Browsing by Author "Chitnis, C."
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Item A Research Agenda to Underpin Malaria Eradication(PLoS Medicine, 2011-01-25) Alonso, P.L.; Brown, G.; Arevalo-Herrera, M.; Binka, F.; Chitnis, C.; Collins, F.; Doumbo, O.K.; Greenwood, B.; Hall, B.F.; Levine, M.M.; Mendis, K.; Newman, R.D.; Plowe, C.V.; Rodrı´guez, M.H.; Sinden, R.; Slutsker, L.; Tanner, M.The interruption of malaria transmission worldwide is one of the greatest challenges for international health and development communities. The current expert view suggests that, by aggressively scaling up control with currently available tools and strategies, much greater gains could be achieved against malaria, including elimination from a number of countries and regions; however, even with maximal effort we will fall short of global eradication. The Malaria Eradication Research Agenda (malERA) complements the current research agenda—primarily directed towards reducing morbidity and mortality—with one that aims to identify key knowledge gaps and define the strategies and tools that will result in reducing the basic reproduction rate to less than 1, with the ultimate aim of eradication of the parasite from the human population. Sustained commitment from local communities, civil society, policy leaders, and the scientific community, together with a massive effort to build a strong base of researchers from the endemic areas will be critical factors in the success of this new agenda.Item RTS,S/AS01E immunization increases antibody responses to vaccine-unrelated Plasmodium falciparum antigens associated with protection against clinical malaria in African children: A case-control study(BMC Medicine, 2019-08-14) Gyan, B.; Dobaño, C.; Ubillos, I.; Jairoce, C.; Vidal, M.; Jiménez, A.; Santano, R.; Dosoo, D.; Nhabomba, A.J.; Ayestaran, A.; Aguilar, R.; Williams, N.A.; Díez-Padrisa, N.; Lanar, D.; Chauhan, V.; Chitnis, C.; Dutta, S.; Gaur, D.; Angov, E.; Asante, K.P.; Owusu-Agyei, S.; Valim, C.; Gamain, B.; Coppel, R.L.; Cavanagh, D.; Beeson, J.G.; Campo, J.J.; Moncunill, G.Background: Vaccination and naturally acquired immunity against microbial pathogens may have complex interactions that influence disease outcomes. To date, only vaccine-specific immune responses have routinely been investigated in malaria vaccine trials conducted in endemic areas. We hypothesized that RTS,S/A01E immunization affects acquisition of antibodies to Plasmodium falciparum antigens not included in the vaccine and that such responses have an impact on overall malaria protective immunity. Methods: We evaluated IgM and IgG responses to 38 P. falciparum proteins putatively involved in naturally acquired immunity to malaria in 195 young children participating in a case-control study nested within the African phase 3 clinical trial of RTS,S/AS01E (MAL055 NCT00866619) in two sites of different transmission intensity (Kintampo high and Manhiça moderate/low). We measured antibody levels by quantitative suspension array technology and applied regression models, multimarker analysis, and machine learning techniques to analyze factors affecting their levels and correlates of protection. Results: RTS,S/AS01E immunization decreased antibody responses to parasite antigens considered as markers of exposure (MSP142, AMA1) and levels correlated with risk of clinical malaria over 1-year follow-up. In addition, we show for the first time that RTS,S vaccination increased IgG levels to a specific group of pre-erythrocytic and blood-stage antigens (MSP5, MSP1 block 2, RH4.2, EBA140, and SSP2/TRAP) which levels correlated with protection against clinical malaria (odds ratio [95% confidence interval] 0.53 [0.3–0.93], p = 0.03, for MSP1; 0.52 [0.26–0.98], p = 0.05, for SSP2) in multivariable logistic regression analysesConclusions: Increased antibody responses to specific P. falciparum antigens in subjects immunized with this partially efficacious vaccine upon natural infection may contribute to overall protective immunity against malaria. Inclusion of such antigens in multivalent constructs could result in more efficacious second-generation multistage vaccines.