Pneumococcal infection Pneumococcal infections, including pneumonia and invasive disease such as bacteremia and meningitis, are important sources of morbidity and mortality in infants and young children, older adults (≥65 years of age), and persons with conditions that affect their ability to make antibody to capsular polysaccharides.

Pneumococcal infection causes an estimated 40,000 deaths annually Pneumococcal infection causes an estimated 40,000 deaths annually* in the United States.

Bacteremic pneumococcal pneumonia 24.8% of CAP cases caused by Bacteremic and Nonbacteremic Pneumococcal Pneumonia Contribute to the Clinical Burden of Pneumonia in Adults According to a 2013 meta-analysis, for every case of bacteremic pneumococcal pneumonia, there are ~3 cases of nonbacteremic pneumococcal pneumonia Radiologically confirmed all-cause CAP Pneumococcal pneumonia (bacteremic and nonbacteremic) 27.3% of CAP cases were attributed to Streptococcus pneumoniae Bacteremic pneumococcal pneumonia 24.8% of CAP cases caused by S. pneumoniae were bacteremic

Patients with chronic lung disease are at increased risk for pneumococcal pneumonia, and patients with conditions such as heart failure are more likely to have adverse outcomes if pneumonia occurs. Asplenia greatly increases the risk for overwhelming pneumococcal sepsis, and cerebrospinal fluid leak or a cochlear implant greatly increases the risk for meningitis.

The highest incidence of invasive pneumococcal disease occurs in children <2 years of age, persons who have conditions that compromise antibody responses (eg, solid organ transplantation, multiple myeloma, HIV infection), and those ≥65 years of age.

The highest mortality rates occur in individuals ≥65 years of age, especially in those who have significant comorbidities.

Age is the Primary Risk Factor for Invasive Pneumococcal Disease Age still primary risk factor

The Risk for Pneumococcal Disease Increases With Age and Certain Chronic Conditions 60 Chronic lung disease 50 40 Diabetes mellitus ~3X the average risk for IPD compared to age-matched healthy adults Chronic heart disease Cases per 100,000 Persons 30 Chronic heart disease Diabetes 20 HEALTHY ADULTS 10 Chronic lung disease ~7X the average risk for IPD compared to age-matched healthy adults 18–49 50–64 Age (years) ≥65

Risk of IPD in Adults with Chronic Conditions 20-fold increase 3- to 7-fold increase Kyaw, et al. J Infect Dis 2005;192:377-86

The incidence of invasive pneumococcal disease in any population is affected by geographic location, time of year, serotype prevalence, age, comorbidities, and vaccination status. in 2010 the incidence of invasive pneumococcal disease in individuals ≥65 years of age was 36.4 cases per 100,000 population and, in infants <1 year, the incidence was 34.2 cases per 100,000 population, compared with 3.8 cases per 100,000 population in individuals between 18 and 34 years of age.

However, some subgroups have markedly higher risks. For example, in adults aged 18 to 64 years of age with a hematologic malignancy, the incidence was 186 per 100,000 population and, for individuals with HIV infection, the incidence was 173 per 100,000 population in 2010 .

The organism was first identified in 1881. Streptococcus pneumoniae occupies an important position in the history of microbiology: The organism was first identified in 1881. Its role in causing lobar pneumonia was appreciated by the late 1880s. The central role of antibody in host defense against extracellular organisms was first described for the pneumococcus.

Cont. The first recognition that antibody directed to the capsular polysaccharide of a bacteria could be protective was shown for the pneumococcus; this observation forms the basis for many current bacterial vaccines. The discovery of DNA as the material for genetic exchange was made from the pneumococcus.

Capsule The surface capsular polysaccharide of S. pneumoniae provokes a type-specific protective immune response and serves as the basis for serotyping of these organisms; currently >90 different pneumococcal serotypes have been identified. Serotypes 6, 14, 18, 19, and 23 are the most prevalent, accounting for between 60 and 80 percent of infections depending upon the area of the world.

The polysaccharide capsule of Streptococcus pneumoniae is the principal means by which this bacterium resists ingestion and killing by phagocytic cells. Antibody to capsule greatly facilitates phagocytosis and killing. Accordingly, capsular polysaccharides are the essential components of all currently available pneumococcal vaccines.

More than 90 different pneumococcal capsular serotypes have been identified. Since it is not possible to include all of the serotypes in a pneumococcal vaccine, available vaccines contain capsular polysaccharides from serotypes that are most commonly implicated as causes of pneumococcal disease.

دراین مرحله تزریق واکسن PPSV23 توصیه میشود. 00:30 زنی 28 ساله مبتلا به سندرم نفروتیک می باشد. در مورد دریافت واکسن پنوموکوک چه توصیه ای به او دارید؟ دراین مرحله تزریق واکسن PPSV23 توصیه میشود.

دراین مرحله تزریق واکسن PPSV23 توصیه میشود. 00:30 در مردی 40 ساله مبتلا به فشار خون مزمن از 10 سال قبل : دراین مرحله تزریق واکسن PPSV23 توصیه میشود.

دراین مرحله تزریق واکسن PPSV23 توصیه میشود. 00:30 مردی 30 ساله مبتلا به آسم جهت دریافت دارو و کنترل ماهیانه مراجعه کرده است. توصیه شما در مورد دریافت واکسن پنوموکوک چیست؟ دراین مرحله تزریق واکسن PPSV23 توصیه میشود.

دراین مرحله تزریق واکسن PPSV23 توصیه میشود. 00:30 بیماری مبتلا به آنمی داسی شکل در سن 30 سالگی است.توصیه شما به دریافت واکسن پنوموکوک چیست؟ دراین مرحله تزریق واکسن PPSV23 توصیه میشود.

دراین مرحله تزریق واکسن PPSV23 توصیه میشود. 00:30 بیماری 35 ساله کاندید پیوند حلزون گوش گردیده است : دراین مرحله تزریق واکسن PPSV23 توصیه میشود.

Pneumococcal Vaccines Pneumococcal polysaccharide vaccines (PPSVs) Pneumococcal conjugate vaccines (PCVs) Serotype-specific capsular polysaccharides Serotype-specific capsular polysaccharides linked (“conjugated”) to a protein carrier 23 serotypes 10 or 13 serotypes

History of Pneumococcal Vaccines Year Vaccine 1977 14-valent polysaccharide vaccine licensed (no longer in U.S.) 1983 23-valent polysaccharide vaccine licensed (PPSV23) 2000 7-valent polysaccharide conjugate vaccine licensed (PCV7) 2010 13-valent PCV licensed (PCV13)

At present, PPSV23 contains capsular polysaccharides from pneumococci that cause about 60 percent of all pneumococcal infection in adults. PPSV is used in selected adults and children ≥2 years of age but not in infants or toddlers <2 years of age since polysaccharide antigens are poorly immunogenic in this age group.

PPV23 Vaccine effectiveness Overall efficacy for preventing infection caused by serotypes included in the vaccine was 57% Case-control study by Butler, et al. JAMA 1993;270:1826-31

Pneumococcal conjugate vaccine was initially marketed in the United States in 2000 as PCV7. The polysaccharides are covalently linked to a nontoxic protein that is nearly identical to diphtheria toxin, which renders the polysaccharides antigenic in infants and toddlers.

Because PCV stimulates mucosal antibody, it greatly suppresses nasal carriage of S. pneumoniae due to vaccine serotypes. Not surprisingly, therefore, widespread use of PCV7 has reduced spread of pneumococci from small children, the usual reservoir of pneumococcal carriage, to unvaccinated older children and adults, an effect that is called an indirect (or "herd") effect.

Because PCV7 is an excellent immunogen in infants and toddlers, it was adopted in the United States for universal use in this age group in 2000.

By 2008 in the United States, disease due to these types had nearly disappeared from the adult population, largely as a result of this indirect effect. In the pre-PCV era, about 65 to 70 percent of pneumococcal pneumonia in adults was caused by strains included in PCV7.

In 2010, PCV7 was replaced by PCV13, a vaccine that has added serotypes commonly implicated in disease to those contained in PCV7. Since 2010, PCV13 has been recommended for infants and children in place of PCV7.

Indication and Time? ACIP = Advisory Committee on Immunization Practices

1 The ACIP states that both PCV13 and PPSV23 should be given to all adults aged ≥65 years .

2 In accordance with the ACIP, we recommend PPSV23 alone for persons aged 19 to 64 years who are at increased risk for pneumococcal infection and/or serious complications of pneumococcal infection.

Adults with the following underlying conditions who are <65 years of age should receive PPSV23 (but should not receive PCV13): Current cigarette smoking Chronic heart disease, including congestive heart failure and cardiomyopathy but excluding hypertension Chronic lung disease, including asthma and chronic obstructive pulmonary disease Diabetes mellitus Alcoholism Chronic liver disease, including cirrhosis

3 The ACIP states that both PCV13 and PPSV23 should be given to adults of any age with:

The ACIP states that both PCV13 and PPSV23 should be given to adults of any age who have the underlying conditions listed below and to all adults aged ≥65 years : Cerebrospinal fluid leak Cochlear implant Functional or anatomic asplenia, including sickle cell disease, other hemoglobinopathies, congenital asplenia, and acquired asplenia Immunocompromising conditions: * In the absence of antibody (most unvaccinated adults lack measurable antibody to most pneumococcal capsular polysaccharides, the only clearance of pneumococci from the bloodstream is by the spleen. Asplenic individuals are at risk for overwhelming pneumococcal sepsis that may occur even in the absence of a focal infection such as pneumonia

Congenital or acquired immunodeficiency, including B or T lymphocyte deficiency, complement deficiencies (particularly C1, C2, C3, and C4 deficiencies), and phagocytic disorders (excluding chronic granulomatous disease HIV infection Chronic renal failure Nephrotic syndrome Leukemia Lymphoma Hodgkin disease Multiple myeloma Generalized malignancy Iatrogenic immunosuppression, including long-term systemic glucocorticoids or radiation Solid organ transplant

For patients with an indication for PCV13 who have previously received one or more doses of PPSV23 but have not received PCV13, a single dose of PCV13 should be given if at least one year has elapsed since the last PPSV23 dose was given. For patients <65 years of age who require revaccination with PPSV23 (eg, immunocompromised patients), the first such dose should be given at least eight weeks after PCV13 and at least 5 years after the previous dose of PPSV23

The CDC Advisory Committee on Immunization Practices recommends influenza and pneumococcal vaccines for all individuals with Chronic Lung Disease ACIP Recommends PCV13 + PPV23 ACIP Recommends PPV23 only ACIP Recommends PCV13 + PPV23 8 weeks later Adults 65+ Adults 19-64 with chronic conditions including: Diabetes Chronic Lung Disease Chronic Heart Disease Chronic Liver Disease Alcoholism Adults who Smoke Cigarettes Immunocompromised patients, including: Solid/hematologic cancers HIV infection Organ transplant Renal failure Nephrotic syndrome Immunosuppressive therapy Functional or anatomic asplenia Cerebrospinal fluid leaks Cochlear implants Which adult pneumococcal vaccines should be given to which subsets of the adult population? Pneumovax 23 is the only vaccine indicated for both patients 50+ and all adult patients at risk.[Pneumovax 23 PI] The ACIP recommends that both adults 65+ and adults with certain chronic conditions who are not immunocompromising receive only Pneumovax 23.[af] Add ACIP rec for immunocompromising conditions. It has been the case for many years that recommending bodies and the medical community have treated those with impaired immune systems differently from other patients. 41

Recommendations for pneumoccal vaccination in immunocompetent adults ≥ 19 and < 65 years of age

the ACIP also recommends that all adults aged ≥65 years of age should receive both PCV13 and PPV23. The rationale for this is that both the incidence of pneumococcal disease and the mortality rate increase after age 50 and more sharply after age 65 . The incidence of pneumococcal disease and the associated mortality are very low in adults under the age of 50. In contrast with the ACIP, we give only PPSV23 (but not PCV13) to otherwise healthy individuals aged ≥65 years. We do not believe that PCV13 is warranted in such individuals because it is not clear that immunizing this group with PCV13 followed by PPSV23 provides benefit beyond that derived from PPSV23 alone. An important point underlying any recommendation for vaccinating adults in most developed countries is that routine administration of PCV13 to all children <2 years produces such profound indirect ("herd") immunity that there will be little if any incremental benefit from using PCV13 in adults.

We do, however, favor the use of both PCV13 and PPSV23 in patients ≥65 years of age who have one of the conditions for which PPSV23 is indicated before age 65 (cigarette smokers; patients with chronic heart disease, chronic lung disease, diabetes mellitus, alcoholism, or chronic liver disease). We also use both PCV13 and PPSV23 for individuals ≥65 years of age who are planning to travel to a country that does not have a universal immunization program mandating pneumococcal conjugate vaccination for all infants and toddlers.

Administration  Both pneumococcal vaccines are administered as a 0.5 mL dose. PCV13 should be given intramuscularly, whereas PPSV23 can be given either intramuscularly or subcutaneously. Intradermal administration can cause severe local reactions and should be avoided.

Administration with other vaccines Either formulation of pneumococcal vaccine may be given concomitantly with other vaccines . When more than one vaccine is given, they should be administered with different syringes and at different injection sites.

Concurrent administration of either PPSV23 or PCV13 with the inactivated influenza vaccine is safe and is unlikely to reduce the effectiveness of either pneumococcal vaccine. (some data suggest a modest suppression of immunogenicity to PCV13 if PCV13 is administered on the same day as an inactivated influenza vaccine, even though different arms were used for injection . Nevertheless, the United States Centers for Disease Control and Prevention (CDC) states that these vaccines can be coadministered).

Adverse reactions injection site pain or tenderness (in 60 percent of vaccinees) swelling or induration (in 20 percent) erythema (in 16 percent) These reactions usually persist for less than 72 hours.

Contraindications  A severe allergic reaction (eg, anaphylaxis) to PPSV23, an exceedingly rare event, is an absolute contraindication to revaccination with PPSV23.

Summary Pneumococcal infections, including pneumonia remain an important source of morbidity and mortality in adults, especially among older adults and those with certain conditions. In 2012, the ACIP recommended PCV13 for selected high- risk adults and, in 2014, the ACIP began recommending PCV13 for all adults ≥65 years of age . for adults 19 to 64 years of age at intermediate risk of pneumococcal disease (ie, cigarette smokers; patients with chronic heart disease, chronic lung disease, diabetes mellitus, alcoholism, or chronic liver disease), it recommend only pneumococcal vaccination ( 23 ) .

Summary For adults aged 19 or older who are at high risk of pneumococcal disease (ie, patients with functional or anatomic asplenia, an immunocompromising condition [eg, HIV infection, cancer], a cerebrospinal fluid leak, a cochlear implant, advanced kidney disease), ACIP recommend pneumococcal vaccination with PCV13 followed at least eight weeks later by PPSV23. For all adults ≥65 years of age, it recommend pneumococcal vaccination . the ACIP states that individuals ≥65 years of age should receive both PCV13 and PPSV23 . PCV13 is not recommended for healthy adults <65 years of age who do not have a specific risk factor for pneumococcal infection.

Summary For immunocompromised patients and individuals with asplenia who are <65 years of age, the ACIP recommends one single revaccination with PPSV23 ≥5 years after the first dose. However, for asplenic individuals, some experts recommend reimmunization with PPSV23 every five years. The ACIP recommends a single revaccination with PPSV23 in adults ≥65 years of age if they received this vaccine before age 65; it should be administered five or more years after the previous dose. Some references also favor revaccinating older adults at 10- year intervals because immunologic responses diminish in older adult patients. Revaccination with PCV13 is not recommended .

دراین مرحله تزریق واکسن PPV23 توصیه میشود. 00:30 زنی 28 ساله مبتلا به سندرم نفروتیک می باشد. در مورد دریافت واکسن پنوموکوک چه توصیه ای به او دارید؟ دراین مرحله تزریق واکسن PPV23 توصیه میشود.

دراین مرحله تزریق واکسن PPV23 توصیه میشود. 00:30 در مردی 40 ساله مبتلا به فشار خون مزمن از 10 سال قبل : دراین مرحله تزریق واکسن PPV23 توصیه میشود.

دراین مرحله تزریق واکسن PPV23 توصیه میشود. 00:30 مردی 30 ساله مبتلا به آسم جهت دریافت دارو و کنترل ماهیانه مراجعه کرده است. توصیه شما در مورد دریافت واکسن پنوموکوک چیست؟ دراین مرحله تزریق واکسن PPV23 توصیه میشود.

دراین مرحله تزریق واکسن PPV23 توصیه میشود. 00:30 بیماری مبتلا به آنمی داسی شکل در سن 30 سالگی است.توصیه شما به دریافت واکسن پنوموکوک چیست؟ دراین مرحله تزریق واکسن PPV23 توصیه میشود.

دراین مرحله تزریق واکسن PPV23 توصیه میشود. 00:30 بیماری 35 ساله کاندید پیوند حلزون گوش گردیده است : دراین مرحله تزریق واکسن PPV23 توصیه میشود.

00:30 نظر شما در مورد ادامه برگزاری کنفرانس های هفتگی گروه داخلی به این صورت و با مشارکت فعال فراگیران چیست؟ بسیار موافق