Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity

Abstract Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and demographic contexts. This systematic review and meta-analysis aimed to consolidate existing data regarding the association bet...

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Main Authors: Manas Kotepui, Aongart Mahittikorn, Polrat Wilairatana, Frederick Ramirez Masangkay, Kinley Wangdi, Kwuntida Uthaisar Kotepui
Format: Article
Language:English
Published: Nature Portfolio 2024-02-01
Series:Scientific Reports
Subjects:
Online Access:https://doi.org/10.1038/s41598-024-53741-6
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author Manas Kotepui
Aongart Mahittikorn
Polrat Wilairatana
Frederick Ramirez Masangkay
Kinley Wangdi
Kwuntida Uthaisar Kotepui
author_facet Manas Kotepui
Aongart Mahittikorn
Polrat Wilairatana
Frederick Ramirez Masangkay
Kinley Wangdi
Kwuntida Uthaisar Kotepui
author_sort Manas Kotepui
collection DOAJ
description Abstract Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and demographic contexts. This systematic review and meta-analysis aimed to consolidate existing data regarding the association between Plasmodium infections and alterations in methemoglobin levels related to the severity of the infection. A comprehensive literature search of several databases, including Ovid, ProQuest, Embase, Scopus, MEDLINE, and PubMed, was conducted to identify relevant studies that examined methemoglobin levels in patients with malaria. Qualitative synthesis and meta-analysis of the pooled standardized mean difference were conducted to synthesize the differences in methemoglobin levels between: (1) patients with malaria and those without malaria and (2) patients with severe malaria and those with uncomplicated malaria based on various themes including publication year, study design, study area, Plasmodium species, age group, symptomatic status, severity status, and method of malaria detection. Of the 1846 studies that were initially identified from the main databases and additional searches on Google Scholar, 10 studies met the eligibility criteria and were selected for this review. The systematic review distinctly highlighted an association between malaria and elevated methemoglobin levels, an observation consistent across diverse geographical regions and various Plasmodium species. Furthermore, the meta-analysis confirmed this by demonstrating increased methemoglobin levels in patients with malaria compared to those without malaria (P < 0.001, Hedges’ g 2.32, 95% CI 1.36–3.29, I 2 97.27, 8 studies). Moreover, the meta-analysis found elevated methemoglobin levels in patients with severe malaria compared to those with uncomplicated malaria (P < 0.001, Hedges’ g 2.20, 95% CI 0.82–3.58, I 2 96.20, 5 studies). This systematic review and meta-analysis revealed increased methemoglobin levels in patients with P. falciparum and P. vivax infections, with a notable association between elevated methemoglobin levels and severe malaria. Future research should focus on elucidating the specific mechanisms by which changes in methemoglobin levels are related to infections by P. falciparum and P. vivax, particularly in terms of severity, and how these alterations could potentially impact patient management and treatment outcomes.
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spelling doaj.art-2885e9d5b30a4782b342c8b8b6ccf8962024-03-05T18:46:09ZengNature PortfolioScientific Reports2045-23222024-02-0114111210.1038/s41598-024-53741-6Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severityManas Kotepui0Aongart Mahittikorn1Polrat Wilairatana2Frederick Ramirez Masangkay3Kinley Wangdi4Kwuntida Uthaisar Kotepui5Medical Technology, School of Allied Health Sciences, Walailak UniversityDepartment of Protozoology, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Clinical Tropical Medicine, Faculty of Tropical Medicine, Mahidol UniversityDepartment of Medical Technology, Faculty of Pharmacy, University of Santo TomasQIMR Medical Research InstituteMedical Technology, School of Allied Health Sciences, Walailak UniversityAbstract Reports indicate that Plasmodium infections influence methemoglobin levels. However, findings have been inconclusive or have varied across different geographic and demographic contexts. This systematic review and meta-analysis aimed to consolidate existing data regarding the association between Plasmodium infections and alterations in methemoglobin levels related to the severity of the infection. A comprehensive literature search of several databases, including Ovid, ProQuest, Embase, Scopus, MEDLINE, and PubMed, was conducted to identify relevant studies that examined methemoglobin levels in patients with malaria. Qualitative synthesis and meta-analysis of the pooled standardized mean difference were conducted to synthesize the differences in methemoglobin levels between: (1) patients with malaria and those without malaria and (2) patients with severe malaria and those with uncomplicated malaria based on various themes including publication year, study design, study area, Plasmodium species, age group, symptomatic status, severity status, and method of malaria detection. Of the 1846 studies that were initially identified from the main databases and additional searches on Google Scholar, 10 studies met the eligibility criteria and were selected for this review. The systematic review distinctly highlighted an association between malaria and elevated methemoglobin levels, an observation consistent across diverse geographical regions and various Plasmodium species. Furthermore, the meta-analysis confirmed this by demonstrating increased methemoglobin levels in patients with malaria compared to those without malaria (P < 0.001, Hedges’ g 2.32, 95% CI 1.36–3.29, I 2 97.27, 8 studies). Moreover, the meta-analysis found elevated methemoglobin levels in patients with severe malaria compared to those with uncomplicated malaria (P < 0.001, Hedges’ g 2.20, 95% CI 0.82–3.58, I 2 96.20, 5 studies). This systematic review and meta-analysis revealed increased methemoglobin levels in patients with P. falciparum and P. vivax infections, with a notable association between elevated methemoglobin levels and severe malaria. Future research should focus on elucidating the specific mechanisms by which changes in methemoglobin levels are related to infections by P. falciparum and P. vivax, particularly in terms of severity, and how these alterations could potentially impact patient management and treatment outcomes.https://doi.org/10.1038/s41598-024-53741-6Oxidized hemoglobinMethemoglobinMalariaPlasmodiumMeta-analysis
spellingShingle Manas Kotepui
Aongart Mahittikorn
Polrat Wilairatana
Frederick Ramirez Masangkay
Kinley Wangdi
Kwuntida Uthaisar Kotepui
Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity
Scientific Reports
Oxidized hemoglobin
Methemoglobin
Malaria
Plasmodium
Meta-analysis
title Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity
title_full Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity
title_fullStr Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity
title_full_unstemmed Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity
title_short Methemoglobin levels in malaria: a systematic review and meta-analysis of its association with Plasmodium falciparum and Plasmodium vivax infections and disease severity
title_sort methemoglobin levels in malaria a systematic review and meta analysis of its association with plasmodium falciparum and plasmodium vivax infections and disease severity
topic Oxidized hemoglobin
Methemoglobin
Malaria
Plasmodium
Meta-analysis
url https://doi.org/10.1038/s41598-024-53741-6
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