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Article ; Online: Targeting Human Transmission Biology for Malaria Elimination.

Nilsson, Sandra K / Childs, Lauren M / Buckee, Caroline / Marti, Matthias

2015 Volume 11, Issue 6, Page(s) e1004871

Abstract: ... virulent human malaria parasite, Plasmodium falciparum. Gametocytes, the only developmental stage ... the transmission biology of P. falciparum gametocytes, featuring important recent discoveries of genes affecting ... efforts. The recent commitment by many endemic countries to eliminate malaria marks a shift away ...

Abstract	Malaria remains one of the leading causes of death worldwide, despite decades of public health efforts. The recent commitment by many endemic countries to eliminate malaria marks a shift away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, Plasmodium falciparum. Gametocytes, the only developmental stage of malaria parasites able to infect mosquitoes, have remained understudied, as they occur in low numbers, do not cause disease, and are difficult to detect in vivo by conventional methods. Here, we review the transmission biology of P. falciparum gametocytes, featuring important recent discoveries of genes affecting parasite commitment to gametocyte formation, microvesicles enabling parasites to communicate with each other, and the anatomical site where immature gametocytes develop. We propose potential parasite targets for future intervention and highlight remaining knowledge gaps.
MeSH term(s)	Animals ; Culicidae/parasitology ; Humans ; Life Cycle Stages ; Malaria, Falciparum/transmission ; Plasmodium falciparum/physiology
Language	English
Publishing date	2015-06-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7366
ISSN (online)	1553-7374
ISSN	1553-7366
DOI	10.1371/journal.ppat.1004871
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Targeting Human Transmission Biology for Malaria Elimination.

Sandra K Nilsson / Lauren M Childs / Caroline Buckee / Matthias Marti

PLoS Pathogens, Vol 11, Iss 6, p e

2015 Volume 1004871

Abstract	Malaria remains one of the leading causes of death worldwide, despite decades of public health efforts. The recent commitment by many endemic countries to eliminate malaria marks a shift away from programs aimed at controlling disease burden towards one that emphasizes reducing transmission of the most virulent human malaria parasite, Plasmodium falciparum. Gametocytes, the only developmental stage of malaria parasites able to infect mosquitoes, have remained understudied, as they occur in low numbers, do not cause disease, and are difficult to detect in vivo by conventional methods. Here, we review the transmission biology of P. falciparum gametocytes, featuring important recent discoveries of genes affecting parasite commitment to gametocyte formation, microvesicles enabling parasites to communicate with each other, and the anatomical site where immature gametocytes develop. We propose potential parasite targets for future intervention and highlight remaining knowledge gaps.
Keywords	Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2015-06-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Adapt or Die: Targeting Unique Transmission-Stage Biology for Malaria Elimination.

van der Watt, Mariëtte E / Reader, Janette / Birkholtz, Lyn-Marié

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 901971

Abstract: ... ...

Abstract	Plasmodium
MeSH term(s)	Animals ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Biology ; Humans ; Life Cycle Stages ; Malaria/parasitology ; Malaria, Falciparum/parasitology ; Mosquito Vectors ; Parasites ; Plasmodium ; Plasmodium falciparum
Chemical Substances	Antimalarials
Language	English
Publishing date	2022-06-09
Publishing country	Switzerland
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.901971
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Increasing the potential for malaria elimination by targeting zoophilic vectors.

Waite, Jessica L / Swain, Sunita / Lynch, Penelope A / Sharma, S K / Haque, Mohammed Asrarul / Montgomery, Jacqui / Thomas, Matthew B

Scientific reports

2017 Volume 7, Page(s) 40551

Abstract: ... transmission region in India, malaria vector populations show a high propensity to feed on livestock (cattle ... species complex towards increased zoophilic behavior in recent years. Using a malaria transmission model ... Countries in the Asia Pacific region aim to eliminate malaria by 2030. A cornerstone of malaria ...

Abstract	Countries in the Asia Pacific region aim to eliminate malaria by 2030. A cornerstone of malaria elimination is the effective management of Anopheles mosquito vectors. Current control tools such as insecticide treated nets or indoor residual sprays target mosquitoes in human dwellings. We find in a high transmission region in India, malaria vector populations show a high propensity to feed on livestock (cattle) and rest in outdoor structures such as cattle shelters. We also find evidence for a shift in vector species complex towards increased zoophilic behavior in recent years. Using a malaria transmission model we demonstrate that in such regions dominated by zoophilic vectors, existing vector control tactics will be insufficient to achieve elimination, even if maximized. However, by increasing mortality in the zoophilic cycle, the elimination threshold can be reached. Current national vector control policy in India restricts use of residual insecticide sprays to domestic dwellings. Our study suggests substantial benefits of extending the approach to treatment of cattle sheds, or deploying other tactics that target zoophilic behavior. Optimizing use of existing tools will be essential to achieving the ambitious 2030 elimination target.
MeSH term(s)	Animals ; Anopheles/physiology ; Cattle ; Disease Eradication ; Feeding Behavior ; Host-Pathogen Interactions ; Humans ; India ; Malaria/parasitology ; Malaria/prevention & control ; Models, Biological ; Mosquito Vectors/physiology ; Sporozoites/physiology
Language	English
Publishing date	2017-01-16
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/srep40551
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Article ; Online: Modelling of malaria risk, rates, and trends: A spatiotemporal approach for identifying and targeting sub-national areas of high and low burden.

Lubinda, Jailos / Bi, Yaxin / Hamainza, Busiku / Haque, Ubydul / Moore, Adrian J

PLoS computational biology

2021 Volume 17, Issue 3, Page(s) e1008669

Abstract: ... those high-burden areas with intensive control measures while at the same time pursue malaria elimination ... our method, we have developed a platform that can enable malaria programs in countries like Zambia to target ... While mortality from malaria continues to decline globally, incidence rates in many countries are ...

Abstract	While mortality from malaria continues to decline globally, incidence rates in many countries are rising. Within countries, spatial and temporal patterns of malaria vary across communities due to many different physical and social environmental factors. To identify those areas most suitable for malaria elimination or targeted control interventions, we used Bayesian models to estimate the spatiotemporal variation of malaria risk, rates, and trends to determine areas of high or low malaria burden compared to their geographical neighbours. We present a methodology using Bayesian hierarchical models with a Markov Chain Monte Carlo (MCMC) based inference to fit a generalised linear mixed model with a conditional autoregressive structure. We modelled clusters of similar spatiotemporal trends in malaria risk, using trend functions with constrained shapes and visualised high and low burden districts using a multi-criterion index derived by combining spatiotemporal risk, rates and trends of districts in Zambia. Our results indicate that over 3 million people in Zambia live in high-burden districts with either high mortality burden or high incidence burden coupled with an increasing trend over 16 years (2000 to 2015) for all age, under-five and over-five cohorts. Approximately 1.6 million people live in high-incidence burden areas alone. Using our method, we have developed a platform that can enable malaria programs in countries like Zambia to target those high-burden areas with intensive control measures while at the same time pursue malaria elimination efforts in all other areas. Our method enhances conventional approaches and measures to identify those districts which had higher rates and increasing trends and risk. This study provides a method and a means that can help policy makers evaluate intervention impact over time and adopt appropriate geographically targeted strategies that address the issues of both high-burden areas, through intensive control approaches, and low-burden areas, via specific elimination programs.
MeSH term(s)	Bayes Theorem ; Child ; Child, Preschool ; Computational Biology ; Humans ; Incidence ; Infant ; Infant, Newborn ; Malaria/epidemiology ; Malaria/transmission ; Models, Biological ; Models, Statistical ; Risk ; Spatio-Temporal Analysis ; Zambia
Language	English
Publishing date	2021-03-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2193340-6
ISSN	1553-7358 ; 1553-734X
ISSN (online)	1553-7358
ISSN	1553-734X
DOI	10.1371/journal.pcbi.1008669
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Article ; Online: Targeting Plasmodium PI(4)K to eliminate malaria.

McNamara, Case W / Lee, Marcus Cs / Lim, Chek Shik / Lim, Siau Hoi / Roland, Jason / Simon, Oliver / Yeung, Bryan Ks / Chatterjee, Arnab K / McCormack, Susan L / Manary, Micah J / Zeeman, Anne-Marie / Dechering, Koen J / Kumar, Tr Santha / Henrich, Philipp P / Gagaring, Kerstin / Ibanez, Maureen / Kato, Nobutaka / Kuhen, Kelli L / Fischli, Christoph /

Nature

2013 Volume 504, Issue 7479, Page(s) 248–253

Abstract: Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential ... potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active ... for the prevention, treatment and elimination of malaria. ...

Abstract	Achieving the goal of malaria elimination will depend on targeting Plasmodium pathways essential across all life stages. Here we identify a lipid kinase, phosphatidylinositol-4-OH kinase (PI(4)K), as the target of imidazopyrazines, a new antimalarial compound class that inhibits the intracellular development of multiple Plasmodium species at each stage of infection in the vertebrate host. Imidazopyrazines demonstrate potent preventive, therapeutic, and transmission-blocking activity in rodent malaria models, are active against blood-stage field isolates of the major human pathogens P. falciparum and P. vivax, and inhibit liver-stage hypnozoites in the simian parasite P. cynomolgi. We show that imidazopyrazines exert their effect through inhibitory interaction with the ATP-binding pocket of PI(4)K, altering the intracellular distribution of phosphatidylinositol-4-phosphate. Collectively, our data define PI(4)K as a key Plasmodium vulnerability, opening up new avenues of target-based discovery to identify drugs with an ideal activity profile for the prevention, treatment and elimination of malaria.
MeSH term(s)	1-Phosphatidylinositol 4-Kinase/antagonists & inhibitors ; 1-Phosphatidylinositol 4-Kinase/chemistry ; 1-Phosphatidylinositol 4-Kinase/genetics ; 1-Phosphatidylinositol 4-Kinase/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Binding Sites ; Cytokinesis/drug effects ; Drug Resistance/drug effects ; Drug Resistance/genetics ; Fatty Acids/metabolism ; Female ; Hepatocytes/parasitology ; Humans ; Imidazoles/metabolism ; Imidazoles/pharmacology ; Life Cycle Stages/drug effects ; Macaca mulatta ; Malaria/drug therapy ; Malaria/parasitology ; Male ; Models, Biological ; Models, Molecular ; Phosphatidylinositol Phosphates/metabolism ; Plasmodium/classification ; Plasmodium/drug effects ; Plasmodium/enzymology ; Plasmodium/growth & development ; Pyrazoles/metabolism ; Pyrazoles/pharmacology ; Quinoxalines/metabolism ; Quinoxalines/pharmacology ; Reproducibility of Results ; Schizonts/cytology ; Schizonts/drug effects ; rab GTP-Binding Proteins/genetics ; rab GTP-Binding Proteins/metabolism
Chemical Substances	Fatty Acids ; Imidazoles ; Phosphatidylinositol Phosphates ; Pyrazoles ; Quinoxalines ; phosphatidylinositol 4-phosphate ; Adenosine Triphosphate (8L70Q75FXE) ; 1-Phosphatidylinositol 4-Kinase (EC 2.7.1.67) ; rab11 protein (EC 3.6.1.-) ; rab GTP-Binding Proteins (EC 3.6.5.2)
Language	English
Publishing date	2013-11-27
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature12782
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Zs.A 26: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Novel strategies targeting pathogen transmission reduction in insect vectors: Tsetse-transmitted trypanosomiasis control

WEISS, Brian L / ATTARDO, Geoffrey M / PAIS, Roshan / WANG, Jingwen / AKSOY, Serap

Entomological research. 2007 Dec., v. 37, no. 4

2007

Abstract: Insect vectors are essential for the transmission of important human diseases such as malaria ... in insect biology and in insect-pathogen interactions as well as by the development of transgenic ... biology to develop novel disease control strategies. ...

Abstract	Insect vectors are essential for the transmission of important human diseases such as malaria, leishmaniasis, Chagas and sleeping sickness. Insects are also responsible for the transmission of agricultural diseases that affect livestock and crops. Traditionally, control of the vector populations has been an effective disease management strategy. Recently, vector control strategies have been fortified by research in insect biology and in insect-pathogen interactions as well as by the development of transgenic technologies. In addition to insect population reduction methods, disease control via selective elimination of pathogens in insects can now be explored. Here we explore the tsetse vectors of African trypanosomes and describe the application of recent knowledge gained in their symbiotic, reproductive and vectorial biology to develop novel disease control strategies.
Keywords	crops ; disease control ; human diseases ; insect biology ; insect vectors ; insects ; leishmaniasis ; livestock ; malaria ; pathogens ; trypanosomiasis ; vector control
Language	English
Dates of publication	2007-12
Size	p. 231-237.
Publisher	Blackwell Publishing Asia
Publishing place	Melbourne, Australia
Document type	Article
ZDB-ID	2227607-5
ISSN	1748-5967 ; 1738-2297
ISSN (online)	1748-5967
ISSN	1738-2297
DOI	10.1111/j.1748-5967.2007.00119.x
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: High-Throughput Antibody Profiling Identifies Targets of Protective Immunity against

Hassan, Ifra / Kanoi, Bernard N / Nagaoka, Hikaru / Sattabongkot, Jetsumon / Udomsangpetch, Rachanee / Tsuboi, Takafumi / Takashima, Eizo

Biomolecules

2023 Volume 13, Issue 8

Abstract: ... implement strategies to reduce malaria transmission and ultimately eliminate the disease, it is crucial ... Malaria poses a significant global health challenge, resulting in approximately 600,000 deaths ... each year. Individuals living in regions with endemic malaria have the potential to develop partial immunity ...

Abstract	Malaria poses a significant global health challenge, resulting in approximately 600,000 deaths each year. Individuals living in regions with endemic malaria have the potential to develop partial immunity, thanks in part to the presence of anti-plasmodium antibodies. As efforts are made to optimize and implement strategies to reduce malaria transmission and ultimately eliminate the disease, it is crucial to understand how these interventions impact naturally acquired protective immunity. To shed light on this, our study focused on assessing antibody responses to a carefully curated library of
MeSH term(s)	Humans ; Thailand ; Malaria, Falciparum ; Malaria ; Antibodies ; Biological Assay
Chemical Substances	Antibodies
Language	English
Publishing date	2023-08-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom13081267
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Article ; Online: Molecular interactions between parasite and mosquito during midgut invasion as targets to block malaria transmission.

Keleta, Yacob / Ramelow, Julian / Cui, Liwang / Li, Jun

NPJ vaccines

2021 Volume 6, Issue 1, Page(s) 140

Abstract: ... in the biology of malaria transmission, focusing on molecular interactions between Plasmodium and Anopheles ... of malaria vaccines against the liver and blood stages has been challenging. Therefore, malaria elimination strategies ... Despite considerable effort, malaria remains a major public health burden. Malaria is caused ...

Abstract	Despite considerable effort, malaria remains a major public health burden. Malaria is caused by five Plasmodium species and is transmitted to humans via the female Anopheles mosquito. The development of malaria vaccines against the liver and blood stages has been challenging. Therefore, malaria elimination strategies advocate integrated measures, including transmission-blocking approaches. Designing an effective transmission-blocking strategy relies on a sophisticated understanding of the molecular mechanisms governing the interactions between the mosquito midgut molecules and the malaria parasite. Here we review recent advances in the biology of malaria transmission, focusing on molecular interactions between Plasmodium and Anopheles mosquito midgut proteins. We provide an overview of parasite and mosquito proteins that are either targets for drugs currently in clinical trials or candidates of promising transmission-blocking vaccines.
Language	English
Publishing date	2021-11-29
Publishing country	England
Document type	Journal Article ; Review
ISSN	2059-0105
ISSN (online)	2059-0105
DOI	10.1038/s41541-021-00401-9
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Article ; Online: Machine learning-based phenotypic imaging to characterise the targetable biology of Plasmodium falciparum male gametocytes for the development of transmission-blocking antimalarials.

Tsebriy, Oleksiy / Khomiak, Andrii / Miguel-Blanco, Celia / Sparkes, Penny C / Gioli, Maurizio / Santelli, Marco / Whitley, Edgar / Gamo, Francisco-Javier / Delves, Michael J

PLoS pathogens

2023 Volume 19, Issue 10, Page(s) e1011711

Abstract: ... for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs ... Preventing parasite transmission from humans to mosquitoes is recognised to be critical ... Plasmodium falciparum stage V gametocytes, or how they affect their underlying cell biology. To respond ...

Abstract	Preventing parasite transmission from humans to mosquitoes is recognised to be critical for achieving elimination and eradication of malaria. Consequently developing new antimalarial drugs with transmission-blocking properties is a priority. Large screening campaigns have identified many new transmission-blocking molecules, however little is known about how they target the mosquito-transmissible Plasmodium falciparum stage V gametocytes, or how they affect their underlying cell biology. To respond to this knowledge gap, we have developed a machine learning image analysis pipeline to characterise and compare the cellular phenotypes generated by transmission-blocking molecules during male gametogenesis. Using this approach, we studied 40 molecules, categorising their activity based upon timing of action and visual effects on the organisation of tubulin and DNA within the cell. Our data both proposes new modes of action and corroborates existing modes of action of identified transmission-blocking molecules. Furthermore, the characterised molecules provide a new armoury of tool compounds to probe gametocyte cell biology and the generated imaging dataset provides a new reference for researchers to correlate molecular target or gene deletion to specific cellular phenotype. Our analysis pipeline is not optimised for a specific organism and could be applied to any fluorescence microscopy dataset containing cells delineated by bounding boxes, and so is potentially extendible to any disease model.
MeSH term(s)	Humans ; Animals ; Male ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Plasmodium falciparum ; Malaria ; Culicidae ; Biology ; Malaria, Falciparum/parasitology
Chemical Substances	Antimalarials
Language	English
Publishing date	2023-10-06
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011711
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