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{"title"=>"Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites", "type"=>"journal", "authors"=>[{"first_name"=>"Selidji Todagbe", "last_name"=>"Agnandji", "scopus_author_id"=>"8938791500"}, {"first_name"=>"Bertrand", "last_name"=>"Lell", "scopus_author_id"=>"35467226900"}, {"first_name"=>"José Francisco", "last_name"=>"Fernandes", "scopus_author_id"=>"36542398800"}, {"first_name"=>"Béatrice Peggy", "last_name"=>"Abossolo", "scopus_author_id"=>"54584816700"}, {"first_name"=>"Anita Lumeka", "last_name"=>"Kabwende", "scopus_author_id"=>"55522694600"}, {"first_name"=>"Ayola Akim", "last_name"=>"Adegnika", "scopus_author_id"=>"6602785245"}, {"first_name"=>"Benjamin", "last_name"=>"Mordmüller", "scopus_author_id"=>"6602694965"}, {"first_name"=>"Saadou", "last_name"=>"Issifou", "scopus_author_id"=>"8863503200"}, {"first_name"=>"Peter Gottfried", 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{"first_name"=>"Salim", "last_name"=>"Abdulla", "scopus_author_id"=>"7003814084"}, {"first_name"=>"Nahya", "last_name"=>"Salim", "scopus_author_id"=>"25926066700"}, {"first_name"=>"Ali Takadir", "last_name"=>"Mtoro", "scopus_author_id"=>"54397314500"}, {"first_name"=>"Paul", "last_name"=>"Mutani", "scopus_author_id"=>"55522796200"}, {"first_name"=>"Marcel", "last_name"=>"Tanner", "scopus_author_id"=>"7202127772"}, {"first_name"=>"Caroline", "last_name"=>"Mavere", "scopus_author_id"=>"55660184200"}, {"first_name"=>"Grace", "last_name"=>"Mwangoka", "scopus_author_id"=>"24473352100"}, {"first_name"=>"Omar", "last_name"=>"Lweno", "scopus_author_id"=>"56067240600"}, {"first_name"=>"Omar Ali", "last_name"=>"Juma", "scopus_author_id"=>"25925778800"}, {"first_name"=>"Seif", "last_name"=>"Shekalaghe", "scopus_author_id"=>"16239751900"}, {"first_name"=>"Halidou", "last_name"=>"Tinto", "scopus_author_id"=>"55975227100"}, {"first_name"=>"Umberto", "last_name"=>"D'Alessandro", 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"last_name"=>"Greenwood", "scopus_author_id"=>"36040863900"}, {"first_name"=>"John", "last_name"=>"Lusingu", "scopus_author_id"=>"6506419869"}, {"first_name"=>"Samwel", "last_name"=>"Gesase", "scopus_author_id"=>"14621527400"}, {"first_name"=>"Anangisye", "last_name"=>"Malabeja", "scopus_author_id"=>"25926015800"}, {"first_name"=>"Omari", "last_name"=>"Abdul", "scopus_author_id"=>"25925747400"}, {"first_name"=>"Coline", "last_name"=>"Mahende", "scopus_author_id"=>"54397507900"}, {"first_name"=>"Edwin", "last_name"=>"Liheluka", "scopus_author_id"=>"54397293400"}, {"first_name"=>"Martha", "last_name"=>"Lemnge", "scopus_author_id"=>"6701643049"}, {"first_name"=>"Thor G.", "last_name"=>"Theander", "scopus_author_id"=>"7006373193"}, {"first_name"=>"Chris", "last_name"=>"Drakeley", "scopus_author_id"=>"7003491251"}, {"first_name"=>"Joyce", "last_name"=>"Mbwana", "scopus_author_id"=>"56308591800"}, {"first_name"=>"Daniel", "last_name"=>"Ansong", "scopus_author_id"=>"6506910959"}, {"first_name"=>"Tsiri", "last_name"=>"Agbenyega", "scopus_author_id"=>"6603394104"}, {"first_name"=>"Samuel", "last_name"=>"Adjei", "scopus_author_id"=>"26642965300"}, {"first_name"=>"Harry Owusu", "last_name"=>"Boateng", "scopus_author_id"=>"37033362900"}, {"first_name"=>"Theresa", "last_name"=>"Rettig", "scopus_author_id"=>"57197311830"}, {"first_name"=>"John", "last_name"=>"Bawa", "scopus_author_id"=>"54584846800"}, {"first_name"=>"Justice", "last_name"=>"Sylverken", "scopus_author_id"=>"15065906800"}, {"first_name"=>"David", "last_name"=>"Sambian", "scopus_author_id"=>"15065889600"}, {"first_name"=>"Anima", "last_name"=>"Sarfo", "scopus_author_id"=>"55522271700"}, {"first_name"=>"Alex", "last_name"=>"Agyekum", "scopus_author_id"=>"36457577400"}, {"first_name"=>"Francis", "last_name"=>"Martinson", "scopus_author_id"=>"7004125502"}, {"first_name"=>"Irving", "last_name"=>"Hoffman", "scopus_author_id"=>"7006682600"}, {"first_name"=>"Tisungane", "last_name"=>"Mvalo", "scopus_author_id"=>"54397224900"}, {"first_name"=>"Portia", "last_name"=>"Kamthunzi", "scopus_author_id"=>"16307383700"}, {"first_name"=>"Rutendo", "last_name"=>"Nkomo", "scopus_author_id"=>"54397398100"}, {"first_name"=>"Tapiwa", "last_name"=>"Tembo", "scopus_author_id"=>"8349862200"}, {"first_name"=>"Gerald Tegha Mercy", "last_name"=>"Tsidya", "scopus_author_id"=>"56307857500"}, {"first_name"=>"Jane", "last_name"=>"Kilembe", "scopus_author_id"=>"55522255000"}, {"first_name"=>"Chimwemwe", "last_name"=>"Chawinga", "scopus_author_id"=>"55522541700"}, {"first_name"=>"W. Ripley", "last_name"=>"Ballou", "scopus_author_id"=>"7006273725"}, {"first_name"=>"Joe", "last_name"=>"Cohen", "scopus_author_id"=>"7410011184"}, {"first_name"=>"Yolanda", "last_name"=>"Guerra", "scopus_author_id"=>"26425038000"}, {"first_name"=>"Erik", "last_name"=>"Jongert", "scopus_author_id"=>"6507157621"}, {"first_name"=>"Didier", "last_name"=>"Lapierre", "scopus_author_id"=>"57191328128"}, {"first_name"=>"Amanda", "last_name"=>"Leach", "scopus_author_id"=>"24534928100"}, {"first_name"=>"Marc", "last_name"=>"Lievens", "scopus_author_id"=>"6603879458"}, {"first_name"=>"Opokua", "last_name"=>"Ofori-Anyinam", "scopus_author_id"=>"8571271900"}, {"first_name"=>"Aurélie", "last_name"=>"Olivier", "scopus_author_id"=>"36997970300"}, {"first_name"=>"Johan", "last_name"=>"Vekemans", "scopus_author_id"=>"7003555847"}, {"first_name"=>"David", "last_name"=>"Kaslow", "scopus_author_id"=>"7005919154"}, {"first_name"=>"Didier", "last_name"=>"Leboulleux", "scopus_author_id"=>"6603432510"}, {"first_name"=>"Barbara", "last_name"=>"Savarese", "scopus_author_id"=>"57188780167"}, {"first_name"=>"David", "last_name"=>"Schellenberg", "scopus_author_id"=>"7003483370"}], "year"=>2014, "source"=>"PLoS Medicine", "identifiers"=>{"pui"=>"373686460", "isbn"=>"10.1371/journal.pmed.1001685", "issn"=>"15491676", "doi"=>"10.1371/journal.pmed.1001685", "scopus"=>"2-s2.0-84905389306", "pmid"=>"25072396", "sgr"=>"84905389306"}, "id"=>"9193b341-bbf4-3ae1-a854-a1d87ba97296", "abstract"=>"BACKGROUND: A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.\\n\\nMETHODS AND FINDINGS: 6,537 infants aged 6-12 wk and 8,923 children aged 5-17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine. VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, p<0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT). VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization. Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol). VE waned over time in both age categories (Schoenfeld residuals p<0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from -1 to 49, respectively; corresponding ranges among infants were -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.\\n\\nCONCLUSIONS: RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.\\n\\nTRIAL REGISTRATION: www.ClinicalTrials.gov NCT00866619 Please see later in the article for the Editors' Summary.", "link"=>"http://www.mendeley.com/research/efficacy-safety-rtssas01-malaria-vaccine-during-18-months-after-vaccination-phase-3-randomized-contr-7", "reader_count"=>22, "reader_count_by_academic_status"=>{"Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>4, "Student > Master"=>6, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Librarian"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>4, "Student > Postgraduate"=>4, "Student > Master"=>6, "Student > Bachelor"=>3, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>1, "Environmental Science"=>1, "Mathematics"=>1, "Medicine and Dentistry"=>3, "Agricultural and Biological Sciences"=>13, "Chemistry"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>3}, "Chemistry"=>{"Chemistry"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Mathematics"=>{"Mathematics"=>1}, "Environmental Science"=>{"Environmental Science"=>1}}, "reader_count_by_country"=>{"Kenya"=>1}, "group_count"=>0}

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• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/b0284188-8d8c-4ffe-9707-e9425320b050", "title"=>"Should we introduce a malaria vaccine which may increase child mortality?", "body"=>"SAGE – WHO’s Strategic Advisory Group of Experts on Immunization – recently conducted a thorough review of the possible non-specific effects (NSE) of BCG, diphtheria-tetanus-pertussis (DTP) and measles (MV) vaccines (1) and concluded that these vaccines may have non-specific effects (2). The SAGE review concluded that the live attenuated MV and BCG vaccines approximately halved the mortality risk and these effects were not fully explained by the prevention of measles infection or tuberculosis. On the other hand, most studies of the inactivated DTP vaccine suggest that this vaccine is associated with increased mortality (1). The findings are supported by recent immunological evidence that vaccines may reprogram the innate immune system changing susceptibility to unrelated infections (3,4). \n\nNon-specific effects have major implications for the public health assessment of vaccines. Importantly, a vaccine’s overall benefit for public health cannot be predicted based on its ability to protect against the target disease. Furthermore, testing a vaccine against a comparator vaccine as ‘placebo’ should not be done, since the comparator vaccine may also have non-specific effects; for example, in initial trials of early MV in the 1980s we used inactivated polio vaccine (IPV) as a comparator vaccine, but subsequently found that IPV was associated with significantly increased female mortality, distorting the assessment of the MV effect (5). \n\nThe current evaluation of the RTS,S/AS01 malaria vaccine may be a good example of the challenges that non-specific effects imply for vaccine research (6). This 11-centre trial recruited 15,460 children in two age groups, at 6-12 weeks of age, the routine immunization age, and at 5-17 months of age. In the intervention group, the children received three doses of RTS,S. For the youngest children, the comparator vaccine was meningococcal C conjugate vaccine; for the oldest age group it was rabies vaccine. After 18 months of follow-up, RTS,S vaccine efficacy against clinical malaria was 46% (42-50%) in the older age group and 27% (20-32%) in the younger group and RTS,S was associated with a 19% (95% CI: 11-27%) reduction in all-cause hospitalization in the older age group and a 5% (-7-15%) reduction in the younger age group. It was concluded that RTS,S/AS01 could be an important addition to current malaria control in Africa(6). GSK is going to submit the vaccine for approval by the European Medicines Agency (EMA) and WHO expects to take a decision on the possible use of this vaccine in 2015 (7).\n\nThere can be little doubt that the vaccine will prevent many cases of malaria and health care costs will be reduced by preventing malaria treatment and malaria hospitalisations. Since a considerable part of infant and child mortality in Africa is due to malaria (8) one would also expect that the vaccine reduced mortality. However, as seen in Table 1, there is no indication that RTS,S is reducing mortality. Between the first dose and the third dose, RTS,S was associated with a mortality risk ratio (MRR) of 1.48 (0.91-2.39). The same slightly negative trend was found in both age groups. This trend was not compensated by lower mortality after all three doses of RTS,S; for the whole period of follow-up the MRR for RTS,S was 1.17 (0.88-1.56) compared with controls receiving the comparator vaccines. Moreover, there was a significant increase in meningitis in the children receiving RTS,S (Table 2); one-third of the children with meningitis died (10/29). \n\nThe authors suggest that the trial was conducted to very high standards with very low mortality and therefore they did not find an impact of RTS,S/AS01 on overall mortality. They speculate that the effect on mortality and co-infections might be greater were the vaccine to be deployed in a non-trial situation (6). \n\nUnfortunately we can have no idea what the effect would be in a real-life setting. The estimate for protection against malaria is based on comparison with vaccines which will not be used in the real-life situation. This is presumably justified by the assumption that the comparator vaccine has no relevant effect. However, several studies have found different inactivated vaccines including DTP, IPV and Hepatitis B vaccine to have deleterious and sometimes sex-differential non-specific effects (5, 9-11). If the comparator vaccines used in the current RTS,S trial (6) also had negative non-specific effects, it would lead to an overestimation of the benefits of RTS,S/AS01; in other words, the negative effect of RTS,S presented in Table 1 may have been underestimated. On the other hand, if the comparator vaccines have beneficial effects, the benefit of the RTS,S/AS01 vaccine may have been underestimated. \n\nAt this moment there is only one conclusion: We do not know what will be the real-life effect of introducing RTS,S for overall health – but there are some indications that the vaccine may be associated some negative consequences. Hopefully placebo controlled trials will be conducted to assure that future decisions about the introduction of RTS,S/AS01 are based on documented survival benefits. Since numerous studies of vaccines and micronutrients have shown that interventions have marked sex-differential effects, results should also be presented by sex (12-14). \n\nIntriguingly, intermittent preventive treatment against malaria in infancy (IPTi) has also been associated with reduced risk of malaria but no beneficial effect on survival (15). The global public health agenda should be to reduce mortality, not just to prevent specific diseases irrespective of the survival implications. \n\nPeter Aaby, Christine S Benn\n\nBandim Health Project, Indepth Network, Apartado 861, Bissau, Guinea-Bissau; and Research Centre for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark \n\n\n \nReferences\n1.\tHiggins JPT, Soares-Weiser K, Reingold A. Systematic review of the non-specific effects of BCG, DTP and measles containing vaccines. http://www.who.int/immunization/sage/meetings/2014/april - accessed June 1, 2014. \n2.\tStrategic Advisory Group of Experts on Immunization. Week Epidemiol Rec 2014;89: 233-235 \n3.\tKleinnijenhuis J, Quintin J, Preijers F, Joosten LA, Ifrim DC, Saeed S, et al. Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A 2012;109:17537-42\n4.\tJensen KJ, Larsen N, Biering-Sørensen S, Andersen A, Eriksen HB, Monteiro I, Hougaard D, Aaby P, Netea MG, Flanagan KL, Benn CB. Immunological heterologous effects of early BCG vaccination in low-birth weight infants in Guinea-Bissau: A randomised-controlled trial. JID 2014;epub \n5.\tAaby P, Garly ML, Nielsen J, Ravn H, Martins C, Balé C, Rodrigues A, Benn CS, Lisse IM. Increased female-male mortality ratio associated with inactivated polio and diphtheria-tetanus-pertussis vaccines: Observations from vaccination trials in Guinea-Bissau. PIDJ 2007;26:247-52\n6.\tThe RTS,S Clinical Trials Partnership. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: A phase 3 randomized, controlled trial and children and young infants at 11 African sites. PLOS Med 2014;11:e1001685\n7.\thttp://www.malariavaccine.org/files/RTSS_18_months_followup_RELEASE_EMBARGOED_UNTIL_0001_BST_08_Oct_2013_.pdf (accessed 21-09-2014)\n8.\tWorld Health Organisation. World malaria report 2012. Geneva, 2012: World Health Organisation\n9.\tGarly ML, Jensen H, Martins CL, Balé C, Balde MA, Lisse IM, Aaby P Hepatitis B vaccination associated with higher female than male mortality in Guinea-Bissau: an observational study. PIDJ 2004;23:1086-92\n10.\tAaby P, Benn CS, Nielsen J, Lisse IM, Rodrigues A, Ravn H. Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries. BMJ Open 2012;2:e000707.\n11.\tSørup S, Benn CS, Poulsen A, Krause T, Aaby P, Ravn H. Live vaccine against measles, mumps, and rubella and the risk of hospital admissions for nontargeted infections. JAMA 2014;311:826-35\n12.\tAaby P, Jensen H, Samb B, Cisse B, Sodeman M, Jakobsen M, et al. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus: re-analysis of West African studies. Lancet 2003;361: 2183-88\n13.\tBenn CS, Fisker A, Napirna BM, Roth A, Diness BR, Lausch KR, Ravn H, Yazdanbakhsh M, Rodrigues A, Whittle H, Aaby P. Vitamin A supplementation and BCG vaccination at birth in low birthweight neonates: two by two factorial randomised controlled trial. BMJ 2010;340:c1101\n14.\tFisker AB, Bale C, Rodrigues A, Balde A, Fernandes M, Jørgensen MJ, Danneskiold-Samsøe N, Hornshøj L, Rasmussen J, Christensen ED, Bibby BM, Aaby P, Benn CS. A randomised trial of high-dose vitamin A at vaccination contacts after 6 months of age. Pediatrics (in press)\n15.\tBenn CS, Aaby P. Does IPTi decrease malaria morbidity but not mortality? Lancet 2012; 380:958-60\n\n\n\n \nTable 1. Mortality risk by randomization group (4)\nTiming of effect and trial sub-groups\tDeath/number in group\tMortality risk ratio (95% CI)\n\tRTS,S\tControls\t\nFrom first dose to third dose\t\t\t\nGroup A\t31/4358\t11/2179\t1.41 (0.71-2.80)\nGroup B\t34/5949\t11/2974\t1.55 (0.78-3.05)\nCombined\t\t\t1.48 (0.91-2.39)\nFrom third dose to 18 months follow-up (per-protocol)\t\t\t\nGroup A\t52/3996\t23/2007\t1.14 (0.70-1.85)\nGroup B\t40/4557\t22/2328\t0.93 (0.55-1.56)\nCombined\t\t\t1.03 (0.73-1.48)\nFrom first dose to 18 months follow-up (intention-to-treat)\t\t\t\nGroup A\t83/4358\t34/2179\t1.22 (0.82-1.81)\nGroup B\t74/5949\t33/2974\t1.12 (0.75-1.69)\nCombined \t\t\t1.17 (0.88-1.56)\n\t\t\t\nNotes: Group A were children recruited at 6-12 weeks of age; Group B were children recruited at 5-17 months of age. The data presented here are based on Supplementary Table 10.\n\nTable 2. Incidence of meningitis by randomization group (4)\nTrial sub-groups\tIncidence of meningitis\tIRR\n\tRTS,S\tControls\t\nGroup A\t9/4358 (2 died)\t3/2179 (2 died)\t1.50 (0.41-5.55)\nGroup B\t16/5949 (5 died)\t1/2974 (1 died)\t8.00 (1.06-60.3)\nCombined\t\t\t3.12 (1.09-8.97)\nNotes: Group A were children recruited at 6-12 weeks of age; Group B were children recruited at 5-17 months of age. The data presented here are based on data presented in the section on ‘Safety’.\n\n\n", "isRemoved"=>false, "created"=>"2014-09-23T12:15:25Z", "lastModified"=>"2014-09-23T12:15:25Z", "creator"=>{"userId"=>"463585"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pmed.1001685", "state"=>"published", "journals"=>{"PLoSMedicine"=>{"journalKey"=>"PLoSMedicine", "eIssn"=>"1549-1676", "title"=>"PLOS Medicine"}}}, "replyTreeSize"=>1, "mostRecentActivity"=>"2014-11-08T18:37:03Z", "replies"=>[{"type"=>"REPLY", "parentID"=>81929, "annotationUri"=>"info:doi/10.1371/reply/44289dd3-b180-451c-b3de-68b2cce39ee0", "title"=>"The RTS,S/AS01 Phase 3 Trial Was Not Designed To Show Efficacy Against Mortality", "body"=>"We recently reported results from the RTS,S/AS01 phase 3 malaria vaccine trial during 18 months follow-up, prior to the administration of a booster dose [1]. Vaccine efficacy against clinical malaria was modest, 46% (95% CI 42% to 50%) in children vaccinated at age 5-17 months and 27% (95% CI 20% to 32%) in young infants vaccinated at age 6-12 weeks (per protocol population), but impact was considerable. The number of clinical malaria cases averted ranged across sites from 37 to 2365 per 1000 children vaccinated and from -10 to 1402 per 1,000 young infants vaccinated. Considering the high impact of the vaccine, Professor Aaby asks why no impact on mortality was demonstrated. The RTS,S/AS01 phase 3 trial was not designed to measure an impact on mortality; rather, in an effort to capture the primary outcome measure, clinical malaria, access to high quality care was enhanced, effective treatment was provided, and as would be expected, mortality was minimized. Thus, no conclusions on the impact of RTS,S/AS01 on mortality can, nor should, be drawn from this phase 3 trial. Given the massive contribution of malaria to childhood mortality, a vaccine with even modest efficacy against malaria episodes would be expected to have a substantial impact on mortality when rolled out in routine practice; whether this is the case for RTS,S/AS01 will need to be assessed in phase 4 studies. \n\nWe observed an imbalance in reported meningitis cases, with more among children who were vaccinated with RTS,S/AS01 at 5-17 months of age than children who received the rabies comparator vaccine. Meningitis cases were not clustered by time to onset, the cause of meningitis differed among cases, and no imbalance was seen in the young infants vaccinated at 6-12 weeks of age. At this time there is no evidence to conclude on the causal association between reported meningitis and RTS,S/AS01.\n\nProfessor Aaby expresses concern over the use of comparator vaccines for children randomized to the control arm, due to potential non-specific effects of the comparator vaccines, which, if present, could confound outcome measures. Study investigators, during the design of the study, considered the advantages and disadvantages of administering a true placebo or a comparator vaccine to children randomized to the control arm. The investigators, most of whom are practicing clinicians in Africa, concluded that participating children, all of whom live in high disease-burden areas, should receive a vaccine from which they might benefit, rather than receiving an injection with an inert substance. This decision is in accordance with recommendations from a WHO expert panel that reviewed placebo use in vaccine trials and recently stated, “Rather than using a true placebo control (i.e. an inert substance), it may be appropriate to use a vaccine against a disease that is not the focus of the trial”.[2] Rabies and meningococcal C vaccines were selected as suitable comparator vaccines for the RTS,S/AS01 trial. Both vaccines are well tolerated, potentially beneficial to study children, and neither have been associated with an overall negative mortality outcome; contrarily, both protect against life threatening illnesses.\n\nThe final analysis will look at vaccine efficacy by gender. \n\n\nMary J. Hamel, M.D.\nCenters for Disease Control and Prevention, Atlanta, GA\n\nTina Lucas Otieno, M.D., MPH\nKenya Medical Research Institute – Walter Reed Project, Kombewa, Kenya\n\nBrian Greenwood, M.D.\nLondon School of Hygiene and Tropical Medicine, London, United Kingdom\n\nfor the RTS,S Synthesis and Writing Committee\n\n\nThe findings and conclusions in this letter have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or policy.\n\n\n1. RTS,S Clinical Trials Partnership (2014) Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med 11: e1001685.\n2. Rid A, Saxena A, Baqui AH, Bhan A, Bines J, et al. (2014) Placebo use in vaccine trials: recommendations of a WHO expert panel. Vaccine 32: 4708-4712.", "isRemoved"=>false, "created"=>"2014-11-08T18:37:03Z", "lastModified"=>"2014-11-08T18:37:03Z", "creator"=>{"userId"=>"475590"}, "highlightedText"=>"", "competingInterestStatement"=>{"creatorWasPrompted"=>true, "hasCompetingInterests"=>false}, "parentArticle"=>{"doi"=>"info:doi/10.1371/journal.pmed.1001685", "state"=>"published", "journals"=>{"PLoSMedicine"=>{"journalKey"=>"PLoSMedicine", "eIssn"=>"1549-1676", "title"=>"PLOS Medicine"}}}, "replyTreeSize"=>0, "mostRecentActivity"=>"2014-11-08T18:37:03Z", "replies"=>[]}]}
• {"type"=>"COMMENT", "annotationUri"=>"info:doi/10.1371/annotation/404e838e-91a9-43e0-b936-6db9ddcc48b0", "title"=>"French Translation of the Article", "body"=>"GSK has provided PLOS Medicine with a French translation of this article which can be viewed below. A fully formatted version including the figures and tables is available at http://malariavaccine.org/files/2014-Plos-RTSS-French.pdf.\n\n-------------------------------------------------------\nEfficacité et sécurité du vaccin contre le paludisme RTS,S/AS01 18 mois après vaccination : Une étude de phase 3 randomisée et contrôlée chez des enfants et nourrissons de 11 sites africains\nThe RTS,S Clinical Trials Partnership¶*\n\n\n* Email: mhamel@cdc.gov (l’auteur correspondant: Mary J. Hamel)\n¶ La liste des membres du RTS,S Clinical Trials Partnership, et leur affiliations, se trouvent dans les remerciements de la version originale de cet article, DOI 10.1371/journal.pmed.1001685. \n\nRESUME\nContexte: Un vaccin contre le paludisme pourrait être un complément important aux stratégies actuelles de contrôle de la maladie. Nous présentons les données de sécurité et d’efficacité du vaccin (EV) RTS,S/AS01 au cours des 18 mois suivant la vaccination dans 11 sites africains présentant différents niveaux de transmission du paludisme.\nMéthodes et Résultats: 6537 nourrissons âgés de 6 à 12 semaines et 8923 enfants âgés de 5 à 17 mois ont été randomisés pour recevoir trois doses du vaccin RTS,S/AS01 ou d’un vaccin comparateur. L’EV contre le paludisme clinique chez les enfants pendant les 18 mois qui ont suivi la 3ème dose de vaccin (population per-protocole) était de 46% (95% CI 42% à 50%) (limites: 40%-77% ; EV, p<0,01 entre tous les sites). L’EV au cours des 20 mois qui ont suivi la première dose du vaccin (population en intention de traiter [ITT]) était de 45% (95% CI 41% à 49%). L’EV contre le paludisme grave, les hospitalisations dues au paludisme et les hospitalisations toutes causes confondues étaient de 34% (95% CI 15% à 48%), 41% (95% CI 30% à 50%), et 19% (95% CI 11% à 27%), respectivement (ITT). L’EV contre le paludisme clinique chez les nourrissons était de 27% (95% CI 20% à 32%, per-protocole; 27% [95% CI 21% à 33%], ITT), sans protection significative contre le paludisme grave, les hospitalisations dues au paludisme, ou les hospitalisations toutes causes confondues. La moyenne géométrique des titres d’anticorps anti-circumsporozoïte post-vaccination variait de 348 à 787 EU/ml selon les sites chez les enfants et de 117 à 335 EU/ml chez les nourrissons (per-protocole). L’EV a décliné au cours du temps dans les deux catégories d’âge (résidus de Schoenfeld p<0,001). Le nombre de cas de paludisme clinique et grave prévenus par 1000 enfants vaccinés allait de 37 à 2365 et de -1 à 49, respectivement; chez les nourrissons, ces nombres étaient de -10 à 1402 et -13 à 37, respectivement (ITT). Des cas de méningites ont été rapportées comme effets indésirables sérieux chez 16/5949 et 1/2974 enfants, et chez 9/4358 et 3/2179 nourrissons dans les groupes RTS,S/AS01 et contrôle, respectivement.\nConclusions: Le vaccin RTS,S/AS01 a prévenu de nombreux cas de paludisme clinique et grave au cours des 18 mois suivant la 3ème dose de vaccination, avec un impact plus important dans les zones où l’incidence du paludisme était la plus élevée. L’EV était plus élevée chez les enfants que chez les nourrissons, mais même avec un niveau d’efficacité modeste, le nombre de cas de paludisme clinique évités était substantiel. RTS,S/AS01 pourrait être un complément important aux mesures de contrôle actuelles du paludisme en Afrique.\nEnregistrement de l’étude: http://www.ClinicalTrials.gov NCT00866619\n \nINTRODUCTION\nDes avancées considérables ont été faites dans le contrôle du paludisme au cours de la dernière décennie, résultant de l’amélioration des moyens de diagnostic, de l’introduction d’un traitement efficace grâce aux combinaisons thérapeutiques à base d’artemisinine (CTA), et d’un déploiement à grande échelle de moustiquaires imprégnées d’insecticide (MII) [1,2]. Entre 2000 et 2012, on estime que la mortalité due au paludisme a baissé de 45% dans toutes les catégories d’âge et de 51% chez les enfants de moins de 5 ans. Cependant, Plasmodium falciparum a tout de même été la cause de 207 millions de cas de paludisme et 627000 morts en 2012, principalement chez de jeunes enfants d’Afrique sub-Saharienne [3], et les avancées récentes dans le contrôle du paludisme sont menacées par l’émergence d’une résistance aux insecticides et aux médicaments [4,5]. De nouvelles interventions sont requises si l’on veut combattre le paludisme dans les grandes zones d’Afrique où la transmission du paludisme reste élevée [6]. Un vaccin contre le paludisme est donc nécessaire pour accompagner les mesures actuelles.\nRTS,S/AS01 est à ce jour le candidat vaccin contre le paludisme le plus avancé et le premier à être évalué dans une étude de phase 3 à large échelle en Afrique. Le vaccin anti-paludisme RTS,S/AS01, qui cible le stade pré-érythrocytaire de P. falciparum, induit une réponse immunitaire humorale et cellulaire contre la protéine circumsporozoïte présente à la surface des sporozoïtes et des schizontes au stade hépatique. RTS,S fut identifié comme un candidat potentiel à un futur développement après que des résultats encourageant aient été obtenus dans une étude challenge expérimentale [7]. Les études de phase 2 qui ont suivi ont montré que chez des adultes et des enfants, le vaccin était sûr, immunogénique, et fournissait une protection contre les épisodes de paludisme clinique dans des limites de 30% à 60% [8-10]. On a montré que l’adjuvant AS01 était plus immunogénique que l’adjuvant AS02 utilisé initialement [11], et que RTS,S/AS01 était bien toléré et efficace [12-14]. Ces résultats encourageants ont incité à conduire une étude de phase 3 à large échelle incluant 15460 enfants recrutés sur 11 sites dans sept pays d’Afrique. Nous avons rapporté précédemment l’efficacité du vaccin (EV) et sa sécurité au cours des 12 mois de suivi [15,16]. La première analyse, menée sur 6000 enfants âgés de 5-17 mois au moment de la première vaccination, a montré que, dans la population per-protocole, RTS,S/AS01 assurait une protection de 56% (97,5% CI 51% à 60%) contre le premier ou le seul épisode de paludisme clinique et une efficacité de 47% (95% CI 22% à 64%) contre le paludisme grave pendant le suivi de 12 mois. L’EV était inférieure chez les nourrissons vaccinés à l’âge de 6-12 semaines quand RTS,S/AS01 était donné en même temps que les vaccins de routine du Programme Elargi de Vaccination (PEV); L’EV contre le premier ou seul épisode de paludisme dans la population per-protocole était de 31% (97,5% CI 24% à 38%) contre le paludisme clinique et de 37% (95% CI 5% à 38%) contre le paludisme grave. Le vaccin était immunogénique et globalement sûr d’utilisation, bien qu’un déséquilibre dans le nombre de cas de méningites a été observé entre les participants ayant reçu RTS,S/AS01 et ceux ayant reçu le vaccin contrôle (vaccin contre la rage pour les enfants de 5-17 mois à l’enrôlement, et vaccin conjugué contre le méningocoque C pour les nourrissons de 6-12 semaines à l’enrôlement), et ce dans les deux catégories d’âge [15,16]. Les objectifs des analyses présentées dans cet article visaient à déterminer l’EV dans les deux catégories d’âge durant 18 mois de suivi, juste avant l’administration d’une dose de rappel de RTS,S/AS01, et pour la première fois, à analyser les variations d’immunogénicité et d’EV par site. Les mesures spécifiques d’EV par site permettent d’estimer les facteurs déterminant de l’EV globale et sont utilisées pour calculer le nombre de cas de paludisme clinique et grave prévenus, mesures importantes de l’impact sur la santé publique et utiles pour les décideurs politiques.\n\nMETHODES\nLe protocole d’étude a été approuvé par le comité d’éthique de chaque site d’étude, par toutes les institutions partenaires et par les autorités nationales de chaque pays (Table S1A). L’étude a été menée dans le respect des recommandations de bonne pratique clinique (BPC) [17].\nDesign de l’Etude\nLes méthodes utilisées dans cette étude ont été rapportées précédemment [15,16,18] et sont disponibles dans le Texte S1. Cette étude randomisée, contrôlée et en double-aveugle du vaccin candidat contre le paludisme RTS,S/AS01 a été conduite dans 11 sites répartis dans sept pays d’Afrique (Figure 1). L’étude a été conçue pour évaluer l’efficacité, la sécurité et l’immunogénicité du vaccin pendant une période moyenne après première administration de 49 mois (limites: 41-55 mois) chez les enfants et 41 mois (limites: 32-48 mois) chez les nourrissons. Le consentement éclairé des parents ou gardiens des participants a été requis. Les enfants ayant à leur présentation une pathologie modérée à sévère, une malformation congénitale importante, une malnutrition requérant une hospitalisation, une concentration en hémoglobine inférieure à 5,0 g/dl ou à 8,0 g/dl avec signes cliniques de décompensation, un historique de convulsions fébriles atypiques, un problème neurologique, ou le SIDA à un stade III ou IV d’après les critères de l’OMS n’étaient pas éligibles pour cette étude. Des MII ont été fournis à tous les enfants qui se sont présentés au screening. L’utilisation de ces moustiquaires ou la protection via pulvérisation d’insecticide dans les maisons a été documentée au cours d’une visite à domicile 12 mois après la 3ème dose de vaccin. Des mesures anthropométriques ont été faites à l’enrôlement, un mois et 18 mois après la 3ème dose de vaccin.\n \n\nRandomisation et Vaccination\nEntre le 27 mars 2009 et le 31 janvier 2011, 15460 enfants et nourrissons ont été randomisés dans l’un des trois groupes de l’étude avec un ratio 1:1:1. Un groupe a reçu trois doses du vaccin RTS,S/AS01 suivie par une dose de rappel 18 mois après la 3ème dose; un 2ème groupe a reçu 3 doses du vaccin RTS,S/AS01 sans dose de rappel; et un 3ème groupe a reçu un vaccin comparateur: vaccin contre la rage (VeroRab, Sanofi-Pasteur) pour les enfants et vaccin conjugué contre le méningocoque C (Menjugate, Novartis) pour les nourrissons. La présente analyse combine les données des deux premiers groupes (que l’on nommera «groupe RTS,S/AS01») avant administration de la dose de rappel et les compare au 3ème groupe (contrôle) (Figure S1). Les nourrissons ont reçu le vaccin en même temps que les vaccins du PEV.\nSurveillance des cas de paludisme clinique et grave\nLes cas de paludisme ont été détectés par surveillance passive. Le paludisme clinique a été définie comme une maladie accompagnée d’une température ≥37,5°C et d’une parasitémie asexuée à P. falciparum (>5000 parasites/mm3). Les cas de paludisme graves ont été définis selon un algorithme. Les autres définitions sont présentées dans les Tables 1, 2, S2 et S5.\nSurveillance de la sécurité d’utilisation\nLes données relatives aux événements indésirables graves(EIGs) ont été collectées par surveillance passive. La classification des EIGs a été faite en utilisant toutes les données cliniques disponibles et n’était pas uniquement liée aux critères diagnostiques et tests de laboratoire. Des autopsies verbales ont été menées pour les décès survenus en-dehors de l’hôpital. Les EIGs ont été encodés en fonction du diagnostic du clinicien et selon les termes d’usage définis par le Medical Dictionary for Regulatory Activities (MedDRA) [19].\nImmunogénicité\nLes anticorps anti-circumsporozoïte (anti-CS) ont été mesurés par la méthode ELISA chez les 200 premiers patients de chaque catégorie d’âge et de chaque site, au moment de l’enrôlement et 1 mois après la 3ème dose de vaccin. Le seuil défini comme titre positif était 0,5 EU/ml [20].\nProcédures pour les tests de laboratoire et de radiologie\nLes procédures de laboratoire et de radiologie sont détaillées entièrement dans le Texte S1. Toutes les lames de frottis sanguins ont été lues par deux microscopistes indépendants, et les densités parasitaires déterminées par des procédures standardisées. Les résultats inconsistants ont été résolus selon un algorithme formel. Des méthodes biochimiques et hématologiques standardisées et automatisées ont été utilisées. Les méthodes de microbiologie standard pour la culture du sang et du liquide cérébrospinal ont été respectées grâce à l’utilisation d’incubateurs Bactec et de bouteilles pédiatriques (Bactec BD Diagnostic Systems). Un contrôle qualité extérieur rigoureux a été mis en place sur chaque site pour tous les tests de laboratoire relatifs aux critères d’évaluation de l’étude.\nAnalyse statistique\nL’efficacité contre tous les épisodes de paludisme a été analysée par régression binomiale négative avec temps de suivi comme variable d’ajustement permettant de tenir compte de l’interdépendance entre les épisodes d’un même sujet. Les estimations générales ont été ajustées par site (effet fixe) tandis que les estimations pour chaque site n’ont pas été ajustées pour les covariables. La variation inter-sites a été évaluée par évaluation de l’interaction statistique entre sites, des analyses univariées préétablies et des modèles multivariés ont été utilisés pour explorer l’impact des covariables sur les réponses anti-CS post-vaccination ou sur l’EV. Dans les modèles, l’intensité de transmission a été définie comme étant l’incidence des épisodes de paludisme chez les enfants ou nourrissons du groupe contrôle, en fonction de la catégorie d’âge inclue dans le modèle. L’EV en fonction des autres critères d’évaluation clinique a été estimée comme une réduction du risque relatif (RR) via la méthode des p-values exactes de Fisher. L’EV en fonction du temps a été évaluée par la méthode des p-values des résidus de Schoenfeld, par les modèles d’Andersen-Gill Cox avec covariables variant dans le temps et par la réduction d’incidence mesurée tous les 6 mois. L’impact du vaccin a été calculé comme étant la différence d’incidence des épisodes de paludisme entre deux groupes, exprimée par 1000 enfants vaccinés et mesurée tous les 6 mois au cours du suivi. Le nombre cumulatif de cas prévenus pour la période de 18 mois a été calculé en additionnant le nombre de cas prévenus durant chaque période de 6 mois. La population per-protocole comprend tous les participants qui ont reçu 3 doses de vaccin et qui ont contribué aux mesures d’efficacité débutant 14 jours après la 3ème dose. La population en intention de traiter (ITT) comprend tous les patients qui ont reçu au moins une dose de vaccin. Pour déterminer l’EV, nous avons utilisé la définition primaire du paludisme clinique, qui est plus spécifique. L’EV calculée en utilisant les définitions secondaires a également été rapportée. Les critères d’évaluation co-primaires d’EV chez les nourrissons et les enfants, présentés dans des publications précédentes, ont été décrits avec 97,5% CI ; tous les autres critères d’efficacité ont été présentés avec 95% CI. Une définition secondaire sensible (fièvre mesurée ou rapportée dans les dernières 24 h et densité en P. falciparum >0 parasites/mm3) a été utilisée pour évaluer l’impact du vaccin RTS,S/AS01 sur le paludisme clinique car dans la pratique clinique, les enfants malades se présentant dans un centre de soin avec une parasitémie de paludisme, quel que soit son niveau, reçoivent un traitement contre le paludisme. Les données ont été censurées au moment où la dose de rappel a été administrée, ou 20 mois après la première dose, ou selon le cas échéant à la date d’émigration, de rétraction du consentement ou de décès.\n\nRESULTATS\n\nPopulation de l’étude\nDans l’ensemble, 8923 enfants et 6537 nourrissons ont été enrôlés. Tous les enfants et nourrissons randomisés ont été inclus dans la population ITT, tandis que 6885 (77%) enfants et 6003 (92%) nourrissons ont été inclus dans la population per-protocole (Figures 2 et 3 ; Table S3). Les caractéristiques de base étaient similaires dans les deux groupes d’étude (vaccinés et contrôles) mais différentes d’un site à l’autre. L’utilisation des MII était de 78% chez les enfants et 86% chez les nourrissons (Figure S2, ITT). L’incidence du paludisme chez les nourrissons du groupe contrôle, une mesure approximative de la force d’infection de la maladie, variait de 0,03 à 4,27 épisodes par nourrisson et par an selon les centres (Table S4, per-protocole).\nEfficacité du vaccin chez les enfants\nL’incidence de tous les épisodes de paludisme clinique (selon la définition primaire) au cours des 18 mois de suivi dans la population per-protocole était de 0,69/personne-année dans le groupe RTS,S/AS01 et 1,17/personne-année dans le groupe contrôle. Ces résultats montrent une EV de 46% (95% CI 42% à 50%), avec dans l’ensemble, des estimations d’EV cohérentes au travers des différentes définitions de cas et cohérentes avec l’analyse dans la population ITT (ITT, EV = 45% [95% CI 41% à 49%]) (Tables 1 et S5 ; Figures 4, 5 et S3). Une hétérogénéité significative de l’EV a été observée entre les sites, avec une EV allant de 40% à 77% (test d’interaction, p<0,001 ; EV, p<0,01 pour tous les sites). L’EV dans la population ITT allait de 41% à 70% selon les sites. L’analyse de l’EV spécifique à chaque site dans la population per-protocole n’a pas suggéré que cette hétérogénéité soit liée à des variations de l’intensité de transmission (interaction entre le groupe d’étude et l’intensité de transmission, p=0,66). Une EV inférieure était associée avec une anémie modérée pré-vaccination (p=0,04) (Table S6). L’EV du vaccin a varié au cours du temps, son niveau le plus haut étant proche de la période de vaccination (résidus de Schoenfeld p<0,001) (Figure S4), mais le vaccin a conservé une efficacité tout au long de la période d’observation. La réduction du taux d’incidence du paludisme clinique par période de 6 mois était de 68% (95% CI 64% à 72%) au cours des mois 1-6, 41% (95% CI 36% à 46%) au cours des mois 7-12, et 26% (95% CI 19% à 33%) au cours des mois 13-18 suivant la 3ème dose de vaccin. Dans la population ITT, ces chiffres étaient de 60% (95% CI 56% à 64%), 41% (95% CI 36% à 46%), et 28% (95% CI 21% à 35%) (Figures S5 et S6). L’EV contre le paludisme clinique et le paludisme grave au cours des 12 premiers mois de suivi est présentée dans la Figure S8 et la Table S15. L’EV contre la parasitémie prévalente, 18 mois après vaccination, était de 31% (95% CI 17% à 42%) (ITT, EV = 29% [95% CI 15% à 40%]) (Table S7). L’EV était de 36% (95% CI 15% à 51%) contre le paludisme grave (ITT, EV contre le paludisme grave = 34% [95% CI 15% à 48%]), 42% (95% CI 29% à 52%) contre les hospitalisations dues au paludisme (ITT, EV contre les hospitalisations dues au paludisme = 41% [95% CI 30% à 50%]), et 19% (95% CI 9% à 28%) contre les hospitalisations toutes causes confondues (ITT, EV contre les hospitalisations toutes causes confondues = 19% [95% CI 11% à 27%]) (Table 1). L’incidence des cas de paludisme grave par période de 6 mois est présentée en Figure S5.\n \n \nPendant la période de suivi de 18 mois, le nombre de cas de paludisme clinique prévenus par 1000 enfants vaccinés avec RTS,S/AS01 dans la population ITT allait de 37 à 2365 en fonction des sites (moyenne pour les 11 sites: 829) et le nombre de cas de paludisme grave prévenus allait de -1 à 49 (moyenne pour tous les sites: 18) (Figures 6-11; Table S8). Le nombre d’hospitalisations dues au paludisme prévenues par 1000 enfants vaccinés allait de 0 à 138 selon les sites (moyenne pour les sites: 43) et les hospitalisations prévenues toutes causes confondues allaient de -3 à 132 (moyenne pour les sites: 52) au cours de la même période (Table S8). La mortalité était faible; 107 enfants (1,2%) sont morts pendant la période d’observation, 74/5949 (1,2%) enfants dans le groupe RTS,S/AS01 et 33/2974 (1,1%) dans le groupe contrôle. Le vaccin n’a pas montré d’efficacité contre la mortalité, la mortalité due au paludisme, les hospitalisations pour pneumonies, les septicémies ou les anémies prévalentes. Il n’a pas eu non plus d’effet notable sur le statut nutritionnel ou la croissance des enfants (Tables S7, S9, et S10 ; Figure S7).\nEfficacité du vaccin chez les nourrissons\nL’incidence de tous les épisodes de paludisme clinique respectant la définition primaire au cours des 18 mois de suivi dans la population per-protocole était de 0,71/personne-année dans le groupe RTS,S/AS01 et 0,92/personne-année dans le groupe contrôle. Ces résultats montrent une EV de 27% (95% CI 20% à 32%). Dans l’ensemble, les estimations étaient cohérentes au travers des différentes définitions et cohérentes avec l’analyse dans la population ITT (ITT, EV = 27% [95% CI 21% à 33%]) (Tables 2 et S5 ; Figures 12, 13, et S3). L’EV n’était pas différente à travers les différents sites (interaction entre le groupe étudié et le site, p = 0,17). L’EV a décliné au fil du temps (résidus de Schoenfeld p<0,001). La diminution de l’incidence du paludisme clinique par période de 6 mois était de 47% (95% CI 39% à 54%) au cours des mois 1-6, 23% (95% CI 15% à 31%) au cours des mois 7-12, et 12% (95% CI 1% à 21%) au cours des mois 13-18 suivant la 3ème dose. Dans la population ITT, ces chiffres étaient de 44% (95% CI 37% à 50%), 23% (95%CI 15% à 31%), et 13% (95% CI 2% à 22%) (Figures S5 et S6). L’EV était de 15% (95% CI -20% à 39%) contre le paludisme grave (ITT, EV contre le paludisme grave = 8% [95% CI -26% à 33%]), 17% (95% CI -7% à 36%) contre les hospitalisations dues au paludisme (ITT, EV contre les hospitalisations dues au paludisme = 13% [95% CI -10% à 31%]), et 6% (95% CI -7% à 17%) contre les hospitalisations toutes causes confondues (ITT, EV contre les hospitalisations toutes causes confondues = 5% [95% CI -7% à 15%]). Une augmentation statistiquement non-significative de l’incidence du paludisme grave a été observée dans le groupe RTS,S/AS01 au cours des 6 derniers mois de suivi (p=0,17) (Figure S5).\nPendant la période de suivi de 18 mois, le nombre de cas de paludisme clinique prévenus par 1000 nourrissons vaccinés avec RTS,S/AS01 dans la population ITT allait de -10 à 1402 en fonction des sites (moyenne pour les sites: 449) et le nombre de cas de paludisme grave prévenus allait de -13 à 37 (moyenne pour les sites: 6) (Figures 6-9, 14, et 15; Table S8). Cent-dix-sept nourrissons (1,8%) sont morts pendant les 20 mois d’observation, 83/4358 (1,9%) nourrissons dans le groupe RTS,S/AS01 et 34/2179 (1,6%) dans le groupe contrôle. Le vaccin n’a pas montré d’efficacité contre la mortalité en général, la mortalité due au paludisme, les hospitalisations pour pneumonies, les septicémies ou les anémies prévalentes. Il n’a pas eu non plus d’effet notable sur le statut nutritionnel ou la croissance des enfants (Table S7, S9, et S10).\n \n \nImmunogénicité\nChez les enfants, la moyenne géométrique des titres (GMT) d’anticorps anti-CS post-vaccination variait de 348 à 787 EU/ml selon le site, dans la population per-protocole (Figures 16 et 17, Table S16) mais les titres d’anticorps post-vaccination n’ont pas permis d’expliquer les différences d’efficacité observées entre les sites (p = 0,24) (Table S11). Une vaccination préalable contre l’hépatite B n’a pas été associée avec une meilleure réponse immunitaire anti-CS post-vaccination par RTS,S/AS01 (p = 0,73, Table S12). Cependant, un âge plus jeune au moment de la vaccination (5-11 mois contre 12-17 mois) et le fait de vivre dans une zone de plus haute transmission de la maladie ont pu être associés significativement avec une réponse anti-CS post-vaccination plus importante (p<0,001 et p<0,001 respectivement) (Table S12). La GMT d’anticorps anti-CS post-vaccination était plus faible chez les nourrissons (limites de GMT d’anticorps anti-CS parmi les sites: 117 à 335 EU/ml, population per-protocole) et, contrairement à ce qu’on a observé chez les enfants, un titre d’anticorps anti-CS plus élevé était associé avec une incidence du paludisme plus faible (p<0,001) (Figures 18 et 19, Tables S11 et S16). Un âge plus jeune (6 semaines contre 7-12 semaines) et la présence d’anticorps anti-CS pré-vaccination ont pu être associés avec une réponse immunitaire anti-CS post-vaccination plus faible (p = 0,003 et p<0,001, respectivement) (Table S12 et S13). Un graphe montrant les relations entre la GMT d’anticorps anti-CS, l’incidence du paludisme, et l’EV est présenté en Figure 20.\nSécurité d’utilisation\nChez les enfants, la fréquence d’EIGs était plus faible dans le groupe RTS,S/AS01 comparativement à celle observée dans le groupe contrôle: 18,6% (95%CI 17,6% à 19,6%) contre 22,7% (95%CI 21,2% à 24,3%). Chez les nourrissons par contre, la fréquence d’EIGs était similaire: 22,0% (95%CI 20,8% à 23,3%) dans le groupe RTS,S/AS01 contre 23,1% (95%CI 21,3% à 24,9%) dans le groupe contrôle (Table S14). Le déséquilibre rapporté précédemment dans l’incidence de méningite s’est maintenu [15,16]. Des cas de méningite ont été rapportés comme EIGs chez 17 enfants (16 cas parmi les 5949 enfants du groupe RTS,S/AS01 et un cas parmi les 2974 enfants du groupe contrôle [RR = 8,0 (95%CI 1,1 à 60,3)]). Dans 11 des 17 cas (10 du groupe RTS,S/AS01 et 1 du groupe contrôle), aucun agent pathogène n’a pu être identifié. Dans les 6 autres cas (tous du groupe RTS,S/AS01), un agent pathogène a pu être identifié (quatre cas de méningocoque, un cas de pneumocoque, et un cas d’Haemophilus influenzae). Six enfants pour lesquels une méningite a été rapportée sont morts, cinq dans le groupe RTS,S/AS01 et un dans le groupe contrôle. Des cas de méningite ont été rapportés comme EIGs chez 12 nourrissons (neuf cas parmi les 4358 nourrissons du groupe RTS,S/AS01 et trois cas parmi les 2179 du groupe contrôle [RR=1,50 (95%CI 0,41 à 5,55)]). Dans cinq cas, trois du groupe RTS,S/AS01 et deux du groupe contrôle, aucun agent pathogène n’a pu être identifié. Dans les sept autres cas, six du groupe RTS,S/AS01 et un du groupe contrôle, un agent pathogène a pu être identifié (quatre cas de pneumocoque et trois cas de salmonelle). Quatre nourrissons pour lesquels une méningite a été rapportée sont morts, deux dans le groupe RTS,S/AS01 et deux dans le groupe contrôle. Il n’y avait pas de relation temporelle entre la vaccination et les cas de méningite (Figure S9A). La plupart des sites d’études ont rapporté 1-3 cas de méningite durant la période de suivi de 18 mois, alors que le site de Lilongwe, Malawi, a rapporté 11 cas et le site de Kombewa, Kenya, a rapporté 5 cas (Figure S9B). Une vue d’ensemble des analyses rapportées ici est donnée en Table S17.\n \n\n \nDISCUSSION\n\nLe vaccin RTS,S/AS01 a eu un effet protecteur contre une série de critères prédéfinis, notamment contre le paludisme clinique et grave, pendant une période de suivi de 18 mois chez des enfants âgés de 5 à 17 mois au moment de la première vaccination, et ce dans un contexte varié de transmission du paludisme. L’EV contre le paludisme clinique était d’au moins 40% quel que soit le niveau de transmission, mais la variabilité inter-sites était significative. Comparativement aux études précédentes de phase 2, qui ont montré que l’efficacité du vaccin diminuait lorsque l’exposition augmentait [21,22], la variation d’EV observée dans cette étude ne pouvait être expliquée par des différences inter-sites de l’intensité de transmission du paludisme (calculée pour chaque site comme étant l’incidence du paludisme clinique chez les enfants ou nourrissons du groupe contrôle et considérée comme niveau moyen de transmission pour tous les participants d’un site donné). Il faut cependant être prudent dans l’interprétation de cette observation. Tout d’abord, la présence d’anémie modérée à l’enrôlement, qui pourrait refléter une exposition au paludisme au niveau individuel, a été associée négativement à l’efficacité du vaccin. Deuxièmement, chez les enfants, pour qui il n’y avait pas de corrélation entre l’EV et la transmission dans un modèle multivarié, l’EV semblait meilleure sur les sites où l’incidence était plus faible (Figure 4). Les différences d’incidence du paludisme clinique entre les différents sites pourraient être influencées par des facteurs génétiques et environnementaux divers indépendants du niveau de transmission. Les différences de réponse immunitaire anti-CS dans les différents sites n’ont pas permis d’expliquer les différences d’efficacité.\nL’EV contre le paludisme clinique était plus faible chez les nourrissons que chez les enfants. Bien que la différence ne fut pas statistiquement significative, les cas de paludisme grave ont été plus fréquents chez les nourrissons du groupe RTS,S/AS01 que chez les nourrissons du groupe contrôle au cours des six derniers mois d’observation (12-18 mois après la 3ème dose de vaccin). Cette observation pourrait être due au hasard ou pourrait indiquer que le vaccin a interféré avec l’acquisition de l’immunité naturelle [23], un effet pouvant également être dû à un accès rapide au diagnostic et au traitement. Un suivi plus approfondi est prévu et inclura une étude détaillée du 1/3 des participants qui ont reçu la série de vaccination primaire avec RTS,S/AS01 mais pas la dose de rappel.\nLa présente analyse a fourni des informations qui pourraient expliquer pourquoi les nourrissons répondent moins bien au vaccin RTS,S/AS01 que les enfants. Les anticorps maternels ont vraisemblablement joué un rôle étant donné que les nourrissons chez qui on a mesuré un niveau détectable d’anticorps anti-CS pré-vaccination ont eu une réponse immunitaire anti-CS plus faible que les enfants sans anticorps anti-CS pré-vaccination, et qu’une concentration élevée d’anticorps anti-CS post-vaccination a pu être associée à une meilleure efficacité chez les nourrissons. Cependant, les anticorps maternels ne peuvent pas entièrement expliquer la réponse anti-CS plus faible chez les nourrissons vaccinés, étant donné que les nourrissons sans anticorps anti-CS détectables ont malgré tout montré une GMT d’anticorps anti-CS post-vaccination plus faible que les enfants vaccinés. Une interférence immunitaire due à l’administration simultanée du vaccin RTS,S/AS01 et des vaccins du PEV reste un facteur possible. Le fait que les études de phase 2 aient montré qu’une co-administration dans un contexte donné a pu être associée avec une réponse anti-CS plus faible par rapport à une administration séparée dans d’autres contextes, supporte cette hypothèse.[9,10] Un effet suppresseur lié à l’exposition aux antigènes du paludisme in-utero pourrait être plus marqué chez les nourrissons que chez les enfants plus âgés qui ont eu une plus longue période pour acquérir leur immunité [24,25]. Enfin, le système immunitaire immature des nourrissons pourrait ne pas répondre aussi bien que celui des enfants plus âgés. Contrairement aux résultats obtenus dans une étude de phase 2 [26], nous n’avons pas pu montrer qu’une vaccination préalable contre l’hépatite B chez les enfants augmentait leur réponse immunitaire anti-CS.\nL’EV a diminué au fil du temps aussi bien chez les enfants que chez les nourrissons, comme rapporté précédemment [15,16]. Une analyse par période de 6 mois a montré que le vaccin protégeait contre le paludisme clinique tout au long de la période de suivi, mais qu’il y avait une diminution progressive de son efficacité. Cependant, ces analyses doivent être interprétées avec prudence. Même si les groupes étudiés étaient bien assortis durant les 6 premiers mois, ce n’était plus le cas par après car plus d’enfants du groupe contrôle ont été frappés par un paludisme clinique que dans le groupe RTS,S/AS01, et peuvent dès lors avoir acquis une immunité naturelle faisant paraître le vaccin moins efficace en comparaison. Il sera important de déterminer si l’EV peut être restaurée grâce à une dose de rappel, telle que celle donnée après 18 mois de suivi à la moitié des patients du groupe RTS,S/AS01.\nL’étude a répondu à des standards éthiques et cliniques élevés, avec des procédures harmonisées à travers les sites [27,28]. Néanmoins, certaines anomalies ont été observées. Le manque d’EV chez les nourrissons à Kintampo, Ghana, malgré une efficacité de 47% chez les enfants et une GMT d’anticorps anti-CS post-vaccination dans la moyenne des autres sites, était inattendu. De même, le manque d’efficacité contre les infections prévalentes de paludisme 18 mois post-vaccination chez les enfants de Siaya, Kenya, reste inexpliqué. Ces résultats pourraient être dus au hasard mais requièrent une analyse approfondie.\nLe niveau élevé des standards de cette étude a requis une facilitation de l’accès des patients de l’étude aux soins dans et hors des hôpitaux; l’achat d’équipements cliniques et laboratoires supplémentaires; la garantie d’un approvisionnement continu des médicaments nécessaires, d’oxygène et de sang; et l’augmentation du personnel clinique. Par conséquent, la mortalité a été très faible dans les deux groupes d’étude. Ceci pourrait expliquer pourquoi, contrairement aux résultats d’études effectuées avec d’autres moyens de contrôle du paludisme tels que les MII ou les médicaments prophylactiques, nous n’avons pas observé un impact de RTS,S/AS01 sur la mortalité générale [29,30] ou sur le statut nutritionnel [31]. Nous n’avons pas non plus observé d’impact du vaccin sur l’incidence des hospitalisations pour pneumonies ou pour septicémies. L’impact du vaccin RTS,S/AS01 sur la mortalité et les co-infections pourrait être plus grand si le vaccin était utilisé dans des situations différentes de l’étude, où un accès rapide à des soins de qualités est moins facilement disponible.\nLa relation observée entre la présence d’anémie modérée et l’efficacité réduite du vaccin chez les enfants plus âgés est intrigante. Comme expliqué précédemment, l’anémie pourrait être un marqueur sensible de l’exposition individuelle au paludisme. D’un autre côté, l’anémie pourrait indiquer une infection active de paludisme, ce qui pourrait interférer avec le développement d’une réponse immunitaire robuste suite à la vaccination [32]. L’infection par des vers intestinaux (Helminthes) est une autre cause fréquente d’anémie chez les bébés et les enfants en Afrique sub-Saharienne et peut aussi induire une réponse immunitaire plus faible après vaccination [33] La malnutrition est fréquemment associée à l’anémie, mais nous n’avons pas montré que la malnutrition avait un impact sur l’EV dans notre modèle multivarié.\nDans l’ensemble, l’incidence d’EIGs était similaire dans les deux groupes mais le déséquilibre au niveau des cas de méningite, déjà remarqué précédemment [15,16], s’est maintenu, et la différence entre les deux groupes est devenue significative chez les enfants plus âgés. Nous n’avons pas trouvé d’explication évidente à cette association; il n’y a pas de relation temporelle avec la vaccination et une relation biologique entre les deux phénomènes semble peu probable. Une relation de cause à effet ne peut ni être confirmé ni exclue pour le moment. La survenue de méningites sera suivie de près pendant le reste de l’étude et une attention particulière sera portée à l’impact possible de la dose de rappel.\nComme toute étude multi-centres à large échelle, cette étude a montré des faiblesses. Bien que des efforts rigoureux aient été entrepris pour standardiser les méthodes cliniques et de laboratoire dans tous les centres de cette étude, il peut y avoir eu des variations dans les caractéristiques cliniques des patients recrutés dans certains centres, ce qui pourrait avoir contribué aux variations du niveau d’EV observées entre les sites. Il est possible que les variations de facteurs tels que la prévalence de co-infections (HIV inclus), la déficience en micronutriments, ou le statut socio-économique aient pu contribuer à l’hétérogénéité de l’immunogénicité et de l’EV entre les sites, mais ces facteurs n’ont pas été évalués de manière systématique. Enfin, l’incidence du paludisme clinique chez les nourrissons a été utilisée comme mesure indirecte de l’intensité de transmission du paludisme pour chaque site, et il est possible que ce ne soit pas un facteur très discriminatoire, parce qu’elle peut être influencée par d’autres variables comme le transfert d’anticorps maternels contre le paludisme ou l’accès au traitement. Une mesure directe de l’exposition telle que le taux d’inoculation entomologique pourrait avoir classé les centres dans un ordre différent. Les variations de l’immunogénicité et de l’EV de RTS,S/AS01 entre les sites ne peuvent être expliquées uniquement par le niveau de transmission du paludisme, mais la nature des autres facteurs ayant pu jouer un rôle reste encore à déterminer.\nAu cours des 18 mois de suivi, le vaccin RTS,S/AS01 a permis de prévenir de nombreux cas de paludisme clinique et grave dans les 11 sites de l’étude. 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Clement F, Dewar V, Van Braeckel E, Desombere I, Dewerchin M, et al. (2012) Validation of an enzyme-linked immunosorbent assay for the quantification of human IgG directed against the repeat region of the circumsporozoite protein of the parasite Plasmodium falciparum. Malar J 11: 384.\n21. Olotu A, Fegan G, Wambua J, Nyangweso G, Awuondo KO, et al. (2013) Four-year efficacy of RTS,S/AS01E and its interaction with malaria exposure. N Engl J Med 368: 1111–1120.\n22. Bejon P, White MT, Olotu A, Bojang K, Lusingu JP, et al. (2013) Efficacy of RTS,S malaria vaccines: individual-participant pooled analysis of phase 2 data. Lancet Infect Dis 13: 319–327.\n23. Gatton ML, Cheng Q (2004) Modeling the development of acquired clinical immunity to Plasmodium falciparum malaria. Infect Immun 72: 6538–6545.\n24. Gbedande K, Varani S, Ibitokou S, Houngbegnon P, Borgella S, et al. (2013) Malaria modifies neonatal and early-life Toll-like receptor cytokine responses. Infect Immun 81: 2686–2696.\n25. Dauby N, Goetghebuer T, Kollmann TR, Levy J, Marchant A (2012) Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections. Lancet Infect Dis 12: 330–340.\n26. Owusu-Agyei S, Ansong D, Asante K, Kwarteng Owusu S, Owusu R, et al. (2009) Randomized controlled trial of RTS,S/AS02D and RTS,S/AS01E malaria candidate vaccines given according to different schedules in Ghanaian children. PLoS ONE 4: e7302.\n27. Swysen C, Vekemans J, Bruls M, Oyakhirome S, Drakeley C, et al. (2011) Development of standardized laboratory methods and quality processes for a phase III study of the RTS, S/AS01 candidate malaria vaccine. Malar J 10: 223.\n28. Vekemans J, Marsh K, Greenwood B, Leach A, Kabore W, et al. (2011) Assessment of severe malaria in a multicenter, phase III, RTS, S/AS01 malaria candidate vaccine trial: case definition, standardization of data collection and patient care. Malar J 10: 221.\n29. Lengeler C (2004) Insecticide-treated bed nets and curtains for preventing malaria. Cochrane Database Syst Rev 2004: CD000363.\n30. Greenwood BM, Greenwood AM, Bradley AK, Snow RW, Byass P, et al. (1988) Comparison of two strategies for control of malaria within a primary health care programme in the Gambia. Lancet 1: 1121–1127.\n31. ter Kuile FO, Terlouw DJ, Phillips-Howard PA, Hawley WA, Friedman JF, et al. (2003) Impact of permethrin-treated bed nets on malaria and all-cause morbidity in young children in an area of intense perennial malaria transmission in western Kenya: cross-sectional survey. Am J Trop Med Hyg 68: 100–107.\n32. Williamson WA, Greenwood BM (1978) Impairment of the immune response to vaccination after acute malaria. Lancet 1: 1328–1329.\n33. Markus MB, Fincham JE (2007) Helminthiasis, bystander diseases and vaccines: analysis of interaction. Trends Parasitol 23: 517–519.\n34. Hay SI, Guerra CA, Gething PW, Patil AP, Tatem AJ, et al. 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• {"id"=>"494219347565346817", "text"=>"Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine : promising news http://t.co/46hWwBZ3ra", "created_at"=>"2014-07-29T20:34:09Z", "user"=>"isieleunou", "user_name"=>"isidore sieleunou", "user_profile_image"=>"http://pbs.twimg.com/profile_images/416783460/SA500033_normal.JPG"}
• {"id"=>"494241730632626177", "text"=>"RT @PeterHotez: Just out in @PLOSMedicine latest results of RTS/S malaria vaccine phase 3 trials http://t.co/OQARAcuXhj", "created_at"=>"2014-07-29T22:03:05Z", "user"=>"emmacarpas", "user_name"=>"Emma_Carmelo", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3384549427/dda1dea1be44860943d24dc8a5f2031e_normal.jpeg"}
• {"id"=>"494252488480923649", "text"=>"RT @PeterHotez: Just out in @PLOSMedicine latest results of RTS/S malaria vaccine phase 3 trials http://t.co/OQARAcuXhj", "created_at"=>"2014-07-29T22:45:50Z", "user"=>"DrFrankBeard", "user_name"=>"Frank Beard", "user_profile_image"=>"http://pbs.twimg.com/profile_images/450590800028520449/AEHIhhlF_normal.jpeg"}
• {"id"=>"494254003191308289", "text"=>"RT @norabar: La nueva vacuna contra la malaria mostró efecto durante 18 meses de seguimiento http://t.co/nHk5N6Oyy4", "created_at"=>"2014-07-29T22:51:51Z", "user"=>"LucasMicheli", "user_name"=>"Lucas Micheli", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1834289102/micheli_1328723617_1_normal.jpg"}
• {"id"=>"494254011265347584", "text"=>"RT @norabar: La malaria provoca 800.000 muertes por año, principalmente en chicos http://t.co/nHk5N6Oyy4", "created_at"=>"2014-07-29T22:51:53Z", "user"=>"LucasMicheli", "user_name"=>"Lucas Micheli", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1834289102/micheli_1328723617_1_normal.jpg"}
• {"id"=>"494261157989867521", "text"=>"woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-29T23:20:17Z", "user"=>"mwpennell", "user_name"=>"mwpennell", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3163007668/9b709ba76f45e2bbdb75ecf9aad66267_normal.jpeg"}
• {"id"=>"494272974422171648", "text"=>"말라리아 백신 개발에 큰 진전이 있었던 모양이다. 기사: http://t.co/LRmTbcKKHr 논문: http://t.co/Vy2mZFzOAM", "created_at"=>"2014-07-30T00:07:14Z", "user"=>"kkendd", "user_name"=>"Victor Yoon", "user_profile_image"=>"http://pbs.twimg.com/profile_images/465608743338508288/H6nYn1F0_normal.jpeg"}
• {"id"=>"494274380743331841", "text"=>"@Marisabastidas ve! \"@norabar: La nueva vacuna contra la malaria mostró efecto durante 18 meses de seguimiento http://t.co/2oksdGG4WQ\"", "created_at"=>"2014-07-30T00:12:50Z", "user"=>"RaulChiT", "user_name"=>"Raul Chirivella", "user_profile_image"=>"http://pbs.twimg.com/profile_images/426777672115421184/srEs4WIU_normal.jpeg"}
• {"id"=>"494276055424069632", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T00:19:29Z", "user"=>"GraemeTLloyd", "user_name"=>"Graeme Lloyd", "user_profile_image"=>"http://pbs.twimg.com/profile_images/462920087863713792/F14GOTWU_normal.jpeg"}
• {"id"=>"494279539640774656", "text"=>"Malaria Vaccine reduces prevalence of Malaria up to at least 18 months. http://t.co/lfz2AWMgcQ", "created_at"=>"2014-07-30T00:33:20Z", "user"=>"Science_Reddit", "user_name"=>"Reddit Science", "user_profile_image"=>"http://pbs.twimg.com/profile_images/480229204919742465/DHLw_QAc_normal.png"}
• {"id"=>"494284465565609984", "text"=>"RTS,S malaria vaccine efficacy isn't great, but effect lasts &gt;18 mo, preventing many cases in new @PLOSMedicine trial http://t.co/wd6G80lvGV", "created_at"=>"2014-07-30T00:52:54Z", "user"=>"CameronNutt", "user_name"=>"Cameron Taylor Nutt", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1785813929/Screen_shot_2012-01-28_at_12.29.43_AM_normal.png"}
• {"id"=>"494285129398120448", "text"=>"RT @CameronNutt: RTS,S malaria vaccine efficacy isn't great, but effect lasts &gt;18 mo, preventing many cases in new @PLOSMedicine trial http…", "created_at"=>"2014-07-30T00:55:32Z", "user"=>"jkhmlf", "user_name"=>"Faisal M Shah", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2557959251/image_normal.jpg"}
• {"id"=>"494290123727458304", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T01:15:23Z", "user"=>"laurentiusme", "user_name"=>"Michael Laurentius", "user_profile_image"=>"http://pbs.twimg.com/profile_images/466019294074007552/6Fk3FmtQ_normal.jpeg"}
• {"id"=>"494293840514150400", "text"=>"Malaria vaccination continues to provide resistance to the parasite for up to 18 months, say intl. scientists http://t.co/O892nLN5F1", "created_at"=>"2014-07-30T01:30:09Z", "user"=>"AusSMC", "user_name"=>"Au Science Media Ctr", "user_profile_image"=>"http://pbs.twimg.com/profile_images/488888199431741440/yPdP6Z2j_normal.jpeg"}
• {"id"=>"494294226583044096", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T01:31:41Z", "user"=>"laurapennell", "user_name"=>"Laura Pennell", "user_profile_image"=>"http://pbs.twimg.com/profile_images/486344355527929856/7ydf0UYT_normal.jpeg"}
• {"id"=>"494305025166815233", "text"=>".@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T02:14:36Z", "user"=>"PLOSMedicine", "user_name"=>"PLOS Medicine", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2436335697/k93oob5au2gllc775hk5_normal.jpeg"}
• {"id"=>"494305118595350528", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T02:14:58Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"494305266192494593", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T02:15:33Z", "user"=>"_sarahtsang", "user_name"=>"Sarah Tsang", "user_profile_image"=>"http://pbs.twimg.com/profile_images/485992840044896256/uux1K1Ou_normal.jpeg"}
• {"id"=>"494305675833802752", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T02:17:11Z", "user"=>"shyduroff", "user_name"=>"shyduroff", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3695201339/dcec331712656e45a8bbeebc392e5ec8_normal.jpeg"}
• {"id"=>"494305758243467264", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T02:17:31Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494307038512435200", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T02:22:36Z", "user"=>"PeterASinger", "user_name"=>"Peter Singer", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467718884544356352/IQHYvXUg_normal.png"}
• {"id"=>"494307300996550656", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T02:23:39Z", "user"=>"sidsingh23", "user_name"=>"Sid Singh", "user_profile_image"=>"http://pbs.twimg.com/profile_images/457250598425878528/ALLxJqcI_normal.jpeg"}
• {"id"=>"494310999537631233", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T02:38:20Z", "user"=>"SusanaDeLeonMD", "user_name"=>"Susana De Leon", "user_profile_image"=>"http://pbs.twimg.com/profile_images/455575711034925056/nTg9qDAu_normal.jpeg"}
• {"id"=>"494313716511682560", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T02:49:08Z", "user"=>"GAVI_Daniel", "user_name"=>"Daniel Thornton", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3348167826/54d8124c88ec3f77043c3ef2434461e5_normal.jpeg"}
• {"id"=>"494323370184683520", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T03:27:30Z", "user"=>"sciencemug", "user_name"=>"SM", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2732112003/92be57ca5dbeab4a1959bd4b2503a00e_normal.png"}
• {"id"=>"494324116678144001", "text"=>"RT @AusSMC: Malaria vaccination continues to provide resistance to the parasite for up to 18 months, say intl. scientists http://t.co/O892n…", "created_at"=>"2014-07-30T03:30:28Z", "user"=>"MelanieBagg", "user_name"=>"Dr Melanie Bagg", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1752003252/Photo_on_13-01-12_at_11.15_PM_normal.jpg"}
• {"id"=>"494324357779689473", "text"=>"RT @AusSMC: Malaria vaccination continues to provide resistance to the parasite for up to 18 months, say intl. scientists http://t.co/O892n…", "created_at"=>"2014-07-30T03:31:25Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494324815545655296", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T03:33:14Z", "user"=>"jovtsang", "user_name"=>"Jovian", "user_profile_image"=>"http://pbs.twimg.com/profile_images/454698943016730624/WjEo9crH_normal.jpeg"}
• {"id"=>"494339828860071936", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T04:32:54Z", "user"=>"ftissandier", "user_name"=>"Fred Tissandier", "user_profile_image"=>"http://pbs.twimg.com/profile_images/471557721053868032/5axhtDP1_normal.jpeg"}
• {"id"=>"494347766009966592", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T05:04:26Z", "user"=>"graysouth", "user_name"=>"Eve Gray", "user_profile_image"=>"http://pbs.twimg.com/profile_images/460045245783105536/F9Z3v9jK_normal.jpeg"}
• {"id"=>"494354938005172224", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T05:32:56Z", "user"=>"yanivbrandvain", "user_name"=>"yaniv brandvain", "user_profile_image"=>"http://pbs.twimg.com/profile_images/471872362535583744/DBntshej_normal.jpeg"}
• {"id"=>"494355040698920960", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T05:33:21Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494360730133889024", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T05:55:57Z", "user"=>"marcotrizzino", "user_name"=>"Marco Trizzino", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000164878982/ab0fea28af867aec54cad75c18f84819_normal.jpeg"}
• {"id"=>"494363818672537600", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T06:08:13Z", "user"=>"MedicinaOS", "user_name"=>"medicinaopensource", "user_profile_image"=>"http://pbs.twimg.com/profile_images/491182235778023424/u3-qEunR_normal.jpeg"}
• {"id"=>"494363942819332096", "text"=>"Malaria Vaccine reduces prevalence of Malaria up to at least 18 months. http://t.co/HKptYxccX6", "created_at"=>"2014-07-30T06:08:43Z", "user"=>"pradt", "user_name"=>"pradt", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494306101840457728/M3aWF5X0_normal.jpeg"}
• {"id"=>"494364096780070912", "text"=>"RT @pradt: Malaria Vaccine reduces prevalence of Malaria up to at least 18 months. http://t.co/HKptYxccX6", "created_at"=>"2014-07-30T06:09:20Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494376909199781890", "text"=>"Malaria Vaccine reduces prevalence of Malaria up to at least 18 months. http://t.co/o18g3KwZvV", "created_at"=>"2014-07-30T07:00:14Z", "user"=>"GeDesPi", "user_name"=>"Gerald Pilcher", "user_profile_image"=>"http://pbs.twimg.com/profile_images/452129616845471744/uhIL4cvN_normal.png"}
• {"id"=>"494378288413175808", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T07:05:43Z", "user"=>"brianglanz", "user_name"=>"Brian Glanz", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1595837245/BGHI2_normal.jpg"}
• {"id"=>"494379351333670913", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T07:09:57Z", "user"=>"petermbenglish", "user_name"=>"Peter English", "user_profile_image"=>"http://pbs.twimg.com/profile_images/470915423374815232/pn-fl_lA_normal.jpeg"}
• {"id"=>"494396951928913920", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-30T08:19:53Z", "user"=>"RPrasad12", "user_name"=>"R. Prasad", "user_profile_image"=>"http://pbs.twimg.com/profile_images/452415046761463809/X4kboMHn_normal.jpeg"}
• {"id"=>"494403872178593792", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T08:47:23Z", "user"=>"Billare", "user_name"=>"Billare", "user_profile_image"=>"http://pbs.twimg.com/profile_images/491654168038219777/CTVDuKWc_normal.jpeg"}
• {"id"=>"494404313289334784", "text"=>"#plos Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Rand.. http://t.co/4krejk0eUR", "created_at"=>"2014-07-30T08:49:08Z", "user"=>"bookapharmacist", "user_name"=>"Kazeem Olalekan", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1859820850/3a_normal.png"}
• {"id"=>"494404968544497664", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T08:51:44Z", "user"=>"VetHuReprodImm", "user_name"=>"JuanMaldonadoEstrada", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000804399105/4801c9966fff8973d65f6a728941f0bd_normal.jpeg"}
• {"id"=>"494421271896416256", "text"=>"Top story: PLOS Medicine: Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine… http://t.co/g4kvOlumic, see more http://t.co/bIL61slAMT", "created_at"=>"2014-07-30T09:56:31Z", "user"=>"ATP_CME", "user_name"=>"ATP EGYPT", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1337289872/DSCF1510_normal.JPG"}
• {"id"=>"494423686800478208", "text"=>"RT @mwpennell: woah -- this is huge. huge trial of new malaria vaccination. it seems to work!!! http://t.co/SUVjV7o4Y1 in @PLOSMedicine", "created_at"=>"2014-07-30T10:06:07Z", "user"=>"WvSchaik", "user_name"=>"WvSchaik", "user_profile_image"=>"http://pbs.twimg.com/profile_images/411955580958289920/rFobzqPe_normal.jpeg"}
• {"id"=>"494423947564576769", "text"=>"Malaria vaccine effective? http://t.co/Uzi5fZCWKc", "created_at"=>"2014-07-30T10:07:09Z", "user"=>"kgusler", "user_name"=>"Ken Gusler", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1159276868/Classic_ken_normal.jpg"}
• {"id"=>"494433542169165824", "text"=>"RT @PLOSMedicine: .@PLOSMedicine hits #1 on #reddit with article on #Malaria vaccine http://t.co/ycDTz3DHvB", "created_at"=>"2014-07-30T10:45:17Z", "user"=>"Boudy_E", "user_name"=>"BoudyE", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3201456660/c255df0564b64ce173c12170592120c7_normal.png"}
• {"id"=>"494446985999839232", "text"=>"Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T11:38:42Z", "user"=>"NatureRevMicro", "user_name"=>"Nature Rev Microbiol", "user_profile_image"=>"http://pbs.twimg.com/profile_images/480994211626373120/jxmDYIr2_normal.jpeg"}
• {"id"=>"494448381629304833", "text"=>"RT @NatureRevMicro: Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T11:44:15Z", "user"=>"ManoloSanchezA", "user_name"=>"Manuel Sánchez", "user_profile_image"=>"http://pbs.twimg.com/profile_images/470790577059930112/xtVqw3Dl_normal.png"}
• {"id"=>"494449387356299264", "text"=>"RT @NatureRevMicro: Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T11:48:15Z", "user"=>"dralpersener", "user_name"=>"alper sener", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3722993945/aa1f2d6fb64564b04460f7a9cfd9ffce_normal.jpeg"}
• {"id"=>"494452127339520000", "text"=>"Malaria vaccine showing promise. #PLOSMedicine http://t.co/stHSM1FzMH", "created_at"=>"2014-07-30T11:59:08Z", "user"=>"thehotbeard", "user_name"=>"Ewan Campbell", "user_profile_image"=>"http://pbs.twimg.com/profile_images/458178955330486272/NnDLtwr0_normal.jpeg"}
• {"id"=>"494455069828345856", "text"=>"Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:10:49Z", "user"=>"blogdokter", "user_name"=>"BlogDokter", "user_profile_image"=>"http://pbs.twimg.com/profile_images/450788329877823488/xDBBrJqM_normal.jpeg"}
• {"id"=>"494455140884025345", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:11:06Z", "user"=>"ekkihessia", "user_name"=>"Ekky Soepadmoyo", "user_profile_image"=>"http://pbs.twimg.com/profile_images/493736712124641281/mXbtI_k2_normal.jpeg"}
• {"id"=>"494455566442307585", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:12:48Z", "user"=>"Wookiester", "user_name"=>"Ester Wu (吳丽珠)", "user_profile_image"=>"http://pbs.twimg.com/profile_images/483343726593331200/fHCPzfwY_normal.jpeg"}
• {"id"=>"494456154840264704", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:15:08Z", "user"=>"Mamaye16", "user_name"=>"Mae", "user_profile_image"=>"http://pbs.twimg.com/profile_images/490370044405112832/aBkLBtRJ_normal.jpeg"}
• {"id"=>"494456545334153217", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:16:41Z", "user"=>"DsyGani_", "user_name"=>"Uchi", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494163057518444546/jn4pyP2V_normal.jpeg"}
• {"id"=>"494456683012173824", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:17:14Z", "user"=>"Rhisnantya_MP", "user_name"=>"♛ R I R I S ♛", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494300331019206657/YTiqsS0J_normal.jpeg"}
• {"id"=>"494456762582695938", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:17:33Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494456942236946432", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:18:16Z", "user"=>"yuyukiskandar", "user_name"=>"Wahyuni Iskandar", "user_profile_image"=>"http://pbs.twimg.com/profile_images/492750096543391745/omCwtdZu_normal.jpeg"}
• {"id"=>"494457557717483521", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:20:43Z", "user"=>"kaknopay", "user_name"=>"N O V I T A ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/491747038497746944/nDFHPsPw_normal.jpeg"}
• {"id"=>"494459897723908096", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:30:00Z", "user"=>"ary_ijah", "user_name"=>"ambarsari", "user_profile_image"=>"http://pbs.twimg.com/profile_images/480223023903948802/6AOqg0gD_normal.jpeg"}
• {"id"=>"494461983601610753", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:38:18Z", "user"=>"ZKhaeria_1", "user_name"=>"Zulfa Khaeria Jufri", "user_profile_image"=>"http://pbs.twimg.com/profile_images/492335272869113856/xtZk4EWz_normal.jpeg"}
• {"id"=>"494464263293919233", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:47:21Z", "user"=>"sa_Imha", "user_name"=>"Sitti Sayma ツ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/493072480387338240/4elPrguu_normal.jpeg"}
• {"id"=>"494465303527440386", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:51:29Z", "user"=>"akoemala", "user_name"=>"Mala ﾑ२ฬĭழαΏ৳๑ ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000858476077/H_GmgsEx_normal.jpeg"}
• {"id"=>"494466133110439938", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T12:54:47Z", "user"=>"TiaraIntanPS", "user_name"=>"B+", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494274559734853633/_808sr-K_normal.jpeg"}
• {"id"=>"494468080454467584", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T13:02:31Z", "user"=>"ShenjaPradendi", "user_name"=>"Shenja dibatas kota", "user_profile_image"=>"http://pbs.twimg.com/profile_images/486413019434340354/sl4SfL81_normal.jpeg"}
• {"id"=>"494472661938888704", "text"=>"\"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/5WQCrU1HrA #studikes\"", "created_at"=>"2014-07-30T13:20:44Z", "user"=>"vinnagin", "user_name"=>"Bripda Vina", "user_profile_image"=>"http://pbs.twimg.com/profile_images/451315443022561280/qtfLWEXO_normal.jpeg"}
• {"id"=>"494473976262168576", "text"=>"RT @NatureRevMicro: Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T13:25:57Z", "user"=>"srijakbhatnagar", "user_name"=>"Srijak Bhatnagar", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2839312947/397460b8dd9349d3408781df60542e54_normal.jpeg"}
• {"id"=>"494477013378281472", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T13:38:01Z", "user"=>"kie_fauziah", "user_name"=>"Siti Rizki Fauziah", "user_profile_image"=>"http://pbs.twimg.com/profile_images/462414431062740995/l61sii4z_normal.jpeg"}
• {"id"=>"494478806518751234", "text"=>"PLOS Medicine: Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 R…http://t.co/V90BRimqi5", "created_at"=>"2014-07-30T13:45:09Z", "user"=>"drmahendrapatel", "user_name"=>"Dr Mahendra G Patel", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3510646527/d630af29012a74ab033e3c7c9c40d538_normal.jpeg"}
• {"id"=>"494478941047246849", "text"=>"RT @drmahendrapatel: PLOS Medicine: Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 R…h…", "created_at"=>"2014-07-30T13:45:41Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494485240782389252", "text"=>"RT @NatureRevMicro: Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T14:10:43Z", "user"=>"hannah_rickman", "user_name"=>"Hannah Rickman", "user_profile_image"=>"http://abs.twimg.com/sticky/default_profile_images/default_profile_2_normal.png"}
• {"id"=>"494486339136802816", "text"=>"Finally --this could be huge. Keep your fingers crossed. http://t.co/VCpUaQUTnV", "created_at"=>"2014-07-30T14:15:05Z", "user"=>"PaulKSue", "user_name"=>"Paul K Sue", "user_profile_image"=>"http://pbs.twimg.com/profile_images/490495203413745664/SWsvv3ys_normal.jpeg"}
• {"id"=>"494487363486498816", "text"=>"[Paper] Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination http://t.co/fsbfhWANAe", "created_at"=>"2014-07-30T14:19:09Z", "user"=>"MrEnkapsis", "user_name"=>"Sebastian", "user_profile_image"=>"http://pbs.twimg.com/profile_images/489384989260144640/BBLUZxu9_normal.jpeg"}
• {"id"=>"494489465768128512", "text"=>"Can someone explain how a 46% vax efficacy can result in 829 cases/1,000 vaccinated being averted? *So* confused. http://t.co/s3fFTcrzIn", "created_at"=>"2014-07-30T14:27:30Z", "user"=>"LamnidaeBlue", "user_name"=>"Justine", "user_profile_image"=>"http://pbs.twimg.com/profile_images/413359933368057856/lsG_cmGE_normal.jpeg"}
• {"id"=>"494492108237975555", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T14:38:00Z", "user"=>"melyzious", "user_name"=>"Melly saktiono ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/493134248870563841/klbBi_LY_normal.jpeg"}
• {"id"=>"494501884980641792", "text"=>"Anyone? “@LamnidaeBlue: someone explain how a 46% vax efficacy can result in 829 cases/1,000 vaccinated averted? http://t.co/UJIWUtncRL”", "created_at"=>"2014-07-30T15:16:51Z", "user"=>"JamieBGall", "user_name"=>"Jamie Gallagher", "user_profile_image"=>"http://pbs.twimg.com/profile_images/460754293977382912/KzVPfkBc_normal.jpeg"}
• {"id"=>"494504046015676416", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T15:25:26Z", "user"=>"dhdika24", "user_name"=>"dika hardika", "user_profile_image"=>"http://pbs.twimg.com/profile_images/479384941021503488/MNE2sXsM_normal.jpeg"}
• {"id"=>"494508184397430784", "text"=>"RT @NatureRevMicro: Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T15:41:53Z", "user"=>"Linda_Brock_PhD", "user_name"=>"Linda Brock", "user_profile_image"=>"http://pbs.twimg.com/profile_images/446049850115624960/LWDlbLFP_normal.jpeg"}
• {"id"=>"494544507820834817", "text"=>"RT @NatureRevMicro: Results from a malaria vaccine trial http://t.co/mb6ORt7x1S @PLOSMedicine #midweekmicro", "created_at"=>"2014-07-30T18:06:13Z", "user"=>"dmrmay", "user_name"=>"Mr. D. ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494380914714357761/28NAOlif_normal.jpeg"}
• {"id"=>"494560260116328448", "text"=>"Important progress on #malaria #vaccine trials for children in #Africa reported @PLoSMedicine http://t.co/k83IqBBuHb", "created_at"=>"2014-07-30T19:08:49Z", "user"=>"UCGHR", "user_name"=>"Umeå Global Health", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2991644928/ec28d1fcc18de14b5a46e288c4fe2d55_normal.jpeg"}
• {"id"=>"494560936586665984", "text"=>"RT @UCGHR: Important progress on #malaria #vaccine trials for children in #Africa reported @PLoSMedicine http://t.co/k83IqBBuHb", "created_at"=>"2014-07-30T19:11:30Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"494565950579302400", "text"=>"RT @UCGHR: Important progress on #malaria #vaccine trials for children in #Africa reported @PLoSMedicine http://t.co/k83IqBBuHb", "created_at"=>"2014-07-30T19:31:25Z", "user"=>"KeseteA", "user_name"=>"Kesete Admasu", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3691581038/0a9a89b07c5a29f07fccf15d5219ee78_normal.jpeg"}
• {"id"=>"494592237594882048", "text"=>"@givingwhatwecan know anything about this http://t.co/O8q9SYyZJc? Malaria vaccination potentially more effective than nets soon?", "created_at"=>"2014-07-30T21:15:53Z", "user"=>"peskymystic", "user_name"=>"Robert Muirhead", "user_profile_image"=>"http://pbs.twimg.com/profile_images/492374187906842624/-CBxG57V_normal.jpeg"}
• {"id"=>"494612259839045632", "text"=>"RT @blogdokter: Yang mau baca abstrak studi tentang vaksin malaria, silakan klik http://t.co/cskfE7UXSh #studikes", "created_at"=>"2014-07-30T22:35:26Z", "user"=>"SorayaGigantika", "user_name"=>"soraya gigantika", "user_profile_image"=>"http://pbs.twimg.com/profile_images/443773940117143552/MvpjaBop_normal.jpeg"}
• {"id"=>"494725955408371713", "text"=>"RT @mac_anas: Vacuna contra la #Malaria muestra una protección continua durante 18 meses de seguimiento http://t.co/QInXcRQ4jh … @PLOSMedic…", "created_at"=>"2014-07-31T06:07:14Z", "user"=>"mimilewissabin", "user_name"=>"Miriam Lewis Sabin", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3530286726/fe01d768c8dad0559291fa320c8ea895_normal.jpeg"}
• {"id"=>"494775997343203328", "text"=>"Wäre ja nicht schlecht, wenn http://t.co/3xorY5vjQb funktioniert und http://t.co/mkVQt3uqeR auch nicht danebenliegt. #malaria", "created_at"=>"2014-07-31T09:26:04Z", "user"=>"hauschke", "user_name"=>"@hauschke", "user_profile_image"=>"http://pbs.twimg.com/profile_images/885710906/hauschke_normal.jpg"}
• {"id"=>"494776385324744704", "text"=>"RT @hauschke: Wäre ja nicht schlecht, wenn http://t.co/3xorY5vjQb funktioniert und http://t.co/mkVQt3uqeR auch nicht danebenliegt. #malaria", "created_at"=>"2014-07-31T09:27:37Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"494776815849046016", "text"=>"RT @hauschke: Wäre ja nicht schlecht, wenn http://t.co/3xorY5vjQb funktioniert und http://t.co/mkVQt3uqeR auch nicht danebenliegt. #malaria", "created_at"=>"2014-07-31T09:29:20Z", "user"=>"NodeSystems", "user_name"=>"Mubdi'Chud'Choudhury", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000737157921/2c494f901e68fe4d117b2970698ce157_normal.jpeg"}
• {"id"=>"494777172713046016", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-07-31T09:30:45Z", "user"=>"ImperialMalaria", "user_name"=>"Malaria Modellers", "user_profile_image"=>"http://pbs.twimg.com/profile_images/452106580301864960/pi1OpjJ1_normal.png"}
• {"id"=>"494817742831513600", "text"=>"malaria vaccines now good for up to 18 months woo hoo http://t.co/wdOEjq3uzE", "created_at"=>"2014-07-31T12:11:57Z", "user"=>"aardvarkwizard", "user_name"=>"ＨＯＧ_ＧＲＥＹＪＯＹ６６６", "user_profile_image"=>"http://pbs.twimg.com/profile_images/418912552123256832/OQzi270b_normal.png"}
• {"id"=>"494817862062977025", "text"=>"RT @aardvarkwizard: malaria vaccines now good for up to 18 months woo hoo http://t.co/wdOEjq3uzE", "created_at"=>"2014-07-31T12:12:26Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494854246001422337", "text"=>"RT @PeterHotez Just out in @PLOSMedicine latest results of RTS/S malaria vaccine phase 3 trials http://t.co/6Gvy1TAaMU", "created_at"=>"2014-07-31T14:37:00Z", "user"=>"sabinvaccine", "user_name"=>"Sabin Vaccine Inst.", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1522511429/sabinlogo_normal.jpg"}
• {"id"=>"494854348225396736", "text"=>"RT @sabinvaccine: RT @PeterHotez Just out in @PLOSMedicine latest results of RTS/S malaria vaccine phase 3 trials http://t.co/6Gvy1TAaMU", "created_at"=>"2014-07-31T14:37:25Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494854649128566785", "text"=>"http://t.co/hmzGmf2pHu Efficacy Safety of RTS,S/AS01 #Malaria Vaccine during 18 Months after Vaccination: 11 African Sites", "created_at"=>"2014-07-31T14:38:36Z", "user"=>"bbbrieger", "user_name"=>"Bill Brieger Malaria", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000061238140/8a9f1c8c30419d943c6c5bde28daf863_normal.jpeg"}
• {"id"=>"494854764841431040", "text"=>"RT @bbbrieger: http://t.co/hmzGmf2pHu Efficacy Safety of RTS,S/AS01 #Malaria Vaccine during 18 Months after Vaccination: 11 African Sites", "created_at"=>"2014-07-31T14:39:04Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"494854886643994624", "text"=>"RT @bbbrieger: http://t.co/hmzGmf2pHu Efficacy Safety of RTS,S/AS01 #Malaria Vaccine during 18 Months after Vaccination: 11 African Sites", "created_at"=>"2014-07-31T14:39:33Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494864857397997569", "text"=>"RT @bbbrieger: http://t.co/hmzGmf2pHu Efficacy Safety of RTS,S/AS01 #Malaria Vaccine during 18 Months after Vaccination: 11 African Sites", "created_at"=>"2014-07-31T15:19:10Z", "user"=>"MESAmalaria", "user_name"=>"MESA Secretariat", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2650904992/c4ab299bb836907a1425e91f33f3bf60_normal.png"}
• {"id"=>"494883008361799680", "text"=>"See last RT: 'vaccination of children, young infants prevented many cases of clinical &amp; severe malaria' http://t.co/6xzcWNgxJn", "created_at"=>"2014-07-31T16:31:18Z", "user"=>"femkevanzeijl", "user_name"=>"Femke van Zeijl", "user_profile_image"=>"http://pbs.twimg.com/profile_images/469738036213719040/LPuCswg8_normal.jpeg"}
• {"id"=>"494883349446819840", "text"=>"'vaccination with RTS,S/AS01 could have a major public health impact in sub-Saharan Africa.' #malaria http://t.co/6xzcWNgxJn", "created_at"=>"2014-07-31T16:32:39Z", "user"=>"femkevanzeijl", "user_name"=>"Femke van Zeijl", "user_profile_image"=>"http://pbs.twimg.com/profile_images/469738036213719040/LPuCswg8_normal.jpeg"}
• {"id"=>"494884275058376704", "text"=>"RT @femkevanzeijl: 'vaccination with RTS,S/AS01 could have a major public health impact in sub-Saharan Africa.' #malaria http://t.co/6xzcWN…", "created_at"=>"2014-07-31T16:36:20Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"494884398698094594", "text"=>"RT @femkevanzeijl: 'vaccination with RTS,S/AS01 could have a major public health impact in sub-Saharan Africa.' #malaria http://t.co/6xzcWN…", "created_at"=>"2014-07-31T16:36:49Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"494885554342068224", "text"=>"RT @femkevanzeijl: See last RT: 'vaccination of children, young infants prevented many cases of clinical &amp; severe malaria' http://t.co/6xzc…", "created_at"=>"2014-07-31T16:41:25Z", "user"=>"agelessrehab", "user_name"=>"#QuarantineCenters.", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494002612258504704/Eg44zH5Q_normal.jpeg"}
• {"id"=>"495283289460977664", "text"=>"#PLOSMedicine: Efficacy and Safety of ... Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomize... http://t.co/EyVIq08RGn", "created_at"=>"2014-08-01T19:01:52Z", "user"=>"dylanbgeorge", "user_name"=>"Dylan George", "user_profile_image"=>"http://pbs.twimg.com/profile_images/77908283/IMG_0007_normal.JPG"}
• {"id"=>"495529208693538816", "text"=>"http://t.co/9j77PoT9Gl 말라리아 RTS,S/AS01 백신 관련 논문이 PLoS에 실렸는데. 저번 NEJM에 실렸던 논문/에디토리얼과 비교해보면 재미있다.", "created_at"=>"2014-08-02T11:19:04Z", "user"=>"byontae", "user_name"=>"붉은여왕", "user_profile_image"=>"http://pbs.twimg.com/profile_images/468152872/b0051932_normal.gif"}
• {"id"=>"495572875550523392", "text"=>"RT @byontae: http://t.co/9j77PoT9Gl 말라리아 RTS,S/AS01 백신 관련 논문이 PLoS에 실렸는데. 저번 NEJM에 실렸던 논문/에디토리얼과 비교해보면 재미있다.", "created_at"=>"2014-08-02T14:12:35Z", "user"=>"desasegurado", "user_name"=>"Taistealai", "user_profile_image"=>"http://pbs.twimg.com/profile_images/486310892917649408/l2WI7VNH_normal.jpeg"}
• {"id"=>"495607607294304257", "text"=>"A new #malaria vaccine? @PLOSMedicine article shows good safety and efficacy in RTS,S/AS01 trial in Africa http://t.co/JuJdXQlKzk", "created_at"=>"2014-08-02T16:30:36Z", "user"=>"MSFsci", "user_name"=>"MSF Science", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000786589529/2cf84488f46a15338f7cd50a0048a8c0_normal.jpeg"}
• {"id"=>"495607771719819264", "text"=>"RT @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety and efficacy in RTS,S/AS01 trial in Africa http://t.co/JuJdXQlK…", "created_at"=>"2014-08-02T16:31:15Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"495608459828948992", "text"=>"RT @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety and efficacy in RTS,S/AS01 trial in Africa http://t.co/JuJdXQlK…", "created_at"=>"2014-08-02T16:33:59Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"495658448797724672", "text"=>"RT @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety and efficacy in RTS,S/AS01 trial in Africa http://t.co/JuJdXQlK…", "created_at"=>"2014-08-02T19:52:37Z", "user"=>"KaberaRene", "user_name"=>"KABERA RENE ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1419177855/DSC_1591_normal.jpg"}
• {"id"=>"495671954968674305", "text"=>"RT @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety and efficacy in RTS,S/AS01 trial in Africa http://t.co/JuJdXQlK…", "created_at"=>"2014-08-02T20:46:17Z", "user"=>"bbbrieger", "user_name"=>"Bill Brieger Malaria", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000061238140/8a9f1c8c30419d943c6c5bde28daf863_normal.jpeg"}
• {"id"=>"495701989972779008", "text"=>"'Milestone' for child malaria vaccine !\nhttp://t.co/FZfcKcIqDY", "created_at"=>"2014-08-02T22:45:38Z", "user"=>"InesLevade", "user_name"=>"Ines Levade", "user_profile_image"=>"http://pbs.twimg.com/profile_images/495401158077214720/0fNVPGGj_normal.jpeg"}
• {"id"=>"495849158218371072", "text"=>"Via @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety &amp; efficacy in RTS,S/AS01 trial in Africa http://t.co/3lxtXQk7aK", "created_at"=>"2014-08-03T08:30:26Z", "user"=>"Peoplesuni", "user_name"=>"People's-uni", "user_profile_image"=>"http://pbs.twimg.com/profile_images/1491946027/logo_normal.jpg"}
• {"id"=>"495849317656461312", "text"=>"RT @Peoplesuni: Via @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety &amp; efficacy in RTS,S/AS01 trial in Africa http:…", "created_at"=>"2014-08-03T08:31:04Z", "user"=>"ianXenRAPID", "user_name"=>"IanXen xRAPID ", "user_profile_image"=>"http://pbs.twimg.com/profile_images/467713850221920256/2ce7WOv7_normal.png"}
• {"id"=>"495850015852879872", "text"=>"RT @Peoplesuni: Via @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety &amp; efficacy in RTS,S/AS01 trial in Africa http:…", "created_at"=>"2014-08-03T08:33:50Z", "user"=>"NodeSystems", "user_name"=>"Mubdi'Chud'Choudhury", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000737157921/2c494f901e68fe4d117b2970698ce157_normal.jpeg"}
• {"id"=>"495850106516946944", "text"=>"RT @Peoplesuni: Via @MSFsci: A new #malaria vaccine? @PLOSMedicine article shows good safety &amp; efficacy in RTS,S/AS01 trial in Africa http:…", "created_at"=>"2014-08-03T08:34:12Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"496281313155239939", "text"=>"New vaccine somewhat effective against malaria in children. Given challenges in delivering vaccines, is it enough? http://t.co/L5naxnf99A", "created_at"=>"2014-08-04T13:07:40Z", "user"=>"LaraSYHo", "user_name"=>"Lara Ho", "user_profile_image"=>"http://pbs.twimg.com/profile_images/484273826788671488/l5GH867s_normal.jpeg"}
• {"id"=>"496281506374250497", "text"=>"RT @LaraSYHo: New vaccine somewhat effective against malaria in children. Given challenges in delivering vaccines, is it enough? http://t.c…", "created_at"=>"2014-08-04T13:08:26Z", "user"=>"NewsMalaria", "user_name"=>"Malaria News", "user_profile_image"=>"http://pbs.twimg.com/profile_images/487195368866586624/2sBu9zY3_normal.jpeg"}
• {"id"=>"496351084344922112", "text"=>"@acronymrequired if interested: http://t.co/ZFO1KY8VY9 @PLOSMedicine", "created_at"=>"2014-08-04T17:44:54Z", "user"=>"healthmap", "user_name"=>"HealthMap", "user_profile_image"=>"http://pbs.twimg.com/profile_images/494473973741019137/wvyoZQwO_normal.jpeg"}
• {"id"=>"496645692086292480", "text"=>"Just to keep perspective: GSK's #malariavaccine is less than 50% effective. Summary from @PLOSMedicine. http://t.co/11lwpS4jaS", "created_at"=>"2014-08-05T13:15:34Z", "user"=>"soniashah", "user_name"=>"soniashah", "user_profile_image"=>"http://pbs.twimg.com/profile_images/869871219/SoniaShah5396_joyceRavidjpeg_normal.jpg"}
• {"id"=>"498909942556786688", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/p17qoyAEqK", "created_at"=>"2014-08-11T19:12:54Z", "user"=>"RulaniyaDr", "user_name"=>"Dr Mukesh Rulaniya", "user_profile_image"=>"http://pbs.twimg.com/profile_images/486777037281972224/CTS27X1s_normal.jpeg"}
• {"id"=>"498953372247281664", "text"=>"RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/qF1GcfSnlK #publichealth", "created_at"=>"2014-08-11T22:05:28Z", "user"=>"jvalaball", "user_name"=>"Dr J Vidal-Alabll", "user_profile_image"=>"http://pbs.twimg.com/profile_images/493836857776799744/iNgXZBrl_normal.jpeg"}
• {"id"=>"498953494448328704", "text"=>"RT @jvalaball: RT @PLOSMedicine: #Malaria Vaccine Shows Continued Protection during 18 Months of Follow-Up http://t.co/qF1GcfSnlK #publich…", "created_at"=>"2014-08-11T22:05:57Z", "user"=>"AnnabelSaavedra", "user_name"=>"Annabel Saavedra", "user_profile_image"=>"http://pbs.twimg.com/profile_images/498952631838965760/HLk8aXG4_normal.jpeg"}
• {"id"=>"499222951661940737", "text"=>"RT @EDCTP: #PLOSMedicine: Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: ... http://t.co/WUG1M8g…", "created_at"=>"2014-08-12T15:56:41Z", "user"=>"NIMRTanga", "user_name"=>"NIMR-TangaCentre", "user_profile_image"=>"http://pbs.twimg.com/profile_images/3191757029/808479e46261708b537a6e3e601e0860_normal.png"}
• {"id"=>"499235436846653441", "text"=>"RT @EDCTP: #PLOSMedicine: Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: ... http://t.co/WUG1M8g…", "created_at"=>"2014-08-12T16:46:18Z", "user"=>"FaithLianne", "user_name"=>"Kijakazi Mashoto", "user_profile_image"=>"http://pbs.twimg.com/profile_images/418636869543288832/G664Cwul_normal.jpeg"}
• {"id"=>"501070195709194240", "text"=>"Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination. Pros and con.\nhttp://t.co/4lJRFy276R", "created_at"=>"2014-08-17T18:16:58Z", "user"=>"JuanGrvas", "user_name"=>"Juan Gérvas", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2627753335/IMGP1408_normal.JPG"}
• {"id"=>"501070242119176192", "text"=>"Paludismo. Eficacia y seguridad de la vacuna RTS,S/AS0. Pros y contras.\nhttp://t.co/4lJRFy276R", "created_at"=>"2014-08-17T18:17:09Z", "user"=>"JuanGrvas", "user_name"=>"Juan Gérvas", "user_profile_image"=>"http://pbs.twimg.com/profile_images/2627753335/IMGP1408_normal.JPG"}
• {"id"=>"501084981696155649", "text"=>"RT @JuanGrvas: Paludismo. Eficacia y seguridad de la vacuna RTS,S/AS0. Pros y contras.\nhttp://t.co/4lJRFy276R", "created_at"=>"2014-08-17T19:15:44Z", "user"=>"sarizor", "user_name"=>"Sara Ortiz Medina", "user_profile_image"=>"http://pbs.twimg.com/profile_images/417747997242691585/qY-cnG50_normal.jpeg"}
• {"id"=>"501288553075458048", "text"=>"RT @JuanGrvas: Paludismo. Eficacia y seguridad de la vacuna RTS,S/AS0. Pros y contras.\nhttp://t.co/4lJRFy276R", "created_at"=>"2014-08-18T08:44:39Z", "user"=>"zorbete", "user_name"=>"Gabriel fernandez", "user_profile_image"=>"http://pbs.twimg.com/profile_images/421575235259740160/rKSUaw92_normal.jpeg"}
• {"id"=>"501288569793949696", "text"=>"RT @JuanGrvas: Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination. Pros and con.\nhttp://t.co/4lJRFy27…", "created_at"=>"2014-08-18T08:44:43Z", "user"=>"zorbete", "user_name"=>"Gabriel fernandez", "user_profile_image"=>"http://pbs.twimg.com/profile_images/421575235259740160/rKSUaw92_normal.jpeg"}
• {"id"=>"501439860360486912", "text"=>"Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomize... http://t.co/M2gRbZCVN0", "created_at"=>"2014-08-18T18:45:53Z", "user"=>"DraSoniaLopez", "user_name"=>"Sonia López", "user_profile_image"=>"http://pbs.twimg.com/profile_images/344513261569832668/e4f4712ad8bfe344e19a1b96dee39b2a_normal.jpeg"}
• {"id"=>"614150246407499776", "text"=>"2015 Shepard Science Awards presented today @CDCgov http://t.co/T8Xoa1mndq \nCongrats to PLOS Med authors http://t.co/39vZFGAfnq", "created_at"=>"2015-06-25T19:16:43Z", "user"=>"LarryPeiperl", "user_name"=>"Larry Peiperl", "user_profile_image"=>"http://pbs.twimg.com/profile_images/378800000471737849/148d2d6588b555c56558e26ecae82a9c_normal.jpeg"}
• {"id"=>"618024085549879296", "text"=>"@notSoJunkDNA sinon faut aller à la page principale http://t.co/Q2vVM5NjG2 puis dans comments", "created_at"=>"2015-07-06T11:49:58Z", "user"=>"Alexis_Verger", "user_name"=>"Alexis Verger", "user_profile_image"=>"http://pbs.twimg.com/profile_images/560719569296588800/hdo6YW1j_normal.jpeg"}

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Figshare

• {"files"=>["https://ndownloader.figshare.com/files/1613781", "https://ndownloader.figshare.com/files/1613782", "https://ndownloader.figshare.com/files/1613783", "https://ndownloader.figshare.com/files/1613784", "https://ndownloader.figshare.com/files/1613785", "https://ndownloader.figshare.com/files/1613786", "https://ndownloader.figshare.com/files/1613787", "https://ndownloader.figshare.com/files/1613788", "https://ndownloader.figshare.com/files/1613789", "https://ndownloader.figshare.com/files/1613790", "https://ndownloader.figshare.com/files/1613791", "https://ndownloader.figshare.com/files/1613792", "https://ndownloader.figshare.com/files/1613793", "https://ndownloader.figshare.com/files/1613794", "https://ndownloader.figshare.com/files/1613795", "https://ndownloader.figshare.com/files/1613796", "https://ndownloader.figshare.com/files/1613797", "https://ndownloader.figshare.com/files/1613798", "https://ndownloader.figshare.com/files/1613799", "https://ndownloader.figshare.com/files/1613800", "https://ndownloader.figshare.com/files/1613801", "https://ndownloader.figshare.com/files/1613802", "https://ndownloader.figshare.com/files/1613803", "https://ndownloader.figshare.com/files/1613804", "https://ndownloader.figshare.com/files/1613805", "https://ndownloader.figshare.com/files/1613806", "https://ndownloader.figshare.com/files/1613807", "https://ndownloader.figshare.com/files/1613808", "https://ndownloader.figshare.com/files/1613809", "https://ndownloader.figshare.com/files/1613810"], "description"=>"<div><p>Background</p><p>A malaria vaccine could be an important addition to current control strategies. We report the safety and vaccine efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following vaccination at 11 African sites with varying malaria transmission.</p><p>Methods and Findings</p><p>6,537 infants aged 6–12 wk and 8,923 children aged 5–17 mo were randomized to receive three doses of RTS,S/AS01 or comparator vaccine.</p><p>VE against clinical malaria in children during the 18 mo after vaccine dose 3 (per protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; VE, <i>p<</i>0.01 across all sites). VE during the 20 mo after vaccine dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 49%). VE against severe malaria, malaria hospitalization, and all-cause hospitalization was 34% (95% CI 15% to 48%), 41% (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), respectively (ITT).</p><p>VE against clinical malaria in infants was 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 33%], ITT), with no significant protection against severe malaria, malaria hospitalization, or all-cause hospitalization.</p><p>Post-vaccination anti-circumsporozoite antibody geometric mean titer varied from 348 to 787 EU/ml across sites in children and from 117 to 335 EU/ml in infants (per protocol).</p><p>VE waned over time in both age categories (Schoenfeld residuals <i>p</i><0.001). The number of clinical and severe malaria cases averted per 1,000 children vaccinated ranged across sites from 37 to 2,365 and from −1 to 49, respectively; corresponding ranges among infants were −10 to 1,402 and −13 to 37, respectively (ITT). Meningitis was reported as a serious adverse event in 16/5,949 and 1/2,974 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and control groups, respectively.</p><p>Conclusions</p><p>RTS,S/AS01 prevented many cases of clinical and severe malaria over the 18 mo after vaccine dose 3, with the highest impact in areas with the greatest malaria incidence. VE was higher in children than in infants, but even at modest levels of VE, the number of malaria cases averted was substantial. RTS,S/AS01 could be an important addition to current malaria control in Africa.</p><p>Trial registration</p><p><a href=\"http://www.ClinicalTrials.gov\" target=\"_blank\">www.ClinicalTrials.gov</a><a href=\"http://clinicaltrials.gov/ct2/show/NCT00866619\" target=\"_blank\">NCT00866619</a></p><p><i>Please see later in the article for the Editors' Summary</i></p></div>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "18", "months", "controlled", "children", "infants", "11", "african"], "article_id"=>1121374, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>["https://dx.doi.org/10.1371/journal.pmed.1001685.s001", "https://dx.doi.org/10.1371/journal.pmed.1001685.s002", "https://dx.doi.org/10.1371/journal.pmed.1001685.s003", "https://dx.doi.org/10.1371/journal.pmed.1001685.s004", "https://dx.doi.org/10.1371/journal.pmed.1001685.s005", "https://dx.doi.org/10.1371/journal.pmed.1001685.s006", "https://dx.doi.org/10.1371/journal.pmed.1001685.s007", "https://dx.doi.org/10.1371/journal.pmed.1001685.s008", "https://dx.doi.org/10.1371/journal.pmed.1001685.s009", "https://dx.doi.org/10.1371/journal.pmed.1001685.s010", "https://dx.doi.org/10.1371/journal.pmed.1001685.s011", "https://dx.doi.org/10.1371/journal.pmed.1001685.s012", "https://dx.doi.org/10.1371/journal.pmed.1001685.s013", "https://dx.doi.org/10.1371/journal.pmed.1001685.s014", "https://dx.doi.org/10.1371/journal.pmed.1001685.s015", "https://dx.doi.org/10.1371/journal.pmed.1001685.s016", "https://dx.doi.org/10.1371/journal.pmed.1001685.s017", "https://dx.doi.org/10.1371/journal.pmed.1001685.s018", "https://dx.doi.org/10.1371/journal.pmed.1001685.s019", "https://dx.doi.org/10.1371/journal.pmed.1001685.s020", "https://dx.doi.org/10.1371/journal.pmed.1001685.s021", "https://dx.doi.org/10.1371/journal.pmed.1001685.s022", "https://dx.doi.org/10.1371/journal.pmed.1001685.s023", "https://dx.doi.org/10.1371/journal.pmed.1001685.s024", "https://dx.doi.org/10.1371/journal.pmed.1001685.s025", "https://dx.doi.org/10.1371/journal.pmed.1001685.s026", "https://dx.doi.org/10.1371/journal.pmed.1001685.s027", "https://dx.doi.org/10.1371/journal.pmed.1001685.s028", "https://dx.doi.org/10.1371/journal.pmed.1001685.s029", "https://dx.doi.org/10.1371/journal.pmed.1001685.s030"], "stats"=>{"downloads"=>43, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Efficacy_and_Safety_of_the_RTS_S_AS01_Malaria_Vaccine_during_18_Months_after_Vaccination_A_Phase_3_Randomized_Controlled_Trial_in_Children_and_Young_Infants_at_11_African_Sites_/1121374", "title"=>"Efficacy and Safety of the RTS,S/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613744"], "description"=>"<p>Severe malaria secondary case definition: <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ with one or more markers of disease severity, including cases in which a coexisting illness was present or could not be ruled out. Markers of severe disease were prostration, respiratory distress, a Blantyre coma score of ≤2 (on a scale of 0 to 5, with higher scores indicating a higher level of consciousness), two or more observed or reported seizures, hypoglycemia, acidosis, elevated lactate level, or a hemoglobin level of <5 g/dl. Coexisting illnesses were defined as radiographically proven pneumonia, meningitis established by analysis of cerebrospinal fluid, bacteremia, or gastroenteritis with severe dehydration.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "cases", "averted", "vaccinated", "18-mo", "follow-up"], "article_id"=>1121338, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g007", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_cases_of_severe_malaria_secondary_case_definition_averted_per_1_000_participants_vaccinated_during_an_18_mo_follow_up_period_per_protocol_population_/1121338", "title"=>"Number of cases of severe malaria (secondary case definition) averted per 1,000 participants vaccinated during an 18-mo follow-up period (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613757"], "description"=>"<p>The blue squares reflect the number of participants in the per-protocol population with a valid assay result available 1 mo after dose 3 in each study site. The horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "antibody", "geometric", "titers", "recipients", "mo", "infants", "wk", "ordered", "incidence"], "article_id"=>1121351, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g018", "stats"=>{"downloads"=>1, "page_views"=>21, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_CS_antibody_geometric_mean_titers_EU_ml_in_RTS_S_AS01_recipients_1_mo_after_dose_3_in_infants_6_8211_12_wk_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_per_protocol_population_/1121351", "title"=>"Anti-CS antibody geometric mean titers (EU/ml) in RTS,S/AS01 recipients 1 mo after dose 3 in infants 6–12 wk of age at enrollment, ordered by increasing malaria incidence at each study site (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613747"], "description"=>"<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³. This definition was used for this analysis because during routine clinical practice these children would normally receive a full course of anti-malarial treatment. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up. A deviation pertaining to study vaccine exposure to temperatures outside recommended ranges resulted in the exclusion from the per-protocol population of all children 5–17 mo old enrolled in Manhiça, Mozambique, therefore no data are presented in this age category for Manhiça (asterisk).</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "cases", "averted", "18-mo", "follow-up", "children", "mo", "ordered", "incidence"], "article_id"=>1121341, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g010", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_cases_of_clinical_malaria_secondary_case_definition_averted_during_an_18_mo_follow_up_period_in_children_5_8211_17_mo_of_age_at_enrollment_by_study_site_ordered_by_increasing_malaria_incidence_at_each_site_per_protocol_population_/1121341", "title"=>"Number of cases of clinical malaria (secondary case definition) averted during an 18-mo follow-up period in children 5–17 mo of age at enrollment, by study site, ordered by increasing malaria incidence at each site (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613760"], "description"=>"1<p>Event rate for clinical malaria; affected rate (percent) for severe malaria and hospitalization.</p>2<p>For clinical malaria: <i>p</i>-value from negative binomial regression. For severe malaria, malaria hospitalization, and all-cause hospitalization: <i>p</i>-value from two-sided Fisher's exact test.</p>3<p>Clinical malaria primary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C and <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ or a case of malaria meeting the primary case definition of severe malaria.</p>4<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³.</p>5<p>Severe malaria primary case definition: <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ with one or more markers of disease severity and without diagnosis of a coexisting illness. Markers of severe disease were prostration, respiratory distress, a Blantyre coma score of ≤2 (on a scale of 0 to 5, with higher scores indicating a higher level of consciousness), two or more observed or reported seizures, hypoglycemia, acidosis, elevated lactate level, or hemoglobin level of <5 g/dl. Coexisting illnesses were defined as radiographically proven pneumonia, meningitis established by analysis of cerebrospinal fluid, bacteremia, or gastroenteritis with severe dehydration.</p>6<p>Malaria hospitalization case definition: a medical hospitalization with confirmed <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³.</p>7<p>All-cause hospitalization primary case definition: a medical hospitalization of any cause, excluding planned admissions for medical investigation/care or elective surgery and admissions for trauma.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "efficacy", "episodes", "children", "aged", "mo"], "article_id"=>1121354, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_efficacy_against_all_episodes_of_clinical_and_severe_malaria_in_children_aged_5_8211_17_mo_at_enrollment_/1121354", "title"=>"Vaccine efficacy against all episodes of clinical and severe malaria in children aged 5–17 mo at enrollment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613756"], "description"=>"<p>The blue squares reflect the number of participants in the per-protocol population with a valid assay result available 1 mo after dose 3 in each study site. The horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "antibody", "geometric", "titers", "recipients", "mo", "children", "ordered", "incidence"], "article_id"=>1121350, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g017", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_CS_antibody_geometric_mean_titers_EU_ml_in_RTS_S_AS01_recipients_1_mo_after_dose_3_in_children_5_8211_17_mo_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_intention_to_treat_population_/1121350", "title"=>"Anti-CS antibody geometric mean titers (EU/ml) in RTS,S/AS01 recipients 1 mo after dose 3 in children 5–17 mo of age at enrollment, ordered by increasing malaria incidence at each study site (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613753"], "description"=>"<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³. This definition was used for this analysis because during routine clinical practice these children would normally receive a full course of anti-malarial treatment. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "averted", "18-mo", "follow-up", "infants", "wk", "ordered", "incidence"], "article_id"=>1121347, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g014", "stats"=>{"downloads"=>0, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cases_of_clinical_malaria_secondary_case_definition_averted_during_an_18_mo_follow_up_period_in_infants_6_8211_12_wk_of_age_at_enrollment_by_study_site_ordered_by_increasing_malaria_incidence_at_each_site_per_protocol_population_/1121347", "title"=>"Cases of clinical malaria (secondary case definition) averted during an 18-mo follow-up period in infants 6–12 wk of age at enrollment, by study site, ordered by increasing malaria incidence at each site (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613746"], "description"=>"<p>Severe malaria secondary case definition: <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ with one or more markers of disease severity, including cases in which a coexisting illness was present or could not be ruled out. Markers of severe disease were prostration, respiratory distress, a Blantyre coma score of ≤2 (on a scale of 0 to 5, with higher scores indicating a higher level of consciousness), two or more observed or reported seizures, hypoglycemia, acidosis, elevated lactate level, or a hemoglobin level of <5 g/dl. Coexisting illnesses were defined as radiographically proven pneumonia, meningitis established by analysis of cerebrospinal fluid, bacteremia, or gastroenteritis with severe dehydration.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "cases", "averted", "vaccinated", "20-mo", "follow-up"], "article_id"=>1121340, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g009", "stats"=>{"downloads"=>2, "page_views"=>27, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_cases_of_severe_malaria_secondary_case_definition_averted_per_1_000_participants_vaccinated_during_a_20_mo_follow_up_period_intention_to_treat_population_/1121340", "title"=>"Number of cases of severe malaria (secondary case definition) averted per 1,000 participants vaccinated during a 20-mo follow-up period (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613736"], "description"=>"<p>Interaction <i>p-</i>value = 0.0006. The size of each blue square reflects the relative number of participants enrolled at each study site; the horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up. VE is VE against all episodes of clinical malaria meeting the primary case definition, unadjusted for covariates. Clinical malaria primary case definition: illness in a child brought to a study facility with a temperature of ≥37.5°C and <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ or a case of malaria meeting the primary case definition of severe malaria.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "efficacy", "episodes", "18-mo", "follow-up", "children", "mo", "ordered", "incidence"], "article_id"=>1121330, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g004", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_efficacy_against_all_episodes_of_clinical_malaria_primary_case_definition_during_an_18_mo_follow_up_period_after_dose_3_in_children_5_8211_17_mo_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_per_protocol_populati/1121330", "title"=>"Vaccine efficacy against all episodes of clinical malaria (primary case definition) during an 18-mo follow-up period after dose 3 in children 5–17 mo of age at enrollment, ordered by increasing malaria incidence at each study site (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613749"], "description"=>"<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³. This definition was used for this analysis because during routine clinical practice these children would normally receive a full course of anti-malarial treatment. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "averted", "18-mo", "follow-up", "children", "mo", "ordered", "incidence"], "article_id"=>1121343, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g011", "stats"=>{"downloads"=>1, "page_views"=>33, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cases_of_clinical_malaria_secondary_case_definition_averted_during_an_18_mo_follow_up_period_in_children_5_8211_17_mo_of_age_at_enrollment_by_study_site_ordered_by_increasing_malaria_incidence_at_each_site_intention_to_treat_population_/1121343", "title"=>"Cases of clinical malaria (secondary case definition) averted during an 18-mo follow-up period in children 5–17 mo of age at enrollment, by study site, ordered by increasing malaria incidence at each site (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613759"], "description"=>"<p>Upper left panel: VE against clinical malaria versus malaria incidence (per-protocol population); lower left panel: anti-CS response versus malaria incidence (per-protocol population); lower right panel: anti-CS response versus VE against clinical malaria (per-protocol population). Blue diamonds (infants 6–12 wk) and red squares (children 5–17 mo) represent the study sites. VE (percent) is VE against all episodes of clinical malaria meeting the primary case definition over 18 mo after dose 3. Anti-CS antibody GMT (EU/ml) was measured at 1 mo after dose 3 in the first 200 participants enrolled at each site. Incidence (<i>n</i>/total [n/T]: episodes per person-year at risk) is the incidence of clinical malaria (primary case definition) in the control group in the corresponding age category over 18 mo after dose 3.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "anti-cs", "geometric", "incidence"], "article_id"=>1121353, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g020", "stats"=>{"downloads"=>1, "page_views"=>28, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Graphical_representation_of_anti_CS_geometric_mean_titers_vaccine_efficacy_and_malaria_incidence_per_protocol_population_/1121353", "title"=>"Graphical representation of anti-CS geometric mean titers, vaccine efficacy, and malaria incidence (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613721"], "description"=>"<p>Adapted from Hay et al. <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001685#pmed.1001685-Hay1\" target=\"_blank\">[34]</a>. The location of each participating study site is shown on this previously published map showing the spatial distribution of <i>P. falciparum</i> (Pf) malaria endemicity. The data are the model-based geostatistical point estimates of the annual mean <i>P. falciparum</i> parasite rate (PR) age-standardized for 2–10 y for 2007 within the stable spatial limits of <i>P. falciparum</i> malaria transmission, displayed as a continuum of yellow to red from 0%–100% (see map legend). The rest of the land area was defined as unstable risk (medium grey) or no risk (light grey). Nanoro, Burkina Faso, has highly seasonal malaria transmission.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "sites"], "article_id"=>1121320, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g001", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_sites_and_malaria_endemicity_/1121320", "title"=>"Study sites and malaria endemicity.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613739"], "description"=>"<p>Interaction <i>p-</i>value = 0.8100. The size of each blue square reflects the relative number of participants enrolled at each study site; the horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up. VE is VE against all episodes of clinical malaria meeting the primary case definition, unadjusted for covariates. Clinical malaria primary case definition: illness in a child brought to a study facility with a temperature of ≥37.5°C and <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ or a case of malaria meeting the primary case definition of severe malaria.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "efficacy", "episodes", "18-mo", "follow-up", "children", "mo", "ordered", "incidence"], "article_id"=>1121333, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g005", "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_efficacy_against_all_episodes_of_clinical_malaria_primary_case_definition_during_an_18_mo_follow_up_period_after_dose_3_in_children_5_8211_17_mo_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_intention_to_treat_po/1121333", "title"=>"Vaccine efficacy against all episodes of clinical malaria (primary case definition) during an 18-mo follow-up period after dose 3 in children 5–17 mo of age at enrollment, ordered by increasing malaria incidence at each study site (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613752"], "description"=>"<p>Interaction <i>p-</i>value = 0.1143. The size of each blue square reflects the relative number of participants enrolled at each study site; the horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up. VE is VE against all episodes of clinical malaria meeting the primary case definition, unadjusted for covariates. Clinical malaria primary case definition: illness in a child brought to a study facility with a temperature of ≥37.5°C and <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ or a case of malaria meeting the primary case definition of severe malaria.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "efficacy", "episodes", "18-mo", "follow-up", "infants", "wk", "ordered", "incidence"], "article_id"=>1121346, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g013", "stats"=>{"downloads"=>0, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_efficacy_against_all_episodes_of_clinical_malaria_primary_case_definition_during_an_18_mo_follow_up_period_after_dose_3_in_infants_6_8211_12_wk_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_intention_to_treat_pop/1121346", "title"=>"Vaccine efficacy against all episodes of clinical malaria (primary case definition) during an 18-mo follow-up period after dose 3 in infants 6–12 wk of age at enrollment, ordered by increasing malaria incidence at each study site (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613732"], "description"=>"<p>^aScreening data had not been reported before the database freeze for the analysis published in 2011 for 22 infants in the 6–12-wk age category, and these participants were not included in the 2011 CONSORT chart. ^bOne infant enrolled in the 6–12-wk age category who was reported to have received three doses of study vaccine (RTS,S/AS01 or comparator vaccine) was included in the per-protocol analyses reported previously, but was subsequently found to have received only the first dose of study vaccine. ^cTwo infants enrolled in the 6–12-wk age category who had been reported as “attending Visit 16 (12 months post dose-3)” in the 2012 CONSORT chart are reported as “migrated/lost to follow-up” in this CONSORT chart. In addition, one infant who was reported as “migrated/lost to follow-up” in the 2012 CONSORT chart has been recorded as “consent withdrawal” in this CONSORT chart <a href=\"http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001685#pmed.1001685-RTS1\" target=\"_blank\">[15]</a>.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "diagram", "infants", "aged", "wk", "enrollment", "followed", "18", "mo"], "article_id"=>1121326, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g003", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CONSORT_diagram_of_infants_aged_6_8211_12_wk_at_enrollment_followed_until_18_mo_post_vaccination_/1121326", "title"=>"CONSORT diagram of infants aged 6–12 wk at enrollment followed until 18 mo post-vaccination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613724"], "description"=>"<p>^aOne child enrolled in the 5–17-mo age category who was reported previously to have received three doses of study vaccine, and was included in the per-protocol analyses reported previously, had received only the first and second doses of study vaccine. ^bThe date of birth of three children who were included in the per-protocol analysis reported previously was corrected, and these children were identified as “out of age range” when they received the first dose of study vaccine. These three children were excluded from the per-protocol analyses reported here. CW, consent withdrawal.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "diagram", "children", "aged", "mo", "enrollment", "followed", "18"], "article_id"=>1121323, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g002", "stats"=>{"downloads"=>2, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CONSORT_diagram_of_children_aged_5_8211_17_mo_at_enrollment_and_followed_until_18_mo_post_vaccination_/1121323", "title"=>"CONSORT diagram of children aged 5–17 mo at enrollment and followed until 18 mo post-vaccination.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613755"], "description"=>"<p>The blue squares reflect the number of participants in the per-protocol population with a valid assay result available 1 mo after dose 3 in each study site. The horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "antibody", "geometric", "titers", "recipients", "mo", "children", "ordered", "incidence"], "article_id"=>1121349, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g016", "stats"=>{"downloads"=>2, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_CS_antibody_geometric_mean_titers_EU_ml_in_RTS_S_AS01_recipients_1_mo_after_dose_3_in_children_5_8211_17_mo_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_per_protocol_population_/1121349", "title"=>"Anti-CS antibody geometric mean titers (EU/ml) in RTS,S/AS01 recipients 1 mo after dose 3 in children 5–17 mo of age at enrollment, ordered by increasing malaria incidence at each study site (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613745"], "description"=>"<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³. This definition was used for this analysis because during routine clinical practice these children would normally receive a full course of anti-malarial treatment.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "cases", "averted", "vaccinated", "20-mo", "follow-up"], "article_id"=>1121339, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g008", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_cases_of_clinical_malaria_secondary_case_definition_averted_per_1_000_participants_vaccinated_during_a_20_mo_follow_up_period_intention_to_treat_population_/1121339", "title"=>"Number of cases of clinical malaria (secondary case definition) averted per 1,000 participants vaccinated during a 20-mo follow-up period (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613758"], "description"=>"<p>The blue squares reflect the number of participants in the per-protocol population with a valid assay result available 1 mo after dose 3 in each study site. The horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "antibody", "geometric", "titers", "recipients", "mo", "infants", "wk", "ordered", "incidence"], "article_id"=>1121352, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g019", "stats"=>{"downloads"=>3, "page_views"=>16, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Anti_CS_antibody_geometric_mean_titers_EU_ml_in_RTS_S_AS01_recipients_1_mo_after_dose_3_in_infants_6_8211_12_wk_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_intention_to_treat_population_/1121352", "title"=>"Anti-CS antibody geometric mean titers (EU/ml) in RTS,S/AS01 recipients 1 mo after dose 3 in infants 6–12 wk of age at enrollment, ordered by increasing malaria incidence at each study site (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613761"], "description"=>"1<p>Event rate for clinical malaria; affected rate (percent) for severe malaria and hospitalization.</p>2<p>For clinical malaria: <i>p</i>-value from negative binomial regression. For severe malaria, malaria hospitalization, and all-cause hospitalization: <i>p</i>-value from two-sided Fisher's exact test.</p>3<p>Clinical malaria primary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C and <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ or a case of malaria meeting the primary case definition of severe malaria.</p>4<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³.</p>5<p>Severe malaria primary case definition: <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ with one or more markers of disease severity and without diagnosis of a coexisting illness. Markers of severe disease were prostration, respiratory distress, a Blantyre coma score of ≤2 (on a scale of 0 to 5, with higher scores indicating a higher level of consciousness), two or more observed or reported seizures, hypoglycemia, acidosis, elevated lactate level, or hemoglobin level of <5 g/dl. Coexisting illnesses were defined as radiographically proven pneumonia, meningitis established by analysis of cerebrospinal fluid, bacteremia, or gastroenteritis with severe dehydration.</p>6<p>Malaria hospitalization case definition: a medical hospitalization with confirmed <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³.</p>7<p>All-cause hospitalization primary case definition: a medical hospitalization of any cause, excluding planned admissions for medical investigation/care or elective surgery and admissions for trauma.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "efficacy", "episodes", "infants", "aged", "wk"], "article_id"=>1121355, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.t002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_efficacy_against_all_episodes_of_clinical_and_severe_malaria_in_infants_aged_6_8211_12_wk_at_enrollment_/1121355", "title"=>"Vaccine efficacy against all episodes of clinical and severe malaria in infants aged 6–12 wk at enrollment.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613741"], "description"=>"<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³. This definition was used for this analysis because during routine clinical practice these children would normally receive a full course of anti-malarial treatment.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "cases", "averted", "vaccinated", "18-mo", "follow-up"], "article_id"=>1121335, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g006", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Number_of_cases_of_clinical_malaria_secondary_case_definition_averted_per_1_000_participants_vaccinated_during_an_18_mo_follow_up_period_per_protocol_population_/1121335", "title"=>"Number of cases of clinical malaria (secondary case definition) averted per 1,000 participants vaccinated during an 18-mo follow-up period (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613754"], "description"=>"<p>Clinical malaria secondary case definition: illness in a child brought to a study facility with a measured temperature of ≥37.5°C or reported fever within the last 24 h and <i>P. falciparum</i> asexual parasitemia at a density of >0 parasites/mm³. This definition was used for this analysis because during routine clinical practice these children would normally receive a full course of anti-malarial treatment. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "averted", "18-mo", "follow-up", "infants", "wk", "ordered", "incidence"], "article_id"=>1121348, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g015", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Cases_of_clinical_malaria_secondary_case_definition_averted_during_an_18_mo_follow_up_period_in_infants_6_8211_12_wk_of_age_at_enrollment_by_study_site_ordered_by_increasing_malaria_incidence_at_each_site_intention_to_treat_population_/1121348", "title"=>"Cases of clinical malaria (secondary case definition) averted during an 18-mo follow-up period in infants 6–12 wk of age at enrollment, by study site, ordered by increasing malaria incidence at each site (intention-to-treat population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}
• {"files"=>["https://ndownloader.figshare.com/files/1613751"], "description"=>"<p>Interaction <i>p-</i>value = 0.1682. The size of each blue square reflects the relative number of participants enrolled at each study site; the horizontal bars show the lower limit (LL) and upper limit (UL) of the 95% confidence interval. Study sites are ordered from lowest (Kilifi) to highest (Siaya) incidence of clinical malaria, defined as a measured or reported fever within previous 24 h and parasite density >0 parasites/mm³ (i.e., clinical malaria secondary case definition), measured in control infants 6–12 wk of age at enrollment during 12 mo of follow-up. VE is VE against all episodes of clinical malaria meeting the primary case definition, unadjusted for covariates. Clinical malaria primary case definition: illness in a child brought to a study facility with a temperature of ≥37.5°C and <i>P. falciparum</i> asexual parasitemia at a density of >5,000 parasites/mm³ or a case of malaria meeting the primary case definition of severe malaria.</p>", "links"=>[], "tags"=>["immunology", "Vaccination and immunization", "Vaccine development", "vaccines", "Clinical immunology", "immunity", "Infectious diseases", "Parasitic diseases", "malaria", "Tropical diseases", "efficacy", "episodes", "18-mo", "follow-up", "infants", "wk", "ordered", "incidence"], "article_id"=>1121345, "categories"=>["Biological Sciences"], "users"=>["The RTS,S Clinical Trials Partnership (2014)"], "doi"=>"https://dx.doi.org/10.1371/journal.pmed.1001685.g012", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Vaccine_efficacy_against_all_episodes_of_clinical_malaria_primary_case_definition_during_an_18_mo_follow_up_period_after_dose_3_in_infants_6_8211_12_wk_of_age_at_enrollment_ordered_by_increasing_malaria_incidence_at_each_study_site_per_protocol_populatio/1121345", "title"=>"Vaccine efficacy against all episodes of clinical malaria (primary case definition) during an 18-mo follow-up period after dose 3 in infants 6–12 wk of age at enrollment, ordered by increasing malaria incidence at each study site (per-protocol population).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-29 03:13:50"}

PMC Usage Stats | Further Information

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Relative Metric

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F1000Prime