Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking
Abstract Background Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is r...
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ftdoajarticles:oai:doaj.org/article:393f1f4a94a84921a0e54bc09166e003 2023-05-15T15:16:21+02:00 Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking Ishan Wadi C. Radhakrishna Pillai Anupkumar R. Anvikar Abhinav Sinha Mahendra Nath Neena Valecha 2018-01-01T00:00:00Z https://doi.org/10.1186/s12936-017-2153-9 https://doaj.org/article/393f1f4a94a84921a0e54bc09166e003 EN eng BMC http://link.springer.com/article/10.1186/s12936-017-2153-9 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-2153-9 1475-2875 https://doaj.org/article/393f1f4a94a84921a0e54bc09166e003 Malaria Journal, Vol 17, Iss 1, Pp 1-9 (2018) Malaria Gametocytes Morphological deformations Microscopy P. falciparum Gametocytocidal activity Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2018 ftdoajarticles https://doi.org/10.1186/s12936-017-2153-9 2022-12-31T01:42:52Z Abstract Background Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients. In present work, methylene blue, which is proposed as an alternative to primaquine is investigated for its gametocytocidal activity amongst Indian field isolates. An effort has been made to establish Indian field isolates of P. falciparum as in vitro model for gametocytocidal drugs screening. Methods Plasmodium falciparum isolates were adapted to in vitro culture and induced to gametocyte production by hypoxanthine and culture was enriched for gametocyte stages using N-acetyl-glucosamine. Gametocytes were incubated with methylene blue for 48 h and stage specific gametocytocidal activity was evaluated by microscopic examination. Results Plasmodium falciparum field isolates RKL-9 and JDP-8 were able to reproducibly produce gametocytes in high yield and were used to screen gametocytocidal drugs. Methylene blue was found to target gametocytes in a concentration dependent manner by either completely eliminating gametocytes or rendering them morphologically deformed with mean IC50 (early stages) as 424.1 nM and mean IC50 (late stages) as 106.4 nM. These morphologically altered gametocytes appeared highly degenerated having shrinkage, distortions and membrane deformations. Conclusions Field isolates that produce gametocytes in high yield in vitro can be identified and used to screen gametocytocidal drugs. These isolates should be used for validation of gametocytocidal hits obtained previously by using lab adapted reference strains. Methylene blue was found to target gametocytes produced from Indian field ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Indian Malaria Journal 17 1 |
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ftdoajarticles |
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topic |
Malaria Gametocytes Morphological deformations Microscopy P. falciparum Gametocytocidal activity Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Malaria Gametocytes Morphological deformations Microscopy P. falciparum Gametocytocidal activity Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Ishan Wadi C. Radhakrishna Pillai Anupkumar R. Anvikar Abhinav Sinha Mahendra Nath Neena Valecha Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking |
topic_facet |
Malaria Gametocytes Morphological deformations Microscopy P. falciparum Gametocytocidal activity Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients. In present work, methylene blue, which is proposed as an alternative to primaquine is investigated for its gametocytocidal activity amongst Indian field isolates. An effort has been made to establish Indian field isolates of P. falciparum as in vitro model for gametocytocidal drugs screening. Methods Plasmodium falciparum isolates were adapted to in vitro culture and induced to gametocyte production by hypoxanthine and culture was enriched for gametocyte stages using N-acetyl-glucosamine. Gametocytes were incubated with methylene blue for 48 h and stage specific gametocytocidal activity was evaluated by microscopic examination. Results Plasmodium falciparum field isolates RKL-9 and JDP-8 were able to reproducibly produce gametocytes in high yield and were used to screen gametocytocidal drugs. Methylene blue was found to target gametocytes in a concentration dependent manner by either completely eliminating gametocytes or rendering them morphologically deformed with mean IC50 (early stages) as 424.1 nM and mean IC50 (late stages) as 106.4 nM. These morphologically altered gametocytes appeared highly degenerated having shrinkage, distortions and membrane deformations. Conclusions Field isolates that produce gametocytes in high yield in vitro can be identified and used to screen gametocytocidal drugs. These isolates should be used for validation of gametocytocidal hits obtained previously by using lab adapted reference strains. Methylene blue was found to target gametocytes produced from Indian field ... |
format |
Article in Journal/Newspaper |
author |
Ishan Wadi C. Radhakrishna Pillai Anupkumar R. Anvikar Abhinav Sinha Mahendra Nath Neena Valecha |
author_facet |
Ishan Wadi C. Radhakrishna Pillai Anupkumar R. Anvikar Abhinav Sinha Mahendra Nath Neena Valecha |
author_sort |
Ishan Wadi |
title |
Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking |
title_short |
Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking |
title_full |
Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking |
title_fullStr |
Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking |
title_full_unstemmed |
Methylene blue induced morphological deformations in Plasmodium falciparum gametocytes: implications for transmission-blocking |
title_sort |
methylene blue induced morphological deformations in plasmodium falciparum gametocytes: implications for transmission-blocking |
publisher |
BMC |
publishDate |
2018 |
url |
https://doi.org/10.1186/s12936-017-2153-9 https://doaj.org/article/393f1f4a94a84921a0e54bc09166e003 |
geographic |
Arctic Indian |
geographic_facet |
Arctic Indian |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 17, Iss 1, Pp 1-9 (2018) |
op_relation |
http://link.springer.com/article/10.1186/s12936-017-2153-9 https://doaj.org/toc/1475-2875 doi:10.1186/s12936-017-2153-9 1475-2875 https://doaj.org/article/393f1f4a94a84921a0e54bc09166e003 |
op_doi |
https://doi.org/10.1186/s12936-017-2153-9 |
container_title |
Malaria Journal |
container_volume |
17 |
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1 |
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1766346640197681152 |