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  • Valentina D Mangano
Valentina D Mangano

Valentina D Mangano
Università di Pisa | UNIPI · Department of Translational Research on New Technologies in Medicine and Surgery

PhD in Immunology

About

56
Publications
7,846
Reads
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2,237
Citations
Citations since 2016
17 Research Items
1567 Citations
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2016201720182019202020212022050100150200250
Introduction
My research activity lies in the field of malaria epidemiology. I do investigate the genetic and immunological basis of the different susceptibility to malaria shown by West-African ethnic groups. I also collaborate on projects investigating host factors in malaria transmission to mosquitoes, and the use of A. gambiae salivary antigens as markers of exposure to malaria vectors. I am involved in the design of a surveillance system of severe malaria among pediatric patients in Burkina Faso.
Additional affiliations
April 2016 - present
Università di Pisa
Position
  • Researcher
April 2016 - present
Università di Pisa
Position
  • Lecturer
Description
  • Module of Parasitology, Course of Sistematic Patology II, Degree in Medicine and Surgery, School of Medicine; Module of Immunology, Course of General Patology I, Degree in Medicine and Surgery, School of Medicine
September 2013 - present
Sapienza University of Rome
Position
  • Lecturer
Description
  • Module of Epidemiology, Course of Quality of Biomedical Services, Degree in Biomedical Technician, Faculty of Medicine
Education
December 2010 - December 2014
October 2008 - October 2010
February 2005 - December 2008
Stockholm University
Field of study
  • Immunology

Publications

Publications (56)
Article
Full-text available
Although HbS and HbC are well known to protect against severe Plasmodium falciparum malaria, conclusive evidence on their role against infection has not yet been obtained. Here we show, in two populations from Burkina Faso (2007-08), that HbS is associated with a 70% reduction of harbouring P. falciparum parasitaemia at the heterozygous state [AS v...
Article
Full-text available
Background Chagas disease (CD) is caused by the protozoan parasite Trypanosoma cruzi and is transmitted by blood‐sucking triatomine insects in endemic areas of Latin America. Transmission can also occur via blood transfusion and is a major cause of CD in non‐endemic areas. Objectives The aim of the study was to assess the prevalence of anti‐T. cru...
Article
Infection with helminths in sub-Saharan Africa could modulate the immune response towards Plasmodium falciparum as well as susceptibility to malaria infection and disease. The aim of this study is to assess the antibody responses to helminths species in in malaria-exposed populations from Burkina Faso. Plasma samples were collected in rural village...
Article
Full-text available
The human genetic factors that affect resistance to infectious disease are poorly understood. Here we report a genome-wide association study in 17,000 severe malaria cases and population controls from 11 countries, informed by sequencing of family trios and by direct typing of candidate loci in an additional 15,000 samples. We identify five replica...
Preprint
Full-text available
We conducted a genome-wide association study of host resistance to severe Plasmodium falciparum malaria in over 17,000 individuals from 11 malaria- endemic countries, undertaking a wide ranging analysis which identifies five replicable associations with genome-wide levels of evidence. Our findings include a newly implicated variant on chromosome 6...
Article
The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA...
Preprint
Full-text available
Plasmodium falciparum invades human red blood cells by a series of interactions between host and parasite surface proteins. Here we analyse whole genome sequence data from worldwide human populations, including 765 new genomes from across sub-Saharan Africa, and identify a diverse array of large copy number variants affecting the host invasion rece...
Data
Single SNP association test results with adjustment for additive effect of G6PD+202.DOI: http://dx.doi.org/10.7554/eLife.15085.007
Data
G6PDd score association test results.DOI: http://dx.doi.org/10.7554/eLife.15085.015
Data
(A) Summary of study designs of contributing partner studies to MalariaGEN Consortial Project 1 (CP1). (B) Genotyped sample distribution. (C) Summary of 65 SNPs selected for analysis and successfully genotyped. (D) G6PD+202 female association test results. (E) G6PD+202 male association test results. (F) G6PD+202 all individuals association test res...
Data
(A) SNP selection across G6PD region for genotyping. (B) SpectroDESIGNER assay design file for 135 G6PD locus SNPs in four multiplexes. (C) SpectroDESIGNER assay design file for 107 G6PD locus SNPs in four multiplexes. (D) SpectroDESIGNER assay design file for 68 G6PD locus SNPs in three multiplexes. DOI: http://dx.doi.org/10.7554/eLife.15085.020
Data
Single SNP association test results.DOI: http://dx.doi.org/10.7554/eLife.15085.006
Article
Full-text available
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is believed to confer protection against Plasmodium falciparum malaria, but the precise nature of the protective effecthas proved difficult to define as G6PD deficiency has multiple allelic variants with different effects in males and females, and it has heterogeneous effects on the clinical outco...
Article
The malaria parasite Plasmodium falciparum invades human red blood cells via interactions between host and parasite surface proteins. By analyzing genome sequence data from human populations, including 1269 individuals from sub-Saharan Africa, we identify a diverse array of large copy number variants affecting the host invasion receptor genes GYPA...
Article
Full-text available
Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a coll...
Article
Similarity between two individuals in the combination of genetic markers along their chromosomes indicates shared ancestry and can be used to identify historical connections between different population groups due to admixture. We use a genome-wide, haplotype-based, analysis to characterise the structure of genetic diversity and gene-flow in a coll...
Preprint
Full-text available
Understanding patterns of genetic diversity is a crucial component of medical research in Africa. Here we use haplotype-based population genetics inference to describe gene-flow and admixture in a collection of 48 African groups with a focus on the major populations of the sub-Sahara. Our analysis presents a framework for interpreting haplotype div...
Article
Full-text available
The high prevalence of sickle haemoglobin in Africa shows that malaria has been a major force for human evolutionary selection, but surprisingly few other polymorphisms have been proven to confer resistance to malaria in large epidemiological studies. To address this problem, we conducted a multi-centre genome-wide association study (GWAS) of life-...
Article
Full-text available
Background: Many studies report associations between human genetic factors and immunity to malaria but few have been reliably replicated. These studies are usually country-specific, use small sample sizes and are not directly comparable due to differences in methodologies. This study brings together samples and data collected from multiple sites a...
Article
Full-text available
Background Mosquito saliva plays crucial roles in blood feeding but also evokes in hosts an anti-saliva antibody response. The IgG response to the Anopheles gambiae salivary protein gSG6 was previously shown to be a reliable indicator of human exposure to Afrotropical malaria vectors. We analyzed here the humoral response to the salivary anti-throm...
Article
Full-text available
Many human genetic associations with resistance to malaria have been reported, but few have been reliably replicated. We collected data on 11,890 cases of severe malaria due to Plasmodium falciparum and 17,441 controls from 12 locations in Africa, Asia and Oceania. We tested 55 SNPs in 27 loci previously reported to associate with severe malaria. T...
Article
Parasites still impose a high death and disability burden on human populations and are therefore likely to act as selective factors for genetic adaptations. Genetic epidemiology of parasitic diseases aims at disentangling the mechanisms underlying immunity and pathogenesis by looking for association or linkage between loci and susceptibility phenot...
Article
Full-text available
Human antibody response to the Anopheles gambiae salivary protein gSG6 has recently emerged as a potentially useful tool for malaria epidemiological studies and for the evaluation of vector control interventions. However, the current understanding of the host immune response to mosquito salivary proteins and of the possible crosstalk with early res...
Article
Full-text available
Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with...
Article
Full-text available
Our understanding of the composition of multi-clonal malarial infections and the epidemiological factors which shape their diversity remain poorly understood. Traditionally within-host diversity has been defined in terms of the multiplicity of infection (MOI) derived by PCR-based genotyping. Massively parallel, single molecule sequencing technologi...
Data
Read depth distribution at the typable SNP positions in the West African samples. Distribution of SNP coverage at read depth (number of sequenced nucleotides covering a given locus) thresholds of 1, 5, 10, 15, 20 and 25. (TIFF)
Data
Distribution of Fws scores in the West African samples. Dashed lines indicate thresholds for highly diverse (Fws≤0.7) and moderately “clonal” (Fws≥0.95) samples. (TIFF)
Data
Full-text available
Seroprevalence to the different antigens in the three surveys according to age. Seroprevalences to the different antigens in the three surveys are indicated in the legends. Age classes are at the bottom and the number of responders on total individuals is shown in parentheses. Whiskers denote the 95% CI. P values were determined by the chi-square t...
Data
IgG response to the different antigens in the three surveys according to age. Box plots of OD values among responders to the indicated antigen (ga, gSG6; fu, fSG6; ga+fu, gSG6+fSG6) in the three different surveys. Box plots display the median OD value, 25th and 75th percentile. Whiskers represent 5-95 percentile and dots the outliers. P values refe...
Article
Full-text available
The Anopheles gambiae gSG6 is an anopheline-specific salivary protein which helps female mosquitoes to efficiently feed on blood. Besides its role in haematophagy, gSG6 is immunogenic and elicits in exposed individuals an IgG response, which may be used as indicator of exposure to the main African malaria vector A. gambiae. However, malaria transmi...
Article
Full-text available
Highly parallel sequencing technologies permit cost-effective whole genome sequencing of hundreds of Plasmodium parasites. The ability to sequence clinical Plasmodium samples, extracted directly from patient blood without a culture step, presents a unique opportunity to sample the diversity of "natural" parasite populations in high resolution clini...
Data
Golden Gate custom assay information. (XLSX)
Data
Assessment of assay performance using 319 “reliable” SNPs in the presence of human DNA. a Total 250 ng genomic DNA. b Filtration criteria A: SNPs with genotype concordance between replicates >0.95. c Filtration criteria B: SNPs with R>0.1 and with genotype concordance between replicates >0.95. d Mean correlation between replicates. (DOCX)
Data
Assessment of assay performance using 319 “reliable” SNPs on whole genome amplified (WGA) samples. a Filtration criteria A: SNPs with genotype concordance between replicates >0.95. b Filtration criteria B: SNPs with R>0.1 and with genotype concordance between replicates >0.95. (DOCX)
Data
Principal Components Analysis plots (x axis represents PC1, and y axis PC2) using molecular barcodes to differentiate the 143 samples and assign geographic origins to the infections. Green = Mali Orange = Burkina Faso, Blue = Kenya, Black = Cambodia, Grey = Thailand, Red = Papua New Guinea. Using a 9-SNP molecular barcode, samples can clearly be as...
Data
Distribution of theta values (proxy to genotype call) at 306 SNPs in (left to right) the laboratory clone 3D7 and 2 clinical samples from Burkina Faso and PNG. Values approximating 0 and 1 correspond to homozygous calls while other values represent heterozygous calls. (TIF)
Article
Full-text available
The diversity in the Plasmodium falciparum genome can be used to explore parasite population dynamics, with practical applications to malaria control. The ability to identify the geographic origin and trace the migratory patterns of parasites with clinically important phenotypes such as drug resistance is particularly relevant. With increasing sing...
Data
Anti-gSG6 IgG response in children (1–10 years) and adults (>20 years). (DOC)
Data
Supplementary info to Figure 6 , panel B: number of individuals analyzed. (DOC)
Article
Full-text available
Salivary proteins injected by blood feeding arthropods into their hosts evoke a saliva-specific humoral response which can be useful to evaluate exposure to bites of disease vectors. However, saliva of hematophagous arthropods is a complex cocktail of bioactive factors and its use in immunoassays can be misleading because of potential cross-reactiv...
Article
The Fulani of west Africa have been shown to be less susceptible to malaria and to mount a stronger immune response to malaria than sympatric ethnic groups. The analysis of HLA diversity is useful for the assessment of the genetic distance between the Fulani and sympatric populations, which represents the necessary theoretical background for the in...
Article
Plasmodium falciparum represents one of the strongest selective forces on the human genome. This stable and perennial pressure has contributed to the progressive accumulation in the exposed populations of genetic adaptations to malaria. Descriptive genetic epidemiology provides the initial step of a logical procedure of consequential phases spannin...
Article
Full-text available
Interferon Regulatory Factor 1 (IRF-1) is a member of the IRF family of transcription factors, which have key and diverse roles in the gene-regulatory networks of the immune system. IRF-1 has been described as a critical mediator of IFN-gamma signalling and as the major player in driving TH1 type responses. It is therefore likely to be crucial in b...
Article
Full-text available
Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consor...
Article
Full-text available
Descriptive genetic epidemiology represents the initial step of a logical procedure of linked and consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control too...
Article
Full-text available
We describe the haplotypic structure of the interferon regulatory factor-1 (IRF-1) locus in two West African ethnic groups, Fulani and Mossi, that differ in their susceptibility and immune response to Plasmodium falciparum malaria. Both populations showed significant associations between IRF-1 polymorphisms and carriage of P. falciparum infection,...
Article
Full-text available
Localising regulatory variants that control gene expression is a challenge for genome research. Several studies have recently identified non-coding polymorphisms associated with inter-individual differences in gene expression. These approaches rely on the identification of signals of association against a background of variation due to other geneti...
Article
Full-text available
Previous interethnic comparative studies on the susceptibility to malaria performed in West Africa showed that Fulani are more resistant to Plasmodium falciparum malaria than are sympatric ethnic groups. This lower susceptibility is not associated to classic malaria-resistance genes, and the analysis of the immune response to P. falciparum sporozoi...
Article
Full-text available
Large-scale studies of genomic variation could assist efforts to eliminate malaria. But there are scientific, ethical and practical challenges to carrying out such studies in developing countries, where the burden of disease is greatest. The Malaria Genomic Epidemiology Network (MalariaGEN) is now working to overcome these obstacles, using a consor...

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Projects

Project (1)
Project
Investigate the impact of S. haematobium infection on immunity and susceptibility to P. falciparum.