Immune System, Infections and Immunisations
30% increased sepsis risk, prophylactic antibiotics for recurrent infections, immunology testing criteria, additional vaccines including annual flu from 6 months and PPV23 from age 2, VZV considerations for immunocompromise
Background
Individuals with Down Syndrome are at increased risk of acquiring infections due to an altered immune system. A 30% increased risk of death from sepsis is reported (Garrison, 2005). Please see Impaired immune competence:
- Reduced T and B lymphocyte subpopulations.
- Reduced neutrophil chemotaxis.
- Thymic abnormalities.
- Alterations of Ig subclasses.
More information: Preventing infection in children with Down Syndrome.
Recurrent Respiratory Infections
A lot of Down Syndrome aspiration is silent, and this is the difficulty in detecting it on history alone. Certainly, if any child with Down Syndrome has above-average respiratory issues compared with a child without Down Syndrome, then aspiration MUST be sought and do not hold back on videofluoroscopy (advice from the Brompton respiratory physicians 2018).
Prophylactic Antibiotics
If significant infection history, it may still be appropriate to commence prophylactic antibiotics even when immunological tests are normal. These should be considered in children with frequent infections, either to be used throughout the year or just from September to April.
- Options - E.g. azithromycin 10mg/kg od 3 days per week.
- The need for prophylactic antibiotics should be reviewed at each visit.
- If stopping, suggest choosing to do this in late spring/early summer.
General Management
- Consider using double the length of the usual antibiotic course.
- Maximise immunity by ensuring appropriate vaccines have been given (as per childhood schedule and any additional vaccines - see below).
Immunological Investigations
Immunoglobulins, Functional Antibodies, Prevnar (pneumococcal) Antibodies and lymphocyte subsets are sometimes done routinely in some DS pathways/boroughs at the 12m review. In Barnet/RFH, we are planning to have a low threshold for immune testing and discuss with our immunology teams and not test routinely in every child, e.g. we would test at any time if ‐ with ≥ 4 infections in 6 months requiring GP visits/ill-health > 5 days or admission for sepsis or there was an unusual infection.
The timing of immunology blood tests is at least 1 month after completion of the 13-month routine Hib/ MenC/ PCV booster immunisations.
Persistent Lymphopenia/ Hypogammaglobulinaemia/ Recurrent Infections
The question relates to the interpretation of lymphocyte subsets in patients with T21. We all talk about the cohort being "relatively immunodeficient"; however, we don't have specific knowledge about the range of "normal" Lymphocyte subsets (LSS) and Immunoglobulins (IgG).
Refer to the local haematology clinic/immunology clinic, but also consider referral to GOSH immunology. Immunologist at GOSH:
We try to see T21 patients at least once here if they have been detected to have lymphopenia/hypogammaglobulinaemia/recurrent infections. We are also happy to see them if they haven't had an LSSMEM/IgGAM/vaccine responses checked and/or a history of infections. We see quite a wide spectrum of immunodeficiency in children with T21.
We have a specific clinic where we see children and young people with syndromes like Down Syndrome.
If they are referred into the Immunology Department - even if, as above, with no LSS/IgGAM/vaccine responses done elsewhere - we will triage them into the most appropriate clinic and see the child.
Immunisations
See: UK Government's current Complete routine immunisation schedule.
Additional Immunisations
Pneumococcal Immunisation
An additional pneumococcal immunisation is now universally agreed (from Autumn 2019 onwards) for every child with Down Syndrome and not only those at "high-risk:: via GP/practice nurse. From 2 years of age: single dose of Pneumovax II (also known as PPV 23, as it protects against 23 different pneumococcal strains). The PPV vaccine is not effective under 2 years of age, hence why they receive the PCV.
Influenza Immunisation
- First vaccine (2 doses 4 weeks apart) from 6 months.
- Annually for life after this.
- Please note that, under 2 years of age, this is an injectable immunisation, and over 2, nasal administration can be offered.
Chickenpox and Vaccines
Vaccines for children with Down Syndrome are under review (2019), and more guidance will be published, including, e.g. the VZV vaccine against chickenpox. For now, professionals need to have a low threshold to consider this vaccine if evidence of immunocompromise, as there have been serious cases of VZV pneumonitis in DS. Also inform GP and parents that sometimes children with Down Syndrome don't show the typical signs and symptoms of chickenpox as other children, so professionals need to consider chickenpox even if it presents in an atypical way, be aware of the complications and monitor them more closely.
Information on Covid Vaccine and T21 Covid Research
- See information on the Down's Syndrome UK website.
Immunisation and Reports to GPs
Include in every report to the GP about the recommended extra vaccinations - annual flu vaccine and the extra pneumococcal vaccine. (There will also be routine letters being distributed around Autumn to GPs to remind them about these vaccinations due for ALL children with Down Syndrome). Ideally, too, ensure that these children are given the first batches of flu vaccine that are made available for the GPs.
Also, have a statement at the end of each report about the increased risk of infection, and that in Down Syndrome, these infections can sometimes present atypically. There is information in the new insert for the PHCR/red book about this as well.
Further Research
Archives of Diseases of Childhood (Nov. 2018)
- All children with Down Syndrome should have annual influenza vaccines from 6 months of age.
- 23-valent pneumococcal vaccine from 2 years.
- Consideration should be given to meningococcal ACWC (and Meningococcal B if not already given).
- Long-term immunogenicity of vaccines is unknown in this group and may require boosters.
- Recurrent vaccine-preventable diseases may have a negative impact on long-term outcomes.
National Child Mortality Database (NCMD)
The National Child Mortality Database (NCMD) national data collection and analysis system is the first of its kind anywhere in the world. It records comprehensive data, standardised across a whole country (England), on the circumstances of children's deaths. The purpose of collating information nationally is to ensure that deaths are learned from, that learning is widely shared and that actions are taken, locally and nationally, to reduce the number of children who die. Go to the NCMD website.
Their reports include:
- Infection-related deaths of children and young people in England: Extract: Of the 425 children aged 5 to 17 years who died with infection, a high proportion (67%) had a learning disability. In the cases where the infection provided a complete and sufficient explanation of death, 52% of the children in this age group had a learning disability. Pneumonia (lower respiratory tract infection) was identified in 75% of the deaths of children with a learning disability.
- Learning from deaths: Children with a learning disability and autistic children aged 4 - 17 years: Extract: This report analyses the deaths of children with a diagnosed learning disability and the deaths of autistic children, aged between 4 and 17 years old. It includes data on 818 children (Figure 1) with either or both diagnoses. The children included in this report died between 1 April 2019 and 31 March 2022 and were reviewed by a Child Death Overview Panel (CDOP) before 27 November 2023. The children were split into two separate groups for further analysis. The first group is children with a learning disability, and the second is autistic children.