Group 1: 148 term infants were born and treated in the Department for healthy infants of the Obstetrics and Gynaecology Hospital, Sofia; in the period from 5 to 18 February 2019. Two to 5 days after discharge respiratory symptoms were observed in 14 of them. Twelve babies were hospitalized in different Paediatric Departments in Sofia with symptoms of LRTI (bronchiolitis). Symptomatic treatment was carried out and a few days later after recovery, they were discharged home. There were no complications established for any of these infants. In 4 of the hospitalized babies, as well as in the 2 outpatient infants, the RSV-PCR tests from nasal/throat swabs were found positive. In the other 8 hospitalized newborns RSV etiology was suggested due to epidemiological contact between them and the typical LRTI symptoms, but PCR was not performed.
The epidemic outbreak in the NICU (Group 2): In the period from 19 February to 15 March 2019 RSV-infection was established for 7 very low birth weight and extremely low birthweight in-born infants, aged 1–3 months, and treated in the Neonatal Intensive Care Unit (NICU). The data for these patients are summarized in Table 1.
Table 1
Data and outcome for RSV-PCR positive preterm infants
P
|
GW
|
BW
(g)
|
Sex
|
D
|
BPD
|
Palivi-sumab
|
RSV-
PCR I
|
RSV-
PCR II
|
RSV related symptoms
|
MV
O2
|
Bacterial
Co-infection
|
RSV-outcome
|
1
|
26
|
1050
|
M
|
95
|
+
|
3
|
(+)
|
(+)
|
Severe LRTI
Pneumonia
|
AV
|
Enterobacter cloacae, MRSE
(tracheal probe)
|
Prolonged hospitalization
|
2
|
27
|
840
|
M
|
84
|
+
|
1
|
(+)
|
(+)
|
Severe LRTI
Pneumonia
|
AV
|
Stenotrofomonas
maltofilia
(tracheal probe)
|
Prolonged hospitalization
|
3
|
33
|
1410
|
M
|
46
|
-
|
-
|
(+)
|
No
data
|
LRTI
(mild)
|
O2
|
-
|
Recovered
|
4
|
34
|
1410
|
M
|
23
|
-
|
-
|
(+)
|
(+)
|
LRTI (moderate)
Pneumonia
|
O2
|
-
|
Recovered
|
5
|
31
|
1470
|
M
|
33
|
-
|
-
|
(+)
|
(+)
|
LRTI
(moderate)
|
O2
|
-
|
Recovered
|
6
|
27
|
1100
|
M
|
69
|
+
|
1
|
-
|
(+)
|
LRTI
(moderate)
|
O2
|
-
|
Recovered
|
7
|
27
|
850
|
F
|
69
|
+
|
1
|
-
|
(+)
|
No symptoms
|
-
|
-
|
Healthy
|
P: Patient N; GW: gestational weeks at birth; BW: birthweight; Sex: M = male, F = Female; D: days after birth with 1st positive RSV-PCR; BPD: O2 at 36 GW; Palivisumab: number of applications before the 1st positive RSV-PCR test; RSV-PCR I and II: first and second RSV-PCR test; MV/O2: Mechanical Ventilation/ Oxygen supplementation; LRTI: Lower Respiratory Tract Infection; |
The first NICU-patient (Р1) was a 3 months old male infant, a twin, born at 26 gestational weeks (GW), with a birth weight of 1050 g. The infant had severe bronchopulmonary dysplasia (BPD) but he was already stable and about to be discharged home. The baby had already received three injections of palivizumab from the in-hospital palivizumab-immunoprophylaxis course. At the age of 94 days, there was a rapid deterioration with progressive respiratory failure and symptoms of acute LRTI. The tested nasal and throat swabs were PCR-RSV positive. Due to critical deterioration during the following days, mechanical ventilation was required, including high-frequency oscillations and assisted/controlled ventilation with 100% oxygen at the beginning. The status of the infant was complicated by superimposed bacterial co-infection – pneumonia. Staphylococcus epidermidis and Enterobacter cloacae were isolated from the probes, taken by bronchial lavage. Antibiotics according to their sensitivity, inhaled corticosteroids (budesonide) and bronchodilators (β2-agonists), cardiotonic treatment, diuretics, an additional (booster) palivizumab injection were administered. There was a slow improvement, the infant was extubated, stabilized, and was transferred to the Paediatric Department for further treatment of the severe BPD. The second RSV-PCR test which was performed at D23 after the onset of the disease remained positive. In summary, RSV infection in this patient significantly deteriorated the clinical course of BPD and delayed discharge home by more than 2 months.
During the period 19 February − 15 March 26 preterm babies, who were treated in the NICU and were in direct (one room) or indirect (medical staff, parents) contact with the first RSV-PCR positive patient, were tested for RSV (33 nasal/throat swabs). All these 26 babies received a prophylactic first or subsequent (booster) dose of palivisumab. We identified 11 positive samples for 7 of the babies with gestational age 26–34 GW, and birthweight 840–1470 g, who were put in isolation (Table 1). In 9 of the samples, RSV-B was typified, in 2 samples typing was not possible. In 4 babies the second RSV-PCR, which was performed from 1 to 3 weeks after the first sample, remained positive, but the clinical symptoms of LRTI were resolved. Due to respiratory deterioration and contact with each other (twins) 2 babies were re-tested after negative first samples and found to be RSV-PCR positive. In 6 of all 7 RSV (+) premature infants, symptoms of LRTI (bronchiolitis) occurred, 2 of them were with severe respiratory failure and mechanical ventilation was performed, 3 babies were with moderate, 1 with mild symptoms of LRTI, 1 baby (P7, a girl twin) remained asymptomatic. All RSV positive babies were stabilized, 6 of them – discharged home, one was transferred to the Paediatric department, and later discharged too.
For Patient 1 (P1) the clinical RSV-related symptoms and the RSV-PCR positive test occurred after 3 injections of palivizumab, in P2, P6, and P7 - after one injection. These infants were of gestational age 26–27 GW and had underlying BPD, only one of them (the girl) remained without respiratory deterioration. For P3, P4 and P5 palivizumab prophylaxis had not yet been started before the first RSV (+) test. Their gestational age was greater (31–33 GW), they were without BPD and the clinical symptoms of LRTI were mild or moderate.
The following measures have been taken to control the epidemic outbreak:
At the Departement for healthy newborns: intensification of the disinfection regime; restricting visits for relatives other than the mother; denied access for medical staff/parents with respiratory symptoms. As a result of these measures, the epidemic situation was put under control, and after 18.02.2019 there were no new cases with RSV-related respiratory symptoms in full-term infants during the stay in the neonatology ward or following their discharge home.
At the NICU: The RSV-positive patients were isolated from those, who were in contact with them, but asymptomatic until RSV-testing was performed, as well as from those who were not in contact. Palivizumab was administered to all symptomatic and in-contact patients (26infants in total): in 22 of them, it was 1st application, in 4–a booster dose.