
==== Front
World J Virol
WJV
World Journal of Virology
2220-3249
Baishideng Publishing Group Inc

jWJV.v13.i3.eid91325
10.5501/wjv.v13.i3.91325
91325
Editorial
Transplacental transmission of dengue infection
Zambrano LEA et al. Transplacental transmission of dengue
Zambrano Leonel Eslatkin Aguilar Department of Medicine, Technical University of Manabi, Manabi 130101, Ecuador

Zevallos Victor Manuel Vasquez Department of Medicine, Technical University of Manabi, Manabi 130101, Ecuador
Department of Pediatrics, Verdi Cevallos Balda Hospital, Portoviejo 130105, Ecuador

Soraya Gita Vita Department of Biochemistry, Hasanuddin University, Makassar 90245, Indonesia

Istifiani Lola Ayu Department of Nutrition, Faculty of Health Sciences, Brawijaya University, Malang 65100, Indonesia

Pamungkas Syafrizal Aji Clinic of Yayasan Dana Sosial Al Falah, Malang 65100, Indonesia

Ulhaq Zulvikar Syambani Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong 16911, Indonesia. zulvikar.syambani.ulhaq@brin.go.id

Author contributions: Zambrano LEA, Zevallos VMV conceived the report and data collection; Zambrano LEA is the main contributor to this article; Soraya GV, Istifiani LA, Pamungkas SA performed a literature review; Ulhaq ZS conceived the report, performed a literature review, and wrote the article.

Corresponding author: Zulvikar Syambani Ulhaq, MD, PhD, Research Scientist, Research Center for Preclinical and Clinical Medicine, National Research and Innovation Agency Republic of Indonesia, Cibinong 16911, Indonesia. zulvikar.syambani.ulhaq@brin.go.id

25 9 2024
25 9 2024
13 3 9132527 12 2023
14 6 2024
4 7 2024
©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
2024
https://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.
We specifically addressed the persistent challenge of dengue in endemic regions, highlighting the potential seriousness of dengue infection through vertical transmission. Vertical dengue transmission has been well documented, particularly in hyper-endemic regions, including Ecuador. Herein, we present a neonate diagnosed with congenital dengue and review similar cases from previously published reports. Although congenital dengue is commonly infected with severe serotypes of DENV (DENV-1 and DENV-2) infections, favorable outcomes are generally observed.

Vertical transmission
Transplacental
Congenital dengue
Infectious disease
DENV
==== Body
pmc Core Tip: Dengue, caused by the dengue virus, poses a significant public health concern in tropical regions. While primarily known for its various clinical presentations, severe forms affecting pregnant women and children have been documented. Although vertical transmission of the virus from mother to fetus is uncommon, it can lead to severe complications, underscoring the need for vigilance and specialized care for both mothers and newborns.

INTRODUCTION

Dengue is an emerging tropical disease caused by the dengue virus (DENV) with various clinical manifestations. Although the viral etiology of dengue fever (DF) was identified many years ago, DENV infection remains a public health problem, particularly in tropical regions[1]. Severe clinical forms of dengue infection have been well-documented in pregnant women and children[2]. Moreover, the incidence of DF in pregnant women is increasingly reported, and in several cases, DENV could be identified in the placenta[3], implying a possible intrauterine (vertical) transmission of dengue infection. Vertical transmission is not considered a common mode of dengue infection, and the transmission rate is likely quite low[4]; thus, the case has been infrequently reported globally. Nonetheless, it should be noted that mothers and newborns are prone to dengue shock syndrome and other bleeding manifestations, which require special attention.

VERTICAL DENGUE INFECTION AND SEVERE LIVER FAILURE

A 17-year-old primigravid woman at 37 weeks of gestation was admitted to the Verdi Cevallos Balda public hospital complaining of fever, retro ocular headache, nausea, arthralgia, and myalgia. One day after the admission, patient progressed with edema in the lower limbs and vomiting. A complete laboratory examination revealed a leucocyte count of 8190/mm3 (93.9% of neutrophils), hemoglobin of 10 g/dL, and thrombocyte of 265000/mm3. Later, it is notable that she lived in a high-risk dengue area, the NS-1 antigen test was then evaluated, and DENV infection was confirmed. On the fifth day of hospitalization, epistaxis and rectal bleeding were noticed. And due to the progression of the disease, an emergency cesarean delivery was performed. Postoperatively, the patient was admitted to the intensive care unit for further observation and treated according to the current dengue management guidelines.

The neonate was a female, weighing 2640 g, with an APGAR score of 9 at the 5th minute of life, and she appeared well at birth. There was no history of mosquito bites after birth. A laboratory examination was conducted on the first day, resulting in negative findings for both NS-1 antigen and IgM anti-dengue virus. Other examinations were normal (Figure 1). However, she developed a fever (38.2 °C) on day 4 after birth, followed by jaundice in Kramer's zone 2 and an increase of bilirubin levels (Figure 1). Dengue infection was confirmed after re-assessment of NS-1 antigen. Patient was then transferred to the neonatal intensive care unit for further evaluation. The complete blood count was checked regularly. Her thrombocyte count reduced significantly, reaching the lowest value of 11000/mm3; thrombocyte transfusion was then initiated (Figure 1). Hemoglobin and leucocyte were within a normal limit throughout the illness. The complete blood count variation is depicted in Figure 1. The neonate was finally diagnosed with congenital dengue and neonatal jaundice. Such findings indicated a potential risk of acute liver failure, especially in endemic regions, which is in line with the study by Singh et al[5]. She and her mother were treated according to the dengue management guidelines. Her treatment also included thrombocyte transfusion, anti-inflammatory and antipyretic drugs. She was discharged from the hospital on day 19 in stable condition. Her mother is responsive to the treatment, with no complications, stable within two weeks with normal white cell and platelet counts, and discharged on day 15.

Figure 1 Complete blood count and bilirubin evaluation throughout the illness.

The hyper-endemicity of dengue in several countries, including Ecuador, poses a potential threat to pregnant women and possible vertical transmission to new babies. The incidence of congenital dengue is rare; nevertheless, clinical manifestations and severity between cases vary depending on the newborn's condition. Similar to our cases, congenital dengue is usually manageable with appropriate treatment, and patients are discharged within 1–8 weeks. In order to understand and synthesize a comprehensive view of the case, we also conducted a literature review presenting similar cases by querying from the following database: PubMed, Scopus, and Google Scholar, with the keyword such as “vertical dengue infection”, “transplacental dengue infection”, “neonate”, and “dengue”, without any restriction on language and year of publication. After removing some duplications, we ended up with 50 publications related to our case from various regions, including South East Asia[3,6-14], South Asia[15-24], Central Asia and the Middle East[25-34], South America[35-44], and other regions[45-54]. Nonetheless, it is worth noting that among 154 previously reported cases, 12 cases (7.8%, Figure 2)[3,20,22,24,29,30,35,37] died due to several complications and secondary illnesses, including heart anomalies, low birth weight, and sepsis. Although in most cases, maternal outcome among newborns who died is generally good and discharged within a week, some died due to severe forms of dengue and possibly associated with hypoxia[3,20]. In principle, treatments of congenital dengue are similar among reported cases. Interestingly, a sudden drop in thrombocyte level was observed after a patient received thrombocyte concentrate. At first, we suspected that patient had a refractory state of thrombocytopenia. However, thrombocyte levels slowly increased over time and thus reflecting a reduction of vascular permeability and an improvement in patient outcomes.

Figure 2 Vertical transmission of dengue infection in previously reported studies.

Although dengue serotype was not determined in this case, DENV-4 is typically prevalent in Ecuador, Venezuela, Colombia, and Brazil[55]. Moreover, a study indicates that the DENV-1 and DENV-2 serotypes are closely linked with dengue severity, marked by low antibody levels, compared to DENV-4-infected patients[56,57]. Indeed, DENV-1 and DENV-2 serotypes are commonly identified in congenital dengue (Figure 2). These results imply that vertical transmission of DENV may occur when mother had a low antibody response against dengue infection, particularly due to DENV-1 and DENV-2 serotypes. The placenta is an organ that can effectively reflect the inflammatory response, virus presence, and maternal hemodynamic alterations[3]. As such, examining the immunolocalization of anti-DENV complex in the placenta can be a reliable method for diagnosing maternal dengue. This approach is particularly advantageous since placenta samples are easily accessible for analysis.

CONCLUSION

In summary, although identification of DENV serotypes may not influence dengue management, early detection of serotypes circulating in the territory may help to prevent severe dengue cases in pregnant women and subsequently prevent possible cases of congenital dengue during dengue outbreaks.

Conflict-of-interest statement: All the authors declare that they have no conflict of interest.

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Infectious diseases

Country of origin: Indonesia

Peer-review report’s classification

Scientific Quality: Grade C

Novelty: Grade B

Creativity or Innovation: Grade C

Scientific Significance: Grade B

P-Reviewer: Sotelo J S-Editor: Liu JH L-Editor: A P-Editor: Wang WB
==== Refs
1 Estofolete CF de Oliveira Mota MT Bernardes Terzian AC de Aguiar Milhim BHG Ribeiro MR Nunes DV Mourão MP Rossi SL Nogueira ML Vasilakis N Unusual clinical manifestations of dengue disease - Real or imagined? Acta Trop 2019 199 105134 31415737
2 Nujum ZT Saritha N Prathibha Raj MR Gayathri AV Nirmala C Vijayakumar K Varghese S Seroprevalence of dengue infection in pregnant women and placental antibody transfer Med J Armed Forces India 2019 75 90 95 30705485
3 Ribeiro CF Lopes VGS Brasil P Pires ARC Rohloff R Nogueira RMR Dengue infection in pregnancy and its impact on the placenta Int J Infect Dis 2017 55 109 112 28088588
4 Ranjan R Kumar K Nagar N Congenital dengue infection: Are we missing the diagnosis? Pediatr Infect Dis 2016 8 120 123
5 Singh L Singh A Agarwal M Mishra S Is dengue emerging as important cause of acute liver failure in endemic regions? World J Clin Cases 2017 5 303 306 28798927
6 Haryanto S Yohan B Santoso MS Hayati RF Denis D Udjung GIVW Herlambang Kendarsari RI Trimarsanto H Sasmono RT Clinical features and virological confirmation of perinatal dengue infection in Jambi, Indonesia: A case report Int J Infect Dis 2019 86 197 200 31357059
7 Yin X Zhong X Pan S Vertical transmission of dengue infection: The first putative case reported in China Rev Inst Med Trop Sao Paulo 2016 58 90 27982356
8 Petdachai W Sila'on J Nimmannitya S Nisalak A Neonatal dengue infection: report of dengue fever in a 1-day-old infant Southeast Asian J Trop Med Public Health 2004 35 403 407 15691146
9 Sirinavin S Nuntnarumit P Supapannachart S Boonkasidecha S Techasaensiri C Yoksarn S Vertical dengue infection: case reports and review Pediatr Infect Dis J 2004 23 1042 1047 15545860
10 Witayathawornwong P Jirachanchai O Kasemsut P Mahawijit N Srisakkwa R Severe perinatal dengue hemorrhagic fever in a low birth weight infant Southeast Asian J Trop Med Public Health 2012 43 62 67 23082555
11 Janjindamai W Pruekprasert P Perinatal dengue infection: a case report and review of literature Southeast Asian J Trop Med Public Health 2003 34 793 796 15115089
12 Phongsamart W Yoksan S Vanaprapa N Chokephaibulkit K Dengue virus infection in late pregnancy and transmission to the infants Pediatr Infect Dis J 2008 27 500 504 18434933
13 Chotigeat U Kalayanarooj S Nisalak A Vertical transmission of dengue infection in Thai infants: two case reports J Med Assoc Thai 2003 86 Suppl 3 S628 S632 14700159
14 Aurpibul L Khumlue P Issaranggoon na ayuthaya S Oberdorfer P Dengue shock syndrome in an infant BMJ Case Rep 2014 2014
15 Thaithumyanon P Thisyakorn U Deerojnawong J Innis BL Dengue infection complicated by severe hemorrhage and vertical transmission in a parturient woman Clin Infect Dis 1994 18 248 249 8161636
16 Restrepo BN Isaza DM Salazar CL Ramírez JL Upegui GE Ospina M Ramírez R [Prenatal and postnatal effects of dengue infection during pregnancy] Biomedica 2003 23 416 423 14968920
17 Alallah J Mohtisham F Saidi N Almehdar A Anees A Sallout A Congenital dengue in a Saudi neonate: A case report J Neonatal Perinatal Med 2020 13 279 282 31658068
18 Maroun SL Marliere RC Barcellus RC Barbosa CN Ramos JR Moreira ME Case report: vertical dengue infection J Pediatr (Rio J) 2008 84 556 559 18949127
19 Manzano Núñez R Zapata JA García-Perdomo HA Gomez DA Solís Velasco MA [Perinatal Dengue: A case Report] Rev Chil Pediatr 2017 88 765 770 29546926
20 Ribeiro CF Lopes VG Brasil P Coelho J Muniz AG Nogueira RM Perinatal transmission of dengue: a report of 7 cases J Pediatr 2013 163 1514 1516 23916226
21 Nguyen TM Huan VT Reda A Morsy S Nam Giang HT Tri VD Mau NK Elfaituri MK Hieu TH Hung NT Hirayama K Huy NT Clinical features and outcomes of neonatal dengue at the Children's Hospital 1, Ho Chi Minh, Vietnam J Clin Virol 2021 138 104758 33862538
22 Gupta S Choudhury V Gupta NP Gupta V Pandita A Congenital dengue in neonate Clin Case Rep 2021 9 704 706 33598228
23 Swaminathan A Kirupanandhan S Rathnavelu E Challenges in a unique presentation of congenital dengue with congenital heart disease BMJ Case Rep 2019 12
24 Kaur G Soni S Aggarwal S Saini AS Vertical transmission of dengue-a case report J Obstet Gynaecol India 2014 64 1 2
25 Suarez-Quimi VL Iglesias A Dengue en neonato: Informe de caso Cienc Ecuad 2021 3 18 23
26 Kotha R Madireddi A Mandala V Bapanpally N Konda K Haripriya R Neonatal dengue as never before - A case series Sahel Med J 2021 24 140
27 Inamdar M Danish A Neonatal Dengue Fever Peinatology 2018 4 3
28 Pothapregada S Neonatal Dengue Infection Indian Pediatr 2017 54 1058 Available from: https://www.indianpediatrics.net/dec2017/dec-1058.htm
29 Kaur N Mangal DK Gupta S Singhal C Singh Kaler GP Perinatal Transmission of Dengue: A Case Report Jemds 2020 9 3167 3168
30 Mounica K Pai TS D'Sa S Bhat KG Acute dengue fever in a neonate secondary to perinatal transmission Iran J Neonatol 2021 12 100 103
31 Choudhry SP Gupta RK Kishan J Dengue shock syndrome in newborn: a case series Indian Pediatr 2004 41 397 399 15123872
32 Kanwaljeet KC Varun S Anita A Postnatally acquired dengue in a neonate--a case report J Commun Dis 2013 45 101 103 25141561
33 Razak A Mohanty PK Nagesh NK Alveolar Capillary Dysplasia as a Cause of Persistent Pulmonary Hypertension Indian Pediatr 2015 52 984 986 26615352
34 Krithika MV Amboiram P Latha SM Ninan B Suman FR Scott J Neonate with haemophagocytic lymphohistiocytosis secondary to dengue infection: a case report Trop Doct 2017 47 253 255 27083493
35 Sinhabahu VP Sathananthan R Malavige GN Perinatal transmission of dengue: a case report BMC Res Notes 2014 7 795 25394748
36 Bopeththa BVKM Hemapriya S Gayan Niranga KK Kotigala DSK A case report of dengue haemorrhagic fever during the peripartum period: challenges in management and a case of vertical dengue transmission BMC Infect Dis 2018 18 427 30153795
37 Ekanayake CD Padumadasa S Premaratna R Rajendrajith S Samaranayake WW Transplacental transfer of dengue Ceylon Med J 2014 59 145 146 25556415
38 Mehndiratta S Singhal R Rajeshwari K Dubey AP Dengue fever in infants: report of three cases Trop Doct 2017 47 173 176 27578857
39 Chye JK Lim CT Ng KB Lim JM George R Lam SK Vertical transmission of dengue Clin Infect Dis 1997 25 1374 1377 9431381
40 Chin PS Khoo AP Asmah Hani AW Chem YK Norizah I Chua KB Acute dengue in a neonate secondary to perinatal transmission Med J Malaysia 2008 63 265 266 19248708
41 Pitchaimuthu J Rosli R Shunmugarajoo A Ang E Rahman AA Mustakim S Vertical transmission of dengue: A case report on severe maternal secondary dengue infection diagnosed post delivery Int J Infect Dis 2020 101 161
42 Fatimil LE Mollah AH Ahmed S Rahman M Vertical transmission of dengue: first case report from Bangladesh Southeast Asian J Trop Med Public Health 2003 34 800 803 15115091
43 Shabbir S Ehsan S Congenital Dengue Infection: A Novel Case of vertical transmission of Dengue virus in Karachi, Pakistan Pak J Med Dent 2021 10 98 101
44 Pérez-Padilla J Rosario-Casablanca R Pérez-Cruz L Rivera-Dipini C Tomashek KM Perinatal transmission of dengue virus in Puerto Rico: a case report Open J Obstet Gynecol 2011 1 90 93 31763063
45 Berberian G Fariña D Rosanova MT Hidalgo S Enría D Mitchenko A Moreno J Sánchez Soto I [Perinatal dengue infection] Arch Argent Pediatr 2011 109 232 236 21660390
46 de Avila Aburdene R Arias Jimenez ME Dengue neonatal, reporte de un caso Rev Soc Boliv Pediatría 2012 51 97 99
47 Silva Delgado H Ruiz Ríos JC Vela Barbarán EL Rengifo Del Aguila D García M M Rodríguez Benavides L Mendoza-Ticona A [Neonatal dengue in Peru: a case report] Rev Peru Med Exp Salud Publica 2011 28 140 144 21537783
48 Morgan-Ortiz F Rodríguez-Lugo SM León-Gil Mdel S Gaxiola-Villa M Martínez-Félix NS Lara-Avila L [Hemorrhagic dengue and vertical transmission to the newborn: a case report and literature review] Ginecol Obstet Mex 2014 82 401 409 25016901
49 Snapshot. Available from: https://www.imbiomed.com.mx/articulo.php?id=104147
50 Arteaga-Livias K Bonilla-Crispin A Panduro-Correa V Martínez-Enríquez C Dámaso-Mata B [Dengue in a newborn] Rev Chilena Infectol 2017 34 494 498 29488594
51 Romero-Santacruz E Lira-Canul JJ Pacheco-Tugores F Palma-Chan AG [Neonatal Dengue. Presentation of clinical cases] Ginecol Obstet Mex 2015 83 308 315 26233977
52 Yang ST Chen HL Yeh CT Lee WT Vertical transmission of dengue fever: First case reported in Taiwan J Formos Med Assoc 2015 114 558 559 25800505
53 Mazarin N Rosenthal JM Devenge J [Mother-infant dengue transmission during the 2009-2010 dengue epidemic: report of four cases] Arch Pediatr 2014 21 745 749 24938916
54 Boussemart T Babe P Sibille G Neyret C Berchel C Prenatal transmission of dengue: two new cases J Perinatol 2001 21 255 257 11533844
55 Stewart-Ibarra AM Ryan SJ Kenneson A King CA Abbott M Barbachano-Guerrero A Beltrán-Ayala E Borbor-Cordova MJ Cárdenas WB Cueva C Finkelstein JL Lupone CD Jarman RG Maljkovic Berry I Mehta S Polhemus M Silva M Endy TP The Burden of Dengue Fever and Chikungunya in Southern Coastal Ecuador: Epidemiology, Clinical Presentation, and Phylogenetics from the First Two Years of a Prospective Study Am J Trop Med Hyg 2018 98 1444 1459 29512482
56 Vicente CR Herbinger KH Fröschl G Malta Romano C de Souza Areias Cabidelle A Cerutti Junior C Serotype influences on dengue severity: a cross-sectional study on 485 confirmed dengue cases in Vitória, Brazil BMC Infect Dis 2016 16 320 27393011
57 Rocha BAM Guilarde AO Argolo AFLT Tassara MP da Silveira LA Junqueira IC Turchi MD Féres VCR Martelli CMT Dengue-specific serotype related to clinical severity during the 2012/2013 epidemic in centre of Brazil Infect Dis Poverty 2017 6 116 28764747
