D Letter

背景

DiGeorge syndrome (also known as velocardiofacial syndrome or 22q11.2 deletion syndrome) is a genetic condition affecting approximately 1 in 2,000 newborns. It involves the deletion of DNA in the q11 region of the long arm of chromosome 22 during foetal development. Most cases occur as the result of a random gene mutation. However, in some instances the mutation can be inherited from a parent.  

The health implications of the deleted DNA sequence can vary between individuals. Common features include congenital heart defects, small or absent thymus, cleft or palate abnormalities, speech/language and developmental delay, hearing and visual problems, and learning difficulties. Immunodeficiency is also commonly associated with DiGeorge syndrome. This may be related to inadequate T-cell function, decreased levels of immunoglobulin or reduced antibody function.   

DiGeorge syndrome and vaccines

The decrease in immune function 为了 many people with DiGeorge syndrome means that vaccination is particularly important 到 provide protection against vaccine-preventable diseases. However, it is important to recognise that the immune response to vaccines may be suboptimal meaning 额外的 doses of vaccines may be recommended. Conversely, some vaccines (live-attenuated vaccines) may be contraindicated due to the potential risk of vaccine-related disease. 

建议

The following guidance outlines recommendations for specific investigations and vaccines for children diagnosed with DiGeorge syndrome. This guidance has been developed as a collaboration between MVEC, Queensland Children’s Hospital, Royal Brisbane and Women’s Hospital and Perth Children’s Hospital. 

Immunological work-up and vaccination recommendations for children with 22q11 microdeletion (PDF)

资源

• Guidance: Immunological work-up and vaccination recommendations for children with 22q11 microdeletion (PDF)
• MVEC：免疫抑制和疫苗
• 22q Foundation Australia and New Zealand

什么是流行性感冒？

Diphtheria is a rare but potentially life-threatening acute illness caused by the bacteria Corynebacterium diphtheriae. This bacteria can produce a potent toxin which causes serious disease. It mostly commonly causes an acute respiratory illness characterised by a “pseudo membrane” which forms over the pharyngeal area (throat).

Other less common forms of illness caused by C. diphtheriae include laryngeal/tracheobronchial diphtheria, nasal diphtheria and cutaneous diphtheria.

流感症状

The incubation period is 2-5 days. Early symptoms include low-grade fever, lethargy and malaise. Affected people may develop a sore throat, which may cause pain on swallowing or a hoarse voice.

One to two days after symptom onset, a “pseudo membrane” develops in 95% of cases, which appears as a thick, grey and leathery membrane at the back of the throat. This is formed from cell debris and inflammatory exudate. Breathing difficulty may occur, especially if part of the membrane dislodges and obstructs the airway.

Toxin-related complications include myocarditis (heart muscle inflammation), neuropathy (nerve damage) and in rare cases, acute tubular nephropathy (kidney damage).

结核病是如何传播的？

Diphtheria is very contagious and is spread by inhalation of respiratory droplets from an infected person. Diphtheria can also be spread via skin lesions, in cases of cutaneous diphtheria, and the bacteria can also survive on environmental surfaces for weeks.  Asymptomatic carriers may transmit the bacteria.

Humans are the only known reservoir for diphtheria.

流行病学

In the pre-vaccine era, young children (< 10 years old) were at highest risk for contracting diphtheria.  Diphtheria previously represented one of the leading causes of death in childhood, with an associated mortality rate of 5-10%.

Diphtheria is now rare in high income countries with high vaccination coverage, but remains endemic in many lower income countries. Outbreaks across the globe continue to be an issue, with 16,000 cases worldwide reported in 2018.

Cases in Australia are more commonly associated with the return of international travellers.

预防措施

Diphtheria is vaccine-preventable, with protection available through administration of combination vaccines routinely administered via the National Immunisation Program (NIP) at:

• 6 weeks, 4 months and 6 months – Infanrix® hexa/Vaxelis®
• 18 months – Infanrix®/Tripacel®
• 4years – Infanrix® IPV/Quadracel®
• 12-13 years (Year 7) – Boostrix®

Additional doses of Boostrix® are recommended and funded for pregnant women during every 怀孕 (regardless of how closely spaced). Further doses are recommended (not funded) for adults at ≥ 50 years of age, if their last dose was more than 10 years ago. Regular boosters are recommended every 10 years for travellers to high risk countries, and for some high-risk laboratory workers.

Injection site pain is commonly reported following diphtheria vaccination. This is usually mild and resolves within a few days. Uncommon side effects reported include headache, lethargy, malaise and fever.

资源

• Australian Immunisation Handbook: Diphtheria
• CDC: Diphtheria
• AIHW: Diphtheria in Australia
• 澳大利亚政府卫生和老年护理部：2023 年 7 月 1 日起国家免疫计划时间表发生变化

背景

Like any medication in development, vaccine candidates must undergo rigorous testing procedures and scientific evaluation to prove not only their effect on the targeted disease, but also to determine their safety, before being licensed and registered for use in vaccination programs. In Australia, the Therapeutic Goods Administration (TGA) is responsible for assessing vaccines and other medicines for use in Australia.

Once vaccines have been introduced into the community, the safety and effectiveness of vaccines then continues to be monitored in the post-licensure phase through active surveillance programs and further post-licensure trials. This is to ensure that there is ongoing monitoring for how the vaccines are working in the ‘real-world’, noting they will be administered to a much larger and more diverse population than during the development phase.

Development phase

During vaccine development, initial safety testing of a vaccine candidate occurs in two stages. Stage one involves pre-clinical assessment in the laboratory. Stage two involves the evaluation of the vaccine candidate in three phases of human clinical trials. If a vaccine candidate is not deemed safe in any stage, it cannot progress into the further stages of clinical trials, with this data being reviewed by an independent data safety monitoring board (DSMB).

• Phase I clinical trials: the vaccine candidate is given to small numbers (25–50) of healthy adults with the primary goal of assessing safety.
• Phase II clinical trials: if the vaccine candidate is found to be safe in Phase I, it is then given to hundreds of people to determine how effectively it stimulates immune responses, the optimal dose regimen, and whether there are any side effects.
• Phase III clinical trials: if the vaccine candidate is found to be effective and safe in Phase I and II, it is then given to many thousands of people to test whether it protects large populations from the target disease and to determine if there are any uncommon or serious side effects.

A vaccine must pass all of these phases before it is registered for use by the TGA. Previously, approval of vaccines could take up to 10 years. However, the process has been streamlined throughout the COVID-19 pandemic and can now be completed in under 12 months, noting all of the appropriate clinical phase trials and data requirements from the regulators have not changed.

Post-licensure phase

Despite the extensive safety testing undertaken in clinical trials before a vaccine is licensed, some side effects are so rare, they cannot be detected in a trial population (e.g., such as with thrombosis with thrombocytopenia syndrome [TTS] following COVID-19 adenoviral vector vaccines). In addition, the efficacy of a vaccine may be different when given to a larger and more diverse population compared with those who participated in the clinical trial (e.g., due to the presence of underlying medical conditions, different age groups etc). For these reasons, assessment of safety and efficacy continues to be monitored in post-licensure assessments through:

• further clinical trials
• surveillance of the impact of the vaccine on the disease it aims to prevent using networks such as PAEDS
• surveillance of adverse events following immunisation using systems such as AusVax安全 and reporting services like SAFEVAC 和 赛维克.

What happens if a problem is suspected?

Any suspected vaccine safety signals undergo a thorough investigation by the TGA, with the support of the jurisdictional vaccine safety services.

If a suspected problem could be serious, authorities will consider a range of actions including modifying the product information (PI) and if extremely serious it may include suspending use of the vaccine during the investigation.

Provisional approval

Provisional approval has been the formal pathway used in Australia for speeding up access to COVID-19 vaccine candidates using preliminary clinical data. The provisional pathway allows for the temporary registration of promising medicines or vaccines based on early data, where the benefits of early access (such as in a pandemic), outweigh any risks.

It is very important to note that this evaluation process remains a full review and a vaccine is still required to pass all the same phases of clinical trials and meet the same requirements for safety and efficacy as any other vaccine in development.

As further clinical data to confirm the safety of a vaccine becomes available, full registration can then be granted (On April 21, 2023 Spikevax (Moderna) was transitioned from the provisional pathway to full registration).

Health Technology Assessment (HTA) of vaccines

Whilst vaccines are undergoing development and regulatory approval, in parallel they also need to undergo health economics assessment if they are going to go onto the National Immunisation Program (NIP). In Australia this assessment of vaccines is undertaken by the Pharmaceutical Benefits Advisory Committee (PBAC).

This pathway was not utilised during the COVID-19 pandemic, due to the speed and complexity of the public health emergency, but PBAC approval will be required for all new vaccines that are coming down the pipeline. As part of this assessment, ATAGI provides advice to the PBAC regarding how these vaccines may be best utilised in the Australian context, taking into account vaccine effectiveness, safety and equity.

资源

• MVEC：疫苗平台
• MVEC COVID19 Road to a Vaccine Podcast, Episode 7: The importance of regulatory bodies in the development of vaccines, with Professor Norman Baylor
• MVEC COVID19 Road to a Vaccine Podcast, Episode 16: COVID19 vaccine candidates regulatory process update, with Professor Norman Baylor
• Australian Academy of Science: How are vaccines shown to be safe?
• The International Coalition of Medicines Regulatory Authorities: ICMRA statement about confidence in vaccine safety and effectiveness (for healthcare professionals)
• The International Coalition of Medicines Regulatory Authorities: ICMRA statement about confidence in vaccine safety and effectiveness (for the general public)

免下车免疫诊所是支持疫苗接种的另一个场所。免下车诊所可以帮助社区成员继续接受建议的免疫接种，同时保持身体距离。

免下车诊所可能不适合所有患者。在免疫接种之前对患者进行筛查以确定其是否适合使用免下车服务非常重要。对患者进行预筛查可以识别既往免疫反应、血管迷走反应史或针恐惧症。

通过预约进行会议可以允许规划所需疫苗的类型和数量，还可以错开患者的流动以防止交通拥堵。

免下车诊所的准备工作

设置此类免疫场所时需要考虑许多不同的因素。

那个地点

考虑选择靠近全科医生服务或医疗保健机构（如果适用）的位置。理想的位置应允许单向交通流，以避免拥堵并确保漫游工作人员的安全。每个单独的停车位应留出足够的空间，以便所有 4 个车门在没有任何障碍的情况下完全打开（以确保在发生 AEFI 时能够完全接触到每位患者）。

设备

仔细考虑建立和维护免下车诊所所需的设备。设备应包括清晰的标牌、用于管理不良事件的床/椅子（如果需要）、过敏反应套件、必要的文件（例如免疫前检查表和疫苗副作用表）、维持冷链的设备以及任何设备准备和接种疫苗所必需的。远程访问患者记录和 澳大利亚免疫登记 (AIR) 建议允许审查免疫记录。以及所接种疫苗的适当文件。

职员

工作人员可能包括免疫护士以及医疗和行政人员。

冷链

在免下车诊所环境中储存疫苗必须符合疫苗制造商提出的冷链建议。疫苗从专用疫苗冰箱中取出到注射之间的时间应尽可能短。

在免下车免疫接种期间

在接种疫苗之前，必须审查和讨论免疫史、免疫前检查表、可能的疫苗副作用和免疫接种的适宜性。

应急设备（过敏反应套件）和电话必须随时可用，以便在需要时使用。

正确的注射技术 至关重要的是，确保整个肢体暴露并识别正确的解剖标志以找到正确的注射部位。如果患者无法在车内安全免疫（例如：坐在中间汽车座椅的儿童）或不适合车内免疫接种，则可以在车外坐在椅子上进行免疫接种，然后返回车内等待建议的 15 分钟等待时间。应建议患者在停车时不要进出汽车。

在免下车会议中进行免疫后

接种疫苗后，患者必须在疫苗接种地点停留至少 15 分钟，并建议患者在接种疫苗后至少 15 分钟内避免开车。如果需要，应指导在车内等候的患者在 15 分钟的观察期内使用汽车喇叭来引起注意。所有疫苗均应记录在 AIR 上，并应填写适当的文件并提供给患者。

资源

• MVEC：冷链
• MVEC：与疫苗接种相关的肩部损伤
• MVEC：与疫苗接种相关的肩部损伤 (SIRVA) 电子学习包
• 国家疫苗储存指南“争取 5”
• MVEC：注射疫苗的管理 - 正确的技术
• ATAGI 关于疫苗观察时间的临床声明
• ATAGI 关于建立免下车 COVID-19 疫苗接种诊所站点考虑因素的声明