ABSTRACT
BACKGROUND: Malaria control remains a challenge in many parts of the Sahel and sub-Sahel regions of Africa. METHODS: We conducted an individually randomized, controlled trial to assess whether seasonal vaccination with RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria and whether the two interventions combined were superior to either one alone in preventing uncomplicated malaria and severe malaria-related outcomes. RESULTS: We randomly assigned 6861 children 5 to 17 months of age to receive sulfadoxine-pyrimethamine and amodiaquine (2287 children [chemoprevention-alone group]), RTS,S/AS01E (2288 children [vaccine-alone group]), or chemoprevention and RTS,S/AS01E (2286 children [combination group]). Of these, 1965, 1988, and 1967 children in the three groups, respectively, received the first dose of the assigned intervention and were followed for 3 years. Febrile seizure developed in 5 children the day after receipt of the vaccine, but the children recovered and had no sequelae. There were 305 events of uncomplicated clinical malaria per 1000 person-years at risk in the chemoprevention-alone group, 278 events per 1000 person-years in the vaccine-alone group, and 113 events per 1000 person-years in the combination group. The hazard ratio for the protective efficacy of RTS,S/AS01E as compared with chemoprevention was 0.92 (95% confidence interval [CI], 0.84 to 1.01), which excluded the prespecified noninferiority margin of 1.20. The protective efficacy of the combination as compared with chemoprevention alone was 62.8% (95% CI, 58.4 to 66.8) against clinical malaria, 70.5% (95% CI, 41.9 to 85.0) against hospital admission with severe malaria according to the World Health Organization definition, and 72.9% (95% CI, 2.9 to 92.4) against death from malaria. The protective efficacy of the combination as compared with the vaccine alone against these outcomes was 59.6% (95% CI, 54.7 to 64.0), 70.6% (95% CI, 42.3 to 85.0), and 75.3% (95% CI, 12.5 to 93.0), respectively. CONCLUSIONS: Administration of RTS,S/AS01E was noninferior to chemoprevention in preventing uncomplicated malaria. The combination of these interventions resulted in a substantially lower incidence of uncomplicated malaria, severe malaria, and death from malaria than either intervention alone. (Funded by the Joint Global Health Trials and PATH; ClinicalTrials.gov number, NCT03143218.).
Subject(s)
Amodiaquine/therapeutic use , Antimalarials/therapeutic use , Malaria Vaccines , Malaria, Falciparum/prevention & control , Pyrimethamine/therapeutic use , Sulfadoxine/therapeutic use , Antimalarials/adverse effects , Burkina Faso/epidemiology , Chemoprevention , Combined Modality Therapy , Double-Blind Method , Drug Combinations , Drug Therapy, Combination , Female , Hospitalization/statistics & numerical data , Humans , Infant , Malaria Vaccines/administration & dosage , Malaria Vaccines/adverse effects , Malaria, Falciparum/epidemiology , Malaria, Falciparum/mortality , Male , Mali/epidemiology , Seasons , Seizures, Febrile/etiologyABSTRACT
INTRODUCTION: The management of cardiovascular pathologies has a high cost for users. PURPOSE OF THE RESEARCH: It is therefore important to assess the costs of hospitalization to gain a better understanding of its impact on care. RESULTS: This was a case series-type, descriptive, observational study with prospective data collection. RESULTS: A total of 103 patients were included, with a mean age of 51 years and extremes ranging from 14 to 86 years. The average length of stay was 7.1 days. Heart failure was the most frequent pathology (61.7%). The average monthly income per patient was 101,360 CFA francs. The average total direct cost during hospitalization was 114,015 CFAF. The average direct cost of drugs and consumables was 60,553.77 CFAF. The average direct cost of paraclinical examinations was 34,360.29 CFAF. Hospitalization costs averaged 16,747.47 CFAF. Total direct costs during hospitalization were 11,737,060 CFAF, dominated by drugs and medical consumables (53.14%), followed by complementary examinations (29.86%) and non-medical expenses (17%). During the study, 13.59% of patients were discharged against medical advice. Expenses were covered by the parents in 71.84% of cases. CONCLUSIONS: The average direct cost of hospitalization is well above the purchasing power of the majority of patients.
Subject(s)
Cardiovascular Diseases , Hospitalization , Humans , Middle Aged , Burkina Faso , Adult , Aged , Female , Male , Aged, 80 and over , Adolescent , Young Adult , Cardiovascular Diseases/therapy , Cardiovascular Diseases/economics , Prospective Studies , Hospitalization/economics , Hospitalization/statistics & numerical data , Health Care Costs/statistics & numerical dataABSTRACT
Introduction: Free health care for children under five years of age in Burkina Faso was introduced in 2016 in order to remove the financial barrier to accessing care. Additional health expenses remain despite this free health care, which may compromise access to health services for the poorest patients. Methods: This partial medico-economic evaluation included a descriptive study of additional health expenses paid by parents. Payment receipts and parents' declarations were consulted. Results: The average monthly income of the parents was 73,026.79 FCFA ($132) with 5.08% of the parents having no income. The total direct cost was 6,043,785 FCFA ($10939). The total additional direct cost was 2,181,150 FCFA ($3,950) or 36.09% of the total direct cost. The average percentage of free care was 65.50%. 7.7% of parents were dissatisfied with the free schooling. 34.48% were unprepared for additional expenses, 43.97% of parents had difficulty paying the additional costs and of these 80% reported that they had exhausted their savings to meet the prescriptions. Conclusions: Additional health expenses remain high despite free care. This can compromise the care of the poorest patients. A reorganization of free health care is necessary.
Introduction: La gratuité des soins chez les enfants de moins de 5 ans au Burkina Faso a été introduite en 2016 afin de lever la barrière financière dans l'accès aux soins. Des dépenses de santé additionnelles subsisteraient malgré cette gratuité, ce qui peut compromettre l'accès aux services de santé des patients les plus démunis. Méthodes: Il s'agit d'une évaluation médico-économique partielle, notamment l'étude descriptive des dépenses de santé additionnelles payées par les parents. Nous avons consulté les reçus de paiement et les déclarations des parents. Résultats: Le revenu mensuel des parents était en moyenne de 73 026,79 FCFA (132 $) avec 5,08 % des parents qui n'ont pas de revenu. Le coût direct total était de 6 043 785 FCFA (10 939 $). Le coût direct total additionnel était de 2 181 150 FCFA (3 950 $), soit 36,09 % du coût direct total. Le pourcentage moyen de prise en charge de la gratuité était de 65,50 %. Près de 10 % (7,7 %) des parents étaient insatisfaits de la gratuité ; ils étaient 34,48 % à ne pas être préparés à honorer des dépenses supplémentaires, 43,97 % avaient eu du mal à payer les frais supplémentaires et parmi ces derniers, 80 % ont déclaré avoir épuisé leur économie pour honorer les prescriptions. Conclusions: Les dépenses de santé additionnelles restent élevées malgré la gratuité des soins. Cela peut compromettre la prise en charge des patients les plus pauvres. Une réorganisation de la gratuité des soins s'avère nécessaire.
Subject(s)
Health Services Accessibility , Health Services , Child , Humans , Child, Preschool , Burkina Faso , Health Expenditures , PovertyABSTRACT
BACKGROUND: A trial in African children showed that combining seasonal vaccination with the RTS,S/AS01E vaccine with seasonal malaria chemoprevention reduced the incidence of uncomplicated and severe malaria compared with either intervention given alone. Here, we report on the anti-circumsporozoite antibody response to seasonal RTS,S/AS01E vaccination in children in this trial. METHODS: Sera from a randomly selected subset of children collected before and 1 month after 3 priming doses of RTS,S/AS01E and before and 1 month after 2 seasonal booster doses were tested for anti-circumsporozoite antibodies using enzyme-linked immunosorbent assay. The association between post-vaccination antibody titer and incidence of malaria was explored. RESULTS: A strong anti-circumsporozoite antibody response to 3 priming doses of RTS,S/AS01E was seen (geometric mean titer, 368.9 enzyme-linked immunosorbent assay units/mL), but titers fell prior to the first booster dose. A strong antibody response to an annual, pre-malaria transmission season booster dose was observed, but this was lower than after the primary vaccination series and lower after the second than after the first booster dose (ratio of geometric mean rise, 0.66; 95% confidence interval [CI], .57-.77). Children whose antibody response was in the upper tercile post-vaccination had a lower incidence of malaria during the following year than children in the lowest tercile (hazard ratio, 0.43; 95% CI, .28-.66). CONCLUSIONS: Seasonal vaccination with RTS,S/AS01E induced a strong booster antibody response that was lower after the second than after the first booster dose. The diminished antibody response to the second booster dose was not associated with diminished efficacy. CLINICAL TRIALS REGISTRATION: NCT03143218.
Subject(s)
Malaria Vaccines , Malaria, Falciparum , Malaria , Antibody Formation , Child , Humans , Infant , Malaria, Falciparum/epidemiology , Malaria, Falciparum/prevention & control , Plasmodium falciparum , Seasons , VaccinationABSTRACT
BACKGROUND: A recent trial of 5920 children in Burkina Faso and Mali showed that the combination of seasonal vaccination with the RTS,S/AS01E malaria vaccine (primary series and two seasonal boosters) and seasonal malaria chemoprevention (four monthly cycles per year) was markedly more effective than either intervention given alone in preventing clinical malaria, severe malaria, and deaths from malaria. METHODS: In order to help optimise the timing of these two interventions, trial data were reanalysed to estimate the duration of protection against clinical malaria provided by RTS,S/AS01E when deployed seasonally, by comparing the group who received the combination of SMC and RTS,S/AS01E with the group who received SMC alone. The duration of protection from SMC was also estimated comparing the combined intervention group with the group who received RTS,S/AS01E alone. Three methods were used: Piecewise Cox regression, Flexible parametric survival models and Smoothed Schoenfeld residuals from Cox models, stratifying on the study area and using robust standard errors to control for within-child clustering of multiple episodes. RESULTS: The overall protective efficacy from RTS,S/AS01E over 6 months was at least 60% following the primary series and the two seasonal booster doses and remained at a high level over the full malaria transmission season. Beyond 6 months, protective efficacy appeared to wane more rapidly, but the uncertainty around the estimates increases due to the lower number of cases during this period (coinciding with the onset of the dry season). Protection from SMC exceeded 90% in the first 2-3 weeks post-administration after several cycles, but was not 100%, even immediately post-administration. Efficacy begins to decline from approximately day 21 and then declines more sharply after day 28, indicating the importance of preserving the delivery interval for SMC cycles at a maximum of four weeks. CONCLUSIONS: The efficacy of both interventions was highest immediately post-administration. Understanding differences between these interventions in their peak efficacy and how rapidly efficacy declines over time will help to optimise the scheduling of SMC, malaria vaccination and the combination in areas of seasonal transmission with differing epidemiology, and using different vaccine delivery systems. TRIAL REGISTRATION: The RTS,S-SMC trial in which these data were collected was registered at clinicaltrials.gov: NCT03143218.
Subject(s)
Malaria Vaccines , Malaria, Falciparum , Malaria , Antibodies, Protozoan , Chemoprevention , Humans , Infant , Malaria/epidemiology , Malaria/prevention & control , Malaria, Falciparum/epidemiology , Plasmodium falciparum , Seasons , VaccinationABSTRACT
BACKGROUND: A recent trial in Burkina Faso and Mali showed that combining seasonal RTS,S/AS01E malaria vaccination with seasonal malaria chemoprevention (SMC) substantially reduced the incidence of uncomplicated and severe malaria in young children compared to either intervention alone. Given the possible negative effect of malaria on nutrition, the study investigated whether these children also experienced lower prevalence of acute and chronic malnutrition. METHODS: In Burkina Faso and Mali 5920 children were randomized to receive either SMC alone, RTS,S/AS01E alone, or SMC combined with RTS,S/AS01E for three malaria transmission seasons (2017-2019). After each transmission season, anthropometric measurements were collected from all study children at a cross-sectional survey and used to derive nutritional status indicators, including the binary variables wasted and stunted (weight-for-height and height-for-age z-scores below - 2, respectively). Binary and continuous outcomes between treatment groups were compared by Poisson and linear regression. RESULTS: In 2017, compared to SMC alone, the combined intervention reduced the prevalence of wasting by approximately 12% [prevalence ratio (PR) = 0.88 (95% CI 0.75, 1.03)], and approximately 21% in 2018 [PR = 0.79 (95% CI 0.62, 1.01)]. Point estimates were similar for comparisons with RTS,S/AS01E, but there was stronger evidence of a difference. There was at least a 30% reduction in the point estimates for the prevalence of severe wasting in the combined group compared to the other two groups in 2017 and 2018. There was no difference in the prevalence of moderate or severe wasting between the groups in 2019. The prevalence of stunting, low-MUAC-for-age or being underweight did not differ between groups for any of the three years. The prevalence of severe stunting was higher in the combined group compared to both other groups in 2018, and compared to RTS,S/AS01E alone in 2017; this observation does not have an obvious explanation and may be a chance finding. Overall, malnutrition was very common in this cohort, but declined over the study as the children became older. CONCLUSIONS: Despite a high burden of malnutrition and malaria in the study populations, and a major reduction in the incidence of malaria in children receiving both interventions, this had only a modest impact on nutritional status. Therefore, other interventions are needed to reduce the high burden of malnutrition in these areas. TRIAL REGISTRATION: https://www.clinicaltrials.gov/ct2/show/NCT03143218 , registered 8th May 2017.
Subject(s)
Antimalarials , Malaria , Antimalarials/therapeutic use , Burkina Faso/epidemiology , Chemoprevention , Child , Child, Preschool , Cross-Sectional Studies , Humans , Infant , Malaria/drug therapy , Malaria/epidemiology , Malaria/prevention & control , Mali/epidemiology , Nutritional Status , Seasons , VaccinationABSTRACT
BACKGROUND: Burkina Faso experienced an epidemic resurgence of dengue in 2016, which led to the implementation of several control strategies. In order to allow a better adaptation of these strategies, we studied the spatio-temporal distribution of dengue. METHODS: Monthly dengue cases from 2016 to 2019, aggregated at the health district level, were used to map the crude incidence, excess risk, and smoothed incidence of dengue in Burkina Faso with GeoDa software. A Kulldoff scan on Satscan software was then used to identify spatio-temporal clustering of cases. RESULTS: The results show that the distribution of dengue fever across the health districts of Burkina Faso is heterogeneous. Dengue was considered non-endemic in 9 out of the 70 health districts, minimally endemic in 45 districts (< 10 incidences), moderately endemic (10-100 incidences) in 12 districts, and highly endemic (> 100 incidences) in 4 districts. The main cluster covered the health districts of Baskuy, Nongr-massom, Sig-noghin, Boulmiougou, and Bogodogo. The months of October and November corresponded to the peak of cases and a significant temporal cluster in 2017. CONCLUSION: This study identified the spatial and temporal clustering of dengue cases in Burkina Faso. These results may help to develop better preventive strategies.
Subject(s)
Dengue , Burkina Faso/epidemiology , Cluster Analysis , Dengue/epidemiology , Humans , Incidence , Spatio-Temporal AnalysisABSTRACT
Computational structural prediction of macromolecular interactions is a fundamental tool toward the global understanding of cellular processes. The Critical Assessment of PRediction of Interactions (CAPRI) community-wide experiment provides excellent opportunities for blind testing computational docking methods and includes original targets, thus widening the range of docking applications. Our participation in CAPRI rounds 38 to 45 enabled us to expand the way we include evolutionary information in structural predictions beyond our standard free docking InterEvDock pipeline. InterEvDock integrates a coarse-grained potential that accounts for interface coevolution based on joint multiple sequence alignments of two protein partners (co-alignments). However, even though such co-alignments could be built for none of the CAPRI targets in rounds 38 to 45, including host-pathogen and protein-oligosaccharide complexes and a redesigned interface, we identified multiple strategies that can be used to incorporate evolutionary constraints, which helped us to identify the most likely macromolecular binding modes. These strategies include template-based modeling where only local adjustments should be applied when query-template sequence identity is above 30% and larger perturbations are needed below this threshold; covariation-based structure prediction for individual protein partners; and the identification of evolutionarily conserved and structurally recurrent anchoring interface motifs. Overall, we submitted correct predictions among the top 5 models for 12 out of 19 interface challenges, including four High- and five Medium-quality predictions. Our top 20 models included correct predictions for three out of the five targets we missed in the top 5, including two targets for which misleading biological data led us to downgrade correct free docking models.
Subject(s)
Molecular Docking Simulation , Oligosaccharides/chemistry , Peptides/chemistry , Proteins/chemistry , Software , Amino Acid Sequence , Binding Sites , Humans , Ligands , Oligosaccharides/metabolism , Peptides/metabolism , Protein Binding , Protein Conformation, alpha-Helical , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Protein Interaction Mapping , Protein Multimerization , Proteins/metabolism , Research Design , Structural Homology, ProteinABSTRACT
One of the main challenges in computational protein design (CPD) is the huge size of the protein sequence and conformational space that has to be computationally explored. Recently, we showed that state-of-the-art combinatorial optimization technologies based on Cost Function Network (CFN) processing allow speeding up provable rigid backbone protein design methods by several orders of magnitudes. Building up on this, we improved and injected CFN technology into the well-established CPD package Osprey to allow all Osprey CPD algorithms to benefit from associated speedups. Because Osprey fundamentally relies on the ability of A* to produce conformations in increasing order of energy, we defined new A* strategies combining CFN lower bounds, with new side-chain positioning-based branching scheme. Beyond the speedups obtained in the new A*-CFN combination, this novel branching scheme enables a much faster enumeration of suboptimal sequences, far beyond what is reachable without it. Together with the immediate and important speedups provided by CFN technology, these developments directly benefit to all the algorithms that previously relied on the DEE/ A* combination inside Osprey* and make it possible to solve larger CPD problems with provable algorithms.
Subject(s)
Algorithms , Computational Biology , Proteins/chemistry , Amino Acid Sequence , Drug Design , Protein ConformationABSTRACT
BACKGROUND: Severe acute malnutrition (SAM) affects almost all organs and has been associated with reduced intestinal absorption of medicines. However, very limited information is available on the pharmacokinetic properties of antimalarial drugs in this vulnerable population. We assessed artemether-lumefantrine (AL) clinical efficacy in children with SAM compared to those without. METHODS: Children under 5 years of age with uncomplicated P. falciparum malaria were enrolled between November 2013 and January 2015 in Mali and Niger, one third with uncomplicated SAM and two thirds without. AL was administered under direct observation with a fat intake consisting of ready-to-use therapeutic food (RUTF - Plumpy'Nut®) in SAM children, twice daily during 3 days. Children were followed for 42 days, with PCR-corrected adequate clinical and parasitological response (ACPR) at day 28 as the primary outcome. Lumefantrine concentrations were assessed in a subset of participants at different time points, including systematic measurements on day 7. RESULTS: A total of 399 children (360 in Mali and 39 in Niger) were enrolled. Children with SAM were younger than their non-SAM counterparts (mean 17 vs. 28 months, P < 0.0001). PCR-corrected ACPR was 100 % (95 % CI, 96.8-100 %) in SAM at both day 28 and 42, versus 98.8 % (96.4-99.7 %) at day 28 and 98.3 % (95.6-99.4 %) at day 42 in non-SAM (P = 0.236 and 0.168, respectively). Compared to younger children, children older than 21 months experienced more reinfections and SAM was associated with a greater risk of reinfection until day 28 (adjusted hazard ratio = 2.10 (1.04-4.22), P = 0.038). Day 7 lumefantrine concentrations were significantly lower in SAM than non-SAM (median 251 vs. 365 ng/mL, P = 0.049). CONCLUSIONS: This study shows comparable therapeutic efficacy of AL in children without SAM and in those with SAM when given in combination with RUTF, but a higher risk of reinfection in older children suffering from SAM. This could be associated with poorer exposure to the antimalarials as documented by a lower lumefantrine concentration on day 7. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01958905 , registration date: October 7, 2013.
Subject(s)
Antimalarials/pharmacokinetics , Artemisinins/pharmacokinetics , Ethanolamines/pharmacokinetics , Fluorenes/pharmacokinetics , Malaria, Falciparum/drug therapy , Severe Acute Malnutrition/metabolism , Antimalarials/administration & dosage , Artemether, Lumefantrine Drug Combination , Artemisinins/administration & dosage , Child, Preschool , Drug Combinations , Ethanolamines/administration & dosage , Female , Fluorenes/administration & dosage , Humans , Infant , Malaria, Falciparum/metabolism , Male , Mali , Niger , Severe Acute Malnutrition/parasitologyABSTRACT
MOTIVATION: The main challenge for structure-based computational protein design (CPD) remains the combinatorial nature of the search space. Even in its simplest fixed-backbone formulation, CPD encompasses a computationally difficult NP-hard problem that prevents the exact exploration of complex systems defining large sequence-conformation spaces. RESULTS: We present here a CPD framework, based on cost function network (CFN) solving, a recent exact combinatorial optimization technique, to efficiently handle highly complex combinatorial spaces encountered in various protein design problems. We show that the CFN-based approach is able to solve optimality a variety of complex designs that could often not be solved using a usual CPD-dedicated tool or state-of-the-art exact operations research tools. Beyond the identification of the optimal solution, the global minimum-energy conformation, the CFN-based method is also able to quickly enumerate large ensembles of suboptimal solutions of interest to rationally build experimental enzyme mutant libraries. AVAILABILITY: The combined pipeline used to generate energetic models (based on a patched version of the open source solver Osprey 2.0), the conversion to CFN models (based on Perl scripts) and CFN solving (based on the open source solver toulbar2) are all available at http://genoweb.toulouse.inra.fr/~tschiex/CPD
Subject(s)
Protein Conformation , Protein Engineering/methods , Algorithms , Models, Molecular , Proteins/chemistry , Sequence Analysis, Protein , SoftwareABSTRACT
BACKGROUND: The aim of this study was to evaluate the impact of telehealth on 1) the diagnosis, and management in obstetrics and cardiology, 2) health care costs from patients' perspectives, 3) attendance at health centres located in remote areas of Mali. METHODS: The impact of telehealth on health care utilization, quality, and costs was assessed using a five-point Likert-scale based questionnaire consisting of three dimensions. It was completed by health care professionals in four district hospitals. The role of telehealth on attendance at health centres was also assessed based on data collected from the consultations logs before and during the project, between project sites and control sites. Referrals specific to the activities of the research study were also evaluated using a questionnaire to measure the real share of telehealth tools in increasing attendance at project sites. Finally, the cost savings achieved was estimated using the transport and lodging costs incurred if patients were to travel to the capital city for the same tests or care. RESULTS: The telehealth activities contributed to improving medical diagnoses in cardiology and obstetrics (92.6%) and the patients' management system on site (96.2%). The attendance records at health centres increased from 8 to 35% at all project sites during the study period. Patients from project sites saved an average of 12380 XOF (CFA Francs) or 25 USD (American dollar) and a maximum of 35000 XOF or 70 USD compared to patients from neighbouring sites, who must go to the capital city to receive the same care. CONCLUSION: We conclude that in Mali, enhanced training in ultrasound / electrocardiography and the introduction of telehealth have improved the health system in remote areas and resulted in high levels of appropriate diagnosis and patient management in the areas of obstetrics and cardiology. Telehealth can also significantly reduce the cost to the patient.
Subject(s)
Cardiology , Obstetrics , Rural Health Services/statistics & numerical data , Telemedicine , Case-Control Studies , Decision Making , Developing Countries , Female , Health Care Costs , Health Services Research , Humans , Male , Mali , Prospective Studies , Quality of Health Care , Remote Consultation , Surveys and QuestionnairesABSTRACT
Introduction: to help reduce neonatal mortality in Burkina Faso, we identified the prognostic factors for neonatal mortality at the Sourô Sanou University Hospital. Methods: we conducted a cross-sectional and analytical study in the neonatal department from July 25, 2019 to June 25, 2020. Patients' medical records, consultation and hospital records were reviewed. Prognostic factors for neonatal mortality were identified using a Cox model. Results: data from 1128 newborn babies were analysed. Neonatal mortality was 29.8%. Most of these deaths (89%) occurred in the early neonatal period. The mean weight of newborns at the admission was 2,285.8 ± 878.7 and 43.6%. They were at a healthy weight. Four out of five newborns had been hospitalized for infection or prematurity. The place of delivery (HR weight <1000g = 5.45[3.81 -7.79]) and the principal diagnosis (HR asphyxiation= 1.64[1.30-2.08]) were prognostic factors for neonatal mortality. Conclusion: improving technical facilities for the etiological investigation of infections and an efficient management of low-weight newborns suffering from respiratory distress would considerably reduce in-hospital neonatal mortality in Bobo-Dioulasso.
Subject(s)
Hospitals, University , Infant Mortality , Humans , Burkina Faso/epidemiology , Cross-Sectional Studies , Infant, Newborn , Prognosis , Male , Female , Infant , Infant, Low Birth Weight , Infant, Premature , Birth Weight , Risk Factors , Asphyxia Neonatorum/mortality , Asphyxia Neonatorum/diagnosis , Delivery, Obstetric/statistics & numerical data , Retrospective StudiesABSTRACT
OBJECTIVES: The association between thrombocytopenia and parasite density or disease severity is described in numerous studies. In recent years, several studies described the protective role of platelets in directly killing Plasmodium parasites, mediated by platelet factor 4 (PF4) binding to Duffy antigen. This study aimed to evaluate the protective role of platelets in young children who are Duffy antigen-negative, such as those in sub-Saharan Africa. METHODS: A zero-inflated negative binomial model was used to relate platelet count and parasite density data collected in a longitudinal birth cohort. Platelet factors were measured by enzyme-linked immunosorbent assay in samples collected from malaria-infected children who participated in a cross-sectional study. RESULTS: We described that an increase of 10,000 platelets/µl was associated with a 2.76% reduction in parasite count. Increasing levels of PF4 and CXCL7 levels were also significantly associated with a reduction in parasite count. CONCLUSIONS: Platelets play a protective role in reducing parasite burden in Duffy-negative children, possibly mediated through activation of the innate immune system.
Subject(s)
Malaria, Falciparum , Malaria , Parasites , Child , Animals , Humans , Child, Preschool , Plasmodium falciparum , Platelet Count , Cross-Sectional Studies , Malaria, Falciparum/parasitologyABSTRACT
BACKGROUND: Seasonal vaccination with the RTS,S/AS01E vaccine combined with seasonal malaria chemoprevention (SMC) prevented malaria in young children more effectively than either intervention given alone over a 3 year period. The objective of this study was to establish whether the added protection provided by the combination could be sustained for a further 2 years. METHODS: This was a double-blind, individually randomised, controlled, non-inferiority and superiority, phase 3 trial done at two sites: the Bougouni district and neighbouring areas in Mali and Houndé district, Burkina Faso. Children who had been enrolled in the initial 3-year trial when aged 5-17 months were initially randomly assigned individually to receive SMC with sulphadoxine-pyrimethamine and amodiaquine plus control vaccines, RTS,S/AS01E plus placebo SMC, or SMC plus RTS,S/AS01E. They continued to receive the same interventions until the age of 5 years. The primary trial endpoint was the incidence of clinical malaria over the 5-year trial period in both the modified intention-to-treat and per-protocol populations. Over the 5-year period, non-inferiority was defined as a 20% increase in clinical malaria in the RTS,S/AS01E-alone group compared with the SMC alone group. Superiority was defined as a 12% difference in the incidence of clinical malaria between the combined and single intervention groups. The study is registered with ClinicalTrials.gov, NCT04319380, and is complete. FINDINGS: In April, 2020, of 6861 children originally recruited, 5098 (94%) of the 5433 children who completed the initial 3-year follow-up were re-enrolled in the extension study. Over 5 years, the incidence of clinical malaria per 1000 person-years at risk was 313 in the SMC alone group, 320 in the RTS,S/AS01E-alone group, and 133 in the combined group. The combination of RTS,S/AS01E and SMC was superior to SMC (protective efficacy 57·7%, 95% CI 53·3 to 61·7) and to RTS,S/AS01E (protective efficacy 59·0%, 54·7 to 62·8) in preventing clinical malaria. RTS,S/AS01E was non-inferior to SMC (hazard ratio 1·03 [95% CI 0·95 to 1·12]). The protective efficacy of the combination versus SMC over the 5-year period of the study was very similar to that seen in the first 3 years with the protective efficacy of the combination versus SMC being 57·7% (53·3 to 61·7) and versus RTS/AS01E-alone being 59·0% (54·7 to 62·8). The comparable figures for the first 3 years of the study were 62·8% (58·4 to 66·8) and 59·6% (54·7 to 64·0%), respectively. Hospital admissions for WHO-defined severe malaria were reduced by 66·8% (95% CI 40·3 to 81·5), for malarial anaemia by 65·9% (34·1 to 82·4), for blood transfusion by 68·1% (32·6 to 84·9), for all-cause deaths by 44·5% (2·8 to 68·3), for deaths excluding external causes or surgery by 41·1% (-9·2 to 68·3), and for deaths from malaria by 66·8% (-2·7 to 89·3) in the combined group compared with the SMC alone group. No safety signals were detected. INTERPRETATION: Substantial protection against malaria was sustained over 5 years by combining seasonal malaria vaccination with seasonal chemoprevention, offering a potential new approach to malaria control in areas with seasonal malaria transmission. FUNDING: UK Joint Global Health Trials and PATH's Malaria Vaccine Initiative (through a grant from the Bill & Melinda Gates Foundation). TRANSLATION: For the French translation of the abstract see Supplementary Materials section.
Subject(s)
Malaria Vaccines , Malaria, Falciparum , Malaria , Child , Humans , Infant , Child, Preschool , Mali/epidemiology , Burkina Faso/epidemiology , Seasons , Malaria/epidemiology , Malaria/prevention & control , Vaccination , Chemoprevention , Malaria, Falciparum/epidemiology , Malaria, Falciparum/prevention & controlABSTRACT
BACKGROUND: Plasmodium falciparum parasitaemia during pregnancy causes maternal, fetal, and infant mortality. Poor pregnancy outcomes are related to blood-stage parasite sequestration and the ensuing inflammatory response in the placenta, which decreases over successive pregnancies. A radiation-attenuated, non-replicating, whole-organism vaccine based on P falciparum sporozoites (PfSPZ Vaccine) has shown efficacy at preventing infection in African adults. Here, we aimed to examine vaccine safety and efficacy of the PfSPZ Vaccine in adults and women who anticipated conception. METHODS: Two randomised, double-blind, placebo-controlled trials (phase 1 MLSPZV3 and phase 2 MLSPZV4) were conducted at a clinical research centre in Mali. MLSPZV3 included adults aged 18-35 years and MLSPZV4 included non-pregnant women aged 18-38 years who anticipated conception within a year of enrolment. In MLSPZV3, participants were stratified by village and randomly assigned (2:1) using block randomisation to receive three doses of 9â×â105 PfSPZ Vaccine or saline placebo at weeks 0, 1, and 4 (4-week schedule) or at weeks 0, 8, and 16 (16-week schedule) and a booster dose around 1 year later. In MLSPZV4, women received presumptive artemether-lumefantrine twice per day for 3 days 2 weeks before dose one and were randomly assigned (1:1:1) using block randomisation to receive three doses of 9â×â105 or 1·8â×â106 PfSPZ Vaccine or saline placebo all administered at weeks 0, 1, and 4 (4-week schedule). Participants in both studies received artemether-lumefantrine 2 weeks before dose three and additionally 2 weeks before dose four (booster dose) in MLSPZV3. Investigators and participants were masked to group assignment. The primary outcome, assessed in the as-treated population, was PfSPZ Vaccine safety and tolerability within 7 days after each dose. The secondary outcome, assessed in the modified intention-to-treat population, was vaccine efficacy against P falciparum parasitaemia (defined as the time-to-first positive blood smear) from dose three until the end of transmission season. In exploratory analyses, MLSPZV4 evaluated incidence of maternal obstetric and neonatal outcomes as safety outcomes, and vaccine efficacy against P falciparum parasitaemia during pregnancy (defined as time-to-first positive blood smear post-conception). In MLSPZV4, women were followed at least once a month with human chorionic gonadotropin testing, and those who became pregnant received standard of care (including intermittent presumptive sulfadoxine-pyrimethamine antimalarial drugs after the first trimester) during routine antenatal visits. These studies are registered with ClinicalTrials.gov, NCT03510481 and NCT03989102. FINDINGS: Participants were enrolled for vaccination during the onset of malaria seasons for two sequential studies conducted from 2018 to 2019 for MLSPZV3 and from 2019 to 2021 for MLSPZV4, with follow-up during malaria seasons across 2 years. In MLSPZV3, 478 adults were assessed for eligibility, of whom 220 were enrolled between May 30 and June 12, 2018, and then between Aug 13 and Aug 18, 2018, and 210 received dose one. 66 (96%) of 69 participants who received the 16-week schedule and 68 (97%) of 70 who received the 4-week schedule of the 9â×â105 PfSPZ Vaccine and 70 (99%) of 71 who received saline completed all three doses in year 1. In MLSPZV4, 407 women were assessed for eligibility, of whom 324 were enrolled from July 3 to July 27, 2019, and 320 received dose one of presumptive artemether-lumefantrine. 300 women were randomly assigned with 100 per group (PfSPZ Vaccine 9â×â105, 1·8â×â106, or saline) receiving dose one. First trimester miscarriages were the most commonly reported serious adverse event but occurred at a similar rate across study groups (eight [15%] of 54 with 9â×â105 PfSPZ Vaccine, 12 [21%] of 58 with 1·8â×â106 PfSPZ Vaccine, and five [12%] of 43 with saline). One unrelated maternal death occurred 425 days after the last vaccine dose in the 1·8â×â106 PfSPZ Vaccine group due to peritonitis shortly after childbirth. Most related adverse events reported in MLSPZV3 and MLSPZV4 were mild (grade 1) and frequency of adverse events in the PfSPZ Vaccine groups did not differ from that in the saline group. Two unrelated serious adverse events occurred in MLSPZV3 (one participant had appendicitis in the 9â×â105 PfSPZ Vaccine group and the other in the saline group died due to a road traffic accident). In MLSPZV3, the 9â×â105 PfSPZ Vaccine did not show vaccine efficacy against parasitaemia with the 4-week (27% [95% CI -18 to 55] in year 1 and 42% [-5 to 68] in year 2) and 16-week schedules (16% [-34 to 48] in year 1 and -14% [-95 to 33] in year 2); efficacies were similar or worse against clinical malaria compared with saline. In MLSPZV4, the PfSPZ Vaccine showed significant efficacy against parasitaemia at doses 9â×â105 (41% [15 to 59]; p=0·0069 in year 1 and 61% [36 to 77]; p=0·0011 in year 2) and 1·8â×â106 (54% [34 to 69]; p<0·0001 in year 1 and 45% [13 to 65]; p=0·029 in year 2); and against clinical malaria at doses 9â×â105 (47% [20 to 65]; p=0·0045 in year 1 and 56% [22 to 75]; p=0·0081 in year 2) and 1·8â×â106 (48% [22 to 65]; p=0·0013 in year 1 and 40% [2 to 64]; p=0·069 in year 2). Vaccine efficacy against post-conception P falciparum parasitaemia during first pregnancies that arose in the 2-year follow-up was 57% (14 to 78; p=0·017) in the 9 × 105 PfSPZ Vaccine group versus 49% (3 to 73; p=0·042) in the 1·8â×â106 PfSPZ Vaccine group. Among 55 women who became pregnant within 24 weeks after dose three, vaccine efficacy against parasitaemia was 65% (23 to 84; p=0·0088) with the 9â×â105 PfSPZ Vaccine and 86% (64 to 94; p<0·0001) with the 1·8â×â106 PfSPZ Vaccine. When combined in a post-hoc analysis, women in the PfSPZ Vaccine groups had a non-significantly reduced time-to-first pregnancy after dose one compared with those in the saline group (log-rank test p=0·056). Exploratory maternal obstetric and neonatal outcomes did not differ significantly between vaccine groups and saline. INTERPRETATION: PfSPZ Vaccine was safe and well tolerated in adults in Mali. The 9â×â105 and 1·8â×â106 doses of PfSPZ Vaccine administered as per the 4-week schedule, which incorporated presumptive antimalarial treatment before the first vaccine dose, showed significant efficacy against P falciparum parasitaemia and clinical malaria for two malaria transmission seasons in women of childbearing age and against pregnancy malaria. PfSPZ Vaccine without presumptive antimalarial treatment before the first vaccine dose did not show efficacy. FUNDING: National Institute of Allergy and Infectious Diseases, National Institutes of Health, and Sanaria.
ABSTRACT
BACKGROUND: Seasonal vaccination with the RTS,S/AS01E malaria vaccine given alongside seasonal malaria chemoprevention (SMC) substantially reduces malaria in young children. The WHO has recommended the use of RTS,S/AS01E, including seasonal vaccination, in areas with seasonal malaria transmission. This study aimed to identify potential strategies to deliver RTS,S/AS01E, and assess the considerations and recommendations for delivery of seasonal malaria vaccination in Mali, a country with highly seasonal malaria. METHODS: Potential delivery strategies for RTS,S/AS01E in areas with seasonal malaria were identified through a series of high level discussions with the RTS,S/AS01E plus SMC trial investigators, international and national immunisation and malaria experts, and through the development of a theory of change. These were explored through qualitative in-depth interviews with 108 participants, including national-level, regional-level and district-level malaria and immunisation programme managers, health workers, caregivers of children under 5 years of age, and community stakeholders. A national-level workshop was held to confirm the qualitative findings and work towards consensus on an appropriate strategy. RESULTS: Four delivery strategies were identified: age-based vaccination delivered via the Essential Programme on Immunisation (EPI); seasonal vaccination via EPI mass vaccination campaigns (MVCs); a combination of age-based priming vaccination doses delivered via the EPI clinics and seasonal booster doses delivered via MVCs; and a combination of age-based priming vaccination doses and seasonal booster doses, all delivered via the EPI clinics, which was the preferred strategy for delivery of RTS,S/AS01E in Mali identified during the national workshop. Participants recommended that supportive interventions, including communications and mobilisation, would be needed for this strategy to achieve required coverage. CONCLUSIONS: Four delivery strategies were identified for administration of RTS,S/AS01E alongside SMC in countries with seasonal malaria transmission. Components of these delivery strategies were defined as the vaccination schedule, and the delivery system(s) plus the supportive interventions needed for the strategies to be effective. Further implementation research and evaluation is needed to explore how, where, when and what effective coverage is achievable via these new strategies and their supportive interventions.
Subject(s)
Malaria Vaccines , Malaria, Falciparum , Malaria , Child , Humans , Child, Preschool , Malaria Vaccines/therapeutic use , Malaria, Falciparum/prevention & control , Seasons , Malaria/prevention & control , VaccinationABSTRACT
The aim of this study was to analyze the spatio-temporal distribution and determinants of the 2017 dengue epidemic in Burkina Faso. A principal component analysis of meteorological and environmental factors was performed to reduce dimensions and avoid collinearities. An initial generalized additive model assessed the impact of the components derived from this analysis on dengue incidence. Dengue incidence increased mainly with relative humidity, precipitation, normalized difference vegetation index and minimum temperature with an 8-week lag. A Kulldoff Satscan scan was used to identify high-risk dengue clusters, and a second generalized additive model assessed the risk of a health area being at high risk according to land-use factors. The spatio-temporal distribution of dengue fever was heterogeneous and strongly correlated with meteorological factors. The rural communes of Sabaa and Koubri were the areas most at risk. This study provides useful information for planning targeted dengue control strategies in Burkina Faso.
ABSTRACT
BACKGROUND: The WHO recommends use of the RTS,S/AS01E (RTS,S) malaria vaccine for young children living in areas of moderate to high Plasmodium falciparum malaria transmission and suggests countries consider seasonal vaccination in areas with highly seasonal malaria. Seasonal vaccination is uncommon and may require adaptations with potential cost consequences. This study prospectively estimates cost of seasonal malaria vaccine delivery in Mali and Burkina Faso. METHODS: Three scenarios for seasonal vaccine delivery are costed (1) mass campaign only, (2) routine Expanded Programme on Immunisation (EPI) and (3) mixed delivery (mass campaign and routine EPI)), from the government's perspective. Resource use data are informed by previous new vaccine introductions, supplemented with primary data from a sample of health facilities and administrative units. FINDINGS: At an assumed vaccine price of US $5 per dose, the economic cost per dose administered ranges between $7.73 and $8.68 (mass campaign), $7.04 and $7.38 (routine EPI) and $7.26 and $7.93 (mixed delivery). Excluding commodities, the cost ranges between $1.17 and $2.12 (mass campaign), $0.48 and $0.82 (routine EPI) and $0.70 and $1.37 (mixed delivery). The financial non-commodity cost per dose administered ranges between $0.99 and $1.99 (mass campaign), $0.39 and $0.76 (routine EPI) and $0.58 and $1.28 (mixed delivery). Excluding commodity costs, service delivery is the main cost driver under the mass campaign scenario, accounting for 36% to 55% of the financial cost. Service delivery accounts for 2%-8% and 12%-23% of the total financial cost under routine EPI and mixed delivery scenarios, respectively. CONCLUSION: Vaccine delivery using the mass campaign approach is most costly followed by mixed delivery and routine EPI delivery approaches, in both countries. Our cost estimates provide useful insights for decisions regarding delivery approaches, as countries plan the malaria vaccine rollout.
Subject(s)
Malaria Vaccines , Malaria , Child , Humans , Child, Preschool , Burkina Faso , Mali , Seasons , Malaria/prevention & controlABSTRACT
Dengue is now a major health concern in sub-Saharan Africa. Understanding the influence of local meteorological factors on the incidence of dengue is an important element for better prediction and control of this disease. This study aims to assess the impact of meteorological factors on dengue transmission in the central region of Burkina Faso. We analyzed the lagged effects of meteorological factors on the weekly incidence of dengue from 2017 to 2019 in the central region of Burkina Faso using a General Additive Model. The results show that maximum and minimum temperature, relative humidity, and wind speed have a significant non-linear effect on dengue cases in the region with 83% of case variance explained. The optimal temperature that increases dengue cases was 27°C to 32°C for the maximum temperature and 18°C to 20°C for the minimum temperature with a decrease beyond that. The maximum temperature shifted by six weeks had the best correlation with dengue incidence. The estimated number of dengue cases increases as the maximum relative humidity increases from 15 to 45% and then from 60 to 70%. In general, an increase in daily wind speed is estimated to decrease the number of daily dengue cases. The relationship between rainfall and dengue cases was not significant. This study provides local information about the effect of meteorological factors on dengue that should help improve predictive models of dengue cases in Burkina Faso and contribute to the control of this disease.