Vertical transmission of dengue haemorrhagic fever; anticipation and early detection leading to success in management

Dengue is a vector borne disease responsible for nearly 4 billion infections annually, prevalent in the tropics with seasonal outbreaks (1). Aedes spp. act as the vector (1). There were 105,049 cases of dengue reported in Sri Lanka in 2019 (2). Neonatal dengue infection can result from vertical transmission through placenta (3). We report a case of a newborn with dengue haemorrhagic fever due to vertical transmission. Anticipation and early detection was the key to successful management.


Introduction
Dengue is a vector borne disease responsible for nearly 4 billion infections annually, prevalent in the tropics with seasonal outbreaks (1). Aedes spp. act as the vector (1). There were 105,049 cases of dengue reported in Sri Lanka in 2019 (2). Neonatal dengue infection can result from vertical transmission through placenta (3). We report a case of a newborn with dengue haemorrhagic fever due to vertical transmission. Anticipation and early detection was the key to successful management.

Case presentation
A baby girl was born by vaginal delivery to a primigravida mother with dengue fever at 38 weeks of gestation. She weighed 2300g at birth. Antenatal period was uncomplicated except maternal fever which developed 2 days prior to the delivery. Mother's febrile illness was initially managed as dengue fever (DF) and it was subsequently progressed to dengue haemorrhagic fever (DHF). She was managed in an intensive care unit where she gave birth. The baby was immediately admitted to the Special Care Baby Unit (SCBU) following birth for observation with the suspicion of vertical transmission of dengue. In baby's blood, NS1 antigen was negative on day 2 but become positive on day 4. Ultrasound scan (USS) of abdomen and thorax did not show evidence of leaking on day 4. Results of serial haematological investigations are shown below (Table 1). Baby was fed with expressed breast milk from day 2 of life and started on prophylactic antibiotics; intravenous crystalline penicillin and cefotaxime on day 4.
She developed a significant drop in platelet count 3 down to 58,000/mm with a rise of total white th cell count on 5 day. Repeat USS of abdomen and thorax on day 5 showed pericholecystic fluid and pericardial effusion confirming the diagnosis of DHF (Figures 1 and 2). She was managed as leaking phase of DHF from day 5 with fluid management and monitoring of haemodynamic parameters (pulse rate, blood pressure, capillary refilling time, urine output). She was given maintenance fluid intravenously according to the day of life starting with 60 ml/kg in day 1. Maintenance fluid was increased 15ml/kg per day till day 7. Urine output was measured and targeted to keep above 1 ml/kg/ hour. Urine output and haemodynamic parameters were used to guide the fluid management. A cocktail mixture of fluids with sodium 2-3 mmol/kg, potassium 1-2 mmol/kg and 5% dextrose was used as intravenous fluids from day 2. Our patient did not need any fluid boluses. Microhaemaocrit centrifugers to measure packed cell volume (PCV) were not available in the hospital. Hence the measurement of PCV frequently was not possible. Oozing from puncture sites was noted on day 7 which settled subsequently. No other bleeding manifestations were noted. Platelet count started to rise on day 7 indicating the beginning of the recovery phase of DHF. Baby's haemodynamic parameters were stable throughout the leaking phase. DEN 3 virus was isolated in a blood sample obtained on day 5 of life by Reverse Transcriptase -Polymerase Chain Reaction (RT -PCR). Mother also had DEN 3 virus isolated in her blood in day 7 of her illness. Baby did not have  Baby recovered fully from the illness without any complications.

Discussion
Vertical transmission of dengue could occur transplacentally or via breast milk. Transplacental transmission of dengue virus can occur in late pregnancy (3). A study in New Caledonia showed a vertical transmission rate of 90% in the perinatal period in mothers who had dengue fever close to delivery and dengue virus was detected in breast milk in 75% of breast feeding mothers with DF (4). As this baby was taken into SCBU following birth, it was highly unlikely to have a mosquito bite. Hence, vertical transmission was the only possible mode of transmission. It was not possible to conclude whether mother had primary or secondary dengue infection. A review of 17 neonates with vertical transmission of DF showed fever occurring from day 1 -11 of life with a median on day 4 (6). There are neonatal dengue cases reported in South Asian region including Sri Lanka and rest of the world (7-9). Most neonates recover without complications. Awareness of the possibility of vertical transmission of DF was very important as our patient never had fever during the course of the illness.

Age in days Day
DENV-1 and DENV-3 serotypes of dengue virus are known to cause DHF on primary dengue infection (9). DENV -3 was isolated in our patient.
Management of neonate with DHF is challenging. Early suspicion of vertical transmission, SCBU care with continuous monitoring and fluid management leads to the successful outcome in our patient. Further studies on the possibility of transmission of dengue via breast milk are needed. A guideline on management of DHF in neonates will be helpful.