48 AJTCCM VOL. 30 NO. 2 2024
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Background. Viral causes of lower respiratory tract infections (LRTIs) are associated with increased mortality in children aged <5 years (U5).
Human adenovirus (HAdV) has been associated with severe LRTI; however, its relationship with HIV and malnutrition in South Africa
(SA) is not understood.
Objectives. To identify the prevalence of and factors associated with HAdV LRTIs in hospitalised U5 childen.
Methods. Clinical and viral data on U5 children hospitalised with severe LRTI from January 2018 to June 2020 at King Edward VIII
Hospital, Durban, SA, including results of a multiplex polymerase chain reaction (PCR) panel assay for respiratory viruses, were retrieved
from inpatient les and laboratory databases and retrospectively analysed. Standard descriptive statistics and Pearson’s χ2, Fisher’s exact
and Mann-Whitney tests were used to determine signicant associations with HAdV LRTI.
Results. Among the 206 viral assays analysed (15.6% of all LRTI admissions), HAdV was the most common virus identied. e cohort had
a median (interquartile range) age of 5 (2 - 13) months, 47.3% had perinatal HIV exposure, and 34.5% had severe acute malnutrition (SAM).
No seasonal pattern with HAdV could be demonstrated. SAM and prematurity were signicant risk factors for readmission, and perinatal
HIV exposure was a signicant risk factor for presence of multiple viruses on analysis of a respiratory specimen. Detection of HAdV was
not associated with an increased risk of requiring oxygen or ventilatory support.
Conclusion. HAdV was the most common virus found on analysis of multiplex PCR panel results in children hospitalised with severe LRTI
in SA, where high rates of HIV exposure may result in increased susceptibility to viral co-infections. e role of HAdV as a cause of severe
LRTI in SA infants, who have high rates of HIV exposure, requires greater scrutiny.
Keywords. Adenovirus, lower respiratory tract infection, HIV, children, pneumonia.
Afr J Thoracic Crit Care Med 2024;30(2):e1208. https://doi.org/10.7196/AJTCCM.2024.v30i2.1208
Lower respiratory tract infections (LRTIs), including bronchitis.
bronchiolitis, and pneumonia with or without pleural eusion, are the
most common cause of morbidity and mortality in children worldwide,
especially in low- to middle-income countries (LMICs).[1] Viruses have
been documented to be the leading cause of LRTIs worldwide, especially
following the introduction and uptake of Haemophilus inuenzae and
pneumococcal vaccinations.[1] Of the viruses, respiratory syncytial
virus (RSV) is the most common LRTI pathogen in both high-income
countries and LMICs.[2] Other viruses that commonly cause LRTIs
are inuenza A and B, human parainuenza virus (HPIV), human
metapneumovirus (HMPV) and human adenovirus (HAdV).[2-5]
Amulticentre prospective observational study in LMICs identied
RSV and HMPV as predictors of hypoxaemia and found an association
between in-hospital mortality and these viruses.[5] HAdV was found to
Severe lower respiratory tract infections are associated with human
adenovirus in hospitalised children in a high HIV prevalence area
N Marafungana,1,2 MB ChB, FC Paed (SA); K L Naidoo,1,2 MB ChB, FC Paed (SA), PhD ;
L Gounder,3,4 MB ChB, FC Path (SA) Viro, MMed (Virol); R Masekela,1 MB BCh, MMed (Paed), Cert Pulmonology (SA) Paed, PhD
1 Department of Paediatrics and Child Health, School of Clinical Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban,
South Africa
2 King Edward VIII Hospital, Durban, South Africa
3 Department of Virology, National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, Durban, South Africa
4 School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban, South Africa
Corresponding author: K L Naidoo (naidook9@ukzn.ac.za)
Study synopsis
What the study adds. is study provides retrospective data identifying human adenovirus (HAdV) as the most common cause of severe
lower respiratory tract infection (LRTI) in children aged <5 years (U5). e impact of respiratory syncytial virus as a common pathogen in
children is well established. e study conrms anecdotal evidence that HAdV is an important disease-causing pathogen associated with
LRTI. Children with perinatal HIV exposure and severe acute malnutrition (SAM) may be particularly susceptible.
Implications of the ndings. HAdV must be considered a major cause of severe LRTI in U5 children. Children with LRTI who had perinatal
HIV exposure and those with SAM need to be tested for HAdV and to be monitored for severe disease.
AJTCCM VOL. 30 NO. 2 2024 49
ORIGINAL RESEARCH: ARTICLES
be an important and under-recognised cause of severe LRTI in South
Africa (SA).[6]
Risk factors for severe complicated RSV LRTI include premature
delivery (<37 weeks’ gestation) and asthma.[2,6] Other risk factors for
morbidity and mortality include severe acute malnutrition (SAM),
severe stunting and underlying cardiac disease.[6,7] With regard to
HAdV and LRTI, risk factors identied in previous studies included
HIV infection and SAM in almost half and one-third of patients,
respectively.[6,7] However, the association of HAdV with LRTI in HIV-
uninfected children who were perinatally HIV exposed is not well
described. In SA, a study on children <5 years of age (U5) between
2009 and 2012 found that HIV-infected children were at increased risk
of hospitalisation for LRTI, with RSV the viral pathogen identied in a
high proportion of these cases.[3] HIV exposure and maternal smoking
were also found to be risk factors for LRTI in children in their rst
year of life.[6] Another important pathogen in HIV-infected children
was cytomegalovirus.[7]
ere is a clear seasonal pattern in RSV infections globally, with
dierences between the Northern and Southern hemispheres.[8] While
the impact of RSV in SA children has been well documented,[6] less is
known about the impact and seasonal pattern of HAdV. ere is robust
evidence on the association of HAdV with severe LRTI, including
long-term sequelae such as chronic lung disease and bronchiolitis
obliterans.[7,9]
The objective of the present study was to describe the clinical
characteristics of U5 children hospitalised with severe LRTI who tested
positive for HAdV on a multiplex polymerase chain reaction (PCR)
panel assay for respiratory viruses. In addition, we aimed to identify
whether a seasonal pattern is associated with HAdV infections, and
to determine whether there are specic risk factors associated with
HAdV LRTI in a population of children with high prevalences of SAM
and perinatal HIV exposure.
Methods
This retrospective cohort study reviewed the respiratory virus
multiplex PCR results obtained from processing respiratory specimens
of hospitalised children with LRTI, aged 1 - 59 months, between
1January 2018 and 30 June 2020 at King Edward VIII Hospital (KEH),
Durban, SA. KEH is a referral hospital that caters for a population
with high U5 rates of SAM (9.1% of all U5 hospitalisations, accounting
for 40.8% of in-hospital mortality in this age range).[10] is nutritional
burden is compounded by a high prevalence of HIV infection in all
paediatric hospitalisations and high mortality due to HIV (36.8% of
all U5 mortality is HIV related).[10,11] Children diagnosed with severe
LRTI are referred from other institutions, especially if they require
higher levels of care, i.e. oxygen therapy, high-care monitoring, and
non-invasive and invasive respiratory support.
Study denitions
For this study, a cohort of patients was selected for inclusion from a
larger group of all doctor-diagnosed LRTI admissions to the institution
(history of cough, tachypnoea with and without chest indrawing).
Patients included in the study cohort were those who satised the
following criteria for severe LRTI: presence of cough or difficult
breathing and tachypnoea (age dependent) in addition to a general
danger sign (usually poor feeding); chest indrawing or stridor in a calm
child; presence of hypoxia at presentation (oxygen saturation <90% in
room air); need for a high-care bed (as determined by the attending
doctor); or need for ventilation as per international guidelines.[12] e
denition of severe LRTI used in this study followed the general practice
of the institution, where resource constraints require these patients
(the potential study cohort) to be admitted to a high-care unit where
more intensive nursing and medical cover can be provided (in a well-
resourced environment, they would be admitted to an intensive care
unit). From this potential study cohort, we excluded those with a proven
bacterial aetiology (i.e. a positive blood culture or positive Gram stain),
those subsequently categorised as having mild LRTI (not requiring
oxygen and discharged within 24 hours), those with moderate LRTI
(not requiring oxygen but requiring >24 hours of admission), and those
with a diagnosis of upper airway obstruction (croup). e patients who
satised all inclusion and exclusion criteria and had been tested with a
multiplex PCR panel for respiratory viruses were included in the study.
The time period of the study was initially intended to reflect
3calendar years, to enable us to fully identify and describe any seasonal
patterns associated with respiratory viral pathogens. e COVID-19
pandemic resulted in premature cessation of data collection in June
2020, aer 30 months.
Demographic and clinical variables
Demographic data were accessed through the DigiData system
(DigiData, South Africa) used for inpatient hospital records. The
nutritional status of each child was determined by calculating the
World Health Organization (WHO) weight-for-age z-score (WAZ
score) and weight for height,[13] using the IGROWUP macro for Stata
(WHO Anthro version 3.2.2; StataCorp, USA). SAM was dened as a
WAZ score ≤3[13] and/or the presence of nutritional oedema. e HIV
status of patients was classied as perinatally HIV exposed or HIV
unexposed, and further as HIV positive or HIV negative. Prematurity
was dened as gestational age <36 weeks at birth documented in the
Road to Health book or neonatal unit discharge documents. Routine
laboratory investigations recorded were total white cell count (WCC)
and C-reactive protein (CRP) level. The predominant radiological
ndings on the admission chest radiograph were described by the
admitting doctor (paediatrician) within 24 hours of admission, using
the following categories: no obvious abnormalities detected; interstitial
inltrates; multifocal opacities/consolidation; pleural eusion; and
features of acute respiratory distress syndrome. ese categories are used
by all admitting doctors and have been adapted from the commonly
used radiological categorisation of paediatric chest radiographs.[14]
Quality control measures included a primary data capture sheet to
enter demographic, clinical, laboratory and radiological information
for every patient who had multiplex PCR panel tests for respiratory
viruses done (Supplementary le 1, available online at https://www.
samedical.org/le/2206), with additional secondary verication of the
radiological categorisation for each patient and the laboratory data.
Laboratory testing
Testing was done on respiratory specimens obtained during the rst
24 - 48 hours of admission. e specimens included nasopharyngeal
aspirates, nasal swabs and endotracheal aspirates. Specimens were
immersed in viral transport medium and transported at 4 - 8°C to the
National Health Laboratory Service (NHLS) Department of Virology
50 AJTCCM VOL. 30 NO. 2 2024
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at Inkosi Albert Luthuli Central Hospital within 72 hours of collection.
Specimens were tested using a real-time multiplex PCR panel assay
for respiratory viruses. Viruses that were reported were adenovirus,
inuenza A and B viruses, HPIV types 1 - 3, and RSV. e PCR panel
testing did not include the subtyping of viruses.
Data management
De-identified data were obtained from the NHLS Central Data
Warehouse, including results of multiplex PCR panel testing for
respiratory viruses from all requesting healthcare facilities in
KwaZulu-Natal (KZN) Province for the stipulated period. The
DigiData system used in the hospital for inpatient hospital records
was used to obtain demographic data and enter them on primary
data capture sheets. All data were curated into a password-protected
database for further analysis.
Data analysis
e data collected were analysed using Stata 17 (StataCorp, USA).
Descriptive statistics such as frequencies and percentages were used to
summarise categorical data. Measures of central tendency mean and
median and measures of dispersion, including standard deviation and
interquartile range (IQR), were used to calculate numerical variables.
Pearson’s χ2 test or Fisher’s exact test was used for categoricalcategories,
and the Mann-Whitney test was used for numerical data to test the
null hypothesis for risk factors such as gestational age, nutritional
status, perinatal HIV exposure, and HIV infection. A p-value <0.05
was considered to be statistically signicant.
Ethics approval
Ethical approval was obtained before data collection from the
University of KwaZulu-Natal Biomedical Research Ethics Committee
(ref. no. BREC/00001178/2020), and gatekeeper permission was
obtained from KwaZulu-Natal Department of Health, King Edward
VIII Hospital and the NHLS.
Results
A total of 216 patients (16.4% of all 1319 LRTI hospitalisations)
fullled the inclusion criteria and had a multiplex PCR panel for
respiratory viruses requested at the time of admission (Fig. 1).
Ofthese, 10 were excluded from analysis because either the specimen
had leaked while in transit to the laboratory or the information
required was unavailable for that patient.
The median (IQR) age of the patients whose specimens were
analysed was 5 (2 - 13) months, and 55.3% of patients were male
(Table1). Over a third (35.9%) were premature deliveries, and 41.6%
had previously been admitted to the hospital for LRTI. With regard to
growth parameters, 37.9% and 27.3% were classied as underweight
and stunted, respectively. Just over a third (34.5%) were classied
as having SAM. Nearly half (47.3%) had perinatal HIV exposure;
however, only 9.9% were HIV infected.
e median (IQR) WCC (n=199 patients) was 11.7 (9.1 - 17) × 109/L
and the median CRP level (n=162) was 13.5 (10 - 35) mg/L. Most
patients (80.8%) required oxygen therapy on admission, and 21.4%
required invasive ventilation during their hospitalisation. Radiological
categorisation by the admitting paediatrician (n=204) showed that
55.9% of the patients had interstitial infiltrates with or without
hyperination, 23.0% multifocal opacities/consolidation, and only
16.2% no documented abnormalities detected.
Of the 206 specimens taken for multiplex PCR panel testing for
respiratory viruses, 90 (43.7%) yielded one virus per specimen,
37 (18%) two viruses and 6 (2.9%) three viruses. No viruses were
identied in the remaining 73 specimens (35.4%). HAdV was the most
common virus isolated (n=69) followed by HPIV-3 (n=49) and RSV
(n=43) (Fig.1).
e positivity rates for HAdV, HPIV-3 and RSV on multiplex PCR
panel testing for repiratory viruses on specimens from all healthcare
facilities in KZN, including KEH, during the 30-month study period
Table1. Clinical characteristics of patients who had multiplex
polymerase chain reaction panel testing for respiratory viruses
Characteristic n (%)
Gender (n=206)
Male 114 (55.3)
Female 92 (44.7)
Gestational age (n=198)
Ter m 127 (64.1)
Preterm (<37 weeks) 71 (35.9)
Nutritional categorisation
Weight for age (n=203)
Normal 126 (62.1)
Underweight (≤2 z-score) 77 (37.9)
Weight for height (n=203)
Not severely malnourished 133 (65.5)
SAM 70 (34.5)
Height for age (n=183)
Normal 133 (72.7)
Stunted (≤2 z-score) 50 (27.3)
HIV status (n=203)
Perinatal HIV exposure
Exposed 96 (47.3)
Not exposed 107 (52.7)
HIV laboratory result
Negative 183 (90.1)
Positive 20 (9.9)
Readmission status (n=197)
First admission 115 (58.4)
Repeat admission 82 (41.6)
Oxygen requirement (n=198)
No oxygen required 38 (19.2)
Oxygen required 160 (80.8)
Invasive ventilation (n=201)
No ventilation required 158 (78.6)
Ventilation required 43 (21.4)
Radiological categorisation (n=204)
No abnormalities noted 33 (16.2)
Interstitial inltrates with or without
hyperination
114 (55.9)
Multifocal opacities/consolidation 47 (23.0)
Pleural eusion 6 (2.9)
ARDS like 4 (2.0)
SAM = severe acute malnutrition; ARDS = adult respiratory distress syndrome.
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Number of viruses per
sample identied
Patients with viruses identied,
n=133
Patients with no viruses identied,
n=73
Two viruses,
n=37
One virus,
n=90
Three viruses,
n=6
Results evaluated,
n=206
Excluded (missing les/leaked specimen),
n=10
LRTI admissions during study period,
N=1 319
Multiplex PCR panel assay for respiratory viruses requested,
n=216
HPIV-3,
n=49
RSV,
n=43
Others,
n=12
Inuenza A,
n=16
HAdV,
n=69
Fig.1. Flow diagram illustrating the results of analysis of specimens from children aged <5 years with LRTIs. (LRTI = lower respiratory tract infection;
PCR = polymerase chain reaction; HAdV = human adenovirus; HPIV-3 = human parainuenza virus type 3; RSV = respiratory syncytial virus.)
Month and year
Positivity rate, %
80
70
60
50
40
30
20
10
0
RSV HAdV HPIV-3
Jan 2018
Feb 2018
Mar 2018
Apr 2018
May 2018
Jun 2018
Jul 2018
Aug 2018
Sep 2018
Oct 2018
Nov 2018
Dec 2018
Jan 2019
Feb 2019
Mar 2019
Apr 2019
May 2019
Jun 2019
Jul 2019
Aug 2019
Sep 2019
Oct 2019
Nov 2019
Dec 2019
Jan 2020
Feb 2020
Mar 2020
Apr 2020
May 2020
Jun 2020
Fig. 2. Seasonal pattern of HAdV, HPIV-3 and RSV in KwaZulu-Natal Province over the study period. (HAdV = human adenovirus;
HPIV-3 = human parainuenza virus type 3; RSV = respiratory syncytial virus.)
52 AJTCCM VOL. 30 NO. 2 2024
ORIGINAL RESEARCH: ARTICLES
is illustrated in Fig.2. e positivity rate was used to demonstrate
the seasonality of these viruses, if any. A clear seasonal pattern was
identied specically for RSV, with average peaks between February
and March over the 30 months. For the 2020 period, the peak for
RSV was between March and April and was lower than the previous
years. ere was an increase in the positivity rate for HPIV-3 from
September to November; however, HPIV-3 was also detected during
other months. For HAdV, no clear pattern was identied over the
30 months.
Patients in whom HAdV was the only virus detected were less
likely to require oxygen on admission or invasive ventilation at any
point in their admission than patients with other viruses or patients
with no virus. Table2 compares oxygen and invasive ventilation
requirements in the analysed groups.
On assessing the risk factors for LRTI readmission, it was found
that children with perinatal HIV exposure or HIV-infected children
appeared less likely to have readmissions. Malnourished and overweight
patients seemed more likely to be readmitted (p=0.02), as were those
who had been born prematurely (p=0.001) (Table3). Afamily history
of asthma did not increase the risk of LRTI readmission.
On assessing the risk factors for having multiple viruses per
specimen, patients with perinatal HIV exposure were more likely to
have multiple viruses than those who were not HIV exposed (p=0.03)
(Table4).
Table2. Comparison of oxygen and invasive ventilation requirements of patients with and without HAdV (N=206)
Management required HAdV, n (%) No HAdV, n (%) Total, N p-value
Oxygen therapy 0.61
No 14 (36.8) 24 (63.2) 38
Yes 52 (32.5) 108 (67.5) 160
Unknown 358
Invasive ventilation 0.54
No 51 (32.3) 107 (67.7) 158
Yes 16 (37.2) 27 (62.8) 43
Unknown 235
HAdV = human adenovirus.
Table3. Risk factors associated with readmission†
Risk factor No, n (%) Yes, n (%) Total, N p-value
Gestational age (n=192) 0.001*
Premature 30 (43.5) 39 (56.5) 69
Ter m 83 (67.5) 40 (32.5) 123
Nutritional category weight/age (n=194) 0.3
Normal 76 (62.8) 45 (37.2) 121
Underweight 38 (52.1) 35 (47.9) 73
Nutritional category height/age (n=194) 0.3
Normal 79 (61.2) 50 (38.8) 129
Stunted 34 (52.3 31 (47.7) 65
Nutritional category weight/height (n=196) 0.02*
Normal 83 (64.8) 45 (35.2) 128
SAM 31 (50.0) 31 (50.0) 62
Obese 1 (16.7) 5 (83.3) 6
Perinatal HIV exposure (n=195) 0.02*
Not exposed 53 (51.5) 50 (44.8) 103
Exposed 62 (67.4) 30 (32.6) 92
HIV infection (n=195) 0.23
Negative 102 (57.6) 75 (42.4) 177
Positive 13 (72.2) 5 (27.8) 18
Family history of asthma (n=191) 0.2
No history of asthma 93 (60.4) 61 (39.6) 154
History of asthma 18 (48.6) 19 (57.4) 37
SAM = severe acute malnutrition.
*Signicant (p<0.05).
†Figures based on patients for whom data on readmission were available.
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Risk factors associated with HAdV in LRTI
hospitalisations
On univariate analysis of various risk factors for children with HAdV,
no signicant associations were found with gestational age, perinatal
HIV exposure, HIV infection and malnutrition when compared with
patients with all other types of viruses found and those without any
viruses detected. Table5 shows these risk factor analyses with the
three most commonly found viruses, HAdV, RSV and HPIV-3.
Nosignicant associations were found when we compared these
risk factors among patients with the three most commonly found
viruses, excluding patients with no virus. When comparing patients
who had been born prematurely with those born at term, more of
the former (n=17/71; 23.9%) than the latter (n=18/124; 14.5%) had
RSV (p=0.1).
Discussion
In the present study, HAdV was the most common viral respiratory
pathogen detected in children hospitalised with severe LRTI. e role
of HAdV in severe LRTI, resulting in hospitalisation and mortality, is
of increasing concern worldwide.[8,9] e prevalence of HAdV in our
cohort was 33.5%, higher than in previous SA studies, which reported
gures ranging between 19% and 26% of isolates in children with
LRTI.[3,6] ese gures are, however, much higher than those reported
elsewhere in Africa and in China.[2,15-18] HAdV has been noted in cases
of severe LRTI, and our cohort had similar disease severity to many of
these studies.[8,15-18] Detection of HAdV on nasopharyngeal aspirate or
nasal swab specimens in the absence of control groups may not prove
that HAdV caused the LRTI; however, the increased frequency with
which HAdV is seen in such cases requires further investigation.[19]
In HIV-infected children in the era of antiretroviral treatment, an
association has been noted with HAdV detection.[20] In our cohort,
of whom nearly half were perinatally HIV exposed, the increased
presence of HAdV in severe LRTI admissions was notable.
Studies have documented that HIV-exposed, uninfected infants are
more susceptible to LRTI than HIV-unexposed infants.[21] e higher
HAdV rates in our cohort may be related to the high rate of HIV
exposure; however, other factors such as the severe LRTI inclusion
criteria and high rates of SAM may also have played a role. Our study
also showed that children with perinatal HIV exposure and HIV-
infected children had a signicantly increased rate of multiple viruses
detected on admission. While HIV-infected children have been noted
to have an increased risk of polymicrobial infections with multiple
bacterial, viral and fungal pathogens,[19,20] further investigation is
required with regard to viral pathogens.
HAdV infections have been noted to be associated with severe
LRTI,[15-18] and the present study corroborates this nding, although
HAdV did not confer an increased risk for oxygen requirement or
invasive ventilation when comparing patients with HAdV and those
with RSV/HPIV-3. A more definitive study comparing patients
with mild, moderate and severe LRTI and the roles of various viral
pathogens within these categories is needed, with HAdV subtyping.
[21] e seasonality of RSV has been well documented in SA, and
the present study conrms the previously described peak between
February and April in KZN,[22] and no HAdV seasonality, as
described elsewhere in Africa.[23]
As found in other studies,[6,7] patients in our cohort who had been
born prematurely were more likely to have readmissions and to be
positive for RSV on testing. However, prematurity in our cohort
Table4. Risk factors associated with detection of multiple viruses at admission†
Risk factor 0 or 1 virus, n (%) Multiple viruses, n (%) Total, N p-value
Gestational age (n=195) 0.3
Premature 94 (75.8) 30 (24.2) 124
Ter m 58 (81.7) 13 (18.3) 71
Nutritional category weight/age (n=201) 0.9
Normal 100 (79.4) 26 (20.6) 126
Underweight 59 (78.7) 16 (21.3) 75
Nutritional category height/age (n=201) 0.9
Normal 106 (79.7) 27 (20.3) 133
Stunted 53 (77.9) 15 (22.1) 68
Nutritional category weight/height (n=203) 0.5
Normal 104 (78.2) 29 (21.8) 133
SAM 53 (82.8) 11 (17.2) 64
Obese 4 (66.7) 2 (33.3) 6
Perinatal HIV exposure (n=203) 0.03*
Not exposed 91 (85.0) 16 (15.0) 107
Exposed 70 (72.9) 26 (27.1) 96
HIV infection (n=203) 0.3
Negative 147 (80.3) 36 (19.7) 183
Positive 14 (70.0) 6 (30.0) 20
SAM = severe acute malnutrition.
*Signicant (p<0.05).
†Figures based on patients for whom data were available.
54 AJTCCM VOL. 30 NO. 2 2024
ORIGINAL RESEARCH: ARTICLES
conferred no increased risk of HAdV.
Larger studies with high-risk premature
cohorts need to assess the association with
HAdV infection.[24]
Children with compromised immune
function have been documented as being
at increased risk of HAdV infection for
various reasons.[18,21,23]. The role of SAM
specifically remains elusive in terms of
the risk of virally induced LRTI.[25] In our
cohort, of whom nearly one-third were
severely acutely malnourished, stunted
or underweight, HAdV did not confer an
increased risk when compared with RSV
or HPIV-3.
Study limitations
is study w as a r etrospective le review
of a cohort with incomplete and missing
data. The sample was from single-
institute data. e C OVID-19 p andemic
and associated lockdowns affected viral
respiratory multiplex PCR panel testing
from March 2020 onwards, impacting on
data collection. Criteria for determining
the need to request a multiplex PCR panel
assay for respiratory viruses were based
on admission practices in the institution,
which could potentially bias the selection
and impact on the generalisability of the
study results. Our study did not assess
mortality, length of stay, or the incidence
of persistent lung disease. e cohort was
restricted to patients with severe LRTI only,
so comparisons with mild and moderate
cases could not be drawn. Lastly, we did
not document longitudinal outcomes in
this study.
Conclusion
e most common virus found on multiplex
PCR panel testing for respiratory viruses in
a cohort of infants with severe LRTI in SA
was HAdV. Perinatal HIV exposure may
result in increased susceptibility to viral
co-infections. e role of HAdV as a cause
of severe LRTI in SA infants with high rates
of perinatal HIV exposure requires greater
scrutiny.
Declaration. RM is a member of the
editorial board. The research for this study
was done in partial fulfilment of the
requirements for NF’s MMed degree in
paediatrics and child health at the
University of KwaZulu-Natal.
Table5. A comparison of risk factors for severe lower respiratory tract infection by virus category (HAdV, RSV and HPIV-3)*
Risk factor
HAdV RSV HPIV-3
Neg., n (%) Pos., n (%) Total, N p-value Neg., n (%) Pos., n (%) Total, N p-value Neg., n (%) Pos., n (%) Total, N p-value
Gestational age 0.6
Premature 53 (74.6) 18 (25.4) 71 0.07 54 (76.1) 17 (23.9) 71 0.1 55 (77.5) 16 (22.5) 71
Ter m 77 (62.1) 47 (37.9) 124 106 (85.5) 18 (14.5) 124 92 (74.2) 32 (25.8) 124
Perinatal HIV exposure 0.7
Not exposed 72 (67.3) 35 (32.7) 107 0.8 93 (86.9) 14 (13.1) 107 0.07 83 (77.6) 24 (22.4) 107
Exposed 63 (65.6) 33 (34.4) 96 74 (77.1) 22 (22.9) 96 72 (75.0) 24 (25.0) 96
HIV infected 0.2
Negative 123 (67.2) 60 (32.8) 183 0.5 152 (83.1) 31 (16.9) 183 0.4 142 (77.6) 41 (22.4) 183
Postive 12 (60.0) 8 (40.0) 20 15 (75.0) 5 (25.0) 20 13 (65.0) 7 (35.0) 20
Nutritional category weight for age 0.2
Normal 80 (63.5) 46 (36.5) 126 0.4 103 (81.7) 23 (18.3) 126 0.8 100 (79.4) 26 (20.6) 126
Wasted 53 (70.7) 22 (29.3) 75 61 (81.3) 14 (18.7) 75 54 (72.0) 21 (28.0) 75
Nutritional category height for age 0.6
Normal 84 (63.2) 49 (36.8) 133 0.3 114 (85.7) 19 (14.3) 133 0.07 102 (76.7) 31 (23.3) 133
Stunted 49 (72.1) 19 (27.9) 68 51 (75.0) 17 (25.0) 68 52 (76.5) 16 (23.5) 68
Nutritional category weight for height and nutrional oedema 0.7
Normal 85 (63.9) 48 (36.1) 133 0.3 108 (81.2) 25 (18.8) 133 0.8 103 (77.4) 30 (22.6) 133
SAM 47 (73.4) 17 (26.6) 64 52 (81.3) 12 (18.8) 64 48 (75.0) 16 (25.0) 64
Overweight 3 (50.0) 3 (50.0) 6 6 (100) 0 6 4 (66.7) 2 (33.3) 6
Family history of asthma 0.73
Yes 107 (68.6) 49 (31.4) 156 0.1 124 (79.5) 32 (20.5) 156 0.07 119 (76.3) 37 (23.7) 156
No 21 (55.3) 17 (44.7) 38 35 (92.1) 3 (7.9) 38 30 (78.9) 8 (21.1) 38
*In this table, patients who were positive for HAdV are compared with all other patients who did not have HAdV (they either had other viruses or no viruses), is comparison is replicated for patients with RSV and HPIV.
HAdV = human adenovirus; RSV = respiratory syncytial virus; HPIV-3 = human parainuenza virus type 3; Neg. = patients with no virus plus patients with virus other than specied; Pos. = virus alone or with other viruses; SAM = severe acute malnutrition.
AJTCCM VOL. 30 NO. 2 2024 55
ORIGINAL RESEARCH: ARTICLES
Acknowledgements. e authors thank Dr Cathy Connolly for assistance with
the statistical analysis, and Ms Leora Sewnarain for assistance with editing.
Author contributions. NM, LG and KLN were responsible for the study design,
data collection, data analysis, and draing the manuscript. RM and KLN were
responsible for the supervision of the entire work, study design and manuscript
review.
Funding.None.
Conicts of interest.None.
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Received 22 June 2023. Accepted 25 March 2024. Published 4 July 2024.
