T Letter

What is it?

Tuberculosis (TB) is caused by an infection with the bacteria Mycobacterium tuberculosis. In rarer cases, TB may be attributed to infection with Mycobacterium bovis or Mycobacterium africanum.

TB is categorised as being an active disease (the infected person is displaying symptoms and is infectious) or a latent infection (the bacteria is dormant and the infected person has no symptoms and is not infectious). Latent TB can become active if an infected person’s immune system becomes weakened (due to a medical condition or taking immunosuppressive therapies), following serious illness, with drug or alcohol abuse, or with increasing age.

What to look for

Approximately 60% of TB cases in Australia present as pulmonary (lung) TB. Common symptoms include a chronic cough which may be accompanied by haemoptysis (coughing blood) as well as fevers, night sweats, weight loss and malaise (generally feeling unwell).

In some cases, infection can also occur in the brain, bones, kidneys or lymph nodes. TB meningitis (brain infection) and TB septicaemia (blood infection) are considered the most serious manifestations of TB disease.

Most people infected with TB are asymptomatic. 10% of people infected with TB will go on to develop clinical disease at some point in their lifetime.

How is it transmitted?

Pulmonary TB can be spread to others via aerosol transmission of infected droplets through coughing or sneezing. People with TB infections without lung or laryngeal involvement generally cannot transmit disease. However, urine is considered infectious in the case of renal TB. In countries where Mycobacterium bovis is prevalent (it is not prevalent in Australia), the bacteria can also be transmitted by ingesting unpasteurised milk.

A person is considered infectious until 14 days after being on active treatment AND until they have tested negative on a sputum sample. Following an active infection the bacteria will remain dormant (non-infectious) within scar tissue where it can be reactivated later in life (even decades later). Once reactivated the bacteria is capable of being transmitted again.

Epidemiology

Australia has one of the lowest rates of TB in the world, affecting less than 7 per 100,000 people. Aboriginal and Torres Strait Islander people residing in the Northern Territory and Far North Queensland have a much greater burden of disease compared with non-Indigenous people in those areas and Aboriginal and Torres Strait Islander people living in other states.

Globally, it is estimated that approximately one-quarter of the world’s population is infected with TB, causing 1.5 million deaths annually. Bangladesh, China, India, Indonesia, Nigeria, Pakistan, Philippines and South Africa have the highest incidence of infection, accounting for almost half of the world’s TB cases.

Children under 5 years of age, the older population, those with immunocompromise (due to medical condition or immunocompromising therapies) and those impacted by poor living conditions have the highest rates of infection.

Prevention

Vaccination with the BCG vaccine is effective in reducing the incidence of TB meningitis and death in children less than 5 years of age in countries where TB is prevalent. Vaccination is not routinely recommended in developed countries like Australia where disease incidence is low. In Australia the following groups of people are recommended to be vaccinated:

• children < 5 years living in Aboriginal and Torres Strait Islander communities in Queensland
• Aboriginal and Torres Strait Islander neonates living in Queensland
• children < 5 years of age travelling internationally to areas where tuberculosis is prevalent.

BCG vaccination for individuals travelling to areas with a high incidence of disease is ideally administered 4-6 weeks prior to travel.

Tuberculin skin testing

Tuberculin skin testing (TST) or Mantoux testing prior to BCG vaccination is recommended on a case-by case basis to determine if a person already has a level of immunity to TB. It involves the intradermal injection of a tuberculin purified protein derivative (PPD).

In people who have previously received a BCG or have previously had TB exposure, a hypersensitivity reaction can be recognised 48-72 hours later.

It is important to note that TST results may be unreliable for 4-6 weeks following a measles infection or receiving a measles-containing vaccine.

Vaccine administration

BCG vaccine is administered via the intradermal route. Only healthcare providers trained in intradermal technique should provide BCG vaccination.

The recommended site for injection is on the left arm over where the deltoid muscle inserts into the humerus. Administration at this site will minimise the risk of keloid scarring.

• In children < 12 months of age the recommended dose is 0.05ml
• In children > 12 months of age the recommended dose is 0.1ml

Other injected live-attenuated vaccines can either be administered on the same day as BCG or 4 weeks apart. There is no recommended interval between BCG and oral live-attenuated vaccines.

Contraindications and precautions

BCG is a live-attenuated vaccine and is therefore contraindicated in individuals with immunosuppression or in those who are pregnant.

If active eczema, dermatitis or psoriasis is present at the site of injection, vaccination should be deferred until the skin can be treated and is clear of symptoms.

Side effects following vaccination

BCG, like all vaccines, has a list of common and expected side effects and a list of rare side effects that may occur in the weeks following vaccine administration.

Common and expected side effects can include:

1. a small red papule will appear at the injection site in the weeks following the vaccine
2. an ulcer (open sore) may develop 2-3 weeks later (usually less than 1 cm in diameter) and last from a few weeks to months
3. the majority of infants will develop a flat scar at the site once the ulcer heals.

Rare or more serious side effects can include:

1. axillary lymphadenopathy (swelling of the lymph nodes under the left arm)
2. persisting ulcer lasting longer than a few months
3. a large abscess (collection of pus) at the injection site
4. keloid scarring at the site.

NB: If you suspect a rare or serious side effect, it is strongly recommended to seek medical advice either from a GP or the medical clinic where the BCG was administered. For specialist immunisation advice or to report an adverse event following immunisation (AEFI), please contact SAEFVIC.

Post vaccination care

Following vaccination the site must be kept clean and dry. Normal activities like bathing and swimming can continue ensuring that the area is patted dry afterwards.

If the ulcer is oozing it may be covered with a dry gauze and can be cleaned with an alcohol swab. Ointments, creams or antiseptics should not be applied directly to the site.

For more information refer to What to expect following the BCG vaccination – RCH parent handout.

Resources

BCG Clinics in Victoria

• The Royal Children’s Hospital: BCG Clinic
• Monash Health Immunisation Service
• Offspring Child Health Specialists
• Family Immunisation & Travel Specialists (FITS)
• A/Prof Mike Starr 
• Craigieburn Specialist Consulting Suites
• Medical One- QV
• Kids Travel Doc
• The Children’s Private Medical Group
• Wyndham Private Medical Centre
• Travel Clinics Australia- Caulfied
• Travel Clinics Australia- Williams Landing

Other

• MVEC: Intradermal vaccination
• RCH Kids Health Information: Tuberculosis disease (TB)
• Australian Immunisation Handbook: Tuberculosis
• RCH Kids Health Information BCG vaccine for TB
• What to expect following the BCG vaccination – RCH parent handout
• What to expect after your child receives the BCG vaccination – Monash Hospital parent handout
• Dhanawade, S. Kumbhar, S. Gore, A. and Patil, V. Scar formation and tuberculin conversion following BCG vaccination in infants: A prospective cohort study, Journal of Family Medicine and Primary Care 2015 Jul-Sep 4(3) 384-387

What is it?

Typhoid and paratyphoid fever are bacterial infections, collectively known as enteric fever and are caused by the bacterias Salmonella enterica subspecies serovars Typhi and Paratyphi A, B and C. Enteric fever is different to the gastroenteritis that can be caused by Salmonella. Symptoms of enteric fever can range from mild to severe, and if left untreated can lead to serious complications or death. Typhoid fever presents more commonly than paratyphoid fever and is associated with higher rates of severe complications and poorer outcomes.

What to look for

Infections caused by typhoid and paratyphoid often present with prolonged fever and fatigue, headache, splenomegaly (enlargement of the spleen), and abdominal symptoms such as pain, lack of appetite, constipation or diarrhoea; often with bacteremia (bacteria in the bloodstream). A rash appearing as small pink clusters on the skin known as ‘rose spots’ can be seen in up to 30% of individuals with enteric fever. In severe cases, complications can include septic shock, gastrointestinal bleeding with perforation, altered conscious state, and death.

How is it transmitted?

Typhoid fever is transmitted via the faecal-oral route and via contaminated food and water sources, most commonly in developing countries with untreated drinking water and poorer sanitation and food handling practices. The incubation period is usually 7-14 days.

Approximately 1 in 20 infected individuals who do not receive treatment for typhoid fever will become an asymptomatic carrier of the disease.

Epidemiology

Whilst not as prevalent in Australia, typhoid fever is a common infective illness in many parts of the world, especially Asia, southeast Asia and sub-Saharan Africa. There were 14.3 million cases of typhoid and paratyphoid fever in 2017, with an estimated global case fatality of 0.95%. Children are disproportionately affected by infection.

Prevention

Prevention of enteric fever includes both vaccination and undertaking food and water precautions whilst travelling in developing countries where typhoid is endemic. There is no specific vaccine for paratyphoid fever however there is some evidence to suggest that administration of the oral typhoid fever vaccine can provide some cross protection against paratyphoid fever.

Vaccines

There are 3 vaccines available in Australia for protection against typhoid fever:

^§Whilst not registered for use in this age group, a number of travel medicine practitioners routinely administer Vivaxim® to children aged 2-15 years. Refer to Lau C. et al The tolerability of a combined hepatitis A and typhoid vaccine in children aged 2-16 years: an observational study Journal of Travel Medicine 2016: 15, 23 (2) for more information.
*If a patient is taking both Vivotif® oral and the oral cholera vaccine (Dukoral®), these should be administered 8 hours apart due to the risk of components of the cholera vaccine impacting how the typhoid vaccine is absorbed in the gut.
^Not to be given to people who are immunocompromised, taking immunosuppressive medications, pregnant women, or those taking oral antibiotics.

Other precautions

In addition to vaccination, travellers should also maintain the following precautions to limit exposure to infections:

• undertaking effective hand washing practices
• drinking bottled or boiled water
• avoiding high-risk foods and drinks including:
  • raw (or undercooked) shellfish
  • cold meats
  • salads
  • untreated water and ice in drinks.

Resources

• Australian Immunisation Handbook: Typhoid fever
• The blue book: guidelines for the control of infectious diseases
• World Health Organization: Typhoid

Thrombosis with thrombocytopenia syndrome (TTS), also known as Vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) or vaccine-induced immune thrombotic thrombocytopenia (VITT), was a rare syndrome reported in people who received adenoviral vector COVID-19 vaccines such as Vaxzevria (AstraZeneca) and the Johnson & Johnson/Janssen COVID-19 vaccine.

Please note: adenoviral vector COVID-19 vaccines are no longer available for use in Australia. The following information remains for reference purposes.

What is TTS?

The syndrome is characterised by thrombosis formation (blood clots) combined with thrombocytopenia (low platelet count) with symptoms typically presenting in the 4-42 days after vaccination.

According to the Center for Diseases Control (CDC) TTS is classified into 2 tiers based on the location of thrombosis and severity of symptoms. Cases are further classified based on if there has been recent exposure to heparin or not.

Tier 1:

• uncommon site of thrombosis (eg. brain – cerebral venous sinus thrombosis [CVST] or gut – eg. splanchnic vein, associated with bowel ischaemia and surgery, portal vein or other rare venous and arterial thromboses)
• may also concurrently have thrombosis in more common locations (eg. deep vein thrombosis or pulmonary embolism)
• platelet count < 150,000 per microliter
• positive (+) anti-PF4 ELISA result is supportive, but not required for diagnosis.

Tier 2:

• common sites of thrombosis such as leg or lungs (eg. venous thromboembolism, deep vein thrombosis, pulmonary embolism)
• platelet count < 150,000 per microliter
• positive anti-PF4 ELISA result is required.

Tier 1 tends to be associated with more severe presentations and carries a higher risk of morbidity and mortality than Tier 2. Evidence suggests that Tier 1 is more common in younger age groups.

How did adenoviral vector vaccines trigger TTS?

The exact mechanism of how TTS is triggered is still under investigation, however the majority of cases were associated with the finding of anti-PF4 antibodies. There are no clear diagnostic markers to indicate who is at risk of this syndrome. This is currently under investigation.

TTS appears to be similar to an autoimmune condition known as heparin induced thrombocytopenia (HIT), which is where an immune reaction to the medication heparin impacts platelet function, leading to thrombosis (clots).

The risk of TTS

It is estimated that the risk of developing TTS after dose 1 of Vaxzevria (AstraZeneca) was approximately 2.6 per 100,000 persons, with those under 60 years experiencing more severe outcomes. The risk of developing TTS following dose 2 occurred at a much lower rate.

The risk of developing other clotting disorders after receiving adenviral vector vaccines

There is currently no evidence that adenoviral vector vaccines increase the overall risk of developing other standalone thromboses (eg. other clotting disorders leading to deep vein thromboses, pulmonary emboli, myocardial infarction, stroke) beyond the baseline rate in the general population.

TTS was different to other commonly diagnosed thromboses as it was triggered by an immune response to a specific type of vaccine which then results in the combination of both thrombosis (clots) and thrombocytopenia (low platelet count).

Resources

• MJA: Australian and New Zealand approach to diagnosis and management of vaccine‐induced immune thrombosis and thrombocytopenia
• Thrombosis and Haemostasis Society of Australia and New Zealand (THANZ) Multidisciplinary VITT Guideline for Doctors
• HealthPathways Thrombosis with Thrombocytopenia Syndrome (TTS) pathway (login required)
• ATAGI statement on revised recommendations on the use of COVID-19 Vaccine AstraZeneca, 17 June 2021
• ATAGI: Joint statement from ATAGI and THANZ on Thrombosis with Thrombocytopenia Syndrome (TTS) and the use of COVID-19 AstraZeneca
• THANZ advisory statement for haemotologists, August 19, 2021: Suspected Vaccine induced immune thrombotic thrombocytopenia (VITT)
• Australasian College of Emergency Medicine: Thrombosis with Thrombocytopenia Syndrome following COVID-19 vaccination
• COVID-19 vaccination – Information for Immunisation Providers on Thrombosis with Thrombocytopenia Syndrome (TTS) following COVID-19 vaccination
• Patient information sheet on AstraZeneca COVID-19 vaccine and thrombosis with thrombocytopenia syndrome (TTS)

What is tetanus?

Tetanus is a bacterial infection caused by the bacteria Clostridium Tetani. It commonly lives in dirt, dust and animal waste and the spores are usually introduced into the body via lacerations or puncture wounds. The spores can survive in a wound for as long as 3 months before becoming active. The most common time frame for presentation of tetanus is around 14 days, but it can also be delayed (up to months), after the injury. Unlike other vaccine preventable diseases, tetanus is not transmissible from person to person.

Examples of wounds that are considered tetanus prone include:

• bites, either animal or human
• deep penetrating wounds
• wounds with foreign bodies i.e. splinters
• burns
• open fractures
• cuts or lacerations with outdoor equipment
• tooth reimplantation post avulsion
• IV drug use sites.

Tetanus can occur following trivial or even unnoticed wounds. Tetanus prophylaxis should be strongly considered for all unimmunised or partially immunised persons, regardless of the nature of the wound.

Signs and Symptoms

People infected with tetanus commonly show signs of muscle spasm, mainly around the face and neck, including lock jaw. Spasms can last for significant amounts of time, requiring large amounts of analgesia.

Severe cases can lead to breathing difficulties, respiratory infections and heart attack. 1 in 10 people with tetanus will die despite receiving prompt medical treatment.

Prevention

Vaccination is the most effective way to prevent tetanus.

As per the National Immunisation Program (NIP), a primary course of tetanus vaccination is given at 6-weeks, 4-months, and 6-months of age (Infanrix® hexa/Vaxelis®).

Boosters doses are then scheduled to be administered at:

• 18 months (Infanrix®/Tripacel®)
• 4 years (Infanrix-IPV®/Quadracel®)
• 12 to 13 years of age/Year 7 high school program (Boostrix®)

A further booster dose as dTpa (Boostrix®/Adacel®) is recommended but not funded, for adults aged ≥ 50 years who have not received a dose of tetanus-containing vaccine in the last 10 years.

Regular booster doses every 10 years are no longer recommended. However immunisation advice regarding the management of a tetanus prone wound varies from this (see below).

Tetanus prone wounds

The correct management of a tetanus prone wound is vital in the prevention of tetanus (see resources: RCH Clinical Practice Guideline).

Key messages include:

• where applicable, wounds should be cleaned, disinfected, and surgically treated if required
• in paediatric patients, a full immunisation history should be taken, ensuring that a primary course of tetanus vaccination has been completed
• if a patient is > 5 years post a tetanus vaccine, then a booster is recommended
• an important age group to consider for a booster are those aged between 9-13 years, as they are 5 years post their 4 year old vaccine, and may not have yet received their Year 7 booster.

Children or adults who are unimmunised or only partially

Every person will receive an injury at some point in their life. Whether it is tetanus prone, will depend on medical assessment. Even the most superficial wounds could be at risk of tetanus depending on the mechanism of injury.

An unimmunised or partially immunised person is at greatest risk of contracting tetanus. The elderly population are often included in this group due to timing of their last booster, most commonly being exposed whilst gardening.

A partially immunised person is one who has not yet completed a primary course, or has received < 3 doses of a tetanus containing vaccine. These people require not only a tetanus-containing vaccine but also tetanus immunoglobulin (TIG) (refer to resources for specific advice).

If immunisation history is in doubt, TIG and a tetanus-containing vaccine should be administered.

Immunoglobulin provides protection for up to 1 month after administration. Vaccination provides protection against the toxin and not the bacteria. A full course of 3 doses of a tetanus-containing vaccine should be completed to ensure ongoing immunity. If individual advice is required consider a referral to a Specialist Immunisation Clinic.

ADT® vaccine

The use of ADT® in children aged < 10 years is not recommended as it does not contain enough antigen to promote an adequate immune response in the unimmunised, however there are unlikely to be safety issues. Parents requesting this option should be made aware of the increased risk of contracting tetanus.

Management of immunosuppressed patients with a tetanus prone-wound

Immunosuppressive medications are becoming more common place in the management of particular medical conditions. Patients who may be immunosuppressed include:

• autoimmune conditions ie: IBD, lupus, rheumatologocial conditions
• solid organ transplant recipients, Haematopoietic stem cell transplant recipients
• all oncology patients.

Patients who are immunosuppressed should be considered unimmunised and treated accordingly with immunoglobulin and a vaccine.

Resources

• Australian Immunisation Handbook: Tetanus
• The Royal Children’s Hospital Clinical Practice Guideline: Management of tetanus prone wound
• Australian Government Department of Health and Aged Care: Changes to the National Immunisation Program schedule from July 1 2023

Travel medicine focuses on disease prevention and injury risk minimisation with advice based upon the travelling person’s individual circumstances such as the location and purpose of travel, duration and time of year, as well as any underlying medical conditions or other risk factors.

Where to get travel advice

General Practitioners and travel medicine clinics can provide recommendations for preventative care and offer vaccination. There are also paediatricians who specialise in infectious diseases or immunisation who can provide advice for children (and their families). There are also a number of excellent websites that can be accessed to obtain country specific updates and information on emerging infections [see Resources below].

When to seek advice

For specific pre-travel advice, consultation with a health care professional is best done a minimum of 4-6 weeks prior to departure, which allows time to develop immunity following any recommended vaccines prior to arrival at the travel destination. Depending on which vaccines are recommended, a course of vaccines over time may be indicated before a person is considered fully protected.

As most travel specialists require a GP referral and may have wait times for an appointment, it is important to factor this into travel planning timelines.

Vaccines

Some routine vaccines can be given earlier than scheduled or as additional doses for the purposes of travel. Examples of this include:

• MMR (measles, mumps and rubella) vaccine: an extra, funded dose can be administered between the age of 6-11 months if travelling to an area where measles are endemic
• Meningococcal vaccines:
  • MenACWY (Nimenrix) vaccines can be administered from 6 weeks of age in order to provide earlier protection (scheduled on the NIP at 12 months of age and in year 10 of secondary school)
  • Meningococcal B (Bexsero) vaccines can also be given from 6 weeks of age (not funded on the National Immunisation Program (NIP) for all, but can be purchased privately for those who do not qualify for a funded dose)
• Influenza vaccine: depending on the time of year and destination of travel, it may be advisable to receive an influenza vaccine
• COVID-19 vaccines: due to ongoing emerging strains of COVID-19 disease, it is important to ensure a primary course of COVID-19 vaccination is complete along with any recommended boosters based on current recommendations.

Other travel-related vaccines, depending on your location and duration of travel might include:

• BCG
• Cholera
• Hepatitis A
• Japanese encephalitis
• Typhoid
• Rabies
• Yellow fever

Other precautions

Other preparations for travel may include:

• considering the need for malaria prophylaxis (medication to prevent malaria)
• measures to prevent mosquito-borne disease such as wearing long-sleeved clothing, mosquito nets, and insect repellent than contains DEET
• food and water safety.

Immunocompromised and pregnant travellers

Individuals who are immunocompromised as a result of a medical condition or specific therapies are encouraged to seek travel advice early to maximise protection against vaccine preventable diseases prior to travel.

Similarly, women who are planning pregnancy or who are pregnant, should seek travel advice as early as possible to ensure optimum protection for both the mother and unborn baby. Women planning pregnancy with a high likelihood of travel, should consider vaccination prior to pregnancy noting that live-attenuated vaccines are contraindicated during pregnancy.

Visiting friends and relatives (VFR)

VFR travel is one of the most common reasons for international travel. A VFR traveller is an immigrant who travels from the high-income country they are living in to their lower-income country of birth to visit friends or relatives. A travel consult prior to VFR travel should consider whether an individual has had routine NIP vaccines or a history of vaccine preventable disease/s as well as vaccines indicated for the country they are travelling to. Rates of some travel-related infections are higher in this population and taking appropriate precautions such as vaccination and considering food and water safety is important in ensuring optimum protection.

Resources

MVEC travel related resources

• BCG vaccine
• Influenza
• Measles
• Rabies
• Yellow fever
• Typhoid 
• Meningococcal

Other resources

• Department of Health Victoria: Yellow fever vaccination centres
• The RCH kids info- travel health advice
• Centres for Disease Control and Prevention (CDC): Travelers’ health
• Bug off
• Travel health pro- travel health website