High Plasma Levels of Neopterin Are Associated with Increased Mortality among Children with Severe Malaria in Benin

Author:

Blankson Samuel Odarkwei12ORCID,Rietmeyer Lauriane1ORCID,Tettey Patrick3ORCID,Dikroh Liliane3ORCID,Tornyigah Bernard13,Adamou Rafiou4ORCID,Moussiliou Azizath4ORCID,Padounou Caroline5,Amoussou Annick6,Mensah Benedicta Ayiedu3,Alao Maroufou J.7,Awandare Gordon2,Ndam Nicaise Tuikue18,Roussilhon Christian9,Tahar Rachida18

Affiliation:

1. MERIT, IRD, Université de Paris Cité, 75006 Paris, France

2. West African Centre for Cell Biology of Infectious Pathogens, Department of Biochemistry, Cell and Molecular Biology, College of Basic and Applied Sciences, University of Ghana, Accra LG 54, Ghana

3. Department of Immunology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra LG 54, Ghana

4. Institut de Recherche Clinique du Benin (IRCB), Calavi, Benin

5. Centre Hospitalier Universitaire de l’Oueme, Porto-Novo, Benin

6. Service de Pédiatrie, Centre Hospitalo-Universitaire, Suruléré (CHU-Suruléré), Cotonou, Benin

7. Département de Pédiatrie, Hôpital Mère-Enfant la Lagune (CHUMEL), Cotonou, Benin

8. Department of Parasitology, Noguchi Memorial Institute for Medical Research, University of Ghana, Accra LG 54, Ghana

9. Institut Pasteur, 28 Rue du Docteur Roux, 75015 Paris, France

Abstract

Among the barriers to accessing adequate treatment and high-level monitoring for malaria febrile patients is the lack of effective prognostic markers. Neopterin, which is a marker of monocyte/macrophage activation, was found have increased during severe malaria. In this study, we used quantitative ELISA in order to assess the levels of plasma soluble neopterin in 151 patients from a cohort of Beninese children with severe malaria. We evaluated the prognostic accuracy of this molecule in order to predict the outcome of the disease. Our results show that neopterin levels were not significantly different between patients with different forms of severe malaria, including severe non-cerebral malaria (SNCM) and cerebral malaria (CM). However, the levels of this molecule were found to be higher in patients with severe malarial anemia (SMA) among both CM and SNCM cases (p-value = 0.02). Additionally, the levels of this molecule were found to be higher in patients who died from these pathologies compared to those who survived among the two clinical groups (p-value < 0.0001) and within the same group (p-value < 0.0001 for the CM group, p-value = 0.0046 for the SNCM group). The AUC-ROC for fatality among all the severe cases was 0.77 with a 95%CI of (0.69–0.85). These results suggest that plasma neopterin levels constitute a potential biomarker for predicting fatality among severe falciparum malaria patients.

Funder

Institut Mérieux at Lyon France

Institut de Recherche pour le Développement

SCAC—Cultural and Cooperation Department—French Embassy

Scholarship Secretariat Ghana

The Danish International Development Agency

Publisher

MDPI AG

Subject

Clinical Biochemistry

Reference53 articles.

1. Neopterin in Diagnosis and Monitoring of Infectious Diseases;Eisenhut;J. Biomark.,2013

2. Neopterin levels and systemic inflammatory response syndrome in pediatric critically ill patients;Milano;An. Pediatría,2017

3. Immune response-associated production of neopterin. Release from macrophages primarily under control of interferon-gamma;Huber;J. Exp. Med.,1984

4. Neopterin as marker for activation of cellular immunity: Immunologic basis and clinical application;Wachter;Adv. Clin. Chem.,1989

5. Urinary neopterin is elevated in patients with malaria;Reibnegger;Trans. R. Soc. Trop. Med. Hyg.,1984

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