D Letter

पृष्ठभूमि

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 के लिए many people with DiGeorge syndrome means that vaccination is particularly important को provide protection against vaccine-preventable diseases. However, it is important to recognise that the immune response to vaccines may be suboptimal meaning अतिरिक्त doses of vaccines may be recommended. Conversely, some vaccines (live-attenuated vaccines) may be contraindicated due to the potential risk of vaccine-related disease. 

Recommendations

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)

संसाधन

• Guidance: Immunological work-up and vaccination recommendations for children with 22q11 microdeletion (PDF)
• एमवीईसी: इम्यूनोसप्रेशन और टीके
• 22q Foundation Australia and New Zealand

इन्फ्लुएंजा क्या है?

Diphtheria is a rare but potentially life-threatening acute illness caused by the bacteria कॉरीनेबैक्टीरियम डिप्थीरिया. 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.

किन लक्षणों पर नज़र रखने की आवश्यकता है?

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).

यह कैसे संचारित होता है?

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.

एपिडेमियोलॉजी (महामारी विज्ञान)

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.

रोकथामं

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 गर्भावस्था (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.

संसाधन

• Australian Immunisation Handbook: Diphtheria
• CDC: Diphtheria
• AIHW: Diphtheria in Australia
• ऑस्ट्रेलियाई सरकार का स्वास्थ्य और वृद्ध देखभाल विभाग: 1 जुलाई 2023 से राष्ट्रीय टीकाकरण कार्यक्रम कार्यक्रम में परिवर्तन

पृष्ठभूमि

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 AusVaxSafety and reporting services like SAFEVAC और सैफविक.

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.

संसाधन

• एमवीईसी: वैक्सीन प्लेटफॉर्म
• 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)

ड्राइव-थ्रू टीकाकरण क्लीनिक वैक्सीन वितरण का समर्थन करने के लिए एक वैकल्पिक स्थान हैं। एक ड्राइव-थ्रू क्लिनिक समुदाय के सदस्यों को शारीरिक दूरी बनाए रखते हुए अनुशंसित टीकाकरण प्राप्त करना जारी रखने में सहायता कर सकता है।

ड्राइव-थ्रू क्लिनिक एक ऐसी सेटिंग नहीं हो सकती है जो सभी रोगियों के लिए अनुशंसित हो। यह महत्वपूर्ण है कि टीकाकरण से पहले ड्राइव-थ्रू सेवा का उपयोग करने के लिए रोगियों की उपयुक्तता की जांच की जाए। रोगियों की पूर्व-जांच से पिछली टीकाकरण प्रतिक्रियाओं, वासोवागल प्रतिक्रियाओं के इतिहास या सुई फोबिया की पहचान की जा सकती है।

नियुक्ति के आधार पर सत्र चलाने से आवश्यक टीकों के प्रकार और मात्रा की योजना बनाने में मदद मिल सकती है और यातायात की भीड़ को रोकने के लिए रोगियों के प्रवाह को क्रमबद्ध करने की भी अनुमति मिलती है।

ड्राइव-थ्रू क्लीनिक की तैयारी

इस प्रकार के टीकाकरण स्थल की स्थापना करते समय कई अलग-अलग कारकों पर विचार करने की आवश्यकता होती है।

स्थान

जीपी सेवा या स्वास्थ्य देखभाल सुविधा (यदि लागू हो) के नजदीक किसी स्थान पर विचार करें। भीड़भाड़ से बचने और घूमने वाले स्टाफ सदस्यों की सुरक्षा सुनिश्चित करने के लिए एक आदर्श स्थान यातायात के एक-दिशात्मक प्रवाह की अनुमति देगा। प्रत्येक व्यक्तिगत पार्किंग बे में सभी 4 कार के दरवाजों को बिना किसी रुकावट के पूरी तरह से खोलने के लिए पर्याप्त जगह होनी चाहिए (एईएफआई होने पर प्रत्येक मरीज तक पूर्ण पहुंच सुनिश्चित करने के लिए)।

उपकरण

ड्राइव-थ्रू क्लिनिक की स्थापना और रखरखाव के लिए आवश्यक उपकरणों पर सावधानीपूर्वक विचार करें। उपकरण में स्पष्ट संकेत, यदि आवश्यक हो तो प्रतिकूल घटनाओं का प्रबंधन करने के लिए बिस्तर/कुर्सी, एक एनाफिलेक्सिस प्रतिक्रिया किट, आवश्यक कागजी कार्रवाई, (जैसे पूर्व-टीकाकरण चेकलिस्ट और टीका साइड इफेक्ट फॉर्म), कोल्ड चेन बनाए रखने के लिए उपकरण, साथ ही कोई भी उपकरण शामिल होना चाहिए। टीके तैयार करने और प्रशासित करने के लिए आवश्यक है। रोगी रिकॉर्ड और तक दूरस्थ पहुंच ऑस्ट्रेलियाई टीकाकरण रजिस्टर (एआईआर) टीकाकरण रिकॉर्ड की समीक्षा की अनुमति देने की अनुशंसा की जाती है। साथ ही प्रशासित किसी भी टीके का उचित दस्तावेजीकरण।

कर्मचारी

स्टाफ में नर्स टीकाकरणकर्ता, साथ ही चिकित्सा और प्रशासनिक कर्मचारी शामिल हो सकते हैं।

कोल्ड चेन

ड्राइव-थ्रू क्लिनिक सेटिंग में टीकों का भंडारण वैक्सीन निर्माता द्वारा निर्धारित कोल्ड चेन सिफारिशों का पालन करना चाहिए। उद्देश्य-निर्मित वैक्सीन फ्रिजों से टीकों को निकालने से लेकर प्रशासित होने तक के बीच का समय यथासंभव कम होना चाहिए।

ड्राइव-थ्रू टीकाकरण सत्र के दौरान

टीकाकरण से पहले टीकाकरण इतिहास, पूर्व-टीकाकरण चेकलिस्ट, संभावित टीके के दुष्प्रभाव और टीकाकरण के लिए उपयुक्तता की समीक्षा और चर्चा की जानी चाहिए।

आवश्यकता पड़ने पर आपातकालीन उपकरण (एनाफिलेक्सिस रिस्पांस किट) और एक टेलीफोन आसानी से उपलब्ध होना चाहिए।

सही इंजेक्शन तकनीक यह सुनिश्चित करना आवश्यक है कि पूरा अंग खुला हो और सही इंजेक्शन स्थल का पता लगाने के लिए सही संरचनात्मक स्थलों की पहचान की जाए। यदि किसी मरीज को कार में सुरक्षित रूप से प्रतिरक्षित नहीं किया जा सकता है (जैसे: बीच की कार की सीट पर बैठा बच्चा) या वह वाहन में टीकाकरण के लिए उपयुक्त उम्मीदवार नहीं है, तो उन्हें कार से बाहर कुर्सी पर बैठाकर प्रतिरक्षित किया जा सकता है, फिर कार में वापस लाया जा सकता है। अनुशंसित 15 मिनट की प्रतीक्षा अवधि की प्रतीक्षा करें। मरीजों को सलाह दी जानी चाहिए कि वे अपनी कारों को पार्क करते समय अंदर और बाहर न निकलें।

ड्राइव-हालाँकि सत्र में टीकाकरण के बाद

टीकाकरण के बाद, रोगियों को टीकाकरण स्थल पर कम से कम 15 मिनट तक रहना चाहिए और टीकाकरण के बाद कम से कम 15 मिनट तक गाड़ी चलाने से बचने की सलाह दी जानी चाहिए। अपने वाहनों में प्रतीक्षा कर रहे मरीजों को निर्देश दिया जाना चाहिए कि यदि आवश्यक हो तो 15 मिनट की अवलोकन अवधि में ध्यान आकर्षित करने के लिए कार के हॉर्न का उपयोग करें। सभी टीकों को एआईआर पर दर्ज किया जाना चाहिए और उचित दस्तावेज पूरा करके रोगी को प्रदान किया जाना चाहिए।

संसाधन

• एमवीईसी: कोल्ड चेन
• एमवीईसी: वैक्सीन प्रशासन से संबंधित कंधे की चोट
• एमवीईसी: वैक्सीन एडमिनिस्ट्रेशन (एसआईआरवीए) ई-लर्निंग पैकेज से संबंधित कंधे की चोट
• राष्ट्रीय वैक्सीन भंडारण दिशानिर्देश '5 के लिए प्रयास करें'
• एमवीईसी: इंजेक्शन वाले टीकों का प्रशासन- सही तकनीक
• टीकाकरण अवलोकन समय पर एटीएजीआई क्लिनिकल वक्तव्य
• ड्राइव-थ्रू COVID-19 टीकाकरण क्लिनिक साइटों की स्थापना के लिए विचार पर ATAGI का वक्तव्य