Departamento de Parasitologia – ICB

MARCELO URBANO FERREIRA

Phone: +55 (11) 3091-7746
Room: 29/33 – ground floor
Email: muferrei@usp.br
Currículo Lattes

Malaria Molecular Epidemiology Laboratory

GROUP MEMBERS

Pablo Secato Fontoura

Priscila Thihara Rodrigues

Susana do Carmo Pinto Barbosa

Laís Camonese Salla

Maria José Menezes

Nathália Ferreira Lima

Raquel Müller Gonçalves Lopes

Thaís Crippa de Oliveira

Vanessa Cristina Nicolete

RESEARCH LINE

  • Genética de populações de plasmódios
  • Epidemiologia e controle de doenças infecciosas e parasitárias
  • Imunorregulação na malária humana

RESEARCH INTERESTS

Our long-term goal is to provide scientific evidence that can be translated into effective public health interventions for malaria control in Amazonia. We aim to determine whether asymptomatic parasite carriage is a major contributor to malaria transmission across the region by: (a) estimating the prevalence, incidence and risk factors for asymptomatic malaria parasite carriage in rural Amazonia; (b) estimating the prevalence, incidence, average duration and risk factors for gametocyte carriage; (c) comparing prospectively the risk of subsequent clinical malaria among asymptomatic parasite carriers and non-infected controls living in the same communities and determining whether these episodes are due to persistent parasite lineages or to new infections; and (d) testing whether intra-host competition of genetically distinct parasite clones contributes to increased parasite virulence, greater risk of disease, and increased gametocyte production. These aims have been achieved with population based surveys in epidemiologically diverse Amazonian settings. Field-based clinical and epidemiological analyses are complemented with measurements of immunological parameters and extensive parasite genotyping, providing a unique multidisciplinary perspective on the public health significance of asymptomatic parasite carriage in the Amazon.

PUBLICATIONS

Professor Ferreira is the author of about 120 peer-reviewed scientific articles and two Parasitology textbooks, Biological Foundations of Human Parasitology (2003) and Contemporary Parasitology (2012), both published in Brazil. His current research is focused on molecular epidemiology, population genetics and control of malaria in low-transmission settings. His field work is carried out in field stations in Acre State, an area in the Amazon Basin of Brazil where Plasmodium vivax is the predominant malaria parasite species. Recent publications include:

Ferreira MU, Karunaweera ND, da Silva-Nunes M, da Silva NS, Wirth DF, Hartl DL. J Infect Dis. 2007 Apr 15;195(8):1218-26

Orjuela-Sánchez P, Karunaweera ND, da Silva-Nunes M, da Silva NS, Scopel KK, Gonçalves RM, Amaratunga C, Sá JM, Socheat D, Fairhust RM, Gunawardena S, Thavakodirasah T, Galapaththy GL, Abeysinghe R, Kawamoto F, Wirth DF, Ferreira MU. BMC Genet. 2010 Jul 13;11:65

Orjuela-Sánchez P, da Silva NS, da Silva-Nunes M, Ferreira MU. Am J Trop Med Hyg. 2009 Dec;81(6):961-8

da Silva-Nunes M, Codeço CT, Malafronte RS, da Silva NS, Juncansen C, Muniz PT, Ferreira MU. Am J Trop Med Hyg. 2008 Oct;79(4):624-35

Barbosa S, Gozze AB, Lima NF, Batista CL, Bastos Mda S, Nicolete VC, Fontoura PS, Gonçalves RM, Viana SA, Menezes MJ, Scopel KK, Cavasini CE, Malafronte Rdos S, da Silva-Nunes M, Vinetz JM, Castro MC, Ferreira MU. PLoS Negl Trop Dis. 2014 Aug 28;8(8):e3109

RESEARCH PROJECTS/FUNDING

Epidemiology of malaria in the Peruvian and Brazilian Amazon (NIAID (U19 AI089681, Sub-Project ID: 6063)

NIAID, NIH  (1U19AI089681-01, Sub-Project ID: 6063) (PI, Ferreira)  07/01/2010 – 06/30/2017 (Ongoing research support)
 
Epidemiology of malaria in the Peruvian and Brazilian Amazon
 
To determine whether asymptomatic parasite carriage is a major contributor to malaria transmission across the region, we aim: (a) to estimate the prevalence, incidence and risk factors for asymptomatic malaria parasite carriage in rural Amazonia; (b) to estimate the prevalence, incidence, average duration and risk factors for gametocyte carriage; (c) to compare the ability of symptomatic and asymptomatic carriers of gametocytes to experimentally infect wild caught local vectors; (d) to compare prospectively the risk of subsequent clinical malaria among asymptomatic parasite carriers and non-infected controls living in the same communities and to determine whether these episodes are due to persistent parasite lineages or to new infections; and (e) to test whether intra-host competition of genetically distinct parasite clones contributes to increased parasite virulence, greater risk of disease, and increased gametocyte production.
Agency: FAPESP, Brazil (07/52771-0, 2008/50645-0) and CNPq, Brazil (470195/2008-8) – Completed research support (2005-14)
 
Immunoregulation of T-cell responses in human malaria
(2007-2010)
 
Clearing blood-stage malaria parasites without inducing major host pathology requires a finely tuned balance between pro- and anti-inflammatory responses. The interplay between regulatory T (Treg) cells and dendritic cells (DCs) is one of the key determinants of this balance. Although experimental models have revealed various patterns of Treg cell expansion, DC maturation, and cytokine production according to the infecting malaria parasite species, no studies have compared all of these parameters in human infections with Plasmodium falciparum and P. vivax in the same setting of endemicity. This project showed that during uncomplicated acute malaria, both species induced a significant expansion of CD4+ CD25+ Foxp3+ Treg cells expressing the key immunomodulatory molecule CTLA-4 and a significant increase in the proportion of DCs that were plasmacytoid (CD123+), with a decrease in the myeloid/plasmacytoid DC ratio.
 
Role: PI
Agency: National Institute of Allergy and Infectious Diseases, National Institutes of Health (R01 AI 075416) – Completed research support (2005-14)
 
Population structure and transmission dynamics of Plasmodium vivax
(2008-2011)
 
The purpose of this research is to characterize the genetic structure and transmission dynamics of the human malaria parasite Plasmodium vivax, with the long-term goal of understanding the evolutionary biology of this species and its potential implications for malaria treatment and control.
 
Role: PI
Agency: Fogarty International Center, National Institutes of Health (5R03TW007966-02) (PI, Wirth) – Completed research support (2005-14)
 
Genetic polymorphism and diversity of Plasmodium vivax malaria
(2007-10)
 
This project aims to examine the population structure and transmission dynamics of variants of P. vivax in a rural community in the Brazilian Amazon. It is based on a cohort of 509 subjects with clinical and epidemiological follow-up since the beginning of 2004, obtaining blood samples for genetic characterization of isolates incident cases of infection by P. vivax and to perform comparisons between sympatric species, also P. falciparum. This is the first population-based study to employ polymorphic DNA microsatellite markers and single base polymorphisms (SNPs), recently standardized on the analysis of natural populations of P. vivax. It is also the first longitudinal study of the transmission dynamics of P. vivax, in a well-defined community, investigating the patterns of circulation of genetically distinct populations of the parasite in space and time.
 
Role: collaborator

COLLABORATORS