398 research outputs found
Plasmodium falciparum Antigens on the Surface of the Gametocyte-Infected Erythrocyte
BACKGROUND: The asexual blood stages of the human malaria parasite Plasmodium falciparum produce highly immunogenic polymorphic antigens that are expressed on the surface of the host cell. In contrast, few studies have examined the surface of the gametocyte-infected erythrocyte. METHODOLOGY/PRINCIPAL FINDINGS: We used flow cytometry to detect antibodies recognising the surface of live cultured erythrocytes infected with gametocytes of P. falciparum strain 3D7 in the plasma of 200 Gambian children. The majority of children had been identified as carrying gametocytes after treatment for malaria, and each donated blood for mosquito-feeding experiments. None of the plasma recognised the surface of erythrocytes infected with developmental stages of gametocytes (I-IV), but 66 of 194 (34.0%) plasma contained IgG that recognised the surface of erythrocytes infected with mature (stage V) gametocytes. Thirty-four (17.0%) of 200 plasma tested recognised erythrocytes infected with trophozoites and schizonts, but there was no association with recognition of the surface of gametocyte-infected erythrocytes (odds ratio 1.08, 95% C.I. 0.434-2.57; P = 0.851). Plasma antibodies with the ability to recognise gametocyte surface antigens (GSA) were associated with the presence of antibodies that recognise the gamete antigen Pfs 230, but not Pfs48/45. Antibodies recognising GSA were associated with donors having lower gametocyte densities 4 weeks after antimalarial treatment. CONCLUSIONS/SIGNIFICANCE: We provide evidence that GSA are distinct from antigens detected on the surface of asexual 3D7 parasites. Our findings suggest a novel strategy for the development of transmission-blocking vaccines
Non-parametric analysis of the rest-frame UV sizes and morphological disturbance amongst L* galaxies at 4<z<8
We present the results of a study investigating the sizes and morphologies of
redshift 4 < z < 8 galaxies in the CANDELS GOODS-S, HUDF and HUDF parallel
fields. Based on non-parametric measurements and incorporating a careful
treatment of measurement biases, we quantify the typical size of galaxies at
each redshift as the peak of the log-normal size distribution, rather than the
arithmetic mean size. Parameterizing the evolution of galaxy half-light radius
as , we find at bright
UV-luminosities () and at faint
luminosities (). Furthermore, simulations based on
artificially redshifting our z~4 galaxy sample show that we cannot reject the
null hypothesis of no size evolution. We show that this result is caused by a
combination of the size-dependent completeness of high-redshift galaxy samples
and the underestimation of the sizes of the largest galaxies at a given epoch.
To explore the evolution of galaxy morphology we first compare asymmetry
measurements to those from a large sample of simulated single S\'ersic
profiles, in order to robustly categorise galaxies as either `smooth' or
`disturbed'. Comparing the disturbed fraction amongst bright () galaxies at each redshift to that obtained by artificially redshifting
our z~4 galaxy sample, while carefully matching the size and UV-luminosity
distributions, we find no clear evidence for evolution in galaxy morphology
over the redshift interval 4 < z < 8. Therefore, based on our results, a bright
() galaxy at z~6 is no more likely to be measured as
`disturbed' than a comparable galaxy at z~4, given the current observational
constraints.Comment: 29 pages, 25 figures, 4 tables, published in MNRA
A mass threshold in the number density of passive galaxies at z2
The process that quenched star formation in galaxies at intermediate and high
redshift is still the subject of considerable debate. One way to investigate
this puzzling issue is to study the number density of quiescent galaxies at
z~2, and its dependence on mass. Here we present the results of a new study
based on very deep Ks-band imaging (with the HAWK-I instrument on the VLT) of
two HST CANDELS fields (the UKIDSS Ultra-deep survey (UDS) field and
GOODS-South). The new HAWK-I data (taken as part of the HUGS VLT Large Program)
reach detection limits of Ks>26 (AB mag). We select a sample of
passively-evolving galaxies in the redshift range 1.4<z<2.5. Thanks to the
depth and large area coverage of our imaging, we have been able to extend the
selection of quiescent galaxies a magnitude fainter than previous analyses.
Through extensive simulations we demonstrate, for the first time, that the
observed turn-over in the number of quiescent galaxies at K>22 is real. This
has enabled us to establish unambiguously that the number counts of quiescent
galaxies at z~2 flatten and slightly decline at magnitudes fainter than
Ks~22(AB mag.). We show that this trend corresponds to a stellar mass threshold
below which the mechanism that halts the star
formation in high-redshift galaxies seems to be inefficient. Finally we compare
the observed pBzK number counts with those of quiescent galaxies extracted from
four different semi-analytic models. We find that none of the models provides a
statistically acceptable description of the number density of quiescent
galaxies at these redshifts. We conclude that the mass function of quiescent
galaxies as a function of redshift continues to present a key and demanding
challenge for proposed models of galaxy formation and evolution.Comment: Accepted for publication on Astronomy and Astrophysic
Galaxies at z = 6 - 9 from the WFC3/IR imaging of the HUDF
We present the results of a systematic search for galaxies in the redshift
range z = 6 - 9, within the new, deep, near-infrared imaging of the Hubble
Ultra Deep Field provided by the Wide Field Camera 3 (WFC3) on HST. We have
performed full SED fitting to the optical+infrared photometry of all
high-redshift galaxy candidates detected at greater than 5-sigma in at least
one of the WFC3/IR broad-band filters. After rejection of contaminants, the
result is a sample of 49 galaxies with primary redshift solutions z > 5.9. Our
sample, selected without recourse to specific colour cuts, re-selects all but
the faintest one of the 16 z-drops selected by Oesch et al. (2009), recovers
all 5 of the Y-drops reported by Bouwens et al. (2009), and adds a further 29
galaxy candidates, of which 12 lie beyond z = 6.3, and 4 lie beyond z = 7. We
also present confidence intervals on our photometric redshift estimates, and
caution that acceptable low-redshift (z < 2) solutions exist for 28 out of the
37 galaxies at z > 6.3, and for all 8 galaxy candidates at z > 7.5.
Nevertheless, the very highest redshift candidates appear to be strongly
clustered in the field. We derive new estimates of the ultraviolet galaxy
luminosity function at z = 7 and z = 8. Where our results are most robust, at a
characteristic luminosity M(1500) ~ -19.5 (AB), we find that the comoving
number density of galaxies declines by a factor of ~ 2.5 between z = 6 and z =
7, and by a further factor of ~ 2 by z = 8. These results suggest that it is
difficult for the observed population of high-redshift star-forming galaxies to
achieve reionisation by z ~ 6 without a significant contribution from galaxies
well below the detection limits, plus alterations in the escape fraction of
ionising photons and/or continued vigorous star formation at z > 15.Comment: 25 Pages, Accepted for publication in MNRA
The evolution of the galaxy UV luminosity function at redshifts z ~ 8-15 from deep JWST and ground-based near-infrared imaging
International audienceWe reduce and analyse the available JWST ERO and ERS NIRCam imaging (SMACS0723, GLASS, CEERS) in combination with the latest deep ground-based near-infrared imaging in the COSMOS field (provided by UltraVISTA DR5) to produce a new measurement of the evolving galaxy UV luminosity function (LF) over the redshift range z = 8 - 15. This yields a new estimate of the evolution of UV luminosity density (ρUV), and hence cosmic star formation rate density (ρSFR) out to within UV (and thus ρSFR), continues to decline gradually and steadily up to z ~ 15 (as anticipated from previous studies which analysed the pre-existing data in a consistent manner to this study). We provide details of the 61 high-redshift galaxy candidates, 47 of which are new, that have enabled this new analysis. Our sample contains 6 galaxies at z ≥ 12, one of which appears to set a new redshift record as an apparently robust galaxy candidate at z ≃ 16.4, the properties of which we therefore consider in detail. The advances presented here emphasize the importance of achieving high dynamic range in studies of early galaxy evolution, and re-affirm the enormous potential of forthcoming larger JWST programmes to transform our understanding of the young Universe
Chloroquine/Sulphadoxine-Pyrimethamine for Gambian Children with Malaria: Transmission to Mosquitoes of Multidrug-Resistant Plasmodium falciparum
OBJECTIVES: In the Gambia, chloroquine (CQ) plus sulphadoxine-pyrimethamine (SP) is the first-line antimalarial treatment. Plasmodium falciparum parasites carrying mutations associated with resistance to each of these drugs were present in 2001 but did not cause a significant loss of therapeutic efficacy among children receiving the combination CQ/SP. We measured their effect on parasite transmission to Anopheles gambiae mosquitoes. DESIGN: We conducted a single-blind, randomised, controlled trial with follow-up over 28 d. Mosquito feeding experiments were carried out 7, 10, or 14 d after treatment. SETTING: The study took place in the town of Farafenni and surrounding villages in the Gambia. PARTICIPANTS: Participants were 500 children aged 6 mo to 10 y with uncomplicated P. falciparum malaria. INTERVENTIONS: Children were randomised to receive CQ, SP, or CQ/SP. OUTCOME MEASURES: Outcomes related to transmission were determined, including posttreatment gametocyte prevalence and density. Infectiousness was assessed by membrane-feeding A. gambiae mosquitoes with blood from 70 gametocyte-positive patients. Mutations at seven loci in four genes associated with drug resistance were measured pre- and posttreatment and in the midguts of infected mosquitoes. RESULTS: After SP treatment, the infectiousness of gametocytes was delayed, compared to the other two treatment groups, despite comparable gametocyte densities. Among bloodmeal gametocytes and the midguts of infected mosquitoes, the presence of the four-locus multidrug-resistant haplotype TYRG (consisting of mutations pfcrt-76T, pfmdr1-86Y, pfdhfr-59R, and pfdhps-437G) was associated with significantly higher oocyst burdens after treatment with the combination CQ/SP. CONCLUSIONS: Parasites with a multidrug-resistant genotype had a substantial transmission advantage after CQ/SP treatment but did not have a significant impact on in vivo efficacy of this drug combination. Protocols that include measuring transmission endpoints as well as therapeutic outcomes may be a useful strategy when monitoring the evolution of drug resistance in malaria parasites in vivo
Randomised Trial of Chloroquine/Sulphadoxine-Pyrimethamine in Gambian Children with Malaria: Impact against Multidrug-Resistant P. falciparum
OBJECTIVES: In the Gambia, the combination of chloroquine (CQ) and sulphadoxine-pyrimethamine (SP) has replaced CQ monotherapy for treatment of malaria caused by Plasmodium falciparum. We measured the efficacy of the combination CQ/SP, and the prevalence of parasites carrying alleles associated with resistance to CQ or SP. DESIGN: We conducted a single-blind, randomised, controlled trial to compare the efficacy of CQ/SP to that of SP or CQ alone. SETTING: The study took place in the town of Farafenni and surrounding villages in the Gambia. PARTICIPANTS: Participants were children aged 12 mo to 10 y presenting as outpatients with uncomplicated P. falciparum malaria. INTERVENTIONS: 500 children were randomised to receive CQ, SP, or CQ/SP as supervised treatment and actively followed over 28 d. OUTCOME MEASURES: Primary outcome was parasitaemia at any time during follow-up. Secondary outcomes were PCR-confirmed recrudescent infections among treatment failures, and clinical failure requiring rescue medication by day 28. Pretreatment parasite isolates from 161 patients were tested for the presence of resistance-associated genetic markers. RESULTS: The prevalence of parasitological failure by day 28 for the CQ group was 60.3%, compared to 17.6% for SP (odds ratio [OR], 0.106; 95% confidence interval [CI], 0.057–0.194; p < 0.001) and 13.9% for CQ/SP (OR versus CQ, 0.140; 95% CI, 0.078–0.250; p < 0.001). There was no difference between the SP and CQ/SP groups (OR, 1.324; 95% CI, 0.705–2.50). The projected prevalence of PCR-corrected treatment failure was 30.2, 6.06, and 3.94% in the CQ, SP, and CQ/SP groups, respectively. The pfdhfr-triple mutant and pfdhps-437G mutation were common, with prevalences of 67.4 and 51.2%, respectively. Pretreatment carriage of pfdhps-437G and of multidrug-resistant parasite genotypes was associated with treatment failure in the SP group, but not in the CQ or CQ/SP groups. CONCLUSIONS: The combination of CQ/SP was an efficacious treatment for uncomplicated malaria in Gambian children in this study, but the frequent occurrence of multidrug-resistant parasites suggests that this observed efficacy is not sustainable
The Hawk-I UDS and GOODS Survey (HUGS): Survey design and deep K-band number counts
We present the results of a new, ultra-deep, near-infrared imaging survey
executed with the Hawk-I imager at the ESO VLT, of which we make all the data
public. This survey, named HUGS (Hawk-I UDS and GOODS Survey), provides deep,
high-quality imaging in the K and Y bands over the CANDELS UDS and GOODS-South
fields. We describe here the survey strategy, the data reduction process, and
the data quality. HUGS delivers the deepest and highest quality K-band images
ever collected over areas of cosmological interest, and ideally complements the
CANDELS data set in terms of image quality and depth. The seeing is exceptional
and homogeneous, confined to the range 0.38"-0.43". In the deepest region of
the GOODS-S field, (which includes most of the HUDF) the K-band exposure time
exceeds 80 hours of integration, yielding a 1-sigma magnitude limit of ~28.0
mag/sqarcsec. In the UDS field the survey matches the shallower depth of the
CANDELS images reaching a 1-sigma limit per sq.arcsec of ~27.3mag in the K band
and ~28.3mag in the Y-band, We show that the HUGS observations are well matched
to the depth of the CANDELS WFC3/IR data, since the majority of even the
faintest galaxies detected in the CANDELS H-band images are also detected in
HUGS. We present the K-band galaxy number counts produced by combining the HUGS
data from the two fields. We show that the slope of the number counts depends
sensitively on the assumed distribution of galaxy sizes, with potential impact
on the estimated extra-galactic background light (abridged).Comment: Accepted for publication on Astronomy and Astrophysic
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