@article{Yameogo2021-bb,

title = {Effect of seasonal malaria chemoprevention plus azithromycin on  Plasmodium falciparum transmission: gametocyte infectivity and  mosquito fitness},

author = {Koudraogo Bienvenue Yam\'{e}ogo and Rakiswend\'{e} Serge Yerbanga and Seydou Bienvenu Ouattara and Franck A Yao and Thierry Lef`evre and Issaka Zongo and Frederic Niki`ema and Yves Daniel Compaor\'{e} and Halidou Tinto and Daniel Chandramohan and Brian Greenwood and Adrien M G Belem and Anna Cohuet and Jean Bosco Ou\'{e}draogo},

doi = {10.1186/s12936-021-03855-3},

issn = {1475-2875},

year  = {2021},

date = {2021-07-27},

urldate = {2021-07-27},

journal = {Malar. J.},

volume = {20},

number = {1},

pages = {326},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children  during the malaria transmission period. Whether the addition of azithromycin (AZ) to  SMC could potentiate the benefit of the intervention was tested through a  double-blind, randomized, placebo-controlled trial. The effect of SMC and the  addition of AZ, on malaria transmission and on the life history traits of Anopheles  gambiae mosquitoes have been investigated. METHODS: The study included 438 children  randomly selected from among participants in the SMC + AZ trial and 198 children  from the same area who did not receive chemoprevention. For each participant in the  SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the  presence of malaria sexual and asexual stages and provided as a blood meal to An.  gambiae females using a direct membrane-feeding assay. RESULTS: The SMC treatment,  with or without AZ, significantly reduced the prevalence of asexual Plasmodium  falciparum (LRT X(2)(2) = 69, P \< 0.0001) and the gametocyte prevalence (LRT  X(2)(2) = 54, P \< 0.0001). In addition, the proportion of infectious feeds (LRT  X(2)(2) = 61, P \< 0.0001) and the prevalence of oocysts among exposed mosquitoes  (LRT X(2)(2) = 22.8, P \< 0.001) was reduced when mosquitoes were fed on blood from  treated children compared to untreated controls. The addition of AZ to SPAQ was  associated with an increased proportion of infectious feeds (LRT X(2)(1) = 5.2,  P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There  was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to  mosquitoes fed with blood from control children (LRTX(2)(2) = 330, P \< 0.0001).  CONCLUSION: This study demonstrates that SMC may contribute to a reduction in human  to mosquito transmission of P. falciparum, and the reduced mosquito longevity  observed for females fed on treated blood may increase the benefit of this  intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to  enhance the infectivity of gametocytes providing further evidence that this  combination is not an appropriate intervention.},

note = {© 2021. The Author(s).

PMID: 34315475 

PMCID: PMC8314489},

keywords = {Amodiaquine/administration \& dosage, Animals, Antimalarials/administration \& dosage, Chemoprevention, Child, Culicidae/physiology, Drug Combinations, Falciparum/prevention \& control/transmission, Gametocytes, Genetic Fitness, Humans, Malaria, Plasmodium falciparum/physiology, Preschool, Pyrimethamine/administration \& dosage, seasonal malaria chemoprevention, Seasons, Sulfadoxine/administration \& dosage, Transmission},

pubstate = {published},

tppubtype = {article}

}

@article{Post2021-oo,

title = {Altered ex-vivo cytokine responses in children with asymptomatic  Plasmodium falciparum infection in Burkina Faso: An additional  argument to treat asymptomatic malaria?},

author = {Annelies Post and Berenger Kabor\'{e} and Mike Berendsen and Salou Diallo and Ousmane Traore and Rob J W Arts and Mihai G Netea and Leo A B Joosten and Halidou Tinto and Jan Jacobs and Quirijn Mast and Andr\'{e} Ven},

doi = {10.3389/fimmu.2021.614817},

issn = {1664-3224},

year  = {2021},

date = {2021-06-09},

urldate = {2021-06-09},

journal = {Front. Immunol.},

volume = {12},

pages = {614817},

publisher = {Frontiers Media SA},

abstract = {Introduction: Patients with clinical malaria have an increased 

 risk for bacterial bloodstream infections. We hypothesized that 

 asymptomatic malaria parasitemia increases susceptibility for 

 bacterial infections through an effect on the innate immune 

 system. We measured circulating cytokine levels and ex-vivo 

 cytokine production capacity in asymptomatic malaria and 

 compared with controls. Methods: Data were collected from 

 asymptomatic participants \<5 years old with and without positive 

 malaria microscopy, as well as from hospitalized patients \<5 

 years old with clinical malaria, bacteremia, or 

 malaria/bacteremia co-infections in a malaria endemic region of 

 Burkina Faso. Circulating cytokines (TNF-$alpha$, IFN-$gamma$, 

 IL-6, IL-10) were measured using multiplex assays. Whole blood 

 from asymptomatic participants with and without positive malaria 

 microscopy were ex-vivo stimulated with S. aureus, E. coli LPS 

 and Salmonella Typhimurium; cytokine concentrations 

 (TNF-$alpha$, IFN-$gamma$, IL-1$beta$, IL-6, IL-10) were 

 measured on supernatants using ELISA. Results: Included were children with clinical malaria (n=118), bacteremia (n=22), malaria and bacteremia co-infection (n=9), asymptomatic malaria (n=125), and asymptomatic controls (n=237). Children with either 

 clinical or asymptomatic malaria had higher plasma cytokine 

 concentrations than controls. Cytokine concentrations correlated 

 positively with malaria parasite density with the strongest correlation for IL-10 in both asymptomatic (r=0.63) and clinical malaria (r=0.53). Patients with bacteremia had lower circulating 

 IL-10, TNF-$alpha$ and IFN-$gamma$ and higher IL-6 

 concentrations, compared to clinical malaria. Ex-vivo whole 

 blood cytokine production to LPS and S. aureus was significantly 

 lower in asymptomatic malaria compared to controls. Whole blood 

 IFN-$gamma$ and IL-10 production in response to Salmonella was 

 also lower in asymptomatic malaria. Interpretation: In children 

 with asymptomatic malaria, cytokine responses upon ex-vivo 

 bacterial stimulation are downregulated. Further studies are 

 needed to explore if the suggested impaired innate immune 

 response to bacterial pathogens also translates into impaired 

 control of pathogens such as Salmonella spp.},

note = {Copyright © 2021 Post, Kabor\'{e}, Berendsen, Diallo, Traore, Arts, Netea, Joosten, Tinto, Jacobs, de Mast and van der Ven.

PMID: 34177883 

PMCID: PMC8220162},

keywords = {Asymptomatic Diseases, asymptomatic malaria, bacteraemia, Bacteremia, bloodstream infection, Burkina Faso/epidemiology, Cells, Child, Cultured, Cytokines/metabolism, Endemic Diseases, Female, Humans, Infant, iNTS, Lipopolysaccharides/immunology, Malaria/epidemiology/immunology, Male, Parasite Load, Plasmodium falciparum/physiology, Preschool, Salmonella},

pubstate = {published},

tppubtype = {article}

}

@article{Natama2021-ft,

title = {Genetic variation in the immune system and malaria  susceptibility in infants: a nested case-control study in  Nanoro, Burkina Faso},

author = {Hamatandi Magloire Natama and Eduard Rovira-Vallbona and Meryam Krit and Pieter Guetens and Hermann Sorgho and M Athanase Som\'{e} and Maminata Traor\'{e}-Coulibaly and Innocent Val\'{e}a and Petra F Mens and Henk D F H Schallig and Dirk Berkvens and Luc Kestens and Halidou Tinto and Anna Rosanas-Urgell},

doi = {10.1186/s12936-021-03628-y},

issn = {1475-2875},

year  = {2021},

date = {2021-02-16},

urldate = {2021-02-01},

journal = {Malar. J.},

volume = {20},

number = {1},

pages = {94},

publisher = {Springer Science and Business Media LLC},

abstract = {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 

 inflammatory mediators.},

note = {PMID: 33593344 

PMCID: PMC7885350},

keywords = {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},

pubstate = {published},

tppubtype = {article}

}

@article{Sondo2021-at,

title = {Plasmodium falciparum gametocyte carriage in symptomatic  patients shows significant association with genetically diverse  infections, anaemia, and asexual stage density},

author = {Paul Sondo and Biebo Bihoun and Marc Christian Tahita and Karim Derra and Toussaint Rouamba and Seydou Nakanabo Diallo and Adama Kazienga and Hamidou Ilboudo and Innocent Valea and Zekiba Tarnagda and Hermann Sorgho and Thierry Lef`evre and Halidou Tinto},

doi = {10.1186/s12936-020-03559-0},

issn = {1475-2875},

year  = {2021},

date = {2021-01-07},

urldate = {2021-01-01},

journal = {Malar. J.},

volume = {20},

number = {1},

pages = {31},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Multi-genotype malaria infections are frequent in 

 endemic area, and people commonly harbour several genetically 

 distinct Plasmodium falciparum variants. The influence of 

 genetic multiplicity and whether some specific genetic variants 

 are more or less likely to invest into gametocyte production is 

 not clearly understood. This study explored host and 

 parasite-related risk factors for gametocyte carriage, and the 

 extent to which some specific P. falciparum genetic variants are 

 associated with gametocyte carriage. METHODS: Gametocytes and 

 asexual forms were detected by light microscopy on thick smears 

 collected between 2010 and 2012 in Nanoro, Burkina Faso. 

 Merozoite surface protein 1 and 2 were genotyped by nested PCR 

 on clinical samples. Associations between gametocyte carriage 

 and factors, including multiplicity of infection, parasite 

 density, patient age, gender, haemoglobin (Hb) level, and body 

 temperature were assessed. The relationship between the presence 

 of a particular msp1 and msp2 genetic variants and gametocyte 

 carriage was also explored. RESULTS: Of the 724 samples positive 

 to P. falciparum and successfully genotyped, gametocytes were 

 found in 48 samples (6.63%). There was no effect of patient 

 gender, age and body temperature on gametocyte carriage. 

 However, the probability of gametocyte carriage significantly 

 increased with increasing values of multiplicity of infection 

 (MOI). Furthermore, there was a negative association between 

 parasite density and gametocyte carriage. MOI decreased with 

 parasite density in gametocyte-negative patients, but increased 

 in gametocyte carriers. The probability of gametocyte carriage 

 decreased with Hb level. Finally, the genetic composition of the 

 infection influenced gametocyte carriage. In particular, the 

 presence of RO33 increased the odds of developing gametocytes by 

 2 while the other allelic families K1, MAD20, FC27, and 3D7 had 

 no significant impact on the occurrence of gametocytes in 

 infected patients. CONCLUSION: This study provides insight into 

 potential factors influencing gametocyte production in 

 symptomatic patients. The findings contribute to enhance 

 understanding of risk factors associated with gametocyte 

 carriage in humans. Trial registration NCT01232530.},

note = {PMID: 33413393 

PMCID: PMC7791700},

keywords = {Anemia/epidemiology/parasitology, Burkina Faso/epidemiology, Falciparum/epidemiology/parasitology, Gametocyte, Humans, Malaria, msp1, msp2, Multiplicity of infection, Plasmodium   falciparum, Plasmodium falciparum/physiology},

pubstate = {published},

tppubtype = {article}

}