OBJECTIVE: Randomized controlled trials (RCT) are a key component in clinical research and they provide the highest quality clinical results. The objective of this study was to describe the main characteristics of RCTs published in Malaria Journal, including research topics, study population and design, funding sources and collaboration between institutions. This may help researchers and funders define future research priorities in this field. METHODS: A retrospective analysis was performed on the RCTs published in Malaria Journal between January 1, 2008 and December 31, 2013. A key-word search by "Randomized controlled trial" or "Random*" was carried out in PubMed. RCT indexed to MEDLINE were selected for the analysis. RESULTS: A total of 108 published articles containing RCTs were analysed. Treatment of uncomplicated Plasmodium falciparum malaria (n=45, 41.6%), especially the efficacy and safety of antimalarial drugs, and malaria prevention (n=34, 31.5%) were the two main research topics. The majority of trials were conducted in Africa (62.2%) and Asia (27%) and received external funding (private, 42.3% and/or public, 38.6%). Paediatric population was the primary study group (n=63, 58.3%), followed by adults (n=29, 26.9%). Pregnant women (n=7) and geriatric population (n=1) remain underrepresented. Nearly 75% of trials were conducted in individual subjects and 25% in groups of subjects (cluster RCTs). A considerable collaboration between researchers and institutions is noteworthy. CONCLUSIONS: RCTs published in Malaria Journal address a wide range of research topics. Paediatric trials conducted in Africa and Asia are frequently performed, and a significant worldwide collaboration to fight against malaria has been identified.
No AccessNov 2017Malaria Elimination and EradicationAuthors/Editors: Rima Shretta, Jenny Liu, Chris Cotter, Justin Cohen, Charlotte Dolenz, Kudzai Makomva, Gretchen Newby, Didier Ménard, Allison Phillips, Allison Tatarsky, Roly Gosling, Richard FeachemRima ShrettaSearch for more papers by this author, Jenny LiuSearch for more papers by this author, Chris CotterSearch for more papers by this author, Justin CohenSearch for more papers by this author, Charlotte DolenzSearch for more papers by this author, Kudzai MakomvaSearch for more papers by this author, Gretchen NewbySearch for more papers by this author, Didier MénardSearch for more papers by this author, Allison PhillipsSearch for more papers by this author, Allison TatarskySearch for more papers by this author, Roly GoslingSearch for more papers by this author, Richard FeachemSearch for more papers by this authorhttps://doi.org/10.1596/978-1-4648-0524-0_ch12AboutView ChaptersFull TextPDF (36.8 MB) ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked In Abstract: Acknowledges that despite gains in controlling malaria, the global burden of the disease remains high with 212 million cases reported in 2015; nevertheless, elimination looms as an attainable goal for 2030 as target date. The major challenges come from infections due to P. vivax, hard-to-reach at-risk populations, and resistance of parasites to artemisinin derivatives. Effective interventions include (1) vector control for mosquitos, (2) new tools for controlling residual transmission, (3) robust entomological surveillance and integrated vector monitoring, and (4) strength of the health system to detect and respond to cases based on the level of investment in malaria programs. Benefits from elimination offer macroeconomic gains from increased productivity, but unfortunately development assistance aimed toward elimination has declined and now strengthening of programs is essential. Elimination may become progressively easier with new drug therapies, simplified treatment regimens, and more effective vaccines, but still external assistance to the last affected countries will be essential. ReferencesAbeyasinghe, R R, G N Galappaththy, C Smith Gueye, J G Kahn, and R G Feachem 2012. “Malaria Control and Elimination in Sri Lanka: Documenting Progress and Success Factors in a Conflict Setting.” PLoS One 7 (8): e43162. CrossrefGoogle ScholarAdams, J S and R Victurine 2011. “Permanent Conservation Trusts: A Study of the Long-Term Benefits of Conservation Endowments.” Wildlife Conservation Society, Bronx, NY. http://www.dcnanature.org/wp-content/uploads/fundraising/Permanent-Conservation-Endowments.pdf. Google ScholarAdjuik, M, T Smith, S Clark, J Todd, and A Garrib others. 2006. “Cause-Specific Mortality Rates in Sub-Saharan Africa and Bangladesh.” Bulletin of the World Health Organization 84 (3): 181–88. CrossrefGoogle ScholarAksan, A M and S Chakraborty 2013. “Childhood Disease and the Precautionary Demand for Children.” Journal of Population Economics 26 (3): 855–85. CrossrefGoogle ScholarAmaratunga, C, P Lim, S Suon, S Sreng, and S Mao others. 2016. “Dihydroartemisinin-Piperaquine Resistance in Plasmodium falciparum Malaria in Cambodia: A Multisite Prospective Cohort Study.” The Lancet Infectious Diseases 16 (3): 357–65. CrossrefGoogle ScholarAPLMA (Asia Pacific Leaders Malaria Alliance). 2015. “Asia-Pacific at the Forefront of a Global Movement to Eliminate Malaria.” APLMA Blog, October 7. http://aplma.org/blog/22/asia-pacific-at-the-forefront-of-a-global-movement-to-eliminate-malaria/. Google ScholarAriey, F, B Witkowski, C Amaratunga, J Beghain, and A C Langlois others. 2014. “A Molecular Marker of Artemisinin-Resistant Plasmodium falciparum Malaria.” Nature 505 (7481): 50–55. CrossrefGoogle ScholarAsante, F A and K Asenso-Okyere. 2003. Economic Burden of Malaria in Ghana. Geneva: WHO, African Regional Office. Google ScholarAshley, E A, M Dhorda, R M Fairhurst, C Amaratunga, and P Lim, others. 2014. “Spread of Artemisinin Resistance in Plasmodium falciparum Malaria.” New England Journal of Medicine 371: 411–23. CrossrefGoogle ScholarAudibert, M, J Mathonnat, and M C Henry 2003. “Malaria and Property Accumulation in Rice Production Systems in the Savannah Zone of Côte d’Ivoire.” Tropical Medicine and International Health 8 (5): 471–83. CrossrefGoogle ScholarAylward, R B, A Acharya, S England, M Agocs, and J Linkins 2003. “Global Health Goals: Lessons from the Worldwide Effort to Eradicate Poliomyelitis.” The Lancet 362 (9387): 909–14. CrossrefGoogle ScholarBadiane, O and J Ulimwengu 2013. “Malaria Incidence and Agricultural Efficiency in Uganda.” Agricultural Economics 44 (1): 15–23. CrossrefGoogle ScholarBaird, J K 2009. “Malaria Zoonoses.” Travel Medicine and Infectious Disease 7 (5): 269–77. CrossrefGoogle ScholarBaird, J K 2015. “Point-of-Care G6PD Diagnostics for Plasmodium vivax Malaria Is a Clinical and Public Health Urgency.” BMC Medicine 13 (December): 296. CrossrefGoogle ScholarBaltzell, K A, D Shakely, M Hsiang, J Kemere, and A S Ali, others. 2013. “Short Report: Prevalence of PCR Detectable Malaria Infection among Febrile Patients with a Negative Plasmodium falciparum Specific Rapid Diagnostic Test in Zanzibar.” American Journal of Tropical Medicine and Hygiene 88 (2): 289–91. CrossrefGoogle ScholarBarclay, V, R Smith, and J Findeis 2012. “Surveillance Considerations for Malaria Elimination.” Malaria Journal 11: 304. CrossrefGoogle ScholarBarlow, R and L M Grobar 1986. “Costs and Benefits of Controlling Parasitic Diseases.” Technical Note PHN 8517, Population, Health, and Nutrition Department, World Bank, Washington, DC. Google ScholarBarreca, A I 2010. “The Long-Term Economic Impact of In Utero and Postnatal Exposure to Malaria.” Journal of Human Resources 45 (4): 865–92. CrossrefGoogle ScholarBarrett, S 2004. Eradication versus Control: The Economics of Global Infectious Disease Policies. Geneva: WHO. Google ScholarBarrett, S 2007. “The Smallpox Eradication Game.” Public Choice 130 (1): 179–207. CrossrefGoogle ScholarBarrett, S 2013. “Economic Considerations for the Eradication Endgame.” Philosophical Transactions of the Royal Society B: Biological Sciences 368 (1623): 20120149. CrossrefGoogle ScholarBart, K J, J Foulds, and P Patriarca 1996. “Global Eradication of Poliomyelitis: Benefit-Cost Analysis.” Bulletin of the World Health Organization 74 (1): 35–45. Google ScholarBawah, A A and F N Binka 2007. “How Many Years of Life Could Be Saved if Malaria Were Eliminated from a Hyperendemic Area of Northern Ghana?” American Journal of Tropical Medicine & Hygiene 77 (Suppl 6):145–52. CrossrefGoogle ScholarBeaver, C 2011. “Application of a Remoteness Index: Funding Malaria Programs.” International Journal of Geoinformatics 7 (1). Google ScholarBhatt, S, D J Weiss, E Cameron, D Bisanzio, and B Mappin, others. 2015. “The Effect of Malaria Control on Plasmodium falciparum in Africa between 2000 and 2015.” Nature 526 (7572): 207–11. CrossrefGoogle ScholarBhumiratana, A, P Sorosjinda-Nunthawarasilp, W Kaewwaen, P Maneekan, and S Pimnon 2013. “Malaria-Associated Rubber Plantations in Thailand.” Travel Medicine and Infectious Disease 11 (1): 37–50. CrossrefGoogle ScholarBlanford, S, N E Jenkins, A F Read, and M B Thomas 2012. “Evaluating the Lethal and Pre-Lethal Effects of a Range of Fungi against Adult Anopheles stephensi Mosquitoes.” Malaria Journal 11: 365. CrossrefGoogle ScholarBleakley, H 2003. “Disease and Development: Evidence from the American South.” Journal of the European Economic Association 1 (2–3):376–86. CrossrefGoogle ScholarBleakley, H 2010. “Malaria Eradication in the Americas: A Retrospective Analysis of Childhood Exposure.” American Economic Journal: Applied Economics 2 (2): 1–45. CrossrefGoogle ScholarBoyd, M F 1939. “Malaria: Retrospect and Prospect.” American Journal of Tropical Medicine and Hygiene 19: 1–6. CrossrefGoogle ScholarBrady, O 2016. “Vectorial Capacity and Vector Control: Reconsidering Sensitivity to Parameters for Malaria Elimination.” Transactions of the Royal Society of Tropical Medicine and Hygiene 110 (2): 107–17. CrossrefGoogle ScholarBruce-Chwatt, L J 1959. “Malaria Research and Eradication in the USSR: A Review of Soviet Achievements in the Field of Malariology.” Bulletin of the World Health Organization 21: 737–72. Google ScholarCarrara, V, K Lwin, A Phyo, E Ashley, and J Wiladphaingern, others. 2013. “Malaria Burden and Artemisinin Resistance in the Mobile and Migrant Population on the Thai-Myanmar Border, 1999–2011: An Observational Study.” PLoS One 10 (3): e1001398. Google ScholarCEPA (Cambridge Economic and Policy Associates). 2013. “Financing for Malaria Elimination.” CEPA and Global Health Group, University of California, San Francisco, CA. Google ScholarChen, I, S E Clarke, R Gosling, B Hamainza, and G Killeen, others. 2016. “‘Asymptomatic’ Malaria: A Chronic and Debilitating Infection That Should Be Treated.” PLoS Medicine 13 (1): e1001942. CrossrefGoogle ScholarChiyaka, C, A J Tatem, J M Cohen, P W Gething, and G Johnston, others. 2013. “The Stability of Malaria Elimination.” Science 339 (6122): 909–10. CrossrefGoogle ScholarChuma, J M, M Thiede, and C S Molyneux 2006. “Rethinking the Economic Costs of Malaria at the Household Level: Evidence from Applying a New Analytical Framework in Rural Kenya.” Malaria Journal 5: 76. CrossrefGoogle ScholarChuquiyauri, R, M Paredes, P Penataro, S Torres, and S Marin, others. 2012. “Socio-Demographics and the Development of Malaria Elimination Strategies in the Low-Transmission Setting.” Acta Tropica 121 (3): 292–302. CrossrefGoogle ScholarCohen, J M, S Dlamini, J M Novotny, D Kandula, and S Kunene, others. 2013. “Rapid Case-Based Mapping of Seasonal Malaria Transmission Risk for Strategic Elimination Planning in Swaziland.” Malaria Journal 12: 61. CrossrefGoogle ScholarCohen, J M, B Moonen, R W Snow, and D L Smith 2010. “How Absolute Is Zero? An Evaluation of Historical and Current Definitions of Malaria Elimination.” Malaria Journal 9: 213. CrossrefGoogle ScholarCohen, J M, D L Smith, C Cotter, A Ward, and G Yamey, others. 2012. “Malaria Resurgence: A Systematic Review and Assessment of Its Causes.” Malaria Journal 11: 122. CrossrefGoogle ScholarCorran, P, P Coleman, E Riley, and C Drakeley 2007. “Serology: A Robust Indicator of Malaria Transmission Intensity?” Trends in Parasitology 23 (12): 575–82. CrossrefGoogle ScholarZulueta, de J and D A Muir 1972. “Malaria Eradication in the Near East.” Transactions of the Royal Society of Tropical Medicine and Hygiene 66 (5): 679–96. CrossrefGoogle ScholarDhingra, N, P Jha, V P Sharma, A A Cohen, and R M Jotkar, others. 2010. “Adult and Child Malaria Mortality in India: A Nationally Representative Mortality Survey.” The Lancet 376 (9754): 1768–74. CrossrefGoogle ScholarDondorp, A M, F Nosten, P Yi, D Das, and A P Phyo, others. 2009. “Artemisinin Resistance in Plasmodium falciparum Malaria.” New England Journal of Medicine 361: 455–67. CrossrefGoogle ScholarDua, V, S Sharma, A Srivastava, and V Sharma 1997. “Bioenvironmental Control of Industrial Malaria at Bharat Heavy Electricals Ltd., Hardwar, India: Results of a Nine-Year Study (1987–95).” Journal of the American Mosquito Control Association 13 (3): 278–85. Google ScholarDurnez, L and M Coosemans 2013. “Residual Transmission of Malaria: An Old Issue for New Approaches.” In Anopheles Mosquitoes: New Insights into Malaria Vectors, edited by Manguin, S 671–704. Rijeka: InTech. CrossrefGoogle ScholarDuru, V, N Khim, R Leang, S Kim, and A Domergue, others. 2015. “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.” BMC Medicine 13: 305. CrossrefGoogle ScholarEckhoff, P, J Gerardin, and E Wenger 2015. “Mass Campaigns with Antimalarial Drugs: A Modelling Comparison of Artemether-Lumefantrine and DHA-Piperaquine with and without Primaquine as Tools for Malaria Control and Elimination.” BMC Infectious Diseases 15: 144. CrossrefGoogle ScholarEl Khyari, T 2001. Malaria Elimination Strategy in Morocco: Plan and Elements of Evaluation. Unpublished report, Morocco Ministry of Health. Google ScholarEziefula, A C, R Gosling, J Hwang, M S Hsiang, and T Bousema, others. 2012. “Rationale for Short Course Primaquine in Africa to Interrupt Malaria Transmission.” Malaria Journal 11 (1): 360. CrossrefGoogle ScholarFeachem, R G, A A Phillips, J Hwang, C Cotter, and B Wielgosz, others. 2010. “Shrinking the Malaria Map: Progress and Prospects.” The Lancet 376 (9752): 1566–78. CrossrefGoogle ScholarFeachem, R G, A A Phillips, and G A T Targett eds. 2009. Shrinking the Malaria Map: A Prospectus on Malaria Elimination. San Francisco, CA: Global Health Group, University of California San Francisco. Google ScholarFiller, S J, J R MacArthur, M Parise, R Wirtz, and M J Eliades, others. 2006. Locally Acquired Mosquito-Transmitted Malaria: A Guide for Investigations in the United States. Atlanta, GA: Centers for Disease Control and Prevention. Google ScholarFloore, T G 2006. “Larval Control Practices: Past and Present.” Journal of the American Mosquito Control Association 22 (3): 527–33. CrossrefGoogle ScholarGallup, J L and J D Sachs 2001. “The Economic Burden of Malaria.” American Journal of Tropical Medicine and Hygiene 64 (Suppl 1–2):85–96. CrossrefGoogle ScholarGates, B and R Chambers 2015. From Aspiration to Action: What Will It Take to End Malaria? Seattle, WA: Bill and Melinda Gates Foundation. Google ScholarGHG (Global Health Group). 2013. “Malaria-Eliminating Country Briefings.” GHG, University of California, San Francisco, CA. Google ScholarGHG (Global Health Group). 2014. “The Impact of the Global Fund’s New Funding Model on the 34 Malaria-Eliminating Countries.” GHG, University of California, San Francisco, CA. Google ScholarGHG (Global Health Group). 2016. “Analysing Technical Efficiency in Malaria Elimination Programs: A Self-Help Toolkit.” Unpublished. Google ScholarGirardin, O, D Dao, B G Koudou, C Esse, and G Cisse others. 2004. “Opportunities and Limiting Factors of Intensive Vegetable Farming in Malaria Endemic Côte d’Ivoire.” Acta Tropica 89 (2): 109–23. CrossrefGoogle ScholarGosling, J, P Case, J Tulloch, D Chandramohan, and C Smith Gueye others. 2014. “Program Management Issues in Implementation of Elimination Strategies.” GHG, University of California, San Francisco, CA. Google ScholarGosling, J, P Case, J Tulloch, D Chandramohan, and J Wegbreit, others. 2015. “Effective Program Management: A Cornerstone of Malaria Elimination.” American Journal of Tropical Medicine and Hygiene 93 (1): 135–38. CrossrefGoogle ScholarGosling, R D, L Okell, J Mosha, and D Chandramohan 2011. “The Role of Antimalarial Treatment in the Elimination of Malaria.” Clinical Microbiology and Infection 17 (11): 1617–23. CrossrefGoogle ScholarGovernment of India, Ministry of Health and Family Welfare. 2016. National Framework for Malaria Elimination in India (2016–2030). New Delhi: Directorate of National Vector Borne Disease Control Programme. http://www.searo.who.int/india/publications/national. Google ScholarGreenwood, B M 2008. “Control to Elimination: Implications for Malaria Research.” Trends in Parasitology 24 (10): 449–54. CrossrefGoogle ScholarGuiguemdé, W A and R K Guy 2012. “An All-Purpose Antimalarial Drug Target.” Cell Host and Microbe 11 (6): 555–57. CrossrefGoogle ScholarGupta, I and S Chowdhury 2014. “Economic Burden of Malaria in India: The Need for Effective Spending.” South-East Asia Journal of Public Health 3 (1): 95–102. CrossrefGoogle ScholarHammond, A, R Galizi, K Kyrou, A Simoni, and C Siniscalchi, others. 2016. “A CRISPR-Cas9 Gene Drive System Targeting Female Reproduction in the Malaria Mosquito Vector Anopheles gambiae.” Nature Biotechnology 34 (4): 78–85. CrossrefGoogle ScholarHarris, I, W W Sharrock, L M Bain, K A Gray, and A Bobogare, others. 2010. “A Large Proportion of Asymptomatic Plasmodium Infections with Low and Sub-Microscopic Parasite Densities in the Low-Transmission Setting of Temotu Province, Solomon Islands: Challenges for Malaria Diagnostics in an Elimination Setting.” Malaria Journal 9: 254. CrossrefGoogle ScholarHelinski, M, M Hassan, W El-Motasim, C A Malcolm, B G Knols, and B El-Sayed. 2008. “Towards a Sterile Insect Technique Field Release of Anopheles arabiensis Mosquitoes in Sudan: Irradiation, Transportation, and Field Case Experimentation.” Malaria Journal 7: 65. CrossrefGoogle ScholarHemingway, J, R Shretta, T N C Wells, D Bell, and A A Djimdé others. 2016. “Tools and Strategies for Malaria Control and Elimination: What Do We Need to Achieve a Grand Convergence in Malaria?” PLoS Biology 12 (3): e1002380. CrossrefGoogle ScholarHenderson, D A 1987. “Principles and Lessons from the Smallpox Eradication Programme.” Bulletin of the World Health Organization 65 (4): 535–46. Google ScholarHien, T T, N T Thuy-Nhien, N H Phu, M F Boni, and N V Thanh, others. 2012. “In Vivo Susceptibility of Plasmodium falciparum to Artesunate in Binh Phuoc Province, Vietnam.” Malaria Journal 11: 355. CrossrefGoogle ScholarHiwat, H, L S Hardjopawiro, W Takken, and L Villegas 2012. “Novel Strategies Lead to Pre-Elimination of Malaria in Previously High-Risk Areas in Suriname, South America.” Malaria Journal 11: 10. CrossrefGoogle ScholarHong, S C 2011. “Malaria and Economic Productivity: A Longitudinal Analysis of the American Case.” Journal of Economic History 71 (3): 654–71. CrossrefGoogle ScholarHong, S C 2013. “Malaria: An Early Indicator of Later Disease and Work Level.” Journal of Health Economics 32 (3): 612–32. CrossrefGoogle ScholarHorton, R 2015. “Vaccines: A Step Change in Malaria Prevention?” The Lancet 385 (9978): 1591. CrossrefGoogle ScholarHotez, P J 2009. “Mass Drug Administration and Integrated Control for the World’s High-Prevalence Neglected Tropical Diseases.” Clinical Pharmacology and Therapeutics 85 (6): 659–64. CrossrefGoogle ScholarHoward, A F, R N’Guessan, C J Koenraadt, A Asidi, and M Farenhorst, others. 2011. “First Report of the Infection of Insecticide-Resistant Malaria Vector Mosquitoes with an Entomopathogenic Fungus under Field Conditions.” Malaria Journal 10: 24. CrossrefGoogle ScholarHowes, R E, F B Piel, A P Patil, O A Nyangiri, and P W Gething, others. 2012. “G6PD Deficiency Prevalence and Estimates of Affected Populations in Malaria Endemic Countries: A Geostatistical Model-Based Map.” PLoS Medicine (11): CrossrefGoogle S, S S Kim, N and N Khim, others. 2012. and Treatment A Strategy to Malaria Parasite and P. PLoS One 7 (1): Google M S, B and P J 2014. of for Malaria Journal of Infectious Diseases (8): CrossrefGoogle M S, J Hwang, S Kunene, C and D Kandula, others. 2012. “Surveillance for Malaria Elimination in A National Study PCR and PLoS One 7 (1): CrossrefGoogle M, S B L and N P others. 2014. Molecular for Malaria Journal of Clinical Microbiology CrossrefGoogle S, C and L of Malaria Control in from and Bulletin of the World Health Organization (8): Google G N M L F Nosten, and J K others. 2012. of Plasmodium A Review of the Malaria Journal 11: CrossrefGoogle R, T and A 2008. Susceptibility to by the Malaria Vector Anopheles in Uganda.” Malaria Journal 7: CrossrefGoogle J G, S C M S Hsiang, and D T others. 2009. “Financing Elimination.” In Shrinking the Malaria Map: A Prospectus on Malaria edited by R G, A A Phillips, and A Targett San Francisco, CA: GHG, University of Google A, G M S T and A “Malaria Eradication on The Lancet CrossrefGoogle T M, H and A A 2008. Historical and New Journal of the American of (5): CrossrefGoogle G C, M A and A 2012. “Malaria Elimination: with Trends in Parasitology CrossrefGoogle M J of Economic due to Malaria in Journal of Health 16 (3): Google M M and J 2003. “Costs and Benefits of A Global CrossrefGoogle G F 2014. Controlling and Transmission.” Malaria Journal 13: CrossrefGoogle E J M I W and F 2006. of for against Malaria: A Malaria Journal 5: CrossrefGoogle A V “Malaria in the Asia Journal of (3): Google A “The Impact of Public Health on Economic Development: Report of a Study of Malaria in Thailand.” International Journal of Health 1 (3): CrossrefGoogle R, A D M D Ménard, and R others. 2013. of Dihydroartemisinin-Piperaquine for Treatment of Plasmodium falciparum and Plasmodium vivax in to and (2): CrossrefGoogle R, W R D M L and J others. 2015. of Plasmodium falciparum Malaria Resistance to Artemisinin and Piperaquine in Cambodia: Dihydroartemisinin-Piperaquine Clinical and (8): Google A, A J Tatem, J M Cohen, S I and H others. 2011. Malaria and Malaria Transmission in Zanzibar.” 1 Google K A, L A S P and L 2013. “The Asymptomatic and Malaria Transmission.” Review of 11 (6): CrossrefGoogle J, C J M and K 2007. for Eradication and Elimination of of Hygiene and Tropical Google J G Newby, A C Gueye Smith, and C J others. 2013. of Malaria Program Elimination: Case Study Evidence from in the PLoS One 8 CrossrefGoogle G and D “The Economic Benefits of Malaria Eradication in de Google A, M V R S and S K others. 2014. for the Treatment and of Plasmodium vivax Malaria A Study.” The Lancet CrossrefGoogle C, J E P M and D others. 2014. of of Dihydroartemisinin-Piperaquine for Malaria in in Northern Cambodia: An PLoS One (3): CrossrefGoogle A P T and S others. 2014. “Artemisinin Modelling the Human and Economic Malaria Journal 13: CrossrefGoogle A M 2010. “The Impact of Malaria Eradication on and of Google S, S W A A and T W 2010. in Vector Biology and Management of PLoS Neglected Tropical Diseases (2): CrossrefGoogle F, B B J and I 2007. “The Impact of Malaria Control on of and Malaria Prevalence in versus Journal of Travel Medicine (2): CrossrefGoogle M, N B and N others. 2007. of for Malaria Control in in the of Tropical Medicine and International Health 13 (3): CrossrefGoogle S, P and J 2008. of Malaria in the Google G C E A C and A others. 2014. Analysis of the Development and Implementation of a System for Malaria Elimination in Solomon Malaria Journal 13: CrossrefGoogle N S, J S E P and I R others. 2013. a New to for and Malaria A Report on and Field Evaluation of the Mosquito Parasites and CrossrefGoogle R, W S R and S others. 2009. “The Is the Artemisinin-Resistant Malaria in Malaria Journal CrossrefGoogle R J, D C P and P others. 2012. Strategies for Plasmodium falciparum Malaria Elimination in Cambodia: Drug Administration and Artemisinin PLoS One 7 (5): CrossrefGoogle F D, H and “The Costs of Malaria.” National of Economic CrossrefGoogle D, N Khim, J Beghain, A A and M and others. 2016. “A Worldwide of Plasmodium falciparum New England Journal of Medicine CrossrefGoogle A M A and G others. 2009. Malaria Control to The Tropical Medicine and International Health CrossrefGoogle A, and K 2008. “Malaria The and Malaria Journal 7 (Suppl CrossrefGoogle S, J Liu, R Gosling, and R G Feachem 2012. “The Economic Benefits of Malaria Elimination: Do in Malaria Journal 11: CrossrefGoogle B, S J and D T 2009. the In Shrinking the Malaria Map: A Prospectus on Malaria edited by R G, A A Phillips, and G San Francisco, CA: GHG, University of Google B, J M Cohen, R W Snow, L and C others. 2010. Strategies to Achieve and Malaria Elimination.” The Lancet 376 (9752): CrossrefGoogle B, J M Cohen, A J Tatem, J Cohen, and S I others. 2010. “A Framework for the of Malaria Elimination.” Malaria Journal 9: CrossrefGoogle J F, H J B B and C J others. 2013. of Plasmodium falciparum Implications for of with Malaria Journal 12: CrossrefGoogle G C, J C S F M B and M M others. 2010. Field of against Malaria in the Anopheles in Malaria Journal 9: CrossrefGoogle D N and E M “The Malaria Science CrossrefGoogle J A “Malaria Control and Strategies.” and Malaria Google J A, M and P L 2011. Lessons for the from the Global Malaria Eradication PLoS Medicine 8 (1): CrossrefGoogle G, A E C Cotter, and R Shretta, others. 2016. “The to A Progress Report on the Malaria-Eliminating Countries.” The Lancet CrossrefGoogle G, J Hwang, K I and B others. 2015. of Drug Administration for Malaria and Its American Journal of Tropical Medicine and Hygiene 93 (1): CrossrefGoogle L and C de 2012. in Malaria and Mortality in Province, South Africa A Retrospective Study.” Malaria Journal 11: CrossrefGoogle C, M E B and N others. 2014.
To determine the prevalence of malaria parasite carriage and anaemia among senior high school students and to identify the demographic, behavioural and residential factors associated with these outcomes. Cross-sectional study. Participants were enrolled from Tempane Senior High School students in the Tempane District of the Upper East Region of Ghana. 290 senior high school students aged 15-22 years. Demographic characteristics, residential status and insecticide-treated bed net (ITN) use were collected using a structured questionnaire. Venous blood samples were obtained for malaria parasite detection by microscopy and haemoglobin measurement. Association analysis was performed using logistic regression models. The prevalence of malaria parasite carriage was 23.1%, while 49.0% of participants were anaemic. Day students had a significantly higher prevalence of malaria (59.2%) than boarding students (15.8%) (p<0.001). Malaria parasite infection was also more common among students who did not use ITNs (39.7%) compared with users (5.0%) (p<0.001). In multivariate analysis, not using ITN (adjusted OR (aOR)=15.97; 95% CI 6.33 to 40.32; p<0.001) and being a day student (aOR=5.65; 95% CI 2.58 to 12.36; p<0.001) were significant predictors of malaria parasite infection. Students infected with malaria parasites had significantly lower mean haemoglobin (11.50±1.43 g/dL) than uninfected students (12.56±1.35 g/dL) (p<0.001). Malaria parasite infection (aOR=9.36; 95% CI 3.91 to 22.42; p<0.001) and male students (aOR=2.26; 95% CI 1.09 to 4.65; p=0.028) were associated with higher odds of anaemia. Whereas age groups 18-20 years (aOR=0.41; 95% CI 0.17 to 0.97; p=0.043) and those above 20 years (aOR=0.07; 95% CI 0.02 to 0.27; p<0.001) were associated with lower odds of anaemia. Malaria and anaemia remain prevalent among senior high school students in the Upper East Region of Ghana, with asymptomatic malaria strongly linked to anaemia. Not using ITN and being a day student significantly increased the odds of malaria parasite infection. These findings underscore the need to extend malaria prevention interventions to adolescents through school-based programmes, including routine screening, treatment and promotion of consistent ITN use, especially among day students.
Malaria constitutes a major public health burden in Sudan, accounting for most outpatient visits and hospital admissions across approximately 80% of the states. The armed conflict beginning in April 2023 severely disrupted an already fragile health system, affecting the surveillance system infrastructure. No prior studies have assessed the impact of conflict on routine malaria surveillance data reported through District Health Information Software 2 (DHIS2). This study evaluated the effects of conflict on completeness and reporting of malaria impact indicators data across Sudanese states. A mixed-methods design combined quantitative analysis of quarterly DHIS2 data (January 2020-March 2025) from 17 states with qualitative exploration of surveillance system functionality. Quantitative analysis included descriptive analyses and interrupted time series analysis (ITSA) of three malaria impact indicators: quarterly reported malaria cases (presumed and confirmed) per 100,000 state population, test positivity rate (RDT + microscopy), and quarterly inpatient malaria deaths per 100,000 state population. Data completeness was quantified as the proportion of missing quarterly reports per state. Descriptive analysis graphs illustrate pre- and post-conflict trends and missing data patterns. ITSA was conducted for 11 states with complete post-conflict time series; six states with incomplete data were excluded. Three key informant interviews with national- and state-level malaria programme managers, selected from severe and less severe conflict-affected states, provided contextual insights. Qualitative data were analyzed using a deductive framework approach. Missing DHIS2 reporting increased substantially after April 2023. Inter-state variation was observed: western and southern states (except North Kordofan) experienced persistent data gaps, whereas northern and eastern states maintained relatively continuous reporting despite declining trends. Qualitative findings indicated stronger surveillance functionality in less-affected states by conflict. ITSA showed a statistically significant decline in quarterly reported malaria case rates per 100,000 state population at conflict quarter (p = 0.02), with no significant post-conflict trend change. Key informants identified health facility destruction, workforce shortages, unpaid salaries, and communication breakdowns as major barriers. The conflict coincided with widening disparities in malaria surveillance across states, reflecting underlying inequalities in health system capacity. Strengthening states' surveillance systems is critical in conflict-affected settings. Future research should examine locality-level impacts to better capture subnational variation.
Chemoprophylaxis (in travellers) and seasonal chemoprophylaxis and preventive treatment (in endemic areas) are important but not exclusive elements of malaria prevention, which hinges on vector repelling in travellers and more comprehensive vector control measures in endemic areas. In malaria-endemic countries, a comprehensive strategy combining drug-based prevention, vaccines and vector control is essential to reduce disease burden. Chemoprophylaxis in endemic settings primarily involves intermittent preventive treatment in vulnerable groups and mass drug administration in communities, rather than continuous daily chemoprophylaxis (as recommended for non-immune travellers). Vaccination has become a groundbreaking addition to the malaria control portfolio in endemic countries. The World Health Organization-endorsed RTS,S/AS01 (Mosquirix®) and R21/Matrix-M vaccines rolled out in many highly malaria-endemic sub-Saharan African countries, in addition to other malaria control tools, provide overall moderate protection in young children but significantly reduce severe disease and death, and are considered safe. For travellers, malaria vaccines are not available to date. Effort is being put into the development of monoclonal antibodies against malaria as a preventive treatment strategy both to provide protection for the immunocompromised or unvaccinated high-risk individuals before exposure and to disrupt seasonal malaria transmission with a single application. The evolution of malaria preventive tools is a dynamic process, with numerous novel developments on the horizon. For travel medicine indications, further harmonisation of recommendations on the one hand, but also more sophisticated personalisation of recommendations, is envisaged.
Saudi Arabia has made significant progress toward malaria elimination; however, imported cases continue to occur, particularly in the southwestern regions. This study aimed to describe the clinical characteristics and outcomes of patients with malaria in the Aseer Region, Saudi Arabia. A retrospective observational study was conducted at Khamis Mushait General Hospital, Aseer Region, Saudi Arabia, including all patients with malaria from January 2022 to December 2025. Demographic, clinical, laboratory, and outcome data were extracted from the electronic medical records. Severe malaria was defined according to the World Health Organization criteria. Multivariate logistic regression using Firth's penalized maximum likelihood estimation was performed to identify independent predictors of severe malaria (≥1 WHO criterion). Statistical analysis was performed using R software (version 4.2.1). A total of 311 patients were included, predominantly male (90.0%), with a mean age of 28.8 ± 11.3 years. Ethiopian nationals comprised nearly half the cases (48.2%), followed by Saudi (16.4%) and Yemeni (15.1%) nationals. Plasmodium vivax was the most common species (51.1%), followed by Plasmodium. falciparum (40.2%). Fever was the most frequent symptom (89.4%), followed by fatigue (50.8%), chills (46.9%), and vomiting (39.5%). Low parasitemia (<1%) was the most frequent finding (33.8%), followed by moderate (27.3%) and mild (18.3%) levels, while high (4.2%) and very high parasitemia (1.9%) were uncommon. Severe malaria (≥1 criterion) was diagnosed at 43.7%, with severe anemia (26.0%) and jaundice (23.2%) being the most frequent WHO severity criteria. Notably, 84% of the cases occurred during 2024-2025, indicating a recent outbreak, with a sharp peak of 43 cases in October 2024. Multivariate logistic regression identified two independent predictors of having at least one WHO severity criterion: higher parasitemia level (adjusted OR = 1.70 per 1% increase, 95% CI: 1.40-2.11, p < 0.001) and non-Saudi nationality (adjusted OR = 2.40, 95% CI: 1.10-5.62, p = 0.027). Malaria in the Aseer Region predominantly affects young adult male expatriates, suggesting its imported nature. The predominance of P. vivax represents a shift from historical patterns. Parasitemia level and being of non-Saudi nationality independently predict severe malaria and may therefore support risk stratification and clinical decision-making. The dramatic case surge in 2024-2025 highlights regional vulnerability to outbreaks despite control progress. These findings support enhanced screening for at-risk populations, maintenance of clinical capacity for severe malaria management, and robust surveillance systems for early outbreak detection.
Quantifying therapeutic responses in clinical malaria is easier than for most other infections as the intraerythrocytic parasites can be counted by microscopy or estimated using quantitative PCR. In treating the blood-stage of malaria, between 107 and 1013 parasites undergo a first-order decline in densities at a rate determined by the concentrations and potency of the antimalarial drug. A simple conceptual framework based on total intravascular parasite biomass and standard sigmoid concentration-effect relationships for parasite killing explains most, but not all, aspects of antimalarial therapeutic responses, and it has proved very useful in designing chemoprevention and treatment regimens and in understanding the selection and spread of resistance. Drugs acting on younger circulating ring-stage asexual parasites (artemisinins, cipargamin, ganaplacide) provide rapid parasite clearance, which translates into faster clinical recoveries and a life-saving benefit in severe malaria. Artemisinin-sensitive Plasmodium falciparum densities decline with a half-life (PC1/2) of usually less than 5 h. Many antimalarial drugs are eliminated slowly and provide protracted exposures, which allows full treatment to be administered in 3 days, and also provides chemosuppression of newly acquired infections for 1 month. Greater availability of drug measurement in malaria-endemic areas would facilitate the field assessment of antimalarial drugs. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.
Malaria is one of the most prevalent infectious diseases worldwide, posing a significant threat in the malaria-endemic areas. The rapid emergence of Plasmodium strains resistant to the existing antimalarial drugs underscores the necessity for discovering the next generation of antimalarial drugs with reduced resistance and enhanced potency. Quinoline-based compounds have been long recognized for their remarkable antimalarial efficacy due to their ability to interfere with heme detoxification within the parasites and have been extensively modified to generate molecules with improved pharmacological potential and overcome the resistance. Among the various strategies employed, the incorporation of piperazine moiety has gained considerable attention, as it can improve pharmacokinetic properties, molecular flexibility, and target interactions. Consequently, quinoline-piperazine hybrids have emerged as promising candidates with enhanced antimalarial potential. This review underscores recent advances in the development of quinoline-piperazine hybrids as antimalarial agents, emphasizing their activity against chloroquine-sensitive and resistant Plasmodium falciparum strains. In addition, structure-activity relationship (SAR) trends influencing potency, selectivity, and resistance profiles are discussed. These insights will facilitate the rational design and development of novel chemical entities as next-generation antimalarials.
Many regions in Africa continue to experience a high malaria burden, highlighting the need for improved intervention tools adapted to local eco-epidemiological contexts. The aims of this study were to develop and evaluate adaptive intervention strategies for malaria vector control tailored to these local conditions. This two-stage, cluster, sequential, multiple-assignment, randomised, open-label trial comprised 84 clusters in Muhoroni and Nyakach, subcounties of Kisumu County, western Kenya. Each cluster included 500-600 residents in an area of approximately 2 km2 and all residents in the clusters were invited to participate in the study. In stage 1, clusters were randomly assigned, in a 1:1:1 ratio, to standard pyrethroid-based long-lasting insecticidal nets (LLINs; henceforth standard LLINs) alone, piperonyl butoxide-treated LLINs (henceforth PBO nets), or standard LLINs plus annual indoor residual spraying (IRS), stratified by subcounty. Due to the nature of the interventions, masking to intervention was not feasible. Clusters with an adjusted incidence rate ratio (aIRR) of 0·8 or more were classified as non-responders. Non-responding clusters were re-randomised in stage 2. The non-responding clusters from the stage 1 PBO nets group were re-randomised, in a 1:1 ratio, to receive either supplemental microbial larviciding or annual IRS. The non-responding clusters from the stage 1 standard LLINs plus annual IRS group were re-randomised, in a 1:1 ratio, to either IRS twice per year (henceforth biannual IRS), or enhanced IRS annually, which included spraying both indoor residential structures and peridomestic resting structures not covered by routine IRS. The coprimary outcomes were clinical malaria incidence at 1-6 months, 7-12 months, and 13-18 months post-intervention, assessed through active surveillance of cohort populations once every 2 weeks and analysed in all participants with available data. Although the study procedures posed minimal risk to participants, adverse event data were regularly reviewed. The trial was registered with ClinicalTrials.gov (NCT04182126) and is complete. Between March 8, 2021, and Aug 31, 2024, the study enrolled 47 614 participants (51·8% male, 48·2% female) from 14 246 households in 84 clusters. In stage 1, PBO nets significantly reduced malaria incidence at 1-6 months post-intervention (aIRR 0·75, 95% CI 0·69-0·81; p<0·0001) and at 7-12 months post-intervention compared with standard LLINs (aIRR 0·87, 95% CI 0·80-0·95; p=0·0012), and standard LLINs plus annual IRS was more effective than standard LLINs alone at 1-6 months (aIRR 0·74, 95% CI 0·68-0·81; p<0·0001). In stage 2, among stage 1 non-responding clusters, adding annual IRS to PBO nets was more effective than supplementing with larviciding at 13-18 months (aIRR 0·89, 95% CI 0·81-0·97; p=0·0081). When added to standard LLINs, enhanced IRS was more effective than biannual IRS 13-18 months post-intervention (aIRR 0·67, 95% CI 0·56-0·80; p<0·0001). Overall, the four adaptive intervention strategies significantly reduced clinical malaria incidence compared with standard LLINs (all p<0·01). Adaptive strategies starting with PBO nets had greater and more sustained incidence reductions than strategies beginning with standard LLINs plus annual IRS. No adverse events or serious adverse events were recorded. This trial supports replacing conventional pyrethroid-only LLINs with PBO nets as the first-line malaria control strategy. In moderate-to-high-risk settings, additional annual IRS or microbial larviciding could be implemented to further reduce malaria burden. US National Institutes of Health. For the Swahili translation of the abstract see Supplementary Materials section.
Malaria remains a critical public health challenge in southeastern Bangladesh, particularly in Cox's Bazar, where the mass displacement of over one million Rohingya refugees since 2017 has heightened transmission risks. The interplay of ecological fragility, overcrowded living conditions, and climatic variability underscores the need for a deeper understanding of malaria epidemiology in this high-risk setting. A 4-year repeated cross-sectional study was conducted (2021-2024) in Camp No. 26, Teknaf, Cox's Bazar. A total of 582 participants were enrolled, comprising 486 individuals from the malaria-endemic refugee camp and 96 healthy controls from a nonendemic region. All were screened for Plasmodium falciparum and Plasmodium vivax using rapid diagnostic tests (RDTs), with microscopy performed to confirm all RDT-positive cases and a subset of RDT-negative samples. Meteorological data (temperature, rainfall, and humidity) were obtained from regional weather stations. Serological profiling assessed total anti-Plasmodium antibodies, while hematological parameters including hemoglobin concentration, RBC and platelet counts, and ESR were measured. Correlation and regression analyses were employed to identify climatic predictors of malaria incidence and their associations with immunohematological changes. Out of 582 individuals, 345 malaria cases were confirmed. Peak transmission occurred during the monsoon season (June-September), particularly in August. P. falciparum infections showed earlier and sharper peaks compared to P. vivax. Relative humidity demonstrated the strongest correlation with incidence (r = 0.724-0.77), followed by rainfall and temperature. Antibody titers were significantly higher in P. falciparum-positive individuals. Infected participants exhibited anemia, thrombocytopenia, and elevated ESR, with more pronounced alterations in P. falciparum cases. This study highlights the seasonal and species-specific nature of malaria transmission in Rohingya refugee camps, driven predominantly by climatic variables, particularly humidity. The observed serological and hematological alterations underscore their potential as biomarkers for surveillance. These findings advocate for climate-sensitive, species-specific malaria control strategies tailored to displaced populations.
Plasmodium vivax malaria is a threat to armed forces operating in the Korean Peninsula. Surges in malaria cases in the Republic of Korea entail increased risk. We report 6 cases from a cluster of P. vivax malaria cases in a non-endemic setting in active duty personnel who had redeployed from the Korean Peninsula. Demographics, disease course, and laboratory data were collected on 6 patients diagnosed with Plasmodium vivax malaria at Fort Bliss in 2022. All patients were males, with a mean age of 23 years (range 20-27 years), exposed in the Dagmar North training area in the Gyeonggi province in 2021, with an average time from symptom onset to diagnosis of 57 days (8-121 days). All had uncomplicated malaria. Laboratory findings included hemoglobin of 12.1g/dL (range 8.1-14.2 g/dL), platelets of 123 × 103/µL (range 40-171 × 103/µL), and parasitemia <1% (0.1%-0.9%) with diagnosis on peripheral smear and/or rapid antigen testing. No cases received chemoprophylaxis. Patients were treated with artemether/lumefantrine and primaquine. Clearance of parasitemia on peripheral smear was seen after an average of 2.8 days (range 2-4 days). Changing vector ecology and increased tempo of training exercises in the Dagmar North Region near the Demilitarized Zone are hypothesized to contribute to this cluster of cases. Malaria diagnosis post-deployment in non-endemic regions is challenging due to the long latency of illness onset and requires clinician vigilance. Preventive measures of pre-deployment should also be emphasized.
Curcumin, a polyphenolic compound exhibits various bioactivities, including antimalarial and anti-inflammatory effects. This study investigated the long-term antimalarial effects of curcumin through in vivo experiments using Plasmodium berghei NK65-infected mice, complemented by in vitro and in silico analyses targeting the plasmodial GSK3 protein. Through in vitro, the antimalarial activity of curcumin was assessed on P. falciparum K1 (multi-drug resistant strain) and 3D7 (sensitive strain) as well as P. knowlesi A1H1 of Plasmodium lactate dehydrogenase (pLDH) assay, alongside cytotoxic effects on Vero cells using the MTT assay. Curcumin demonstrated its bioactivity to disrupt the parasite's growth and replication based on the effective inhibition on both P. falciparum (3D7 EC50=8.11µM; K1 EC50=31.21µM) and P. knowlesi (EC50=4.51µM). Molecular docking studies explored curcumin's interaction with the ATP-binding pocket of P. falciparum glycogen synthase kinase-3 (PfGSK3) with favourable binding affinity (-8.72kcal/mol), revealing it potential as a selective inhibitor. Further, in vivo experiments validated curcumin's immunomodulatory activities and therapeutic effects in P. berghei-infected mice. Prolonged curcumin treatment has shown to significantly reduce the parasitaemia compared to the controls. Cytokine profiling via ELISA showed enhanced levels of anti-inflammatory cytokines (IL-10, IL-4) and decreased pro-inflammatory markers (TNF-α, IFN-γ), mitigating systemic inflammation associated with malaria. Histopathological analysis revealed reduction of tissue damage in the curcumin-treated mice, including decreasing parasite sequestration, inflammatory cell infiltration, hepatocyte necrosis and hemorrhages. This study highlights curcumin's potentials in inhibiting PfGSK3, regulating immune responses, and attenuating tissue damage which support its therapeutic role against malarial infection.
A recent study conducted in West Khasi Hills (WKH) and West Jaintia Hills (WJH) districts of Meghalaya has documented a low occurrence of the primary malaria vectors, Anopheles baimaii and An. minimus, alongside a relatively higher abundance of other anophelines, particularly members of the Maculatus Group. Plasmodium infection in the An. maculatus sensu lato (s.l.) was last reported in 1941, with no subsequent implication of An. maculatus s.l. in malaria transmission from Meghalaya or Northeast (NE) India for over eight decades. Given this apparent gap between species abundance and its recognised vector status, the present study was undertaken to examine the species composition and vector potential of predominant species using molecular tools in the Khasi Hills and Garo Hills regions of Meghalaya. In this study, we employed molecular techniques for precise species identification and detection of parasites. Our findings confirm natural infections of Plasmodium falciparum in An. maculatus sensu stricto (s.s.) and An. pseudowillmori-two member species of the Maculatus Group in Meghalaya. Resting adult Anopheles mosquitoes were collected between 2019 and 2023 (excluding 2021 due to the COVID-19 pandemic) in the Khasi Hills and Garo Hills regions using a mouth aspirator and torchlight, both indoors and outdoors. Out of 215 specimens analysed, 177 (82.32%) were identified as An. maculatus s.s., 33 (15.34%) as An. pseudowillmori, and 5 (2.32%) as An. willmori. Notably, Plasmodium infection was detected in 49 (27.68%) of 177 An. maculatus s.s. specimens and 16 (48.48%) of 33 An. pseudowillmori specimens, reinforcing their potential vectorial role in malaria transmission. FST analysis revealed significant genetic differentiation between An. maculatus s.s. populations from the Khasi Hills Region (KHR) and Garo Hills Region (GHR), further supported by haplotype network analysis. Additionally, blood meal analysis of specimens collected from cattle sheds during evening resting hours indicated diverse host feeding patterns: 15% had fed on humans, 16% on cattle, and 17% on both. The presence of mixed blood meals suggests that An. maculatus s.s. exhibits opportunistic and flexible feeding behaviour. These results provide molecular evidence of malaria transmission by specific members of the Maculatus Group in Meghalaya, underscoring their epidemiological importance. The genetic divergence and feeding plasticity highlight the need for targeted vector control in the region.
Ethiopia has experienced a marked malaria resurgence in recent years, with the Amhara Region disproportionately affected. Although Ethiopia's national strategy emphasizes test-before-treat and a public-private mix, implementation fidelity of the malaria test-and-treat guideline during resurgence has not been well characterized. This study assessed fidelity to malaria diagnosis and treatment guidelines in public and private health facilities in the Amhara Region within this resurgence context. We conducted a convergent parallel mixed-methods study from February to March 2025 in 53 health facilities (38 public, 15 private) in Amhara Region. The facility was the unit of analysis; one provider primarily responsible for malaria case management was interviewed per facility (n = 53). Implementation fidelity was operationalized using Carroll's framework across three domains: content (adherence to key diagnostic/treatment steps), coverage (proportion of suspected cases tested before treatment, extracted from facility registers), and frequency (self-reported consistency of testing for febrile patients in the preceding month). Domain scores were standardized to 0-100 and averaged with equal weights to form a composite fidelity score; ≥ 75% indicated high fidelity. To explain quantitative patterns, we conducted 32 in-depth interviews and analyzed data using inductive thematic analysis with CFIR-informed interpretation. Quantitative analysis used nonparametric tests and parsimonious multivariable linear regression, with prespecified sensitivity analyses excluding the self-reported frequency domain. Overall mean implementation fidelity was 64.3% (SD 12.1); 40% of facilities had high fidelity (≥75%), and 13% scored <50%. Public facilities had higher fidelity than private facilities (median 67% [IQR 60-77] vs 63% [IQR 56-70]; Wilcoxon rank-sum p = 0.041). In multivariable analysis, higher fidelity was associated with higher participant responsiveness (β = 3.4, p < 0.001), stronger facilitation strategies (β = 2.8, p < 0.001), and lower perceived intervention complexity (reverse-coded; β = 2.1, p < 0.001). Interviews indicated that fidelity gaps were driven by diagnostic and treatment deviations (including non-species-specific prescribing), inconsistent counseling and follow-up mechanisms, supply constraints, and patient pressure, with challenges more frequently emphasized in private facilities. Implementation fidelity to Ethiopia's malaria test-and-treat guideline in Amhara during resurgence was moderate, with lower fidelity in private facilities. Provider responsiveness, facilitation strategies, and lower intervention complexity were identified as factors associated with implementation fidelity. Strengthening supportive supervision and mentorship with explicit inclusion of private facilities, improving supply reliability, and simplifying decision supports may improve adherence during resurgence.
Due to the emergence of resistance to both artemisinin derivatives, and their partner drugs, new antimalarials are urgently needed. Ideally, new orally active antimalarials would not only engage new targets but also demonstrate a high barrier to resistance selection, and the ability to kill both proliferating rings and growth-arrested rings resulting from artemisinin exposure. In this report we disclose a novel antimalarial chemotype, the imidazo[4,5-c]pyridine-6-carboxamides, and a representative compound 10b that possesses all these qualities. Orally dosed 10b (4 × 60 mg/kg/day or 1 × 160 mg/kg) cures Plasmodium yoelii-infected mice out to 28 days. This compound is unaffected by over 40 distinct target- and efflux-based resistance mutations in the AReBaR resistome screen, suggesting a novel mode of action. Furthermore, at a minimum inoculum of resistance of 109 parasites, 10b proved refractory to resistance selection. Lastly, with a 6 h exposure, 250 nM 10b kills both proliferating rings and dihydroartemisinin-induced dormant parasites.
Malaria is endemic in Burkina Faso, with seasonal transmission during the rainy season. Environmental changes such as dam construction may influence mosquito ecology and malaria transmission; however, entomological data from this area remain limited. This study aimed to characterize malaria vector dynamics, including species composition, blood meal sources, and sporozoite infection rates, in five villages at varying distances from the Soum dam located in the Nanoro Health District catchment area in Burkina Faso. From March 2022 to February 2023, mosquitoes were collected monthly via pyrethrum spray catches (PSCs) targeting indoor resting vectors. Mosquitoes were identified morphologically via taxonomic keys. PCR analyses were performed to identify species within the Anopheles gambiae complex, determine blood meal sources, and assess Plasmodium falciparum infection. A total of 11,378 Anopheles mosquitoes were collected, including 3,432 males (30.1%) and 7,948 females (69.9%). An. gambiae s.l. was the most abundant species (86.5%), followed by An. funestus (10.6%). Within the An. gambiae complex, 91.5% were An. coluzzii, 8.3% An. arabiensis, and 0.2% An. gambiae sensu stricto. The vector density was highest in Soum (49.7%) and decreased with distance from the dam. The overall sporozoite rate was 6.2%, with higher rates in Seguedin (9.5%) and Soala (8.7%). Among the tested mosquitoes, 34.7% fed on humans, 14.2% on animals, and 23.6% on both. Anopheles coluzzii was the predominant vector and showed moderate anthropophilic behavior. Despite higher vector density near the dam, infection rates were greater in distant villages, highlighting the complexity of vector dynamics in dam-associated areas and the need for localized control strategies.
Malaria remains a major infectious disease worldwide, with a particularly high incidence in sub-Saharan Africa. For travelers visiting endemic areas, awareness of the risk of infection and the rigorous application of appropriate preventive measures are essential to prevent this life-threatening disease. In Switzerland, a transparent methodology was developed in collaboration with other European countries classifying malaria risk areas based on current epidemiological data and presenting harmonized preventive measures in detailed maps. These maps support travel medicine experts as well as primary care physicians in providing consistent, evidence-based, and practice-oriented travel medicine advice. They are available on the Swiss reference website for travel medicine: www.healthytravel.ch. Le paludisme reste une maladie infectieuse majeure dans le monde, avec une incidence particulièrement élevée en Afrique subsaharienne. Pour les voyageurs se rendant dans des zones endémiques, la connaissance du risque d’infection et l’application rigoureuse de mesures de prévention appropriées sont essentielles. En Suisse, une méthodologie transparente a été élaborée en collaboration avec d’autres pays européens, permettant de classer les zones à risque de paludisme sur la base de données épidémiologiques récentes et de représenter les mesures de prévention harmonisées dans des cartes détaillées. Ces cartes aident les médecins de premier recours et de médecine des voyages à donner des conseils uniformes, fondés sur des preuves et adaptés à la pratique, et sont disponibles sur le site de référence suisse de médecine des voyages : www.healthytravel.ch.
The role of gut inflammation for intestinal schistosomiasis remains poorly understood in chronically infected and repeatedly treated populations. We conducted a cross-sectional study nested in the SchistoTrack cohort within Pakwach district, Uganda. In 2024, 640 participants aged 6-85 years were examined for Schistosoma mansoni by Kato-Katz. Fecal calprotectin (fCal) concentration was measured by enzyme-linked immunosorbent assays. Fecal calprotectin was analyzed as binary outcomes (detectable, ≥100 µg/g, >250 µg/g) and natural log-transformed continuous values. Co-endemic infections (malaria, HIV, hepatitis B [HBV]) and sociodemographic covariates were investigated in logistic regressions with covariate selection. 74.4% of participants had detectable fCal, 22.3% had fCal ≥100 µg/g, and 7% had fCal >250 µg/g. Schistosoma mansoni prevalence was 49.1%. Infection intensity was positively associated with all fCal outcomes (detectable: OR 1.20, ≥100 µg/g: OR 1.11, >250 µg/g: OR 1.26; continuous: β .06) while infection status was positively related to all but the continuous fCal outcome. HIV was associated with fCal ≥100 µg/g (OR 2.52), while malaria and HBV were uninformative. Schistosoma mansoni infections are characterized by persistent, clinically concerning levels of gut inflammation in chronically infected populations with repeated praziquantel treatment. Integration of fCal thresholds into clinical guidelines may improve management of schistosomiasis-related morbidity.
Background: The Democratic Republic of the Congo accounts for approximately 12-13% of the global malaria burden. While international guidelines oppose the use of Artemisia annua infusions due to risks of sub-therapeutic dosing and resistance selection, the plant remains widely used in resource-limited regions. This study evaluates the clinical acceptability and perceptions of healthcare providers regarding the integration of Artemisia annua tea into formal malaria control in the Maniema province. Methods: A cross-sectional survey was conducted among 337 healthcare professionals in the Kalima health district using the KoboCollect digital platform. Multivariate logistic regression was employed to identify the primary socio-professional determinants of clinical acceptability. Results: The overall clinical acceptability of Artemisia annua integration was 81.0%, with 82.8% of providers perceiving the preparation as effective. Rural residency was the strongest predictor of adherence (AOR = 6.847; p = 0.003), reflecting a pragmatic response to frequent ACT stockouts and high treatment costs. Despite high acceptability, 49.0% of providers identified the lack of clinical evidence as a major barrier, and 91.4% demanded formal training on standardized dosage and biological mechanisms. Conclusions: A significant "policy-practice gap" exists between international guidelines and field realities in the DRC. Healthcare providers demonstrate high readiness for integration but emphasize the absolute necessity of galenic standardization to mitigate resistance risks. To address these concerns, a complementary genomic investigation is currently underway in the same study area, comparing PfKelch13 mutation prevalence among Artemisia tea users versus ACT-treated patients. This molecular surveillance will provide essential evidence to define safety parameters for future phytopharmaceutical integration.
Malaria parasites are obligately sexual hermaphrodite protozoans, with gamete fusion occurring in the mosquito midgut, followed by meiosis and recombination. Parasite populations display a range of mating structures, from predominantly selfing to highly outcrossed; yet, the fitness consequences of selfing versus outcrossing remain poorly understood. This project investigated gamete fusion dynamics within mosquitoes and compared the fitness of selfed and outcrossed zygotes. We generated fluorescently labelled clones of NF54 (mCherry; African) and NHP4026 (GFP; Thai), crossed these parasites and genotyped 8540 oocysts from 435 mosquitoes collected 7-14 days post-infection. In two independent crosses, we observed decreasing proportions of outcrossed oocysts and increasing selfing over time. This pattern is consistent with the faster maturation of outcrossed oocysts compared with selfed oocysts. Our results suggest a substantial fitness advantage of outcrossing, potentially due to the removal of deleterious mutations accumulated during asexual replication in the vertebrate host. We also found that selfed NF54 oocysts were larger than either outcrossed or selfed NHP4026 oocysts, which may influence sporozoite production and transmission potential. Fluorescently labelled parasites provide clear resolution of mating patterns, temporal dynamics and transmission potential in mosquitoes. Importantly, faster maturation of outcrossed parasites may maximize levels of recombination in transmitted malaria parasite populations.