Children over two with invasive pneumococcal disease (IPD) should be tested for underlying primary immunodeficiency (PID), according to a new study from the Murdoch Children’s Research Institute.
Despite vaccination rates now being over 70% in many countries, about 830,000 children still die from IPD globally each year.
Prematurity, HIV, malnutrition and exposure to smoke and air pollution all predispose children to IPD; so do immune problems including immunoglobulin deficiency, specific antibody deficiency, complement disorder and congenital asplenia, grouped together as primary immunodeficiency.
A systematic review led by Dr Coen Butters, an infectious diseases fellow at the Royal Children’s Hospital in Melbourne, looked at 17 studies involving more than 6000 children and adolescents around the world.
The study, published in JAMA Pediatrics, found more than a quarter of children with a case of IPD – bacteraemia, meningitis, pneumonia, septic arthritis or osteomyelitis – who did not have another predisposing factor had an underlying PID. In children with recurrent IPD, the rate of PID was up to 67%.
This makes IPD an important biomarker of PID, the authors write, at a time when the “widely published ‘warning signs of primary immunodeficiency’ have been shown to be neither sensitive nor specific”.
An early diagnosis of PID allowed timely treatment, prophylaxis and genetic counselling.
“Often there’s unexplained prolonged illness before that’s identified, so picking that up early can prevent stress for the family,” Dr Butters told The Medical Republic.
“And with a severe immunodeficiency, earlier identification prevents the accumulation of morbidity from recurrent infections through the delivery of prophylaxis – preventing infections such as PJP [Pneumocystis jiroveci pneumonia].”
He said there was the potential for survivorship bias in the study, since PID rates were only recorded for children who survived to follow-up testing. This meant the true rates of immunodeficiency could be higher.
In the future, the authors write, “whole-exome sequencing could characterise an individual’s immune system and aid in predicting the risk of recurrent IPD or severe infection to allow a personalised approach to secondary prevention and treatment”.
According to a surveillance report for the Communicable Diseases Network Australia, there were 279 IPD cases in the first quarter of this year and 13 deaths.
PID is a class of hundreds of rare disorders of the innate and adaptive immune system, the most common of which is immunoglobulin A deficiency, estimated to affect one in 300 to 500. PID overall is thought to affect one in 1200, though estimates vary widely.
JAMA Pediatrics, online September 30