The authors have declared that no competing interests exist.
Despite a high burden of respiratory syncytial virus (RSV) infections among children, data on demographic and clinical characteristics of RSV are scarce in low and middle income countries. This study aims to describe the viral etiologies, the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections (LRTI), focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity.
A prospective study among children under two years of age, hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City, Vietnam, from May 2009 to December 2010. Socio-demographic, clinical data and nasopharyngeal swabs were collected on enrolment and discharge. Multiplex real-time RT-PCR (13 viruses) and quantitative RSV RT-PCR were used to identify viral pathogens, RSV load and subgroups.
Among 632 cases, 48% were RSV positive. RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus (RV), metapneumovirus (MPV), parainfluenza virus (PIV-3) and were significantly more frequent in the first 6 months of life. Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV. In multivariate analysis, RV infection was significantly associated with severity while RSV infection was not. Among RSV infections, neither viral load nor viral co-infections were significantly associated with severity. Young age and having fever at admission were significantly associated with both RSV and LRTI severity. A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity.
We report etiologies, the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity.
Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections (LRTIs) in young children. 50% of children are infected by RSV during their first year of life, and by 3 years of age, 100% have experienced at least one infection [
Here, we aimed to describe the viral etiologies and the demographic, epidemiological, and clinical characteristics of children under two years of age who were hospitalized with a LRTI, focusing on RSV (prevalence, seasonality, subgroups, viral load) and its association with disease severity.
The study was conducted from May 2009 to December 2010 (to cover two RSV seasons, that normally coincide with the rainy season) at Children’s Hospital 1 (CH1) and Children’s Hospital 2 (CH2), the two largest pediatric referral centers for southern Vietnam, located in Ho Chi Minh City. Children from the Respiratory Wards (RW), Emergency Care Units (ECU) and Intensive Care Units (ICU) were eligible for inclusion in the study. Patients admitted to the RW are typically those that initially present to the outpatient clinics and were subsequently indicated for admission, while those admitted to ECU or ICU typically presented with more severe symptoms. Inclusion criteria were age between 1 month to 2 years, cough, a clinical diagnosis of LRTI based on WHO criteria [
Socio-demographic data, medical history, clinical data from enrolment to discharge were recorded in standardized case report forms (CRFs). Nasopharyngeal swabs and EDTA blood were collected on the day of enrolment (day 1) and on day 7 or discharge (if patients were discharged before day 7). EDTA blood were used for whole blood cells counting, and liver enzyme measurement by CH1 and CH2 laboratory. Swabs were placed in viral transport medium [
The study was approved by the Institutional Review Board of Children’s Hospitals 1 and 2, the Scientific and Ethics Committee of the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam and by the Oxford University Tropical Research Ethics Committee (OxTREC), Oxford, UK. Written informed consent was obtained from parents or legal guardians of children prior to enrolment into the study.
RNA extraction from nasopharyngeal swabs was done as described previously [
Severe disease on admission was defined as having an oxygen saturation of SpO2<92 or requiring supplemental oxygen or ventilatory support (by nasal cannula, nasal continuous positive airway pressure (NCPAP), mask CPAP or mechanical ventilation/intubation) or clinical cyanosis. A clinical severity score (adapted from [
Clinical symptoms | Score given |
---|---|
Mild fever (37.5 to 38.5°C) | 1 |
High fever (>38.5°C) | 2 |
Respiratory rates from 45–59 per min | 1 |
Respiratory rates from 60–74 per min | 2 |
Respiratory rates from > 75 per min | 3 |
Chest indrawing | 2 |
Wheezing | 1 |
Stridor | 1 |
Apnea | 3 |
Cyanosis | 3 |
Low SpO2 (<92) or under oxygen | 3 |
NCPAP or CPAP or ventilated during hospitalization | 4 |
High ALT |
1 |
High AST |
1 |
* A higher clinical score indicates more severe disease.
** Liver enzymes ALT and AST levels were considered to be elevated if above 36 IU/l and above 58 IU/l, respectively.
Associations between categorical and continuous variables were analyzed using the Mann-Whitney-U test or Kruskal-Wallis test for continuous variables, and the Fisher exact test for dichotomous variables. Spearman’s rank correlation coefficient was used to assess a general monotonic trend between two continuous variables. A simple linear regression model was used to measure linear associations between RSV viral load and age or day of illness or number of leucocytes in blood. Multivariable logistic regression analysis was performed to assess risk factors for severe disease or long hospitalization. The following variables were considered for the models: age, sex, premature birth, previous hospitalization for respiratory illness, other household members sick at home, living with smoker(s), number of members at home, fever, RSV infection (RSV positivity, viral load, and subgroup) and RV infection (RV positivity as single infection or co-infection with RSV). The models’ predictive ability was investigated by calculating the area under the receiver operating characteristic (ROC) curve of the model (AUC), i.e the higher the AUC the better prediction power the model has. The Hosmer—Lemeshow goodness-of-fit test was done to assess model adequacy. The Hosmer-Lemeshow test of goodness-of-fit tests the null hypothesis that there is no difference between the observed and predicted values of the response variables. Therefore, when the test is not significant (p>0.05) the null hypothesis cannot be rejected and this means that the model fits the data well. Risk factors for disease severity or long hospitalization were further assessed using odds ratios (OR) and 95% confidence intervals (95% CIs). All statistical tests were performed as two-tailed tests at 5% significance in either R version 2.13.1 (R Foundation for Statistical Computing, Vienna, Austria) or Intercooled Stata version 9.2 (College Station, TX, USA).
A total of 632 children aged 1–24 months (median 7, IQR 4–12 months) were enrolled into the study between May 2009 and December 2010. 10/632 (2%) patients were admitted to ICU, 36/632 (6%) to the ECU and 586/632 (92%) to the Respiratory Ward. The monthly distribution of children hospitalized for LRTI and enrolled in this study during the study period are shown in
A total of 106/632 (17%)of cases met at least one clinical criterion for severe disease, and 43% (271/632) were hospitalized for >7 days. Among the children requiring supplemental oxygen or ventilatory support, 16/93 (17%) received NCPAP, 2/93 (2%) were intubated.
Diagnoses on admission were based on clinical symptoms, routine laboratory tests and chest radiography; physicians were unaware of viral diagnostic laboratory results. 438/632 (69%) patients were diagnosed with bronchiolitis; 164/632 (26%) with pneumonia, 22/632 (3%) with combined bronchiolitis and pneumonia, 3/632 (0.4%) with laryngotracheitis, and 5/632 (0.8%) with undifferentiated LRTI. In addition to respiratory symptoms, 21/632 (3%) patients had diarrhoea on admission, and 4/632(0.6%) had congenital heart disease (ventricular or atrial septum defects). Only 18/598 (3%) had blood culture test which was part of standard clinical care at hospitals and only 5/18 were positive (
Discharge information was available for 596/632 (94%) cases: 363/596 (61%) of patients fully recovered; 226/596 (38%) had incomplete recovery at the time of discharge; 4/596 (1%) went home without permission (mostly due to economic reasons, patients could not pay hospitalization fee) or formal hospital discharge; and 3 patients (1%) died in the hospital. One fatal case (8 months old) was diagnosed with septicemia and severe pneumonia (
Viral etiologies were identified in the vast majority (91%, 574/632) of patients; single viral infections accounted for 375/632 (59%) of cases and co-infections with multiple viruses were found in 199/632 (31%) (
VIRUSES | All | Single infections | Co- infection | p-value |
---|---|---|---|---|
N = 632 | N = 375 | N = 199 | ||
RSV, n(%) | 302 (48) | 201 (54) | 101 (51) | 0.9 |
RSV A, n(%) | 156 (25) | 101 (27) | 55 (28) | 0.9 |
Median log copies/ml RSVA (IQR) | 7.5 (6.7–8.2) | 7.7 (6.7–8.1) | 7.4 (6.3–8.2) | 0.2 |
RSV B, n(%) | 139 (22) | 93 (25) | 46 (23) | 0.7 |
Median log copies/ml RSVB (IQR) | 7.6 (6.9–8.2) | 7.7 (7.1–8.2) | 7.5 (6.6–8.0) | 0.2 |
Flu, n(%) | 16 (3) | 8 (2) | 8 (4) | 0.2 |
Flu A, n(%) | 10 (2) | 5 (1) | 5 (3) | 0.3 |
Median Cp-value flu A (IQR) | 31 (29–34) | 30 (30–31) | 33 (29–35) | 0.5 |
InflV B, n(%) | 6 (1) | 3 (1) | 3 (2) | 0.4 |
Median Cp-value flu B (IQR) | 31 (29–33) | 32 (29–33) | 30 (20–34) | 0.8 |
AdV, n(%) | 37(6) | 3 (1) | 34 (17) | |
Median Cp-value AdV (IQR) | 35 (31–36) | 35 (30–35) | 34 (31–36) | 0.8 |
EnV, n(%) | 65 (10) | 2 (1) | 63 (32) | |
Median Cp-value EnV (IQR) | 33 (30–35) | 32 (29–35) | 33 (30–35) | 0.8 |
MPV, n(%) | 30 (5) | 17 (5) | 13 (7) | 0.3 |
Median Cp-value MPV (IQR) | 27 (24–36) | 26 (23–29) | 36 (27–36) | |
RV, n(%) | 206 (33) | 87 (23) | 119 (60) | |
Median Cp-value RV (IQR) | 27 (25–30) | 26 (24–28) | 28 (26–31) | |
PIV-1, n(%) | 9 (1) | 5 (1) | 4 (2) | 0.5 |
Median Cp-value PIV-1 (IQR) | 27 (25–30) | 28 (26–30) | 26 (22–32) | 0.5 |
PIV-2, n(%) | 14 (2) | 4 (1) | 10 (5) | |
Median Cp-value PIV-2 (IQR) | 26 (23–30) | 22 (22–23) | 33 (26–36) | |
PIV-3, n(%) | 47 (7) | 18 (5) | 29 (15) | |
Median Cp-value PIV-3 (IQR) | 29 (24–35) | 25 (23–32) | 32 (25–37) | |
PIV-4, n(%) | 25 (4) | 13 (4) | 12 (6) | 0.2 |
Median Cp-value PIV-4 (IQR) | 31 (27–34) | 29 (25–33) | 33 (30–35) | |
hCoV, n(%) | 25 (4) | 8 (2) | 17 (9) | |
Median Cp-value hCoV (IQR) | 29 (27–32) | 27 (24–29) | 30 (28–33) | 0.1 |
PeV, n(%) | 12 (2) | 2 (1) | 10 (5) | |
Median Cp-value PeV (IQR) | 28 (26–29) | 28 (26–31) | 28 (27–29) | 0.7 |
BoV, n(%) | 42 (7) | 7 (2) | 35 (18) | |
Median Cp-value BoV (IQR) | 29 (25–33) | 23 (22–30) | 30 (25–35) | 0.1 |
P-value was calculated between single infections and co-infections groups,
(1) Mann-Whitney test,
(2) Fisher’s exact test,
N.A: not applicable.
A significantly higher proportion of RV, EnV, BoV, AdV, PIV-2, PIV-3, CoV and PeV were detected among co-infections when compared to the single infections (
In the univariate analysis, LRTI severity was associated with younger age (median age in months [IQR] = 5 [3–10] in severe cases versus 7 [4–12] in non-severe cases, Mann- Whitney test p-value = 0.001 –
In multivariate analyses, significant predictors of severity within the entire study population were younger age, presence of fever, and RV single infection (
Independent predictors | Outcome measure | |||||||
---|---|---|---|---|---|---|---|---|
Disease severity | Long hospitalization | |||||||
LRTI children (N = 605) | RSV-infected children (N = 293) | LRTI children (N = 605) | RSV-infected children (N = 293) | |||||
OR(95%) | P-value | OR(95%) | P-value | OR(95%) | P-value | OR(95%) | P-value | |
0.89 (0.85–0.94) | 0.89 (0.81–0.95) | 0.93 (0.90–0.96) | 0.95 (0.91–1.00) | |||||
0.83 (0.51–1.36) | 0.46 | 0.92 (0.44–1.90) | 0.83 | 1.17 (0.81–1.69) | 0.39 | 1.41 (0.82–2.43) | 0.21 | |
1.06 (0.47–2.39) | 0.88 | 1.20 (0.37–3.89) | 0.75 | 1.79 (0.96–3.29) | 0.06 | 2.34 (0.91–5.99) | 0.07 | |
0.99 (0.53–1.83) | 0.96 | 0.43 (0.13–1.42) | 0.17 | 2.49 (1.59–3.92) | 1.29 (0.61–2.72) | 0.49 | ||
1.41 (0.87–2.26) | 0.15 | 1.98 (0.99–3.94) | 1.15 (0.81–1.64) | 0.42 | 1.26 (0.74–2.14) | 0.38 | ||
1.31 (0.81–2.11) | 0.26 | 1.24 (0.63–2.45) | 0.53 | 0.92 (0.66–1.31) | 0.67 | 1.31 (0.79–2.17) | 0.28 | |
1.04 (0.95–1.15) | 0.88 | 1.03 (0.89–1.10) | 0.63 | 1.02 (0.97–1.11) | 0.49 | 0.95 (0.85–1.07) | 0.42 | |
3.82 (2.29–6.36) | 4.84 (2.27–10.30) | 1.77 (1.25–2.51) | 2.66 (1.58–4.47) | |||||
1.39 (0.82–2.39) | 0.22 | 0.60 (0.30–1.17) | 0.13 | 0.79 (0.54–1.15) | 0.22 | 0.79 (0.48–1.30) | 0.36 | |
2.31 (1.17–4.59) | 0.30 (0.08–1.07) | 0.06 | 1.1 (0.63–1.84) | 0.77 | 1.17 (0.58–2.35) | 0.65 | ||
N.A | N.A | 1.03 (0.78–1.35) | 0.85 | N.A | N.A | 1.14 (0.93–1.39) | 0.19 |
(1) RSV single infection factor was used for the model of the whole population and RSV subgroup (RSV B versus A) was used for the model of RSV-infected patients
(2) RV single infection factor for the model of the whole population and RV co-infection with RSV for the model of RSV-infected patients
N.A: not applicable
RSV infections occurred at a younger age than the 3 other leading single viral infections, i.e RV, MPV, PIV-3 (Tables
Virus name | Age groups | ||||
---|---|---|---|---|---|
<2m | 2m-6m | 7m-11m | 12m–24m | Total | |
n = 41 | n = 277 | n = 174 | n = 140 | N = 632 | |
RSV positive, n(%) | 22 (54) | 152 (55) | 74 (43) | 54 (39) | 302 (48) |
RSVA, n(%) | 13 (32) | 84 (30) | 31 (18) | 28 (20) | 156 (25) |
RSV B, n(%) | 9 (22) | 63 (23) | 42 (27) | 25 (18) | 139 (22) |
Both RSVA and RSVB, n(%) | 0 (0) | 5 (2) | 1 (1) | 1 (1) | 7 (1) |
Flu V positive, n(%) | 0 (0) | 6 (2) | 5 (3) | 5 (4) | 16 (3) |
Flu A, n(%) | 0 (0) | 4 (1) | 4 (2) | 2 (1) | 10 (2) |
Flu B, n(%) | 0 (0) | 2 (1) | 1 (1) | 3 (2) | 6 (1) |
AdV, n(%) | 1 (2) | 11 (4) | 15 (9) | 10 (7) | 37 (6) |
EnV, n(%) | 5 (12) | 29 (10) | 17 (10) | 14 (10) | 65 (10) |
MPV, n(%) | 3 (7) | 9 (3) | 9 (5) | 9 (6) | 30 (5) |
RV, n(%) | 10 (24) | 91 (33) | 61(35) | 44 (31) | 206 (33) |
PIV-1, n(%) | 0 (0) | 5 (2) | 2 (1) | 2 (1) | 9 (1) |
PIV-2, n(%) | 0 (0) | 8 (3) | 5 (3) | 1 (1) | 14 (2) |
PIV-3, n(%) | 2 (5) | 16 (6) | 14 (8) | 15 (11) | 47 (7) |
PIV-4, n(%) | 0 (0) | 12 (4) | 7 (4) | 6 (4) | 25 (4) |
CoV, n(%) | 1 (2) | 14 (5) | 6 (3) | 4 (3) | 25 (4) |
PeV, n(%) | 0 (0) | 9 (3) | 2 (1) | 1 (1) | 12 (2) |
BoV, n(%) | 3 (7) | 13 (5) | 12 (7) | 14 (10) | 42 (7) |
26 (63) | 160 (58) | 104 (60) | 85 (61) | 375 (59) | |
9 (22) | 94 (34) | 55 (31) | 41 (29) | 199 (31) | |
6 (15) | 23 (8) | 15 (9) | 14 (10) | 58 (9) |
Single RSV infection | Single RV infection | Single MPV infection | Single PIV-3 infections | ||||
---|---|---|---|---|---|---|---|
N = 201 | N = 87 | p-value | N = 17 | p-value | N = 18 | p-value | |
Median age in months (IQR) | 6 (3–10) | 8 (4–12) | 0.09 |
11 (8–14) | 9 (6–16) | ||
Infant (less than 2months), n(%) | 15 (7) | 5 (6) | 2 (12) | 2 (11) | |||
Infant (2 to 6months), n(%) | 103 (51) | 31 (36) | 2 (12) | 3 (17) | |||
Infant (7 to 11months), n(%) | 47 (24) | 31 (36) | 6 (35) | 7 (39) | |||
Infant (12 to 24months), n(%) | 36 (18) | 20 (23) | 7 (41) | 6 (33) | |||
Male, n(%) | 138 (69) | 62 (71) | 0.7 |
12 (71) | 0.9 |
10 (56) | 0.3 |
Median number of household members (IQR) | 4 (4–6) | 4 (4–6) | 0.7 |
4 (3–5) | 0.3 |
4 (3–6) | 0.4 |
Living with smokers, n (%) | 102/196 (52) | 51/86 (59) | 0.3 |
5 (29) | 0.07 |
12 (67) | 0.2 |
Median birth weight (kg) (IQR) | 3.9 (2.2–3.3) | 2.7 (2.3–3.2) | 0.3 |
3.3 (2.8–3.8) | 0.5 |
3 (2.6–3.4) | 0.7 |
Breastfeeding, n(%) | 148/197 (75) | 59/86 (69) | 0.3 |
16 (94) | 0.07 |
13 (72) | 0.8 |
Premature birth, n(%) | 20/199 (10) | 14/85 (16) | 0.1 |
0/16 (0) | N.A | 1/17 (6) | 0.5 |
Daycare, n (%) | 25/197 (13) | 10/84 (12) | 0.9 |
2/16 (13) | 1.0 |
5/18 (28) | 0.08 |
Previous hospitalization with respiratory illness, n (%) | 22 (11) | 23 (26) | 2 (12) | 0.9 |
3 (17) | 0.5 |
|
Other household members sick at home, n (%) | 76/197 (39) | 36/85 (42) | 0.6 |
5 (29) | 0.5 |
5 (28) | 0.4 |
Fast breathing, n(%) | 166 (83) | 75 (86) | 0.4 |
14 (82) | 1.0 |
14 (78) | 0.6 |
Cyanosis, n(%) | 6 (3) | 3 (4) | N.A | 0 (0) | N.A | 0 (0) | N.A |
Chest indrawings, n(%) | 193 (96) | 81 (94) | 0.3 |
15 (88) | 0.1 |
15 (83) | 0.01 |
Stridor, n(%) | 1 (1) | 1 (1) | 0.5 |
0 (0) | N.A | 0 (0) | N.A |
Wheezing, n(%) | 192 (96) | 76 (88) | 16 (94) | 0.8 |
17 (94) | 0.8 |
|
Fever (>37.5°C), n(%) | 112 (56) | 50 (57) | 0.8 |
7 (41) | 0.2 |
6 (33) | 0.07 |
Fever (≥ 38.5°C), n(%) | 46 (23) | 13 (15) | 0.1 |
5 (29) | 0.5 |
2 (11) | 0.2 |
Rash, n(%) | 2 (1) | 3 (3) | 0.1 |
0 (0) | N.A | 1 (6) | 0.1 |
Runny nose, n(%) | 181 (91) | 70 (81) | 15 (88) | 0.8 |
17 (94) | 0.5 |
|
Low SpO2, n(%) | 19/140 (14) | 6/60 (10) | 0.5 |
1/14 (7) | 0.5 |
1/17 (6) | 0.4 |
Median of duration of hospitalization (IQR) | 6 (5–7) | 6 (5–8) | 6 (4–7) | 0.9 |
6 (5–7) | 0.9 |
|
Duration of hospitalization ≥ 7 days, n(%) | 77 (38) | 43 (49) | 0.08 |
7 (41) | 0.8 |
7 (39) | 1.0 |
High ALT, n(%) | 54 (27) | 16 (18) | 0.1 |
2 (12) | 0.2 |
3 (17) | 0.3 |
High AST, n(%) | 44 (22) | 9 (10) | 4 (23) | 0.9 |
3 (17) | 0.6 |
|
Median of number of white cells in blood (K/mm3) (IQR) | 10 (8–14) | 13 (11–17) | 11 (9–13) | 0.8 |
11 (8–17) | 0.6 |
|
Severe cases, n(%) | 36 (18) | 22 (25) | 0.2 |
3 (18) | 1.0 |
3 (17) | 1.0 |
Median of clinical score (IQR) | 6 (4–7) (n = 186) | 5 (4–7) (n = 80) | 0.5 |
5 (4–6) | 0.4 |
4.5 (4–6) | |
Bronchiolitis, n(%) | 162 (81) | 65 (75) | 0.3 |
10 (59) | 0.06 |
9 (50) | 0.005 |
Antimicrobial agents, n(%) | 169 (84) | 62 (71) | 17 (100) | 0.07 |
17 (94) | 0.2 |
|
Corticosteroids, n(%) | 9 (4) | 6 (7) | 0.4 |
1 (6) | 0.8 |
0 (0) | N.A |
Bronchodilators, n(%) | 168 (84) | 67 (77) | 0.2 |
9 (52) | 10 (56) | ||
Supplemental oxygen, n(%) | 31 (15) | 21 (24) | 0.08 |
2 (12) | 0.7 |
2 (11) | 0.6 |
Full recovery, n(%) | 119/195 (61) | 46/81 (57) | 0.5 |
11 (73) | 0.8 |
11 (65) | 0.9 |
Severe cases, n(%) | 36 (18) | 22 (25) | 0.2 |
3 (18) | 1.0 |
3 (17) | 0.9 |
Death, n(%) | 0 (0) | 1(1) | N.A | 0 (0) | N.A | 0 (0) | N.A |
p-values were based on comparison with children having RSV single infections.
(1) Mann-Withney test,
(2) Fisher’s exact test,
N.A: not applicable
A higher clinical severity score was found only among RSV single infection cases compared to those of PIV-3 single infection cases (Mann-Withney test p-value = 0.02,
Among 302 RSV positive cases, 156/302 (52%) were RSV A, 139/302 (46%) were RSV B, and 7/302 (2%) were both RSV A and B. There was no difference in proportion of A and B subgroups between single and co-infections, and no difference in viral load among subgroups at enrolment (
Strong seasonal variations of RSV prevalence with peaks during the rainy season from May to October were observed over the two seasons of the study. RSV B was dominant during the first season and RSV A during the second season (
The most frequently detected viruses in RSV co-infection were RV, EnV and AdV (
In multivariate analyses for the RSV-infected population, the logistic regression analysis of ten selected predictors identified age (OR = 0.88, 95%CI:0.81–0.95, p-value = 0.001), fever (OR = 4.80, 95%CI:2.26–10.19, p-value = 0.001), and having another household member sick at home (OR = 2.04, 95%CI: 1.03–4.02, p-value = 0.04) as independent variables associated with disease severity in RSV-infected children (
Over the last decade, multiplex molecular diagnostics have revolutionized the diagnostics of respiratory infections and greatly expanded the available data on viral etiologies and coinfection [
Our study confirms the importance of RSV infection in children under two as shown by many other studies [
One of our aims was to determine risk factors for severity and long hospitalization among all study patients and among RSV-infected patients. We observed that RSV load at enrolment was significantly related to long hospitalization in univariate analysis, but this was not confirmed in the multivariate analysis; and RSV infection, RSV viral load, RSV subgroups and RSV slope (i.e RSV load dynamic between two time points: admission and discharge, it was calculated by dividing the difference of viral load at admission and at discharge by the number of days between these two time points—data not shown), did not correlate to disease severity or long hospitalization. Only young age and fever were independent predictors for disease severity in both populations (study population and RSV population). Reports about the relation between RSV infection [
Thus far, observations regarding the relation between viral co-infections and disease severity have been contradictory and biased by different study designs and viral diagnostic tools used [
Despite the fact that the study population from our current study and our previous study [
From this cohort, we have recently reported analysis of RSV whole genomes [
There are a number of limitations to our study. Firstly, few bacterial diagnostic results were obtained from patients. The role of bacteria as a cause of LRTI or as cause of superinfection, especially in RSV and influenza virus infection [
In summary, our study has contributed detailed clinical and virological data on RSV and other viruses in respiratory infections among children under 2 years old, the most vulnerable age group, in a lower middle income setting in Asia: Vietnam. The data on seasonality of viruses are crucial for health care management, such as preparedness for the annual epidemics in terms of hospital capacity and RSV prevention in high-risk children using Palivizumab.
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We acknowledge study nurses Hoang thi Minh Tu, Nguyen thi Hong Ngoc, Nguyen Viet Truong, Nguyen thi Ngoc Ha, Nguyen thi Thanh Nha, Le thi Kim Loan, Ho Huynh Nhu, Tran thi Tuyet Nhung, Huynh thi Phuong Thao, for sample collection; staff in Data Management at OUCRU for entering data; Vo Nhi Ha and Nguyen thi Thanh Thuy and the Clinical Trials Unit at OUCRU and Children’s Hospital 1 and 2 for coordinating the trial.
This study was funded by the Wellcome Trust of Great Britain (077078/Z/05/Z). The funder had no role in study design, data collection or analysis, the decision to publish, or preparation of the manuscript.