D Letter

पृष्ठभूमि

Discoloured leg syndrome (DLS) is a rare phenomenon that कर सकना occur after receipt of an injected vaccine. It is a transient condition involv

 either an even or patchy colour change to the skin in the lower extremities (red, blue or purple) और may or may not involve petechiae (pin-point red spots on the skin) या swelling.

Diagnosis

DLS है be diagnosed based on clinical presentation (e.g. symptom profile, onset of symptoms and symptom resolution).

Unlike injection site reactions (ISRs), DLS does not radiate from the site of injection, and can impact one or both legएस, even if only one injection has been administered. Discolouration can also extend up to the pelvis.

Investigations are generally not required. Despite the presence of petechiae, there is no drop in platelet count.

As DLS involves skin changes and symptoms can occur quickly, it is important to differentiate it from anaphylaxis, especially if symptoms start within 30 minutes of vaccination.

Association and incidence

DLS is reported at a rate of 58 per 100,000 children vaccinated. Although the median onset time for colour change is approximately 3.5 hours, DLS can be seen quite quickly post-vaccination (within 30 minutes). Where symptoms of petechiae occur, the median onset time is 12 hours following vaccination. Generally, colour change (median duration = approximately 2 hours) does not last as long as petechiae (median duration = 54 hours).

इलाज

As a precaution, assessment of airway, breathing and circulation is advised.

Symptoms of DLS are transient and will resolve on their own without treatment.

Any adverse event following immunisation (AEFI), including DLS, should be reported to the adverse event reporting service in your jurisdiction. In Victoria, this is सैफविक.

भविष्य की खुराक के लिए निहितार्थ

Recurrence of DLS है uncommon, but can occur. एचowever, DLS है not a contraindication to receiving future vaccines. Given that DLS appears to be age-related, families can be reassured that children are less likely to experience symपीtoms as they get older.

संसाधन

• Finnish Institute for Health and Welfare: Swelling in a lower limb and changes in skin colour after a vaccination
• Kemmeren JM, Vermeer-de Bondt PE, van der Maas NA. Discolored leg syndrome after vaccination–descriptive epidemiology. Eur जे Pediatr. 2009;168(1):43-50. doi:10.1007/s00431-008-0707-0

इन्फ्लुएंजा क्या है?

Dengue, or dengue fever, is a viral illness caused by infection with the dengue virus (DENV).

DENV is a single‑stranded RNA virus that, like yellow fever virus और Japanese encephalitis virus, belongs to the genus Flavivirus. There are four serotypes of DENV. Immunity against one serotype does not provide protection against the other serotypes, meaning a person can experience dengue more than once in their lifetime. Severe disease is more likely with subsequent infections.

किन लक्षणों पर नज़र रखने की आवश्यकता है?

Dengue has an incubation period of 3 to 14 days. Most people who are infected experience no symptoms or have mild symptoms which resolve in 1 to 2 weeks. Common symptoms include:

• high fever (40°C)
• severe headache
• muscle and joint pains
• खरोंच
• pain behind the eyes
• abdominal pain, nausea and vomiting
• swollen glands.

In rare cases, infection can progress to severe disease (dengue haemorrhagic fever, dengue shock syndrome) and display symptoms of severe abdominal pain, haematemesis (vomit with blood in it), tachypnoea (rapid breathing), bleeding from the gums or nose, fatigue, lethargy, pale and cold skin, or other unexplained bleeding. Severe dengue is a medical emergency.

यह कैसे संचारित होता है?

DENV is primarily transmitted to humans via mosquitoes. Humans who are symptomatic can transmit the virus 2 days prior to symptom onset until 2 days after the fever has resolved. Asymptomatic cases (without symptoms) are also infectious. In rare cases, DENV can be transmitted through mucous membranes, blood transfusions, needle stick injuries and organ transplants. Maternal transmission during pregnancy (from mother to infant) has been reported and is linked to pre‑term birth, low birthweight and post‑partum haemorrhage (severe bleeding).

एपिडेमियोलॉजी (महामारी विज्ञान)

Dengue is now endemic in more than 100 countries across tropical and sub‑tropical areas in the Pacific, Asia, Africa and the Americas. There were 14.6 million cases of dengue reported to the World Health Organization (WHO) in 2024.

DENV is not routinely found in Australia although imported cases (where a person is infected overseas) do occur. Mosquitoes capable of carrying dengue can be found in central and northern Queensland, the Northern Territory, northern Western Australia, and the Torres Strait. Local outbreaks of dengue, although rare, have historically occurred in northern Queensland and the Torres Strait.

रोकथामं

वास्तविक बाधाएं

The mosquitoes capable of carrying dengue are active during the day. Care should be taken to avoid exposure by:

• बाहर जाने पर लंबे, ढीले-ढाले कपड़े पहनना
• पिकारिडिन या डीईईटी युक्त मच्छर निरोधकों का उपयोग करना
• यदि बहुत सारे मच्छर हों तो बाहरी गतिविधियों को सीमित कर दें
• using fly sprays, mosquito coils and plug‑in repellent devices
• sleeping under mosquito nets treated with insecticides if sleeping indoors where windows, doors and vents are not covered by insect‑proof mesh (flywire screens), or if sleeping outdoors in an untreated tent or in the open.

Vaccination

Dengvaxia is a live‑attenuated recombinant tetravalent vaccine used for the prevention of

dengue infections only. It is given as a 3‑dose course, with 6 months between each dose, and is suitable only where the all following conditions are met:

• Aged 9–45 years
  और
• Previously infected with DENV
  और
• Intending to reside in highly dengue
  endemic regions for extended periods
  और
  
• The potential benefits of vaccination outweigh the risks.

It is only available through the Special Access Scheme (SAS), on a case‑by‑case basis, through specific application to the Therapeutic Goods Administration (TGA).

मतभेद और सावधानियां

Dengvaxia is not safe for people who have never been infected with DENV before. Given approximately 40 to 80% of dengue infections are asymptomatic and there is no blood test sensitive enough to adequately confirm previous immunity, identifying who can safely be vaccinated is challenging.

Dengvaxia has been linked to vaccine-associated enhanced disease (VAED), a rare phenomenon where a person who has been vaccinated experiences a (usually) more severe clinical presentation of an infection than would normally be seen in an unvaccinated person.

It is a live-attenuated vaccine and therefore must not be given during गर्भावस्था or to immunosuppressed individuals.

संसाधन

• World Health Organization: Dengue
• Australian Centre for Disease Control: Dengue – CDNA National Guidelines for Public Health Units
• ATAGI advice on the use of Dengvaxia for Australians
• Victorian Department of Health: Dengue virus disease
• European Medicines Agency: Dengvaxia
• Australian Centre for Disease Control: Dengue

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

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) – December 2025

संसाधन

• Guidance: Immunological work-up and vaccination recommendations for children with 22q11 microdeletion (PDF) – December 2025
• 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)