High blood glucose levels occur in diabetes because the body does not respond properly to the hormone insulin, which controls glucose levels.

In type 2 diabetes, insulin is less effective in controlling blood glucose levels. This is because the key targets of insulin, liver and muscle cells, are less sensitive to its effects. This condition is termed ‘insulin resistance’.

Insulin resistance may be triggered by chronic inflammation. This is caused by immune cells within fat tissue releasing substances that inflame neighbouring tissues. The fatter a person becomes, the more inflammation their fat tissue generates.

Insulin resistance leads to high levels of glucose in the blood. This can reinforce insulin resistance, potentially by exacerbating inflammation. At the same time, high levels of glucose in the blood trigger more insulin release from the pancreas. This triggers inflammation within the pancreas, which kills the insulin-secreting beta cells. This leads to less insulin being produced, worsening the blood glucose levels and increasing inflammation.

Around 1.3 million Australians have been diagnosed with type 2 diabetes. It is estimated that another 500,000 Australians have the condition but have not been diagnosed, putting them at increased risk of complications. Complications of type 2 diabetes are a significant health burden for Australia.

A person’s risk of developing type 2 diabetes depends on their age and their genetic makeup, but also on ‘lifestyle’ factors.

Certain inherited, genetic factors increase a person’s chances of developing type 2 diabetes. This explains why relatives of someone with type 2 diabetes are more likely to also have this condition. It also explains why type 2 diabetes rates are higher in people from certain racial and ethnic groups. Aboriginal Australians have a high risk of developing type 2 diabetes.

A person’s chances of developing type 2 diabetes are increased if they:

• Are older: type 2 diabetes risk increases with age
• Are overweight or obese
• Have high blood pressure
• Have previously had gestational diabetes
• Are female

Reducing body weight and increasing physical fitness can reduce a person’s chances of developing type 2 diabetes.

The severity of type 2 diabetes can differ between people. Some people show insulin resistance but normal levels of insulin production; in other people, the condition is predominantly associated with reduced insulin production. These factors can also change with time.

The severity and characteristics of a person’s type 2 diabetes influences how they are treated. Blood glucose levels can often be controlled by regular exercise and eating a healthy diet, which does not raise blood sugar rapidly.

Our researchers are trialing whether weight loss can be used as a treatment for type 2 diabetes.

Some people with type 2 diabetes also require medications that:

• Reduce blood sugar levels.
• Improve how cells respond to insulin.
• Stimulate insulin production by the pancreas.

When insufficient insulin is produced, a person with type 2 diabetes needs to start taking additional insulin. This is given by injections or through a pump.

In the long term, people with type 2 diabetes may need additional treatments for complications of their condition. Common complications of type 2 diabetes include:

• Kidney disease (diabetic nephropathy)
• Eye disease and blindness (diabetic retinopathy)
• Nerve damage (diabetic neuropathy)
• Damage to blood vessels, which together with nerve damage can lead to serious problems in the hands and feet
• Heart disease and stroke.

For more information, and support for people with type 2 diabetes please visit Diabetes Australia.

Influenza is an infectious disease caused by viral infection of the cells lining the nose, throat and lungs. The influenza virus lives and reproduces within cells, causing symptoms including:

• A high fever
• Headache and body aches
• Extreme fatigue
• Coughing, nasal discharge and sneezing

Influenza can cause serious, potentially fatal, complications including:

• Lung disease, and subsequent bacterial infections
• Heart inflammation and failure
• Brain and liver inflammation, a condition called Reye syndrome

Many of the symptoms of influenza are a consequence of the immune response to the influenza infection.

Influenza occurs when the influenza virus is inhaled. It can be spread between people, or, in some strains, from animals such as birds or pigs, to humans.

Different strains of influenza virus exist. These have different severity and infect different species. Most human influenza is caused by the ‘influenza A’ virus. Influenza strains can be distinguished by variations in two surface proteins called haemagglutinin (H) and neuraminidase (N).

Influenza strains differ in the species they infect – some influenza viruses cannot infect humans. They also differ in the severity of their disease.

Influenza occurs more frequently in cooler months. This is termed ‘seasonal influenza’. Each year, different strains of influenza virus occur. Exposure to these viruses leads to people becoming immune to them – they are protected against a second infection.

Occasionally a strain of influenza emerges that spreads more widely and causes more serious disease and death. This is called ‘pandemic influenza’. Factors enabling an influenza virus causing a pandemic include:

Emergence of a new influenza virus strain that few people have already established immunity to.
The virus triggering a larger-than-usual immune response, which causes illness and death, particularly in young, otherwise healthy people.

Illness and death from influenza are a substantial global health burden. There are 290,000 – 650,000 influenza-related deaths annually. Previous influenza pandemics have claimed the lives of millions of people in one or two years.

Some people are at elevated risk of serious illness from influenza infection. These include:

• Young children
• Older people
• Pregnant women
• People with a weakened immune system, such as people infected with HIV
• People with diabetes
• People with other chronic diseases including heart disease and lung disease

Outbreaks of pandemic influenza often cause death in young, otherwise healthy adults. This may be because pandemic influenza triggers a harmful immune response.

Influenza can be prevented by vaccination. Current vaccines can only trigger protective immune responses to individual strains of influenza virus, not all strains. For this reason, influenza vaccination does not offer lifelong immunity and annual vaccination is required.

Influenza spread can be reduced by good hygiene, and by avoiding contact with infected people.

The World Health Organization and government agencies oversee influenza surveillance programs to enable early responses to new strains of influenza to reduce the spread of the virus and prevent pandemics.

Hepatitis B is a liver disease caused by infection with the hepatitis B virus. In the short term this causes liver inflammation, which can cause illness and is occasionally fatal.

In most people, this ‘acute’ infection can be controlled within several months. This means the virus is no longer reproducing within the liver, and the person is no longer infectious.

In some people, the hepatitis B virus continues to grow within their liver cells. This is called a chronic infection. It can cause cirrhosis, a scarring of the liver that impairs its function.

Both acute and chronic hepatitis B infections put people at risk of developing liver cancer. The presence of the viral genome within liver cells can increase the chances that the liver cells develop genetic changes, allowing cancer development.

People who are at greater risk of developing chronic hepatitis B after initial infection include:

• Infants and young children.
• People with impaired immunity such as people infected with HIV.

One-third of the world’s population has been infected with hepatitis B virus. The virus is carried as a chronic infection by 250 million people, including more than 230,000 Australians. Chronic hepatitis B infection is more prevalent in Aboriginal and Torres Strait Islander Australians than the wider population.

More than 880,000 people die each year from the consequences of hepatitis B infection. The prevalence of hepatitis B virus globally contributes to liver cancer being one of the leading causes of cancer-related deaths. In Australia, the number of deaths from liver cancer is increasing faster than deaths from any other cancer.

Hepatitis B virus is spread between people through infected blood and bodily fluids, such as semen and saliva. When hepatitis B virus enters the body, it infects liver cells. Here the virus can replicate, and release new viruses into the blood stream.

There is a vaccine that can protect against hepatitis B virus infection. It triggers the production of antibodies to hepatitis B virus. This prevents newly acquired virus from surviving within the body.

In Australia, hepatitis vaccination is recommended for:

• Newborns.
• People working in close contact with other people, such as healthcare and childcare workers.
• People living with someone infected with hepatitis B
• People with weakened immune systems, such as people with HIV.

Unvaccinated people who may have been exposed to hepatitis B virus can be treated with antibodies to hepatitis B. These antibodies bind to hepatitis B virus in the body, preventing them from infecting cells. The antibodies are produced from the donated blood of people who have been vaccinated against hepatitis B.

Acute hepatitis B is usually a mild illness that does not require treatment.

People who have chronic hepatitis B infection can be treated with antiviral medications. These do not cure the disease. Instead they reduce the growth of the virus, and reduce liver damage. Our researchers aim to discover how the immune system can be triggered to cure chronic hepatitis B infection.

Serious liver damage caused by hepatitis B is sometimes treated by liver transplantation.

Giardiasis is a diarrhoeal disease caused by the parasite Giardia duodenalis.

Giardia is a tiny, single-celled organism with multiple whip-like tails, called flagella. The parasite lives in the small intestine of mammals – including humans – where it interferes with the absorption of nutrients from food. As the parasite travels down the digestive tract, it develops into cysts that are shed in faeces. The cysts can survive in the environment for weeks or months.

The Giardia parasite is transmitted when people swallow cysts via hand-to-mouth contact. For example, outbreaks are common in childcare centres due to poor hand hygiene after changing nappies.

Transmission can also occur through contaminated water supplies: the parasite is spread when people drink the water, use it to wash their food or ingest it during recreational activities such as swimming. This is a common route of infection for travellers and people hiking or camping in the wilderness.

There are up to 600,000 cases of giardiasis in Australia each year, and more than 280 million cases worldwide. The disease has a disproportionately high impact on children in impoverished communities, including in remote Indigenous communities in Australia.

Symptoms of giardiasis usually develop one to three weeks following infection and can include:

• Diarrhoea and greasy stools that float
• Nausea/vomiting
• Gas
• Abdominal cramps
• Dehydration
• Post-infectious irritable bowel syndrome
• Chronic giardiasis can lead to significant long-term effects including malnutrition, weight loss, delayed physical and mental growth and predisposition to other diseases.

Some people with giardiasis show no symptoms but can still transmit the disease.

People at risk of giardiasis include:

• Children and staff at childcare centres
• Family members of people with giardiasis
• Travellers to areas where giardiasis is common
• Hikers or campers who drink untreated water from lakes and rivers
• People who swim in contaminated water, such as lakes, rivers and swimming pools
• Practising good hygiene and avoiding contaminated food and water when travelling reduces the risk of giardiasis

Many cases of giardiasis are self-limiting and resolve on their own. Other cases are more persistent and require treatment to clear the infection.

The drugs currently available to treat giardiasis have significant side effects and are not always effective; drug resistance is emerging, leading to treatment failure. Chronic giardiasis remains a major health and economic burden, particularly in resource-poor communities. These limitations highlight the need for new drugs to treat giardiasis.

Our researchers are using advanced genome technologies to study the Giardia parasite. The parasite has a compact genome and can be readily grown in the lab, making it possible to investigate genes that regulate fundamental aspects of parasite biology, including:

• Invasion of and development within the host
• Development, transmission and detection of drug resistance
• Identification of novel targets for new drug development

These genomic tools can also be used to explore how the parasites develop resistance to common drugs.

Ultimately, understanding the genes that control key aspects of parasite biology will underpin approaches to detect, treat and control giardiasis.

The term ‘arthritis’ means pain, stiffness and other signs of inflammation in the joints. In rheumatoid arthritis, this inflammation is caused by the immune system attacking the body’s own joint tissues.

A major site of immune attack in rheumatoid arthritis is the small joints of the hands and feet, called ‘synovial joints’.

Rheumatoid arthritis occurs when immune cells are activated to recognise components of these synovial joints, causing inflammation of the joint lining, known as synovitis. Synovitis causes pain, swelling, warmth and reduced function of the involved joint.

Persistent joint inflammation eventually damages the joint, including cartilage, adjacent bone, and surrounding structures, such as tendons.

Rheumatoid arthritis can also lead to inflammation outside of the joints. This can damage blood vessels, eyes, nerves and lungs, amongst other organs. Rheumatoid arthritis can also exacerbate cardiovascular disease and increase the risk of heart attack and stroke.

Around 2 in 100 Australians has rheumatoid arthritis. Despite major improvements in treatments in the past 20 years, rheumatoid arthritis remains a significant cause of disability and lost personal and economic productivity in Australia.

Rheumatoid arthritis can begin at any age, but most often appears in early adult life.

The cause of rheumatoid arthritis is not well understood, although there are a number of potential clues. A person’s chance of developing rheumatoid arthritis is increased if they:

• Have relatives with rheumatoid arthritis or other autoimmune diseases. Some rheumatoid arthritis risk genes have been discovered.
• Are female.
• Smoke.

There is currently no cure for rheumatoid arthritis, but early diagnosis and treatment can reduce the damage to joints and other tissues, and lessen disability.

Medications for rheumatoid arthritis currently include:

• Symptomatic treatments temporarily reduce joint inflammation and pain, such as painkillers (analgesics), corticosteroids and non-steroidal anti-inflammatory drugs. Unfortunately these treatments do not slow the progression of the underlying disease.
• Disease-modifying anti-rheumatic drugs (DMARDs) do slow the progression of disease, as well as relieving symptoms. DMARDs work by decreasing the abnormal function of the immune system that drives rheumatoid arthritis.

Physiotherapy and occupational therapy are very helpful in people with rheumatoid arthritis for maintaining strength and physical activity and performing activities of daily living, including work. Psychological therapy can help negotiate the difficulties of a chronic, painful illness and the impact this has on the person and the person’s family.

Maintaining physical and psychological health is vital in rheumatoid arthritis. Good working relationships between the patient, the GP and specialists are important. Rheumatologists are expert in the management of this complex condition, including the role of new therapies. GPs can coordinate care and help navigate the health system.

The Australian Rheumatology Association and Arthritis Australia can provide more detailed information about managing rheumatoid arthritis.

Immunodeficiencies are a broad class of conditions where one or more components of the immune system are missing. A person with an immunodeficiency has trouble fighting infections. They may contract more illnesses than other people, and may become infected with microbes that do not normally cause disease in humans.

When someone is born lacking a component of the immune system, it is termed ‘primary immunodeficiency’.

Secondary immunodeficiency describes immunodeficiencies arising as the result of another event such as HIV infection or taking immune suppressing medication.

The Immune Deficiencies Foundation Australia provides information and support for people with immunodeficiencies, their carers and relatives.

Many primary immunodeficiencies are caused by changes in the genes that contribute to immune cell development and function. This means they can be passed from parents to a child, or can occur frequently in an extended family.

Common variable immunodeficiency (CVID) is the most common primary immunodeficiency, both in Australia and worldwide. It is estimated that approximately one in 10,000 Australians have CVID.

People with CVID have problems making antibodies, which are important in fighting infections and building immune protection. Low levels of antibodies put people with CVID at risk of recurrent bacterial infections. These people are also unable to develop a normal immune response to vaccines.

Diagnosing CVID is difficult and requires exclusion of other primary immunodeficiencies. As symptoms of CVID can be quite different between people, many people with this condition are not diagnosed until they are adults.

CVID appears to be caused by faulty genes. However, it appears there are many different genes that can contribute to CVID. Only in a few cases have the gene changes causing CVID been identified. For most people, the underlying cause of CVID is not known.

Our research into CVID aims to find the underlying cause of CVID. To do this we need help from people with CVID, as well as people with another immune deficiency called X-linked agammaglobulinemia (XLA). Find out more about our study into the causes of CVID.

Around a quarter of people with CVID have autoimmune diseases. This suggests that the cause of CVID could be part of a broader problem with the control of the immune system, where appropriate immune responses to microbes are stifled, but harmful attacks on normal body tissues occur.

Malaria is a disease that is caused by a parasite. The parasite can get into our bodies when we are bitten by certain types of mosquitoes that are infected with the parasite. These mosquitoes are most common in hot, tropical regions like Africa and Asia.

While malaria is preventable and curable, it still claims the lives of more than 600,000 people worldwide every year. The disease is most deadly to pregnant women and children aged under five, particularly in poorer countries where malaria-fighting medicine is not always accessible.

Malaria is a major cause of death and loss of productivity in many countries in South-East Asia, the Pacific and Africa.

The parasite Plasmodium causes malaria. It is transmitted to humans through the bite of an infected Anopheles mosquito.

See this process in the WEHI.TV biomedical animation Malaria Lifecycle Part 1: Human Host

The malaria parasite has a complex lifecycle. When a malaria parasite enters the blood, via mosquito saliva, it travels to a person’s liver. Here it undergoes a ‘silent’ development stage. It multiplies in the liver cells but does not cause illness.

Parasites then move into the blood, where they infect red blood cells. This stage makes a person sick and causes symptoms of malaria, such as:

• fever and chills
• headache
• fatigue
• nausea and vomiting
• difficulty breathing
• blockage of blood vessels in critical organs like the brain
• organ failure
• anaemia (too few red blood cells)
• coma.

There are five species of parasite that can cause malaria in humans. Our research is focused on the two species that cause the greatest devastation:

• Plasmodium falciparum causes rapid and severe illness, and more deaths globally than any other type of malaria. It is most common in Africa.
• Plasmodium vivax is the most widespread type of malaria worldwide and is a significant cause of illness in the Asia-Pacific region. Its ability to lie dormant and undetectable for months in humans makes it tricky to treat and stop from spreading. It can reactivate, causing multiple episodes of sickness from a single bite. It also means the parasite has more opportunities to pass back to mosquitos, spreading the disease further.

If someone has malaria, there are antimalarial drugs that can help. Sometimes the drugs don’t work as well because the malaria is getting stronger and becoming resistant to the drugs. That’s why we need new drugs to fight it.

Vaccines could help stop malaria from spreading. Our scientists are trialling two different vaccines to see if they could be effective in treating malaria.

Malaria can be prevented by:

• avoiding mosquito bites by sleeping under bed nets, wearing long-sleeved clothing or using repellents
• taking antimalarial medicines to prevent malaria or stop mild cases from getting worse.

People who are at greatest risk of falling sick to malaria include:

• young children and travellers who have no immunity to malaria
• pregnant women or people with HIV/AIDS who have low or compromised immune systems
• people living in poor or remote locations who struggle to access doctors or medicines.

More information about malaria may be found on the following websites:

• World Health Organisation – Malaria
• Malaria – Patient information
• Malaria in Australia

Diabetes (or diabetes mellitus) describes conditions in which levels of glucose in the blood are abnormally high. Glucose is an energy source that comes from food. It is stored in the liver and muscles in a form called glycogen.

It is critical for health that the level of glucose is tightly controlled in the blood. Without enough glucose, organs cannot function properly, but too much glucose can cause organ damage.

Normally blood glucose levels are tightly controlled by two hormones released by the pancreas:

• Insulin: decreases blood glucose when it is high, such as after a meal, by increasing glucose uptake by cells and blocking the glucose release from the liver.
• Glucagon: increases blood glucose when it is low, such as after exercise, by opposing the actions of insulin and releasing glucose from the liver.

Blood glucose can be elevated for a variety of reasons. The three most common types of diabetes in Australia are:

• Type 1 diabetes: caused by immune destruction of the insulin-producing cells in the pancreas.
• Type 2 diabetes: a condition in which the body does not respond appropriately to its own insulin, called ‘insulin resistance’, together with gradual loss of beta cell function and evidence of low-grade inflammation.
• Gestational diabetes is a form of insulin resistance that occurs during pregnancy. For more information about this and other rarer forms of diabetes, visit Diabetes Australia.

People with diabetes are at risk of short-term and long-term health problems caused by high blood glucose. People with diabetes can experience immediate symptoms of very low or high blood glucose.

High levels of glucose can cause immediate and serious problems for people with diabetes. A lack of insulin, particularly in type 1 diabetes, can rapidly lead to a serious condition called diabetic ketoacidosis. This is caused by cells switching away from glucose as an energy source, instead metabolising fatty acids, a process that generates toxic byproducts.

In the long-term, consistently high levels of blood sugar caused by diabetes can cause damage to many organs. This can lead to serious health problems including:

• Kidney disease (diabetic nephropathy)
• Eye disease and blindness (diabetic retinopathy)
• Nerve damage (diabetic neuropathy)
• Damage to blood vessels, which together with nerve damage can lead to serious problems in the hands and feet
• Heart disease and stroke.

Good control of blood sugar greatly reduces the risk of diabetic complications.

For more information, and support for people with diabetes please visit Diabetes Australia.

Insulin is a critical treatment for people with type 1 diabetes, and for some people with type 2 diabetes. Currently, insulin cannot be given as a tablet, but must be injected.

Different forms of insulin are available, which act over different time frames. ‘Short-acting’ insulin rapidly decreases blood glucose, so is best taken after a meal. ‘Long-acting’ insulin can control blood glucose levels over longer periods. Combinations of different insulin types offer people with diabetes the best opportunity to maintain healthy blood glucose levels.

Our structural biology researchers have revealed how insulin uses the insulin receptor to bind to the surface of cells. They hope this discovery could lead to the development of new types of artificial insulin that could be given without injections. Understanding how insulin functions may also contribute to more stable, longer-acting forms. The goal of this research is to improve the control of blood glucose in people taking insulin to treat diabetes.

Toxoplasmosis is caused by infection with Toxoplasma gondii, a parasite that infects up to 60% per cent of the population in some places. It is related to the parasites that cause malaria and cryptosporidiosis, two other globally significant illnesses.

Humans become infected with Toxoplasma through contact with parasites shed into the environment from infected cat faeces, or by eating raw infected meat. In most people, the initial infection causes mild, or no, symptoms.

In people with weakened immune systems, toxoplasmosis can lead to:

• Brain damage, including encephalitis (inflammation), which can cause confusion and loss of coordination
• Eye damage, impairing vision. Toxoplasmosis is a leading cause of blindness in some communities
• Lung infections
• Coma and death

Pregnant women with toxoplasmosis can transmit the parasite through the placenta to their foetus. This can cause problems including:

• Premature birth
• Brain damage, potentially causing abnormal brain size, seizures and intellectual disability
• Eye damage, potentially causing blindness
• Ear damage, causing hearing loss

Often these symptoms do not become apparent in the child until a decade or more after birth.

As well as causing an immediate ‘acute’ infection, Toxoplasma parasites can form cysts in the infected person’s muscles, heart, brain and eyes. These cysts are found in an estimate of 25 to 30 per cent of people world wide. The parasite can lie dormant in cysts for years. If a person’s immune system is later weakened, the parasite can emerge to cause severe toxoplasmosis.

Re-emergence of a dormant Toxoplasma infection is a significant cause of illness and death in people infected with HIV.

Chronic infection with Toxoplasma has been associated with mental disorders such as schizophrenia and bipolar disorder. It has recently been suggested that chronic infection of Toxoplasma in the brain might exacerbate symptoms in these conditions due to changes in neurotransmitter pathways.

Most people infected with Toxoplasma do not require any treatment. People with compromised immunity, and pregnant women, can be treated with anti-parasitic medications.

Toxoplasma infections can be reduced in people with HIV by treating with antiretroviral medications, which slow the loss of immune function.

Toxoplasma is a parasite that is closely related to Plasmodium, which causes malaria. Many of the genes and proteins that are used by Toxoplasma to infect cells are similar to those used by Plasmodium.

Research into Toxoplasma can provide insights into processes that are also used by Plasmodium. Toxoplasma is easier to work with in the laboratory than Plasmodium because:

• Toxoplasma is more easily grown in the laboratory.
• It is easier to manipulate or disrupt genes in Toxoplasma than in Plasmodium.

The amount of glucose in the blood is normally tightly controlled. But in diabetes blood glucose levels are abnormally high.

The hormone insulin normally reduces blood glucose levels and is produced by cells in the pancreas called ‘beta cells’. However, in type 1 diabetes there is a misdirected ‘autoimmune’ reaction to the insulin-producing beta cells in the pancreas, which leads to insufficient insulin being produced. Without insulin, high levels of glucose accumulate in the blood.

The immune system protects our body from invading microbes. There are normally many safeguards that prevent it from attacking the body’s own tissues. In type 1 diabetes, these safeguards fail, and immune cells specifically destroy beta cells.

Type 1 diabetes is the most common chronic (long-term) childhood illness in Australia. More than 120,000 Australians have type 1 diabetes. The incidence of type 1 diabetes in Australia has increased in the past 30 years.

Most people with type 1 diabetes are diagnosed as children or young adults. Even with a lifetime of the best available care, they are at increased risk of serious complications such as

• Kidney disease (diabetic nephropathy)
• Eye disease and blindness (diabetic retinopathy)
• Nerve damage (diabetic neuropathy)
• Damage to blood vessels, which together with nerve damage can lead to serious problems in the hands and feet
• Heart disease and stroke

Type 1 diabetes is caused by a combination of genetic risk and environmental factors. Our researchers have shown that changes in our environment have contributed to the increase in the incidence of type 1 diabetes in the past few decades.

Many environmental factors have been proposed to trigger or promote type 1 diabetes. These include infections, diet and weight gain.

Known risk factors for type 1 diabetes include:

• Having other autoimmune or inflammatory diseases such as coeliac disease or autoimmune thyroid disease. These conditions all involve aberrant immune responses.
• Having a parent or sibling with type 1 diabetes or other autoimmune diseases. One in five Australians diagnosed with type 1 diabetes have a family history of the condition.
• Living at higher latitudes: the incidence of type 1 diabetes is increased in populations who live furthest from the equator. This may be partly genetic. It may also be related to environmental factors such as vitamin D deficiency and hygiene.

Almost all people with type 1 diabetes rely on insulin injections for their entire lives. They must closely monitor their blood glucose levels. When blood glucose rises, such as after a meal, an appropriate insulin dose is calculated and injected. Insulin is available in ‘slow acting’ and ‘fast acting’ forms. These can aid the smoother control of blood glucose levels.

There is no orally available (tablet) form of insulin. Insulin can only be given by injection, such as with a syringe. Recently, small, attachable insulin pumps have been introduced instead of multiple daily injections. Insulin pumps may control blood glucose better by providing a more steady release of insulin into the body.

The only cure for type 1 diabetes is transplantation or regeneration of insulin-producing cells.

Transplantation of the whole pancreas or the parts of the pancreas containing insulin-secreting beta cells can be performed. It is limited by a shortage of organ donors, and the need for life-long immune suppression to prevent transplant rejection. Thus, transplantation is restricted to people with poorly controlled diabetes and serious complications.

Our researchers have shown that the pancreas contains stem cells that can be transformed into beta cells. Their hope is that it may one day be possible to cure type 1 diabetes by stimulating the regrowth of beta cells. This would depend on stifling the immune cells that originally destroyed the beta cells.

Diabetes Australia has more detailed information about diabetes treatment.

Cryptococcosis is a disease caused by infection with the fungus Cryptococcus. It is potentially fatal, particularly in people with a weakened immune system.

The Cryptococcus fungus is present in the environment, particularly in areas contaminated with bird droppings. It can infect skin and wounds. The most common way Cryptococcus infects humans is by being inhaled.

When Cryptococcus is inhaled, it can grow within the lungs. In some people this causes a slowly developing lung disease. Within the lungs, immune cells called macrophages can also be infected. The Cryptococcus cells can survive and divide within macrophages.

Cryptococcus lung infections can lie dormant for months to years. The infection can also spread to other parts of the body. This is more likely to occur in people with a weakened immune system.

In the brain, Cryptococcus infection causes cryptococcal meningitis. This is a serious inflammatory disease that can cause:

• Confusion and hallucinations
• Brain damage
• Hearing loss
• Hydrocephalus (accumulation of fluid on the brain)
• Coma

Untreated cryptococcal meningitis is fatal in an estimated 30 to 70 per cent of people.

More than 180,000 people die from cryptococcosis every year, mostly in sub-Saharan Africa. It is the leading cause of death in people with HIV and AIDS in this region.

Severe Cryptococcus infections, especially cryptococcal meningitis, are most often associated with a weakened immune system. This is often caused by:

• HIV infection and AIDS
• Lymphoma
• Immunosuppressive medications

Cryptococcus infections can be cured by treatment with anti-fungal agents. This often takes months to completely eliminate the infection. In people with HIV, anti-retroviral treatment that maintains immune system function can prevent cryptococcal meningitis.

Many people infected with cryptococcal infections live in resource-poor communities. Many deaths occur in people who have not been able to access appropriate treatment. Our research into cryptococcosis aims to develop more effective treatments that can be made available to all people with this infection.

Tuberculosis is caused by infection with the bacterium Mycobacterium tuberculosis. Most commonly, tuberculosis occurs in the lungs.

People become infected with M. tuberculosis by inhaling the bacterium. Within the lungs, the bacterium is engulfed by immune cells called macrophages. For other types of bacteria, this will kill the bacteria. However, M. tuberculosis bacteria can survive and reproduce within macrophages.

Tuberculosis-infected macrophages trigger other immune cells to attack them. This leads to inflammation, with a mass of immune cells surrounding the infected macrophages.

In 90 per cent of people infected with M. tuberculosis, the infection becomes ‘dormant’. They do not show any symptoms of the infection, but the infection persists within their body.

In some people, the infection becomes ‘active’. The growth of M. tuberculosis bacteria leads to lung damage. Symptoms of active tuberculosis in the lungs include:

• Cough
• Bleeding into the lungs
• Weight loss
• Fever

When someone has an active tuberculosis infection, they are able to spread bacteria to other people through their respiratory fluids.

Occasionally M. tuberculosis bacteria can spread from the lungs to other parts of the body such as bones or the central nervous system. This can cause a variety of symptoms depending on the site of the infection, such as, for bone tuberculosis, swelling, pain and deformation of joints; or for central nervous system tuberculosis, headaches, confusion and seizures.

It is estimated that 1.8 billion people worldwide are infected with M. tuberculosis. Of these, around 10 million have active illness. Tuberculosis causes 1.5 million deaths each year.

Active tuberculosis is more common in people who:

• Have a weakened immune system, particularly those with HIV infection
• Are malnourished
• Have diabetes
• Smoke

There is a vaccine for tuberculosis, called BCG, but it is not effective in all people. Vaccination may reduce the risk of children developing serious tuberculosis disease. Researchers are working to develop a more effective vaccine for tuberculosis.

Tuberculosis is treated with antibiotics that kill the bacteria. Treatment must be given for six to nine months to completely eliminate the infection.

M. tuberculosis can become resistant to antibiotics. The spread of these antibiotic-resistant strains is reducing the success of current treatments. The increasing prevalence of ‘multidrug resistant’ or ‘extensively drug resistant’ tuberculosis strains is leading to the possibility of tuberculosis becoming an incurable disease. Our research into new treatments for tuberculosis is focused on bolstering immune responses to clear infection.

Scabies is a skin infection caused by the microscopic scabies mite, Sarcoptes scabiei. Female mites burrow into the top layers of human skin to lay eggs. This causes irritation, a rash and intense itching, which is particularly bad at night.

Scabies mites release proteins that suppress immune reactions in the skin. These can lead to bacterial skin infections and sores. Bacteria carried by scabies mites and excessive scratching in people with scabies may also contribute to skin infections. Often people with scabies also have trouble sleeping. This can make it hard for them to work, or to attend school.

Scabies mites are spread between people by:

• Prolonged skin-to-skin contact
• Sharing of clothes and bedding
• Living in overcrowded conditions

It is estimated that around 300 million people worldwide are infected with scabies. It occurs in all communities. Scabies, and the complications of scabies infection, are especially prevalent in overcrowded and resource-poor communities in tropical areas.

In Australia, some remote Aboriginal communities have very high rates of scabies. Up to half of the children in some communities are infected. These scabies infections begin at a young age, on average, at two months. They may have lifelong recurrences.

People with scabies in remote Aboriginal communities frequently have skin sores infected with group A streptococcus (‘group A strep’) and Staphylococcus aureus bacteria. These bacterial infections can lead to acute rheumatic heart disease and chronic kidney disease. These serious health burdens can potentially be reduced by preventing scabies infections in a community.

Most people with scabies are infected with only five to 10 mites. People with a weakened immune system, including the elderly and those with conditions such as AIDS, can develop a disease called crusted scabies. In this severe form of infection, a person can carry millions of mites. People with crusted scabies can be debilitated and disfigured. They may be socially isolated and avoid medical attention. People with crusted scabies often act as a ‘reservoir’ for scabies infection in their community. They can re-infect those around them who may have previously been treated and cured of their infection.

Scabies can be cured by treating the infected person with a cream or lotion containing a pesticide. It is easy for scabies mites to re-infect someone who was previously cured of scabies. For this reason, it is important that all people who are close contacts of someone with scabies are treated at the same time. Clothes and bedding should also be thoroughly washed at the same time to kill any mites within them.

In communities with high rates of scabies it is important that everyone infected with the mite is treated at the same time. This ensures people are not re-infected. It is also important that everyone receiving treatment undergoes the full course of treatment.

Scabies mites that are resistant to certain pesticides have been reported. This limits the options for treating people with scabies. Pesticide resistance is most likely to develop when infected people do not complete the full treatment course.

The scabies mite is poorly understood compared to many other parasites. Our researchers are determining the sequence of the scabies mite genome, which contains the genes that control how the scabies mite functions. The goal is to use this information to advance our understanding of scabies mite biology.

It is hoped that deciphering the scabies mite genome will accelerate research into scabies. This has occurred in the aftermath of genome projects for other infectious agents, including for the malaria parasite, Plasmodium.

Analysing the scabies mite genome may reveal better strategies to treat scabies. In particular, it may help accelerate the development of vaccines. Genome sequencing may also explain how scabies mites become resistant to pesticides. This may lead to new ways to overcome resistance.

HIV is a virus, meaning it can only reproduce within another organism’s cells. HIV reproduces in certain human immune cells, particularly a type of immune cell called CD4 T cells. These cells are critical for many immune responses that protect against infections.

When a person is infected with HIV, they may initially be healthy and not realise they are carrying the virus. Without treatment, people infected with HIV usually stay healthy for around 10 years. However, the infection gradually kills their CD4 T cells. This means their immune system cannot function properly.

Someone infected with HIV and not receiving treatment will eventually develop a condition called Acquired Immune Deficiency Syndrome (AIDS). In this condition, the loss of CD4 T cells means the person’s immune system cannot fight infections. People with AIDS are at risk of severe infections by viruses, bacteria and fungi. Often these are infections that a healthy immune system can prevent. A person with AIDS will ultimately die from an overwhelming infection.

More than 27,000 Australians are infected with HIV. Most of these people receive appropriate treatment. This prevents their disease progressing to AIDS. The Education and Resource Centre at the Alfred provides support and information for Victorians living with HIV.

Globally, around 37.9 million people are infected with HIV. The majority of people living with HIV are aged 15 to 49. AIDS-related illnesses cause 770,000 deaths annually, mostly in resource-poor communities. HIV infection is an enormous health, social and economic burden globally.

HIV is a type of virus called a retrovirus. It consists of:

• An outer membrane, or envelope, made of lipids and proteins
• The virus’s genetic content, or genome. This is made of the DNA-like molecule, RNA.
• Internal proteins that help the virus infect cells.

HIV can be transmitted between people through contact with infected bodily fluids. The main sources of HIV infection globally are:

• HIV-infected blood: In Australia, blood donations are screened to ensure they do not contain HIV or other viruses. Syringe needles contaminated with HIV are another potential source of infection.
• Sexual contact: HIV is present in semen and vaginal fluids.
• From mother to child: during pregnancy or birth, or through infected breast milk. This can be reduced by medical interventions including appropriate medical treatment of pregnant women infected with HIV.

When an HIV viral particle enters the body it can infect immune cells called CD4 T cells.

The stages of HIV infection of CD4 T cells are:

• Entry into the cell: The virus binds to certain proteins on the outside of CD4 T cells. This allows the viral proteins and genome to enter the cell.
• Reverse transcription: A viral protein converts the viral genome, made of RNA, to DNA. The genome of human cells is made of DNA.
• Integration: The viral DNA joins into the cell’s DNA. This allows the virus to hide within the cell. It may lie dormant for several years.
• Production of new viruses: The HIV DNA within the cell directs the formation of new viral genomes and proteins. These assemble into new viral particles.
• Release from the cell: The new HIV particles leave the cell, and can infect other cells.

Not all CD4 T cells that are infected with HIV go on to produce new viruses. Often, the CD4 T cells will detect the viral DNA that is produced by reverse transcription. This can trigger the death of the infected cell as a protective response.

There is currently no cure for HIV, and no preventive vaccine.

Understanding how HIV infects cells has led to anti-viral medications that block the different stages. These agents prevent HIV from spreading between cells within the body. This stops the loss of CD4 T cells, allowing the HIV-infected person to stay healthy.

People infected with HIV can receive lifelong anti-viral treatments that stop the loss of CD4 T cells. This prevents AIDS, and allows a near-normal life. Appropriate treatment can also reduce the chance that someone infected with HIV infects other people, particularly for mother to child transmission. Anti-viral treatments can also prevent HIV infections if given immediately after exposure.

When HIV replicates, its genome and proteins may slightly change (mutate). Occasionally these changes mean that the new HIV viral particles are resistant to the actions of an anti-viral medication. If this occurs, the resistant virus will spread unhindered in the body, and the treatment will be ineffective. The best strategies to treat HIV use several different anti-viral medications at once. This reduces the chance that resistance to one treatment can occur.

In poorer communities, the cost of long-term treatment for HIV can prevent people from accessing the best treatment. This increases the chance that they will develop AIDS and die. There is an urgent need for a cure or preventive vaccine for HIV.

What is lupus?

Lupus is a serious condition in which the body’s own immune system mistakenly produces molecules, called antibodies, that recognise a person’s own tissue. This ‘autoimmune’ attack can result in damage to a variety of organs.

The most severe form of lupus is systemic lupus erythematosus (SLE), which often affects many organs. Usually, the skin and joints are most affected, but damage can also occur to the kidneys, lungs, heart, brain and blood vessels.

Lupus can be difficult to diagnose. Many of its symptoms can be confused with other conditions. Symptoms can also vary between people, depending on which tissues the disease-causing antibodies attack.

In the long term, and also as a result of treatment, people with lupus are at an increased risk of:

• infection
• cancer
• bone thinning
• complications associated with pregnancy

In Australia, it is estimated that at least 20,000 people have lupus. Lupus places a substantial economic burden on our community. People with lupus have long-term healthcare needs and often have reduced quality of life.

It is not known what triggers the misdirected immune response that causes lupus. Immune cells called B cells normally produce antibodies that protect the body against infection. There are many safeguards to prevent the production of harmful antibodies that target body tissues rather than foreign organisms. In lupus these safeguards seem to be circumvented. Find out how the immune system is normally controlled.

Immunology research has provided many clues to how changes in the immune system contribute to lupus. For example, defects in the machinery that controls cell death can lead to ‘autoimmune’ B cells that can cause lupus.

The immune system also contains cells that stifle unwanted immune responses. If these cells are not functioning properly, autoimmune attacks on body tissues can occur.

The triggers for lupus are poorly understood. Some factors that are associated with developing lupus are:

• being female: 90 per cent of Australians with lupus are women.
• early adulthood: most cases of lupus are detected in people aged between 15 and 45.
• genetic susceptibility: lupus is more prevalent in some families and some racial groups. Lupus is more prevalent and more severe in Aboriginal Australians than in the wider Australian population.
• sunlight exposure can be a trigger in susceptible people.

There is no cure for lupus, but treatment can reduce symptoms and help prevent long-term organ damage.

Treatments are aimed at dampening the immune response, and reducing inflammation. Some of the medicines prescribed to treat lupus are:

• anti-inflammatory drugs: reduce tissue inflammation in the short term.
• certain antimalarial drugs: work gradually to reduce some of the symptoms of lupus.
• immune suppressing drugs and biologic drugs: powerful drugs that dampen the immune system and are used for more severe cases of lupus.

The current treatment options for lupus are limited. They all come with a risk of potentially serious side-effects, such as susceptibility to infection. There is a need for more effective treatments for lupus, and a better understanding of how the disease develops.

Further information for people living with lupus can be found at:

• State lupus organisations such as the Lupus Association of NSW
• Australasian Society of Clinical Immunology and Allergy
• Arthritis Australia

Lung cancer is the abnormal, uncontrolled growth of lung cells. This is caused by changes to their genetic material. Different types of lung cancers arise from different cell types within the lung. The process by which this occurs is poorly understood.

Most lung cancer types are classified by their microscopic appearance. These include:

• Small cell lung cancer
• Non-small cell lung cancer: squamous cell carcinoma, adenocarcinoma and large cell carcinoma.

Other types of cancer can also occur in the lung. Some of these are rare types of cancer that arise from lung tissue.

Of lung cancers in Australia:

• 10% are small cell lung cancers.
• 60% are non-small cell lung cancer.
• 30% are rare types of lung cancer or cannot be definitively classified.

Cancer cells from other organs can also spread (metastasise) to the lung.

Mesothelioma is a type of cancer that starts in the lining of the chest and spreads into the lungs. Exposure to asbestos is strongly linked to mesothelioma. For more information about mesothelioma, please visit Cancer Council Victoria.

The treatment and outlook for lung cancer depends on the type of cancer, and how far the cancer cells have spread. Lung cancers may be:

• Contained within one part of a lung.
• Spread to several sites across the lungs.
• Spread (metastasised) to other parts of the body.

Most cases of lung cancer in Australia are detected at later, harder-to-treat stages.

Lung cancer occurs because of genetic changes in lung cells. These occur more frequently in people exposed to DNA-damaging agents such as tobacco smoke.

People who have smoked are 10 times more likely to develop lung cancer than non-smokers. Lung cancer is often associated with smoking (tobacco), however 1 in 3 women and 1 in 10 men diagnosed with lung cancer have no history of smoking. People who have never smoked tend to develop adenocarcinoma.

Specific cancer-promoting genetic changes have been discovered in adenocarcinomas in non-smokers. Understanding the genes that drive lung cancer growth and spread is allowing new treatments to be designed that can be matched to the genetic changes found in a patient’s lung cancer cells.

• Exposure to tobacco smoke or other forms of smoke, including smog or traffic fumes.
• Exposure to radiation such as the radioactive gas radon, or chest radiation to treat another cancer.
• Exposure to other cancer-causing (‘carcinogenic’) substances.
• Gender: amongst non-smokers, females are at higher risk of developing non-small cell lung cancer.
• Age: lung cancer rates increase with age.
• Lung inflammation and scarring, from other lung diseases.
• Family history: close relatives of a non-smoker with lung cancer are more likely to get the same disease.

Treatment for lung cancer depends on the type of lung cancer and how far the cancer cells have spread. Currently, most lung cancers are only discovered when they have spread beyond the lungs, which reduces the likelihood of treatment curing the disease.

Lung cancers that are small and confined to one section of a lung can often be successfully removed by surgery.

Lung cancers are often treated with:

• Chemotherapy and radiotherapy to kill rapidly growing cells
• Targeted therapies that match medicines to the proteins that are driving the cancer’s growth. For example, lung cancers with high levels of the EGFR protein can be successfully treated with medications that block EGFR function

For more information about how lung cancer is treated and patient support, please visit Cancer Council Victoria or the Lung Foundation Australia.

WEHI researchers are not able to provide specific medical advice specific to individuals. If you have lung cancer and wish to find out more information about clinical trials, please visit the Australian Cancer Trials or the Australian New Zealand Clinical Trials Registry, or consult your medical specialist.