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2. Smartphone-Supported Malaria Diagnosis Based on Deep Learning

Author

Yang, Feng, Yu, Hang, Silamut, Kamolrat, Maude, Richard J., Jaeger, Stefan, Antani, Sameer, Goos, Gerhard, Founding Editor, Hartmanis, Juris, Founding Editor, Bertino, Elisa, Editorial Board Member, Gao, Wen, Editorial Board Member, Steffen, Bernhard, Editorial Board Member, Woeginger, Gerhard, Editorial Board Member, Yung, Moti, Editorial Board Member, Suk, Heung-Il, editor, Liu, Mingxia, editor, Yan, Pingkun, editor, and Lian, Chunfeng, editor

Published
2019
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3. Acetaminophen as a Renoprotective Adjunctive Treatment in Patients With Severe and Moderately Severe Falciparum Malaria : A Randomized, Controlled, Open-Label Trial

Author

Plewes, Katherine, Kingston, Hugh W. F., Ghose, Aniruddha, Wattanakul, Thanaporn, Hassan, Md. Mahtab Uddin, Haider, Md. Shafiul, Dutta, Prodip K., Islam, Md. Akhterul, Alam, Shamsul, Jahangir, Selim Md., Zahed, A. S. M., Sattar, Md. Abdus, Chowdhury, M. A. Hassan, Herdman, M. Trent, Leopold, Stije J., Ishioka, Haruhiko, Piera, Kim A., Charunwatthana, Prakaykaew, Silamut, Kamolrat, Yeo, Tsin W., Lee, Sue J., Mukaka, Mavuto, Maude, Richard J., Turner, Gareth D. H., Faiz, Md. Abul, Tarning, Joel, Oates, John A., Anstey, Nicholas M., White, Nicholas J., Day, Nicholas P. J., Hossain, Md. Amir, Roberts, L. Jackson, and Dondorp, Arjen M.

Published
2018

8. Randomized Controlled Trial of Levamisole Hydrochloride as Adjunctive Therapy in Severe Falciparum Malaria With High Parasitemia

Author

Maude, Richard J., Silamut, Kamolrat, Plewes, Katherine, Charunwatthana, Prakaykaew, Ho, May, Faiz, M. Abul, Rahman, Ridwanur, Hossain, Md Amir, Hassan, Mahtab U., Yunus, Emran Bin, Hoque, Gofranul, Islam, Faridul, Ghose, Aniruddha, Hanson, Josh, Schlatter, Joel, Lacey, Rachel, Eastaugh, Alison, Taming, Joel, Lee, Sue J., White, Nicholas J., Chotivanich, Kesinee, Day, Nicholas P. J., and Dondorp, Arjen M.

Published
2014

9. Defining Falciparum-Malaria-Attributable Severe Febrile Illness in Moderate-to-High Transmission Settings on the Basis of Plasma PfHRP2 Concentration

Author

Hendriksen, Ilse C. E., White, Lisa J., Veenemans, Jacobien, Mtove, George, Woodrow, Charles, Amos, Ben, Saiwaew, Somporn, Gesase, Samwel, Nadjm, Behzad, Silamut, Kamolrat, Joseph, Sarah, Chotivanich, Kesinee, Day, Nicholas P. J., von Seidlein, Lorenz, Verhoef, Hans, Reyburn, Hugh, White, Nicholas J., and Dondorp, Arjen M.

Published
2013
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11. Predicting the Clinical Outcome of Severe Falciparum Malaria in African Children: Findings From a Large Randomized Trial

Author

von Seidlein, Lorenz, Olaosebikan, Rasaq, Hendriksen, Ilse C. E., Lee, Sue J., Adedoyin, Olanrewaju Timothy, Agbenyega, Tsiri, Nguah, Samuel Blay, Bojang, Kalifa, Deen, Jacqueline L., Evans, Jennifer, Fanello, Caterina I., Gomes, Ermelinda, Pedro, Alínia José, Kahabuka, Catherine, Karema, Corine, Kivaya, Esther, Maitland, Kathryn, Mokuolu, Olugbenga A., Mtove, George, Mwanga-Amumpaire, Juliet, Nadjm, Behzad, Nansumba, Margaret, Ngum, Wirichada Pan, Onyamboko, Marie A., Reyburn, Hugh, Sakulthaew, Tharisara, Silamut, Kamolrat, Tshefu, Antoinette K., Umulisa, Noella, Gesase, Samwel, Day, Nicholas P. J., White, Nicholas J., and Dondorp, Arjen M.

Published
2012
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16. Artesunate versus quinine in the treatment of severe falciparum malaria in African children (AQUAMAT): an open-label, randomised trial

Author

Dondorp, Arjen M, Fanello, Caterina I, Hendriksen, Ilse CE, Gomes, Ermelinda, Seni, Amir, Chhaganlal, Kajal D, Bojang, Kalifa, Olaosebikan, Rasaq, Anunobi, Nkechinyere, Maitland, Kathryn, Kivaya, Esther, Agbenyega, Tsiri, Nguah, Samuel Blay, Evans, Jennifer, Gesase, Samwel, Kahabuka, Catherine, Mtove, George, Nadjm, Behzad, Deen, Jacqueline, Mwanga-Amumpaire, Juliet, Nansumba, Margaret, Karema, Corine, Umulisa, Noella, Uwimana, Aline, Mokuolu, Olugbenga A, Adedoyin, Olanrewaju T, Johnson, Wahab BR, Tshefu, Antoinette K, Onyamboko, Marie A, Sakulthaew, Tharisara, Ngum, Wirichada Pan, Silamut, Kamolrat, Stepniewska, Kasia, Woodrow, Charles J, Bethell, Delia, Wills, Bridget, Oneko, Martina, Peto, Tim E, von Seidlein, Lorenz, Day, Nicholas PJ, and White, Nicholas J

Published
2010
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17. The prognostic and diagnostic value of intraleukocytic malaria pigment: an individual patient data pooled meta-analysis of 32,000 patients with severe falciparum malaria in Africa and Asia

Author

Srinamon, Ketsanee, primary, Watson, James A, additional, Silamut, Kamolrat, additional, Intharabut, Benjamas, additional, Phu, Nguyen Hoan, additional, Diep, Pham Thi, additional, Lyke, Kirsten E, additional, Fanello, Caterina, additional, Seidlein, Lorenz von, additional, Chotivanich, Kesinee, additional, Dondorp, Arjen M, additional, Day, Nicholas PJ, additional, and White, Nicholas J, additional

Published
2021
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18. Spread of Artemisinin Resistance in Plasmodium falciparum Malaria

Author

Ashley, Elizabeth A., Dhorda, Mehul, Fairhurst, Rick M., Amaratunga, Chanaki, Lim, Parath, Suon, Seila, Sreng, Sokunthea, Anderson, Jennifer M., Mao, Sivanna, Sam, Baramey, Sopha, Chantha, Chuor, Char Meng, Nguon, Chea, Sovannaroth, Siv, Pukrittayakamee, Sasithon, Jittamala, Podjanee, Chotivanich, Kesinee, Chutasmit, Kitipumi, Suchatsoonthorn, Chaiyaporn, Runcharoen, Ratchadaporn, Hien, Tran Tinh, Thuy-Nhien, Nguyen Thanh, Thanh, Ngo Viet, Phu, Nguyen Hoan, Htut, Ye, Han, Kay-Thwe, Aye, Kyin Hla, Mokuolu, Olugbenga A., Olaosebikan, Rasaq R., Folaranmi, Olaleke O., Mayxay, Mayfong, Khanthavong, Maniphone, Hongvanthong, Bouasy, Newton, Paul N., Onyamboko, Marie A., Fanello, Caterina I., Tshefu, Antoinette K., Mishra, Neelima, Valecha, Neena, Phyo, Aung Pyae, Nosten, Francois, Yi, Poravuth, Tripura, Rupam, Borrmann, Steffen, Bashraheil, Mahfudh, Peshu, Judy, Faiz, M. Abul, Ghose, Aniruddha, Hossain, M. Amir, Samad, Rasheda, Rahman, M. Ridwanur, Hasan, M. Mahtabuddin, Islam, Akhterul, Miotto, Olivo, Amato, Roberto, MacInnis, Bronwyn, Stalker, Jim, Kwiatkowski, Dominic P., Bozdech, Zbynek, Jeeyapant, Atthanee, Cheah, Phaik Yeong, Sakulthaew, Tharisara, Chalk, Jeremy, Intharabut, Benjamas, Silamut, Kamolrat, Lee, Sue J., Vihokhern, Benchawan, Kunasol, Chanon, Imwong, Mallika, Tarning, Joel, Taylor, Walter J., Yeung, Shunmay, Woodrow, Charles J., Flegg, Jennifer A., Das, Debashish, Smith, Jeffery, Venkatesan, Meera, Plowe, Christopher V., Stepniewska, Kasia, Guerin, Philippe J., Dondorp, Arjen M., Day, Nicholas P., and White, Nicholas J.

Published
2014
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19. The role of previously unmeasured organic acids in the pathogenesis of severe malaria

Author

Herdman, M. Trent, Sriboonvorakul, Natthida, Leopold, Stije J., Douthwaite, Sam, Mohanty, Sanjib, Hassan, M. Mahtab Uddin, Maude, Richard J., Kingston, Hugh WF, Plewes, Katherine, Charunwatthana, Prakaykaew, Silamut, Kamolrat, Woodrow, Charles J., Chotinavich, Kesinee, Hossain, Md. Amir, Faiz, M. Abul, Mishra, Saroj, Leepipatpiboon, Natchanun, White, Nicholas J., Day, Nicholas PJ, Tarning, Joel, and Dondorp, Arjen M.

Published
2015
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20. Erratum to: the role of previously unmeasured organic acids in the pathogenesis of severe malaria

Author

Herdman, M. Trent, Sriboonvorakul, Natthida, Leopold, Stije J., Douthwaite, Sam, Mohanty, Sanjib, Hassan, M. Mahtab Uddin, Maude, Richard J., Kingston, Hugh W. F., Plewes, Katherine, Charunwatthana, Prakaykaew, Silamut, Kamolrat, Woodrow, Charles J., Ghose, Aniruddha, Chotinavich, Kesinee, Hossain, Md Amir, Faiz, M. Abul, Mishra, Saroj, Leepipatpiboon, Natchanun, White, Nicholas J., Day, Nicholas P. J., Tarning, Joel, and Dondorp, Arjen M.

Published
2015
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21. Artemisinin resistance in Plasmodium falciparum malaria

Author

Dondorp, Arjen M., Nosten, Francois, Yi, Porvuth, Das, Debashish, Phyo, Aung Phae, Tarning, Joel, Lwin, Khin Maung, Ariey, Frederic, Hanpithakpong, Warunee, Lee, Sue J., Ringwald, Pascal, Silamut, Kamolrat, Imwong, Mallika, chotivanich, Kesinee, Lim, Pharath, Herdman, Trent, An, Sen Sam, Yeung, Shunmay, Singhasivanon, Pratap, Day, Nicholas, P.J., Lindegardh, Niklas, Socheat, Duong, and White, Nicholas J.

Subjects
Drug resistance -- Research, Malaria -- Drug therapy, Mefloquine -- Dosage and administration, Antimalarials -- Health aspects, Drug therapy, Combination
Abstract

A study was conducted to ascertain the efficacy of artemisinin -based combination therapies as a main treatment for Plasmodium falciparum malaria following reports of declined efficacy of this drug along the Thai-Cambodian border. Results revealed that P. falciparum manifests reduced susceptibility in vivo to artesunate in western Cambodia compared to northwestern Thailand and urgent measures should be taken to address the problem.

Published
2009

22. Towards harmonization of microscopy methods for malaria clinical research studies

Author

Dhorda, Mehul, Ba, El Hadji, Kevin Baird, J., Barnwell, John, Bell, David, Carter, Jane Y., Dondorp, Arjen, Ekawati, Lenny, Gatton, Michelle, González, Iveth, Guérin, Philippe J., Incardona, Sandra, Lilley, Ken, Menard, Didier, Nosten, François, Obare, Peter, Ogutu, Bernhards, Olliaro, Piero L., Price, Ric N., Proux, Stéphane, Ramsay, Andrew R., Reeder, John C., Silamut, Kamolrat, Sokhna, Cheikh, Dhorda, Mehul, Ba, El Hadji, Kevin Baird, J., Barnwell, John, Bell, David, Carter, Jane Y., Dondorp, Arjen, Ekawati, Lenny, Gatton, Michelle, González, Iveth, Guérin, Philippe J., Incardona, Sandra, Lilley, Ken, Menard, Didier, Nosten, François, Obare, Peter, Ogutu, Bernhards, Olliaro, Piero L., Price, Ric N., Proux, Stéphane, Ramsay, Andrew R., Reeder, John C., Silamut, Kamolrat, and Sokhna, Cheikh

Abstract

Microscopy performed on stained films of peripheral blood for detection, identification and quantification of malaria parasites is an essential reference standard for clinical trials of drugs, vaccines and diagnostic tests for malaria. The value of data from such research is greatly enhanced if this reference standard is consistent across time and geography. Adherence to common standards and practices is a prerequisite to achieve this. The rationale for proposed research standards and procedures for the preparation, staining and microscopic examination of blood films for malaria parasites is presented here with the aim of improving the consistency and reliability of malaria microscopy performed in such studies. These standards constitute the core of a quality management system for clinical research studies employing microscopy as a reference standard. They can be used as the basis for the design of training and proficiency testing programmes as well as for procedures and quality assurance of malaria microscopy in clinical research.

Published
2020

27. Defining the in vivo phenotype of artemisinin-resistant falciparum malaria: a modelling approach

Author

White, Lisa J., Flegg, Jennifer A., Phyo, Aung Pyae, Wiladpai-Ngern, Ja Hser, Bethell, Delia, Plowe, Christopher, Anderson, Tim, Nkhoma, Standwell, Nair, Shalini, Tripura, Rupam, Stepniewska, Kasia, Pan-Ngum, Wirichada, Silamut, Kamolrat, Cooper, Ben S., Lubell, Yoel, Ashley, Elizabeth A., Nguon, Chea, Nosten, Francois, White, Nicholas J., and Dondorp, Arjen M.

Subjects
Drug resistance in microorganisms -- Genetic aspects, Phenotype -- Identification and classification, Plasmodium falciparum -- Genetic aspects -- Health aspects, Biological sciences
Abstract

Background Artemisinin-resistant falciparum malaria has emerged in Southeast Asia, posing a major threat to malaria control. It is characterised by delayed asexual-stage parasite clearance, which is the reference comparator for the molecular marker 'Kelch 13' and in vitro sensitivity tests. However, current cut-off values denoting slow clearance based on the proportion of individuals remaining parasitaemic on the third day of treatment ('day-3'), or on peripheral blood parasite half-life, are not well supported. We here explore the parasite clearance distributions in an area of artemisinin resistance with the aim refining the in vivo phenotypic definitions. Methods and Findings Data from 1,518 patients on the Thai-Myanmar and Thai-Cambodian borders with parasite half-life assessments after artesunate treatment were analysed. Half-lives followed a bimodal distribution. A statistical approach was developed to infer the characteristics of the component distributions and their relative contribution to the composite mixture. A model representing two parasite subpopulations with geometric mean (IQR) parasite half-lives of 3.0 (2.4-3.9) hours and 6.50 (5.7-7.4) hours was consistent with the data. For individual patients, the parasite half-life provided a predicted likelihood of an artemisinin-resistant infection which depends on the population prevalence of resistance in that area. Consequently, a half-life where the probability is 0.5 varied between 3.5 and 5.5 hours. Using this model, the current 'day-3' cut-off value of 10% predicts the potential presence of artemisinin-resistant infections in most but not all scenarios. These findings are relevant to the low-transmission setting of Southeast Asia. Generalisation to a high transmission setting as in regions of Sub-Saharan Africa will need additional evaluation. Conclusions Characterisation of overlapping distributions of parasite half-lives provides quantitative insight into the relationship between parasite clearance and artemisinin resistance, as well as the predictive value of the 10% cut-off in 'day-3' parasitaemia. The findings are important for the interpretation of in vitro sensitivity tests and molecular markers for artemisinin resistance and for contextualising the 'day 3' threshold to account for initial parasitaemia and sample size., Introduction Artemisinin combination therapies (ACTs) are currently the cornerstone of antimalarial treatment of uncomplicated falciparum malaria throughout the tropical world. There are no new antimalarial drugs of equivalent efficacy available [...]

Published
2015
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28. Sequence variation does not confound the measurement of plasma PfHRP2 concentration in African children presenting with severe malaria

Author

Ramutton Thiranut, Hendriksen Ilse CE, Mwanga-Amumpaire Juliet, Mtove George, Olaosebikan Rasaq, Tshefu Antoinette K, Onyamboko Marie A, Karema Corine, Maitland Kathryn, Gomes Ermelinda, Gesase Samwel, Reyburn Hugh, Silamut Kamolrat, Chotivanich Kesinee, Promnares Kamoltip, Fanello Caterina I, von Seidlein Lorenz, Day Nicholas PJ, White Nicholas J, Dondorp Arjen M, Imwong Mallika, and Woodrow Charles J

Subjects
Malaria, Falciparum, Severe, Africa, Histidine-rich protein, Tandem repeat, Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Plasmodium falciparum histidine-rich protein PFHRP2 measurement is used widely for diagnosis, and more recently for severity assessment in falciparum malaria. The Pfhrp2 gene is highly polymorphic, with deletion of the entire gene reported in both laboratory and field isolates. These issues potentially confound the interpretation of PFHRP2 measurements. Methods Studies designed to detect deletion of Pfhrp2 and its paralog Pfhrp3 were undertaken with samples from patients in seven countries contributing to the largest hospital-based severe malaria trial (AQUAMAT). The quantitative relationship between sequence polymorphism and PFHRP2 plasma concentration was examined in samples from selected sites in Mozambique and Tanzania. Results There was no evidence for deletion of either Pfhrp2 or Pfhrp3 in the 77 samples with lowest PFHRP2 plasma concentrations across the seven countries. Pfhrp2 sequence diversity was very high with no haplotypes shared among 66 samples sequenced. There was no correlation between Pfhrp2 sequence length or repeat type and PFHRP2 plasma concentration. Conclusions These findings indicate that sequence polymorphism is not a significant cause of variation in PFHRP2 concentration in plasma samples from African children. This justifies the further development of plasma PFHRP2 concentration as a method for assessing African children who may have severe falciparum malaria. The data also add to the existing evidence base supporting the use of rapid diagnostic tests based on PFHRP2 detection.

Published
2012
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30. Clinically uncomplicated Plasmodium falciparum malaria with high schizontaemia: A case report

Author

Ashley Elizabeth A, Lwin Khin, Proux Stephane, Silamut Kamolrat, Nosten François, and McGready Rose

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background The treatment options for acute Plasmodium falciparum malaria are based on the clinician classifying the patient as uncomplicated or severe according to the clinical and parasitological findings. This process is not always straightforward. Case presentation An adult male presented to a clinic on the western border of Thailand with a physical examination and P. falciparum trophozoite count (1.2% of infected red blood cells, IRBC) from malaria blood smear, consistent with a diagnosis of uncomplicated P. falciparum infection. However, the physician on duty treated the patient for severe malaria based on the reported P. falciparum schizont count, which was very high (0.3% IRBC), noticeably in relation to the trophozoite count and schizont:trophozoite ratio 0.25:1. On intravenous artesunate, the patient deteriorated clinically in the first 24 hours. The trophozoite count increased from 1.2% IRBC at baseline to 20.5% IRBC 18 hours following the start of treatment. By day three, the patient recovered and was discharged on day seven having completed a seven-day treatment with artesunate and mefloquine. Conclusion The malaria blood smear provides only a guide to the overall parasite biomass in the body, due to the ability of P. falciparum to sequester in the microvasculature. In severe malaria, high schizont counts are associated with worse prognosis. In low transmission areas or in non-immune travelers the presence of schizonts in the peripheral circulation is an indication for close patient supervision. In this case, an unusually high schizont count in a clinically uncomplicated patient was indicative of potential deterioration. Prompt treatment with intravenous artesunate is likely to have been responsible for the good clinical outcome in this case.

Published
2008
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39. Inhibition of merozoite invasion and transient de-sequestration by sevuparin in humans with Plasmodium falciparum malaria

Author

Leitgeb, Anna M., primary, Charunwatthana, Prakaykaew, additional, Rueangveerayut, Ronnatrai, additional, Uthaisin, Chirapong, additional, Silamut, Kamolrat, additional, Chotivanich, Kesinee, additional, Sila, Patima, additional, Moll, Kirsten, additional, Lee, Sue J., additional, Lindgren, Maria, additional, Holmer, Erik, additional, Färnert, Anna, additional, Kiwuwa, Mpungu S., additional, Kristensen, Jens, additional, Herder, Christina, additional, Tarning, Joel, additional, Wahlgren, Mats, additional, and Dondorp, Arjen M., additional

Published
2017
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41. Cell-free hemoglobin mediated oxidative stress is associated with acute kidney injury and renal replacement therapy in severe falciparum malaria: an observational study

Author

Plewes, Katherine, primary, Kingston, Hugh W.F., additional, Ghose, Aniruddha, additional, Maude, Richard J., additional, Herdman, M. Trent, additional, Leopold, Stije J., additional, Ishioka, Haruhiko, additional, Hasan, Md. Mahtab Uddin, additional, Haider, Md. Shafiul, additional, Alam, Shamsul, additional, Piera, Kim A., additional, Charunwatthana, Prakaykaew, additional, Silamut, Kamolrat, additional, Yeo, Tsin W., additional, Faiz, Md. Abul, additional, Lee, Sue J, additional, Mukaka, Mavuto, additional, Turner, Gareth D.H., additional, Anstey, Nicholas M., additional, Jackson Roberts, L., additional, White, Nicholas J., additional, Day, Nicholas P.J., additional, Hossain, Md. Amir, additional, and Dondorp, Arjen M., additional

Published
2017
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44. Artemisinin Resistance and Stage Dependency of Parasite Clearance in Falciparum Malaria.

Author

Intharabut, Benjamas, Kingston, Hugh W, Srinamon, Ketsanee, Ashley, Elizabeth A, Imwong, Mallika, Dhorda, Mehul, Woodrow, Charles, Stepniewska, Kasia, Silamut, Kamolrat, Day, Nicholas P J, Dondorp, Arjen M, White, Nicholas J, and Tracking Resistance to Artemisinin Collaboration

Subjects
ARTEMISININ, MALARIA, BLOOD parasites, DEVELOPMENTAL biology, PARASITES, DRUG therapy for malaria, ANTIMALARIALS, COMBINATION drug therapy, COMPARATIVE studies, DRUG resistance, HUMAN life cycle, RESEARCH methodology, MEDICAL cooperation, GENETIC mutation, PROTEINS, PROTOZOA, RESEARCH, RESEARCH funding, EVALUATION research, PARASITEMIA, GENOTYPES, PHARMACODYNAMICS
Abstract

Background: Artemisinin resistance in falciparum malaria is associated with kelch13 propeller mutations, reduced ring stage parasite killing, and, consequently, slow parasite clearance. We assessed how parasite age affects parasite clearance in artemisinin resistance.Methods: Developmental stages of Plasmodium falciparum parasites on blood films performed at hospital admission and their kelch13 genotypes were assessed for 816 patients enrolled in a multinational clinical trial of artemisinin combination therapy.Results: Early changes in parasitemia level (ie, 0-6 hours after admission) were determined mainly by modal stage of asexual parasite development, whereas the subsequent log-linear decline was determined mainly by kelch13 propeller mutations. Older circulating parasites on admission were associated with more-rapid parasite clearance, particularly in kelch13 mutant infections. The geometric mean parasite clearance half-life decreased by 11.6% (95% CI 3.4%-19.1%) in kelch13 wild-type infections and by 30% (95% CI 17.8%-40.4%) in kelch13 mutant infections as the mean age of circulating parasites rose from 3 to 21 hours.Conclusion: Following the start of antimalarial treatment, ongoing parasite sequestration and schizogony both affect initial changes in parasitemia. The greater dependency of parasite clearance half-life on parasite age in artemisinin resistant infections is consistent with ring stage resistance and consequent parasite clearance by sequestration. The stage of parasite development should be incorporated in individual assessments of artemisinin resistance. [ABSTRACT FROM AUTHOR]

Published
2019
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45. CNN-based image analysis for malaria diagnosis

Author

Liang, Zhaohui, primary, Powell, Andrew, additional, Ersoy, Ilker, additional, Poostchi, Mahdieh, additional, Silamut, Kamolrat, additional, Palaniappan, Kannappan, additional, Guo, Peng, additional, Hossain, Md Amir, additional, Sameer, Antani, additional, Maude, Richard James, additional, Huang, Jimmy Xiangji, additional, Jaeger, Stefan, additional, and Thoma, George, additional

Published
2016
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46. Pharmacokinetic properties of intramuscular versus oral syrup paracetamol in Plasmodium falciparum malaria

Author

Wattanakul, Thanaporn, primary, Teerapong, Pramote, additional, Plewes, Katherine, additional, Newton, Paul N., additional, Chierakul, Wirongrong, additional, Silamut, Kamolrat, additional, Chotivanich, Kesinee, additional, Ruengweerayut, Ronnatrai, additional, White, Nicholas J., additional, Dondorp, Arjen M., additional, and Tarning, Joel, additional

Published
2016
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47. The role of previously unmeasured organic acids in the pathogenesis of severe malaria

Author

Herdman, M. Trend, Sriboonvorakul, Natthida, Leopold, Stije J., Douthwaite, Sam, Mohanty, Sanjib, Hassan, M. Mahtab Uddin, Maude, Richard J., Kingston, Hugh W. F., Plewes, Katherine, Charunwatthana, Prakaykaew, Silamut, Kamolrat, Woodrow, Charles J., Chotinavich, Kesinee, Hossain, Md. Amir, Faiz, M. Abdul, Mishra, Saroj, White, Nicholas J., Day, Nicholas P. J., Dondorp, Arjen M., et al., Herdman, M. Trend, Sriboonvorakul, Natthida, Leopold, Stije J., Douthwaite, Sam, Mohanty, Sanjib, Hassan, M. Mahtab Uddin, Maude, Richard J., Kingston, Hugh W. F., Plewes, Katherine, Charunwatthana, Prakaykaew, Silamut, Kamolrat, Woodrow, Charles J., Chotinavich, Kesinee, Hossain, Md. Amir, Faiz, M. Abdul, Mishra, Saroj, White, Nicholas J., Day, Nicholas P. J., Dondorp, Arjen M., and et al.

Abstract

IntroductionSevere falciparum malaria is commonly complicated by metabolic acidosis. Together with lactic acid (LA), other previously unmeasured acids have been implicated in the pathogenesis of falciparum malaria.MethodsIn this prospective study, we characterised organic acids in adults with severe falciparum malaria in India and Bangladesh. Liquid chromatography-mass spectrometry was used to measure organic acids in plasma and urine. Patients were followed until recovery or death.ResultsPatients with severe malaria (n=138), uncomplicated malaria (n=102), sepsis (n=32) and febrile encephalopathy (n=35) were included. Strong ion gap (mean±SD) was elevated in severe malaria (8.2 mEq/L±4.5) and severe sepsis (8.6 mEq/L±7.7) compared with uncomplicated malaria (6.0 mEq/L±5.1) and encephalopathy (6.6 mEq/L±4.7). Compared with uncomplicated malaria, severe malaria was characterised by elevated plasma LA, hydroxyphenyllactic acid (HPLA), α-hydroxybutyric acid and β-hydroxybutyric acid (all P<0.05). In urine, concentrations of methylmalonic, ethylmalonic and α-ketoglutaric acids were also elevated. Multivariate logistic regression showed that plasma HPLA was a strong independent predictor of death (odds ratio [OR] 3.5, 95 % confidence interval [CI] 1.6–7.5, P=0.001), comparable to LA (OR 3.5, 95 % CI 1.5–7.8, P=0.003) (combined area under the receiver operating characteristic curve 0.81).ConclusionsNewly identified acids, in addition to LA, are elevated in patients with severe malaria and are highly predictive of fatal outcome. Further characterisation of their sources and metabolic pathways is now needed.

Published
2015

48. Magnetic resonance imaging of the brain in adults with severe falciparum malaria

Author

Maude, Richard J., Barkhof, Frederik, Hassan, Mahtab, Ghose, Aniruddha, Hossain, Amir, Faiz, M. Abul, Choudhury, Ehsan, Rashid, Rehnuma, Sayeed, Abdullah, Charunwatthana, Prakaykaew, Plewes, Katherine, Kingston, Hugh W. F., Maude, Rapeephan, Silamut, Kamolrat, Day, Nicholas P. J., White, Nicholas J., Dondorp, Arjen M., Maude, Richard J., Barkhof, Frederik, Hassan, Mahtab, Ghose, Aniruddha, Hossain, Amir, Faiz, M. Abul, Choudhury, Ehsan, Rashid, Rehnuma, Sayeed, Abdullah, Charunwatthana, Prakaykaew, Plewes, Katherine, Kingston, Hugh W. F., Maude, Rapeephan, Silamut, Kamolrat, Day, Nicholas P. J., White, Nicholas J., and Dondorp, Arjen M.

Abstract

Background: Magnetic resonance imaging (MRI) allows detailed study of structural and functional changes in thebrain in patients with cerebral malaria.Methods: In a prospective observational study in adult Bangladeshi patients with severe falciparum malaria, MRIfindings in the brain were correlated with clinical and laboratory parameters, retinal photography and optic nervesheath diameter (ONSD) ultrasound (a marker of intracranial pressure).Results: Of 43 enrolled patients, 31 (72%) had coma and 12 (28%) died. MRI abnormalities were present in 79%overall with mostly mild changes in a wide range of anatomical sites. There were no differences in MRI findingsbetween patients with cerebral and non-cerebral or fatal and non-fatal disease. Subtle diffuse cerebral swellingwas common (n = 22/43), but mostly without vasogenic oedema or raised intracranial pressure (ONSD). Also seenwere focal extracellular oedema (n = 11/43), cytotoxic oedema (n = 8/23) and mildly raised brain lactate on magneticresonance spectroscopy (n = 5/14). Abnormalities were much less prominent than previously described in Malawianchildren. Retinal whitening was present in 36/43 (84%) patients and was more common and severe in patientswith coma.Conclusion: Cerebral swelling is mild and not specific to coma or death in adult severe falciparum malaria. Thisdiffers markedly from African children. Retinal whitening, reflecting heterogeneous obstruction of the centralnervous system microcirculation by sequestered parasites resulting in small patches of ischemia, is associatedwith coma and this process is likely important in the pathogenesis.

Published
2014

49. Measuring Hidden Parasites in Falciparum Malaria

Author

Dondorp, Arjen M, Desakorn, Varunee, Pongtavornpinyo, Wirichada, Sahassananda, Duangjai, Silamut, Kamolrat, Chotivanich, Kesinee, Newton, Paul N, Pitisuttithum, Punnee, Smithyman, A. M, White, Nicholas J, and Day, Nicholas P. J

Subjects
Infectious Diseases, Medicine in Developing Countries, parasitic diseases, Research Article, Malaria
Abstract

Background In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2) into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria. Methods and Findings We measured plasma concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked immunosorbent assay, in 337 adult patients with falciparum malaria of varying severity hospitalised on the Thai–Burmese border. Based on in vitro production rates, we constructed a model to link this measure to the total parasite burden in the patient. The estimated geometric mean parasite burden was 7 × 1011 (95% confidence interval [CI] 5.8 × 1011 to 8.5 × 1011) parasites per body, and was over six times higher in severe malaria (geometric mean 1.7 × 1012, 95% CI 1.3 × 1012 to 2.3 × 1012) than in patients hospitalised without signs of severity (geometric mean 2.8 × 1011, 95% CI 2.3 × 1011 to 3.5 × 1011; p < 0.001). Parasite burden was highest in patients who died (geometric mean 3.4 × 1012, 95% CI 1.9 × 1012 to 6.3 × 1012; p = 0.03). The calculated number of sequestered parasites increased with disease severity and was higher in patients with late developmental stages of P. falciparum present on peripheral blood smears. Comparing model and laboratory estimates of the time of sequestration suggested that admission to hospital with uncomplicated malaria often follows schizogony—but in severe malaria is unrelated to stage of parasite development. Conclusion Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in acute falciparum malaria. Severe malaria results from extensive sequestration of parasitised erythrocytes., Measuring sequestered parasites using plasma PfHRP2 concentrations may provide a more accurate estimate of total parasite mass and hence severity in falciparum malaria.

Published
2005

50. Magnetic resonance imaging of the brain in adults with severe falciparum malaria

Author

Maude, Richard James, primary, Barkhof, Frederik, additional, Hassan, Mahtab Uddin, additional, Ghose, Aniruddha, additional, Hossain, Amir, additional, Abul Faiz, M, additional, Choudhury, Ehsan, additional, Rashid, Rehnuma, additional, Sayeed, Abdullah Abu, additional, Charunwatthana, Prakaykaew, additional, Plewes, Katherine, additional, Kingston, Hugh, additional, Maude, Rapeephan Rattanawongnara, additional, Silamut, Kamolrat, additional, Day, Nicholas Philip John, additional, White, Nicholas John, additional, and Dondorp, Arjen Mattheus, additional

Published
2014
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