Plasmodium Falciparum neonatal malaria with atypical presentation: A case series from southwestern Ethiopia

Plasmodium Falciparum neonatal malaria with atypical presentation: A case series from southwestern Ethiopia | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Plasmodium Falciparum neonatal malaria with atypical presentation: A case series from southwestern Ethiopia Zerubabel Girma Tesso, Tariku Yigremachew Gossaye, Dereje Sileshi Bekena, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3970701/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Introduction: Neonatal malaria detection of asexual stages of plasmodium species within the first 28 days of life. It can be congenital or acquired through mosquito bites or blood transfusions. Neonatal malaria is generally considered to be rare due to the multiple innate and acquired physiological protective effects present in neonates. However, in areas where malaria is endemic, the prevalence of malaria in neonates is high. The predominant clinical feature of malaria in neonates is fever. respiratory distress, pallor and anemia, hepatomegaly, refusal to feed, jaundice and diarrhea can be manifestations. Atypical presentations without fever can lead to inaccurate diagnosis and contribute to neonatal morbidity and mortality. Neonates from endemic areas with any of the above symptoms should be screened for malaria. Case presentation: We present a series of three cases of Neonatal plasmodium falciparum malaria Presented atypically without febrile episodes, who were diagnosed at Mizan-Tepi University Teaching Hospital between July and September 2023. The first patient presented with vomiting, refusal to feed, pallor, severe anemia, and splenomegaly. The second patient presented with an inconsolable cry, failure to pass feces, abdominal distention, and anemia. The third patient presented with vomiting and anemia. All patients received a 7-day course of intravenous artesunate; the first patient also received a blood transfusion. All patients recovered and were discharged. Conclusions Partial immunity resulting from repeated malaria infections in endemic regions may result in the transfer of high levels of maternal Immunoglobulin G (IgG) antibodies through the placenta, which bind to various plasmodial components and can produce different atypical clinical presentations. In malaria-endemic areas, neonates presenting with any of the presenting signs and symptoms of malaria, including afebrile presentation, require malaria screening to avoid delays in diagnosis. Neonatal malaria Plasmodium falciparum atypical presentations Afebrile Figures Figure 1 INTRODUCTION Malaria is a protozoal infectious disease caused by Plasmodium species, which is common in tropical and subtropical areas of the world. [ 1 ] The sub-Saharan African region is responsible for more than 90% of all global malaria cases and deaths related to malaria. Within this region, children under the age of 5 account for 78.1% of all deaths, making it one of the primary causes of death in this age group [ 2 , 3 ]. Ethiopia accounts for 2.1% of the total cases and 1.7% of the Deaths globally [ 2 ]. The estimated prevalence of malaria in under-five children is around 22.03% [ 4 ]. Approximately 60% of the Ethiopian population lives in malaria-risky areas [ 5 , 6 ]. Mizan-Tepi University Teaching Hospital is located in a high malaria endemic area that is characterized by stable transmission [ 6 ]. Neonatal malaria is considered to be rare in neonates due to the Protective effects of transplacental transferred maternal antibodies, breast milk components (e.g., lactoferrin, secretory immunoglobulin A (IgA) and low levels of para-aminobenzoic acid), high levels of fetal hemoglobin, and the placental barrier, but neonatal and congenital malaria still have prevalence rates of 12.9% and 33.7%, respectively, in malaria-endemic areas. [ 7 – 9 ]. The exact prevalence of neonatal malaria in Ethiopia is not known. Neonatal malaria is defined as the detection of asexual plasmodial stages in the peripheral blood smear or cord blood within the first 28 days of life. It can be congenital or acquired. Congenital malaria is diagnosed in newborns within seven days of birth or later if postpartum infection is not possible. Transmission via mosquito bite or blood transfusion within the first 28 days of life is called acquired neonatal malaria [ 9 , 10 ]. The predominant clinical feature of malaria in neonates is fever (88–100%). Other manifestations include respiratory distress, pallor and anemia, hepatomegaly, refusal to feed, jaundice, and diarrhea [ 11 , 12 ]. The signs and symptoms are similar to those of neonatal sepsis and congenital TORCH (Toxoplasmosis, Others (syphilis, hepatitis B), Rubella, Cytomegalovirus, Herpes simplex) infections and may cause misdiagnoses. Furthermore, atypical presentations, particularly those without febrile episodes, may result in the inability to suspect malaria or inaccurate alternative diagnosis, contributing to neonatal death and morbidity rates. Neonates from endemic areas with any one of these presenting symptoms require high-index suspicion of malaria and screening. In this series, we describe plasmodium falciparum neonatal malaria with atypical clinical manifestations that were treated successfully in the neonatal intensive care unit of the Mizan-Tepi University Teaching Hospital from July to September 2023. The main objective of this series is to create a higher index of suspicion among physicians when it comes to diagnosing neonatal malaria. CASE PRESENTATION Patient 01 A 25-day-old female baby presented with complaints of vomiting of ingested matter and refusal to breastfeed for 2 days. The baby was born to a para 2 mother after a full-term pregnancy. The mother had a history of Plasmodium falciparum malaria in the 9th month of pregnancy, 10 days before delivery, and was treated with artemether/lumefantrine. Otherwise, the baby has no fever, cough, fast breathing, or jaundice. On admission, a physical examination revealed a temperature of 37.3, a pulse Rate of 179, and a Respiratory Rate of 40. The baby has pallor, splenomegaly, and a weak suckling reflex. Complete blood count showed hemoglobin level of 4.6 g/dl, hematocrit 10.5%, white blood cell (WBC) count of 10.93 × 10 3 /µL (granulocytes 27.3%, lymphocytes 66%, MID 6.7%), and platelet count 320 × 10 3 /µL. No ABO or Rh incompatibility was detected, the TORCH screen was negative, the maternal Venereal Disease Research Laboratory (VDRL) test was nonreactive, and peripheral smear morphology revealed normal and normochromic red blood cells (RBCs). The blood film shows the trophozoite stages of Plasmodium falciparum infection (Fig. 1 ). The neonate was transfused with crossmatched whole blood, and treated with intravenous Artesunate 3mg/kg/dose for 7 days and recovered fully. Patient 02 An 18-day-old female neonate was brought to the neonatal unit with complaints of inconsolable crying, failure to pass feces, and abdominal distention of 3 days. The baby had no vomiting, fever, or feeding refusal. The baby was born to a para 2 mother after a full-term pregnancy and passed meconium with in the first 24 hours after delivery and had no prior similar episodes of illness. The mother was receiving antenatal care and had no history of malaria diagnosis or malaria symptoms during pregnancy. Physical examination revealed a temperature of 36.8, a pulse rate of 150, and a respiratory rate of 38. The patient had a protuberant and soft abdomen, and a digital rectal exam revealed stool on the fingers and no blast sign. Complete blood count showed severe anemia with hemoglobin 11.4 g/dl, hematocrit 32.1%, WBC count of 9.99 × 103/µL(granulocytes 41.3%, lymphocytes 48.9%, MID 9.8%), and platelet count 546,000 × 103/µL. No ABO or Rh incompatibility was detected, the TORCH screen was negative, the maternal VDRL test was nonreactive, and the peripheral smear morphology showed normocytic and normochromic RBCs. The blood film shows the trophozoite stages of Plasmodium falciparum infection. The patient started Artesunate intravenous injections. The patient experienced a reduction in abdominal distention and was able to pass stool on the second day of admission. The baby was discharged after 7 days of treatment. Patient 03 A 22-day-old male baby presented with a complaint of vomiting of ingested matter of 4–5 episodes per day of 2 days. The baby was from para 3 mother after a full-term pregnancy. The mother was receiving antenatal care and had no history of malaria diagnosis or symptoms of malaria during pregnancy. Physical examination revealed normal vital signs and negligible systemic evaluation. Complete blood count showed a hemoglobin of 12.2 g/dl, hematocrit of 34.6%, WBC count of 9.96 × 10 3 /µL (Granulocytes 42.2%, lymphocytes 48.7%, MID 9.1%) and platelet count of 64 × 10 3 /µL. No ABO or Rh incompatibility was detected, the TORCH screen was negative, the maternal VDRL test was nonreactive, and the peripheral smear morphology showed normocytic and normochromic RBCs. Blood film showed the trophozoite stages of Plasmodium falciparum infection. The neonate was treated with 3 mg/kg/dose intravenous artesunate for a total duration of 7 days, and the discharge improved. DISCUSSION Malaria in neonates is caused by Plasmodium infection. Mother-to-newborn transmission, a bite from an infected anopheles mosquito, and transfusion of infected blood are the modes of transmission [ 12 – 13 ]. Even though one of the mothers in the case series had a malaria diagnosis during pregnancy, it was challenging to determine whether the malaria infection in the case series was congenital or acquired neonatal malaria. Typically, congenital malaria shows its first signs or symptoms between 10 and 30 days after birth [ 14 ]. However, it is important to note that acquired malaria cannot be ruled out. The typical incubation periods after a mosquito bite are 9–14 days for Plasmodium falciparum, 12–17 days for Plasmodium vivax, 16–18 days for Plasmodium ovale, and 18–40 days for Plasmodium malariae [ 14 ]. The babies in the case series were older than the minimum incubation period of the aforementioned types of malaria. The predominant clinical feature of malaria in neonates is fever (88–100%). Other manifestations include respiratory distress (20–57%), pallor and anemia (38% each), hepatomegaly (31–80%), refusal to feed (40–70%), and jaundice and diarrhea (25% each) [ 11 – 12 , 15 ]. In this case series, none of the neonates had fever at presentation. The first patient presented with vomiting of ingested matter, difficulty breastfeeding, pallor with severe anemia, and splenomegaly as the main clinical manifestations. In the second patient, the clinical features were inconsolable crying, failure to pass feces, abdominal distention, and mild anemia. Finally, the third patient experienced vomiting, mild anemia, and thrombocytopenia. The absence of fever does not rule out malaria, and atypical presentation with the absence of febrile episodes has been described in previous reports [ 16 – 19 ]. Mothers living in malaria-endemic areas can develop partial immunity to the disease after repeated infections, which can protect them from severe attacks and death. The transfer of high levels of IgG antibodies (which are acquired from repeated infections) from the mother to the fetus provides temporary immunity that leads to delayed presentation after infection and modifies clinical manifestations [ 16 – 18 ]. The clinical features of neonatal malaria can be mistaken for neonatal sepsis and congenital TORCH infections, causing a delay in diagnosis [ 20 ]. Sepsis in neonates requires evidence of systemic inflammatory response syndrome (SIRS) as a prerequisite for meeting the criteria for sepsis. SIRS requires either 1) an abnormal WBC count (total WBC increased or decreased for age or > 10% immature neutrophils) or 2) an abnormal core temperature (> 38.5°C or < 36°C), which are absent in our patients [ 21 ]. The improvement observed after treatment with only artesunate reduces the likelihood of alternative differential diagnoses. Diagnosis requires a high index of suspicion, so in malaria-endemic areas or neonates whose mothers have recently traveled to such areas, a neonate presenting with any of the signs and symptoms of malaria even in the absence of fever requires proper malaria screening. In this case series, parasitological diagnosis was performed via examination of Giemsa-stained peripheral blood films via microscopy. The World Health Organization recommends the use of Malaria rapid diagnostic tests (RDTs) only in the absence of microscopy and for patients who have received incomplete antimalarial treatment and for whom blood films can be negative [ 22 ]. In previous studies, both P. falciparum histidine-rich protein 2 (pfHRP2) and lactate dehydrogenase (LDH)-based RDTs showed poor sensitivity in the diagnosis of congenital or acquired neonatal Plasmodium falciparum malaria and cross-reactivity with transplacentally passed parasite antigens [ 23 – 24 ]. The highly sensitive and specific PCR testing remains unavailable in resource-limited setups. The treatment chosen for these patients was based on the National Guidelines and WHO Guidelines for malaria, which is an Artesunate Injection is 3 mg/kg administered intravenously at 0 hours, 12 hours, and 24 hours and thereafter, administered once daily for a total duration of 7 days [ 22 ]. Except for artesunate + sulfadoxine-pyrimethamine, other Artemisinin derivatives are safe and well tolerated by neonates. Eventhough oral artemisinin-based combination therapies are recommended for children weighing less than 5 kg who have uncomplicated malaria or complicated malaria after they can tolerate oral antimalarial therapy, in this case series we used a full course of IV artesunate instead. Due to their physiological immaturity, the pharmacokinetic and dynamic profiles of antimalarial drugs may vary among neonates. Slow gastric emptying, villous formation, and intestinal motor activity are not fully developed until week 20 of life and can affect the enteral absorption of most medications [ 10 , 25 ]. Additionally, the lack of infant formulations of most antimalarial drugs often necessitates the division of adult tablets, which can lead to inaccurate dosing. In this series presenting symptoms were resolved within 2–3 days of treatment with the antimalarial agents. For neonates with severe anemia, hemoglobin becomes normal after blood transfusion. Due to a lack of packed RBCs at our facility, whole blood was administered instead. The second and third neonates received iron supplements before they were discharged. During the follow-up examination, which was conducted two weeks and at 1 month after discharge, the spleen was not palpable on physical examination for the first patient, and anemia was corrected for the last two patients. CONCLUSION Neonatal malaria is a life-threatening condition that can present atypically without febrile episodes. In areas where malaria is endemic, every effort must be made to avoid delays in malaria diagnosis in neonates, which may result in complications and death. By adding malaria tests to regular examinations for newborns with any symptoms of malaria or neonatal sepsis, including afebrile presentations, we can help prevent cases of neonatal malaria from being missed. Abbreviations IgA : Immunoglobulin A IgG: Immunoglobulin G RBCs: Red blood cells RDTs: Rapid diagnostic tests SIRS: systemic inflammatory response syndrome TORCH: Toxoplasmosis, Others (syphilis, hepatitis B), Rubella, Cytomegalovirus, Herpes simplex VDRL: Venereal Disease Research Laboratory WBC: white blood cell Declarations Acknowledgments All those who provided technical assistance and guidance, including the Pediatrics and Child Health Department at Mizan-Tepi University, the staff members of the Neonatal ICU unit, and the study participants, are sincerely acknowledged by the authors. Authors' contributions Study conception: ZGT, TYG, DSB, MAK. Study design, execution and collection of data: ZGT, TYG, DSB, MAK, FDB, NED. Data interpretation: ZGT, TYG, DSB, MAK, FDB, NED. Drafting of the manuscript: ZGT, TYG, DSB, MAK, FDB, NED All of the authors have read and approved the final manuscript. Authors' information Zerubabel Girma Tesso: MD, Lecturer and General Medical Practitioner, Department of Medicine, School of Medicine, College of Medicine and Health Sciences at Mizan-Tepi University, Ethiopia. Tariku Yigremachew Gossaye: MD, Assistant Professor of Pediatrics and Child Health, Department of Pediatrics and Child Health, School of Medicine, College of Medicine and Health Sciences at Mizan-Tepi University, Ethiopia. Dereje Sileshi Bekena: MD, Assistant Professor of Pediatrics and Child Health, Department of Pediatrics and Child Health, School of Medicine, College of Medicine and Health Sciences at Mizan-Tepi University, Ethiopia. Fikretsion Degemu Besir: MD, Assistant Professor of Pediatrics and Child Health, Department of Pediatrics and Child Health, School of Medicine, College of Medicine and Health Sciences at Wolkite University, Ethiopia. Molla Asnake Kebede MD , Assistant Professor of General Medicine, Department of Medicine, School of Medicine, College of Medicine and Health Sciences at Mizan-Tepi University, Ethiopia. Nikodimos Eshetu Dabe : Assistant Professor of Anatomy, Department of Biomedical Science, College of College of Medicine Health Sciences, Mizan-Tepi University, Ethiopia. Funding We received no funding for this case series. Competing interests The authors declare that they have no competing interests. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Consent for publication After the patients recovered, the patients’ parents were informed of the case series and agreed to the publication of this case report and accompanying images. Written informed consent was obtained from the parents after ensuring that no issues hindered their understanding. Ethics approval and consent to participate Ethical approval for this report was obtained from the Research and Ethics Review Committee College of Medicine and Health Science, Mizan-Tepi University. References Rodriguez, J. A., Roa, A. A., Leonso-Bravo, A. A., Khatiwada, P., Eckardt, P., & Lemos-Ramirez, J. (2020). A Case of Plasmodium falciparum Malaria Treated with Artesunate in a 55-Year-Old Woman on Return to Florida from a Visit to Ghana. The American journal of case reports , 21 , e926097. https://doi.org/10.12659/AJCR.926097 World Health Organization. World malaria report 2023. 2023. Geneva. World Health Organization. Child mortality (under 5 years) . Updated 28 January 2022. Accessed October 28, 2023. Available from: https://www.who.int/news-room/fact-sheets/detail/levels-and-trends-in-child-under-5-mortality-in-2020 Biset, G., Tadess, A. W., Tegegne, K. D., Tilahun, L., & Atnafu, N. (2022). Malaria among under-five children in Ethiopia: a systematic review and meta-analysis. 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Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 27 Mar, 2024 Reviews received at journal 23 Mar, 2024 Reviewers agreed at journal 14 Mar, 2024 Reviewers invited by journal 23 Feb, 2024 Submission checks completed at journal 20 Feb, 2024 Editor assigned by journal 20 Feb, 2024 First submitted to journal 19 Feb, 2024 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies 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-3970701","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":273866317,"identity":"c9e8b7d8-d2c3-49b7-98ab-d59c0a345d80","order_by":0,"name":"Zerubabel Girma Tesso","email":"data:image/png;base64,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","orcid":"","institution":"Mizan-Tepi University","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zerubabel","middleName":"Girma","lastName":"Tesso","suffix":""},{"id":273866318,"identity":"5c83337c-9632-4e2f-bc1b-329a8bf2ca84","order_by":1,"name":"Tariku Yigremachew Gossaye","email":"","orcid":"","institution":"Mizan-Tepi University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Tariku","middleName":"Yigremachew","lastName":"Gossaye","suffix":""},{"id":273866319,"identity":"86e15e06-d617-463e-ae15-2b56949fe3f7","order_by":2,"name":"Dereje Sileshi Bekena","email":"","orcid":"","institution":"Mizan-Tepi University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Dereje","middleName":"Sileshi","lastName":"Bekena","suffix":""},{"id":273866320,"identity":"52547173-c6ca-4d47-aa7a-a6f273709ecc","order_by":3,"name":"Molla Asnake Kebede","email":"","orcid":"","institution":"Mizan-Tepi University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Molla","middleName":"Asnake","lastName":"Kebede","suffix":""},{"id":273866321,"identity":"7ea2eeb8-69e2-4dcb-925b-d7e43c7baec3","order_by":4,"name":"Fikretsion Degemu Besir","email":"","orcid":"","institution":"Wolkite University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Fikretsion","middleName":"Degemu","lastName":"Besir","suffix":""},{"id":273866322,"identity":"aef85a6f-4532-44ca-9df2-a57b55a4ac57","order_by":5,"name":"Nikodimos Eshetu Dabe","email":"","orcid":"","institution":"Mizan-Tepi University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nikodimos","middleName":"Eshetu","lastName":"Dabe","suffix":""}],"badges":[],"createdAt":"2024-02-19 18:53:00","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3970701/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3970701/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":51512411,"identity":"56d49a2d-93dc-4a5c-bed4-e92ce451570f","added_by":"auto","created_at":"2024-02-22 21:17:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":696937,"visible":true,"origin":"","legend":"\u003cp\u003eThin blood film showing Trophozoite stages of Plasmodium falciparum\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-3970701/v1/8792b43e76e9b51fc6a9bdec.png"},{"id":51512993,"identity":"3d4e5192-67fe-4ffd-b1f3-e0c733be2c3c","added_by":"auto","created_at":"2024-02-22 21:25:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1351630,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3970701/v1/1de533e3-4951-4113-a6d2-ca22832841bd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003ePlasmodium Falciparum neonatal malaria with atypical presentation: A case series from southwestern Ethiopia\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eMalaria is a protozoal infectious disease caused by \u003cem\u003ePlasmodium\u003c/em\u003e species, which is common in tropical and subtropical areas of the world. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The sub-Saharan African region is responsible for more than 90% of all global malaria cases and deaths related to malaria. Within this region, children under the age of 5 account for 78.1% of all deaths, making it one of the primary causes of death in this age group [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Ethiopia accounts for 2.1% of the total cases and 1.7% of the Deaths globally [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The estimated prevalence of malaria in under-five children is around 22.03% [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Approximately 60% of the Ethiopian population lives in malaria-risky areas [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Mizan-Tepi University Teaching Hospital is located in a high malaria endemic area that is characterized by stable transmission [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eNeonatal malaria is considered to be rare in neonates due to the Protective effects of transplacental transferred maternal antibodies, breast milk components (e.g., lactoferrin, secretory immunoglobulin A (IgA) and low levels of para-aminobenzoic acid), high levels of fetal hemoglobin, and the placental barrier, but neonatal and congenital malaria still have prevalence rates of 12.9% and 33.7%, respectively, in malaria-endemic areas. [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The exact prevalence of neonatal malaria in Ethiopia is not known.\u003c/p\u003e \u003cp\u003eNeonatal malaria is defined as the detection of asexual plasmodial stages in the peripheral blood smear or cord blood within the first 28 days of life. It can be congenital or acquired. Congenital malaria is diagnosed in newborns within seven days of birth or later if postpartum infection is not possible. Transmission via mosquito bite or blood transfusion within the first 28 days of life is called acquired neonatal malaria [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe predominant clinical feature of malaria in neonates is fever (88\u0026ndash;100%). Other manifestations include respiratory distress, pallor and anemia, hepatomegaly, refusal to feed, jaundice, and diarrhea [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The signs and symptoms are similar to those of neonatal sepsis and congenital TORCH (Toxoplasmosis, Others (syphilis, hepatitis B), Rubella, Cytomegalovirus, Herpes simplex) infections and may cause misdiagnoses. Furthermore, atypical presentations, particularly those without febrile episodes, may result in the inability to suspect malaria or inaccurate alternative diagnosis, contributing to neonatal death and morbidity rates. Neonates from endemic areas with any one of these presenting symptoms require high-index suspicion of malaria and screening.\u003c/p\u003e \u003cp\u003eIn this series, we describe plasmodium falciparum neonatal malaria with atypical clinical manifestations that were treated successfully in the neonatal intensive care unit of the Mizan-Tepi University Teaching Hospital from July to September 2023. The main objective of this series is to create a higher index of suspicion among physicians when it comes to diagnosing neonatal malaria.\u003c/p\u003e"},{"header":"CASE PRESENTATION","content":"\u003cp\u003ePatient 01\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eA 25-day-old female baby presented with complaints of vomiting of ingested matter and refusal to breastfeed for 2 days. The baby was born to a para 2 mother after a full-term pregnancy. The mother had a history of Plasmodium falciparum malaria in the 9th month of pregnancy, 10 days before delivery, and was treated with artemether/lumefantrine. Otherwise, the baby has no fever, cough, fast breathing, or jaundice. On admission, a physical examination revealed a temperature of 37.3, a pulse Rate of 179, and a Respiratory Rate of 40. The baby has pallor, splenomegaly, and a weak suckling reflex. Complete blood count showed hemoglobin level of 4.6 g/dl, hematocrit 10.5%, white blood cell (WBC) count of 10.93 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L (granulocytes 27.3%, lymphocytes 66%, MID 6.7%), and platelet count 320 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L. No ABO or Rh incompatibility was detected, the TORCH screen was negative, the maternal Venereal Disease Research Laboratory (VDRL) test was nonreactive, and peripheral smear morphology revealed normal and normochromic red blood cells (RBCs). The blood film shows the trophozoite stages of Plasmodium falciparum infection (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The neonate was transfused with crossmatched whole blood, and treated with intravenous Artesunate 3mg/kg/dose for 7 days and recovered fully.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePatient 02\u003c/p\u003e \u003cp\u003eAn 18-day-old female neonate was brought to the neonatal unit with complaints of inconsolable crying, failure to pass feces, and abdominal distention of 3 days. The baby had no vomiting, fever, or feeding refusal. The baby was born to a para 2 mother after a full-term pregnancy and passed meconium with in the first 24 hours after delivery and had no prior similar episodes of illness. The mother was receiving antenatal care and had no history of malaria diagnosis or malaria symptoms during pregnancy. Physical examination revealed a temperature of 36.8, a pulse rate of 150, and a respiratory rate of 38. The patient had a protuberant and soft abdomen, and a digital rectal exam revealed stool on the fingers and no blast sign. Complete blood count showed severe anemia with hemoglobin 11.4 g/dl, hematocrit 32.1%, WBC count of 9.99 \u0026times; 103/\u0026micro;L(granulocytes 41.3%, lymphocytes 48.9%, MID 9.8%), and platelet count 546,000 \u0026times; 103/\u0026micro;L. No ABO or Rh incompatibility was detected, the TORCH screen was negative, the maternal VDRL test was nonreactive, and the peripheral smear morphology showed normocytic and normochromic RBCs. The blood film shows the trophozoite stages of Plasmodium falciparum infection. The patient started Artesunate intravenous injections. The patient experienced a reduction in abdominal distention and was able to pass stool on the second day of admission. The baby was discharged after 7 days of treatment.\u003c/p\u003e \u003cp\u003ePatient 03\u003c/p\u003e \u003cp\u003eA 22-day-old male baby presented with a complaint of vomiting of ingested matter of 4\u0026ndash;5 episodes per day of 2 days. The baby was from para 3 mother after a full-term pregnancy. The mother was receiving antenatal care and had no history of malaria diagnosis or symptoms of malaria during pregnancy. Physical examination revealed normal vital signs and negligible systemic evaluation. Complete blood count showed a hemoglobin of 12.2 g/dl, hematocrit of 34.6%, WBC count of 9.96 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L (Granulocytes 42.2%, lymphocytes 48.7%, MID 9.1%) and platelet count of 64 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e/\u0026micro;L. No ABO or Rh incompatibility was detected, the TORCH screen was negative, the maternal VDRL test was nonreactive, and the peripheral smear morphology showed normocytic and normochromic RBCs. Blood film showed the trophozoite stages of Plasmodium falciparum infection. The neonate was treated with 3 mg/kg/dose intravenous artesunate for a total duration of 7 days, and the discharge improved.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eMalaria in neonates is caused by Plasmodium infection. Mother-to-newborn transmission, a bite from an infected anopheles mosquito, and transfusion of infected blood are the modes of transmission [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Even though one of the mothers in the case series had a malaria diagnosis during pregnancy, it was challenging to determine whether the malaria infection in the case series was congenital or acquired neonatal malaria. Typically, congenital malaria shows its first signs or symptoms between 10 and 30 days after birth [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, it is important to note that acquired malaria cannot be ruled out. The typical incubation periods after a mosquito bite are 9\u0026ndash;14 days for Plasmodium falciparum, 12\u0026ndash;17 days for Plasmodium vivax, 16\u0026ndash;18 days for Plasmodium ovale, and 18\u0026ndash;40 days for Plasmodium malariae [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The babies in the case series were older than the minimum incubation period of the aforementioned types of malaria.\u003c/p\u003e \u003cp\u003eThe predominant clinical feature of malaria in neonates is fever (88\u0026ndash;100%). Other manifestations include respiratory distress (20\u0026ndash;57%), pallor and anemia (38% each), hepatomegaly (31\u0026ndash;80%), refusal to feed (40\u0026ndash;70%), and jaundice and diarrhea (25% each) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. In this case series, none of the neonates had fever at presentation. The first patient presented with vomiting of ingested matter, difficulty breastfeeding, pallor with severe anemia, and splenomegaly as the main clinical manifestations. In the second patient, the clinical features were inconsolable crying, failure to pass feces, abdominal distention, and mild anemia. Finally, the third patient experienced vomiting, mild anemia, and thrombocytopenia. The absence of fever does not rule out malaria, and atypical presentation with the absence of febrile episodes has been described in previous reports [\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Mothers living in malaria-endemic areas can develop partial immunity to the disease after repeated infections, which can protect them from severe attacks and death. The transfer of high levels of IgG antibodies (which are acquired from repeated infections) from the mother to the fetus provides temporary immunity that leads to delayed presentation after infection and modifies clinical manifestations [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe clinical features of neonatal malaria can be mistaken for neonatal sepsis and congenital TORCH infections, causing a delay in diagnosis [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Sepsis in neonates requires evidence of systemic inflammatory response syndrome (SIRS) as a prerequisite for meeting the criteria for sepsis. SIRS requires either 1) an abnormal WBC count (total WBC increased or decreased for age or \u0026gt;\u0026thinsp;10% immature neutrophils) or 2) an abnormal core temperature (\u0026gt;\u0026thinsp;38.5\u0026deg;C or \u0026lt;\u0026thinsp;36\u0026deg;C), which are absent in our patients [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. The improvement observed after treatment with only artesunate reduces the likelihood of alternative differential diagnoses.\u003c/p\u003e \u003cp\u003eDiagnosis requires a high index of suspicion, so in malaria-endemic areas or neonates whose mothers have recently traveled to such areas, a neonate presenting with any of the signs and symptoms of malaria even in the absence of fever requires proper malaria screening. In this case series, parasitological diagnosis was performed via examination of Giemsa-stained peripheral blood films via microscopy. The World Health Organization recommends the use of Malaria rapid diagnostic tests (RDTs) only in the absence of microscopy and for patients who have received incomplete antimalarial treatment and for whom blood films can be negative [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In previous studies, both P. falciparum histidine-rich protein 2 (pfHRP2) and lactate dehydrogenase (LDH)-based RDTs showed poor sensitivity in the diagnosis of congenital or acquired neonatal Plasmodium falciparum malaria and cross-reactivity with transplacentally passed parasite antigens [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The highly sensitive and specific PCR testing remains unavailable in resource-limited setups.\u003c/p\u003e \u003cp\u003eThe treatment chosen for these patients was based on the National Guidelines and WHO Guidelines for malaria, which is an Artesunate Injection is 3 mg/kg administered intravenously at 0 hours, 12 hours, and 24 hours and thereafter, administered once daily for a total duration of 7 days [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Except for artesunate\u0026thinsp;+\u0026thinsp;sulfadoxine-pyrimethamine, other Artemisinin derivatives are safe and well tolerated by neonates. Eventhough oral artemisinin-based combination therapies are recommended for children weighing less than 5 kg who have uncomplicated malaria or complicated malaria after they can tolerate oral antimalarial therapy, in this case series we used a full course of IV artesunate instead. Due to their physiological immaturity, the pharmacokinetic and dynamic profiles of antimalarial drugs may vary among neonates. Slow gastric emptying, villous formation, and intestinal motor activity are not fully developed until week 20 of life and can affect the enteral absorption of most medications [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Additionally, the lack of infant formulations of most antimalarial drugs often necessitates the division of adult tablets, which can lead to inaccurate dosing.\u003c/p\u003e \u003cp\u003eIn this series presenting symptoms were resolved within 2\u0026ndash;3 days of treatment with the antimalarial agents. For neonates with severe anemia, hemoglobin becomes normal after blood transfusion. Due to a lack of packed RBCs at our facility, whole blood was administered instead. The second and third neonates received iron supplements before they were discharged. During the follow-up examination, which was conducted two weeks and at 1 month after discharge, the spleen was not palpable on physical examination for the first patient, and anemia was corrected for the last two patients.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eNeonatal malaria is a life-threatening condition that can present atypically without febrile episodes. In areas where malaria is endemic, every effort must be made to avoid delays in malaria diagnosis in neonates, which may result in complications and death. By adding malaria tests to regular examinations for newborns with any symptoms of malaria or neonatal sepsis, including afebrile presentations, we can help prevent cases of neonatal malaria from being missed.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003eIgA\u003c/strong\u003e: Immunoglobulin A\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIgG:\u003c/strong\u003e Immunoglobulin G\u003c/p\u003e\n\u003cp\u003eRBCs: Red blood cells\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRDTs:\u003c/strong\u003e Rapid diagnostic tests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSIRS:\u003c/strong\u003e systemic inflammatory response syndrome\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTORCH:\u003c/strong\u003e Toxoplasmosis, Others (syphilis, hepatitis B), Rubella, Cytomegalovirus, Herpes simplex\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVDRL:\u003c/strong\u003e Venereal Disease Research Laboratory\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWBC:\u003c/strong\u003e white blood cell\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll those who provided technical assistance and guidance, including the Pediatrics and Child Health Department at Mizan-Tepi University, the staff members of the Neonatal ICU unit, and the study participants, are sincerely acknowledged by the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy conception: ZGT, TYG, DSB, MAK.\u003c/p\u003e\n\u003cp\u003eStudy design, execution and collection of data:\u0026nbsp;ZGT, TYG, DSB, MAK, FDB, NED.\u003c/p\u003e\n\u003cp\u003eData interpretation: ZGT, TYG, DSB, MAK, FDB, NED.\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript:\u0026nbsp;ZGT, TYG, DSB, MAK, FDB, NED\u003c/p\u003e\n\u003cp\u003eAll of the authors have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; information\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eZerubabel Girma Tesso:\u003c/strong\u003e MD, Lecturer and General Medical Practitioner, Department of Medicine, School of Medicine, College of Medicine and Health Sciences at Mizan-Tepi University, Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTariku Yigremachew Gossaye:\u003c/strong\u003e MD, Assistant Professor of\u0026nbsp;Pediatrics\u0026nbsp;and\u0026nbsp;Child Health, Department of\u0026nbsp;Pediatrics\u0026nbsp;and\u0026nbsp;Child Health, School of Medicine, College of Medicine and Health Sciences\u0026nbsp;at Mizan-Tepi University, Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDereje Sileshi Bekena:\u003c/strong\u003e MD, Assistant Professor of\u0026nbsp;Pediatrics\u0026nbsp;and\u0026nbsp;Child Health, Department of\u0026nbsp;Pediatrics\u0026nbsp;and\u0026nbsp;Child Health, School of Medicine, College of Medicine and Health Sciences\u0026nbsp;at Mizan-Tepi University, Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFikretsion Degemu Besir:\u003c/strong\u003e MD, Assistant Professor of\u0026nbsp;Pediatrics\u0026nbsp;and\u0026nbsp;Child Health, Department of\u0026nbsp;Pediatrics\u0026nbsp;and\u0026nbsp;Child Health, School of Medicine, College of Medicine and Health Sciences\u0026nbsp;at Wolkite University, Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMolla Asnake\u003csup\u003e\u0026nbsp;\u003c/sup\u003eKebede MD\u003c/strong\u003e, Assistant Professor of General Medicine, Department of Medicine, School of Medicine, College of Medicine and Health Sciences at Mizan-Tepi University, Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eNikodimos Eshetu Dabe\u003c/strong\u003e: Assistant Professor of Anatomy, Department of Biomedical Science, College of\u0026nbsp;College of Medicine\u0026nbsp;Health Sciences, Mizan-Tepi University, Ethiopia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe received no funding for this case\u0026nbsp;series.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author\u0026nbsp;upon\u0026nbsp;reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter the\u0026nbsp;patients recovered,\u0026nbsp;the patients\u0026rsquo; parents were informed of the case series and agreed to the publication of this case report and accompanying images. Written informed consent was obtained from\u0026nbsp;the parents\u0026nbsp;after ensuring\u0026nbsp;that no issues hindered their understanding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthical approval for this report was obtained from the Research and Ethics Review Committee College of Medicine and Health Science, Mizan-Tepi University.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eRodriguez, J. A., Roa, A. A., Leonso-Bravo, A. A., Khatiwada, P., Eckardt, P., \u0026amp; Lemos-Ramirez, J. (2020). A Case of Plasmodium falciparum Malaria Treated with Artesunate in a 55-Year-Old Woman on Return to Florida from a Visit to Ghana. \u003cem\u003eThe American journal of case reports\u003c/em\u003e, \u003cem\u003e21\u003c/em\u003e, e926097. https://doi.org/10.12659/AJCR.926097\u003c/li\u003e\n \u003cli\u003eWorld Health Organization. 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Elsevier\u0026apos;s Saunders; 2011. Perinatal protozoal and fungal infections; pp. 775\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eGathwala, Geeta; Dalal, Poonam; Gupta, Mohit. Congenital Malaria with Atypical Presentation: A Series of Three Case Reports. Journal of Clinical Neonatology 4(3): p 206-208, Jul\u0026ndash;Sep 2015. | DOI: 10.4103/2249-4847.154128\u003c/li\u003e\n \u003cli\u003eBehrman RE, Keligman R, Jenson HB (2011) Nelson Text book of Pediatrics. Philadelphia. Nelson textbook of pediatrics (Edition 21). P. 1853-5\u003c/li\u003e\n \u003cli\u003eKarlsson S, Nienhuis AW: Developmental regulation of human globin genes. Ann Rev Biochem 1985, 54:1071\u0026ndash;1108.\u003c/li\u003e\n \u003cli\u003eDas, Joydeep \u0026amp; Choudhury, Saugata. (2021). Case series on congenital malaria from a tertiary care hospital in North Eastern India. 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Clinical presentation and management of neonatal malaria: a review. \u003cem\u003eMalar Chemoth Cont Elimination\u003c/em\u003e, \u003cem\u003e3\u003c/em\u003e(2), 126.\u003c/li\u003e\n \u003cli\u003eWynn J. L. (2016). Defining neonatal sepsis. \u003cem\u003eCurrent opinion in pediatrics\u003c/em\u003e, \u003cem\u003e28\u003c/em\u003e(2), 135\u0026ndash;140. https://doi.org/10.1097/MOP.0000000000000315\u003c/li\u003e\n \u003cli\u003eWorld Health Organization. WHO Guidelines for malaria, 14 March 2023. Geneva. 2023\u003c/li\u003e\n \u003cli\u003eAdeniji, Y. R., Jalo, I., Okonkwo, I., Poksireni, M. R., Manga, M., Wariri, O., Alhassan, H. A., \u0026amp; Warnow, E. I. (2023). 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Developmental pharmacology--drug disposition, action, and therapy in infants and children. \u003cem\u003eThe New England journal of medicine\u003c/em\u003e, \u003cem\u003e349\u003c/em\u003e(12), 1157\u0026ndash;1167. https://doi.org/10.1056/NEJMra035092\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Neonatal malaria, Plasmodium falciparum, atypical presentations, Afebrile","lastPublishedDoi":"10.21203/rs.3.rs-3970701/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3970701/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eNeonatal malaria detection of asexual stages of plasmodium species within the first 28 days of life. It can be congenital or acquired through mosquito bites or blood transfusions. Neonatal malaria is generally considered to be rare due to the multiple innate and acquired physiological protective effects present in neonates. However, in areas where malaria is endemic, the prevalence of malaria in neonates is high. The predominant clinical feature of malaria in neonates is fever. respiratory distress, pallor and anemia, hepatomegaly, refusal to feed, jaundice and diarrhea can be manifestations. Atypical presentations without fever can lead to inaccurate diagnosis and contribute to neonatal morbidity and mortality. Neonates from endemic areas with any of the above symptoms should be screened for malaria.\u003c/p\u003e\u003ch2\u003eCase presentation:\u003c/h2\u003e \u003cp\u003eWe present a series of three cases of Neonatal plasmodium falciparum malaria Presented atypically without febrile episodes, who were diagnosed at Mizan-Tepi University Teaching Hospital between July and September 2023. The first patient presented with vomiting, refusal to feed, pallor, severe anemia, and splenomegaly. The second patient presented with an inconsolable cry, failure to pass feces, abdominal distention, and anemia. The third patient presented with vomiting and anemia. All patients received a 7-day course of intravenous artesunate; the first patient also received a blood transfusion. All patients recovered and were discharged.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003ePartial immunity resulting from repeated malaria infections in endemic regions may result in the transfer of high levels of maternal Immunoglobulin G (IgG) antibodies through the placenta, which bind to various plasmodial components and can produce different atypical clinical presentations. In malaria-endemic areas, neonates presenting with any of the presenting signs and symptoms of malaria, including afebrile presentation, require malaria screening to avoid delays in diagnosis.\u003c/p\u003e","manuscriptTitle":"Plasmodium Falciparum neonatal malaria with atypical presentation: A case series from southwestern Ethiopia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-22 21:17:04","doi":"10.21203/rs.3.rs-3970701/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-03-27T04:03:32+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-23T22:13:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"bdcecee7-6257-479d-983b-e7bead9d152b","date":"2024-03-14T11:57:25+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-23T07:25:37+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-20T11:56:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-20T11:56:50+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2024-02-19T18:49:47+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"malaria-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"malj","sideBox":"Learn more about [Malaria Journal](http://malariajournal.biomedcentral.com/)","snPcode":"12936","submissionUrl":"https://submission.nature.com/new-submission/12936/3","title":"Malaria Journal","twitterHandle":"@malariajournal","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"04c29eec-4815-41b8-8e27-bcf4107a9ded","owner":[],"postedDate":"February 22nd, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-05-15T12:16:32+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-22 21:17:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3970701","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3970701","identity":"rs-3970701","version":["v1"]},"buildId":"CiT4i_kKBbxQbnFL0ufpk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}