Preventing pneumococcal disease in people without spleens (asplenia) and with poorly functioning spleens (hyposplenia)

Background There are thousands of Australians who live without a spleen (asplenia) or have a poorly functioning one (hyposplenia). These people are at a significantly increased risk of life-threatening infections (sepsis).The spleen’s main function is to remove bacteria (bugs) from the blood and therefore plays a very important role in the body’s immune system. The most common bacteria that causes problems for people without or with poorly functioning spleens is the pneumococcus bacteria. Asplenic/hyposplenic patients are more than 200 times more likely to develop pneumococcal sepsis than those with normal spleen function. The mortality rate from pneumococcal sepsis for patients without functioning spleens is extremely high at 40-70%. Even if patients do survive they can be left with severe impairment (morbidity). It is well known that this increased risk of acquiring severe sepsis is a lifelong risk with the majority of life-threatening episodes of infection occurring more than 10 years after spleen removal. Patients that take antibiotics every day have been shown to have some protection against pneumococcal sepsis. Asplenic/hyposplenic patients are also routinely vaccinated against pneumococcus in an attempt to reduce morbidity and mortality. It is currently not very clear to medical practitioners what the optimal vaccine regimes are to protect this group of patients against pneumococcus, either initially, or for repeat immunisations later in life. Newer pneumococcal vaccines have proven safe and effective in reducing pneumococcal sepsis in young children and may also offer promise for asplenic/hyposplenic older children and adults in addition to the existing pneumococcal vaccine. 2. What is the purpose of this study? This study aims to identify the best way to immunise children and adults, who either do not have a spleen or have a poorly functioning one, against pneumococcal disease. There are three main ways to prevent getting bacterial infections in people like you. These are (i) taking antibiotics every day and/or having an emergency supply of antibiotics, (ii) immunisations and (iii) education. However sometimes patients, despite following the recommendations, get pneumococcal infections. Many pneumococcal vaccine research studies in the past have not included people without spleens or poorly functioning ones, so little is known about how these patients respond to the well known vaccinations. There are some new pneumococcal vaccines that have been shown to work better in young children than the older type vaccines. The study team is particularly interested in finding out if these newer vaccines might, in addition to using the routine vaccines, provide better antibody levels to protect against pneumococcal disease and will give the researchers information on when is the best time to administer the new vaccine, This vaccine study will not only target older children and adults who have not had any previous doses of pneumococcal vaccines but it will also include those who may have had at least one pneumococcal vaccine and or those who will require further “booster” doses of vaccine. 3. How many people are involved in this study? This study will be conducted in three sites in Melbourne (the Royal Children’s Hospital, Monash Medical Centre and The Alfred hospital) and a further site in Sydney (Prince of Wales Hospital). A total of 220 people will be invited to participate, 110 participants who have previously received the routinely used pneumococcal polysaccharide vaccine (PPV23) and 110 people who have not. Participants will be adults and children aged over 10 years who are asplenic/hyposplenic. 4. What type of research is this study? This is a study comparing different ways of immunising asplenic/hyposplenic children and adults to see which gives the highest and longer lasting levels of protective antibodies against pneumococcus. Children and adults with asplenia/hyposplenia will be randomly assigned (like flipping a coin) to one of two treatment groups based on whether or not they have previously received the PPV23 vaccine. This research study has been reviewed and approved by the Human Research Ethics Committee at each of the four hospital sites. It is the role of this committee to make sure that research participants are protected from harm.