Aetiology of childhood pneumonia in low- and middle-income countries in the era of vaccination: a systematic review

Abstract

Background This systematic review aimed to describe common aetiologies of severe and non-severe community acquired pneumonia among children aged 1 month to 9 years in low- and middle-income countries. Methods We searched the MEDLINE, EMBASE, and PubMed online databases for studies published from January 2010 to August 30, 2020. We included studies on acute community-acquired pneumonia or acute lower respiratory tract infection with ≥1 year of continuous data collection; clear consistent case definition for pneumonia; >1 specimen type (except empyema studies where only pleural fluid was required); testing for >1 pathogen including both viruses and bacteria. Two researchers reviewed the studies independently. Results were presented as a narrative summary. Quality of evidence was assessed with the Quality Assessment Tool for Quantitative Studies. The study was registered on PROSPERO [CRD42020206830]. Results We screened 5184 records; 1305 duplicates were removed. The remaining 3879 titles and abstracts were screened. Of these, 557 articles were identified for full-text review, and 55 met the inclusion criteria – 10 case-control studies, three post-mortem studies, 11 surveillance studies, eight cohort studies, five cross-sectional studies, 12 studies with another design and six studies that included patients with pleural effusions or empyema. Studies which described disease by severity showed higher bacterial detection ( Streptococcus pneumoniae , Staphylococcus aureus ) in severe vs non-severe cases. The most common virus causing severe disease was respiratory syncytial virus (RSV). Pathogens varied by age, with RSV and adenovirus more common in younger children. Influenza and atypical bacteria were more common in children 5-14 years than younger children. Malnourished and HIV-infected children had higher rates of pneumonia due to bacteria or tuberculosis. Conclusions Several viral and bacterial pathogens were identified as important targets for prevention and treatment. Bacterial pathogens remain an important cause of moderate to severe disease, particularly in children with comorbidities despite widespread PCV and Hib vaccination.

Nasopharyngeal aspirates in children with severe community-acquired pneumonia collected within 3 days before bronchoscopy can partially reflect the pathogens in bronchoalveolar lavage fluids

“…Respiratory viruses are frequently detected in community-acquired pneumonia (CAP) among children of all ages globally [ 16 – 18 ]. The majority of pathogens associated with hospitalized SCAP in children were viruses in this study, which were consistent with the finding in this field over the past decade in high disease burden low and middle income countries (LMICs) as well as in Europe and the USA [ 11 , 16 , 19 – 23 ]. In this study, seven common respiratory viruses were found in 32.3% (66/204) of the BALFs tested by DFA, and such results were consistent with what we had seen over the past decade [ 12 ].…”

“…Second, we did not use more sensitive molecular biological diagnostic methods, which might lead to low detention rates of pathogens [ 18 , 31 , 32 ]. Third, the human rhinovirus (HRV) was not studied which has become identified as a more prominent lower airway pathogen than previously suspected [ 5 , 7 , 9 , 16 , 17 , 19 , 21 , 28 , 30 ]. We still believed that our study had unique significances, given that the DFA method was based on the existent of viruses antigens judged by naked eyes with fluorescence microscope, and the routine bacterial culture, which are the two classical methods for pathogens detection.…”

A systematic review of clinical, epidemiological and demographic predictors of tuberculosis in children with pneumonia

“…However, while TB is commonly reported in older children and adolescents (5-19 years) in TB endemic countries [ 38 ], the contribution of TB to severe pneumonia and pneumonia-related mortality in this age group is not known. Bacteriological confirmation of pulmonary TB has a higher yield in this age group than in young children, and older children and adolescents should be included in future aetiological studies [ 39 ]. Many of the WHO high-burden TB countries are in the Asia-Pacific region [ 40 ] and the PERCH study recently reported that TB was common in Asian children with severe pneumonia and an abnormal CXR, with a prevalence of 10% and 3.6% in Thailand and Bangladesh respectively [ 38 , 41 ].…”

The dilemma of improving rational antibiotic use in pediatric community-acquired pneumonia

“…Disease causing pathogens are influenced by the child's age, geographic locality, and vaccination coverage. Recent studies from multiple settings have identified respiratory viruses as the most common cause of community acquired pneumonia in young children ( 6 , 8 ). Table 2 provides an overview of common pathogens associated with paediatric pneumonia in otherwise healthy children.…”

“…Recent studies demonstrated that viruses contribute more to lower respiratory tract infections than previously appreciated, also in developing country settings and in children with severe disease (6)(7)(8). Strict social restrictions implemented to contain the COVID-19 pandemic and use of personal protective equipment (PPE) reduced respiratory virus transmission and associated secondary bacterial pneumonia, as demonstrated by a significant decrease in influenza infections and pneumonia due to Streptococcus pneumoniae in children (9,10).…”