Neonatal and Congenital malaria (NCM): A Case Series in Tigray region, Ethiopia

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Neonatal malaria (NM) is acquired through mosquito bites after birth in the neonatal period. Both neonatal and congenital malaria (NCM) are potentially life-threatening conditions that can mimic other neonatal conditions, such as neonatal sepsis; therefore, these conditions can be misdiagnosed and mistreated. Although NCM is widely recognized in most parts of the world, including Africa, there is currently a scarcity of data and experience regarding NCM in the Tigray region specifically and in Ethiopia generally. The purpose of this case series was to increase awareness of clinicians to the practice of screening, treatment and prevention of NCM, particularly in endemic areas. Case presentation : We present a series of six cases (four congenital and two neonatal malaria cases). The age of their mothers ranged from 23–30 years, and their birth experience ranged from 1–5. Four of the six mothers had a history of malaria attack and treatment, three of whom were during the present pregnancy and one of whom had an attack in the immediate postpartum period. The age of the neonates at admission ranged from 1 day to 16 days. All six neonates were brought by their parents with the primary complaint of fever. Blood smears of four of the six neonates revealed ring stages of Plasmodium falciparum, and Plasmodium vivax was detected in one of the neonates. Additionally, a mixture of Plasmodium falciparum and P. vivax was detected in another neonate. Antimalarial and first-line antibiotics were administered to all six neonates. Five of them were treated successfully and recovered, and one of them died while she was on treatment. Conclusion Neonatal congenital malaria should be considered in any newborn with clinical features of neonatal sepsis from a malaria-endemic area, particularly those who present with fever. Routine malaria prevention strategies and malaria screening tests should be considered for neonates in malaria-endemic areas. Congenital malaria Neonatal malaria Neonate Malaria Tigray Background The World Health Organization (WHO) Global Technical Strategy calls for a reduction in malaria case incidence and mortality rate of at least 90% by 2030 from its baseline in 2015( 1 ). To meet this goal, early identification, prevention, and treatment of malaria in all age groups, including neonates, is crucial. Ethiopia is a malaria high-burden country, with 75% of its total area being malarious and approximately 52% of the population living in malaria risk areas( 2 ). P. falciparum and P. vivax are the two dominant parasite species causing malaria in Ethiopia, with relative frequencies of approximately 60% and 40%, respectively ( 2 ). Congenital malaria results from transplacental transmission of malaria parasites from the mother to the baby in utero or from feto-maternal transmission during labor and delivery ( 3 ). The diagnosis of malaria is similar to that of other age groups in that it involves the detection of asexual forms of malaria parasites via blood smears that are thick and thin and rapid diagnostic tests, which are particularly useful in resource-limited and endemic areas. Although the definitions of neonatal and congenital malaria are controversial, most studies define congenital malaria when it occurs in the early neonatal period (the first seven days of life). However, they can manifest beyond the first week of life and the neonatal period for various reasons, including persistent maternal IgG in the newborn's blood, fast clearance of parasites from fetal circulation and fetal hemoglobin ( 3 , 4 ). Neonatal malaria is considered when it occurs in the late neonatal period (8th − 28th days of life)( 3 – 5 ). However, the incubation period for P. falciparum is more than 9 days, and in malaria-endemic areas, the neonates could still be at risk of mosquito bites even after delivery and thereby acquire malaria. This controversy can be solved by PCR testing for malaria in mothers and neonates, which can establish a temporal relationship( 5 ). However, PCR tests for malaria are very limited in low-resource countries. The placenta can be infected in one-third of mothers living in endemic areas even though they are asymptomatic( 6 , 7 ). The placental transfer of antibodies prevents the clinical manifestation of malaria in neonates despite the presence of malaria parasites in their blood. Furthermore, the presence of fetal hemoglobin, which has a different morphology than adult hemoglobin does, prevents malaria infection in neonates ( 6 , 8 ). Both the maternal transfer of immunoglobulin and fetal hemoglobin wane at similar times, with a half-life ranging from 3–6 months, at which time malaria attacks and severe cases appear ( 6 , 9 ). Maternal breast milk is also unfavorable for the multiplication of malaria parasites because of the presence of low iron and amino acid (p-amino benzoic acid) contents, which the parasite uses during replication in the human body. The reported incidence of congenital malaria in endemic regions is variable( 5 , 10 – 12 ). However, even in the absence of congenital malaria, placental malaria significantly increases the risk of perinatal morbidity and mortality, including low birth weight, intrauterine growth restriction, preterm labor, and intrauterine fetal death( 3 ). This case series aims to increase awareness of clinicians to the practice of screening, treatment and prevention of NCM in endemic areas, such as our setup, where there are overlapping clinical signs and symptoms of malaria and sepsis. Although NCM is widely recognized in most parts of the world, little is known about the burden of NCM in the Tigray region specifically and in Ethiopia generally. We reported a series of six cases of NCM (four congenital malaria cases and two neonatal malaria cases) that were initially admitted with features of sepsis at Miani General Hospital, which is located in the northwestern part of the Tigray region, northern Ethiopia, where malaria is endemic in its catchment area. The study period was from January to May 2024. We reported those whose blood smears revealed malaria parasites despite many patients who were clinically treated and responded to anti-malaria therapy while being on treatment for sepsis. This indicates that the burden of NCM might be beyond what we are reporting. Summary of the Case Presentation We reported a series of six cases, four of which were congenital malaria cases and two of which were neonatal malaria cases. The age of their mothers ranged from 23–30 years, and their birth experience (parity) ranged from 1–5. All mothers had regular antenatal care follow-up at nearby health centers. Four of the six mothers had a history of malarial attack and treatment during their present pregnancy, and one had a history of malaria in the immediate postpartum period. The ratio of males to females was 1:2. The admission age of the neonates ranged from 1 day to 16 days, and all of them were born at term gestation. The birth weights of the four neonates ranged from 3 kg to 3.5 kg, whereas those of the other two neonates were unknown. In addition, the admission weight of the neonates ranged from 2 kg to 2.8 kg. All the patients were brought with the primary complaint of fever by their parents. In addition to fever, one of the neonates complained of changes in mentation and abnormal body movement. On physical examination, all six neonates were febrile, ranging from 38 to 40 degrees Celsius. The other system findings were variable and are detailed in subsequent case discussions. They were investigated via routine laboratory investigations, and the results were as follows. In two of the patients, the blood sugar level was low (hypoglycemia), and five had normal complete blood count parameters, while one had severe anemia and thrombocytopenia. Blood smears revealed ring stages with variable densities of Plasmodium falciparum in four of the cases, Plasmodium vivax in one of them and mixed P. falciparum and P. vivax in another neonate. All patients had received antimalarial and first-line antibiotics on the basis of the Ethiopian national malaria protocol and WHO recommendations, with variable durations of hospitalization. In addition, two of the patients were treated for hypoglycemia with 10% dextrose in the water of the bolus, followed by normalization of the standard glucose infusion rate until normalization. One of the patients was transfused with cross matched whole blood two times. Among the six neonates, five were treated successfully and discharged with variable hospital durations, and one died while he was receiving treatment. The cases are detailed below, and Table 1 summarizes the most important parameters. Patient 1 A 32-hour-old female neonate was born to a 30-year-old para-V mother vaginally at a nearby health center. The total duration of labor was 5 hours, and the membrane ruptured intrapartum. The birth weight (wt.) was 3000 grams, and the Apgar score was unknown, but the mother reported that she cried immediately. She had regular antenatal care (ANC) follow-up at the nearby health center four times, was screened for TORCH infection, and was told that the results were nonreactive. She had no history of malaria attacks. She brought her neonate with the complaint of high-grade fever and excessive crying that started at the age of one day. On physical examination at admission, she was irritable, her pulse rate was 140, her temperature was 38 degrees Celsius (febrile), and her weight was 3000 grams. Other vital signs were within the normal range. She was investigated with a thin and thick blood film, which was positive for Plasmodium falciparum +. Her blood sugar level was 69 mg/dl, and her hemoglobin level was 14 g/dl. A diagnosis of congenital malaria and early-onset neonatal sepsis (EONS) was made. She was treated with artesunate 3 mg/kg/dose for five days on the basis of the national guidelines of Ethiopia and the World Health Organization. In addition to antimalarial agents, first-line antibiotics (ampicillin and gentamicin) were given for seven days. She had recovered and was discharged after 7 days of hospital stay. She appeared well at the follow-up clinic. Patient 2 A 3-day-old male neonate was born to a 23-year-old para I mother via spontaneous vaginal delivery at a nearby health center, and the total duration of labor was 8 hours. The membrane was ruptured intrapartum. The birth weight was 3500 grams, and the Apgar score was unknown, but the mother reported that he cried immediately after birth. She had regular ANC follow-up at a nearby health facility. She had a history of a malaria attack in the seventh month of the present pregnancy, and she was treated according to the guidelines. The neonate was brought with the complaint of high-grade fever and intense crying since birth. He also had decreased breast feeding and a decreased amount of urine after one day. On examination, the patient was acutely sick, his pulse rate was 178 bpm, his temperature was 40 degrees Celsius (febrile), and his admission weight was 3000 grams. The other vital signs were within the normal range. The other system examinations were unremarkable. He was investigated with a thin and thick blood film, and the result was positive for Plasmodium falciparum ++. His blood sugar level was 40 mg/dl, indicating hypoglycemia, and his hemoglobin level was 14.9 g/dl. A diagnosis of congenital malaria, hypoglycemia, and neonatal dehydration secondary to poor intake and EONS was made. He was given a bolus of 10% dextrose in water and then put on a continuous glucose infusion rate of 6 mg/kg/min until his blood glucose normalized. He was also resuscitated with 10 ml/kg normal saline once. He was given 3 mg/kg artesunate according to the national malaria protocol of Ethiopia for five days. He also received first-line antibiotics, i.e., ampicillin and cefotaxime, for sepsis. He was discharged after 7 days of hospital stay. At the follow-up clinic, the patient was in stable health with optimal growth. Patient 3 This is a 24-hour-old male neonate born to a 26-year-old Para III mother via spontaneous vaginal delivery at a nearby health center. The total duration of labor was 6 hours, and the membrane ruptured intrapartum. The birth weight was 3000 grams, and the Apgar score was unknown, but the mother reported that he cried immediately after birth. She had regular ANC follow-up at her nearby health center, which was uneventful. She had no history of malaria attacks. The neonate was brought with the complaint of high-grade fever since he was born. On examination, he was acutely sick, his pulse rate was 150 bpm, his temperature was 39 degrees Celsius, and his admission weight was 3000 grams. The other system examinations were negative. He was investigated with a thin and thick blood film, which revealed Plasmodium falciparum ++. His hemoglobin level was 16.2 g/dl. A diagnosis of congenital malaria and EONS was made. He was treated with 3 mg/kg artesunate for five days according to the national protocol. First-line antibiotics were administered for 7 days. He improved and was discharged after 7 days of hospital stay. At the follow-up clinic, the patient appeared stable, with optimal growth patterns. Patient 4 A 3-day-old male neonate was born to a 26-year-old Para III mother via spontaneous vaginal delivery at a nearby health center with an unknown birth weight and Apgar score, but he cried immediately after birth. She had regular ANC follow-up, which was uneventful. She had a history of malaria attacks soon after birth in her immediate postpartum period. Accordingly, she was treated at the referring health center. The neonate was brought with the complaint of high-grade fever since birth, and he was referred to our hospital for neonatal intensive care. A malaria rapid diagnostic test (RDT), which was performed at the referring health center, was positive for P. vivax. He was referred after one dose of chloroquine was given. At admission to our center, on physical examination, the patient was acutely sick, his pulse rate was 152 b/m, his temperature was 39 degrees Celsius (febrile), and his weight was 3000 grams. The other system examinations were unremarkable. A thin and thick blood smear was obtained and revealed Plasmodium vivax++, which is consistent with RDT. A diagnosis of congenital malaria and EONS was made. He was treated with artesunate 3 mg/kg/dose for five days according to the national malaria protocol of Ethiopia. Additionally, first-line antibiotics were given for 7 days. The patient was in good health and had optimal growth at the follow-up clinic. Patient 5 A 16-day-old male neonate was born to a 30-year-old mother. His birth weight was 3200 grams. The Apgar scores at the 1st and 5th minutes were 8 and 9, respectively. She had regular ANC follow-up at her nearby health facility, which was uneventful. She had a history of malaria attacks before the present pregnancy. The neonate was brought with the complaint of abdominal distention, vomiting of breast milk and decreased urine for 3 days. On examination, the patient was acutely sick, his pulse rate was 180 bpm, his temperature was 39 degrees Celsius (febrile), and his weight was 2700 grams. The other vital signs were within the normal range. The abdomen was distended and soft with out-of-organomegally on palpation. The other system examinations were not revealing. He was investigated with a thin and thick blood smear, and the results revealed Plasmodium falciparum+. A diagnosis of neonatal malaria and EONS was made. He was treated with 3 mg/kg artesunate for 7 days according to the national malaria protocol. A course of first-line antibiotics was also given. However, the abdominal distension persisted, and the antibiotics were continued for two weeks. Further evaluations via abdominal ultrasound and vital signs were normal. After two weeks of hospital stay, the patient was discharged with improvement. At the follow-up clinic, the patient was stable with optimal growth patterns. Patient 6 A 10-day-old female neonate, with an unknown birth weight and Apgar score, was born vaginally to a 30-year-old IV mother at a nearby health center, but she cried immediately after birth. She had regular ANC follow-up three times at a nearby health facility, and it was uneventful. She had a history of malaria treatment in the early stage of pregnancy. She presented with a complaint of high-grade fever for 3 days. She had a history of abnormal body movement for two to three episodes per day, vomiting of breast milk, decreased mentation and failure to pass through urine, which was associated with significant weight loss of the same duration. Otherwise, she had no history of any external bleeding. On examination at admission, she was lethargic, her pulse rate was 180 bpm, her respiratory rate was 68 bpm, which was interpreted as tachypnic, and her temperature was 40 degrees Celsius, which was translated as febrile. In addition, she was desaturated to 80% with atmospheric oxygen. Her weight at admission was 2000 grams. She had pale conjunctiva and icteric sclera. Chest examination revealed subcostal and intercostal retraction and good air entry in the bilateral lung fields. Abdominal examination revealed splenomegaly. On musculoskeletal examination, she had a bony and skin appearance, the skin pinch returned slowly, she appeared pale, her capillary refill was fast, and she was jaundiced up to the level of the chest. Neurologic examination indicated lethargy and depressed primitive reflexes. She was investigated with a thin and thick blood film, which was positive for mixed Plasmodium falciparum + and P. vivax +. Her blood glucose level was 35 g/dl, indicating hypoglycemia. The complete blood count revealed a white blood cell count of 10,000, a platelet count of 123,000, which suggested mild thrombocytopenia, and a hemoglobin level of 6.7 g/dl, which was interpreted as severe anemia. She was admitted with a diagnosis of neonatal malaria, neonatal seizures secondary to cerebral malaria, meningitis and hypoglycemia. In addition, prerenal azotemia secondary to sepsis and malaria was also considered. A diagnosis of severe sepsis involving the central nervous system, hematology and respiratory system was also included. She was managed with intranasal oxygen (1 liter per min), a bolus of 4 ml/kg 10% dextrose in water followed by a glucose infusion rate of 6 mg/kg/min until it normalized. She was resuscitated with 20 ml/kg normal saline twice, but she did not pass through the urine. She was transfused with 20 ml/kg fresh whole blood two times, and she was started on 3 mg/kg artesunate according to the national malaria protocol. She was also started on first-line antibiotics, i.e., ampicillin and cefotaxime, at a meningeal dose. She was also initially loaded and reloaded with phenobarbital, and she did not respond; then, she was again loaded with phenytoin and then continued with maintenance doses of both drugs. In addition, diazepam was given as needed. The families were advised to refer to a level III NICU center for further management and investigations, such as renal function tests and electrolyte determination. However, the families refused the referral, and the physician in charge advised them on the prognosis. She was on treatment and routine intensive care unit (ICU) care at our center until she died after 48 hours. Table 1 Summary of admission characteristics and treatment outcomes, cases of congenital and neonatal malaria, Tigray region, northern Ethiopia Characteristics Congenital malaria Neonatal malaria Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Maternal Age (year) 30 23 26 26 30 30 Parity 5 1 3 3 NA 4 Malaria treatment history No Yes No Yes Yes Yes Neonate Age (d/H) 32 H 3d 1d 3d 16d 10d Sex Female Male Male Male Male Female Birth wt(kg) 3 3.5 3 Unknown 3.2 Unknown Admission wt (kg) 2.8 3 3 3 2.7 2 Symptoms Fever Yes Yes Yes Yes Yes Yes Duration of fever (d) 01 03 1 3 3 03 Fast breathing No No No No No Yes Poor breastfeeding No Yes No No No Yes Signs Temperature(Celsius) 38 40 39 39 39 39 Jaundice No No No No No Yes Pallor No No No No No Yes RR(breath/min) 44 46 42 45 50 72 SPO 2 (atm oxygen) 93% 92% 95% 94% 94% 80 Hepatomegaly No No No No No No Splenomegaly No No No No No Yes Laboratory Hemoglobin(g/dl) 14 14.9 16.2 15.6 16.4 6.7 Malaria Blood smear P.f P.f P.f P.V P.f P.f and P.V Treatment Oxygen No No No No No Yes Antimalarial Yes Yes Yes Yes Yes Yes Antibiotics Yes Yes Yes Yes Yes Yes Blood transfusion No No No No No Yes Outcome at discharge Recovered Recovered Recovered Recovered Recovered died D –day, H - Hour, Pf - Plasmodium falciparum, Pv - Plasmodium vivax, NA- Not available, wt - weight Discussion Ethiopia remains one of the countries with a high malaria burden, with 75% of the total area being malarious and approximately 52% of the population living in a malaria risk area( 2 ). P. falciparum and P. vivax are the two dominant parasite species causing malaria in Ethiopia, with relative frequencies of approximately 60% and 40%, respectively( 2 ). The epidemiology of congenital and neonatal malaria is elusive in Ethiopia, except for a few case reports and series, particularly in the Tigray region of Ethiopia. Studies have indicated that the main presentation of NCM is variable degrees of fever starting from the first day of life and beyond( 5 , 10 , 11 ). All our patients were brought by their parents primarily with the complaint of fever. Similarly, Olupot‑Olupot et al. and colleagues in their case series reported that 3 of the 4 NCMs presented with fever( 5 ). Fever can also be a manifestation of sepsis. Malaria should be considered a cause of fever in the neonatal period, and appropriate malaria tests should be performed, particularly in malaria endemic areas. However, a significant number of NCM cases in endemic areas can present with atypical manifestations, including poor feeding, jaundice, excessive crying, diarrhea and vomiting, convulsion, anemia, thrombocytopenia, hypoglycemia, respiratory distress, hepatomegaly, splenomegaly, bloody stools, hypothermia, apnea and cyanosis, and can be asymptomatic ( 7 , 10 , 13 – 15 ). Tesso et al. and associates from southern Ethiopia in their case series reported three neonates with NCM who presented without fever ( 16 ). The sole presentations of these patients were anemia and jaundice( 16 ). Initially, neonates usually present with features of sepsis. The concomitant presence of sepsis and malaria in neonates is characterized by fever, vomiting, abdominal distension, decreased breastfeeding, irritability, changes in mentation and abnormal laboratory parameters such as low blood glucose levels and anemia( 11 ). Therefore, it might be misdiagnosed and hence may result in mistreatment. A high suspicion of malaria, especially when fever persists while the patients are on standard antibiotic management, may be an important clue. In such cases, appropriate malaria work-up should ensue. All six of our patients had features of neonatal sepsis, and at the beginning of their admission, antibiotics were initiated. However, despite on antibiotics fever persisted and the patients were screened early for malaria; thus, the results were positive for various species of malaria. However, a significant number of patients whose malaria tests were negative responded well to the clinical addition of antimalarial medications. This highlights that the clinical consideration of NCM should not be ignored in malaria-endemic areas. Malaria endemicity has been suggested to play a role in the prevalence of NCM. Vertical transmission is low in hyperendemic areas and high in low endemic areas due to immune development ( 3 ). The diagnostic modalities of NCM include thin and thick blood smears, RDT and molecular tests such as PCR. Although there is a low density of circulating parasites in neonates, a thin and thick blood film is regarded as the standard diagnostic modality( 1 ). All six of our patients were diagnosed with blood film. One of our patients underwent a malaria rapid diagnostic (RDT) test at the referring health center, and the results were positive for p. vivax. The blood film obtained at our center for this patient also revealed P. vivax, which was consistent with the RDT results. One study indicated that real-time PCR yields higher positivity rates than blood smears from the peripheral smears of neonates ( 7 ). When available, PCR tests are excellent in cases of low-density parasites such as neonates( 7 ). In this study, all placental malaria confirmed by real-time PCR were also confirmed to be positive microscopically( 7 ). However, this diagnostic method is difficult to use in low-income countries such as ours for obvious reasons. The treatment of NCM is usually off-label, similar to older children. Indeed, parenteral treatments are better in neonates and young infants for various reasons ( 5 ). In our cases, we used artesunate 3 mg/kg/dose, which is in line with the Ethiopian and WHO malaria guidelines. The duration of treatment mainly depends on the patient’s condition, including the presence of complications, which can last five to seven days. All our patients were on first-line antibiotics because of overlapping signs and symptoms and coincidence of bacterial infection. Although artemisinin-based combination therapy is the recommended treatment for uncomplicated malaria in infants, neonates have been largely excluded from ACT clinical trials ( 3 ). Furthermore, the WHO currently allows those under 5 kilograms to be treated in a similar way to older infants ( 17 ). The WHO acknowledges that most anti-malaria drugs lack infant formulations, which can lead to either under- or overdosing ( 5 ). This was observed in one of our patients, where he took a higher dose of chloroquine prior to his referral to our hospital. In addition, infants can deteriorate rapidly; therefore, there should be a low threshold for parenteral treatment( 5 ). The other standard treatment for malaria in older children is primaquine. However, primaquine is contraindicated during pregnancy, breastfeeding mothers and infants under six months of age due to insufficient data in these populations ( 17 ). Nonetheless, studies have reported that there are no significant side effects in those aged greater than 28 days( 5 ). Similar to the other drugs the physiological immaturity and rapid changes that occur in neonates, the pharmacokinetic and dynamic profiles of antimalarial drugs are likely different from those of older children( 18 ). Conclusion In conclusion, NCM is an important diagnosis to consider in any newborn with clinical features of neonatal sepsis from a malaria-endemic area. Focusing on prevention, routine blood smears for malaria screening and early treatment of malaria in neonates with features of sepsis in endemic areas will help reduce morbidity and mortality related to NCM. Moreover, this case series highlights the need for standard routine malaria tests in neonates, particularly in malaria-endemic areas. Abbreviations ANC antenatal care CM congenital malaria EONS Early-Onset Neonatal Sepsis NCM Neonatal and Congenital Malaria PCR Polymerase Chain Reaction TORCH Toxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes WHO World Health Organization Declarations Ethics approval and consent to participate Ethical approval for the publication of this case report was obtained from the Aksum University College of Health Science ethics committee with approval number IRB098/2025. Consent for publication Written informed consent was obtained from the patients’ parents for publication of this case series. A copy of the written consent is available for review by the editor-in-chief of this journal upon request. Availability of data and materials Data sharing is not applicable to this article, as no data sets were generated or analyzed during the current study. Competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Funding This study did not receive any grants or funding from either for-profit or nonprofit organizations. Authors’ contributions Yemane Leake Gebremichael : Conceptualization, Visualization, Supervision, Writing- Original draft preparation. Hindeya Hailu Hagos : Data curation, Writing- Original draft preparation. Birhanu Kassie Reta : Visualization, Investigation, Writing review and editing. Tiegst Bahta Woldu; Writing review and editing, Kinfe Redae Berhe ; Writing review and editing, Fantay G/mariam G/Aregay ; Writing review and editing, Gebremskel Kiros Tsegay ; Writing review and editing Acknowledgment Miani Hospital NICU and Laboratory Team References World Health Organization. WHO guidelines for malaria, 30 November 2024 [Internet]. World Health Organization; 2024 [cited 2025 Feb 8]. Available from: https://iris.who.int/handle/10665/379635 Malaria Case Management. Training Manual for Health Professionals in Ethiopia Participants Manual. ministry of health, ethiopia; 2022. Menendez C, Mayor A. Congenital malaria: The least known consequence of malaria in pregnancy. Semin Fetal Neonatal Med. 2007;12(3):207–13. Danwang C, Bigna JJ, Nzalie RNT, Robert A. Epidemiology of clinical congenital and neonatal malaria in endemic settings: a systematic review and meta-analysis. Malar J. 2020;19(1):312. Olupot-Olupot P, Eregu EIE, Naizuli K, Ikiror J, Acom L, Burgoine K. 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Available from:https://books.google.com/books?hl=en&lr=&id=In0OEQAAQBAJ&oi=fnd&pg=PA7&dq=WHO+malaria+guideline+2022&ots=mQmn64m8WM&sig=AaSyc_xIQjCF2EN8BtpVi0Cr7sY Rupa DKM. Clinical Presentation and Management of Neonatal Malaria: A Review. Malar Chemother Control Elimin [Internet]. 2014 [cited 2025 Mar 2];03(02). Available from: https://www.omicsonline.com/open-access/clinical-presentation-and-management-of-neonatal-malaria-a-review-2090-2778.1000126.php?aid=37135 Additional Declarations No competing interests reported. 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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-6227110","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":443758415,"identity":"cf6ae8dd-652a-43e1-8a4d-416753a68b3e","order_by":0,"name":"Yemane Leake Gebremichael","email":"","orcid":"","institution":"Aksum University College of Health Science","correspondingAuthor":false,"prefix":"","firstName":"Yemane","middleName":"Leake","lastName":"Gebremichael","suffix":""},{"id":443758416,"identity":"a3318aa7-b198-47e9-bfb1-fb1c325407d2","order_by":1,"name":"Hindeya Hailu Hagos","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABBUlEQVRIiWNgGAWjYBACAwbGxgOMDQxAxMD44EOFDVAMKEJASwNMC7PhjDNpIC0NBLQwMMC0sAnzth0Gi+LVYs5+uOEw7447sv0Syc+Yec6ct1vbfhhoS41NNC4tlj2JQC1nnhnPnJFm9nBOxe3kbWcSgVqOpeU24HLYAZCWtsOJG24kmBu8OXM72QwoAnTqYdxazj+EaNl/I/2bBG/buWQzoAh+LTdgtkjkmEnyth2wM7tByJYbDxsOzm07bDzjzJtiYCAnJ5gBRQ4k4PPL+fSHD962HZbtb0/fCIxKO3szkMiHGhucWhBAIAFMJYJVJhBUDgL8B8CUPVGKR8EoGAWjYEQBABSld26vH5dSAAAAAElFTkSuQmCC","orcid":"","institution":"Aksum University College of Health Science","correspondingAuthor":true,"prefix":"","firstName":"Hindeya","middleName":"Hailu","lastName":"Hagos","suffix":""},{"id":443758417,"identity":"36d0b054-700a-4753-bf0e-ca64a6e32fe0","order_by":2,"name":"Birhanu Kassie Reta","email":"","orcid":"","institution":"Aksum University College of Health Science","correspondingAuthor":false,"prefix":"","firstName":"Birhanu","middleName":"Kassie","lastName":"Reta","suffix":""},{"id":443758418,"identity":"35a529b6-6d4a-42fd-adf3-8c24b7bf17f9","order_by":3,"name":"Tiegst Bahta Woldu","email":"","orcid":"","institution":"Aksum University College of Health Science","correspondingAuthor":false,"prefix":"","firstName":"Tiegst","middleName":"Bahta","lastName":"Woldu","suffix":""},{"id":443758420,"identity":"478c1cec-d231-4e1a-8d4a-3ae12b4661a6","order_by":4,"name":"Kinfe Redae Berhe","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Kinfe","middleName":"Redae","lastName":"Berhe","suffix":""},{"id":443758426,"identity":"5366ecca-7212-439d-87ad-8f1510c98de7","order_by":5,"name":"Fantay G/mariam G/aregay","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Fantay","middleName":"G/mariam","lastName":"G/aregay","suffix":""},{"id":443758430,"identity":"75e187eb-cee8-401d-8fed-26970c691bf7","order_by":6,"name":"Gebremeskel Kiros Tsegay","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Gebremeskel","middleName":"Kiros","lastName":"Tsegay","suffix":""}],"badges":[],"createdAt":"2025-03-14 14:08:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6227110/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6227110/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12936-025-05466-8","type":"published","date":"2025-07-01T15:57:48+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":86179828,"identity":"9685c7ea-a996-4993-9d6a-033ee41d6246","added_by":"auto","created_at":"2025-07-07 16:19:48","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":717526,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6227110/v1/caf61a24-6199-4b07-951c-beb0f3480f58.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neonatal and Congenital malaria (NCM): A Case Series in Tigray region, Ethiopia","fulltext":[{"header":"Background","content":"\u003cp\u003eThe World Health Organization (WHO) Global Technical Strategy calls for a reduction in malaria case incidence and mortality rate of at least 90% by 2030 from its baseline in 2015(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). To meet this goal, early identification, prevention, and treatment of malaria in all age groups, including neonates, is crucial. Ethiopia is a malaria high-burden country, with 75% of its total area being malarious and approximately 52% of the population living in malaria risk areas(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). P. falciparum and P. vivax are the two dominant parasite species causing malaria in Ethiopia, with relative frequencies of approximately 60% and 40%, respectively (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). Congenital malaria results from transplacental transmission of malaria parasites from the mother to the baby in utero or from feto-maternal transmission during labor and delivery (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The diagnosis of malaria is similar to that of other age groups in that it involves the detection of asexual forms of malaria parasites via blood smears that are thick and thin and rapid diagnostic tests, which are particularly useful in resource-limited and endemic areas.\u003c/p\u003e \u003cp\u003eAlthough the definitions of neonatal and congenital malaria are controversial, most studies define congenital malaria when it occurs in the early neonatal period (the first seven days of life). However, they can manifest beyond the first week of life and the neonatal period for various reasons, including persistent maternal IgG in the newborn's blood, fast clearance of parasites from fetal circulation and fetal hemoglobin (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Neonatal malaria is considered when it occurs in the late neonatal period (8th \u0026minus;\u0026thinsp;28th days of life)(\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, the incubation period for P. falciparum is more than 9 days, and in malaria-endemic areas, the neonates could still be at risk of mosquito bites even after delivery and thereby acquire malaria. This controversy can be solved by PCR testing for malaria in mothers and neonates, which can establish a temporal relationship(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). However, PCR tests for malaria are very limited in low-resource countries. The placenta can be infected in one-third of mothers living in endemic areas even though they are asymptomatic(\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The placental transfer of antibodies prevents the clinical manifestation of malaria in neonates despite the presence of malaria parasites in their blood. Furthermore, the presence of fetal hemoglobin, which has a different morphology than adult hemoglobin does, prevents malaria infection in neonates (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). Both the maternal transfer of immunoglobulin and fetal hemoglobin wane at similar times, with a half-life ranging from 3\u0026ndash;6 months, at which time malaria attacks and severe cases appear (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eMaternal breast milk is also unfavorable for the multiplication of malaria parasites because of the presence of low iron and amino acid (p-amino benzoic acid) contents, which the parasite uses during replication in the human body. The reported incidence of congenital malaria in endemic regions is variable(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). However, even in the absence of congenital malaria, placental malaria significantly increases the risk of perinatal morbidity and mortality, including low birth weight, intrauterine growth restriction, preterm labor, and intrauterine fetal death(\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). This case series aims to increase awareness of clinicians to the practice of screening, treatment and prevention of NCM in endemic areas, such as our setup, where there are overlapping clinical signs and symptoms of malaria and sepsis. Although NCM is widely recognized in most parts of the world, little is known about the burden of NCM in the Tigray region specifically and in Ethiopia generally. We reported a series of six cases of NCM (four congenital malaria cases and two neonatal malaria cases) that were initially admitted with features of sepsis at Miani General Hospital, which is located in the northwestern part of the Tigray region, northern Ethiopia, where malaria is endemic in its catchment area. The study period was from January to May 2024. We reported those whose blood smears revealed malaria parasites despite many patients who were clinically treated and responded to anti-malaria therapy while being on treatment for sepsis. This indicates that the burden of NCM might be beyond what we are reporting.\u003c/p\u003e"},{"header":"Summary of the Case Presentation","content":"\u003cp\u003eWe reported a series of six cases, four of which were congenital malaria cases and two of which were neonatal malaria cases. The age of their mothers ranged from 23\u0026ndash;30 years, and their birth experience (parity) ranged from 1\u0026ndash;5. All mothers had regular antenatal care follow-up at nearby health centers. Four of the six mothers had a history of malarial attack and treatment during their present pregnancy, and one had a history of malaria in the immediate postpartum period. The ratio of males to females was 1:2. The admission age of the neonates ranged from 1 day to 16 days, and all of them were born at term gestation. The birth weights of the four neonates ranged from 3 kg to 3.5 kg, whereas those of the other two neonates were unknown. In addition, the admission weight of the neonates ranged from 2 kg to 2.8 kg. All the patients were brought with the primary complaint of fever by their parents. In addition to fever, one of the neonates complained of changes in mentation and abnormal body movement. On physical examination, all six neonates were febrile, ranging from 38 to 40 degrees Celsius. The other system findings were variable and are detailed in subsequent case discussions.\u003c/p\u003e \u003cp\u003eThey were investigated via routine laboratory investigations, and the results were as follows. In two of the patients, the blood sugar level was low (hypoglycemia), and five had normal complete blood count parameters, while one had severe anemia and thrombocytopenia. Blood smears revealed ring stages with variable densities of Plasmodium falciparum in four of the cases, Plasmodium vivax in one of them and mixed P. falciparum and P. vivax in another neonate. All patients had received antimalarial and first-line antibiotics on the basis of the Ethiopian national malaria protocol and WHO recommendations, with variable durations of hospitalization. In addition, two of the patients were treated for hypoglycemia with 10% dextrose in the water of the bolus, followed by normalization of the standard glucose infusion rate until normalization. One of the patients was transfused with cross matched whole blood two times. Among the six neonates, five were treated successfully and discharged with variable hospital durations, and one died while he was receiving treatment. The cases are detailed below, and Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the most important parameters.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient 1\u003c/h2\u003e \u003cp\u003eA 32-hour-old female neonate was born to a 30-year-old para-V mother vaginally at a nearby health center. The total duration of labor was 5 hours, and the membrane ruptured intrapartum. The birth weight (wt.) was 3000 grams, and the Apgar score was unknown, but the mother reported that she cried immediately. She had regular antenatal care (ANC) follow-up at the nearby health center four times, was screened for TORCH infection, and was told that the results were nonreactive. She had no history of malaria attacks. She brought her neonate with the complaint of high-grade fever and excessive crying that started at the age of one day. On physical examination at admission, she was irritable, her pulse rate was 140, her temperature was 38 degrees Celsius (febrile), and her weight was 3000 grams. Other vital signs were within the normal range. She was investigated with a thin and thick blood film, which was positive for Plasmodium falciparum +. Her blood sugar level was 69 mg/dl, and her hemoglobin level was 14 g/dl. A diagnosis of congenital malaria and early-onset neonatal sepsis (EONS) was made. She was treated with artesunate 3 mg/kg/dose for five days on the basis of the national guidelines of Ethiopia and the World Health Organization. In addition to antimalarial agents, first-line antibiotics (ampicillin and gentamicin) were given for seven days. She had recovered and was discharged after 7 days of hospital stay. She appeared well at the follow-up clinic.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient 2\u003c/h3\u003e\n\u003cp\u003eA 3-day-old male neonate was born to a 23-year-old para I mother via spontaneous vaginal delivery at a nearby health center, and the total duration of labor was 8 hours. The membrane was ruptured intrapartum. The birth weight was 3500 grams, and the Apgar score was unknown, but the mother reported that he cried immediately after birth. She had regular ANC follow-up at a nearby health facility. She had a history of a malaria attack in the seventh month of the present pregnancy, and she was treated according to the guidelines. The neonate was brought with the complaint of high-grade fever and intense crying since birth. He also had decreased breast feeding and a decreased amount of urine after one day. On examination, the patient was acutely sick, his pulse rate was 178 bpm, his temperature was 40 degrees Celsius (febrile), and his admission weight was 3000 grams. The other vital signs were within the normal range. The other system examinations were unremarkable. He was investigated with a thin and thick blood film, and the result was positive for Plasmodium falciparum ++. His blood sugar level was 40 mg/dl, indicating hypoglycemia, and his hemoglobin level was 14.9 g/dl. A diagnosis of congenital malaria, hypoglycemia, and neonatal dehydration secondary to poor intake and EONS was made. He was given a bolus of 10% dextrose in water and then put on a continuous glucose infusion rate of 6 mg/kg/min until his blood glucose normalized. He was also resuscitated with 10 ml/kg normal saline once. He was given 3 mg/kg artesunate according to the national malaria protocol of Ethiopia for five days. He also received first-line antibiotics, i.e., ampicillin and cefotaxime, for sepsis. He was discharged after 7 days of hospital stay. At the follow-up clinic, the patient was in stable health with optimal growth.\u003c/p\u003e\n\u003ch3\u003ePatient 3\u003c/h3\u003e\n\u003cp\u003eThis is a 24-hour-old male neonate born to a 26-year-old Para III mother via spontaneous vaginal delivery at a nearby health center. The total duration of labor was 6 hours, and the membrane ruptured intrapartum. The birth weight was 3000 grams, and the Apgar score was unknown, but the mother reported that he cried immediately after birth. She had regular ANC follow-up at her nearby health center, which was uneventful. She had no history of malaria attacks. The neonate was brought with the complaint of high-grade fever since he was born. On examination, he was acutely sick, his pulse rate was 150 bpm, his temperature was 39 degrees Celsius, and his admission weight was 3000 grams. The other system examinations were negative. He was investigated with a thin and thick blood film, which revealed Plasmodium falciparum ++. His hemoglobin level was 16.2 g/dl. A diagnosis of congenital malaria and EONS was made. He was treated with 3 mg/kg artesunate for five days according to the national protocol. First-line antibiotics were administered for 7 days. He improved and was discharged after 7 days of hospital stay. At the follow-up clinic, the patient appeared stable, with optimal growth patterns.\u003c/p\u003e\n\u003ch3\u003ePatient 4\u003c/h3\u003e\n\u003cp\u003eA 3-day-old male neonate was born to a 26-year-old Para III mother via spontaneous vaginal delivery at a nearby health center with an unknown birth weight and Apgar score, but he cried immediately after birth. She had regular ANC follow-up, which was uneventful. She had a history of malaria attacks soon after birth in her immediate postpartum period. Accordingly, she was treated at the referring health center. The neonate was brought with the complaint of high-grade fever since birth, and he was referred to our hospital for neonatal intensive care. A malaria rapid diagnostic test (RDT), which was performed at the referring health center, was positive for P. vivax. He was referred after one dose of chloroquine was given. At admission to our center, on physical examination, the patient was acutely sick, his pulse rate was 152 b/m, his temperature was 39 degrees Celsius (febrile), and his weight was 3000 grams. The other system examinations were unremarkable. A thin and thick blood smear was obtained and revealed Plasmodium vivax++, which is consistent with RDT. A diagnosis of congenital malaria and EONS was made. He was treated with artesunate 3 mg/kg/dose for five days according to the national malaria protocol of Ethiopia. Additionally, first-line antibiotics were given for 7 days. The patient was in good health and had optimal growth at the follow-up clinic.\u003c/p\u003e\n\u003ch3\u003ePatient 5\u003c/h3\u003e\n\u003cp\u003eA 16-day-old male neonate was born to a 30-year-old mother. His birth weight was 3200 grams. The Apgar scores at the 1st and 5th minutes were 8 and 9, respectively. She had regular ANC follow-up at her nearby health facility, which was uneventful. She had a history of malaria attacks before the present pregnancy. The neonate was brought with the complaint of abdominal distention, vomiting of breast milk and decreased urine for 3 days. On examination, the patient was acutely sick, his pulse rate was 180 bpm, his temperature was 39 degrees Celsius (febrile), and his weight was 2700 grams. The other vital signs were within the normal range. The abdomen was distended and soft with out-of-organomegally on palpation. The other system examinations were not revealing. He was investigated with a thin and thick blood smear, and the results revealed Plasmodium falciparum+. A diagnosis of neonatal malaria and EONS was made. He was treated with 3 mg/kg artesunate for 7 days according to the national malaria protocol. A course of first-line antibiotics was also given. However, the abdominal distension persisted, and the antibiotics were continued for two weeks. Further evaluations via abdominal ultrasound and vital signs were normal. After two weeks of hospital stay, the patient was discharged with improvement. At the follow-up clinic, the patient was stable with optimal growth patterns.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient 6\u003c/h2\u003e \u003cp\u003eA 10-day-old female neonate, with an unknown birth weight and Apgar score, was born vaginally to a 30-year-old IV mother at a nearby health center, but she cried immediately after birth. She had regular ANC follow-up three times at a nearby health facility, and it was uneventful. She had a history of malaria treatment in the early stage of pregnancy. She presented with a complaint of high-grade fever for 3 days. She had a history of abnormal body movement for two to three episodes per day, vomiting of breast milk, decreased mentation and failure to pass through urine, which was associated with significant weight loss of the same duration. Otherwise, she had no history of any external bleeding. On examination at admission, she was lethargic, her pulse rate was 180 bpm, her respiratory rate was 68 bpm, which was interpreted as tachypnic, and her temperature was 40 degrees Celsius, which was translated as febrile. In addition, she was desaturated to 80% with atmospheric oxygen. Her weight at admission was 2000 grams. She had pale conjunctiva and icteric sclera. Chest examination revealed subcostal and intercostal retraction and good air entry in the bilateral lung fields. Abdominal examination revealed splenomegaly. On musculoskeletal examination, she had a bony and skin appearance, the skin pinch returned slowly, she appeared pale, her capillary refill was fast, and she was jaundiced up to the level of the chest. Neurologic examination indicated lethargy and depressed primitive reflexes. She was investigated with a thin and thick blood film, which was positive for mixed Plasmodium falciparum\u0026thinsp;+\u0026thinsp;and P. vivax +. Her blood glucose level was 35 g/dl, indicating hypoglycemia. The complete blood count revealed a white blood cell count of 10,000, a platelet count of 123,000, which suggested mild thrombocytopenia, and a hemoglobin level of 6.7 g/dl, which was interpreted as severe anemia. She was admitted with a diagnosis of neonatal malaria, neonatal seizures secondary to cerebral malaria, meningitis and hypoglycemia. In addition, prerenal azotemia secondary to sepsis and malaria was also considered. A diagnosis of severe sepsis involving the central nervous system, hematology and respiratory system was also included. She was managed with intranasal oxygen (1 liter per min), a bolus of 4 ml/kg 10% dextrose in water followed by a glucose infusion rate of 6 mg/kg/min until it normalized. She was resuscitated with 20 ml/kg normal saline twice, but she did not pass through the urine. She was transfused with 20 ml/kg fresh whole blood two times, and she was started on 3 mg/kg artesunate according to the national malaria protocol. She was also started on first-line antibiotics, i.e., ampicillin and cefotaxime, at a meningeal dose. She was also initially loaded and reloaded with phenobarbital, and she did not respond; then, she was again loaded with phenytoin and then continued with maintenance doses of both drugs. In addition, diazepam was given as needed. The families were advised to refer to a level III NICU center for further management and investigations, such as renal function tests and electrolyte determination. However, the families refused the referral, and the physician in charge advised them on the prognosis. She was on treatment and routine intensive care unit (ICU) care at our center until she died after 48 hours.\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\u003eSummary of admission characteristics and treatment outcomes, cases of congenital and neonatal malaria, Tigray region, northern Ethiopia\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\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCharacteristics\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eCongenital malaria\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eNeonatal malaria\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCase 1\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCase 2\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCase 3\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eCase 4\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCase 5\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eCase 6\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMaternal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalaria treatment history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeonate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (d/H)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 H\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth wt(kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eUnknown\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdmission wt (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of fever (d)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFast breathing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePoor breastfeeding\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSigns\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTemperature(Celsius)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJaundice\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePallor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRR(breath/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSPO\u003csub\u003e2\u003c/sub\u003e(atm oxygen)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e92%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e94%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatomegaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSplenomegaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLaboratory\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemoglobin(g/dl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e16.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMalaria\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood smear\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eP.f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eP.f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP.f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP.V\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP.f\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eP.f and P.V\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOxygen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntimalarial\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood transfusion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome at discharge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eRecovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRecovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRecovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRecovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eRecovered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003edied\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eD \u0026ndash;day, H - Hour, Pf - Plasmodium falciparum, Pv - Plasmodium vivax, NA- Not available, wt - weight\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eEthiopia remains one of the countries with a high malaria burden, with 75% of the total area being malarious and approximately 52% of the population living in a malaria risk area(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). P. falciparum and P. vivax are the two dominant parasite species causing malaria in Ethiopia, with relative frequencies of approximately 60% and 40%, respectively(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The epidemiology of congenital and neonatal malaria is elusive in Ethiopia, except for a few case reports and series, particularly in the Tigray region of Ethiopia.\u003c/p\u003e \u003cp\u003eStudies have indicated that the main presentation of NCM is variable degrees of fever starting from the first day of life and beyond(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). All our patients were brought by their parents primarily with the complaint of fever. Similarly, Olupot‑Olupot et al. and colleagues in their case series reported that 3 of the 4 NCMs presented with fever(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Fever can also be a manifestation of sepsis. Malaria should be considered a cause of fever in the neonatal period, and appropriate malaria tests should be performed, particularly in malaria endemic areas. However, a significant number of NCM cases in endemic areas can present with atypical manifestations, including poor feeding, jaundice, excessive crying, diarrhea and vomiting, convulsion, anemia, thrombocytopenia, hypoglycemia, respiratory distress, hepatomegaly, splenomegaly, bloody stools, hypothermia, apnea and cyanosis, and can be asymptomatic (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Tesso et al. and associates from southern Ethiopia in their case series reported three neonates with NCM who presented without fever (\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). The sole presentations of these patients were anemia and jaundice(\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e). Initially, neonates usually present with features of sepsis. The concomitant presence of sepsis and malaria in neonates is characterized by fever, vomiting, abdominal distension, decreased breastfeeding, irritability, changes in mentation and abnormal laboratory parameters such as low blood glucose levels and anemia(\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Therefore, it might be misdiagnosed and hence may result in mistreatment. A high suspicion of malaria, especially when fever persists while the patients are on standard antibiotic management, may be an important clue. In such cases, appropriate malaria work-up should ensue. All six of our patients had features of neonatal sepsis, and at the beginning of their admission, antibiotics were initiated. However, despite on antibiotics fever persisted and the patients were screened early for malaria; thus, the results were positive for various species of malaria. However, a significant number of patients whose malaria tests were negative responded well to the clinical addition of antimalarial medications. This highlights that the clinical consideration of NCM should not be ignored in malaria-endemic areas.\u003c/p\u003e \u003cp\u003eMalaria endemicity has been suggested to play a role in the prevalence of NCM. Vertical transmission is low in hyperendemic areas and high in low endemic areas due to immune development (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The diagnostic modalities of NCM include thin and thick blood smears, RDT and molecular tests such as PCR. Although there is a low density of circulating parasites in neonates, a thin and thick blood film is regarded as the standard diagnostic modality(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). All six of our patients were diagnosed with blood film. One of our patients underwent a malaria rapid diagnostic (RDT) test at the referring health center, and the results were positive for p. vivax. The blood film obtained at our center for this patient also revealed P. vivax, which was consistent with the RDT results. One study indicated that real-time PCR yields higher positivity rates than blood smears from the peripheral smears of neonates (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). When available, PCR tests are excellent in cases of low-density parasites such as neonates(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). In this study, all placental malaria confirmed by real-time PCR were also confirmed to be positive microscopically(\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, this diagnostic method is difficult to use in low-income countries such as ours for obvious reasons.\u003c/p\u003e \u003cp\u003eThe treatment of NCM is usually off-label, similar to older children. Indeed, parenteral treatments are better in neonates and young infants for various reasons (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). In our cases, we used artesunate 3 mg/kg/dose, which is in line with the Ethiopian and WHO malaria guidelines. The duration of treatment mainly depends on the patient\u0026rsquo;s condition, including the presence of complications, which can last five to seven days. All our patients were on first-line antibiotics because of overlapping signs and symptoms and coincidence of bacterial infection. Although artemisinin-based combination therapy is the recommended treatment for uncomplicated malaria in infants, neonates have been largely excluded from ACT clinical trials (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Furthermore, the WHO currently allows those under 5 kilograms to be treated in a similar way to older infants (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe WHO acknowledges that most anti-malaria drugs lack infant formulations, which can lead to either under- or overdosing (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This was observed in one of our patients, where he took a higher dose of chloroquine prior to his referral to our hospital. In addition, infants can deteriorate rapidly; therefore, there should be a low threshold for parenteral treatment(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). The other standard treatment for malaria in older children is primaquine. However, primaquine is contraindicated during pregnancy, breastfeeding mothers and infants under six months of age due to insufficient data in these populations (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). Nonetheless, studies have reported that there are no significant side effects in those aged greater than 28 days(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Similar to the other drugs the physiological immaturity and rapid changes that occur in neonates, the pharmacokinetic and dynamic profiles of antimalarial drugs are likely different from those of older children(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, NCM is an important diagnosis to consider in any newborn with clinical features of neonatal sepsis from a malaria-endemic area. Focusing on prevention, routine blood smears for malaria screening and early treatment of malaria in neonates with features of sepsis in endemic areas will help reduce morbidity and mortality related to NCM. Moreover, this case series highlights the need for standard routine malaria tests in neonates, particularly in malaria-endemic areas.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eANC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eantenatal care\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003econgenital malaria\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEONS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEarly-Onset Neonatal Sepsis\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eNCM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eNeonatal and Congenital Malaria\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePCR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePolymerase Chain Reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTORCH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eToxoplasmosis, Others, Rubella, Cytomegalovirus, Herpes\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eWHO\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eWorld Health Organization\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\u003eEthical approval for the publication of this case report was obtained from the Aksum University College of Health Science ethics committee with approval number IRB098/2025.\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 patients\u0026rsquo; parents for publication of this case series. A copy of the written consent is available for review by the editor-in-chief of this journal upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData sharing is not applicable to this article, as no data sets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study did not receive any grants or funding from either for-profit or nonprofit organizations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo;\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003econtributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eYemane Leake Gebremichael\u003c/strong\u003e: Conceptualization, Visualization, Supervision, Writing- Original draft preparation. \u003cstrong\u003eHindeya Hailu Hagos\u003c/strong\u003e: Data curation, Writing- Original draft preparation.\u0026nbsp;\u003cstrong\u003eBirhanu Kassie Reta\u003c/strong\u003e: Visualization, Investigation, Writing review and editing.\u0026nbsp;\u003cstrong\u003eTiegst Bahta Woldu;\u003c/strong\u003e Writing review and editing, \u003cstrong\u003eKinfe Redae Berhe\u003c/strong\u003e; Writing review and editing, \u003cstrong\u003eFantay G/mariam G/Aregay\u003c/strong\u003e; Writing review and editing, \u003cstrong\u003eGebremskel Kiros Tsegay\u003c/strong\u003e; Writing review and editing\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMiani Hospital NICU and Laboratory Team\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eWorld Health Organization. WHO guidelines for malaria, 30 November 2024 [Internet]. World Health Organization; 2024 [cited 2025 Feb 8]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://iris.who.int/handle/10665/379635\u003c/span\u003e\u003cspan address=\"https://iris.who.int/handle/10665/379635\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalaria Case Management. Training Manual for Health Professionals in Ethiopia Participants Manual. ministry of health, ethiopia; 2022.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMenendez C, Mayor A. Congenital malaria: The least known consequence of malaria in pregnancy. Semin Fetal Neonatal Med. 2007;12(3):207\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDanwang C, Bigna JJ, Nzalie RNT, Robert A. Epidemiology of clinical congenital and neonatal malaria in endemic settings: a systematic review and meta-analysis. Malar J. 2020;19(1):312.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOlupot-Olupot P, Eregu EIE, Naizuli K, Ikiror J, Acom L, Burgoine K. Neonatal and congenital malaria: a case series in malaria endemic eastern Uganda. Malar J. 2018;17(1):171.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAmaratunga C, Lopera-Mesa TM, Brittain NJ, Cholera R, Arie T, Fujioka H et al. A Role for Fetal Hemoglobin and Maternal Immune IgG in Infant Resistance to Plasmodium falciparum Malaria. Gruner AC, editor. PLoS ONE. 2011;6(4):e14798.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOmer SA, Adam I, Noureldien A, Elhaj H, Guerrero-Latorre L, Silgado A, et al. Congenital Malaria in Newborns Delivered to Mothers with Malaria-Infected Placenta in Blue Nile State, Sudan. J Trop Pediatr. 2020;66(4):428\u0026ndash;34.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSotimehin SA, Runsewe-Abiodun TI, Oladapo OT, Njokanma OF, Olanrewaju DM. Performance of a rapid antigen test for the diagnosis of congenital malaria. Ann Trop Paediatr. 2007;27(4):297\u0026ndash;301.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBillig EM, McQueen PG, McKenzie FE. Foetal haemoglobin and the dynamics of paediatric malaria. Malar J. 2012;11(1):396.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEkanem AD, Anah MU, Udo JJ. The prevalence of congenital malaria among neonates with suspected sepsis in Calabar, Nigeria. Trop Doct. 2008;38(2):73\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMwaniki MK, Talbert AW, Mturi FN, Berkley JA, Kager P, Marsh K, et al. Congenital and neonatal malaria in a rural Kenyan district hospital: An eight-year analysis. Malar J. 2010;9(1):313.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBilal JA, Malik EE, Al-Nafeesah A, Adam I. Global prevalence of congenital malaria: A systematic review and meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2020;252:534\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIbhanesebhor SE. Clinical Characteristics of Neonatal Malaria. J Trop Pediatr. 1995;41(6):330\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUneke CJ. Congenital malaria: an overview. Tanzan J Health Res. 2011;13(3):264\u0026ndash;80.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThapa BR, Narang A, Bhakoo ON. Neonatal Malaria: a Clinical Study of Congenital and Transfusional Malaria. J Trop Pediatr. 1987;33(5):266\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTesso ZG, Gossaye TY, Bekana DS, Kebede MA, Besir FD, Dabe NE. Plasmodium falciparum neonatal malaria with atypical presentation: a case series from southwestern Ethiopia. Malar J. 2024;23(1):178.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWHO guidelines for malaria [Internet]. Geneva: WHO; 2022. 425 p. Available from:https://books.google.com/books?hl=en\u0026amp;lr=\u0026amp;id=In0OEQAAQBAJ\u0026amp;oi=fnd\u0026amp;pg=PA7\u0026amp;dq=WHO+malaria+guideline+2022\u0026amp;ots=mQmn64m8WM\u0026amp;sig=AaSyc_xIQjCF2EN8BtpVi0Cr7sY\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRupa DKM. Clinical Presentation and Management of Neonatal Malaria: A Review. Malar Chemother Control Elimin [Internet]. 2014 [cited 2025 Mar 2];03(02). Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.omicsonline.com/open-access/clinical-presentation-and-management-of-neonatal-malaria-a-review-2090-2778.1000126.php?aid=37135\u003c/span\u003e\u003cspan address=\"https://www.omicsonline.com/open-access/clinical-presentation-and-management-of-neonatal-malaria-a-review-2090-2778.1000126.php?aid=37135\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\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":"Congenital malaria, Neonatal malaria, Neonate, Malaria, Tigray","lastPublishedDoi":"10.21203/rs.3.rs-6227110/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6227110/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCongenital malaria (CM) is the direct infection of a neonate with malaria parasites from their mother prior to or during birth. Neonatal malaria (NM) is acquired through mosquito bites after birth in the neonatal period. Both neonatal and congenital malaria (NCM) are potentially life-threatening conditions that can mimic other neonatal conditions, such as neonatal sepsis; therefore, these conditions can be misdiagnosed and mistreated. Although NCM is widely recognized in most parts of the world, including Africa, there is currently a scarcity of data and experience regarding NCM in the Tigray region specifically and in Ethiopia generally. The purpose of this case series was to increase awareness of clinicians to the practice of screening, treatment and prevention of NCM, particularly in endemic areas.\u003c/p\u003e\u003ch2\u003eCase presentation\u003c/h2\u003e \u003cp\u003e: We present a series of six cases (four congenital and two neonatal malaria cases). The age of their mothers ranged from 23\u0026ndash;30 years, and their birth experience ranged from 1\u0026ndash;5. Four of the six mothers had a history of malaria attack and treatment, three of whom were during the present pregnancy and one of whom had an attack in the immediate postpartum period. The age of the neonates at admission ranged from 1 day to 16 days. All six neonates were brought by their parents with the primary complaint of fever. Blood smears of four of the six neonates revealed ring stages of Plasmodium falciparum, and Plasmodium vivax was detected in one of the neonates. Additionally, a mixture of Plasmodium falciparum and P. vivax was detected in another neonate. Antimalarial and first-line antibiotics were administered to all six neonates. Five of them were treated successfully and recovered, and one of them died while she was on treatment.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eNeonatal congenital malaria should be considered in any newborn with clinical features of neonatal sepsis from a malaria-endemic area, particularly those who present with fever. Routine malaria prevention strategies and malaria screening tests should be considered for neonates in malaria-endemic areas.\u003c/p\u003e","manuscriptTitle":"Neonatal and Congenital malaria (NCM): A Case Series in Tigray region, Ethiopia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-22 07:46:19","doi":"10.21203/rs.3.rs-6227110/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-04-28T04:00:38+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-26T15:26:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-04-16T09:56:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"336215293483739306418310635103096934820","date":"2025-04-05T23:25:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"332582580541745028516739015953692422660","date":"2025-04-04T11:48:23+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-04-01T14:31:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-01T04:44:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Malaria Journal","date":"2025-03-30T10:11:10+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":"6799afa5-8219-4a85-960a-8590a0f28aa5","owner":[],"postedDate":"April 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-07-07T16:10:50+00:00","versionOfRecord":{"articleIdentity":"rs-6227110","link":"https://doi.org/10.1186/s12936-025-05466-8","journal":{"identity":"malaria-journal","isVorOnly":false,"title":"Malaria Journal"},"publishedOn":"2025-07-01 15:57:48","publishedOnDateReadable":"July 1st, 2025"},"versionCreatedAt":"2025-04-22 07:46:19","video":"","vorDoi":"10.1186/s12936-025-05466-8","vorDoiUrl":"https://doi.org/10.1186/s12936-025-05466-8","workflowStages":[]},"version":"v1","identity":"rs-6227110","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6227110","identity":"rs-6227110","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}