Alpha1 Germany eV.

Everything you need to know about autumn, summarized for you!

Autumn time,

After a very busy year so far, we would like to use the days when you might prefer to stay indoors to provide you with new information.
With this newsletter, we would like to start the month of November, which is also "Alpha-1 Awareness Month", the month that is used worldwide to raise awareness of the disease!

In the coming weeks, we would like to launch a newsletter series reporting on new developments in research, naturally always combined with everyday tips and upcoming dates.

But today we're talking about the important things that make autumn special – no, unfortunately not about autumn leaves, pumpkin soup, or cozy tea times…

1. Influenza (Flu): 

2. Pneumococci (pneumonia): 

A pneumococcal vaccine (PCV 20) has been available since the beginning of 2022. We recommend vaccination for all individuals aged 60 and over, as well as for those aged 18 and over with risk factors (such as alpha-1 antitrypsin deficiency) that can lead to severe pneumococcal disease.

For adults who have already received a vaccination with PPSV23 or sequentially (PCV13 or PCV15 + PPSV23), we recommend a vaccination with PCV20 after a 6-year interval. For individuals aged 18 and older, vaccination with PCV20 after a 1-year interval is recommended if risk factors for severe pneumococcal disease are present and their sequential vaccination series has already begun with PCV13 but has not yet been completed with PPSV23.

3. COVID (SARS-CoV-2):

We recommend a primary immunization series of two vaccine doses administered at least three weeks apart. For individuals aged 60 and over with underlying health conditions that put them at increased risk of severe illness, booster vaccinations are recommended. This also applies particularly to those infected with the Alpha-1 virus. Booster vaccinations should be administered at least six months apart. Variant-adapted vaccines should generally be given at least 12 months after the last vaccination or infection. Vaccination should preferably take place in the autumn, as infection rates are expected to rise during the autumn and winter months.

4. RSV:

A single RSV vaccination is recommended as a standard vaccination for all individuals over 75 years of age, ideally before the start of the RSV season (preferably in September/early October). A single RSV vaccination is recommended as an indicated vaccination for individuals aged 60 to 74 years with severe forms of certain underlying diseases (e.g., low alpha-1 antitrypsin levels and a high symptom burden) or for residents of nursing homes. These underlying diseases include severe forms of chronic respiratory, cardiovascular, and renal diseases, neurological and neuromuscular disorders, hematological and oncological diseases, diabetes mellitus with complications, and congenital or acquired immunodeficiency. According to current knowledge, mild or well-controlled forms of these diseases do not require vaccination.

Since August 2024, three RSV vaccines have been approved in the EU: Arexvy (for ages 60 and up), Abreysvo (also for pregnant women), and mResvia (mRNA vaccine). Reimbursement can be requested from your health insurance provider.

According to current data, RSV vaccination is a one-time vaccination and does not need to be repeated annually. Whether booster vaccinations are necessary is currently unclear. The STIKO (Standing Committee on Vaccination) will continue to carefully review the data and adjust its recommendations if necessary.

The video, recorded with Dr. Kardos, also reflects the current status of RSV vaccination.

Click here for the video

Whether it's a cold, bronchiectasis, or the effects of Covid-19, many people are familiar with the problem of struggling with mucus in the body, and especially in the lungs.

Our lung exercise trainer Peter Kukry (Peddar), himself also an Alpha-1 patient, therefore got to work and recorded the following video for us. He is supported in this by Dr. Heike Isensee, herself an active participant in the pulmonary exercise program and group leader of the Stuttgart self-help group. The entire program is complemented by the expert advice of Dr. Alexander Rupp, a pulmonology practice in the center of Stuttgart.

Sometimes simple techniques and exercises can make everyday life significantly easier, try them out!

Click here to watch the video!

• The basics of Alpha-1 (AATD) 
• Living with Alpha-1 
• The latest research + patient participation in clinical trials
• Treatment and therapy options

You can find all events up to the end of 2024 on our event overview page. Take a look, perhaps something will interest you!

Dr. Malin Fromme, Prof. Dr. Pavel Strnad, as published in Alpha1 Journal 2/2023.

Many Alpha patients receive a recommendation for vaccination against hepatitis A and B in their medical reports. To explain the background, we will briefly introduce the two infections and explain why we consider these vaccinations to be beneficial.

With approximately 350 million carriers worldwide, hepatitis B is one of the most common viral infections in humans. However, its distribution varies considerably across regions, with particularly high prevalence found in Asia, sub-Saharan Africa, South America, the South Pacific, and the Middle East (Cornberg et al. 2021). The infection is caused by the hepatitis B virus, which can be transmitted through blood and bodily fluids, and thus sexually, via needlestick injuries, contaminated blood products, and perinatally (during childbirth). However, transmission via blood transfusion is virtually impossible in Western countries due to appropriate safety precautions.

After an incubation period of usually several months, asymptomatic hepatitis develops in the vast majority of cases. Sometimes this presents with mild symptoms, but in about one-third of cases, acute, icteric hepatitis (i.e., accompanied by jaundice) can occur. This often manifests with nonspecific symptoms such as flu-like symptoms, upper abdominal pain, or fatigue. In over 90% of cases, the hepatitis resolves completely. However, in approximately 5% of cases, the infection leads to persistent, asymptomatic carrier status of the virus (Robert Koch Institute 2016). This can develop into chronic hepatitis with an increased risk of liver cirrhosis and associated complications, such as the development of liver cancer. Diagnosis is made via blood tests. Various antiviral medications are available for the treatment of the chronic form (Cornberg et al. 2021; Robert Koch Institute 2016).

A complication of hepatitis B infection can be coinfection with hepatitis D. Because the hepatitis D virus is an "incomplete virus," it can only occur together with hepatitis B. Approximately 5% of chronically hepatitis B-infected individuals also carry the hepatitis D virus and experience a significantly more severe course of the disease compared to mono-infected individuals.

Hepatitis A is frequently acquired through travel to Mediterranean, tropical, or subtropical regions. The causative agent is the hepatitis A virus, which is transmitted via the fecal-oral route, for example, through contaminated food or water (Robert Koch Institute 2023). While the infection is usually asymptomatic in children, the risk of severe symptoms and fulminant (intense) courses increases with age. In adults with hepatitis A levels above 80, acute hepatitis with jaundice (icterus) develops. Other symptoms can include fever, a rash, abdominal pain, nausea, and diarrhea. A fulminant course with liver failure is very rare overall, and the infection almost never becomes chronic (Robert Koch Institute 2023). Diagnosis is made via a blood test. Treatment is symptomatic, and the disease is usually self-limiting, meaning it resolves without external influences (Robert Koch Institute 2023).

Preventive vaccinations are available for both hepatitis B and hepatitis A.

For over 20 years, the Standing Committee on Vaccination (STIKO) has recommended hepatitis B vaccination as a standard immunization for all children (STIKO 2023). The primary immunization series consists of three doses administered within the first year of life. In addition, there is an indication-based vaccination for individuals with immunosuppression or underlying medical conditions that suggest a severe course of the disease (e.g., dialysis patients) and for individuals with an increased risk of exposure (e.g., intravenous drug use or contact with infected individuals in the household) (STIKO 2023). This is administered when the antibody titer in the blood is low, meaning that the body does not have sufficient antibodies to protect against the pathogen. Hepatitis B vaccination can also be administered as an occupational or travel vaccination (Commission on Vaccination 2021). A booster vaccination is not generally recommended. Exceptions are the aforementioned vaccinations for specific indications or occupational reasons (Commission on Vaccination 2021; STIKO 2023). Additionally, hepatitis B vaccination can protect against hepatitis D infection. In contrast, there is no general vaccination recommendation for hepatitis A vaccination. It is frequently administered for specific indications (e.g., in cases of sexual activity with an increased risk of exposure), for occupational reasons, or for travel (STIKO 2023).

Influenza, pneumococcus and other diseases:
Which vaccinations make sense for Alphas now?

Dr. Gerhard Wacker

At the end of the 18th century, the English country doctor Edward Jenner observed that people who developed a pox-like rash after contact with cows did not contract the dreaded smallpox. In 1796, he inoculated an 8-year-old boy with the pustule secretion of a maid suffering from cowpox. The boy contracted cowpox but remained unaffected by smallpox. Thus, "vaccination" (from the Latin *vacca* – cow) was born! Centuries earlier, healthy individuals in Asian countries had been treated with the pustule secretion of people infected with smallpox, which mitigated the severity of the disease. This procedure, known as "variolation," had already reached England before Jenner's method. After a smallpox epidemic claimed 125,000 lives in 1870/71, compulsory vaccination against smallpox was introduced in the German Empire in 1874. In 1979, the WHO was able to declare the earth free of smallpox – a scourge of humanity that had previously claimed 15 million lives was defeated.

Infectious diseases have accompanied humankind since the beginning. Plague epidemics killed approximately 40 million people in Europe between 1347 and 1352. In Hamburg, around 9,000 people died of cholera in 1892. From spring 1918 to mid-1919, the so-called Spanish flu claimed at least 50 million lives worldwide; in Germany alone, 320,000 people died, primarily during the second wave from September to November 1918. 500 million people (a quarter of the world's population) fell ill. The misleading name stems from the fact that Spanish newspapers first reported on the disease in April 1918, as the pandemic likely originated in a US Army training camp in Kansas and was brought to Europe by soldiers. Just two years after the discovery of the diphtheria pathogen in 1892 at the Pasteur Institute in Paris, a serum was produced there after immunizing a horse, which was used to successfully treat diphtheria patients. In the same year, Emil von Behring, together with the Hoechst dye works, established a large-scale plant for the production of the serum. In 1897, Paul Ehrlich isolated an inactivated "toxoid" from this raw material, which is still in use today. The tetanus vaccine was subsequently developed based on these fundamental findings. The oral polio vaccine—a vaccination with attenuated viruses—was largely developed by Jonas Salk and, as a mandatory vaccination since the 1960s, led to the eradication of the disease in Germany. Since 1998, an inactivated polio vaccine has been administered by injection, as the disease is still active in other countries.

Vaccinations are intended to make the immune system more effective at fighting off pathogens. In "active immunization," either live but weakened pathogens are injected (e.g., measles, mumps, rubella, chickenpox, typhoid, yellow fever), or inactivated vaccines containing virus particles or antigens of the pathogen (split vaccines, toxoids), which are often coupled with an immune-enhancing agent (adsorbed vaccines). "Passive immunization" involves administering pre-formed antibodies in the form of hyperimmune globulin, which are obtained after infection of humans, and initially also from animals (nowadays only in the case of diphtheria). An example is the administration of Tetagam in addition to Tetanol after deep, contaminated wounds. The former merely acts as a barrier against the already formed tetanus toxin and does not induce a true immune response in the recipient.

The goal of active immunization is the production of the body's own protective substances from the group of immunoglobulins and of special lymphocytes as "memory cells". Upon renewed contact with the pathogen, the immune system is then well prepared and can successfully ward off the infection.

In general, vaccinations should not be administered during acute, febrile illnesses; malignant blood disorders are also considered a contraindication. An allergy to egg protein can prevent vaccination with vaccines cultivated on chicken eggs (e.g., influenza). Live vaccines must not be given during pregnancy. A congenital or acquired immunodeficiency often leads to a weakened or even absent immune response. Generally, however, vaccinations are well tolerated, even though serious adverse reactions are very rare, and always represent a balancing of benefits against the risks of an unprevented infection.

Pneumococci are bacteria that colonize the nasopharynx and can cause inflammation in the upper respiratory tract and lungs. In severe cases, they can also spread into the bloodstream (sepsis), leading to higher mortality. The incidence of the disease peaks in the first two years of life and in older adults. The frequency of asymptomatic carriers is estimated at approximately 20% in children and adolescents and 8% in adults. In Germany, two vaccine types are available: a polysaccharide vaccine (PPSV 23/Pneumovax 23) and a newer conjugate vaccine (PCV 13/Prevenar 13). The former stimulates an immune response against 23 pneumococcal antigens, which, unfortunately, is relatively weak without the formation of memory cells. In contrast, PCV 13 also leads to the formation of memory cells, but only against 13 serovariates.

The STIKO, as our „supreme vaccination authority“, distinguishes between standard vaccinations for healthy people and indication-based vaccinations for certain population groups with pre-existing conditions and risk profiles.

The standard vaccination for infants is PCV 13, administered in up to three doses by the age of two, with the aim of achieving herd immunity that is also relevant for the adult population. This standard vaccination has led to a significant decline in the incidence of meningitis, a serious condition. For healthy adults aged 60 and over, the STIKO (Standing Committee on Vaccination) continues to recommend the PPSV 23 vaccine due to its broader coverage of 23 serotypes, even though it is not as immunogenic.

The recommended vaccination of chronically ill individuals with immunodeficiency, cancer, after splenectomy, or with chronic renal or hepatic insufficiency should be administered sequentially with PCV 13 (Prevenar 13) followed 6–12 weeks later by PPSV 23 (Pneumovax 23). However, this does not apply to individuals with chronic respiratory, pulmonary, or cardiac diseases! These individuals should continue to be vaccinated only with PPSV 23 due to its broader serotype coverage (the proportion of the 23 serotypes contained in PPSV 23 in invasive pneumococcal diseases in Germany is approximately twice as high as the proportion of serotypes contained in PCV 13), and these diseases should not be associated with immunodeficiency. A booster vaccination with PPSV after six years is still recommended for all risk groups, even though the booster effect decreases with age.

Seasonal influenza is caused by influenza A and B viruses. The dominant A virus has many subtypes, named according to their H and N antigens (e.g., H1N1), while the B virus is genetically more stable with only two lineages. Approximately every 10–15 years, the B virus becomes dominant over the A virus. Infection usually occurs via respiratory droplets; infectivity often begins before the first symptoms and lasts for 4–5 days after symptom onset. A feared complication is pneumonia with bacterial superinfection, particularly in high-risk patients with underlying bronchopulmonary diseases, diabetes, or obesity.

The WHO decides on the composition of the vaccine for the Northern Hemisphere in the spring and for the Southern Hemisphere in September. It is an inactivated vaccine (split vaccine) containing two inactivated subtypes of the A virus and the two B lineages (tetravalent since 2018, standard in Germany).

The vaccination rate among high-risk patients in Germany, at 24 per 100,000 doses (%), is unfortunately far below the WHO recommendations (75 per 100,000 doses). Only doctors, at 61 per 100,000 doses (%), come close to meeting the target. This modest vaccination rate is due to both a lack of information and the significant fluctuations in vaccine effectiveness from year to year. Nevertheless, the effectiveness in the 2019/20 season was estimated at 62 per 100,000 doses, compared to a disappointing 21 per 100,000 doses in the 2018/19 season. However, given the current COVID-19 pandemic, there should be no doubt about the importance of influenza vaccination.

Vaccine development against the current scourge of humanity, the SARS-CoV-2 virus, is in full swing, with at least 190 vaccine projects at various stages of development. Numerous different "vaccine platforms" are in the running. The usual approval process is being shortened by parallel safety studies in different countries; interim results are evaluated promptly by regulatory authorities before a final application for approval is submitted. Conditional approval may be granted, requiring the submission of missing long-term safety data. People with severe alpha-1 antitrypsin deficiency and the associated pulmonary emphysema belong to a high-risk population that is particularly vulnerable to infections with influenza viruses and pneumococci. Pneumonia is not even a necessary condition; high fever alone leads to an increased metabolism with higher oxygen demand and CO2 production, which in some cases can result in respiratory failure. Optimal vaccination protection with annual influenza vaccination and pneumococcal vaccination, preferably with PPSV 23 according to the current STIKO recommendation, as well as a booster vaccination with PPSV 23 after six years, is definitely advisable, even if 100% protection against pneumococcal disease is not achievable and serious adverse effects are possible in exceptional cases. Additional vaccination with PCV 13 is not "wrong" when considering an individual's immunodeficiency (e.g., years of treatment with cortisone tablets), but it is not recommended as the sole vaccination.

Ultimately, the great hope remains for effective vaccines against SARS-CoV-2. Until then, the well-known distancing and hygiene rules are all the more important, especially for those in high-risk groups. Don't be discouraged and stay healthy!