A UNSW Sydney-led medical research team has called for a new vaccine, improved strategies and enhanced monitoring to combat serious complications from childhood pneumonia.
The researchers examined the impact of the 13-valent pneumococcal conjugate vaccine (13vPCV) on childhood pneumonia and empyema – complicated pneumonia – after its introduction to the Australian National Immunisation Program about a decade ago.
The new study, published in Thorax recently, found that while 13vPCV resulted in a 21% decrease in childhood pneumonia hospitalisations, there was a contemporaneous 25% increase in admissions for empyema.
Approximately 7,000 Australians under the age of 18 are hospitalized with pneumonia each year.
Senior author Professor Adam Jaffe, Head of the School of Women’s and Children’s Health at UNSW Medicine & Health, said the researchers’ findings suggested an emergence of non-vaccine serotypes – those which 13vPCV does not cover.
13vPCV was introduced to cover the 13 most common serotypes responsible for invasive pneumococcal infection, extending coverage to six additional serotypes including 1 and 3.
The previous vaccine (7vPCV) covered seven serotypes. A serotype is a distinct variation within a bacteria species.
Prof. Jaffe said: “Although we found a substantial reduction in serotype 1, serotype 3 is now the predominant organism which causes childhood empyema – in 76% of cases – so, efforts must be made to create a vaccine which is more effective against serotype 3.
“In fact, Australia recently changed the vaccination dosage schedule to try and improve the effectiveness of 13vPCV against serotype 3, but we need to continue monitoring patients using molecular techniques to see if this change has had an impact.
Empyema is infected fluid around the lungs and about 1% of children hospitalized with pneumonia develop it.
Although children are highly unlikely to die from empyema, they can expect a long stay in hospital for treatment with antibiotics and surgery, or the insertion of a drain. If adults develop empyema, about a third are likely to die.
Continuing enhanced surveillance needed
The researchers conducted a similar study during the period of the superseded 7vPCV. Their new study – which took four years to complete – is part of a broader research project on 13vPCV.
The first part of the research used publicly available hospitalisations data – about 36,000 admissions – to assess whether the introduction of 13vPCV changed how many children were admitted to hospital with pneumonia and empyema.
The enhanced surveillance study involved the collection of blood and lung fluid samples from 401 children with empyema from February 2015 to September 2018.
The children were receiving treatment in 11 major children’s hospitals across Australia.
Most children were boys (208 or 52%) and the median age was four years old.
The researchers then conducted molecular testing on these samples and compared the results to their previous study undertaken during the period of 7vPCV.
The multidisciplinary team included Dr. Nusrat Homaira, of the Discipline of Paediatrics at UNSW Medicine & Health, and pediatric research nurse Roxanne Strachan of Sydney Children’s Hospital.
“We are currently working on our larger study, of which this was a subset, to examine the effectiveness of 13vPCV on children with bacterial pneumonia. We will need to repeat the study in a few years’ time to help with monitoring.
“In the meantime, it would make a big difference if molecular testing of patients’ lung fluid was routine in laboratories, because that would ensure we had the best real-time data available which will help rationalize antibiotic choice; also, we would have no need to seek funding to undertake this much-needed research.”
Streptococcus pneumoniae (pneumococcus) is the leading cause of pneumonia deaths in children under 5 years of age [1]. The pneumococcus is also a leading cause of meningitis, bacteraemia and otitis media [2]. Young children in the highlands of Papua New Guinea (PNG), where this study was performed, experience one of the highest rates of pneumococcal disease in the world, with approximately 5 out of 100 children experiencing invasive pneumococcal disease (IPD) in the first year of life [3].
S. pneumoniae is a common colonizer of the nasopharynx of children [4]. Pneumococcal colonization is a major risk factor for mucosal and invasive pneumococcal disease [5]. In the highlands of PNG, pneumococcal colonization starts within a few weeks of birth, with half of children being colonized before 3 weeks of age [6].
In addition, the range of colonizing pneumococcal serotypes is broad and more diverse than in low-endemicity settings and children can carry multiple serotypes at the same time [7], [8].
Nasopharyngeal colonization also drives immune development. The mucosal immune system rapidly develops shortly after birth in response to bacterial colonization [9], [10]. Immunoglobulin A (IgA) is the major class of antibodies found in mucosal secretions.
The development of specific secretory (S)IgA antibodies in infants depends on the degree of natural exposure or vaccination. In a low-endemicity setting, infants as young as 6 months old were shown to have elevated serotype-specific salivary IgA antibodies if they had previously been colonized with pneumococci of the same serotype [11].
This early mucosal IgA response may protect children against subsequent carriage and potential disease of the same pneumococcal serotype [12], [13], [14]. It is not known whether children in high-endemicity settings, where colonization occurs at a younger age, also produce potentially protective mucosal antibody responses.
Pneumococcal conjugate vaccines (PCVs) induce systemic immune responses that are highly effective in preventing IPD due to vaccine serotypes in children in both low- and high-risk settings [15], [16]. In low-endemicity settings PCVs also reduce vaccine-serotype-specific carriage and mucosal infections [17], [18] and specific IgA and IgG antibodies can be detected in saliva of children who have completed their primary PCV immunizations, although levels vary between vaccine serotypes and between children [19], [20], [21].
Subsequent booster vaccination with pneumococcal polysaccharide vaccine (PPV) or PCV was shown to increase salivary IgA responses for PCV serotypes, which has led to the suggestion that primary PCV vaccination induces mucosal immune memory [19], [20], [21].
In contrast to low-endemicity settings, PCVs offer no or limited protection against pneumococcal colonization in high-endemicity settings [3], [22], [23], which raises questions about the induction of mucosal immunity by PCV under these conditions. Apart from a small study that measured salivary IgA responses in ten high-risk Aboriginal Australian children primed with PCV followed by a PPV booster [24], there are to our knowledge no studies on the development of salivary antibodies following primary and booster vaccination with pneumococcal vaccines in high-risk children.
Whether PCV can induce mucosal immunity or prime for mucosal immune memory in children in high-endemicity settings is important to our understanding of the epidemiology of pneumococcal disease after implementation of PCV and for optimizing vaccination schedules. This includes understanding mucosal immune responses to a PCV-prime and PPV-boost schedule as a potential strategy to protect high-risk children against replacement carriage and disease.
The objectives of this study were to assess the induction, kinetics and persistence of mucosal IgA and IgG responses in children in the highlands of PNG in the first months of life in the absence or presence of primary vaccination with PCV; after vaccination with PPV in later infancy; and to study correlations between mucosal and systemic IgG responses after PCV primary immunization and PPV vaccination.
These analyses were conducted in saliva and serum samples collected from children participating in a randomized placebo-controlled trial of accelerated 7-valent PCV (7vPCV) vaccination (Neonatal Pneumococcal Conjugate Vaccine Trial) conducted in the highlands of PNG between 2005 and 2009 [25]. We previously reported results for serum serotype-specific IgG responses following 7vPCV-priming and 23-valent PPV (23vPPV) booster vaccination, showing that PCV is immunogenic and induces systemic memory responses, but has limited impact on pneumococcal carriage in these high-risk children [3], [4].
reference link : https://europepmc.org/articles/pmc7684155/bin/mmc1.docx
More information: Roxanne Strachan et al. Assessing the impact of the 13 valent pneumococcal vaccine on childhood empyema in Australia, Thorax (2021). DOI: 10.1136/thoraxjnl-2020-216032
