AJTCCM VOL. 30 NO. 2 2024 37
EDITORIAL
Acute lower respiratory tract infection (LRTI) is one of the leading
causes of mortality in children aged <5 years, globally and especially in
Africa.[1,2] Infants are at the highest risk of requiring hospitalisation and
developing the most severe disease. Further specic environmental
and host risk factors are associated with more severe disease, such
as exposure to tobacco smoke, indoor air pollution, prematurity,
malnutrition, and HIV infection or HIV exposure in infants. Besides
the acute illness, LRTI, especially severe disease, may be associated with
long-term morbidity including chronic lung disease and lung function
impairment.[3] Timely identication of the cause of LRTI is therefore
crucial to initiate appropriate therapy while preventing overuse of
unnecessary treatment, especially in the era of antibiotic resistance.
In addition, accurate diagnosis is important for epidemiological data,
for informing new vaccines and interventions that may be needed,
and for guiding cohorting of patients and infection control measures.
The development of highly effective conjugate vaccines against
Haemophilus inuenzae type b and 10- or 13-valent pneumococcal
conjugate vaccines against Streptococcus pneumoniae has led to a shi
in the spectrum of pathogens causing pneumonia, with a reduced
proportion of bacterial infections, while viruses contribute to a greater
proportion of severe LRTI episodes.[4,5]
In this issue of AJTCCM, Marafungana et al.[6] describe viral pathogens
in children with LRTI admitted to King Edward VIII Hospital, Durban,
South Africa, from January 2018 to June 2020. Clinical and viral data
were retrieved from inpatient les and laboratory records. Multiplex
polymerase chain reaction testing was used for detection of viruses on
dierent respiratory samples. e cohort represents children at high
risk of severe LRTI, with a young age (median 5 months), and almost
50% being HIV exposed and a third malnourished. Adenovirus was the
most commonly detected virus, followed by parainuenza virus and
respiratory syncytial virus (RSV). No seasonal pattern was identied
for adenovirus-associated LRTI, in contrast to RSV- or parainuenza-
associated LRTI. However, viral data were only available in 16% of
children admitted with LRTI over this time, and no data on bacterial or
mycobacterial pathogens were obtained.
Globally, viral pathogens have been identied as a common cause
of LRTI in children aged <5 years, with RSV being the most common
cause of severe viral LRTI in infancy.[7] In a large case-control study of
severe and very severe pneumonia in children hospitalised in seven low-
and-middle-income countries including SA, the Pneumonia Etiology
Research for Child Health (PERCH) Study, RSV was also the most
common pathogen, identied in almost a third of cases.[8,9] Identication
of adenovirus-associated LRTI may not be straightforward because
detection of adenovirus is not invariably associated with LRTI, as
adenovirus can be detected in the nasopharynx of children with upper
respiratory tract infection as well as in healthy asymptomatic children.
[8] A case-control approach would therefore be valuable in attributing
aetiology. Further typing of adenovirus isolates may be helpful, as
specic variants are associated with disease and long-term morbidity,[10]
but these were not undertaken in the study by Marafungana et al.[6]
Determining the aetiology of LRTI may be challenging, especially in
young children. Samples are oen taken from the upper respiratory
tract, such as nasopharyngeal aspirates or swabs, as these are relatively
easy to obtain and have a high yield for PCR-based testing. However,
testing of samples obtained from the upper respiratory tract may not
discriminate between colonising and pathogenic organisms, making
it dicult to attribute aetiology, unless the organism is invariably
pathogenic, such as Bordetella pertussis, RSV or Mycobacterium
tuberculosis. Use of a case-control design with healthy age-matched
children enrolled during a similar time period serving as controls
would be helpful in attributing aetiology. Multiplex PCR testing
is highly sensitive for viral detection, allowing for multiple viral
pathogens to be detected, even when these are colonising organisms.
Obtaining samples of induced sputum may provide more accurate
data on pathogens in the lower respiratory tract, and may be especially
important for detection of M. tuberculosis.[11]
The role of co-infections in LRTI pathogenesis has also been
increasingly appreciated. Co-infection including viral-bacterial
co-infection and viral-mycobacterial infection is common, especially
in severe LRTI. HIV exposure and malnutrition are well-recognised
risk factors for LRTI in infants, as shown in this cohort. Among such
vulnerable infants, additional pathogens such as M. tuberculosis and
Gram-negative bacterial organisms including Klebsiella pneumoniae
have also been found to be important pathogens.[12,13] Finally, the
study also included a period of the COVID-19 pandemic in SA and
the national lockdown that impacted on LRTI hospitalisations and
circulation of viral pathogens, which were significantly reduced
during this time, globally and in SA.[14]
Detection of adenovirus as a cause of LRTI may have important
implications for long-term morbidity, as adenovirus LRTI may
result in post-infectious bronchiolitis obliterans and bronchiectasis,
requiring long-term follow-up.[15] However, the impact of all-
cause LRTI on long-term health in children through adulthood is
increasingly appreciated, including in the development of chronic
obstructive pulmonary disease.[16,17] Data indicate that early-life
LRTI is associated with reduced lung function and an increased risk
of all-cause premature or respiratory mortality.[3,16] ese ndings
underscore the importance of strategies to reduce risk factors,
including nutritional support, avoidance of tobacco smoking and
indoor air pollution exposure from the antenatal period through
childhood, HIV prevention and control, tuberculosis preventive
strategies, and optimal immunisation coverage.
e study highlights the increasing importance of viral pathogens
in the pathogenesis of severe LRTI in children, including those with
underlying comorbidities. Stronger strategies to prevent or ameliorate
comorbidities are needed and new interventions to prevent viral LRTI
are essential, as have recently been developed for RSV in infants.[18]
Finally, the study highlights the need for long-term follow-up of
children with severe LRTI who may have subsequent morbidity, to
optimise their future health.
Determining the aetiology of lower respiratory tract illness
inchildren
38 AJTCCM VOL. 30 NO. 2 2024
EDITORIAL
L aver, FC Paed(SA)
Department of Paediatrics and Child Health and MRC Unit on Child and
Adolescent Health, Faculty of Health Sciences, University of Cape Town,
SouthAfrica
H J Zar, PhD
Department of Paediatrics and Child Health and MRC Unit on Child and
Adolescent Health, Faculty of Health Sciences, University of Cape Town,
SouthAfrica
heather.zar@uct.ac.za
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