Neutropenia: Vaccine recommendations for children with chronic neutropenia

Background

Children with neutropenia are at increased risk of bacterial and fungal infections. Preventing infections is this group is therefore a priority and we should be aiming to protect these children against vaccine preventable diseases (VPDs) according to the National Immunisation Program (NIP).

There is a lack of direct data to base vaccine recommendations in this group. This group of patients is not addressed in the Australian Immunisation Handbook. A number of international expert groups have however published recommendations in this area (see resources).

Inactivated vaccines are considered safe, and international guidelines recommend they be administered to patients with neutropenia as per routine immunisation schedules. Given patients with neutropenia are at increased risk of bacterial infections, some also recommend additional pneumococcal vaccines, as for patients at increased risk of invasive pneumococcal disease (IPD).

Live-attenuated viral vaccines are contraindicated in patients who are severely immunocompromised, due to the risk of unchecked viral replication and vaccine associated disease. Neutropenia itself, however, is not a contraindication to live-attenuated viral vaccines as patients with an isolated neutropenia would be expected to handle viral infections, and live-attenuated viral vaccines in most circumstances. International guidelines recommend these vaccines be given to patients with congenital or cyclical neutropenia, or neutropenia in general. However, some recommend against these vaccines in patients with undefined phagocytic cell defects or phagocytic cell defects undefined at a molecular level, and others recommend prior immunology review. This is because some conditions which affect neutrophil number or function may also affect lymphocyte number or function. Live-attenuated viral vaccines are contraindicated in patients with leucocyte adhesion disorder, Chediak Higashi syndrome or other defects in cytolytic granule release.

Live bacterial vaccines (including the BCG vaccine) are contraindicated in patients who are immunocompromised including those with some phagocytic cell defects. This is due to an increased risk of vaccine associated adverse events in this group.

Our recommendations are based on these international guidelines and local consensus.

Recommendations

Inactivated vaccines

Inactivated vaccines are recommended as per the NIP. We also recommend additional pneumococcal vaccines, as for patients at high risk of invasive pneumococcal disease (see resources).

Live-attenuated viral vaccines

Neutropenia itself is not a contraindication to live-attenuated viral vaccines. In cases of an undefined neutropenia some caution should be exercised, given neutropenia can occur in the setting of conditions which also affect lymphocyte number and function

For patients with congenital neutropenia or cyclical neutropenia caused by a known molecular defect (which is not associated with any other immune dysfunction), live-attenuated viral vaccines are recommended as per the NIP.

A number of patients with chronic moderate-severe neutropenia (neutrophil count <1 x10^9/L) will not have a defined molecular defect, the cause may be unclear, or they may have suspected immune neutropenia for which there is no diagnostic test. In these patients, an evaluation for an underlying immune defect is recommended prior to administration of live-attenuated viral vaccines (see MVEC Flowchart: Live attenuated viral vaccines in patients with chronic neutropenia). If there are no concerning features on history, examination or screening investigations, live-attenuated viral vaccines are recommended, as per the NIP. If any abnormalities or concerns are raised, a formal immunology consult should be sought prior.

In patients for whom the neutropenia is expected to be transient, or further investigation is planned in the near future (e.g. bone marrow examination or molecular studies), consideration should be given to delaying live-attenuated viral vaccines until this information is available.

Live-attenuated viral vaccines are contraindicated in patients with leucocyte adhesion disorder, Chediak Higashi syndrome or other defects in cytolytic granule release.

Live bacterial vaccines

Live bacterial vaccines (e.g. the BCG vaccine, oral typhoid vaccine) are generally contraindicated in patients with neutropenia. Typhoid protection can be provided by using an inactivated vaccine. If there is a high risk of Tuberculosis in an individual with neutropenia, BCG vaccine should be discussed with both an immunisation specialist and haematologist.

Resources

 

Authors: Luisa Clucas (Clinical Haematology Registrar, Royal Children’s Hospital), Anthea Greenway (Head of Clinical Haematology, Royal Children’s Hospital), Theresa Cole (Consultant, Allergy and Immunology, Royal Children’s Hospital), and Nigel Crawford (Director SAEFVIC, Murdoch Children’s Research Institute)

Date: August 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Novavax (Nuvaxovid) COVID-19 vaccine

Name of vaccineNuvaxovid (generic name NVX-CoV2373)
Vaccine platformProtein vaccine (nanoparticle-based vaccine)
Developer of vaccineNovavax Inc
RegistrationProvisional registration granted by TGA on 20 January 2022
For use≥ 18 years
Primary course in immunocompetent individuals2 doses (3-8 weeks apart)
Primary course in immunocompromised individual3 dose primary schedule, with the third dose 2-6 months post dose 2
Booster dose recommendationsNot TGA-registered for use as a booster dose, however ATAGI recommends that it may be used in individuals aged ≥ 18 years in certain circumstances
ManufacturerDoses for Australia will be manufactured in several locations across Europe and Asia
Storage requirementsCan be stored, transported and handled at standard refrigerator temperatures (2-8°C)
Preparation and injectionEach multi-dose vial contains 10 doses of 0.5ml of vaccine, to be administered intramuscularly (IM). Nuvaxovid does not require reconstitution.

Immunogenicity

Pre-clinical trials of Nuvaxovid (Novavax) were conducted in baboons and mice. In animal models, the vaccine induced high levels of anti-spike antibodies and neutralising antibodies, which exceeded the responses measured in humans recovered from natural COVID-19 infection.

Phase 1 clinical trials were conducted in 131 healthy adults aged 18-59 years in Australia and the United States of America (USA). The study assessed the safety and immunogenicity of two doses (low dose 5-μg and high dose 25-μg) with or without Matrix-M1 adjuvant in healthy adults aged 18 to 59 years, compared to a placebo. Overall the vaccine elicited a good immune response, with immunogenicity comparable in both low and high dose groups. An enhanced immune response was seen in the adjuvant group.

A phase 2 trial in Australia and the USA expanded the age of participants to include 1,288 participants aged 18-84. Results of this study indicated that a two-dose regimen of 5-µg NVX-CoV2373 administered 21 days apart was the optimal vaccine dose to proceed to phase 3 trials.

Safety profile

Side effects following administration of Nuvaxovid (Novavax) have been generally mild to moderate, and short-lived. Injection site pain and tenderness, as well as fatigue, headache and muscle pain were the most commonly reported side effects, particularly after dose 2, and more commonly in younger recipients (18-64 years). The incidence of serious adverse events was low and reported in similar numbers in both the vaccine arm and placebo group. Three cases of myocarditis were reported in the phase III clinical trials, two of which were in the vaccine arm and one in the placebo group.

Vaccine efficacy

United Kingdom (UK)

Phase 3 clinical trials in the UK enrolled more than 15,000 participants aged between 18-84 years of age. Overall efficacy of 89.7% against PCR confirmed disease was demonstrated 7 days following receipt of dose 2.  It was 96.4% efficacious against the original COVID-19 strain and 86.3% against the circulating Alpha strain. There was 100% protection against severe disease (hospitalisation and death) for both strains.

South Africa

A phase 2b clinical trial  conducted in South Africa included 4387 participants (HIV-negative and HIV-positive). The vaccine demonstrated 49.4% efficacy in preventing COVID-19 disease caused by the Beta variant for all participants. This increased to 60.1% efficacy for the HIV-negative only cohort. All COVID-19 infections in the vaccine group were mild/moderate, and there were no severe cases. Serious adverse events were rare and unrelated to the vaccine.

United States of America (USA)

Approximately 30,000 participants were enrolled in PREVENT-19 (PRE-fusion protein subunit Vaccine Efficacy Novavax Trial COVID-19), a phase 3 trial in Mexico and the USA. The vaccine demonstrated 90.4% efficacy overall for preventing symptomatic COVID-19 disease, with 100% protection against moderate and severe disease. For “high-risk” populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure) the vaccine was reported to be 91.0% efficacious.

Further studies

Paediatric clinical trials

Children were not included in the initial Novavax COVID-19 vaccines clinical trials due to the decrease in severity of symptoms experienced by children infected with SARS-CoV-2 compared with infected adults. Various clinical trials are currently underway to determine the safety and efficacy of Nuvaxovid (Novavax) in the paediatric population (12-17 years).

For further information refer to MVEC: COVID-19 vaccination in children.

Clinical trial crossover

In April 2021, Novavax announced that they would introduce crossover arms for all three trials in the UK, South Africa and USA. Participants in the UK and the US who were given the placebo in the initial trial will now be offered the active vaccine. In South Africa all participants will be offered the active vaccine, meaning that those who previously received the placebo will be vaccinated and those who received the vaccine previously will receive a booster dose. This will give all participants the opportunity to receive protection with ongoing follow up. All participants will remain blinded.

Booster study

From December 2021, an extension of the PREVENT-19 phase 3 clinical trial commenced. Participants will be offered a booster dose of Nuvaxovid 6 months following the completion of their primary course. The safety and efficacy of a booster dose of Nuvaxovid administered in two other groups will also be assessed (those who received alternate brands of COVID-19 vaccine as the initial course and those who only received 1 dose of Nuvaxovid as their primary course).

Resources

Authors: MVEC Education Team

Reviewed by: Rachael McGuire, (MVEC Education Nurse Coordinator), Francesca Machingaifa (MVEC Education Nurse Coordinator)

Date: February 14, 2022

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Nuvaxovid (Novavax) COVID-19 vaccine

Name of vaccineNuvaxovid (generic name NVX-CoV2373)
Vaccine platformProtein vaccine (nanoparticle-based vaccine)
Developer of vaccineNovavax Inc
RegistrationProvisional registration granted by TGA on 20 January 2022
For use≥ 18 years
Primary course in immunocompetent individuals2 doses (3-8 weeks apart)
Primary course in immunocompromised individual3 dose primary schedule, with the third dose 2-6 months post dose 2
Booster dose recommendationsNot TGA-registered for use as a booster dose, however ATAGI recommends that it may be used in individuals aged ≥ 18 years in certain circumstances
ManufacturerDoses for Australia will be manufactured in several locations across Europe and Asia
Storage requirementsCan be stored, transported and handled at standard refrigerator temperatures (2-8°C)
Preparation and injectionEach multi-dose vial contains 10 doses of 0.5ml of vaccine, to be administered intramuscularly (IM). Nuvaxovid does not require reconstitution.

Immunogenicity

Pre-clinical trials of Nuvaxovid (Novavax) were conducted in baboons and mice. In animal models, the vaccine induced high levels of anti-spike antibodies and neutralising antibodies, which exceeded the responses measured in humans recovered from natural COVID-19 infection.

Phase 1 clinical trials were conducted in 131 healthy adults aged 18-59 years in Australia and the United States of America (USA). The study assessed the safety and immunogenicity of two doses (low dose 5-μg and high dose 25-μg) with or without Matrix-M1 adjuvant in healthy adults aged 18 to 59 years, compared to a placebo. Overall the vaccine elicited a good immune response, with immunogenicity comparable in both low and high dose groups. An enhanced immune response was seen in the adjuvant group.

A phase 2 trial in Australia and the USA expanded the age of participants to include 1,288 participants aged 18-84. Results of this study indicated that a two-dose regimen of 5-µg NVX-CoV2373 administered 21 days apart was the optimal vaccine dose to proceed to phase 3 trials.

Safety profile

Side effects following administration of Nuvaxovid (Novavax) have been generally mild to moderate, and short-lived. Injection site pain and tenderness, as well as fatigue, headache and muscle pain were the most commonly reported side effects, particularly after dose 2, and more commonly in younger recipients (18-64 years). The incidence of serious adverse events was low and reported in similar numbers in both the vaccine arm and placebo group. Three cases of myocarditis were reported in the phase III clinical trials, two of which were in the vaccine arm and one in the placebo group.

Vaccine efficacy

United Kingdom (UK)

Phase 3 clinical trials in the UK enrolled more than 15,000 participants aged between 18-84 years of age. Overall efficacy of 89.7% against PCR confirmed disease was demonstrated 7 days following receipt of dose 2.  It was 96.4% efficacious against the original COVID-19 strain and 86.3% against the circulating Alpha strain. There was 100% protection against severe disease (hospitalisation and death) for both strains.

South Africa

A phase 2b clinical trial  conducted in South Africa included 4387 participants (HIV-negative and HIV-positive). The vaccine demonstrated 49.4% efficacy in preventing COVID-19 disease caused by the Beta variant for all participants. This increased to 60.1% efficacy for the HIV-negative only cohort. All COVID-19 infections in the vaccine group were mild/moderate, and there were no severe cases. Serious adverse events were rare and unrelated to the vaccine.

United States of America (USA)

Approximately 30,000 participants were enrolled in PREVENT-19 (PRE-fusion protein subunit Vaccine Efficacy Novavax Trial COVID-19), a phase 3 trial in Mexico and the USA. The vaccine demonstrated 90.4% efficacy overall for preventing symptomatic COVID-19 disease, with 100% protection against moderate and severe disease. For “high-risk” populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure) the vaccine was reported to be 91.0% efficacious.

Further studies

Paediatric clinical trials

Children were not included in the initial Novavax COVID-19 vaccines clinical trials due to the decrease in severity of symptoms experienced by children infected with SARS-CoV-2 compared with infected adults. Various clinical trials are currently underway to determine the safety and efficacy of Nuvaxovid (Novavax) in the paediatric population (12-17 years).

For further information refer to MVEC: COVID-19 vaccination in children.

Clinical trial crossover

In April 2021, Novavax announced that they would introduce crossover arms for all three trials in the UK, South Africa and USA. Participants in the UK and the US who were given the placebo in the initial trial will now be offered the active vaccine. In South Africa all participants will be offered the active vaccine, meaning that those who previously received the placebo will be vaccinated and those who received the vaccine previously will receive a booster dose. This will give all participants the opportunity to receive protection with ongoing follow up. All participants will remain blinded.

Booster study

From December 2021, an extension of the PREVENT-19 phase 3 clinical trial commenced. Participants will be offered a booster dose of Nuvaxovid 6 months following the completion of their primary course. The safety and efficacy of a booster dose of Nuvaxovid administered in two other groups will also be assessed (those who received alternate brands of COVID-19 vaccine as the initial course and those who only received 1 dose of Nuvaxovid as their primary course).

Resources

Authors: MVEC Education Team

Reviewed by: Rachael McGuire, (MVEC Education Nurse Coordinator), Francesca Machingaifa (MVEC Education Nurse Coordinator)

Date: February 14, 2022

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Needle phobia

Background

Many people may find the experience of having a needle an unpleasant one. However, for some people, the experience is much more difficult, presenting as a real phobia characterised by both severe and persistent anxiety and fear. As a result, this patient group often avoid needle-related experiences. This needle avoidance extends to the area of immunisation, resulting in the individual being left susceptible to vaccine preventable diseases. This can result in further procedures involving needles should they become unwell.

Generally speaking, it is recommended that children and adults with anxiety, intellectual disabilities and needle phobia’s avoid attending large scale vaccination sites for immunisation. These sites are loud and busy and can increase distress. Smaller settings such as a GP clinic or pharmacy may be preferred. It is important to have a discussion with your immunisation provider prior to the appointment in order to make an individualised plan for how to approach the immunisation experience.

Strategies to manage needle phobia and immunisation- information for individuals and care givers

  • needle phobia is real and it’s ok to be scared
  • do not criticise the child or individual, this can make it worse
  • with young children, it may be best not to tell them until you arrive at clinic, as this will stop them overthinking the needle
  • use words such as “arm medicine” or “vaccine” and avoid using words like “needle” or “injection” when descibing what is about to happen
  • the use of rewards for children may help encourage bravery
  • the application of local anaesthetic cream patches to the site a minimum of 45 minutes prior to appointment (available for purchase from chemists), may help to settle the fear of pain
  • needle phobia can be a lifelong problem if not treated appropriately.

Specialist phobia treatments

Specialist trained psychologists and more recently hypnotherapists have had significant success in giving an individual mechanisms and strategies to help overcome or manage their needle phobia. Considering either pathway is recommended as a long term strategy to overcome needle phobia.

Strategies to manage needle phobia and immunisation- information for health care providers

Effective preparation, distraction techniques, pain management strategies and addressing the core reason for the phobia are all important steps in ensuring successful immunisation.

Children and adolescents

  • encourage parents not to over discuss the vaccine/needle with the children prior to arrival as this can build up their fear
  • have a plan in place with the parents prior to their arrival at the clinic (in known phobic children)
  • carry out pre-immunisation checks and side effect explanation with parents when the child is out of the room or prior to arrival
  • minimise discussions in front of the child as this can increase distress
  • an individualised approach is more likely to lead to success
  • do not rush or attempt to force children to be vaccinated, this is likely to result in failure to vaccinate
  • take you time with clearly distressed patients, calmly talk them through the procedure and tips to manage their anxiety (deep breathing, looking away or counting).

People with autism spectrum disorder (ASD)

The following strategies may assist in managing needle phobia in individuals with ASD:

  • discuss the individual’s communication style and capabilities with their parent/carer
  • explain everything you are going to do using clear, simple language
  • involve the individual as much as possible by considering their likes/dislikes
  • provide support and positive reassurance
  • remove distracting/disturbing stimuli
  • try not to stop stimming behaviours (eg. rocking, flapping) that may help the individual deal with distress
  • do not attempt to restrain the individual
  • older individuals with ASD can be very difficult to immunise due to significant needle phobias. Restraining these children can result in injury to the carer, child or health care provider
  • have a low threshold to refer to a specialist immunisation provider for sedation.

Distraction techniques

Young children or the intellectually disabled:

  • bubbles upon entering the room and before and after needle
  • musical toys
  • if able have one person blowing bubbles or creating noise with toy intermittently to maintain attention of child
  • TV on with kids shows
  • child watching their favourite show on parents’ phone.

Older children, adolescents or adults:

  • phone/iPad with headphones watching their favourite show or music (give them time to settle into watching it)
  • make conversation eg. sport, upcoming holidays
  • countdown so they know when to be ready
  • strongly encourage them to look away.

Administration techniques

  • prepare the vaccine out of view of the individual or before they come into room
  • avoid showing the individual the prepared vaccine and needle prior to administration
    • place the tray containing vaccines out of sight
    • hold the vaccine to your side or behind you back until about to inject
    • encourage the individual to close their eyes, look away or focus on the distraction method
  • don’t over discuss the needle and administration of the vaccine
    • do necessary pre-vaccination checks and side effects only
    • make the process as quick as possible to give the patient minimal time to over-think the needle
  • encourage adult individuals to bring a support person if they wish
  • a phobia in adolescents or adults can lead to a vasovagal or faint response. It is important that the individual is supported to lay down if needed.

Sedation

If immunisation attempts are unsuccessful, a referral for vaccines to be administered under sedation may be considered.

COVID-19 vaccines

Paediatric services

Any needle phobic children (< 16 years) requiring sedation in a public hospital to facilitate COVID-19 vaccination can be seen at Monash Health only. Referrals for this service can be made through the VicSIS eReferral portal.

The Royal Children’s Hospital (RCH) can provide sedation to facilitate COVID-19 vaccination in children (<16 years) for RCH patients only. Referrals for this service can be submitted via email to Nurse Practitioner Immunisation via screferrals@rch.org.au

Family Immunisation Travel Specialists (FITS) is a private immunisation clinic offering COVID-19 vaccination under sedation for needle phobic children and adolescents (< 18 years). For information on how to make an appointment please call (03) 9508 6000.

Adult services

Individuals (with and without a disability) aged 16 years and over can access sedation services for COVID-19 vaccination through the Disability Liaison Officer (DLO) pathway. To access this service please complete a Request for Disability Liaison Officer Support form. Please note that on this form it is essential to select that the individual requiring support has a disability that requires significant assistance in order to progress through the pathway.

Non COVID-19 vaccines

Paediatric services (< 18 years)

Needle phobic children and adolescents requiring sedation to facilitate vaccination with routine NIP vaccines +/- influenza and travel vaccines can be referred to one of the following hospitals:

Family Immunisation and Travel Specialists (FITS) is a private immunisation clinic offering COVID-19 vaccination under sedation for needle phobic children and adolescents. For information on how to make an appointment please call (03) 9508 6000.

Resources

RCH resources

Other resources

Authors: Georgie Lewis (Clinical Manager, SAEFVIC, Murdoch Children’s Research Institute) and Rachael McGuire (SAEFVIC Research Nurse, Murdoch Children’s Research Institute)

Reviewed by: Rachael McGuire (MVEC Education Nurse Coordinator)

Date: July 19, 2022

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.


Neurologic and neurodevelopmental conditions

There are a number of neurological conditions that are associated with an increased risk of vaccine preventable diseases. These include:

  1. Epilepsy and seizure disorders
  2. Developmental delay and intellectual disability
  3. Cerebral palsy
  4. Neuromuscular disorders
  5. Hydrocephalus and children with ventricular-peritoneal shunts

Children with any of these underlying conditions should have routine vaccinations according to the Australian National Immunisation Program Schedule.

In children where epilepsy is unstable, or there is a progressive neurological disorder of unclear aetiology, specialist consultation is recommended to advise on the appropriate vaccination course. In Victoria, referrals for this service should be made to SAEFVIC.

Influenza vaccination

All children with neurologic and neurodevelopmental conditions are at high risk of severe and complicated influenza infection.

This includes disorders that do not have an obvious compromise in respiratory function such as intellectual disability and epilepsy. Influenza infection can also markedly increase seizures in children with epilepsy.

These children should all be offered annual influenza vaccination from 6 months of age. Two doses are required in the first year the vaccine is received if less than 9 years of age [see Resources].

Pneumococcal vaccination

Children with CSF leaks and intracranial shunts are at higher risk of invasive pneumococcal disease. This includes brain inflammation (meningitis) and blood infection (bacteraemia). These children should be offered additional vaccines, including an extra pneumococcal conjugate vaccine to optimise protection.  See the Pneumococcal chapter in the Australian Immunisation Handbook for the latest recommendations [see Resources]

Human Papillomavirus (HPV) Vaccination

Transmission of the HPV virus is primarily through sexual intercourse and can also occur via non- penetrative sexual contact.

There is some evidence for potential virus transmission via viral particles on hands.

HPV infection is associated with the potential development of serious disease such as cervical and anogenital cancers. The infection is also the primary cause of anogenital warts.

As transmission can be varied, children with neurodevelopmental conditions should be offered HPV vaccination as per the routine secondary school program.

Resources

Author: Teresa Lazzaro (Paediatrician, Immunisation Service, Royal Children’s Hospital Melbourne)

Date: September 2018

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

You should not consider the information in this site to be specific, professional medical advice for your personal health or for your family’s personal health. For medical concerns, including decisions about vaccinations, medications and other treatments, you should always consult a healthcare professional.