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2. A Pfs48/45-based vaccine to block Plasmodium falciparum transmission:phase 1, open-label, clinical trial

Author

Alkema, M., Smit, M. J., Marin-Mogollon, C., Totté, K., Teelen, K., van Gemert, G. J., van de Vegte-Bolmer, M., Mordmüller, B. G., Reimer, J. M., Lövgren-Bengtsson, K. L., Sauerwein, R. W., Bousema, T., Plieskatt, J., Theisen, M., Jore, M. M., McCall, M. B.B., Alkema, M., Smit, M. J., Marin-Mogollon, C., Totté, K., Teelen, K., van Gemert, G. J., van de Vegte-Bolmer, M., Mordmüller, B. G., Reimer, J. M., Lövgren-Bengtsson, K. L., Sauerwein, R. W., Bousema, T., Plieskatt, J., Theisen, M., Jore, M. M., and McCall, M. B.B.

Abstract

Background: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P. falciparum glutamate-rich protein (R0), has previously been produced in Lactococcus lactis and elicited functional antibodies in rodents. Here, we assess the safety and transmission-reducing efficacy of R0.6C adsorbed to aluminium hydroxide with and without Matrix-M™ adjuvant in humans. Methods: In this first-in-human, open-label clinical trial, malaria-naïve adults, aged 18–55 years, were recruited at the Radboudumc in Nijmegen, the Netherlands. Participants received four intramuscular vaccinations on days 0, 28, 56 and 168 with either 30 µg or 100 µg of R0.6C and were randomised for the allocation of one of the two different adjuvant combinations: aluminium hydroxide alone, or aluminium hydroxide combined with Matrix-M1™ adjuvant. Adverse events were recorded from inclusion until 84 days after the fourth vaccination. Anti-R0.6C and anti-6C IgG titres were measured by enzyme-linked immunosorbent assay. Transmission-reducing activity of participants’ serum and purified vaccine-specific immunoglobulin G was assessed by standard membrane feeding assays using laboratory-reared Anopheles stephensi mosquitoes and cultured P. falciparum gametocytes. Results: Thirty-one participants completed four vaccinations and were included in the analysis. Administration of all doses was safe and well-tolerated, with one related grade 3 adverse event (transient fever) and no serious adverse events occurring. Anti-R0.6C and anti-6C IgG titres were similar between the 30 and 100 µg R0.6C arms

Published
2024

3. Import- en reizigersziekten

Author

Sauerwein, R. W., Visser, L. G., Hoepelman, A. I. M., editor, Kroes, A. C. M., editor, Sauerwein, R. W., editor, Verbrugh, H. A., editor, and Nouwen, J. L., editor

Published
2016
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11. CRISPR/Cas9-engineered inducible gametocyte producer lines as a valuable tool for; Plasmodium falciparum; malaria transmission research

Author

Boltryk, S. D., Passecker, A., Alder, A., Carrington, E., van de Vegte-Bolmer, M., van Gemert, G. J., van der Starre, A., Beck, H. P., Sauerwein, R. W., Kooij, T. W. A., Brancucci, N. M. B., Proellochs, N. I., Gilberger, T. W., and Voss, T. S.

Abstract

The malaria parasite Plasmodium falciparum replicates inside erythrocytes in the blood of infected humans. During each replication cycle, a small proportion of parasites commits to sexual development and differentiates into gametocytes, which are essential for parasite transmission via the mosquito vector. Detailed molecular investigation of gametocyte biology and transmission has been hampered by difficulties in generating large numbers of these highly specialised cells. Here, we engineer P. falciparum NF54 inducible gametocyte producer (iGP) lines for the routine mass production of synchronous gametocytes via conditional overexpression of the sexual commitment factor GDV1. NF54/iGP lines consistently achieve sexual commitment rates of 75% and produce viable gametocytes that are transmissible by mosquitoes. We also demonstrate that further genetic engineering of NF54/iGP parasites is a valuable tool for the targeted exploration of gametocyte biology. In summary, we believe the iGP approach developed here will greatly expedite basic and applied malaria transmission stage research.

Published
2021
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12. Viewpoint of a WHO Advisory Group Tasked to Consider Establishing a Closely-monitored Challenge Model of Coronavirus Disease 2019 (COVID-19) in Healthy Volunteers

Author

Levine, MM, Abdullah, S, Arabi, YM, Darko, DM, Durbin, AP, Estrada, V, Jamrozik, E, Kremsner, PG, Lagos, R, Pitisuttithum, P, Plotkin, SA, Sauerwein, R, Shi, S-L, Sommerfelt, H, Subbarao, K, Treanor, JJ, Vrati, S, King, D, Balasingam, S, Weller, C, Aguilar, AO, Cassetti, MC, Krause, PR, Restrepo, AMH, Levine, MM, Abdullah, S, Arabi, YM, Darko, DM, Durbin, AP, Estrada, V, Jamrozik, E, Kremsner, PG, Lagos, R, Pitisuttithum, P, Plotkin, SA, Sauerwein, R, Shi, S-L, Sommerfelt, H, Subbarao, K, Treanor, JJ, Vrati, S, King, D, Balasingam, S, Weller, C, Aguilar, AO, Cassetti, MC, Krause, PR, and Restrepo, AMH

Abstract

WHO convened an Advisory Group (AG) to consider the feasibility, potential value, and limitations of establishing a closely-monitored challenge model of experimental severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) in healthy adult volunteers. The AG included experts in design, establishment, and performance of challenges. This report summarizes issues that render a COVID-19 model daunting to establish (the potential of SARS-CoV-2 to cause severe/fatal illness, its high transmissibility, and lack of a "rescue treatment" to prevent progression from mild/moderate to severe clinical illness) and it proffers prudent strategies for stepwise model development, challenge virus selection, guidelines for manufacturing challenge doses, and ways to contain SARS-CoV-2 and prevent transmission to household/community contacts. A COVID-19 model could demonstrate protection against virus shedding and/or illness induced by prior SARS-CoV-2 challenge or vaccination. A limitation of the model is that vaccine efficacy in experimentally challenged healthy young adults cannot per se be extrapolated to predict efficacy in elderly/high-risk adults.

Published
2021

13. A Randomized Clinical Trial to Compare Plasmodium falciparum Gametocytemia and Infectivity After Blood-Stage or Mosquito Bite-Induced Controlled Malaria Infection (vol 222, jiaa157, 2020)

Author

Alkema, M, Reuling, IJ, de Jong, GM, Lanke, K, Coffeng, LE, van Gemert, G-J, van de Vegte-Bolmer, M, de Mast, Q, van Crevel, R, Ivinson, K, Ockenhouse, CF, McCarthy, JS, Sauerwein, R, Collins, KA, Bousema, T, Alkema, M, Reuling, IJ, de Jong, GM, Lanke, K, Coffeng, LE, van Gemert, G-J, van de Vegte-Bolmer, M, de Mast, Q, van Crevel, R, Ivinson, K, Ockenhouse, CF, McCarthy, JS, Sauerwein, R, Collins, KA, and Bousema, T

Published
2020

14. Structural basis for recognition of the malaria vaccine candidate Pfs48/45 by a transmission blocking antibody

Author

Lennartz, F, Brod, F, Dabbs, R, Miura, K, Mekhaiel, D, Marini, A, Jore, M, Søgaard, M, Jørgensen, T, De Jongh, W, Sauerwein, R, Long, C, Biswas, S, and Higgins, M

Subjects
Membrane Glycoproteins, Science, Protozoan Proteins, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], Antibodies, Monoclonal, Malaria, Epitopes, Mice, All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Protein Domains, Malaria Vaccines, Protein Interaction Mapping, Animals, Immunization, lcsh:Q, Antibodies, Blocking, lcsh:Science
Abstract

Contains fulltext : 201378.pdf (Publisher’s version ) (Open Access) The quest to develop an effective malaria vaccine remains a major priority in the fight against global infectious disease. An approach with great potential is a transmission-blocking vaccine which induces antibodies that prevent establishment of a productive infection in mosquitos that feed on infected humans, thereby stopping the transmission cycle. One of the most promising targets for such a vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for production of full-length Pfs48/45 and use this to raise a panel of monoclonal antibodies. We map the binding regions of these antibodies on Pfs48/45 and correlate the location of their epitopes with their transmission-blocking activity. Finally, we present the structure of the C-terminal domain of Pfs48/45 bound to the most potent transmission-blocking antibody, and provide key molecular information for future structure-guided immunogen design.

Published
2018

19. Antibody responses to antigenic targets of recent exposure are associated with low-density parasitemia in controlled human Plasmodium falciparum infections

Author

van Den Hoogen, L, Walk, J, Oulton, T, Reuling, I, Reiling, L, Beeson, J, Coppel, R, Singh, S, Draper, S, Bousema, T, Drakeley, C, Sauerwein, R, and Tetteh, K

Subjects
exposure, controlled human malaria infection (CHMI), parasitic diseases, malaria, antibodies, sero-surveillance, seroepidemiology
Abstract

The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the Plasmodium parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray. All participants developed a blood-stage infection with peak parasite densities up to 100 parasites/μl in the majority of participants (50/54), while the remaining four participants had peak densities between 100 and 200 parasites/μl. There was a strong correlation between parasite density and antibody responses associated with the most reactive blood-stage targets 1 month after CHMI (Etramp 5, GLURP-R2, MSP4 and MSP1-19; Spearman’s ρ = 0.82, p < 0.001). Most volunteers developed antibodies against a potential marker of recent exposure: Etramp 5 (37/45, 82%). Our findings justify validation in endemic populations to define a minimum set of antigens needed to detect exposure to natural low-density infections.

Published
2019

28. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density (vol 10, 1433, 2019)

Author

Slater, HC, Ross, A, Felger, I, Hofmann, NE, Robinson, L, Cook, J, Goncalves, BP, Bjorkman, A, Ouedraogo, AL, Morris, U, Msellem, M, Koepfli, C, Mueller, I, Tadesse, F, Gadisa, E, Das, S, Domingo, G, Kapulu, M, Midega, J, Owusu-Agyei, S, Nabet, C, Piarroux, R, Doumbo, O, Doumbo, SN, Koram, K, Lucchi, N, Udhayakumar, V, Mosha, J, Tiono, A, Chandramohan, D, Gosling, R, Mwingira, F, Sauerwein, R, Paul, R, Riley, EM, White, NJ, Nosten, F, Imwong, M, Bousema, T, Drakeley, C, Okell, LC, Slater, HC, Ross, A, Felger, I, Hofmann, NE, Robinson, L, Cook, J, Goncalves, BP, Bjorkman, A, Ouedraogo, AL, Morris, U, Msellem, M, Koepfli, C, Mueller, I, Tadesse, F, Gadisa, E, Das, S, Domingo, G, Kapulu, M, Midega, J, Owusu-Agyei, S, Nabet, C, Piarroux, R, Doumbo, O, Doumbo, SN, Koram, K, Lucchi, N, Udhayakumar, V, Mosha, J, Tiono, A, Chandramohan, D, Gosling, R, Mwingira, F, Sauerwein, R, Paul, R, Riley, EM, White, NJ, Nosten, F, Imwong, M, Bousema, T, Drakeley, C, and Okell, LC

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

29. The temporal dynamics and infectiousness of subpatent Plasmodium falciparum infections in relation to parasite density

Author

Slater, HC, Ross, A, Felger, I, Hofmann, NE, Robinson, L, Cook, J, Goncalves, BP, Bjorkman, A, Ouedraogo, AL, Morris, U, Msellem, M, Koepfli, C, Mueller, I, Tadesse, F, Gadisa, E, Das, S, Domingo, G, Kapulu, M, Midega, J, Owusu-Agyei, S, Nabet, C, Piarroux, R, Doumbo, O, Doumbo, SN, Koram, K, Lucchi, N, Udhayakumar, V, Mosha, J, Tiono, A, Chandramohan, D, Gosling, R, Mwingira, F, Sauerwein, R, Riley, EM, White, NJ, Nosten, F, Imwong, M, Bousema, T, Drakeley, C, Okell, LC, Slater, HC, Ross, A, Felger, I, Hofmann, NE, Robinson, L, Cook, J, Goncalves, BP, Bjorkman, A, Ouedraogo, AL, Morris, U, Msellem, M, Koepfli, C, Mueller, I, Tadesse, F, Gadisa, E, Das, S, Domingo, G, Kapulu, M, Midega, J, Owusu-Agyei, S, Nabet, C, Piarroux, R, Doumbo, O, Doumbo, SN, Koram, K, Lucchi, N, Udhayakumar, V, Mosha, J, Tiono, A, Chandramohan, D, Gosling, R, Mwingira, F, Sauerwein, R, Riley, EM, White, NJ, Nosten, F, Imwong, M, Bousema, T, Drakeley, C, and Okell, LC

Abstract

Malaria infections occurring below the limit of detection of standard diagnostics are common in all endemic settings. However, key questions remain surrounding their contribution to sustaining transmission and whether they need to be detected and targeted to achieve malaria elimination. In this study we analyse a range of malaria datasets to quantify the density, detectability, course of infection and infectiousness of subpatent infections. Asymptomatically infected individuals have lower parasite densities on average in low transmission settings compared to individuals in higher transmission settings. In cohort studies, subpatent infections are found to be predictive of future periods of patent infection and in membrane feeding studies, individuals infected with subpatent asexual parasite densities are found to be approximately a third as infectious to mosquitoes as individuals with patent (asexual parasite) infection. These results indicate that subpatent infections contribute to the infectious reservoir, may be long lasting, and require more sensitive diagnostics to detect them in lower transmission settings.

Published
2019

35. Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity (vol 9, 558, 2018)

Author

Stone, W.J.R., Campo, J.J., Ouedraogo, A.L., Meerstein-Kessel, L., Morlais, I., D. da, Cohuet, A., Nsango, S., Sutherland, C.J., Vegte-Bolmer, M.V. van de, Siebelink-Stoter, R., Gemert, G.J. van, Graumans, W., Lanke, K., Shandling, A.D., Pablo, J.V., Teng, A.A., Jones, S., Jong, R.M. de, Fabra-Garcia, A., Bradley, J., Roeffen, W., Lasonder, E., Gremo, G., Schwarzer, E., Janse, C.J., Singh, S.K., Theisen, M., Felgner, P., Marti, M., Drakeley, C., Sauerwein, R., Bousema, T., and Jore, M.M.

Published
2018

41. A controlled human malaria infection model enabling evaluation of transmission-blocking interventions

Author

Collins, KA, Wang, CYT, Adams, M, Mitchell, H, Rampton, M, Elliott, S, Reuling, IJ, Bousema, T, Sauerwein, R, Chalon, S, Mohrle, JJ, McCarthy, JS, Collins, KA, Wang, CYT, Adams, M, Mitchell, H, Rampton, M, Elliott, S, Reuling, IJ, Bousema, T, Sauerwein, R, Chalon, S, Mohrle, JJ, and McCarthy, JS

Abstract

BACKGROUND: Drugs and vaccines that can interrupt the transmission of Plasmodium falciparum will be important for malaria control and elimination. However, models for early clinical evaluation of candidate transmission-blocking interventions are currently unavailable. Here, we describe a new model for evaluating malaria transmission from humans to Anopheles mosquitoes using controlled human malaria infection (CHMI). METHODS: Seventeen healthy malaria-naive volunteers underwent CHMI by intravenous inoculation of P. falciparum-infected erythrocytes to initiate blood-stage infection. Seven to eight days after inoculation, participants received piperaquine (480 mg) to attenuate asexual parasite replication while allowing gametocytes to develop and mature. Primary end points were development of gametocytemia, the transmissibility of gametocytes from humans to mosquitoes, and the safety and tolerability of the CHMI transmission model. To investigate in vivo gametocytocidal drug activity in this model, participants were either given an experimental antimalarial, artefenomel (500 mg), or a known gametocytocidal drug, primaquine (15 mg), or remained untreated during the period of gametocyte carriage. RESULTS: Male and female gametocytes were detected in all participants, and transmission to mosquitoes was achieved from 8 of 11 (73%) participants evaluated. Compared with results in untreated controls (n = 7), primaquine (15 mg, n = 5) significantly reduced gametocyte burden (P = 0.01), while artefenomel (500 mg, n = 4) had no effect. Adverse events (AEs) were mostly mild or moderate. Three AEs were assessed as severe - fatigue, elevated alanine aminotransferase, and elevated aspartate aminotransferase - and were attributed to malaria infection. Transaminase elevations were transient, asymptomatic, and resolved without intervention. CONCLUSION: We report the safe and reproducible induction of P. falciparum gametocytes in healthy malaria-naive volunteers at densities infectious

Published
2018

42. A long-duration dihydroorotate dehydrogenase inhibitor (DSM265) for prevention and treatment of malaria

Author

Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Harvard University--MIT Division of Health Sciences and Technology, Bhatia, Sangeeta N, March-Riera, Sandra, Phillips, M. A., Lotharius, J., Marsh, K., White, J., Dayan, A., White, K. L., Njoroge, J. W., El Mazouni, F., Lao, Y., Kokkonda, S., Tomchick, D. R., Deng, X., Laird, T., Ng, C. L., Fidock, D. A., Wittlin, S., Lafuente-Monasterio, M., Benito, F. J. G., Alonso, L. M. S., Martinez, M. S., Jimenez-Diaz, M. B., Bazaga, S. F., Angulo-Barturen, I., Haselden, J. N., Louttit, J., Cui, Y., Sridhar, A., Zeeman, A.-M., Kocken, C., Sauerwein, R., Dechering, K., Avery, V. M., Duffy, S., Delves, M., Sinden, R., Ruecker, A., Wickham, K. S., Rochford, R., Gahagen, J., Iyer, L., Riccio, E., Mirsalis, J., Bathhurst, I., Rueckle, T., Ding, X., Campo, B., Leroy, D., Rogers, M. J., Rathod, P. K., Burrows, J. N., Charman, S. A., Massachusetts Institute of Technology. Institute for Medical Engineering & Science, Harvard University--MIT Division of Health Sciences and Technology, Bhatia, Sangeeta N, March-Riera, Sandra, Phillips, M. A., Lotharius, J., Marsh, K., White, J., Dayan, A., White, K. L., Njoroge, J. W., El Mazouni, F., Lao, Y., Kokkonda, S., Tomchick, D. R., Deng, X., Laird, T., Ng, C. L., Fidock, D. A., Wittlin, S., Lafuente-Monasterio, M., Benito, F. J. G., Alonso, L. M. S., Martinez, M. S., Jimenez-Diaz, M. B., Bazaga, S. F., Angulo-Barturen, I., Haselden, J. N., Louttit, J., Cui, Y., Sridhar, A., Zeeman, A.-M., Kocken, C., Sauerwein, R., Dechering, K., Avery, V. M., Duffy, S., Delves, M., Sinden, R., Ruecker, A., Wickham, K. S., Rochford, R., Gahagen, J., Iyer, L., Riccio, E., Mirsalis, J., Bathhurst, I., Rueckle, T., Ding, X., Campo, B., Leroy, D., Rogers, M. J., Rathod, P. K., Burrows, J. N., and Charman, S. A.

Abstract

Malaria is one of the most significant causes of childhood mortality, but disease control efforts are threatened by resistance of the Plasmodium parasite to current therapies. Continued progress in combating malaria requires development of new, easy to administer drug combinations with broad-ranging activity against all manifestations of the disease. DSM265, a triazolopyrimidine-based inhibitor of the pyrimidine biosynthetic enzyme dihydroorotate dehydrogenase (DHODH), is the first DHODH inhibitor to reach clinical development for treatment of malaria. We describe studies profiling the biological activity, pharmacological and pharmacokinetic properties, and safety of DSM265, which supported its advancement to human trials. DSM265 is highly selective toward DHODH of the malaria parasite Plasmodium, efficacious against both blood and liver stages of P. falciparum, and active against drug-resistant parasite isolates. Favorable pharmacokinetic properties of DSM265 are predicted to provide therapeutic concentrations for more than 8 days after a single oral dose in the range of 200 to 400 mg. DSM265 was well tolerated in repeat-dose and cardiovascular safety studies in mice and dogs, was not mutagenic, and was inactive against panels of human enzymes/receptors. The excellent safety profile, blood- and liver-stage activity, and predicted long half-life in humans position DSM265 as a new potential drug combination partner for either single-dose treatment or once-weekly chemoprevention. DSM265 has advantages over current treatment options that are dosed daily or are inactive against the parasite liver stage.

Published
2017

45. [Splenomegaly in an Eritrean refugee: the hyper-reactive malaria splenomegaly syndrome.]

Author

Cruijsen, M. M., Isaie Reuling, Keuter, M., Sauerwein, R. W., Ven, A. J., and Mast, Q.

Subjects
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4]
Abstract

Item does not contain fulltext

Published
2016

48. Infections

Author

Holzapfel, L., Chastang, Cl., Carme, Ph., Joffre, T., Demingeon, G., Clément, C., Chevret, S., Lestavel, P., Poulain, D., Fourrier, F., Fruit, J., Medhaoui, H., Chopin, C., Jordá, R., Serra, J., Nava, J., Maraví, E., Alvarez, F., Salord, F., Eynard, N., Grando, J., Chacornac, R., van Deuren, M., van Dalen, R., Sauerwein, R. W., Bartelink, A. K. M., van der Meer, J. W. M., Guidet, B., Nicola, I., Staikowsky, F., Barakett, V., Petit, J. C., Offenstadt, G., and SEMIUC Group of CNSI Research.

Published
1992
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49. malERA: An updated research agenda for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication

Author

Kaslow, DC, Okumu, F, Wells, TNC, Rabinovich, R, Bassat, Q, Birkett, A, Bompart, F, Burt, A, Chaccour, C, Chitnis, C, Culpepper, J, Domingo, G, Duffy, P, Ghani, A, Greenwood, B, Hall, BF, Hamon, N, Jacobs-Lorena, M, James, S, Koram, KA, Kremsner, P, Kumar, A, Leroy, D, Leroy, O, Lindsay, S, Majambere, S, Mbogo, C, McCarthy, J, Qi, G, Rasgon, J, Richardson, J, Richie, T, Sauerwein, R, Slutsker, L, Vekemans, J, Bill & Melinda Gates Foundation, and Medical Research Council (MRC)

Subjects
0301 basic medicine, Plasmodium, GENE DRIVE SYSTEM, Biomedical Research, Mosquito Control, Computer science, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], law.invention, DOUBLE-BLIND, 0302 clinical medicine, law, Medicine and Health Sciences, HIGH-THROUGHPUT ASSAY, Protozoans, Vaccines, Collection Review, Vector control, Malarial Parasites, Eukaryota, Drugs, General Medicine, 11 Medical And Health Sciences, TRANSMISSION-BLOCKING ACTIVITY, Parasitic diseases, 3. Good health, Infectious Diseases, Transmission (mechanics), Malalties parasitàries, Risk analysis (engineering), Medicine, Malaria control, Life Sciences & Biomedicine, Drug Research and Development, Infectious Disease Control, RESISTANT ANOPHELES-GAMBIAE, 030231 tropical medicine, Severe disease, Malària, Antimalarials, 03 medical and health sciences, Medicine, General & Internal, All institutes and research themes of the Radboud University Medical Center, Malaria elimination, General & Internal Medicine, Malaria Vaccines, Parasite Groups, Parasitic Diseases, medicine, Animals, Humans, Disease Eradication, VIVAX INFECTION, Pharmacology, Science & Technology, NUCLEIC-ACID AMPLIFICATION, Organisms, Biology and Life Sciences, PLASMODIUM-FALCIPARUM MALARIA, PYRIPROXYFEN MIXTURE NET, Tropical Diseases, medicine.disease, Parasitic Protozoans, Insect Vectors, Malaria, 030104 developmental biology, Direct Treatment, Insecticide resistance, BLOOD-STAGE MALARIA, Parasitology, Apicomplexa
Abstract

Since the turn of the century, a remarkable expansion has been achieved in the range and effectiveness of products and strategies available to prevent, treat, and control malaria, including advances in diagnostics, drugs, vaccines, and vector control. These advances have once again put malaria elimination on the agenda. However, it is clear that even with the means available today, malaria control and elimination pose a formidable challenge in many settings. Thus, currently available resources must be used more effectively, and new products and approaches likely to achieve these goals must be developed. This paper considers tools (both those available and others that may be required) to achieve and maintain malaria elimination. New diagnostics are needed to direct treatment and detect transmission potential; new drugs and vaccines to overcome existing resistance and protect against clinical and severe disease, as well as block transmission and prevent relapses; and new vector control measures to overcome insecticide resistance and more powerfully interrupt transmission. It is also essential that strategies for combining new and existing approaches are developed for different settings to maximise their longevity and effectiveness in areas with continuing transmission and receptivity. For areas where local elimination has been recently achieved, understanding which measures are needed to maintain elimination is necessary to prevent rebound and the reestablishment of transmission. This becomes increasingly important as more countries move towards elimination., David Kaslow and colleagues examine the progress in reasearch for diagnostics, drugs, vaccines, and vector control in malaria elimination and eradication and propose a research agenda.

Published
2017

50. Pion and Kaon Pair Production in Photon-Photon Collisions

Author

TPC/Two-Gamma Collaboration, 相原, 博昭, Alston-Garnjost, M., Avery, R. E., Barbaro-Galtieri, A., Barker, A. R., Barnes, A. V., Barnett, B. A., Bauer, D. A., Bengtsson, H-U., Bintinger, D. L., Blumenfeld, B. J., Bobbink, G. J., Bross, A. D., Buchanan, C. D., Buijs, A., Cain, M. P., Caldwell, D. O., Chamberlain, O., Chien, C. -Y., Clark, A. R., Cowan, G. D., Crane, D. A., Dahl, O. I., Derby, K. A., Eastman, J. J., Eberhard, P. H., Eisner, A. M., 榎本, 良治, Erne, F. C., Fujii, T., Gabioud, B., Gary, J. W., Gorn, W., Hauptman, J. M., Hofmann, W., Huth, J. E., Hylen, J., Joshi, U. P., 釜江, 常好, Kaye, H. S., Kees, K. H., Kenney, R. W., Kerth, L. T., Ko, Winston, Koda, R. I., Kofler, R. R., Kwong, K. K., Lander, R. L., Langeveld, W. G. J., Layter, J. G., Linde, F. L., Lindsey, C. S., Loken, S. C., Lu, A., Lu, X.-Q., Lynch, G. R., Madaras, R. J., Maeshima, K., Magnuson, B. D., Marx, J. N., Maruyama, K., Masek, G. E., Mathis, L. G., Matthews, J. A. J., Maxfield, S. J., Melnikoff, S. O., Miller, E. S., Moses, W., McNeil, R. R., Nemethy, P., Nygren, D. R., Oddone, P. J., Paar, H. P., Park, D. A., Pellett, D. E., Pripstein, M., Ronan, M. T., Ross, R. R., Rouse, F. R., Sauerwein, R. R., Schwitkis, K. A., Sens, J. C., Shapiro, G., Shapiro, M. D., Shen, B. C., Slater, W. E., Smith, J. R., Steinman, J. S., Stevenson, M. L., Stork, D. H., Strauss, M. G., Sullivan, M. K., 高橋, 忠幸, Thompson, J. R., Toge, N., van Tyen, R., van Uitert, B., VanDalen, G. J., van Daalen Wetters, R. F., Vernon, W., Wagner, W., Wang, E. M., Wang, Y. X., Wayne, M. R., Wenzel, W. A., White, J. T., Williams, M. C. S., Wolf, Z. R., Yamamoto, H., Yamauchi, M., Yellin, S. J., Zeitlin, C., Zhang, W. -M., TPC/Two-Gamma Collaboration, Aihara, H., Enomoto, R., Kamae, T., Takahashi, Tadayuki, TPC/Two-Gamma Collaboration, 相原, 博昭, Alston-Garnjost, M., Avery, R. E., Barbaro-Galtieri, A., Barker, A. R., Barnes, A. V., Barnett, B. A., Bauer, D. A., Bengtsson, H-U., Bintinger, D. L., Blumenfeld, B. J., Bobbink, G. J., Bross, A. D., Buchanan, C. D., Buijs, A., Cain, M. P., Caldwell, D. O., Chamberlain, O., Chien, C. -Y., Clark, A. R., Cowan, G. D., Crane, D. A., Dahl, O. I., Derby, K. A., Eastman, J. J., Eberhard, P. H., Eisner, A. M., 榎本, 良治, Erne, F. C., Fujii, T., Gabioud, B., Gary, J. W., Gorn, W., Hauptman, J. M., Hofmann, W., Huth, J. E., Hylen, J., Joshi, U. P., 釜江, 常好, Kaye, H. S., Kees, K. H., Kenney, R. W., Kerth, L. T., Ko, Winston, Koda, R. I., Kofler, R. R., Kwong, K. K., Lander, R. L., Langeveld, W. G. J., Layter, J. G., Linde, F. L., Lindsey, C. S., Loken, S. C., Lu, A., Lu, X.-Q., Lynch, G. R., Madaras, R. J., Maeshima, K., Magnuson, B. D., Marx, J. N., Maruyama, K., Masek, G. E., Mathis, L. G., Matthews, J. A. J., Maxfield, S. J., Melnikoff, S. O., Miller, E. S., Moses, W., McNeil, R. R., Nemethy, P., Nygren, D. R., Oddone, P. J., Paar, H. P., Park, D. A., Pellett, D. E., Pripstein, M., Ronan, M. T., Ross, R. R., Rouse, F. R., Sauerwein, R. R., Schwitkis, K. A., Sens, J. C., Shapiro, G., Shapiro, M. D., Shen, B. C., Slater, W. E., Smith, J. R., Steinman, J. S., Stevenson, M. L., Stork, D. H., Strauss, M. G., Sullivan, M. K., 高橋, 忠幸, Thompson, J. R., Toge, N., van Tyen, R., van Uitert, B., VanDalen, G. J., van Daalen Wetters, R. F., Vernon, W., Wagner, W., Wang, E. M., Wang, Y. X., Wayne, M. R., Wenzel, W. A., White, J. T., Williams, M. C. S., Wolf, Z. R., Yamamoto, H., Yamauchi, M., Yellin, S. J., Zeitlin, C., Zhang, W. -M., TPC/Two-Gamma Collaboration, Aihara, H., Enomoto, R., Kamae, T., and Takahashi, Tadayuki

Abstract

著者人数：113名

Published
2015

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