Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus–Associated Pneumonia Among Children Aged &lt;5 Years in the PERCH Study

Higdon, Melissa M.; Le, Tham Thi; O’Brien, Katherine L.; Murdoch, David R.; Prosperi, Christine; Baggett, Henry C.; Brooks, W. Abdullah; Feikin, Daniel R.; Hammitt, Laura L.; Howie, Stephen R. C.; Kotloff, Karen L.; Levine, Orin S.; Scott, J. Anthony G.; Thea, Donald M.; Awori, Juliet O.; Baillie, Vicky L.; Cascio, Stephanie; Chuananon, Somchai; DeLuca, Andrea N.; Driscoll, Amanda J.; Ebruke, Bernard E.; Endtz, Hubert P.; Kaewpan, Anek; Kahn, Geoff; Karani, Angela; Karron, Ruth A.; Moore, David P.; Park, Daniel E.; Rahman, Mohammed Ziaur; Salaudeen, Rasheed; Seidenberg, Phil; Somwe, Somwe Wa; Sylla, Mamadou; Tapia, Milagritos D.; Zeger, Scott L.; Knoll, Maria Deloria; Madhi, Shabir А.; Fancourt, Nicholas; Fu, Wei; Kagucia, E. Wangeci; Li, Mengying; Wu, Zhenke; Watson, Nora; Crawley, Jane; Zaman, Khalequ; Goswami, Doli; Hossain, Lokman; Jahan, Yasmin; Ashraf, Hasan; Antonio, Martín; McLellan, Jessica; Machuka, Eunice; Shamsul, Arifin; Zaman, Syed; Mackenzie, Grant; Morpeth, Susan; Kamau, Alice; Kazungu, Sidi; Ominde, Micah Silaba; Sow, Samba O.; Tamboura, Boubou; Onwuchekwa, Uma; Kourouma, Nana; Touré, Aliou; Adrian, Peter V.; Kuwanda, Locadiah; Mudau, Azwifarwi; Groome, Michelle; Mahomed, Nasreen; Thamthitiwat, Somsak; Maloney, Susan A.; Bunthi, Charatdao; Rhodes, Julia; Sawatwong, Pongpun; Akarasewi, Pasakorn; Mwananyanda, Lawrence; Chipeta, James; Mwansa, James; Kwenda, Geoffrey; Anderson, Trevor P.; Mitchell, Joanne

doi:10.1093/cid/cix150

Cited by 96 publications

(107 citation statements)

References 41 publications

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“…After duplicate removal, the title and abstracts were manually sorted and matched according to the inclusion and exclusion criteria. A total of 16 articles were fully reviewed [7,[10][11][12][13][14][15][16][17][18][19][20][21][22][23]. Afterward, details were extracted for each article as described in methods.…”

Section: Resultsmentioning

confidence: 99%

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Blood biomarkers differentiating viral versus bacterial pneumonia aetiology: a literature review

Thomas¹,

Pociūtė

Kėvalas

et al. 2020

Ital J Pediatr

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Background and objectives: The goal of this literature review is to compare current studies regarding the accuracy of different serum markers in differentiating viral from bacterial pneumonia in the pediatric population with what is employed in the medical settings at present. Currently there is still a lack of significant research, that would give us evaluation on biomarkers benefits towards getting a definite diagnosis of pneumonia. Finding out the potential of biomarkers to differentiate between viral and bacterial pneumonia is also important because knowing the exact pathogen would prevent irrational use of antibiotics. At present, irrational, broad-spectrum antibiotic use and increasing antibiotic resistance in microorganisms are still one of the greatest challenges in clinical settings. The use of biomarkers in clinical practice would not only facilitate accurate diagnosis, but would also help to reduce the amount of antibiotics overuse. Materials and methods: Literature search conducted on Medline and Google Scholar using a combination of terms. Articles that were in English and within ten years of the search date were manually sorted according to inclusion and exclusion criteria. Results: Initial search returned n = 13,408. After activating filters, n = 140 were identified of which n = 12 included for literature review. Conclusions: Rise or drop in the concentration of a single marker is not accurate enough for predicting viral/ bacterial community acquired pneumonia. This is because there is overlapping to a varying extent depending on the marker cutoff values, detection methods, analyses, the desired specificity, and sensitivity. Furthermore, the presence of mixed infection makes almost all markers suboptimal to be used universally. New markers such as MxA1 and HMGB1 gave promising results. However, to replicate a similar testing condition in a clinical environment may not be practical. Another approach is to make use of more than one marker and combine with clinical signs and symptoms. This may not be cost-effective in many clinical settings; nevertheless, in many studies, marker combination greatly improved the predictive power.

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Section: Resultsmentioning

confidence: 99%

“…A total of eleven studies involved CRP [14,16,17,19,20,22,23,[25][26][27][28][29]. In all the studies analysing CRP as a diagnostic marker, the average CRP level was higher in the bacterial group than viral group [14,20,22,23,[25][26][27][28][29].…”

Section: Standard Biomarkers In Community-acquired Pneumonia C Reactimentioning

confidence: 99%

Blood biomarkers differentiating viral versus bacterial pneumonia aetiology: a literature review

Thomas¹,

Pociūtė

Kėvalas

et al. 2020

Ital J Pediatr

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“…O uso de biomarcadores inflamatórios no sangue para distinguir a PAC bacteriana da viral tem sido investigado. A procalcitonina (PCT) e a proteína C-reativa (CRP, do inglês C-Reactive Protein) têm demonstrado algum valor na identificação de infecções bacterianas, 34,35 mas ainda não foi estabelecido um ponto de corte clínico relevante para seu uso. 36 Por exemplo, em um ensaio clínico randomizado italiano, crianças com PAC não grave foram admitidas no hospital especificamente para serem incluídas nessa investigação de PCT: 155 receberam antibióticos se a média de PCT sérica à hospitalização fosse ≥ 0,25 ng /mL e as demais 155 crianças receberam antibióticos com base na avaliação clínica do médico assistente; 133 indivíduos (85,8%) do primeiro grupo e 155 crianças (100%) do segundo grupo receberam antibióticos, respectivamente (p < 0,05).…”

Section: Diagnósticounclassified

Community-acquired pneumonia among children: the latest evidence for an updated management

Nascimento‐Carvalho¹

2020

Jornal de Pediatria

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Objective: To provide cutting-edge information for the management of community-acquired pneumonia in children under 5 years, based on the latest evidence published in the literature. Data source: A comprehensive search was conducted in PubMed, by using the expressionsAll articles retrieved had the title and the abstract read, when the papers reporting the latest evidence on each subject were identified and downloaded for complete reading. Data synthesis: In the era of largely implemented bacterial conjugate vaccines and widespread use of amplification nucleic acid techniques, respiratory viruses have been identified as the most frequent causative agents of community-acquired pneumonia in patients under 5 years. Hypoxemia (oxygen saturation ≤96%) and increased work of breathing are signs most associated with community-acquired pneumonia. Wheezing detected on physical examination independently predicts viral infection and the negative predictive value (95% confidence interval) of normal chest X-ray and serum procalcitonin <0.25 ng/dL was 92% (77---98%) and 93% (90---99%), respectively. Inability to drink/feed, vomiting everything, convulsions, lower chest indrawing, central cyanosis, lethargy, nasal flaring, grunting, head nodding, and oxygen saturation <90% are predictors of death and can be used as indicators for hospitalization. Moderate/large pleural effusions and multilobar infiltrates are predictors of severe disease. Orally administered amoxicillin is the first line outpatient treatment, while ampicillin, aqueous penicillin G, or amoxicillin (initiated initially by intravenous route) are the first line options to treat inpatients. Conclusions: Distinct aspects of childhood community-acquired pneumonia have changed during the last three decades.

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“…The classification scheme was modified from similar schemes for the development of novel diagnostic tests to discriminate between bacterial and viral infection (Herberg et al, 2016;Kaforou et al, 2017). Recent data have estimated a threshold to discriminate between bacterial and viral pneumonia at a CRP concentration of ∼50-60 mg/l in children in South Asia and in low and middle-income countries in the PERCH study (Lubell et al, 2015;Higdon et al, 2017b). We chose NP carriage of pneumococcal serotype 1 (by culture) as a predictor of pneumococcal infection.…”

Section: Classification Of Childhood Pneumonia Etiology By Comparatormentioning

confidence: 99%

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

Carter

Gurung

Jones

et al. 2020

Front. Cell. Infect. Microbiol.

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New diagnostic tests for the etiology of childhood pneumonia are needed. We evaluated the antibody-in-lymphocyte supernatant (ALS) assay to detect immunoglobulin (Ig) G secretion from ex vivo peripheral blood mononuclear cell (PBMC) culture, as a potential diagnostic test for pneumococcal pneumonia. We enrolled 348 children with pneumonia admitted to Patan Hospital, Kathmandu, Nepal between December 2015 and September 2016. PBMCs sampled from participants were incubated for 48 h before harvesting of cell culture supernatant (ALS). We used a fluorescence-based multiplexed immunoassay to measure the concentration of IgG in ALS against five conserved pneumococcal protein antigens. Of children with pneumonia, 68 had a confirmed etiological diagnosis: 12 children had pneumococcal pneumonia (defined as blood or pleural fluid culture-confirmed; or plasma CRP concentration ≥60 mg/l and nasopharyngeal carriage of serotype 1 pneumococci), and 56 children had non-pneumococcal pneumonia. Children with non-pneumococcal pneumonia had either a bacterial pathogen isolated from blood (six children); or C-reactive protein <60 mg/l, absence of radiographic consolidation and detection of a pathogenic virus by multiplex PCR (respiratory syncytial virus, influenza viruses, or parainfluenza viruses; 23 children). Concentrations of ALS IgG to all five pneumococcal proteins were significantly higher in children with pneumococcal pneumonia than in children with non-pneumococcal pneumonia. The concentration of IgG in ALS to the best-performing antigen discriminated between children with pneumococcal and non-pneumococcal pneumonia with a sensitivity of 1.0 (95% CI Carter et al.Antibody-in-Lymphocyte Supernatant for Pneumococcal Pneumonia 0.73-1.0), specificity of 0.66 (95% CI 0.52-0.78) and area under the receiver-operating characteristic curve (AUROCC) 0.85 (95% CI 0.75-0.94). Children with pneumococcal pneumonia were older than children with non-pneumococcal pneumonia (median 5.6 and 2.0 years, respectively, p < 0.001). When the analysis was limited to children ≥2 years of age, assay of IgG ALS to pneumococcal proteins was unable to discriminate between children with pneumococcal pneumonia and non-pneumococcal pneumonia (AUROCC 0.67, 95% CI 0.47-0.88). This method detected spontaneous secretion of IgG to pneumococcal protein antigens from cultured PBMCs. However, when stratified by age group, assay of IgG in ALS to pneumococcal proteins showed limited utility as a test to discriminate between pneumococcal and non-pneumococcal pneumonia in children.

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Association of C-Reactive Protein With Bacterial and Respiratory Syncytial Virus–Associated Pneumonia Among Children Aged <5 Years in the PERCH Study

Cited by 96 publications

References 41 publications

Blood biomarkers differentiating viral versus bacterial pneumonia aetiology: a literature review

Blood biomarkers differentiating viral versus bacterial pneumonia aetiology: a literature review

Community-acquired pneumonia among children: the latest evidence for an updated management

Assessment of an Antibody-in-Lymphocyte Supernatant Assay for the Etiological Diagnosis of Pneumococcal Pneumonia in Children

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