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Cycle 5 (2016 Deadline)
Implementing a combination of rapid diagnostic tests, biomarkers and standard of care procedures for the diagnosis of pneumonia in pediatric patients to improve clinical management in Indonesia
PI: Herman Kosasih (hermaninarespond@gmail.com), INA RESPOND
U.S. Partner: Clifford Lane, National Institute of Allergy and Infectious Diseases, National Institutes of Health
Project dates: December 2016 - February 2021
Project Overview
While advances have been made in the management of childhood pneumonia, gaps remain that may hinder efforts to reduce morbidity and mortality. These gaps include the absence of a universally accepted diagnostic gold standard for childhood pneumonia, especially one that can also differentiate between bacterial and nonbacterial pneumonia. This PEER project evaluated an algorithm using several rapid diagnostic tests (RDT), biomarkers, and standard of care (SOC) procedures in differentiating these different pathogens in pediatric patients admitted to Tangerang and Kariadi hospitals in Indonesia. The study’s secondary goals included identifying the etiologies of pneumonia in children in Indonesia; documenting outcomes; evaluating the use of each RDT (influenza, respiratory syncytial virus, Pneumococcus), biomarkers (C-reactive protein, procalcitonin), and SOC in distinguishing viral and bacterial pathogens; and providing updated strains of circulating viruses, bacteria, and antibiotic resistance.
The researchers aimed to help impact case management in children with pneumonia, from accurate diagnosis to appropriate treatment and development of prevention strategies, reducing childhood morbidity and mortality in Indonesia. Improved information regarding the pathogens causing pneumonia will help to identify and highlight research priorities in pediatric pneumonia and also enable health programs to develop improved control and prevention measures at the community level.
Final Summary of Project Activities
Pneumonia accounts for 15% of all deaths in children under five years of age. The high rate of morbidity in children with pneumonia may be prevented by promoting exclusive breastfeeding, vaccination, and an improved environment, whereas mortality can be reduced by providing appropriate management, including appropriate antibiotic treatment for bacterial infection. Diagnosing pneumonia using current World Health Organization pneumonia diagnostic criteria is challenging, as no one clinical feature is sufficient to diagnose pneumonia definitively. To improve diagnostic performance, a combination of clinical features has to be used. Chest X-rays are neither sensitive nor specific. Radiological findings lag behind clinical findings and are unable to differentiate between viral and bacterial etiologies of pneumonia. Differentiation between viral and bacterial pathogens is becoming more important since the introduction of Hib and pneumococcal vaccines that may shift the substantial causes of pneumonia to viruses. This distinction is also important for guiding appropriate antibiotic treatment. The gold-standard for microbiological pathogen assays require specimens that are difficult to collect, such as nasopharyngeal wash or bronchoalveolar lavage, and may need several days for the results to be available.
To develop an algorithm for the diagnosis of viral and bacterial pathogens in pediatric patients with pneumonia, Dr. Kosasih and his team conducted an observational cohort study among pneumonia patients aged between 2 months and 5 years. The PEER team undertook screening enrollment for the study across five hospitals and conducted monitoring visits at each site. They screened a total of 564 patients, and enrolled 188 subjects in the study, 55% of whom were male. The median age of the subjects was 9 months. The researchers developed approaches to determining the causative pathogen(s) of pneumonia in children using common techniques (culture, molecular assays, and serology) on routinely collected specimens (blood, sputum, induced sputum, and nasopharyngeal swab). Using those approaches, they found 48 (26%) subjects had a bacterial pathogen, 31 (16%) had a viral pathogen, 76 (40%) had both confirmed bacterial and viral pathogens, while in 33 (18%) subjects, the etiological agent could not be determined.
The researchers then analyzed blood biomarkers to help to differentiate bacterial and viral infections. Using five simple laboratory markers (leukocyte count, neutrophil to lymphocyte ratio, absolute neutrophil count, C-reactive protein (CRP), and procalcitonin), they found that procalcitonin has the best single predictor of bacterial status. A combination of leukocyte count with CRP yielded the best predictor of bacterial status overall. They also used biomarkers and characteristics of enrolled subjects, determining several factors as a proxy to predict worse outcomes, which can help to reduce mortality in hospitalized pediatrics pneumonia. In addition to publishing their work in scientific journals, Dr. Kosasih and his group shared their findings with the U.S. Centers for Disease Control and Prevention and the Indonesian National Institute of Health Research and Development (NIHRD). The PI reports that NIHRD has used the results of this study to develop pneumococcal vaccination policy for Indonesia.
Publications
Dewi Lokida, Helmia Farida, Rina Triasih, Yan Mardian, Herman Kosasih, Adhella Menur Naysilla, Arif Budiman, Chakrawati Hayuningsih, Moh Syarofil Anam, Dwi Wastoro, Mujahidah Mujahidah, Setya Dipayana, Amalia Setyati, Abu Tholib Aman, Nurhayati Lukman, Muhammad Karyana, Ahnika Kline, Aaron Neal, Chuen-Yen Lau, and Clifford Lane. 2022. Epidemiology of community-acquired pneumonia among hospitalised children in Indonesia: a multicentre, prospective study. BMJ Open 2022 12:e057957. https://doi.org/10.1136/bmjopen-2021-057957
Yan Mardian, Adhella Menur Naysilla, Dewi Lokida, Helmia Farida, Abu Tholib Aman, Muhammad Karyana, Nurhayati Lukman, Herman Kosasih, Ahnika Kline, and Chuen-Yen Lau. 2021. Approach to identifying causative pathogens of community-acquired pneumonia in children using culture, molecular, and serology tests. Frontiers in Pediatrics 9: 629318. https://doi.org/10.3389/fped.2021.629318
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