21 research outputs found
Framework For Performance Analysis of Optical Circuit Switched Network Planning Algorithms
Projecte final de carrera realitzat en col.laboració amb Ecole Polytechnique Fédérale de Lausann
Framework For Performance Analysis of Optical Circuit Switched Network Planning Algorithms
Projecte final de carrera realitzat en col.laboració amb Ecole Polytechnique Fédérale de Lausann
Host age and expression of genes involved in red blood cell invasion in Plasmodium falciparum field isolates
Plasmodium falciparum proteins involved in erythrocyte invasion
are main targets of acquired immunity and important vaccine
candidates. We hypothesized that anti-parasite immunity acquired
upon exposure would limit invasion-related gene (IRG) expression
and affect the clinical impact of the infection. 11 IRG
transcript levels were measured in P. falciparum isolates by
RT-PCR, and IgG/IgM against invasion ligands by Luminex(R), in
50 Mozambican adults, 25 children with severe malaria (SM) and
25 with uncomplicated malaria (UM). IRG expression differences
among groups and associations between IRG expression and
clinical/immunologic parameters were assessed. IRG expression
diversity was higher in parasites infecting children than adults
(p = 0.022). eba140 and ptramp expression decreased with age (p
= 0.003 and 0.007, respectively) whereas p41 expression
increased (p = 0.022). pfrh5 reduction in expression was abrupt
early in life. Parasite density decreased with increasing pfrh5
expression (p < 0.001) and, only in children, parasite
density increased with p41 expression (p = 0.007), and decreased
with eba175 (p = 0.013). Antibody responses and IRG expression
were not associated. In conclusion, IRG expression is associated
with age and parasite density, but not with specific antibody
responses in the acute phase of infection. Our results confirm
the importance of multi-antigen vaccines development to avoid
parasite immune escape when tested in malaria-exposed
individuals
Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy.
BACKGROUND: Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known. METHODS: We assessed the prevalence of Plasmodium falciparum infection among 1819 Mozambican women who delivered infants between 2003 and 2012. We used microscopic and histologic examination and a quantitative polymerase-chain-reaction (qPCR) assay, as well as flow-cytometric analysis of IgG antibody responses against two parasite lines. RESULTS: Positive qPCR tests for P. falciparum decreased from 33% in 2003 to 2% in 2010 and increased to 6% in 2012, with antimalarial IgG antibody responses mirroring these trends. Parasite densities in peripheral blood on qPCR assay were higher in 2010-2012 (geometric mean [±SD], 409±1569 genomes per microliter) than in 2003-2005 (44±169 genomes per microliter, P=0.02), as were parasite densities in placental blood on histologic assessment (50±39% of infected erythrocytes vs. 4±6%, P<0.001). The malaria-associated reduction in maternal hemoglobin levels was larger in 2010-2012 (10.1±1.8 g per deciliter in infected women vs. 10.9±1.7 g per deciliter in uninfected women; mean difference, -0.82 g per deciliter; 95% confidence interval [CI], -1.39 to -0.25) than in 2003-2005 (10.5±1.1 g per deciliter vs. 10.6±1.5 g per deciliter; difference, -0.12 g per deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth weight (2863±440 g in women with past or chronic infections vs. 3070±482 g in uninfected women in 2010-2012; mean difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994±487 g vs. 3117±455 g in 2003-2005; difference, -44.8 g; 95% CI, -139.1 to 49.5). CONCLUSIONS: Antimalarial antibodies were reduced and the adverse consequences of P. falciparum infections were increased in pregnant women after 5 years of a decline in the prevalence of malaria. (Funded by Malaria Eradication Scientific Alliance and others.)
Setting the scene and generating evidence for malaria elimination in Southern Mozambique
Mozambique has historically been one of the countries
with the highest malaria burden in the world. Starting in the
1960s, malaria control efforts were intensified in the southern
region of the country, especially in Maputo city and Maputo
province, to aid regional initiatives aimed to eliminate malaria
in South Africa and eSwatini. Despite significant reductions in
malaria prevalence, elimination was never achieved. Following
the World Health Organization's renewed vision of a
malaria-free-world, and considering the achievements from the
past, the Mozambican National Malaria Control Programme (NMCP)
embarked on the development and implementation of a strategic
plan to accelerate from malaria control to malaria elimination
in southern Mozambique. An initial partnership, supported by the
Bill and Melinda Gates Foundation and the La Caixa Foundation,
led to the creation of the Mozambican Alliance Towards the
Elimination of Malaria (MALTEM) and the Malaria Technical and
Advisory Committee (MTAC) to promote national ownership and
partner coordination to work towards the goal of malaria
elimination in local and cross-border initiatives. Surveillance
systems to generate epidemiological and entomological
intelligence to inform the malaria control strategies were
strengthened, and an impact and feasibility assessment of
various interventions aimed to interrupt malaria transmission
were conducted in Magude district (Maputo Province) through the
"Magude Project". The primary aim of this project was to
generate evidence to inform malaria elimination strategies for
southern Mozambique. The goal of malaria elimination in areas of
low transmission intensity is now included in the national
malaria strategic plan for 2017-22 and the NMCP and its partners
have started to work towards this goal while evidence continues
to be generated to move the national elimination agenda forward
Cytoadhesion to gC1qR through Plasmodium falciparum Erythrocyte Membrane Protein 1 in Severe Malaria
Cytoadhesion of Plasmodium falciparum infected erythrocytes to
gC1qR has been associated with severe malaria, but the parasite
ligand involved is currently unknown. To assess if binding to
gC1qR is mediated through the P. falciparum erythrocyte membrane
protein 1 (PfEMP1) family, we analyzed by static binding assays
and qPCR the cytoadhesion and var gene transcriptional profile
of 86 P. falciparum isolates from Mozambican children with
severe and uncomplicated malaria, as well as of a P. falciparum
3D7 line selected for binding to gC1qR (Pf3D7gC1qR). Transcript
levels of DC8 correlated positively with cytoadhesion to gC1qR
(rho = 0.287, P = 0.007), were higher in isolates from children
with severe anemia than with uncomplicated malaria, as well as
in isolates from Europeans presenting a first episode of malaria
(n = 21) than Mozambican adults (n = 25), and were associated
with an increased IgG recognition of infected erythrocytes by
flow cytometry. Pf3D7gC1qR overexpressed the DC8 type PFD0020c
(5.3-fold transcript levels relative to Seryl-tRNA-synthetase
gene) compared to the unselected line (0.001-fold). DBLbeta12
from PFD0020c bound to gC1qR in ELISA-based binding assays and
polyclonal antibodies against this domain were able to inhibit
binding to gC1qR of Pf3D7gC1qR and four Mozambican P. falciparum
isolates by 50%. Our results show that DC8-type PfEMP1s mediate
binding to gC1qR through conserved surface epitopes in DBLbeta12
domain which can be inhibited by strain-transcending functional
antibodies. This study supports a key role for gC1qR in
malaria-associated endovascular pathogenesis and suggests the
feasibility of designing interventions against severe malaria
targeting this specific interaction
Changing Trends in P. falciparum Burden, Immunity, and Disease in Pregnancy
Background Prevention of reinfection and resurgence is an integral component of the goal to eradicate malaria. However, the adverse effects of malaria resurgences are not known.
Methods We assessed the prevalence of Plasmodium falciparum
infection among 1819 Mozambican women who delivered infants
between 2003 and 2012. We used microscopic and histologic
examination and a quantitative polymerase-chain-reaction (qPCR)
assay, as well as flow-cytometric analysis of IgG antibody
responses against two parasite lines. Results Positive qPCR
tests for P. falciparum decreased from 33% in 2003 to 2% in 2010
and increased to 6% in 2012, with antimalarial IgG antibody
responses mirroring these trends. Parasite densities in
peripheral blood on qPCR assay were higher in 2010-2012
(geometric mean [+/-SD], 409+/-1569 genomes per microliter) than
in 2003-2005 (44+/-169 genomes per microliter, P=0.02), as were
parasite densities in placental blood on histologic assessment
(50+/-39% of infected erythrocytes vs. 4+/-6%, P<0.001). The
malaria-associated reduction in maternal hemoglobin levels was
larger in 2010-2012 (10.1+/-1.8 g per deciliter in infected
women vs. 10.9+/-1.7 g per deciliter in uninfected women; mean
difference, -0.82 g per deciliter; 95% confidence interval [CI],
-1.39 to -0.25) than in 2003-2005 (10.5+/-1.1 g per deciliter
vs. 10.6+/-1.5 g per deciliter; difference, -0.12 g per
deciliter; 95% CI, -0.67 to 0.43), as was the reduction in birth
weight (2863+/-440 g in women with past or chronic infections
vs. 3070+/-482 g in uninfected women in 2010-2012; mean
difference, -164.5 g; 95% CI, -289.7 to -39.4; and 2994+/-487 g
vs. 3117+/-455 g in 2003-2005; difference, -44.8 g; 95% CI,
-139.1 to 49.5). Conclusions Antimalarial antibodies were
reduced and the adverse consequences of P. falciparum infections
were increased in pregnant women after 5 years of a decline in
the prevalence of malaria. (Funded by Malaria Eradication
Scientific Alliance and others.)
Framework For Performance Analysis of Optical Circuit Switched Network Planning Algorithms
Projecte final de carrera realitzat en col.laboració amb Ecole Polytechnique Fédérale de Lausann
RTS,S/AS02A malaria vaccine does not induce parasite CSP T cell epitope selection and reduces multiplicity of infection.
OBJECTIVE: The candidate malaria vaccine RTS,S/AS02A is a recombinant protein containing part of the circumsporozoite protein (CSP) sequence of Plasmodium falciparum, linked to the hepatitis B surface antigen and formulated in the proprietary adjuvant system AS02A. In a recent trial conducted in children younger than age five in southern Mozambique, the vaccine demonstrated significant and sustained efficacy against both infection and clinical disease. In a follow-up study to the main trial, breakthrough infections identified in the trial were examined to determine whether the distribution of csp sequences was affected by the vaccine and to measure the multiplicity of infecting parasite genotypes. DESIGN: P. falciparum DNA from isolates collected during the trial was used for genotype studies. SETTING: The main trial was carried out in the Manhiça district, Maputo province, Mozambique, between April 2003 and May 2004. PARTICIPANTS: Children from the two cohorts of the main trial provided parasite isolates as follows: children from Cohort 1 who were admitted to hospital with clinical malaria; children from Cohort 1 who were parasite-positive in a cross-sectional survey at study month 8.5; children from Cohort 2 identified as parasite-positive during follow-up by active detection of infection. OUTCOME: Divergence of DNA sequence encoding the CSP T cell-epitope region sequence from that of the vaccine sequence was measured in 521 isolates. The number of distinct P. falciparum genotypes was also determined. RESULTS: We found no evidence that parasite genotypes from children in the RTS,S/AS02A arm were more divergent than those receiving control vaccines. For Cohort 1 (survey at study month 8.5) and Cohort 2, infections in the vaccine group contained significantly fewer genotypes than those in the control group, (p = 0.035, p = 0.006), respectively, for the two cohorts. This was not the case for children in Cohort 1 who were admitted to hospital (p = 0.478). CONCLUSIONS: RTS,S/AS02A did not select for genotypes encoding divergent T cell epitopes in the C-terminal region of CSP in this trial. In both cohorts, there was a modest reduction in the mean number of parasite genotypes harboured by vaccinated children compared with controls, but only among those with asymptomatic infections