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Combating malaria: research, prevention and treatment

Guest editor: Prof James Beeson

Malaria is present in over 100 countries worldwide, including large areas of South America, Africa and Southeast Asia, and it is estimated that over 40% of the world’s population is at risk of infection. The disease is caught through the bite of an infected mosquito carrying plasmodium parasites in its saliva. It is estimated that malaria caused 627 000 deaths in 2012; infections caused by Plasmodium falciparum are the most severe and have the highest mortality rate, but Plasmodium vivax is increasingly recognized as an important cause of clinical symptoms.

Antimalarial drugs can be used to prevent and treat malaria, but parasites frequently develop resistance to these agents. Continued research aims to understand the mechanisms of resistance, develop new antimalarial drugs, and identify the best way to prevent being bitten by an infected mosquito. There is currently no licensed vaccine for malaria, although a number of candidate agents are currently being evaluated, and the World Health Organization aims to license vaccines against P. falciparum and P. vivax malaria for use in endemic areas by 2030. Understanding the mechanisms of naturally-acquired malaria immunity is essential to inform vaccine design; many studies are currently underway to explore these immunological mechanisms and identify promising vaccine candidates.

This article collection in BMC Medicine aims to highlight recent progress in all areas of malaria research, including vaccine development, investigations into new antimalarial agents, vector control and disease epidemiology.

  1. Commentary

    How important is gametocyte clearance after malaria therapy?

    There has been increasing interest in the role of malaria drugs in preventing malaria transmission from humans to mosquitoes, which would help augment malaria control and elimination strategies. Nevertheless, ...

    Harin A. Karunajeewa and Ivo Mueller

    BMC Medicine 2016 14:93

    Published on: 18 June 2016

  2. Research article

    Plasmodium falciparum dihydroartemisinin-piperaquine failures in Cambodia are associated with mutant K13 parasites presenting high survival rates in novel piperaquine in vitro assays: retrospective and prospective investigations

    The declining efficacy of dihydroartemisinin-piperaquine against Plasmodium falciparum in Cambodia, along with increasing numbers of recrudescent cases, suggests resistance to both artemisinin and piperaquine. Av...

    Valentine Duru, Nimol Khim, Rithea Leang, Saorin Kim, Anais Domergue, Nimol Kloeung, Sopheakvatey Ke, Sophy Chy, Rotha Eam, Chanra Khean, Kaknika Loch, Malen Ken, Dysoley Lek, Johann Beghain, Frédéric Ariey, Philippe J. Guerin…

    BMC Medicine 2015 13:305

    Published on: 22 December 2015

  3. Research article

    Randomized trial of primaquine hypnozoitocidal efficacy when administered with artemisinin-combined blood schizontocides for radical cure of Plasmodium vivax in Indonesia

    Safety and efficacy of primaquine against repeated attacks of Plasmodium vivax depends upon co-administered blood schizontocidal therapy in radical cure. We assessed primaquine (PQ) as hypnozoitocide when adminis...

    Erni J. Nelwan, Lenny L. Ekawati, Bagus Tjahjono, Rianto Setiabudy, Inge Sutanto, Krisin Chand, Tyas Ekasari, Dwi Djoko, Hasan Basri, W. Robert Taylor, Stephan Duparc, Decy Subekti, Iqbal Elyazar, Rintis Noviyanti, Herawati Sudoyo and J. Kevin Baird

    BMC Medicine 2015 13:294

    Published on: 11 December 2015

  4. Research article

    Tolerability and safety of weekly primaquine against relapse of Plasmodium vivax in Cambodians with glucose-6-phosphate dehydrogenase deficiency

    Primaquine is used to prevent Plasmodium vivax relapse; however, it is not implemented in many malaria-endemic countries, including Cambodia, for fear of precipitating primaquine-induced acute haemolytic anaemia ...

    Sim Kheng, Sinoun Muth, Walter R. J. Taylor, Narann Tops, Khem Kosal, Khon Sothea, Phum Souy, Saorin Kim, Chuor Meng Char, Chan Vanna, Po Ly, Pascal Ringwald, Virak Khieu, Alexandra Kerleguer, Pety Tor, John K. Baird…

    BMC Medicine 2015 13:203

    Published on: 25 August 2015

  5. Research article

    Antimalarial drugs for preventing malaria during pregnancy and the risk of low birth weight: a systematic review and meta-analysis of randomized and quasi-randomized trials

    It is known that antimalarial drugs reduce the risk of low birth weight (LBW) in pregnant patients. However, a previous Cochrane review did not evaluate whether the level of antimalarial drug resistance could ...

    Flory Tsobo Muanda, Sonia Chaabane, Takoua Boukhris, Fabiano Santos, Odile Sheehy, Sylvie Perreault, Lucie Blais and Anick Bérard

    BMC Medicine 2015 13:193

    Published on: 14 August 2015

  6. Research Article

    The public health impact of malaria vaccine RTS,S in malaria endemic Africa: country-specific predictions using 18 month follow-up Phase III data and simulation models

    The RTS,S/AS01 malaria vaccine candidate recently completed Phase III trials in 11 African sites. Recommendations for its deployment will partly depend on predictions of public health impact in endemic countri...

    Melissa A Penny, Katya Galactionova, Michael Tarantino, Marcel Tanner and Thomas A Smith

    BMC Medicine 2015 13:170

    Published on: 29 July 2015

  7. Forum

    Malaria eradication and elimination: views on how to translate a vision into reality

    Although global efforts in the past decade have halved the number of deaths due to malaria, there are still an estimated 219 million cases of malaria a year, causing more than half a million deaths. In this fo...

    Marcel Tanner, Brian Greenwood, Christopher J. M. Whitty, Evelyn K. Ansah, Ric N. Price, Arjen M. Dondorp, Lorenz von Seidlein, J. Kevin Baird, James G. Beeson, Freya J.I. Fowkes, Janet Hemingway, Kevin Marsh and Faith Osier

    BMC Medicine 2015 13:167

    Published on: 25 July 2015

  8. Research article

    CD14hiCD16+ monocytes phagocytose antibody-opsonised Plasmodium falciparum infected erythrocytes more efficiently than other monocyte subsets, and require CD16 and complement to do so

    With more than 600,000 deaths from malaria, mainly of children under five years old and caused by infection with Plasmodium falciparum, comes an urgent need for an effective anti-malaria vaccine. Limited details ...

    Jingling Zhou, Gaoqian Feng, James Beeson, P. Mark Hogarth, Stephen J. Rogerson, Yan Yan and Anthony Jaworowski

    BMC Medicine 2015 13:154

    Published on: 7 July 2015

    The Erratum to this article has been published in BMC Medicine 2015 13:290

  9. Research article

    Severe malaria in children leads to a significant impairment of transitory otoacoustic emissions - a prospective multicenter cohort study

    Severe malaria may influence inner ear function, although this possibility has not been examined prospectively. In a retrospective analysis, hearing impairment was found in 9 of 23 patients with cerebral malar...

    Joachim Schmutzhard, Peter Lackner, Raimund Helbok, Helene Verena Hurth, Fabian Cedric Aregger, Veronika Muigg, Josua Kegele, Sebastian Bunk, Lukas Oberhammer, Natalie Fischer, Leyla Pinggera, Allan Otieno, Bernards Ogutu, Tsiri Agbenyega, Daniel Ansong, Ayola A. Adegnika…

    BMC Medicine 2015 13:125

    Published on: 28 May 2015

    The Erratum to this article has been published in BMC Medicine 2016 14:70

  10. Research article

    Microvascular obstruction and endothelial activation are independently associated with the clinical manifestations of severe falciparum malaria in adults: an observational study

    Microvascular obstruction and endothelial dysfunction have both been linked to tissue hypoperfusion in falciparum malaria, but their relative contributions to the disease’s pathogenesis and outcome are unknown.

    Josh Hanson, Sue J. Lee, Md Amir Hossain, Nicholas M. Anstey, Prakaykaew Charunwatthana, Richard J. Maude, Hugh W. F. Kingston, Saroj K. Mishra, Sanjib Mohanty, Katherine Plewes, Kim Piera, Mahtab U. Hassan, Aniruddha Ghose, M. Abul Faiz, Nicholas J. White, Nicholas P. J. Day…

    BMC Medicine 2015 13:122

    Published on: 27 May 2015

  11. Research article

    Prescriber and patient-oriented behavioural interventions to improve use of malaria rapid diagnostic tests in Tanzania: facility-based cluster randomised trial

    The increasing investment in malaria rapid diagnostic tests (RDTs) to differentiate malarial and non-malarial fevers, and an awareness of the need to improve case management of non-malarial fever, indicates an...

    Bonnie Cundill, Hilda Mbakilwa, Clare IR Chandler, George Mtove, Frank Mtei, Annie Willetts, Emily Foster, Florida Muro, Rahim Mwinyishehe, Renata Mandike, Raimos Olomi, Christopher JM Whitty and Hugh Reyburn

    BMC Medicine 2015 13:118

    Published on: 15 May 2015

  12. Research article

    Multiple clinical episodes of Plasmodium falciparum malaria in a low transmission intensity setting: exposure versus immunity

    Epidemiological studies indicate that some children experience many more episodes of clinical malaria than their age mates in a given location. Whether this is as a result of the micro-heterogeneity of malaria...

    Josea Rono, Anna Färnert, Linda Murungi, John Ojal, Gathoni Kamuyu, Fatuma Guleid, George Nyangweso, Juliana Wambua, Barnes Kitsao, Ally Olotu, Kevin Marsh and Faith HA Osier

    BMC Medicine 2015 13:114

    Published on: 13 May 2015

  13. Research article

    The clinical implications of thrombocytopenia in adults with severe falciparum malaria: a retrospective analysis

    Thrombocytopenia is a common finding in adults with severe falciparum malaria, but its clinical and prognostic utility is incompletely defined.

    Josh Hanson, Nguyen Hoan Phu, Mahtab Uddin Hasan, Prakaykaew Charunwatthana, Katherine Plewes, Richard J Maude, Panote Prapansilp, Hugh WF Kingston, Saroj K Mishra, Sanjib Mohanty, Ric N Price, M Abul Faiz, Arjen M Dondorp, Nicholas J White, Tran Tinh Hien and Nicholas PJ Day

    BMC Medicine 2015 13:97

    Published on: 24 April 2015

  14. Research article

    Characterization of Plasmodium vivax-associated admissions to reference hospitals in Brazil and India

    The benign character formerly attributed to Plasmodium vivax infection has been dismantled by the increasing number of reports of severe disease associated with infection with this parasite, prompting the need fo...

    André M Siqueira, Marcus VG Lacerda, Belisa M L Magalhães, Maria PG Mourão, Gisely C Melo, Márcia AA Alexandre, Maria GC Alecrim, Dhanpat Kochar, Sanjay Kochar, Abhishek Kochar, Kailash Nayak, Hernando del Portillo, Caterina Guinovart, Pedro Alonso and Quique Bassat

    BMC Medicine 2015 13:57

    Published on: 20 March 2015

  15. Research article

    Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial

    Intermittent preventive treatment in pregnancy has not been evaluated outside of Africa. Low birthweight (LBW, <2,500 g) is common in Papua New Guinea (PNG) and contributing factors include malaria and reprodu...

    Holger W Unger, Maria Ome-Kaius, Regina A Wangnapi, Alexandra J Umbers, Sarah Hanieh, Connie SN Li Wai Suen, Leanne J Robinson, Anna Rosanas-Urgell, Johanna Wapling, Elvin Lufele, Charles Kongs, Paula Samol, Desmond Sui, Dupain Singirok, Azucena Bardaji, Louis Schofield…

    BMC Medicine 2015 13:9

    Published on: 16 January 2015

  16. Research article

    Mortality attributable to Plasmodium vivaxmalaria: a clinical audit from Papua, Indonesia

    Plasmodium vivax causes almost half of all malaria cases in Asia and is recognised as a significant cause of morbidity. In recent years it has been associated with severe and fatal disease. The extent to which P...

    Nicholas M Douglas, Gysje J Pontororing, Daniel A Lampah, Tsin W Yeo, Enny Kenangalem, Jeanne Rini Poespoprodjo, Anna P Ralph, Michael J Bangs, Paulus Sugiarto, Nicholas M Anstey and Ric N Price

    BMC Medicine 2014 12:217

    Published on: 18 November 2014

  17. Research article

    Limited antigenic diversity of Plasmodium falciparumapical membrane antigen 1 supports the development of effective multi-allele vaccines

    Polymorphism in antigens is a common mechanism for immune evasion used by many important pathogens, and presents major challenges in vaccine development. In malaria, many key immune targets and vaccine candida...

    Ulrich Terheggen, Damien R Drew, Anthony N Hodder, Nadia J Cross, Cleopatra K Mugyenyi, Alyssa E Barry, Robin F Anders, Sheetij Dutta, Faith HA Osier, Salenna R Elliott, Nicolas Senn, Danielle I Stanisic, Kevin Marsh, Peter M Siba, Ivo Mueller, Jack S Richards…

    BMC Medicine 2014 12:183

    Published on: 16 October 2014

  18. Research article

    Immunological markers of Plasmodium vivaxexposure and immunity: a systematic review and meta-analysis

    Identifying Plasmodium vivax antigen-specific antibodies associated with P. vivax infection and protective immunity is key to the development of serosurveillance tools and vaccines for malaria. Antibody targets o...

    Julia C Cutts, Rosanna Powell, Paul A Agius, James G Beeson, Julie A Simpson and Freya J I Fowkes

    BMC Medicine 2014 12:150

    Published on: 9 September 2014

  19. Research article

    A combined analysis of immunogenicity, antibody kinetics and vaccine efficacy from phase 2 trials of the RTS,S malaria vaccine

    The RTS,S malaria vaccine is currently undergoing phase 3 trials. High vaccine-induced antibody titres to the circumsporozoite protein (CSP) antigen have been associated with protection from infection and epis...

    Michael T White, Philip Bejon, Ally Olotu, Jamie T Griffin, Kalifa Bojang, John Lusingu, Nahya Salim, Salim Abdulla, Nekoye Otsyula, Selidji T Agnandji, Bertrand Lell, Kwaku Poku Asante, Seth Owusu-Agyei, Emmanuel Mahama, Tsiri Agbenyega, Daniel Ansong…

    BMC Medicine 2014 12:117

    Published on: 10 July 2014

  20. Research article

    Opsonic phagocytosis of Plasmodium falciparummerozoites: mechanism in human immunity and a correlate of protection against malaria

    An understanding of the mechanisms mediating protective immunity against malaria in humans is currently lacking, but critically important to advance the development of highly efficacious vaccines. Antibodies p...

    Faith HA Osier, Gaoqian Feng, Michelle J Boyle, Christine Langer, Jingling Zhou, Jack S Richards, Fiona J McCallum, Linda Reiling, Anthony Jaworowski, Robin F Anders, Kevin Marsh and James G Beeson

    BMC Medicine 2014 12:108

    Published on: 1 July 2014

  21. Research article

    Peripheral blood monocyte-to-lymphocyte ratio at study enrollment predicts efficacy of the RTS,S malaria vaccine: analysis of pooled phase II clinical trial data

    RTS,S is the most advanced candidate malaria vaccine but it is only partially protective and the causes of inter-individual variation in efficacy are poorly understood. Here, we investigated whether peripheral...

    George M Warimwe, Helen A Fletcher, Ally Olotu, Selidji T Agnandji, Adrian VS Hill, Kevin Marsh and Philip Bejon

    BMC Medicine 2013 11:184

    Published on: 21 August 2013