Transplacental transmission of dengue infection

Abstract

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.

Key Words: Vertical transmission; Transplacental; Congenital dengue; Infectious disease; DENV

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 5^th 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.