Nasopharyngeal bacterial load as a marker for rapid and easy diagnosis of invasive pneumococcal disease in children from Mozambique

Abstract

BackgroundCurrent diagnostic methods for detection of Streptococcus pneumoniae in children with suspected invasive pneumococcal disease have limitations of accuracy, timeliness, and patient convenience. This study aimed to determine the performance of pneumococcal load quantified with a real-time polymerase-chain reaction in nasopharyngeal samples to diagnose invasive pneumococcal disease in children.MethodsMatched case-control study of patients <5 years of age with invasive pneumococcal disease admitted to the Manhiça District Hospital (Mozambique) and asymptomatic controls recruited in different periods between 2006 and 2014. Cases were confirmed by a positive bacterial culture for S. pneumoniae in blood or cerebrospinal fluid. Nasopharyngeal aspirates were collected from cases and controls and pneumococcal density was quantified by lytA real-time polymerase-chain reaction.ResultsThirty cases (median age 12.8 months) and sixty controls (median age 11.7 months) were enrolled and 70% of them were male. Nasopharyngeal pneumococcal carriage was high in both groups: 28/30 (93.3%) for cases vs. 53/60 (88.3%) for controls (p = 0.71). Mean nasopharyngeal pneumococcal load was identified as a marker for invasive pneumococcal disease (7.0 log10 copies/mL in cases vs. 5.8 log10 copies/mL in controls, p<0.001) and showed good discriminatory power (AUC-ROC: 82.1%, 95% CI 72.5%-91.8%). A colonization density of 6.5 log10 copies/mL was determined as the optimal cut-off value to distinguish cases from controls (sensitivity 75.0%, specificity 73.6%).ConclusionUse of non-invasive nasopharyngeal aspirates coupled with rapid and accurate quantification of pneumococcal load by real-time polymerase chain reaction has the potential to become a useful surrogate marker for early diagnosis of invasive pneumococcal disease in children.

Pneumococcal carriage, density, and co-colonization dynamics: A longitudinal study in Indonesian infants

“…High pneumococcal density in the nasopharynx has been linked to pneumococcal pneumonia and invasive pneumococcal disease, and investigated as a potential diagnostic tool (Baggett et al, 2017;Brotons et al, 2017). The present study provides new insights into pneumococcal density during a carriage episode, highlighting the fact that carriage is a dynamic process, affected by multiple factors including antibiotic exposure and URTIs, as well as the presence of co-colonizing pneumococcal serotypes.…”

Pneumococcal colonization prevalence and density among Thai children with severe pneumonia and community controls

“…Two studies in Vietnam found pneumococcal NP density among children with radiographicallyconfirmed pneumonia was significantly higher than density among healthy controls and children with acute lower respiratory tract infection [9,10]. Studies in South Africa and Mozambique also found higher colonization density among children with IPD compared to controls [8,11]. The colonization density among PERCH cases in Thailand was lower than the density among cases without microbiologically-confirmed pneumococcal disease at other PERCH sites, suggesting that pneumococcal disease may be less common among those presenting to hospital with severe pneumonia in Thailand compared to the other sites.…”

“…Prevalence of pneumococcal colonization is usually much higher in low-and middleincome countries [6], and the first acquisition happens at a younger age compared with highincome settings [3]. Although detecting pneumococcus in the nasopharynx or oropharynx of a child with pneumonia does not indicate an etiologic role, the density of colonization has been associated with pneumococcal disease [7][8][9][10][11], and while of uncertain value for individual diagnosis, may help to improve estimates of pneumococcal pneumonia prevalence in surveillance or observational studies. However, colonization prevalence and density vary by geographic location [7][8][9][10][11], so local data are needed to understand local epidemiology.…”

“…Although detecting pneumococcus in the nasopharynx or oropharynx of a child with pneumonia does not indicate an etiologic role, the density of colonization has been associated with pneumococcal disease [7][8][9][10][11], and while of uncertain value for individual diagnosis, may help to improve estimates of pneumococcal pneumonia prevalence in surveillance or observational studies. However, colonization prevalence and density vary by geographic location [7][8][9][10][11], so local data are needed to understand local epidemiology. Further, because pneumococcal conjugate vaccine (PCV) is serotype-specific, understanding the serotype distribution among colonized individuals informs estimates of potential vaccine effectiveness and is useful to monitor the impact of vaccine when introduced [3].…”

Unraveling the seasonal epidemiology of pneumococcus

“…Because we did not explicitly model carriage density, this interpretation is speculative. However, previous experimental (25) and epidemiological (37) studies have suggested that carriage density in an important factor in transmission and invasion.…”