Above photo obtained from PATH/Satvir Malhotra. A worker at Serum Institute of India inspects vaccine vials at the company’s vaccine manufacturing division where PNEUMOSIL® and other conjugate vaccines are made.
A Comment from the Coordinator
Happy new year from the Pneumonia Innovations Network (PIN)! Some exciting news to greet the new year. After over a decade of development and research, Serum Institute of India’s PNEUMOSIL®, a new and highly anticipated 10-valent pneumococcal conjugate vaccine has received World Health Organization pre-qualification with a target price of US$2 per dose.
In addition, this month in our Deep Breaths Blog, we will hear from PIN Member Ron Dagan as he discusses whether pneumococcal vaccines can help answer the question: What is pneumococcal pneumonia?
January 29-31 at CosmoCaixa in Barcelona, Spain, the Global Forum on Childhood Pneumonia will host a call to action to deliver concrete measures to address pneumonia.
The PIN is looking to feature more member-generated content in our coming newsletters and on our website. Submit your interests for blog authorship, your member updates, and any suggestions or comments via the PIN webpage Contact Us field.
DEEP BREATHS: Blogs from PIN Members
What is pneumococcal pneumonia? Can pneumococcal conjugate vaccines help answer the question? By Ron Dagan
It is well accepted that acute lower respiratory tract infection (LRI) is the leading cause of death in children in developing countries, and the most common cause of hospital visits in young children in the developed world. However, no appropriate clinical definition exists as to what is pneumonia and how to distinguish it from other LRIs. Without such “gold standard” we were unable to predict the potential impact of pneumococcal conjugate vaccines (PCVs) before their implementation.
Furthermore, we know that LRIs are often caused by more than a single pathogen, either because one pathogen paves the way for another (e.g., influenza with bacterial secondary infections) or because two or more pathogens co-infect the lung simultaneously. The important involvement of Streptococcus pneumoniae (pneumococcus) in LRIs has always been recognized, but the actual extent of this involvement has not been clear, especially in those presenting with non-alveolar pneumonia (also termed lobar pneumonia or consolidated pneumonia). Since PCVs currently cover up to 13 pneumococcal serotypes, and one can only rarely isolate the organism in pneumonia, the extent to which the vaccines could reduce LRIs, even if pneumococcus had an important role, constituted a great enigma. This is why PCV experts have decided that prospective surveillance projects looking at the impact of PCVs on LRIs should be initiated and long-term follow-up implemented. This could allow us to look separately at various LRI outcomes (e.g., consolidated pneumonia, all-cause clinically diagnosed pneumonia [consolidated and non-consolidated], or even all-cause LRIs, including what is considered to be viral LRI). The impact of PCV on each of these outcomes can provide insights regarding the pneumococcal etiology or cost-benefit analyses, and also could shed light on the true role of PCVs in reducing LRIs, the number one killer of young children worldwide. Gaining insights on vaccine-preventable disease burden by observing the impact of vaccines, is termed the “vaccine probe” approach.
The first hint that PCVs could do much more than just reduce classical consolidated pneumococcal pneumonia came from South Africa, where during a clinical trial of an experimental PCV, they observed a substantial reduction in pneumonia in which viruses were detected, until then classified as “viral pneumonia.” The insight gained from that study was the importance of bacterial-viral co-infections. Currently, 20 years after the first implementation of a PCV - PCV7 in the USA in 2000 - we have enormously advanced our understanding of PCVs’ potential to reduce all-cause LRIs. Multiple studies have shown a reduction of consolidated pneumonia in young children, with an observed decline in 50% or higher, attesting to the important role of vaccine serotypes in this entity. The big enigma was whether a considerable reduction could also be observed in non-consolidated LRIs, indicating the important involvement of pneumococcal vaccine-serotypes.
The message deriving from the vaccine probe approach measuring the impact of PCVs on all-cause LRIs was very loud and clear: There was a decline of up to one-third (and sometimes even more) of any of the currently used diagnoses of LRIs (all-cause clinical pneumonia, all-cause LRI, viral-bacterial co-infections), in each region/country where PCVs were implemented and high vaccination coverage was achieved.
The impact of PCVs on all-cause LRIs is therefore many fold higher than expected. Two decades ago, we wondered “What is pneumococcal pneumonia?” Currently, using the vaccine probe approach, we can answer - the spectrum of pneumococcal pneumonia ranges from simple “viral” LRI all the way to consolidated pneumonia. Pneumococci, and in particular the serotypes included in the PCVs, are frequently involved in LRIs of all sorts, which then makes the entire spectrum of LRIs vaccine-preventable. The currently widely implemented PCVs have made the world a better place to be born into.
Author: Professor Ron Dagan is Distinguished Professor of Pediatrics and Infectious Diseases and Gunzburger Chair for Study of Infectious Diseases at the Faculty of Health Sciences of the Ben-Gurion University of the Negev in Beer-Sheva, Israel. His contribution to the field of infectious diseases prevention, in particular pneumococcal diseases, is globally recognized.
ARTICLES AND NEWS
Recent selected articles from PIN members:
Variability in the use of pulse oximeters with children in Kenyan hospitals: A mixed-methods analysis
By AJ Enoch, M English, Clinical Information Network, G McGivern, S Shepperd. Published in PLoS Med. Dec 31, 2019.
The authors carried out statistical analyses on a data set of 27,906 children admitted to 7 Kenyan hospitals and interviews with 30 healthcare workers and staff at 14 Kenyan hospitals. They found that there was variability in the use of pulse oximeters and that healthcare workers were most likely to use pulse oximeters with children in certain hospitals, at later time periods, and with children who were not alert or had chest indrawing or a high respiratory rate. The main factors that prevent healthcare workers from using pulse oximeters appropriately are if there is an inadequate supply, a delay in repairing broken pulse oximeters, and the healthcare workers have not had sufficient training on when, how, and why to use pulse oximeters and interpret their results. The authors noted that the findings suggest that healthcare workers are likely to use pulse oximeters with more children if there are efficient and transparent systems for procurement and repair, oxygen therapy is available, training and feedback are provided, and senior doctors advocate for the use of pulse oximeters. If healthcare workers use pulse oximeters with more children at admission, this may increase the number of children who are correctly diagnosed and appropriately treated, potentially leading to fewer child deaths.
Challenges in the diagnosis of paediatric pneumonia in intervention field trials: recommendations from a pneumonia field trial working group
By D Goodman, ME Crocker, F Pervaiz, ED McCollum, K Steenland, SM Simkovich, CH Miele, LL Hammitt, P Herrera, HJ Zar, H Campbell, CF Lanata, JP McCracken, LM Thompson, G Rosa, MA Kirby, S Garg, G Thangavel, V Thanasekaraan, K Balakrishnan, C King, T Clasen, W Checkley, HAPIN Investigators. Published in Lancet Respir Med. Dec 1, 2019.
Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia.
Usability and acceptability of an automated respiratory rate counter to assess childhood pneumonia in Nepal
By K Kallander, C Ward, H Smith, R Bhattarai, A KC, D Timsina, B Lamichhane, A Maurel, PR Shrestha, S Baral, C McWhorter, P LaBarre, MA de Cola, K Baker. Published in Acta Paediatr. Nov 24, 2019.
Diagnosis of pneumonia based on counting respiratory rate is challenging, and misdiagnosis and inappropriate treatment of children are common. The results from this usability and acceptability study show that the usability of a new automated respiratory rate counter, the Philips ChARM device, among community health workers (CHWs) in Nepal was limited. The authors found that ChARM alone does not support low‐literate CHWs sufficiently in assessing and classifying sick children with symptoms of pneumonia.
Hypoxaemia in hospitalized children and neonates: A prospective cohort study in Nigerian secondary-level hospitals
By H Graham, AA Bakare, AI Ayede, OB Oyewole, A Gray, D Peel, B McPake, E Neal, SA Qazi, R Izadnegahdar, T Duke, AG Falade. Published in EClinicalMedicine. Nov 1, 2019.
This multi-centre cohort study was nested in the Nigerian Oxygen Implementation project, a large stepped wedge field trial evaluating pulse oximetry and improved oxygen systems. The authors’ cohort included over 23,000 hospitalised children from birth to adolescence with various conditions, enabling them to describe the epidemiology of hypoxaemia in children and neonates admitted to secondary-level hospitals in low-altitude African towns. They found high hypoxaemia prevalence in pneumonia and other common childhood conditions, and particularly high prevalence in neonates. They found that hypoxaemia increased the risk of death across all age groups and all diagnostic categories, with higher risk in non-respiratory conditions. They found that clinical signs recorded during routine care were particularly poor at predicting hypoxaemia in children and neonates with non-respiratory conditions, having much lower sensitivity for hypoxaemia in non-respiratory conditions than respiratory conditions. They determined that the predictive value of the World Health Organisation combination of signs for hypoxaemia was reasonably good for child pneumonia, but was much poorer for non-respiratory conditions (particularly for children over the age of 1 year). They found that most hypoxaemic children required oxygen therapy for 2–3 days and calculated the mean annual oxygen requirements for small- and medium-sized hospitals that admit children.