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Find video protocols related to scientific articles indexed in Pubmed.
A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine.
BMC Med
PUBLISHED: 03-14-2014
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The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and episodes of clinical malaria.
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CD4+ T cell responses to the Plasmodium falciparum erythrocyte membrane protein 1 in children with mild malaria.
J. Immunol.
PUBLISHED: 01-22-2014
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The immune response against the variant surface Ag Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is a key component of clinical immunity against malaria. We have investigated the development and maintenance of CD4(+) T cell responses to a small semiconserved area of the Duffy binding-like domain (DBL)?-domain of PfEMP1, the DBL?-tag. Young children were followed up longitudinally, and parasites and PBMCs were isolated from 35 patients presenting with an acute case of uncomplicated malaria. The DBL?-tag from the PfEMP1 dominantly expressed by the homologous parasite isolate was cloned and expressed as recombinant protein. The recombinant DBL?-tag was used to activate PBMCs collected from each acute episode and from an annual cross-sectional survey performed after the acute malaria episode. In this article, we report that CD4(+) T cell responses to the homologous DBL?-tag were induced in 75% of the children at the time of the acute episode and in 62% of the children at the following cross-sectional survey on average 235 d later. Furthermore, children who had induced DBL?-tag-specific CD4(+)IL-4(+) T cells at the acute episode remained episode free for longer than children who induced other types of CD4(+) T cell responses. These results suggest that a wide range of DBL?-tag-specific CD4(+) T cell responses were induced in children with mild malaria and, in the case of CD4(+)IL-4(+) T cell responses, were associated with protection from clinical episodes.
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Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data.
BMC Med
PUBLISHED: 05-22-2013
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RTS,S is the most advanced candidate malaria vaccine but it is only partially protective and the causes of inter-individual variation in efficacy are poorly understood. Here, we investigated whether peripheral blood monocyte-to-lymphocyte ratios (ML ratio), previously shown to correlate with clinical malaria risk, could account for differences in RTS,S efficacy among phase II trial participants in Africa.
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Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure.
N. Engl. J. Med.
PUBLISHED: 03-22-2013
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The candidate malaria vaccine RTS,S/AS01E has entered phase 3 trials, but data on long-term outcomes are limited.
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Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data.
Lancet Infect Dis
PUBLISHED: 03-01-2013
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The efficacy of RTS,S/AS01 as a vaccine for malaria is being tested in a phase 3 clinical trial. Early results show significant, albeit partial, protection against clinical malaria and severe malaria. To ascertain variations in vaccine efficacy according to covariates such as transmission intensity, choice of adjuvant, age at vaccination, and bednet use, we did an individual-participant pooled analysis of phase 2 clinical data.
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Feedback of research findings for vaccine trials: experiences from two malaria vaccine trials involving healthy children on the Kenyan Coast.
Dev World Bioeth
PUBLISHED: 02-21-2013
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Internationally, calls for feedback of findings to be made an ethical imperative or mandatory have been met with both strong support and opposition. Challenges include differences in issues by type of study and context, disentangling between aggregate and individual study results, and inadequate empirical evidence on which to draw. In this paper we present data from observations and interviews with key stakeholders involved in feeding back aggregate study findings for two Phase II malaria vaccine trials among children under the age of 5 years old on the Kenyan Coast. In our setting, feeding back of aggregate findings was an appreciated set of activities. The inclusion of individual results was important from the point of view of both participants and researchers, to reassure participants of trial safety, and to ensure that positive results were not over-interpreted and that individual level issues around blinding and control were clarified. Feedback sessions also offered an opportunity to re-evaluate and re-negotiate trial relationships and benefits, with potentially important implications for perceptions of and involvement in follow-up work for the trials and in future research. We found that feedback of findings is a complex but key step in a continuing set of social interactions between community members and research staff (particularly field staff who work at the interface with communities), and among community members themselves; a step which needs careful planning from the outset. We agree with others that individual and aggregate results need to be considered separately, and that for individual results, both the nature and value of the information, and the context, including social relationships, need to be taken into account.
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Phenotypic and functional profiling of CD4 T cell compartment in distinct populations of healthy adults with different antigenic exposure.
PLoS ONE
PUBLISHED: 01-28-2013
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Multiparameter flow cytometry has revealed extensive phenotypic and functional heterogeneity of CD4 T cell responses in mice and humans, emphasizing the importance of assessing multiple aspects of the immune response in correlation with infection or vaccination outcome. The aim of this study was to establish and validate reliable and feasible flow cytometry assays, which will allow us to characterize CD4 T cell population in humans in field studies more fully.
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The relationship between RTS,S vaccine-induced antibodies, CD4? T cell responses and protection against Plasmodium falciparum infection.
PLoS ONE
PUBLISHED: 01-01-2013
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Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4(+) T cells specific for the circumsporozoite protein (CSP). Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and subjected to experimental P. falciparum challenge, we characterised the relationship between antibodies, CD4(+) T cell responses and protection from infection. Both anti-CSP antibody titres and CSP-specific CD4(+) T cells were identified as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32% (95% confidence interval (CI) 24%-41%) of infections. The addition of RTS,S-induced CSP-specific CD4(+) T cells was estimated to increase vaccine efficacy against infection to 40% (95% CI, 34%-48%). This protective efficacy is estimated to result from a 96.1% (95% CI, 93.4%-97.8%) reduction in the liver-to-blood parasite inoculum, indicating that in volunteers who developed P. falciparum infection, a small number of parasites (often the progeny of a single surviving sporozoite) are responsible for breakthrough blood-stage infections.
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First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children.
Selidji Todagbe Agnandji, Bertrand Lell, Solange Solmeheim Soulanoudjingar, José Francisco Fernandes, Béatrice Peggy Abossolo, Cornelia Conzelmann, Barbara Gaelle Nfono Ondo Methogo, Yannick Doucka, Arnaud Flamen, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J Aponte, Arlindo Nhamuave, Diana Quelhas, Quique Bassat, Sofia Mandjate, Eusébio Macete, Pedro Alonso, Salim Abdulla, Nahya Salim, Omar Juma, Mwanajaa Shomari, Kafuruki Shubis, Francisca Machera, Ali Said Hamad, Rose Minja, Ali Mtoro, Alma Sykes, Saumu Ahmed, Alwisa Martin Urassa, Ali Mohammed Ali, Grace Mwangoka, Marcel Tanner, Halidou Tinto, Umberto D'Alessandro, Hermann Sorgho, Innocent Valea, Marc Christian Tahita, William Kaboré, Sayouba Ouédraogo, Yara Sandrine, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J Hamel, Simon Kariuki, Chris Odero, Martina Oneko, Kephas Otieno, Norbert Awino, Jackton Omoto, John Williamson, Vincent Muturi-Kioi, Kayla F Laserson, Laurence Slutsker, Walter Otieno, Lucas Otieno, Otsyula Nekoye, Stacey Gondi, Allan Otieno, Bernhards Ogutu, Ruth Wasuna, Victorine Owira, David Jones, Agnes Akoth Onyango, Patricia Njuguna, Roma Chilengi, Pauline Akoo, Christine Kerubo, Jesse Gitaka, Charity Maingi, Trudie Lang, Ally Olotu, Benjamin Tsofa, Philip Bejon, Norbert Peshu, Kevin Marsh, Seth Owusu-Agyei, Kwaku Poku Asante, Kingsley Osei-Kwakye, Owusu Boahen, Samuel Ayamba, Kingsley Kayan, Ruth Owusu-Ofori, David Dosoo, Isaac Asante, George Adjei, Daniel Chandramohan, Brian Greenwood, John Lusingu, Samwel Gesase, Anangisye Malabeja, Omari Abdul, Hassan Kilavo, Coline Mahende, Edwin Liheluka, Martha Lemnge, Thor Theander, Chris Drakeley, Daniel Ansong, Tsiri Agbenyega, Samuel Adjei, Harry Owusu Boateng, Theresa Rettig, John Bawa, Justice Sylverken, David Sambian, Alex Agyekum, Larko Owusu, Francis Martinson, Irving Hoffman, Tisungane Mvalo, Portia Kamthunzi, Ruthendo Nkomo, Albans Msika, Allan Jumbe, Nelecy Chome, Dalitso Nyakuipa, Joseph Chintedza, W Ripley Ballou, Myriam Bruls, Joe Cohen, Yolanda Guerra, Erik Jongert, Didier Lapierre, Amanda Leach, Marc Lievens, Opokua Ofori-Anyinam, Johan Vekemans, Terrell Carter, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia, .
N. Engl. J. Med.
PUBLISHED: 10-18-2011
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An ongoing phase 3 study of the efficacy, safety, and immunogenicity of candidate malaria vaccine RTS,S/AS01 is being conducted in seven African countries.
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Circumsporozoite-specific T cell responses in children vaccinated with RTS,S/AS01E and protection against P falciparum clinical malaria.
PLoS ONE
PUBLISHED: 07-11-2011
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RTS,S/AS01(E) is the lead candidate pre-erythrocytic malaria vaccine. In Phase IIb field trials the safety profile was acceptable and the efficacy was 53% (95%CI 31%-72%) for protecting children against clinical malaria caused by P. falciparum. We studied CS-specific T cell responses in order to identify correlates of protection.
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Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children.
J. Infect. Dis.
PUBLISHED: 06-02-2011
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RTS,S/AS01(E) is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection.
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Acute seizures attributable to falciparum malaria in an endemic area on the Kenyan coast.
Brain
PUBLISHED: 04-10-2011
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Falciparum malaria is an important cause of acute symptomatic seizures in children admitted to hospitals in sub-Saharan Africa, and these seizures are associated with neurological disabilities and epilepsy. However, it is difficult to determine the proportion of seizures attributable to malaria in endemic areas since a significant proportion of asymptomatic children have malaria parasitaemia. We studied children aged 0-13 years who had been admitted with a history of seizures to a rural Kenyan hospital between 2002 and 2008. We examined the changes in the incidence of seizures with the reduction of malaria. Logistic regression was used to model malaria-attributable fractions for seizures (the proportion of seizures caused by malaria) to determine if the observed decrease in acute symptomatic seizures was a measure of seizures that are attributable to malaria. The overall incidence of acute symptomatic seizures over the period was 651/100,000/year (95% confidence interval 632-670) and it was 400/100,000/year (95% confidence interval 385-415) for acute complex symptomatic seizures (convulsive status epilepticus, repetitive or focal) and 163/100,000/year (95% confidence interval 154-173) for febrile seizures. From 2002 to 2008, the incidence of all acute symptomatic seizures decreased by 809/100,000/year (69.2%) with 93.1% of this decrease in malaria-associated seizures. The decrease in the incidence of acute complex symptomatic seizures during the period was 111/100,000/year (57.2%) for convulsive status epilepticus, 440/100,000/year (73.7%) for repetitive seizures and 153/100,000/year (80.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures with parasitaemia were 92.9% (95% confidence interval 90.4-95.1%) for all acute symptomatic seizures, 92.9% (95% confidence interval 89.4-95.5%) for convulsive status epilepticus, 93.6% (95% confidence interval 90.9-95.9%) for repetitive seizures and 91.8% (95% confidence interval 85.6-95.5%) for focal seizures. The adjusted malaria-attributable fractions for seizures in children above 6 months of age decreased with age. The observed decrease in all acute symptomatic seizures (809/100?000/year) was similar to the predicted decline (794/100,000/year) estimated by malaria-attributable fractions at the beginning of the study. In endemic areas, falciparum malaria is the most common cause of seizures and the risk for seizures in malaria decreases with age. The reduction in malaria has decreased the burden of seizures that are attributable to malaria and this could lead to reduced neurological disabilities and epilepsy in the area.
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Serological evidence of discrete spatial clusters of Plasmodium falciparum parasites.
PLoS ONE
PUBLISHED: 03-01-2011
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Malaria transmission may be considered to be homogenous with well-mixed parasite populations (as in the classic Ross/Macdonald models). Marked fine-scale heterogeneity of transmission has been observed in the field (i.e., over a few kilometres), but there are relatively few data on the degree of mixing. Since the Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) is highly polymorphic, the hosts serological responses may be used to infer exposure to parasite sub-populations.
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Defining clinical malaria: the specificity and incidence of endpoints from active and passive surveillance of children in rural Kenya.
PLoS ONE
PUBLISHED: 07-30-2010
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Febrile malaria is the most common clinical manifestation of P. falciparum infection, and is often the primary endpoint in clinical trials and epidemiological studies. Subjective and objective fevers are both used to define the endpoint, but have not been carefully compared, and the relative incidence of clinical malaria by active and passive case detection is unknown.
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Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children.
PLoS ONE
PUBLISHED: 07-19-2010
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The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccines safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1?1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.
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Stable and unstable malaria hotspots in longitudinal cohort studies in Kenya.
PLoS Med.
PUBLISHED: 03-22-2010
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Infectious diseases often demonstrate heterogeneity of transmission among host populations. This heterogeneity reduces the efficacy of control strategies, but also implies that focusing control strategies on "hotspots" of transmission could be highly effective.
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Lack of avidity maturation of merozoite antigen-specific antibodies with increasing exposure to Plasmodium falciparum amongst children and adults exposed to endemic malaria in Kenya.
PLoS ONE
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Although antibodies are critical for immunity to malaria, their functional attributes that determine protection remain unclear. We tested for associations between antibody avidities to Plasmodium falciparum (Pf) antigens and age, asymptomatic parasitaemia, malaria exposure index (a distance weighted local malaria prevalence) and immunity to febrile malaria during 10-months of prospective follow up.
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A statistical interaction between circumsporozoite protein-specific T cell and antibody responses and risk of clinical malaria episodes following vaccination with RTS,S/AS01E.
PLoS ONE
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The candidate malaria vaccine RTS,S/AS01(E) provides significant but partial protection from clinical malaria. On in vitro circumsporozoite protein (CSP) peptide stimulation and intra-cellular cytokine staining of whole blood taken from 407 5-17 month-old children in a phase IIb trial of RTS,S/AS01(E), we identified significantly increased frequencies of two CSP-specific CD4+ T cells phenotypes among RTS,S/AS01(E) vaccinees (IFN?-IL2+TNF- and IFN?-IL2+TNF+ CD4+ T cells), and increased frequency of IFN?-IL2-TNF+ CD4+ T cells after natural exposure. All these T cells phenotypes were individually associated with reductions in the risk of clinical malaria, but IFN?-IL2-TNF+ CD4+ T cells independently predicted reduced risk of clinical malaria on multi-variable analysis (HR?=?0.29, 95% confidence intervals 0.15-0.54, p<0.0005). Furthermore, there was a strongly significant synergistic interaction between CSP-specific IFN?-IL2-TNF+ CD4+ T cells and anti-CSP antibodies in determining protection against clinical malaria (p?=?0.002). Vaccination strategies that combine potent cellular and antibody responses may enhance protection against malaria.
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A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants.
, Selidji Todagbe Agnandji, Bertrand Lell, José Francisco Fernandes, Béatrice Peggy Abossolo, Barbara Gaelle Nfono Ondo Methogo, Anita Lumeka Kabwende, Ayola Akim Adegnika, Benjamin Mordmüller, Saadou Issifou, Peter Gottfried Kremsner, Jahit Sacarlal, Pedro Aide, Miguel Lanaspa, John J Aponte, Sónia Machevo, Sozinho Acacio, Helder Bulo, Betuel Sigaúque, Eusébio Macete, Pedro Alonso, Salim Abdulla, Nahya Salim, Rose Minja, Maxmillian Mpina, Saumu Ahmed, Ali Mohammed Ali, Ali Takadir Mtoro, Ali Said Hamad, Paul Mutani, Marcel Tanner, Halidou Tinto, Umberto D'Alessandro, Hermann Sorgho, Innocent Valea, Biébo Bihoun, Issa Guiraud, Berenger Kaboré, Olivier Sombié, Robert Tinga Guiguemdé, Jean Bosco Ouédraogo, Mary J Hamel, Simon Kariuki, Martina Oneko, Chris Odero, Kephas Otieno, Norbert Awino, Meredith McMorrow, Vincent Muturi-Kioi, Kayla F Laserson, Laurence Slutsker, Walter Otieno, Lucas Otieno, Nekoye Otsyula, Stacey Gondi, Allan Otieno, Victorine Owira, Esther Oguk, George Odongo, Jon Ben Woods, Bernhards Ogutu, Patricia Njuguna, Roma Chilengi, Pauline Akoo, Christine Kerubo, Charity Maingi, Trudie Lang, Ally Olotu, Philip Bejon, Kevin Marsh, Gabriel Mwambingu, Seth Owusu-Agyei, Kwaku Poku Asante, Kingsley Osei-Kwakye, Owusu Boahen, David Dosoo, Isaac Asante, George Adjei, Evans Kwara, Daniel Chandramohan, Brian Greenwood, John Lusingu, Samwel Gesase, Anangisye Malabeja, Omari Abdul, Coline Mahende, Edwin Liheluka, Lincoln Malle, Martha Lemnge, Thor G Theander, Chris Drakeley, Daniel Ansong, Tsiri Agbenyega, Samuel Adjei, Harry Owusu Boateng, Theresa Rettig, John Bawa, Justice Sylverken, David Sambian, Anima Sarfo, Alex Agyekum, Francis Martinson, Irving Hoffman, Tisungane Mvalo, Portia Kamthunzi, Rutendo Nkomo, Tapiwa Tembo, Gerald Tegha, Mercy Tsidya, Jane Kilembe, Chimwemwe Chawinga, W Ripley Ballou, Joe Cohen, Yolanda Guerra, Erik Jongert, Didier Lapierre, Amanda Leach, Marc Lievens, Opokua Ofori-Anyinam, Aurélie Olivier, Johan Vekemans, Terrell Carter, David Kaslow, Didier Leboulleux, Christian Loucq, Afiya Radford, Barbara Savarese, David Schellenberg, Marla Sillman, Preeti Vansadia.
N. Engl. J. Med.
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The candidate malaria vaccine RTS,S/AS01 reduced episodes of both clinical and severe malaria in children 5 to 17 months of age by approximately 50% in an ongoing phase 3 trial. We studied infants 6 to 12 weeks of age recruited for the same trial.
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Memory B cells are a more reliable archive for historical antimalarial responses than plasma antibodies in no-longer exposed children.
Proc. Natl. Acad. Sci. U.S.A.
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Humans respond to foreign antigen by generating plasma Abs and memory B cells (MBCs). The Ab response then declines, sometimes to below the limit of detection. In contrast, MBCs are generally thought to be long-lived. We tested and compared Plasmodium falciparum (Pf)-specific Ab and MBC responses in two populations of children: (i) previously exposed children who had documented Pf infections several years ago, but minimal exposure since then; and (ii) persistently exposed children living in a separate but nearby endemic area. We found that although Pf-specific plasma Abs were lower in previously exposed children compared with persistently exposed children, their cognate MBCs were maintained at similar frequencies. We conclude that serological analysis by itself would greatly underestimate the true memory of Pf-specific Ab responses in previously exposed children living in areas where Pf transmission has been reduced or eliminated.
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Estimating individual exposure to malaria using local prevalence of malaria infection in the field.
PLoS ONE
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Heterogeneity in malaria exposure complicates survival analyses of vaccine efficacy trials and confounds the association between immune correlates of protection and malaria infection in longitudinal studies. Analysis may be facilitated by taking into account the variability in individual exposure levels, but it is unclear how exposure can be estimated at an individual level.
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Wind direction and proximity to larval sites determines malaria risk in Kilifi District in Kenya.
Nat Commun
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Studies of the fine-scale spatial epidemiology of malaria consistently identify malaria hotspots, comprising clusters of homesteads at high transmission intensity. These hotspots sustain transmission, and may be targeted by malaria-control programmes. Here we describe the spatial relationship between the location of Anopheles larval sites and human malaria infection in a cohort study of 642 children, aged 1-10-years-old. Our data suggest that proximity to larval sites predict human malaria infection, when homesteads are upwind of larval sites, but not when homesteads are downwind of larval sites. We conclude that following oviposition, female Anophelines fly upwind in search for human hosts and, thus, malaria transmission may be disrupted by targeting vector larval sites in close proximity, and downwind to malaria hotspots.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.