WorldWide Antimalarial Resistance Network Falciparum Haematology Study Group
In: BMC medicine, vol. 20, iss. 1, no. 1, pp. 85, 2022, ISSN: 1741-7015.
BACKGROUND: Plasmodium falciparum malaria is associated with anaemia-related morbidity, attributable to host, parasite and drug factors. We quantified the haematological response following treatment of uncomplicated P. falciparum malaria to identify the factors associated with malarial anaemia. METHODS: Individual patient data from eligible antimalarial efficacy studies of uncomplicated P. falciparum malaria, available through the WorldWide Antimalarial Resistance Network data repository prior to August 2015, were pooled using standardised methodology. The haematological response over time was quantified using a multivariable linear mixed effects model with nonlinear terms for time, and the model was then used to estimate the mean haemoglobin at day of nadir and day 7. Multivariable logistic regression quantified risk factors for moderately severe anaemia (haemoglobin < 7 g/dL) at day 0, day 3 and day 7 as well as a fractional fall ≥ 25% at day 3 and day 7. RESULTS: A total of 70,226 patients, recruited into 200 studies between 1991 and 2013, were included in the analysis: 50,859 (72.4%) enrolled in Africa, 18,451 (26.3%) in Asia and 916 (1.3%) in South America. The median haemoglobin concentration at presentation was 9.9 g/dL (range 5.0-19.7 g/dL) in Africa, 11.6 g/dL (range 5.0-20.0 g/dL) in Asia and 12.3 g/dL (range 6.9-17.9 g/dL) in South America. Moderately severe anaemia (Hb < 7g/dl) was present in 8.4% (4284/50,859) of patients from Africa, 3.3% (606/18,451) from Asia and 0.1% (1/916) from South America. The nadir haemoglobin occurred on day 2 post treatment with a mean fall from baseline of 0.57 g/dL in Africa and 1.13 g/dL in Asia. Independent risk factors for moderately severe anaemia on day 7, in both Africa and Asia, included moderately severe anaemia at baseline (adjusted odds ratio (AOR) = 16.10 and AOR = 23.00, respectively), young age (age < 1 compared to ≥ 12 years AOR = 12.81 and AOR = 6.79, respectively), high parasitaemia (AOR = 1.78 and AOR = 1.58, respectively) and delayed parasite clearance (AOR = 2.44 and AOR = 2.59, respectively). In Asia, patients treated with an artemisinin-based regimen were at significantly greater risk of moderately severe anaemia on day 7 compared to those treated with a non-artemisinin-based regimen (AOR = 2.06 [95%CI 1.39-3.05], p < 0.001). CONCLUSIONS: In patients with uncomplicated P. falciparum malaria, the nadir haemoglobin occurs 2 days after starting treatment. Although artemisinin-based treatments increase the rate of parasite clearance, in Asia they are associated with a greater risk of anaemia during recovery.
Paul Sondo, Marc Christian Tahita, Hamidou Ilboudo, Toussaint Rouamba, Karim Derra, Gauthier Tougri, Florence Ouédraogo, Béatrice Marie Adélaïde Konseibo, Eli Roamba, Sabina Dahlström Otienoburu, Bérenger Kaboré, Kalynn Kennon, Kadija Ouédraogo, Wend-Timbe-Noma Arlette Raïssa Zongo, Fadima Yaya Bocoum, Kasia Stepniewska, Mehul Dhorda, Philippe J. Guérin, Halidou Tinto
Boosting the impact of seasonal malaria chemoprevention (SMC) through simultaneous screening and treatment of household members of children receiving SMC in Burkina Faso: a protocol for a randomized open label trial. (Journal Article)
In: Archives of Public Health, vol. 80, iss. 1, pp. 41, 2022.
BACKGROUND: Plasmodium falciparum malaria remains a major public health concern in sub-Sahara Africa. Seasonal malaria chemoprevention (SMC) with amodiaquine + sulfadoxine-pyrimethamine is one of the most important preventive interventions. Despite its implementation, the burden of malaria is still very high in children under five years old in Burkina Faso, suggesting that the expected impact of this promising strategy might not be attained. Development of innovative strategies to improve the efficacy of these existing malaria control measures is essential. In such context, we postulate that screening and treatment of malaria in household members of children receiving SMC could greatly improve the impact of SMC intervention and reduce malaria transmission in endemic settings. METHODS: This randomized superiority trial will be carried out in the Nanoro health district, Burkina Faso. The unit of randomisation will be the household and all eligible children from a household will be allocated to the same study group. Households with 3-59 months old children will be assigned to either (i) control group (SMC alone) or (ii) intervention (SMC+ screening of household members with standard Histidin Rich Protein Rapid Diagnostic Test (HRP2-RDT) and treatment if positive). The sample size will be 526 isolated households per arm, i.e., around 1052 children under SMC coverage and an expected 1315 household members. Included children will be followed-up for 24 months to fully cover two consecutive malaria transmission seasons and two SMC cycles. Children will be actively followed-up during the malaria transmission seasons while in the dry seasons the follow-up will be passive. CONCLUSION: The study will respond to a major public health concern by providing evidence of the efficacy of an innovative strategy to boost the impact of SMC intervention.
Paul Sondo, Biebo Bihoun, Bérenger Kabore, Marc Christian Tahita, Karim Derra, Toussaint Rouamba, Seydou Nakanabo Diallo, Adama Kazienga, Hamidou Ilboudo, Innocent Valea, Zekiba Tarnagda, Hermann Sorgho, Thierry Lefevre, Halidou Tinto
In: Pan Afr. Med. J., vol. 39, pp. 118, 2021, ISSN: 1937-8688, (Copyright: Paul Sondo et al. PMID: 34512854 PMCID: PMC8396377).
(Tags: Antimalarials/pharmacology, Burkina Faso, Drug Resistance, Falciparum/drug therapy/parasitology, GeneticRestriction Fragment Length, Genotype, Humans, Malaria, Membrane Transport Proteins/genetics, msp1, msp2, Multidrug Resistance-Associated Proteins/genetics, Mutation, Pfcrt, Pfmdr1, Plasmodium falciparum, Plasmodium falciparum/drug effects/genetics/isolation & purification, Polymerase Chain Reaction, Polymorphism, Protozoan Proteins/genetics)| | | |
Introduction: from a genetic point of view P. falciparumis
extremely polymorphic. There is a variety of parasite strains
infesting individuals living in malaria endemic areas. The
purpose of this study is to investigate the relationship between
polymorphisms in Plasmodium falciparum parasites and Pfcrt and
Pfmdr1 gene mutations in Nanoro area, Burkina Faso. Methods:
blood samples from plasmodium carriers residing in the Nanoro
Health District were genotyped using nested PCR. Parasite gene
mutations associated with resistance to antimalarial drugs were
detected by PCR-RFLP. Results: samples of 672 patients were
successfully genotyped. No msp1and msp2allelic families
exhibited an increase in developing mutations in resistance
genes. However, mutant strains of these genes were present at
greater levels in monoclonal infections than in multi-clonal
infections. Conclusion: this study provides an overview of the
relationship between polymorphisms in Plasmodium falciparum
parasites and mutations in resistance genes. These data will
undoubtedly contribute to improving knowledge of the parasite´s
biology and its mechanisms of resistance to antimalarial drugs.
Hamatandi Magloire Natama, Eduard Rovira-Vallbona, Meryam Krit, Pieter Guetens, Hermann Sorgho, M Athanase Somé, Maminata Traoré-Coulibaly, Innocent Valéa, Petra F Mens, Henk D F H Schallig, Dirk Berkvens, Luc Kestens, Halidou Tinto, Anna Rosanas-Urgell
In: Malar. J., vol. 20, no. 1, pp. 94, 2021, ISSN: 1475-2875, (PMID: 33593344 PMCID: PMC7885350).
(Tags: Burkina Faso, Case-Control Studies, Cytokines, Falciparum/parasitology, Female, Genetic Predisposition to Disease/genetics, Humans, Immunity, Immunogenetic variants, Infant, Innate immunity, Innate/genetics, Malaria, Male, Plasmodium falciparum, Plasmodium falciparum/physiology)| | | |
BACKGROUND: Genetic polymorphisms in the human immune system
modulate susceptibility to malaria. However, there is a paucity
of data on the contribution of immunogenetic variants to malaria
susceptibility in infants, who present differential biological
features related to the immaturity of their adaptive immune
system, the protective effect of maternal antibodies and fetal
haemoglobin. This study investigated the association between
genetic variation in innate immune response genes and malaria
susceptibility during the first year of life in 656 infants from
a birth cohort survey performed in Nanoro, Burkina Faso.
METHODS: Seventeen single nucleotide polymorphisms (SNPs) in 11
genes of the immune system previously associated with different
malaria phenotypes were genotyped using TaqMan allelic
hybridization assays in a Fluidigm platform. Plasmodium
falciparum infection and clinical disease were documented by
active and passive case detection. Case-control association
analyses for both alleles and genotypes were carried out using
univariate and multivariate logistic regression. For cytokines
showing significant SNP associations in multivariate analyses,
cord blood supernatant concentrations were measured by
quantitative suspension array technology (Luminex). RESULTS:
Genetic variants in IL-1$beta$ (rs1143634) and
Fc$gamma$RIIA/CD32 (rs1801274)-both in allelic, dominant and
co-dominant models-were significantly associated with protection
from both P. falciparum infection and clinical malaria.
Furthermore, heterozygote individuals with rs1801274 SNP in
Fc$gamma$RIIA/CD32 showed higher IL-1RA levels compared to wild-type homozygotes (P = 0.024), a cytokine whose production
is promoted by the binding of IgG immune complexes to Fc$gamma$
receptors on effector immune cells. CONCLUSIONS: These findings
indicate that genetic polymorphisms in genes driving innate
immune responses are associated to malaria susceptibility during
the first year of life, possibly by modulating production of
Adama Gansané, Leah F Moriarty, Didier Ménard, Isidore Yerbanga, Esperance Ouedraogo, Paul Sondo, Rene Kinda, Casimir Tarama, Edwige Soulama, Madou Tapsoba, David Kangoye, Cheick Said Compaore, Ousmane Badolo, Blami Dao, Samuel Tchwenko, Halidou Tinto, Innocent Valea
In: Malar. J., vol. 20, no. 1, pp. 48, 2021, ISSN: 1475-2875.
(Tags: Antimalarial, Antimalarials/pharmacology, Artemether, Artemether-lumefantrine, Artemisinins/pharmacology, Burkina Faso, Child, Dihydroartemisinin-piperaquine, Drug Resistance, Efficacy, Falciparum/drug therapy, Female, Lumefantrine Drug Combination/pharmacology, Malaria, Male, Plasmodium falciparum, Preschool, Quinolines/pharmacology)| | | |
BACKGROUND: The World Health Organization recommends regularly
assessing the efficacy of artemisinin-based combination therapy
(ACT), which is a critical tool in the fight against malaria.
This study evaluated the efficacy of two artemisinin-based
combinations recommended to treat uncomplicated Plasmodium
falciparum malaria in Burkina Faso in three sites: Niangoloko,
Nanoro, and Gourcy. METHODS: This was a two-arm randomized
control trial of the efficacy of artemether-lumefantrine (AL)
and dihydroartemisinin-piperaquine (DP). Children aged 6-59
months old were monitored for 42 days. The primary outcomes of
the study were uncorrected and PCR-corrected efficacies to day
28 for AL and 42 for DP. Molecular markers of resistance to
artemisinin derivatives and partner drugs were also analysed.
RESULTS: Of 720 children enrolled, 672 reached study endpoints
at day 28, 333 in the AL arm and 339 in the DP arm.
PCR-corrected 28-day per protocol efficacy in the AL arm was
74% (64-83%) in Nanoro, 76% (66-83%) in Gourcy, and 92%
(84-96%) in Niangoloko. The PCR-corrected 42-day per protocol
efficacy in the DP arm was 84% (75-89%) in Gourcy, 89%
(81-94%) in Nanoro, and 97% (92-99%) in Niangoloko. No Pfk13
mutation previously associated with artemisinin-resistance was
observed. No statistically significant association was found
between treatment outcome and presence of the 86Y mutation in
the Pfmdr1 gene. There was also no association observed between
treatment outcome and Pfpm2 or Pfmdr1 copy number variation.
CONCLUSION: The results of this study indicate evidence of
inadequate efficacy of AL at day 28 and DP at day 42 in the same
two sites. A change of first-line ACT may be warranted in
Burkina Faso. Trial Registry Pan African Clinical Trial Registry
Identifier: PACTR201708002499311. Date of registration: 8/3/2017
Paul Sondo, Karim Derra, Toussaint Rouamba, Seydou Nakanabo Diallo, Paul Taconet, Adama Kazienga, Hamidou Ilboudo, Marc Christian Tahita, Innocent Valéa, Hermann Sorgho, Thierry Lefèvre, Halidou Tinto
Determinants of Plasmodium falciparum multiplicity of infection and genetic diversity in Burkina Faso. (Journal Article)
In: Parasites & vectors, vol. 13, iss. 1, pp. 427, 2020.
(Tags: Age Factors, Antigens, Burkina Faso/epidemiology, Falciparum/epidemiology/parasitology, Genetic Variation, Genotype, Humans, Incidence, Malaria, Merozoite Surface Protein 1/genetics, msp1, msp2, Multiplicity of infection, Parasite Load, Plasmodium falciparum, Plasmodium falciparum/*genetics, Protozoan Proteins/genetics, Protozoan/genetics, Seasons)| |
BACKGROUND: Investigating malaria transmission dynamics is essential to inform policy decision making. Whether multiplicity of infection (MOI) dynamic from individual infections could be a reliable malaria metric in high transmission settings with marked variation in seasons of malaria transmission has been poorly assessed. This study aimed at investigating factors driving Plasmodium falciparum MOI and genetic diversity in a hyperendemic area of Burkina Faso. METHODS: Blood samples collected from a pharmacovigilance trial were used for polymerase chain reaction genotyping of the merozoite surface proteins 1 and 2. MOI was defined as the number of distinct parasite genotypes co-existing within a particular infection. Monthly rainfall data were obtained from satellite data of the Global Precipitation Measurement Database while monthly malaria incidence aggregated data were extracted from District Health Information Software 2 medical data of the Center-West health regional direction. RESULTS: In the study area, infected people harboured an average of 2.732 (± 0.056) different parasite genotypes. A significant correlation between the monthly MOI and the monthly malaria incidence was observed, suggesting that MOI could be a good predictor of transmission intensity. A strong effect of season on MOI was observed, with infected patients harbouring higher number of parasite genotypes during the rainy season as compared to the dry season. There was a negative relationship between MOI and host age. In addition, MOI decreased with increasing parasite densities, suggesting that there was a within-host competition among co-infecting genetically distinct P. falciparum variants. Each allelic family of the msp1 and msp2 genes was present all year round with no significant monthly fluctuation. CONCLUSIONS: In high malaria endemic settings with marked variation in seasons of malaria transmission, MOI represents an appropriate malaria metric which provides useful information about the longitudinal changes in malaria transmission in a given area. Besides transmission season, patient age and parasite density are important factors to consider for better understanding of variations in MOI. All allelic families of msp1 and msp2 genes were found in both dry and rainy season. The approach offers the opportunity of translating genotyping data into relevant epidemiological information for malaria control.
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