Among developed nations, the UK has one of the highest death rates among children at approximately 18/100,000 children per year. Much of this is due to childhood infection.
A new study published in the journal Archives of Diseases of Childhood in March 2020 reveals that despite a drop to less than half, compared to 25 years ago, infection is still a cause of significant mortality among children. The most common cause of infection-related deaths in this age group is respiratory infections.
Previous research by the same authors showed that a fifth of childhood deaths from 2003 to 2005 was due to infections – the "largest single cause of death in children dying of an acute physical illness," according to the Confidential Enquiry into Maternal and Child Health report at the time.
In a later 2014 report by the Royal College of Paediatrics and Child Health (RCPCH), the rate has apparently come down to 9% in children below the age of 4 years, and 4% to 7% in children above this age. This is probably the result of including only deaths caused primarily by infection, however, and not an actual reduction.
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The current study was motivated by the need to find out if things had changed since their last analysis in 2003-05. The researchers used electronic death registration records in England and Wales during 2013 to 2015 for children aged 28 days to 15 years. Any death certificate on which infection was mentioned was counted as indicating an infection-related death. Any existing illnesses apart from infection were separately noted. If the focus of infection was mentioned, the death was so categorized, and systemic infection was recorded for other deaths where the infection was recorded but not the focus of infection.
They compared their findings with the previous study of 2003 to 2005, to detect high-priority areas for future intervention.
The researchers found over 5,000 deaths registered in children from 28 days to 15 years or less in England and Wales over the period 2013 to 2015, compared to 6900 deaths in 2003-05. In other words, the annual incidence of deaths went down from 24/100 000 in 2003-05 to about 18/100 000 in 2013-15. This corresponded to a reduction by over a quarter over this period of 10 years.
Less than 19% of the deaths in 2013-15 were linked to infection, but 20% in 2003-05, for an infection-related mortality rate of 3.3/100 000 and 5/100 000 in 2013-15 and 2003-05 respectively – a reduction by about 31%.
The researchers thus found that infection-related deaths went down by half in young children and infants, but increased by 22% among older children. There were more deaths in winter than in summer, though there was no apparent relationship with comorbidities.
In the current study, children who died of infection or related conditions were 1.3 years old, on average, with 41% of such deaths among infants 28 days to 1 year of age. Young and older children made up about 26% and 33%, respectively.
Overall, the study found that infections caused 17%, 20%, and 20% of deaths in infants, young children, and older children, respectively. In the earlier study, the figures were 21%, 27%, and 12% respectively.
Deaths in sick children
Over half the deaths registered in the study were in children with comorbidities, about 48% in infants, 54% in young children, and 64% of older children.
The most commonly reported cause among those recorded were respiratory infections, in 42%, while in 29%, there was evidence of systemic infection without any focus. This is a change from the earlier study where almost half the infections were without a known focus, and respiratory infections made up about 30%. In 63% of cases, there was a recorded pathogen, almost 2 out of every 3 of these being bacterial.
Gram-negative infections were more common in children with other illnesses, at almost 60%, compared to healthy children. Group B and group A streptococcus (GBS and GAS) were more common in healthy infants and children older than one year, respectively. The number of GAS infections went up, especially in this group.
Vaccine-preventable diseases (pneumococcal and meningococcal infections) contributing to death occurred in only a few cases (below 40) in 2013-15 compared to almost 230 cases in the earlier study.
Viral infections leading to death accounted for 34%. They were more common (9% more) among previously healthy children compared with the sick. This includes respiratory syncytial virus (RSV), adenovirus, influenza, and cytomegalovirus. The RSV-related deaths occurred mostly in sick children, especially younger children, as well as in healthy infants. A few fungal infections were seen mostly in children with underlying sicknesses.
Even though the UK continues to have high rates of childhood death among developed nations, the mortality from all causes is showing an encouraging decline, according to the current study. Moreover, deaths of children due to infection-linked causes are also going down, although about 20% of all deaths are still due to such conditions. It is estimated that about 5% to 10% of people have underlying sicknesses. If half of the deaths related to infection occur in such children, the authors point out that "infections contribute to a more significant proportion of deaths (10-fold to 20-fold higher) in children with comorbidity compared with healthy children. "
The authors note, "In healthy children, there were large reductions in pneumococcal and meningococcal deaths. The UK implemented a childhood pneumococcal immunization program in 2006, which led to large declines in childhood pneumococcal disease."
A disturbing feature is that the proportion of children with comorbidity who die of an infection-related cause is still going up. The authors feel, however, that in the present study, this may be because younger children who are already sick may be surviving better, causing an increase in the number of deaths in older children who are sick and then develop an infection.
The priority is to develop safe and effective vaccines, given the high rate of infection-related deaths because of Gram-negative bacterial infections, which are often multi-drug resistant. Again, GAS is now responsible for 33 cases of infection/100 000 person-years. This is the highest incidence over the last 50 years or so. From 15% to 30% of these are linked to chickenpox infection. Varicella vaccination could reduce such infections by up to 70%, according to reports from other countries.
The flu vaccine could also be useful in reducing the burden of death in young children. Other vaccines which remain experimental are the GBS vaccine for pregnant women and several RSV vaccines.
The authors say, "Our results provide an evidence-base to prioritize research and recommendations to reduce infection-related childhood mortality in the UK."
Ferreras-Antolín L, Oligbu G, Okike IO, et al, Infection is associated with one in five childhood deaths in England and Wales: analysis of national death registrations data, 2013–15Archives of Disease in Childhood Published Online First: 24 March 2020. doi: 10.1136/archdischild-2019-318001