixed-species malaria infections or other specific Plasmodium species, parasite counts outside the set study ranges, and refusal of consent.Nearly two-thirds of the malaria-positive subjects who present to health facilities are systematically excluded from anti-malarial treatment trials. Reasons for exclusions are largely under-reported. Anti-malarial treatment in the general population is informed by studies on a narrow selection of patients who do not fully represent the totality of those seeking antimalarial treatment in routine practice. While entry criteria ensure consistency across trials, pragmatic trials are also necessary to supplement the information currently available and improve the external validity of the findings of malaria clinical trials.
1 citations
TL;DR: In this article, the authors correct the article DOI: 10.1371/journal.pntd.0009144, and present a new version of the article, with the same title.
Abstract: [This corrects the article DOI: 10.1371/journal.pntd.0009144.].
1 citations
TL;DR: In this paper , the authors describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.
Abstract: The World Health Organization (WHO) recommends that when peripheral malarial parasitaemia is quantified by thick film microscopy, an actual white blood cell (WBC) count from a concurrently collected blood sample is used in calculations. However, in resource-limited settings an assumed WBC count is often used instead. The aim of this study was to describe the variability in WBC count during acute uncomplicated malaria, and estimate the impact of using an assumed value of WBC on estimates of parasite density and clearance.Uncomplicated malaria drug efficacy studies that measured WBC count were selected from the WorldWide Antimalarial Resistance Network data repository for an individual patient data meta-analysis of WBC counts. Regression models with random intercepts for study-site were used to assess WBC count variability at presentation and during follow-up. Inflation factors for parasitaemia density, and clearance estimates were calculated for methods using assumed WBC counts (8000 cells/µL and age-stratified values) using estimates derived from the measured WBC value as reference.Eighty-four studies enrolling 27,656 patients with clinically uncomplicated malaria were included. Geometric mean WBC counts (× 1000 cells/µL) in age groups < 1, 1-4, 5-14 and ≥ 15 years were 10.5, 8.3, 7.1, 5.7 and 7.5, 7.0, 6.5, 6.0 for individuals with falciparum (n = 24,978) and vivax (n = 2678) malaria, respectively. At presentation, higher WBC counts were seen among patients with higher parasitaemia, severe anaemia and, for individuals with vivax malaria, in regions with shorter regional relapse periodicity. Among falciparum malaria patients, using an assumed WBC count of 8000 cells/µL resulted in parasite density underestimation by a median (IQR) of 26% (4-41%) in infants < 1 year old but an overestimation by 50% (16-91%) in adults aged ≥ 15 years. Use of age-stratified assumed WBC values removed systematic bias but did not improve precision of parasitaemia estimation. Imprecision of parasite clearance estimates was only affected by the within-patient WBC variability over time, and remained < 10% for 79% of patients.Using an assumed WBC value for parasite density estimation from a thick smear may lead to underdiagnosis of hyperparasitaemia and could adversely affect clinical management; but does not result in clinically consequential inaccuracies in the estimation of the prevalence of prolonged parasite clearance and artemisinin resistance.
TL;DR: A systematic review of the available noma literature is presented in this paper , which aims to generate an account of the present state of knowledge about the various aspects of noma to aid in framing effective strategies and interventions to curb this disease which disproportionately afflicts the poorest in society.
Abstract: Introduction: Noma (cancrum oris) is a devastating opportunistic infection resulting in severe tissue destruction that affects mouth and oro-facial structures. There are substantial gaps in our current knowledge and understanding of its aetiology, pathogenesis, prevention and treatment efficacy, as well as its distribution and burden. Although observed worldwide, the disease impacts the most vulnerable and marginalised populations, and is most reported in young children from sub-Saharan Africa. Noma often presents alongside conditions of extreme poverty, malnutrition and poor environmental sanitation. This protocol paper outlines the methodology for a systematic review planned to exhaustively synthesize the findings of the available noma literature. The project aims to generate an account of the present state of knowledge about the various aspects of noma to aid in framing effective strategies and interventions to curb this disease which disproportionately afflicts the poorest in society. Methods and analysis: The following databases have been searched by a medical librarian from database inception to 7 December 2022: OVID (MEDLINE/ Embase/ CAB abstracts/ Global Health), Scopus, Web of Science, African Index Medicus, African Journals Online: Health, French language search: Pascal, ClinicalTrials.gov, and WHO ICTRP. All primary research studies reporting on patients of any age diagnosed with noma will be eligible for inclusion in the review, including clinical trials, cohort studies, case-control, cross-sectional, other observational studies, case studies and case series. Data will be extracted from included studies to analyse the current evidence-based knowledge on the distribution, risk factors, microbiology, prevention and treatment modalities, and outcomes of noma. Ethics and dissemination: Results of this systematic review will be published in a peer-reviewed journal upon completion. PROSPERO Registration: CRD42019124839 (08/03/2019)
TL;DR: In this article , the authors estimate the proportion of uncomplicated falciparum malaria patients at risk of being sub-optimally dosed with the current World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs) is unknown.
Abstract: Introduction: Selection of resistant malaria strains occurs when parasites are exposed to inadequate antimalarial drug concentrations. The proportion of uncomplicated falciparum malaria patients at risk of being sub-optimally dosed with the current World Health Organization (WHO) recommended artemisinin-based combination therapies (ACTs) is unknown. This study aims to estimate this proportion and the excess number of treatment failures (recrudescences) associated with sub-optimal dosing in Sub-Saharan Africa. Methods: Sub-populations at risk of sub-optimal dosing include wasted children <5 years of age; patients with hyperparasitaemia; pregnant women; people living with HIV; and overweight adults. Country-level data on population structure were extracted from openly accessible data sources. Pooled adjusted Hazard Ratios for PCR-confirmed recrudescence were estimated for each risk group from published meta-analyses using fixed-effect meta-analysis. Results: In 2020, of 153.1 million uncomplicated P. falciparum malaria patients in Africa, the largest risk groups were the hyperparasitaemic patients (13.2 million, 8.6% of uncomplicated malaria cases) and overweight adults (10.3 million, 6.7% of uncomplicated cases). The excess total number of treatment failures ranged from 323,247 for a 98% baseline ACT efficacy to 1,292,987 for a 92% baseline ACT efficacy. Conclusion: An estimated 1 in nearly 4 people with uncomplicated confirmed P. falciparum malaria in Africa are at risk of receiving a sub-optimal antimalarial drug dosing. This increases the risk of antimalarial drug resistance and poses a serious threat to malaria control and elimination efforts. Changes in antimalarial dosing or treatment duration of current antimalarials may be needed and new antimalarials development should ensure sufficient drug concentration levels in these sub-populations that carry a high malaria burden.