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Will J R Stone, Joseph J Campo, André Lin Ouédraogo, Lisette Meerstein-Kessel, Isabelle Morlais, Dari Da, Anna Cohuet, Sandrine Nsango, Colin J Sutherland, Marga van de Vegte-Bolmer, Rianne Siebelink-Stoter, Geert-Jan van Gemert, Wouter Graumans, Kjerstin Lanke, Adam D Shandling, Jozelyn V Pablo, Andy A Teng, Sophie Jones, Roos M de Jong, Amanda Fabra-García, John Bradley, Will Roeffen, Edwin Lasonder, Giuliana Gremo, Evelin Schwarzer, Chris J Janse, Susheel K Singh, Michael Theisen, Phil Felgner, Matthias Marti, Chris Drakeley, Robert Sauerwein, Teun Bousema, Matthijs M Jore
Infection with Plasmodium can elicit antibodies that inhibit parasite survival in the mosquito, when they are ingested in an infectious blood meal. Here, we determine the transmission-reducing activity (TRA) of naturally acquired antibodies from 648 malaria-exposed individuals using lab-based mosquito-feeding assays. Transmission inhibition is significantly associated with antibody responses to Pfs48/45, Pfs230, and to 43 novel gametocyte proteins assessed by protein microarray. In field-based mosquito-feeding assays the likelihood and rate of mosquito infection are significantly lower for individuals reactive to Pfs48/45, Pfs230 or to combinations of the novel TRA-associated proteins...
February 8, 2018: Nature Communications
Alassane Dicko, Michelle E Roh, Halimatou Diawara, Almahamoudou Mahamar, Harouna M Soumare, Kjerstin Lanke, John Bradley, Koualy Sanogo, Daouda T Kone, Kalifa Diarra, Sekouba Keita, Djibrilla Issiaka, Sekou F Traore, Charles McCulloch, Will J R Stone, Jimee Hwang, Olaf Müller, Joelle M Brown, Vinay Srinivasan, Chris Drakeley, Roly Gosling, Ingrid Chen, Teun Bousema
BACKGROUND: Primaquine and methylene blue are gametocytocidal compounds that could prevent Plasmodium falciparum transmission to mosquitoes. We aimed to assess the efficacy and safety of primaquine and methylene blue in preventing human to mosquito transmission of P falciparum among glucose-6-phosphate dehydrogenase (G6PD)-normal, gametocytaemic male participants. METHODS: This was a phase 2, single-blind, randomised controlled trial done at the Clinical Research Centre of the Malaria Research and Training Centre (MRTC) of the University of Bamako (Bamako, Mali)...
February 5, 2018: Lancet Infectious Diseases
Matt Ravenhall, Susana Campino, Nuno Sepúlveda, Alphaxard Manjurano, Behzad Nadjm, George Mtove, Hannah Wangai, Caroline Maxwell, Raimos Olomi, Hugh Reyburn, Christopher J Drakeley, Eleanor M Riley, Taane G Clark
Significant selection pressure has been exerted on the genomes of human populations exposed to Plasmodium falciparum infection, resulting in the acquisition of mechanisms of resistance against severe malarial disease. Many host genetic factors, including sickle cell trait, have been associated with reduced risk of developing severe malaria, but do not account for all of the observed phenotypic variation. Identification of novel inherited risk factors relies upon high-resolution genome-wide association studies (GWAS)...
January 2018: PLoS Genetics
Wamdaogo M Guelbéogo, Bronner Pamplona Gonçalves, Lynn Grignard, John Bradley, Samuel S Serme, Joel Hellewell, Kjerstin Lanke, Soumanaba Zongo, Nuno Sepúlveda, Issiaka Soulama, Dimitri W Wangrawa, Laith Yakob, N'Falé Sagnon, Teun Bousema, Chris Drakeley
Variation in biting frequency by Anopheles mosquitoes can explain some of the heterogeneity in malaria transmission in endemic areas. In this study in Burkina Faso, we assessed natural exposure to mosquitoes by matching the genotype of blood meals from 1066 mosquitoes with blood from residents of local households. We observed that the distribution of mosquito bites exceeded the Pareto rule (20/80) in two of the three surveys performed (20/85, 76, and 96) and, at its most pronounced, is estimated to have profound epidemiological consequences, inflating the basic reproduction number of malaria by 8-fold...
January 23, 2018: ELife
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
Lisette Meerstein-Kessel, Robin van der Lee, Will Stone, Kjerstin Lanke, David A Baker, Pietro Alano, Francesco Silvestrini, Chris J Janse, Shahid M Khan, Marga van de Vegte-Bolmer, Wouter Graumans, Rianne Siebelink-Stoter, Taco W A Kooij, Matthias Marti, Chris Drakeley, Joseph J Campo, Teunis J P van Dam, Robert Sauerwein, Teun Bousema, Martijn A Huynen
Plasmodium gametocytes are the sexual forms of the malaria parasite essential for transmission to mosquitoes. To better understand how gametocytes differ from asexual blood-stage parasites, we performed a systematic analysis of available 'omics data for P. falciparum and other Plasmodium species. 18 transcriptomic and proteomic data sets were evaluated for the presence of curated "gold standards" of 41 gametocyte-specific versus 46 non-gametocyte genes and integrated using Bayesian probabilities, resulting in gametocyte-specificity scores for all P...
January 11, 2018: Scientific Reports
Fitsum G Tadesse, Hannah C Slater, Wakweya Chali, Karina Teelen, Kjerstin Lanke, Mulualem Belachew, Temesgen Menberu, Girma Shumie, Getasew Shitaye, Lucy C Okell, Wouter Graumans, Geert-Jan van Gemert, Soriya Kedir, Addisu Tesfaye, Feleke Belachew, Wake Abebe, Hassen Mamo, Robert Sauerwein, Taye Balcha, Abraham Aseffa, Delenasaw Yewhalaw, Endalamaw Gadisa, Chris Drakeley, Teun Bousema
Background: The majority of P. vivax and P. falciparum infections in low-endemic settings are asymptomatic. The relative contribution to the infectious reservoir of these infections, often of low-parasite-density, compared to clinical malaria cases, is currently unknown but important for malaria elimination strategies. Methods: We assessed infectivity of passively-recruited symptomatic malaria patients (n=41) and community-recruited asymptomatic individuals with microscopy- (n=41) and PCR-detected infections (n=82) using membrane feeding assays with Anopheles arabiensis mosquitoes in Adama, Ethiopia...
January 3, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Ernest Diez Benavente, Paola Florez de Sessions, Robert W Moon, Munira Grainger, Anthony A Holder, Michael J Blackman, Cally Roper, Christopher J Drakeley, Arnab Pain, Colin J Sutherland, Martin L Hibberd, Susana Campino, Taane G Clark
Plasmodium knowlesi, a common parasite of macaques, is recognised as a significant cause of human malaria in Malaysia. The P. knowlesi A1H1 line has been adapted to continuous culture in human erythrocytes, successfully providing an in vitro model to study the parasite. We have assembled a reference genome for the PkA1-H.1 line using PacBio long read combined with Illumina short read sequence data. Compared with the H-strain reference, the new reference has improved genome coverage and a novel description of methylation sites...
December 16, 2017: International Journal for Parasitology
Regina N Rabinovich, Chris Drakeley, Abdoulaye A Djimde, B Fenton Hall, Simon I Hay, Janet Hemingway, David C Kaslow, Abdisalan Noor, Fredros Okumu, Richard Steketee, Marcel Tanner, Timothy N C Wells, Maxine A Whittaker, Elizabeth A Winzeler, Dyann F Wirth, Kate Whitfield, Pedro L Alonso
Achieving a malaria-free world presents exciting scientific challenges as well as overwhelming health, equity, and economic benefits. WHO and countries are setting ambitious goals for reducing the burden and eliminating malaria through the "Global Technical Strategy" and 21 countries are aiming to eliminate malaria by 2020. The commitment to achieve these targets should be celebrated. However, the need for innovation to achieve these goals, sustain elimination, and free the world of malaria is greater than ever...
November 2017: PLoS Medicine
Julia Mwesigwa, Jane Achan, Gian Luca Di Tanna, Muna Affara, Musa Jawara, Archibald Worwui, Majidah Hamid-Adiamoh, Fatoumatta Kanuteh, Sainey Ceesay, Teun Bousema, Chris Drakeley, Koen Peeters Grietens, Steve W Lindsay, Jean-Pierre Van Geertruyden, Umberto D'Alessandro
Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The Gambia. Blood samples were collected monthly during the transmission season (June-December) from all residents aged ≥6 months (4,194 individuals) and then in April (dry season)...
2017: PloS One
Chris Drakeley, Salim Abdulla, Selidji Todagbe Agnandji, José Francisco Fernandes, Peter Kremsner, Bertrand Lell, Ludovic Mewono, Bache Emmanuel Bache, Michael Gabriel Mihayo, Omar Juma, Marcel Tanner, Marc Christian Tahita, Halidou Tinto, Salou Diallo, Palpouguini Lompo, Umberto D'Alessandro, Bernhards Ogutu, Lucas Otieno, Solomon Otieno, Walter Otieno, Janet Oyieko, Kwaku Poku Asante, Dominic Bon-Ereme Dery, George Adjei, Elisha Adeniji, Dorcas Atibilla, Seth Owusu-Agyei, Brian Greenwood, Samwel Gesase, John Lusingu, Coline Mahende, Robert Mongi, Method Segeja, Samuel Adjei, Tsiri Agbenyega, Alex Agyekum, Daniel Ansong, John Tanko Bawa, Harry Owusu Boateng, Léonard Dandalo, Veronica Escamilla, Irving Hoffman, Peter Maenje, Francis Martinson, Terrell Carter, Didier Leboulleux, David C Kaslow, Effua Usuf, Jean-Yves Pirçon, Edith Roset Bahmanyar
BACKGROUND: Plasmodium falciparum prevalence (PfPR) is a widely used metric for assessing malaria transmission intensity. This study was carried out concurrently with the RTS,S/AS01 candidate malaria vaccine Phase III trial and estimated PfPR over ≤ 4 standardized cross-sectional surveys. METHODS: This epidemiology study (NCT01190202) was conducted in 8 sites from 6 countries (Burkina Faso, Gabon, Ghana, Kenya, Malawi, and Tanzania), between March 2011 and December 2013...
October 27, 2017: Malaria Journal
Bronner P Gonçalves, Melissa C Kapulu, Patrick Sawa, Wamdaogo M Guelbéogo, Alfred B Tiono, Lynn Grignard, Will Stone, Joel Hellewell, Kjerstin Lanke, Guido J H Bastiaens, John Bradley, Issa Nébié, Joyce M Ngoi, Robin Oriango, Dora Mkabili, Maureen Nyaurah, Janet Midega, Dyann F Wirth, Kevin Marsh, Thomas S Churcher, Philip Bejon, Sodiomon B Sirima, Chris Drakeley, Teun Bousema
A detailed understanding of the human infectious reservoir is essential for improving malaria transmission-reducing interventions. Here we report a multi-regional assessment of population-wide malaria transmission potential based on 1209 mosquito feeding assays in endemic areas of Burkina Faso and Kenya. Across both sites, we identified 39 infectious individuals. In high endemicity settings, infectious individuals were identifiable by research-grade microscopy (92.6%; 25/27), whilst one of three infectious individuals in the lowest endemicity setting was detected by molecular techniques alone...
October 26, 2017: Nature Communications
Tock H Chua, Benny O Manin, Sylvia Daim, Indra Vythilingam, Chris Drakeley
BACKGROUND: Anopheles balabacensis of the Leucospyrus group has been confirmed as the primary knowlesi malaria vector in Sabah, Malaysian Borneo for some time now. Presently, knowlesi malaria is the only zoonotic simian malaria in Malaysia with a high prevalence recorded in the states of Sabah and Sarawak. METHODOLOGY/PRINCIPAL FINDINGS: Anopheles spp. were sampled using human landing catch (HLC) method at Paradason village in Kudat district of Sabah. The collected Anopheles were identified morphologically and then subjected to total DNA extraction and polymerase chain reaction (PCR) to detect Plasmodium parasites in the mosquitoes...
October 2017: PLoS Neglected Tropical Diseases
Andrew Walakira, Stephen Tukwasibwe, Moses Kiggundu, Federica Verra, Patrick Kakeeto, Emmanuel Ruhamyankaka, Chris Drakeley, Grant Dorsey, Moses R Kamya, Samuel L Nsobya, Philip J Rosenthal
A number of human genetic polymorphisms are prevalent in tropical populations and appear to offer protection against symptomatic and/or severe malaria. We compared the prevalence of four polymorphisms, the sickle hemoglobin mutation (β globin E6V), the α-thalassemia 3.7kb deletion, glucose-6-phosphate dehydrogenase deficiency caused by the common African variant (G6PD A-), and the CD36 T188G mutation in 1344 individuals residing in districts in eastern (Tororo), south-central (Jinja), and southwestern (Kanungu) Uganda...
November 2017: Infection, Genetics and Evolution
Will Stone, Patrick Sawa, Kjerstin Lanke, Sanna Rijpma, Robin Oriango, Maureen Nyaurah, Paul Osodo, Victor Osoti, Almahamoudou Mahamar, Halimatou Diawara, Rob Woestenenk, Wouter Graumans, Marga van de Vegte-Bolmer, John Bradley, Ingrid Chen, Joelle Brown, Giulia Siciliano, Pietro Alano, Roly Gosling, Alassane Dicko, Chris Drakeley, Teun Bousema
Background: Single low-dose primaquine (PQ) reduces Plasmodium falciparum infectivity before it impacts gametocyte density. Here, we examined the effect of PQ on gametocyte sex ratio as a possible explanation for this early sterilizing effect. Methods: Quantitative reverse-transcription polymerase chain reaction assays were developed to quantify female gametocytes (targeting Pfs25 messenger RNA [mRNA]) and male gametocytes (targeting Pf3D7_1469900 mRNA) in 2 randomized trials in Kenya and Mali, comparing dihydroartemisinin-piperaquine (DP) alone to DP with PQ...
August 15, 2017: Journal of Infectious Diseases
Ernest Diez Benavente, Paola Florez de Sessions, Robert W Moon, Anthony A Holder, Michael J Blackman, Cally Roper, Christopher J Drakeley, Arnab Pain, Colin J Sutherland, Martin L Hibberd, Susana Campino, Taane G Clark
The macaque parasite Plasmodium knowlesi is a significant concern in Malaysia where cases of human infection are increasing. Parasites infecting humans originate from genetically distinct subpopulations associated with the long-tailed (Macaca fascicularis (Mf)) or pig-tailed macaques (Macaca nemestrina (Mn)). We used a new high-quality reference genome to re-evaluate previously described subpopulations among human and macaque isolates from Malaysian-Borneo and Peninsular-Malaysia. Nuclear genomes were dimorphic, as expected, but new evidence of chromosomal-segment exchanges between subpopulations was found...
September 2017: PLoS Genetics
Zulkarnain Md Idris, Chim W Chan, James Kongere, Tom Hall, John Logedi, Jesse Gitaka, Chris Drakeley, Akira Kaneko
As markers of exposure anti-malaria antibody responses can help characterise heterogeneity in malaria transmission. In the present study antibody responses to Plasmodium falciparum AMA-1, MSP-119 and CSP were measured with the aim to describe transmission patterns in meso-endemic settings in Lake Victoria. Two cross-sectional surveys were conducted in Lake Victoria in January and August 2012. The study area comprised of three settings: mainland (Ungoye), large island (Mfangano) and small islands (Takawiri, Kibuogi, Ngodhe)...
August 22, 2017: Scientific Reports
Ryan A Simmons, Leonard Mboera, Marie Lynn Miranda, Alison Morris, Gillian Stresman, Elizabeth L Turner, Randall Kramer, Chris Drakeley, Wendy P O'Meara
BACKGROUND: Measurements of anti-malarial antibodies are increasingly used as a proxy of transmission intensity. Most serological surveys are based on the use of cross-sectional data that, when age-stratified, approximates historical patterns of transmission within a population. Comparatively few studies leverage longitudinal data to explicitly relate individual infection events with subsequent antibody responses. METHODS: The occurrence of seroconversion and seroreversion events for two Plasmodium falciparum asexual stage antigens (MSP-1 and AMA-1) was examined using three annual measurements of 691 individuals from a cohort of individuals in a malaria-endemic area of rural east-central Tanzania...
August 2, 2017: Malaria Journal
Matthew J Grigg, Jonathan Cox, Timothy William, Jenarun Jelip, Kimberly M Fornace, Patrick M Brock, Lorenz von Seidlein, Bridget E Barber, Nicholas M Anstey, Tsin W Yeo, Christopher J Drakeley
BACKGROUND: The emergence of human malaria due to the monkey parasite Plasmodium knowlesi threatens elimination efforts in southeast Asia. Changes in land use are thought to be driving the rise in reported P knowlesi cases, but the role of individual-level factors is unclear. To address this knowledge gap we assessed human and environmental factors associated with zoonotic knowlesi malaria risk. METHODS: We did this population-based case-control study over a 2 year period in the state of Sabah in Malaysia...
June 9, 2017: Lancet. Planetary Health
Frances Hawkes, Benny Obrain Manin, Sui Han Ng, Stephen J Torr, Chris Drakeley, Tock H Chua, Heather M Ferguson
BACKGROUND: Plasmodium knowlesi is found in macaques and is the only major zoonotic malaria to affect humans. Transmission of P. knowlesi between people and macaques depends on the host species preferences and feeding behavior of mosquito vectors. However, these behaviours are difficult to measure due to the lack of standardized methods for sampling potential vectors attracted to different host species. This study evaluated electrocuting net traps as a safe, standardised method for sampling P...
July 18, 2017: Parasites & Vectors
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