Plasmodium vivax severe malaria case in a children patient in Saint- Louis, Senegal

Plasmodium vivax severe malaria case in a children patient in Saint- Louis, Senegal | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Plasmodium vivax severe malaria case in a children patient in Saint- Louis, Senegal Doudou Sow, Aminata Sall, Aminata Lo, Demba Makalou, Sara Lodholz, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3825024/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Infections caused by Plasmodium vivax are underestimated in Sub-Saharan Africa. Several cases have been reported in recent years including in Duffy-negative individuals. Most of the cases are uncomplicated, however severe infections can occur with sometimes poor outcomes. Here, we report the first case of Plasmodium vivax severe infection reported in the north of Senegal. Case presentation: MDD, 12 years old female patient aged has been received at the hospital for fever, abdominal pain and vomiting. The physical examination has revealed a jaundice and a hepatomegaly. The ultrasound exam has confirmed a hepatomegaly and splenomegaly. The biological examination has revealed a severe anemia (Hb=5.5 g/dl), a low level of platelets (92 10 3 /mm 3 ). The thick and thin blood film yielded negative result at the admission. However, 10 days after hospitalization, the microscopic parasitological examination yielded for the first-time positive result for Plasmodium with parasite density at 660 trophozoites/mL. The medical staff has retained the diagnosis of severe malaria and started the treatment with artesunate. The control of the Giemsa-stained blood smear done several days after was still positive. A first real time PCR has revealed the diagnosis of Plasmodium vivax and the primaquine has been added to the treatment. The case was confirmed by a sequencing method which has revealed three single nucleotide polymorphisms (SNPs). Among these SNPs, two have never been described before. Conclusion: This report has shown the presence of Plasmodium vivax in the north of Senegal which shared a border with Mauritania, an endemic Plasmodium vivax setting. Suggesting a need to improve the surveillance of this pathogen in Senegal and surrounding regions. Plasmodium vivax Severe malaria Children New Single Nucleotide Polymorphism Figures Figure 1 Figure 2 Background Every year, malaria kills nearly 600,000 people, mainly children in sub-Saharan Africa. ( 1 ). Plasmodium (P.) falciparum remains the most important species and is responsible of a high number of severe cases ( 1 ). However, more than one-third of population is at risk of P. vivax , the second most common Plasmodium species after P. falciparum , infection worldwide ( 2 ). Epidemiological data have long suggested that P. vivax can only infect reticulocytes expressing the Duffy protein (or DARC for Duffy Antigen Receptor for Chemokines) on their surface. However, many studies have revealed the ability of P. vivax to infect Duffy-negative subjects, threaten elimination efforts ( 3 – 5 ). Additionally, Sub-Saharan Africa Duffy-negative populations were assumed to be naturally protected against P. vivax infection, thus underestimation of the importance of this parasite on the African continent. The clinical features of P. vivax infection are similar to those of other types of malaria but may have some distinct characteristics. Despite P. vivax infection cause mainly uncomplicated cases however, severe infections can occur with poor outcomes ( 6 ). Severe infections are characterized by severe anemia (haemoglobin < 50g/L), thrombocytopenia, jaundice, and acute respiratory distress syndrome (ARDS)( 7 ). Furthermore, the risk of relapses following the reactivation of dormant hypnozoites in the liver coupled with diagnostics and treatment limitations increases the risk of morbidity and adds complexity to P. vivax infection management ( 6 ). In endemic areas, infants and children are more susceptible to the disease and P. vivax incidence decreases with age due to clinical immunity development. The prevalence and transmission dynamics of P. vivax in sub-Saharan Africa are currently being investigated to improve our knowledge of its prevalence, genetic diversity, and transmission dynamics ( 6 , 8 – 10 ). Here, we report the first case of severe malaria in a child caused by P. vivax in Senegal. Case presentation A 12-year-old Senegalese female presented at the hospital located in the north of Senegal, in July 2022 (Fig. 1 ), with high-grade fever, abdominal pain and vomiting 5 days prior to the visit. On physical examination, she was observed to be jaundiced with an enlarged liver. Hepatomegaly and splenomegaly were confirmed by a subsequent ultrasound examination. The complete blood count examination has revealed a severe anemia (haemoglobin (Hb) = 5.5 g/dl) and a low level of platelets (92,000 cells /mm 3 ) (Table 1 ). The liver function tests showed high alanine transaminase (ALT) at 287.2 UI/L and aspartate transaminase (AST) at 816 UI/L (Table 1 ). Renal parameters were normal and she was negative for hepatitis B infection. Microscopic evaluation of Giemsa-stained thick and thin smears for malaria parasites and the HRP2 based rapid diagnosis test (RDT) for P. falciparum malaria resulted negative. Based on the above results, due to the lack of a precise diagnosis, and in view of the serious state of health, the patient was admitted to the hospital and kept under observation. Without any improvement in clinical condition 10 days after hospitalization the thick and thin Giemsa-stained blood smear for malaria parasites yielded for the first-time positive result for Plasmodium with parasite density at 660 parasites/mL. The medical staff made a diagnosis of severe malaria due to P. falciparum and started intravenous artesunate treatment (2.4 mg/kg administered intravenously at 0, 12, and 24 hours, and thereafter, administered once daily until the patient is able to tolerate oral antimalarial therapy) following the WHO guidelines recommendations ( 11 ), the same dose was repeated up to seven total administrations (Fig. 1 ). After four days course of artesunate blood film for microscopy was check and resulted positive (2526 parasites/mL) (Fig. 1 ) and artesunate treatment was continued. The patient was discharged two days after artesunate treatment ended as clinical signs and symptoms resolved. However, the blood film microscopy examination done at a follow up visit day 21 post hospital admission (4 days post hospital discharge) still revealed parasites (10 3 parasites/mL) in the blood. At this point, an in-depth analysis was then requested with additional tests. Quantitative real-time polymerase chain reaction (qPCR) assay using 18S small subunit ribosomal RNA (18S rRNA) gene multiplex PCR primers, as previously described ( 12 ), was performed and showed P. vivax (Cq 33.68 cycles) infection instead of P. falciparum and primaquine (7,5 mg single oral dose) was added to the treatment following the WHO guidelines recommendations to effectively clear hypnozoites. Table 1 Progression of clinical parameters Parameter Units Day 0 Day 10 Day 14 Day 21 Ref. AST U/L 816 - - - < 30 ALT U/L 287.2 - - - < 45 WBC 10 3 /ml 6.07 7.1 - - 4–10 Hb g/mL 7.7 5.5 - - 12–16 MCV Fl 80.2 79.4 - - 83–98 MCH Pg 26.3 23.6 - - 27–32 MCHC g/dl 32.8 29.7 - - 32–36 Platelets 10 3 /ml 103 92 - - 100–400 Urea g/l - - 0.28 - 0.13–0.50 Creatine mg/l - - 6.6 - 5–13 PT % - - 78% - 70–100 PTT Secondes - - 29’’6 - 26–38 INR* - - 1.21 - 0.85–1.20 *International Normalized Ratio; NA (-) We performed both immunological and genomic analysis to confirm P. vivax infection. Anti-parasite antibodies against Plasmodium spp. , as markers of host immunity development during infection were screened. Serological investigation of MSP1 total IgG antibody titers showed a higher Mean Fluorescence Intensity (MFI) for antibody production against PvMSP1 antigen with a value 4660,5 that could be associate with a an ongoing or previous P.vivax infection (Table 2 ). Table 2 Mean Fluorescence Intensity (MFI) of total IgG against Plasmodium spp. PoMSP1 PfMSP1 PvMSP1 PmMSP1 MFI 3377.5 3304 4660.5 3516 These qPCR results were corroborated by sequencing the 18S rRNA of all Plasmodium species with the extracted gDNA ( 10 , 11 ). Of the analyzed species, only P. vivax reads matched their reference genome ( P. vivax P01 from PlasmoDB, GenBank assembly GCA_900093555.2), unequivocally confirm previous results. Three single nucleotide polymorphisms (SNPs) were identified by mapping reads to the reference strain genome. The most occurring SNP identified during the analysis have approximately 40% (at position 64: A→G, Fig. 1 ) of reads identical to previously reported in P. vivax sequences from Iran and India (India GenBank Sequence ID: JQ627156.1 and Iran GenBank Sequence ID: OM418791.1 and MT710334.1). While the other two SNPs observed in approximately 7% (at position 47: G→A) and 10% (at position 48: A→G) of the reads, respectively, have never been described before (Fig. 2 ). Discussion and conclusion The prevalence of P. vivax infection is increasing worldwide however, the burden of infection in Sub-Saharan Africa is unknown or at best, underestimated ( 2 ). This is largely due to some evidence of protection against infection by P. vivax due to the high prevalence of Duffy negative individuals ( 8 ). In this study we reported the first case of severe malaria due to P. vivax infection in the northern Senegal and highlight the need for attention to the accurate diagnosis of Plasmodium spp. infections. This is especially important as the risk of mixed infections involving multiple parasite species are likely to increase. Furthermore, the scarcity of specific epidemiological data for pediatric P. vivax malaria in Africa affects the ability to provide targeted interventions and the further development of monitoring initiatives. The patient described in this report lives in Saint-Louis, a region located in the north of Senegal with low transmission rates of P. falciparum . In addition, the region borders with Mauritania, an endemic region for P. vivax . ( 13 ). Although P. falciparum is often considered the most harmful species, P. vivax can also lead to significant health problems. Symptoms of P. vivax malaria are similar to those of other infectious diseases, making diagnosis challenging. A major complication associated with P. vivax infection is severe anemia ( 7 ), as observed during this case's blood analysis. This is due to the death of P. vivax -infected reticulocytes by stopping mature red blood cell supply, which can be more severe than anemia caused by P. falciparum ( 14 ). In non-immune populations, symptomatic disease can occur at low parasitemia levels and be undetected by standard diagnostic tests such us microscopic examination or RDTs ( 15 ). Microscopy analysis of stained blood smears is commonly used in endemic areas and is considered the gold standard. However, misidentification by microscopy has been reported in areas co-endemic for P. vivax and P. falciparum malaria impacting correct diagnosis and leading to inappropriate treatment, including artemisinin-based combination therapies (ACTs) therapy for P. falciparum and a lack of anti-relapse therapy for P. vivax ( 16 ). A further complicating factor in the diagnosis of P. vivax malaria is that the parasite is mostly accumulated/sequestrated in the bone marrow or other tissues ( 17 ). As a result, bloodstream detection by microscopy can be delayed and occur when parasite levels exceed a certain threshold. This may explain why the Giemsa-stained blood smear only tested positive a few days after the onset of symptoms and the observed fluctuation. In addition, different studies have shown higher rates of P. vivax parasitemia following P. falciparum infection treatment with ACTs. A possible explanation is that P. falciparum treatment may somehow activate dormant hypnozoites leading to P. vivax relapse ( 18 ). Because of the limitation of microscopy reading and absence of the slides, it was important to confirm the result using more sensitive diagnosis techniques. Firstly, we identify the P. vivax malaria using real time PCR targeting the 18S small subunit ribosomal RNA as previously described ( 12 ) against all the principal four Plasmodium strains. This analysis allowed us to confirm the presence of P. vivax and the absence of the other Plasmodium species, in contrast to the microscopy results. Then, we have performed a serology test where we highlighted a high production of anti-PvMSP1 antibodies which probably means presence or recent exposure to P. vivax . In a second step, the NGS confirmed the presence of P. vivax and the absence of the other Plasmodium species. This suggest that the severe clinical symptoms observed in this patient are caused by P. vivax infection. Previously, studies in Africa have only reported mild infections due to P. vivax ( 8 ). However, it is hypothesized that continued mutations may be playing an important role in the adaptation of the parasite and could rise in a more virulent P. vivax parasite and, an increase in clinical P. vivax infections ( 19 , 20 ). Moreover, the two new SNPs identified in this study suggest a possible variation from what is reported in P. vivax endemic settings. However more studies are needed to understand the role of these mutations in the occurrence of severe symptoms. In conclusion, the misdiagnosis of P. vivax has significant implications for clinical care and malaria control, as failure to administer anti-hypnozoite treatment may lead to increased transmission. The spread of P. vivax in the northern part of Senegal could complicate the current malaria control program. This first case of severe P. vivax malaria reported here highlights the need to review current control strategies to include studies on P. vivax epidemiology, surveillance and primaquine drug administration. Also, improvements in diagnosis of P. vivax infections are urgently needed. This should include training laboratory technicians on microscopic analysis and molecular analysis platforms. List Of Abbreviations AST Aspartate Transaminase ALT Alanine Transaminase WBC White Blood Cells Hb Haemoglobin MCV Mean Cell Volume MCH Mean Cell Haemoglobin MCHC Mean Cell Haemoglobin Concentration PT Prothrombin Test PTT Activated Partial Thromboplastin Time Test RTD Rapid Diagnostic Test. Declarations Ethics approval and consent to participate The parents of the patient gave written informed consent in accordance with the Declaration of Helsinki. Written informed consent was obtained from the parents of the patient before any study procedures were performed. Consent for publication Written informed consent was obtained from the parents of the patient for publication of this case report and all materials. These materials include clinical details, characteristic phenotypic information, and other related data used in this report. Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author on reasonable request. Competing interest CDG is employed by Ares Trading S.A., Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany. SL and ME are employed by Merck KGaA, Darmstadt, Germany. All the other authors declare that they have no competing interests. Funding Not applicable. Author contributions All authors have read the manuscript and provided intellectual content. AS diagnosed the patient; AL, DM, SL and ME analyzed the samples and interpreted the data; and DW, CDG, and JLN wrote the manuscript and produced the figures. Acknowledgments Funding from Merck KGaA, Darmstadt, Germany is gratefully acknowledged. References By-Nc-Sa C. World malaria report 2022. 2022; Drysdale M, Tan L, Martin A, Fuhrer IB, Duparc S, Sharma H. Plasmodium vivax in Children: Hidden Burden and Conspicuous Challenges, a Narrative Review. Infect Dis Ther. 2023 Jan;12(1):33–51. Wilairatana P, Masangkay FR, Kotepui KU, De Jesus Milanez G, Kotepui M. Prevalence and risk of Plasmodium vivax infection among Duffy-negative individuals: a systematic review and meta-analysis. Sci Rep. 2022 Mar 7;12(1):3998. Oboh-Imafidon MA, Zimmerman PA. Plasmodium vivax in Sub-Saharan Africa: An Advancing Threat to Malaria Elimination? Am J Trop Med Hyg. 2023 Sep 6;109(3):497–8. Bouyssou I, El Hoss S, Doderer-Lang C, Schoenhals M, Rasoloharimanana LT, Vigan-Womas I, et al. Unveiling P. vivax invasion pathways in Duffy-negative individuals. Cell Host Microbe. 2023 Dec;31(12):2080-2092.e5. Kotepui M, Kotepui KU, Milanez GDJ, Masangkay FR. Prevalence and risk factors related to poor outcome of patients with severe Plasmodium vivax infection: a systematic review, meta-analysis, and analysis of case reports. BMC Infect Dis. 2020 Dec;20(1):363. Kochar DK, Saxena V, Singh N, Kochar SK, Kumar SV, Das A. Plasmodium vivax Malaria. Emerg Infect Dis. 2005 Jan;11(1):132–4. Zimmerman PA. Plasmodium vivax Infection in Duffy-Negative People in Africa. Am J Trop Med Hyg. 2017 Sep 7;97(3):636–8. Oboh MA, Singh US, Ndiaye D, Badiane AS, Ali NA, Bharti PK, et al. Presence of additional Plasmodium vivax malaria in Duffy negative individuals from Southwestern Nigeria. Malar J. 2020 Dec;19(1):229. Quaye IK, Aleksenko L, Paganotti GM, Peloewetse E, Haiyambo DH, Ntebela D, et al. Malaria Elimination in Africa: Rethinking Strategies for Plasmodium vivax and Lessons from Botswana. Trop Med Infect Dis. 2023 Jul 31;8(8):392. World Health Organization. Management of severe malaria: a practical handbook [Internet]. 3rd ed. La prise en charge du paludisme grave : guide pratique – 3ème ed. Geneva: World Health Organization; 2012 [cited 2023 Dec 12]. 83 p. Available from: https://iris.who.int/handle/10665/79317 Shokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK. Multiplexed Real-Time PCR Assay for Discrimination of Plasmodium Species with Improved Sensitivity for Mixed Infections. J Clin Microbiol. 2009 Apr;47(4):975–80. El Moustapha I, Deida J, Dadina M, El Ghassem A, Begnoug M, Hamdinou M, et al. Changing epidemiology of Plasmodium vivax malaria in Nouakchott, Mauritania: a six-year (2015–2020) prospective study. Malar J. 2023 Jan 17;22(1):18. Kotepui M, Kotepui KU, Milanez GDJ, Masangkay FR. Prevalence and risk factors related to poor outcome of patients with severe Plasmodium vivax infection: a systematic review, meta-analysis, and analysis of case reports. BMC Infect Dis. 2020 May 24;20(1):363. Kakkilaya BS. Rapid Diagnosis of Malaria. Lab Med. 2003 Aug 1;34(8):602–8. Barber BE, William T, Grigg MJ, Yeo TW, Anstey NM. Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi. Malar J. 2013 Dec;12(1):8. Obaldia N, Meibalan E, Sa JM, Ma S, Clark MA, Mejia P, et al. Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection. Boyle JP, editor. mBio. 2018 Jul 5;9(3):e00625-18. Douglas NM, Anstey NM, Angus BJ, Nosten F, Price RN. Artemisinin combination therapy for vivax malaria. Lancet Infect Dis. 2010 Jun;10(6):405–16. Karthigayan Gunalan, Plowe CV, Sá JM, Travassos MA, Thera MA, Laurens MB, et al. Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in Bandiagara, Mali. Am J Trop Med Hyg. 2017 Sep 7;97(3):744–52. Gunalan K, Lo E, Hostetler JB, Yewhalaw D, Mu J, Neafsey DE, et al. Role of Plasmodium vivax Duffy-binding protein 1 in invasion of Duffy-null Africans. Proc Natl Acad Sci. 2016 May 31;113(22):6271–6. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3825024","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":268428978,"identity":"1a18a8d9-ebf7-4eaa-b962-ccea004fa7e8","order_by":0,"name":"Doudou Sow","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYDCCAwwMEhAW8wEGxgaICLFa2BJI1sJjQJwWvuM9hjc+tjHY80vkfJP8uoNBju9GAvPnAjxaJM+cMbac2caQOHNG7jZp2TMMxpI3EtikZ+DRYnAjx0yat40hweA2UIskUO8GoBZmHiK02BvcznkG0lK/AeQwYrQwbridwyb5EWTdjQQGaXxaJM8cK7accU4iceb8Z8bWjGckDGeeediGVwvf8eaNNz6U2djz8xx+ePPnDht5vuPJh/E6DAogUQP0NYgBjh0iAeMP4tWOglEwCkbBCAIAcNNM6s498moAAAAASUVORK5CYII=","orcid":"","institution":"Université Gaston Berger de Saint Louis","correspondingAuthor":true,"prefix":"","firstName":"Doudou","middleName":"","lastName":"Sow","suffix":""},{"id":268428979,"identity":"0587aa2b-e092-45d3-a36f-111977f02750","order_by":1,"name":"Aminata Sall","email":"","orcid":"","institution":"Centre Hospitalier Régional de Saint-Louis","correspondingAuthor":false,"prefix":"","firstName":"Aminata","middleName":"","lastName":"Sall","suffix":""},{"id":268428980,"identity":"6161236a-f883-4a2f-bad4-0b91dcfc6004","order_by":2,"name":"Aminata Lo","email":"","orcid":"","institution":"Université Iba Der Thiam de Thiès","correspondingAuthor":false,"prefix":"","firstName":"Aminata","middleName":"","lastName":"Lo","suffix":""},{"id":268428981,"identity":"2f4705cb-e20d-427f-95f7-4632db994c18","order_by":3,"name":"Demba Makalou","email":"","orcid":"","institution":"Université Gaston Berger de Saint Louis","correspondingAuthor":false,"prefix":"","firstName":"Demba","middleName":"","lastName":"Makalou","suffix":""},{"id":268428982,"identity":"389730f1-7c11-4a17-8215-e27ae4f6a414","order_by":4,"name":"Sara Lodholz","email":"","orcid":"","institution":"Merck KGaA","correspondingAuthor":false,"prefix":"","firstName":"Sara","middleName":"","lastName":"Lodholz","suffix":""},{"id":268428983,"identity":"4bd642a8-4422-4330-8b2b-3be431658eec","order_by":5,"name":"Markus Esser","email":"","orcid":"","institution":"Merck KGaA","correspondingAuthor":false,"prefix":"","firstName":"Markus","middleName":"","lastName":"Esser","suffix":""},{"id":268428984,"identity":"b4d38c75-f91a-401a-a065-be86693e5d42","order_by":6,"name":"Claudia Demarta-Gatsi","email":"","orcid":"","institution":"Global Health Institute of Merck, Ares Trading S.A","correspondingAuthor":false,"prefix":"","firstName":"Claudia","middleName":"","lastName":"Demarta-Gatsi","suffix":""},{"id":268428985,"identity":"21405d8f-dc46-47f4-97b0-5abc4e5ca22f","order_by":7,"name":"Jean Louis Abdourahim Ndiaye","email":"","orcid":"","institution":"Université Iba Der Thiam de Thiès","correspondingAuthor":false,"prefix":"","firstName":"Jean","middleName":"Louis Abdourahim","lastName":"Ndiaye","suffix":""}],"badges":[],"createdAt":"2023-12-31 02:29:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3825024/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3825024/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":49994662,"identity":"00d68249-6708-4960-9cc0-21c86dda3300","added_by":"auto","created_at":"2024-01-22 19:37:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":79357,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eTimeline of clinical course.\u003c/strong\u003e Day 0 is defined as the day of patient presentation resulting in hospital admission.\u003c/p\u003e","description":"","filename":"Picture1.png","url":"https://assets-eu.researchsquare.com/files/rs-3825024/v1/5f6c0b7e341a64a67672b628.png"},{"id":49994663,"identity":"54831152-b125-439d-94f2-0dc6b748b115","added_by":"auto","created_at":"2024-01-22 19:37:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1539274,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eSequencing results of the 18S rRNA locus via NGS.\u003c/strong\u003e (A) Agarose gel electrophoresis of amplicons and their expected sizes after first PCR of Illumina library preparation. (B) Exemplary alignment of a read (Vivax01_Seq) with a SNP at position 64 (A→G). (C) Exemplary alignment of a read (Vivax02_Seq) with a SNP at position 47 (G→A). (D) Exemplary alignment of a read (Vivax03_Seq) with a SNP at position 48 (A→G).\u003c/p\u003e","description":"","filename":"Picture2.png","url":"https://assets-eu.researchsquare.com/files/rs-3825024/v1/ebe15eef633bbc06229534de.png"},{"id":54507342,"identity":"81b71796-18ec-4c1c-a2f7-83230800eba9","added_by":"auto","created_at":"2024-04-11 14:37:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1332160,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3825024/v1/7bea4344-dd0f-4a25-a60f-dc64fd17fd5a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Plasmodium vivax severe malaria case in a children patient in Saint- Louis, Senegal","fulltext":[{"header":"Background","content":"\u003cp\u003eEvery year, malaria kills nearly 600,000 people, mainly children in sub-Saharan Africa. (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). \u003cem\u003ePlasmodium (P.) falciparum\u003c/em\u003e remains the most important species and is responsible of a high number of severe cases (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). However, more than one-third of population is at risk of \u003cem\u003eP. vivax\u003c/em\u003e, the second most common \u003cem\u003ePlasmodium\u003c/em\u003e species after \u003cem\u003eP. falciparum\u003c/em\u003e, infection worldwide (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Epidemiological data have long suggested that \u003cem\u003eP. vivax\u003c/em\u003e can only infect reticulocytes expressing the Duffy protein (or DARC for Duffy Antigen Receptor for Chemokines) on their surface. However, many studies have revealed the ability of \u003cem\u003eP. vivax\u003c/em\u003e to infect Duffy-negative subjects, threaten elimination efforts (\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Additionally, Sub-Saharan Africa Duffy-negative populations were assumed to be naturally protected against \u003cem\u003eP. vivax\u003c/em\u003e infection, thus underestimation of the importance of this parasite on the African continent. The clinical features of \u003cem\u003eP. vivax\u003c/em\u003e infection are similar to those of other types of malaria but may have some distinct characteristics. Despite \u003cem\u003eP. vivax\u003c/em\u003e infection cause mainly uncomplicated cases however, severe infections can occur with poor outcomes (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Severe infections are characterized by severe anemia (haemoglobin\u0026thinsp;\u0026lt;\u0026thinsp;50g/L), thrombocytopenia, jaundice, and acute respiratory distress syndrome (ARDS)(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Furthermore, the risk of relapses following the reactivation of dormant hypnozoites in the liver coupled with diagnostics and treatment limitations increases the risk of morbidity and adds complexity to \u003cem\u003eP. vivax\u003c/em\u003e infection management (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In endemic areas, infants and children are more susceptible to the disease and \u003cem\u003eP. vivax\u003c/em\u003e incidence decreases with age due to clinical immunity development. The prevalence and transmission dynamics of \u003cem\u003eP. vivax\u003c/em\u003e in sub-Saharan Africa are currently being investigated to improve our knowledge of its prevalence, genetic diversity, and transmission dynamics (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Here, we report the first case of severe malaria in a child caused by \u003cem\u003eP. vivax\u003c/em\u003e in Senegal.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 12-year-old Senegalese female presented at the hospital located in the north of Senegal, in July 2022 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), with high-grade fever, abdominal pain and vomiting 5 days prior to the visit. On physical examination, she was observed to be jaundiced with an enlarged liver. Hepatomegaly and splenomegaly were confirmed by a subsequent ultrasound examination.\u003c/p\u003e \u003cp\u003eThe complete blood count examination has revealed a severe anemia (haemoglobin (Hb)\u0026thinsp;=\u0026thinsp;5.5 g/dl) and a low level of platelets (92,000 cells /mm\u003csup\u003e3\u003c/sup\u003e) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The liver function tests showed high alanine transaminase (ALT) at 287.2 UI/L and aspartate transaminase (AST) at 816 UI/L (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Renal parameters were normal and she was negative for hepatitis B infection. Microscopic evaluation of Giemsa-stained thick and thin smears for malaria parasites and the HRP2 based rapid diagnosis test (RDT) for \u003cem\u003eP. falciparum\u003c/em\u003e malaria resulted negative. Based on the above results, due to the lack of a precise diagnosis, and in view of the serious state of health, the patient was admitted to the hospital and kept under observation. Without any improvement in clinical condition 10 days after hospitalization the thick and thin Giemsa-stained blood smear for malaria parasites yielded for the first-time positive result for \u003cem\u003ePlasmodium\u003c/em\u003e with parasite density at 660 parasites/mL. The medical staff made a diagnosis of severe malaria due to \u003cem\u003eP. falciparum\u003c/em\u003e and started intravenous artesunate treatment (2.4 mg/kg administered intravenously at 0, 12, and 24 hours, and thereafter, administered once daily until the patient is able to tolerate oral antimalarial therapy) following the WHO guidelines recommendations (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e), the same dose was repeated up to seven total administrations (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). After four days course of artesunate blood film for microscopy was check and resulted positive (2526 parasites/mL) (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) and artesunate treatment was continued. The patient was discharged two days after artesunate treatment ended as clinical signs and symptoms resolved. However, the blood film microscopy examination done at a follow up visit day 21 post hospital admission (4 days post hospital discharge) still revealed parasites (10\u003csup\u003e3\u003c/sup\u003e parasites/mL) in the blood. At this point, an in-depth analysis was then requested with additional tests. Quantitative real-time polymerase chain reaction (qPCR) assay using 18S small subunit ribosomal RNA (18S rRNA) gene multiplex PCR primers, as previously described (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e), was performed and showed \u003cem\u003eP. vivax\u003c/em\u003e (Cq 33.68 cycles) infection instead of \u003cem\u003eP. falciparum\u003c/em\u003e and primaquine (7,5 mg single oral dose) was added to the treatment following the WHO guidelines recommendations to effectively clear hypnozoites.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eProgression of clinical parameters\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnits\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDay 0\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDay 10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eDay 14\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDay 21\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRef.\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e816\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eU/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e287.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e /ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u0026ndash;10\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eg/mL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12\u0026ndash;16\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e83\u0026ndash;98\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27\u0026ndash;32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMCHC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eg/dl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e32\u0026ndash;36\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelets\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003csup\u003e3\u003c/sup\u003e /ml\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e100\u0026ndash;400\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUrea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eg/l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.13\u0026ndash;0.50\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emg/l\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5\u0026ndash;13\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e70\u0026ndash;100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTT\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSecondes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29\u0026rsquo;\u0026rsquo;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26\u0026ndash;38\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINR*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.85\u0026ndash;1.20\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003e*International Normalized Ratio; NA (-)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eWe performed both immunological and genomic analysis to confirm \u003cem\u003eP. vivax\u003c/em\u003e infection. Anti-parasite antibodies against \u003cem\u003ePlasmodium spp.\u003c/em\u003e, as markers of host immunity development during infection were screened. Serological investigation of MSP1 total IgG antibody titers showed a higher Mean Fluorescence Intensity (MFI) for antibody production against PvMSP1 antigen with a value 4660,5 that could be associate with a an ongoing or previous \u003cem\u003eP.vivax\u003c/em\u003e infection (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMean Fluorescence Intensity (MFI) of total IgG against \u003cem\u003ePlasmodium\u003c/em\u003e spp.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePoMSP1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePfMSP1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePvMSP1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePmMSP1\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMFI\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3377.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3304\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4660.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3516\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThese qPCR results were corroborated by sequencing the 18S rRNA of all \u003cem\u003ePlasmodium\u003c/em\u003e species with the extracted gDNA (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Of the analyzed species, only \u003cem\u003eP. vivax\u003c/em\u003e reads matched their reference genome (\u003cem\u003eP. vivax\u003c/em\u003e P01 from PlasmoDB, GenBank assembly GCA_900093555.2), unequivocally confirm previous results. Three single nucleotide polymorphisms (SNPs) were identified by mapping reads to the reference strain genome. The most occurring SNP identified during the analysis have approximately 40% (at position 64: A→G, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) of reads identical to previously reported in \u003cem\u003eP. vivax\u003c/em\u003e sequences from Iran and India (India GenBank Sequence ID: JQ627156.1 and Iran GenBank Sequence ID: OM418791.1 and MT710334.1). While the other two SNPs observed in approximately 7% (at position 47: G→A) and 10% (at position 48: A→G) of the reads, respectively, have never been described before (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e "},{"header":"Discussion and conclusion","content":"\u003cp\u003eThe prevalence of \u003cem\u003eP. vivax\u003c/em\u003e infection is increasing worldwide however, the burden of infection in Sub-Saharan Africa is unknown or at best, underestimated (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). This is largely due to some evidence of protection against infection by \u003cem\u003eP. vivax\u003c/em\u003e due to the high prevalence of Duffy negative individuals (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). In this study we reported the first case of severe malaria due to \u003cem\u003eP. vivax\u003c/em\u003e infection in the northern Senegal and highlight the need for attention to the accurate diagnosis of \u003cem\u003ePlasmodium\u003c/em\u003e spp. infections. This is especially important as the risk of mixed infections involving multiple parasite species are likely to increase. Furthermore, the scarcity of specific epidemiological data for pediatric \u003cem\u003eP. vivax\u003c/em\u003e malaria in Africa affects the ability to provide targeted interventions and the further development of monitoring initiatives. The patient described in this report lives in Saint-Louis, a region located in the north of Senegal with low transmission rates of \u003cem\u003eP. falciparum\u003c/em\u003e. In addition, the region borders with Mauritania, an endemic region for \u003cem\u003eP. vivax\u003c/em\u003e. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Although \u003cem\u003eP. falciparum\u003c/em\u003e is often considered the most harmful species, \u003cem\u003eP. vivax\u003c/em\u003e can also lead to significant health problems. Symptoms of P. vivax malaria are similar to those of other infectious diseases, making diagnosis challenging. A major complication associated with \u003cem\u003eP. vivax\u003c/em\u003e infection is severe anemia (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e), as observed during this case's blood analysis. This is due to the death of \u003cem\u003eP. vivax\u003c/em\u003e-infected reticulocytes by stopping mature red blood cell supply, which can be more severe than anemia caused by \u003cem\u003eP. falciparum\u003c/em\u003e (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). In non-immune populations, symptomatic disease can occur at low parasitemia levels and be undetected by standard diagnostic tests such us microscopic examination or RDTs (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Microscopy analysis of stained blood smears is commonly used in endemic areas and is considered the gold standard. However, misidentification by microscopy has been reported in areas co-endemic for \u003cem\u003eP. vivax\u003c/em\u003e and \u003cem\u003eP. falciparum\u003c/em\u003e malaria impacting correct diagnosis and leading to inappropriate treatment, including artemisinin-based combination therapies (ACTs) therapy for \u003cem\u003eP. falciparum\u003c/em\u003e and a lack of anti-relapse therapy for \u003cem\u003eP. vivax\u003c/em\u003e (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). A further complicating factor in the diagnosis of \u003cem\u003eP. vivax\u003c/em\u003e malaria is that the parasite is mostly accumulated/sequestrated in the bone marrow or other tissues (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). As a result, bloodstream detection by microscopy can be delayed and occur when parasite levels exceed a certain threshold. This may explain why the Giemsa-stained blood smear only tested positive a few days after the onset of symptoms and the observed fluctuation. In addition, different studies have shown higher rates of \u003cem\u003eP. vivax\u003c/em\u003e parasitemia following \u003cem\u003eP. falciparum\u003c/em\u003e infection treatment with ACTs. A possible explanation is that \u003cem\u003eP. falciparum\u003c/em\u003e treatment may somehow activate dormant hypnozoites leading to \u003cem\u003eP. vivax\u003c/em\u003e relapse (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eBecause of the limitation of microscopy reading and absence of the slides, it was important to confirm the result using more sensitive diagnosis techniques. Firstly, we identify the \u003cem\u003eP. vivax\u003c/em\u003e malaria using real time PCR targeting the 18S small subunit ribosomal RNA as previously described (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) against all the principal four \u003cem\u003ePlasmodium\u003c/em\u003e strains. This analysis allowed us to confirm the presence of \u003cem\u003eP. vivax\u003c/em\u003e and the absence of the other \u003cem\u003ePlasmodium\u003c/em\u003e species, in contrast to the microscopy results.\u003c/p\u003e \u003cp\u003eThen, we have performed a serology test where we highlighted a high production of anti-PvMSP1 antibodies which probably means presence or recent exposure to \u003cem\u003eP. vivax\u003c/em\u003e. In a second step, the NGS confirmed the presence of \u003cem\u003eP. vivax\u003c/em\u003e and the absence of the other \u003cem\u003ePlasmodium\u003c/em\u003e species. This suggest that the severe clinical symptoms observed in this patient are caused by \u003cem\u003eP. vivax\u003c/em\u003e infection. Previously, studies in Africa have only reported mild infections due to \u003cem\u003eP. vivax\u003c/em\u003e (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). However, it is hypothesized that continued mutations may be playing an important role in the adaptation of the parasite and could rise in a more virulent \u003cem\u003eP. vivax\u003c/em\u003e parasite and, an increase in clinical P. vivax infections (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). Moreover, the two new SNPs identified in this study suggest a possible variation from what is reported in \u003cem\u003eP. vivax\u003c/em\u003e endemic settings. However more studies are needed to understand the role of these mutations in the occurrence of severe symptoms.\u003c/p\u003e \u003cp\u003eIn conclusion, the misdiagnosis of \u003cem\u003eP. vivax\u003c/em\u003e has significant implications for clinical care and malaria control, as failure to administer anti-hypnozoite treatment may lead to increased transmission. The spread of \u003cem\u003eP. vivax\u003c/em\u003e in the northern part of Senegal could complicate the current malaria control program. This first case of severe \u003cem\u003eP. vivax\u003c/em\u003e malaria reported here highlights the need to review current control strategies to include studies on P. vivax epidemiology, surveillance and primaquine drug administration. Also, improvements in diagnosis of \u003cem\u003eP. vivax\u003c/em\u003e infections are urgently needed. This should include training laboratory technicians on microscopic analysis and molecular analysis platforms.\u003c/p\u003e"},{"header":"List Of Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAspartate Transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eALT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlanine Transaminase\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWBC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWhite Blood Cells\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eHb\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eHaemoglobin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCV\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMean Cell Volume\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMean Cell Haemoglobin\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCHC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMean Cell Haemoglobin Concentration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProthrombin Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePTT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eActivated Partial Thromboplastin Time Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRTD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eRapid Diagnostic Test.\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe parents of the patient gave written informed consent in accordance with the Declaration of Helsinki. Written informed consent was obtained from the parents of the patient before any study procedures were performed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the parents of the patient for publication of this case report and all materials. These materials include clinical details, characteristic phenotypic information, and other related data used in this report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCDG is employed by Ares Trading S.A., Switzerland, an affiliate of Merck KGaA, Darmstadt, Germany. SL and ME are employed by Merck KGaA, Darmstadt, Germany. All the other authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors have read the manuscript and provided intellectual content. AS diagnosed the patient; AL, DM, SL and ME analyzed the samples and interpreted the data; and DW, CDG, and JLN wrote the manuscript and produced the figures.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFunding from Merck KGaA, Darmstadt, Germany is gratefully acknowledged.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBy-Nc-Sa C. World malaria report 2022. 2022; \u003c/li\u003e\n\u003cli\u003eDrysdale M, Tan L, Martin A, Fuhrer IB, Duparc S, Sharma H. Plasmodium vivax in Children: Hidden Burden and Conspicuous Challenges, a Narrative Review. Infect Dis Ther. 2023 Jan;12(1):33\u0026ndash;51. \u003c/li\u003e\n\u003cli\u003eWilairatana P, Masangkay FR, Kotepui KU, De Jesus Milanez G, Kotepui M. Prevalence and risk of Plasmodium vivax infection among Duffy-negative individuals: a systematic review and meta-analysis. Sci Rep. 2022 Mar 7;12(1):3998. \u003c/li\u003e\n\u003cli\u003eOboh-Imafidon MA, Zimmerman PA. Plasmodium vivax in Sub-Saharan Africa: An Advancing Threat to Malaria Elimination? Am J Trop Med Hyg. 2023 Sep 6;109(3):497\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eBouyssou I, El Hoss S, Doderer-Lang C, Schoenhals M, Rasoloharimanana LT, Vigan-Womas I, et al. Unveiling P. vivax invasion pathways in Duffy-negative individuals. Cell Host Microbe. 2023 Dec;31(12):2080-2092.e5. \u003c/li\u003e\n\u003cli\u003eKotepui M, Kotepui KU, Milanez GDJ, Masangkay FR. Prevalence and risk factors related to poor outcome of patients with severe Plasmodium vivax infection: a systematic review, meta-analysis, and analysis of case reports. BMC Infect Dis. 2020 Dec;20(1):363. \u003c/li\u003e\n\u003cli\u003eKochar DK, Saxena V, Singh N, Kochar SK, Kumar SV, Das A. \u003cem\u003ePlasmodium vivax\u003c/em\u003e Malaria. Emerg Infect Dis. 2005 Jan;11(1):132\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eZimmerman PA. Plasmodium vivax Infection in Duffy-Negative People in Africa. Am J Trop Med Hyg. 2017 Sep 7;97(3):636\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eOboh MA, Singh US, Ndiaye D, Badiane AS, Ali NA, Bharti PK, et al. Presence of additional Plasmodium vivax malaria in Duffy negative individuals from Southwestern Nigeria. Malar J. 2020 Dec;19(1):229. \u003c/li\u003e\n\u003cli\u003eQuaye IK, Aleksenko L, Paganotti GM, Peloewetse E, Haiyambo DH, Ntebela D, et al. Malaria Elimination in Africa: Rethinking Strategies for Plasmodium vivax and Lessons from Botswana. Trop Med Infect Dis. 2023 Jul 31;8(8):392. \u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Management of severe malaria: a practical handbook [Internet]. 3rd ed. La prise en charge du paludisme grave : guide pratique \u0026ndash; 3\u0026egrave;me ed. Geneva: World Health Organization; 2012 [cited 2023 Dec 12]. 83 p. Available from: https://iris.who.int/handle/10665/79317\u003c/li\u003e\n\u003cli\u003eShokoples SE, Ndao M, Kowalewska-Grochowska K, Yanow SK. Multiplexed Real-Time PCR Assay for Discrimination of \u003cem\u003ePlasmodium\u003c/em\u003e Species with Improved Sensitivity for Mixed Infections. J Clin Microbiol. 2009 Apr;47(4):975\u0026ndash;80. \u003c/li\u003e\n\u003cli\u003eEl Moustapha I, Deida J, Dadina M, El Ghassem A, Begnoug M, Hamdinou M, et al. Changing epidemiology of Plasmodium vivax malaria in Nouakchott, Mauritania: a six-year (2015\u0026ndash;2020) prospective study. Malar J. 2023 Jan 17;22(1):18. \u003c/li\u003e\n\u003cli\u003eKotepui M, Kotepui KU, Milanez GDJ, Masangkay FR. Prevalence and risk factors related to poor outcome of patients with severe Plasmodium vivax infection: a systematic review, meta-analysis, and analysis of case reports. BMC Infect Dis. 2020 May 24;20(1):363. \u003c/li\u003e\n\u003cli\u003eKakkilaya BS. Rapid Diagnosis of Malaria. Lab Med. 2003 Aug 1;34(8):602\u0026ndash;8. \u003c/li\u003e\n\u003cli\u003eBarber BE, William T, Grigg MJ, Yeo TW, Anstey NM. Limitations of microscopy to differentiate Plasmodium species in a region co-endemic for Plasmodium falciparum, Plasmodium vivax and Plasmodium knowlesi. Malar J. 2013 Dec;12(1):8. \u003c/li\u003e\n\u003cli\u003eObaldia N, Meibalan E, Sa JM, Ma S, Clark MA, Mejia P, et al. Bone Marrow Is a Major Parasite Reservoir in Plasmodium vivax Infection. Boyle JP, editor. mBio. 2018 Jul 5;9(3):e00625-18. \u003c/li\u003e\n\u003cli\u003eDouglas NM, Anstey NM, Angus BJ, Nosten F, Price RN. Artemisinin combination therapy for vivax malaria. Lancet Infect Dis. 2010 Jun;10(6):405\u0026ndash;16. \u003c/li\u003e\n\u003cli\u003eKarthigayan Gunalan, Plowe CV, S\u0026aacute; JM, Travassos MA, Thera MA, Laurens MB, et al. Plasmodium vivax Infections over 3 Years in Duffy Blood Group Negative Malians in Bandiagara, Mali. Am J Trop Med Hyg. 2017 Sep 7;97(3):744\u0026ndash;52. \u003c/li\u003e\n\u003cli\u003eGunalan K, Lo E, Hostetler JB, Yewhalaw D, Mu J, Neafsey DE, et al. Role of \u003cem\u003ePlasmodium vivax\u003c/em\u003e Duffy-binding protein 1 in invasion of Duffy-null Africans. Proc Natl Acad Sci. 2016 May 31;113(22):6271\u0026ndash;6. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Plasmodium vivax, Severe malaria, Children, New Single Nucleotide Polymorphism","lastPublishedDoi":"10.21203/rs.3.rs-3825024/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3825024/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eInfections caused by \u003cem\u003ePlasmodium vivax \u003c/em\u003eare underestimated in Sub-Saharan Africa. Several cases have been reported in recent years including in Duffy-negative individuals. Most of the cases are uncomplicated, however severe infections can occur with sometimes poor outcomes. Here, we report the first case of \u003cem\u003ePlasmodium vivax\u003c/em\u003e severe infection reported in the north of Senegal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation: \u003c/strong\u003eMDD, 12 years old female patient aged has been received at the hospital for fever, abdominal pain and vomiting. The physical examination has revealed a jaundice and a hepatomegaly. The ultrasound exam has confirmed a hepatomegaly and splenomegaly. The biological examination has revealed a severe anemia (Hb=5.5 g/dl), a low level of platelets (92 10\u003csup\u003e3 \u003c/sup\u003e/mm\u003csup\u003e3\u003c/sup\u003e). The thick and thin blood film yielded negative result at the admission. However, 10 days after hospitalization, the microscopic parasitological examination yielded for the first-time positive result for \u003cem\u003ePlasmodium\u003c/em\u003e with parasite density at 660 trophozoites/mL. The medical staff has retained the diagnosis of severe malaria and started the treatment with artesunate. The control of the Giemsa-stained blood smear done several days after was still positive. A first real time PCR has revealed the diagnosis of \u003cem\u003ePlasmodium vivax\u003c/em\u003e and the primaquine has been added to the treatment.\u003c/p\u003e\n\u003cp\u003eThe case was confirmed by a sequencing method which has revealed three single nucleotide polymorphisms (SNPs). Among these SNPs, two have never been described before.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This report has shown the presence of \u003cem\u003ePlasmodium vivax\u003c/em\u003e in the north of Senegal which shared a border with Mauritania, an endemic \u003cem\u003ePlasmodium vivax\u003c/em\u003e setting. Suggesting a need to improve the surveillance of this pathogen in Senegal and surrounding regions.\u003c/p\u003e","manuscriptTitle":"Plasmodium vivax severe malaria case in a children patient in Saint- Louis, Senegal","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-22 19:37:02","doi":"10.21203/rs.3.rs-3825024/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"aa6f5992-c32c-4195-bef2-63b734e832b0","owner":[],"postedDate":"January 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-16T05:43:04+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-22 19:37:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3825024","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3825024","identity":"rs-3825024","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}