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| {{Infobox Disease
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| | '''For patient information, click [[Pneumococcal infections (patient information)|here]]''' |
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| {{Editor Help}} | | {{Pneumococcal infections}} |
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| '''Pneumococcal infection''' refers to an infection caused by ''[[Streptococcus pneumoniae]]''.
| | ==[[Pneumococcal infections overview|Overview]]== |
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| == Pathogenesis == | | ==[[Pneumococcal infections historical perspective|Historical Perspective]]== |
| ''S. pneumoniae'' is normally found in the [[nasopharynx]] of 5-10% of healthy adults, and 20-40% of healthy children.<ref name=Sherris>{{cite book | author = Ryan KJ; Ray CG (editors) | title = Sherris Medical Microbiology | edition = 4th ed. | publisher = McGraw Hill | year = 2004 | id = ISBN 0-8385-8529-9 }}</ref> It can be found in higher amounts in certain environments, especially those where people are spending a great deal of time in close proximity to each other (day care centers, army barracks). It attaches to nasopharyngeal cells through interaction of bacterial surface [[adhesin]]s. This normal colonization can become infectious if the organisms are carried into areas such as the [[Eustachian tube]] or [[nasal sinus]]es where it can cause [[otitis media]] and [[sinusitis]], respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or [[Tobacco smoking|smoking]]-induced ciliary paralysis might be contributing factors). Once the organism makes its way to a site where it is not normally found, it activates the [[Complement system|complement]] protein group, stimulates [[cytokine]] production, and attracts [[white blood cell]]s (specifically [[neutrophil granulocyte|neutrophil]]s). The organism's [[polysaccharide]] capsule makes it resistant to [[phagocytosis]], and if there is no pre-existing anticapsular antibody, alveolar [[macrophage]]s cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can cause [[bacteremia]]) and is carried to the [[meninges]], joint spaces, [[bone]]s, and [[peritoneal cavity]], and may result in [[meningitis]], [[brain abscess]], [[septic arthritis]], or [[osteomyelitis]].
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| ''S. pneumoniae'' has several virulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibit complement-mediated opsonization, and it secretes IgA1 protease that will destroy secretory IgA produced by the body.
| | ==[[Pneumococcal infections classification|Classification]]== |
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| The risk of pneumococcal infection is much increased in persons with impaired IgG synthesis, impaired phagocytosis, or defective clearance of pneumococci. In particular, the absence of a functional [[spleen]], through [[congenital asplenia]], [[splenectomy]], or [[sickle-cell disease]] predisposes one to a more severe course of infection ([[Overwhelming post-splenectomy infection]]) and prevention measures are indicated (see [[asplenia]]).
| | ==[[Pneumococcal infections pathophysiology|Pathophysiology]]== |
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| ==Virulence Factors== | | ==[[Pneumococcal infections causes|Causes]]== |
| ''S. pneumoniae'' expresses different virulence factors on its cell surface and inside the organism. These virulence factors contribute to some of the clinical manifestations during infection with ''S. pneumoniae''.
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| *'''Polysaccharide capsule''' -prevents phagocytosis by host immune cells by inhibiting C3b opsonization of the bacterial cells
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| *'''Pneumolysin''' (Ply) -a 53-kDa protein that can cause lysis of host cells and activate complement
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| *'''Autolysin''' (LytA) -activation of this protein lyses the bacteria releasing its internal contents (i.e. pneumolysin)
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| *'''[[Hydrogen peroxide]]''' - causes damage to host cells (can cause apoptosis in neuronal cells during meningitis) and has bactericidal effects against competing bacteria ([[Haemophilus influenzae]], [[Neisseria meningitidis]], [[Staphylococcus aureus]])<ref>{{cite journal |author=Pericone, Christopher D., Overweg, Karin, Hermans, Peter W. M., Weiser, Jeffrey N. |title=Inhibitory and Bactericidal Effects of Hydrogen Peroxide Production by Streptococcus pneumoniae on Other Inhabitants of the Upper Respiratory Tract |journal=Infect Immun |volume=68 |issue=7 |pages=3990–3997 |year=2000 |pmid=10858213 |doi=10.1128/IAI.68.7.3990-3997.2000}}</ref><ref>{{cite journal |author=Regev-Yochay G, Trzcinski K, Thompson CM, Malley R, Lipsitch M. |title=Interference between Streptococcus pneumoniae and Staphylococcus aureus: In vitro hydrogen peroxide-mediated killing by Streptococcus pneumoniae |journal=J Bacteriol |volume=188|issue=13 |pages=4996–5001| year=2006 |pmid=16788209 |doi=10.1128/JB.00317-06}}</ref>
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| *'''[[Pilus|Pili]]''' - hair-like structures that extend from the surface of many strains of ''S. pneumoniae''. They contribute to colonization of upper respiratory tract and increase the formation of large amounts of [[tumor necrosis factors|TNF]] by the immune system during [[sepsis]], raising the possibility of [[septic shock]]<ref>{{cite journal |author=Barocchi M, Ries J, Zogaj X, Hemsley C, Albiger B, Kanth A, Dahlberg S, Fernebro J, Moschioni M, Masignani V, Hultenby K, Taddei A, Beiter K, Wartha F, von Euler A, Covacci A, Holden D, Normark S, Rappuoli R, Henriques-Normark B |title=A pneumococcal pilus influences virulence and host inflammatory responses |journal=Proc Natl Acad Sci U S A |volume=103 |issue=8 |pages=2857–2862 |year=2006 |pmid=16481624 |doi=10.1073/pnas.0511017103}}</ref>
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| *'''Choline binding protein A/Pneumococcal surface protein A''' (CbpA/PspA) -an adhesin that can interact with carbohydrates on the cell surface of pulmonary epithelial cells and can inhibit complement-mediated opsonization of pneumococci
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| == Humoral immunity == | | ==[[Pneumococcal infections differential diagnosis|Differentiating Pneumococcal infections from other Diseases]]== |
| In the 19<sup>th</sup> century, it was demonstrated that immunization of rabbits with killed pneumococci protected them against subsequent challenge with viable pneumococci. [[blood plasma|Serum]] from immunized rabbits or from humans who had recovered from pneumococcal pneumonia also conferred protection. In the 20<sup>th</sup> century, the efficacy of immunization was demonstrated in South African miners.
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| It was discovered that the pneumococcus's capsule made it resistant to phagocytosis, and in the 1920s it was shown that an antibody specific for capsular polysaccharide aided the killing of ''S. pneumoniae''. In 1936, a pneumococcal capsular polysaccharide vaccine was used to abort an epidemic of pneumococcal pneumonia. In the 1940s, experiments on capsular transformation by pneumococci first identified [[DNA]] as the material that carries genetic information.
| | ==[[Pneumococcal infections epidemiology and demographics|Epidemiology and Demographics]]== |
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| In 1900, it was recognized that different [[serovar]]s of pneumococci exist, and that immunization with a given serovar did not protect against infection with other serovars. Since then over ninety serovars have been discovered, each with a unique polysaccharide capsule which can be identified by the [[quellung reaction]]. Because some of these serovars cause disease more commonly than others, it is possible to provide reasonable protection by immunizing with less than 90 serovars; the current vaccine contains 23 serovars (i.e., it is "23-valent").
| | ==[[Pneumococcal infections risk factors|Risk Factors]]== |
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| The serovars are numbered according to two systems: the American system, which numbers them in the order in which they were discovered, and the Danish system which groups them according to antigenic similarities.
| | ==[[Pneumococcal infections natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
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| ==Diagnosis== | | ==Diagnosis== |
| Depending on the nature of infection, an appropriate sample is collected for laboratory identification. Pneumococci are typically gram positive, cocci, seen in pairs or chains. When cultured on [[blood agar]] plates with added [[optochin]] antibiotic disk, they show [[hemolysis (microbiology)|alpha-hemolytic]] colonies and a clear zone of inhibition around the disk meaning they're sensitive to the antibiotic. Pneumococci are also bile soluble. Just like other [[streptococci]], they are [[catalase]] negative. A [[Quellung]] test can identify specific capsular polysaccharides.<ref name=Werno>{{cite journal |author=Werno AM, Murdoch DR |title=Medical microbiology: laboratory diagnosis of invasive pneumococcal disease |journal=Clin. Infect. Dis. |volume=46 |issue=6 |pages=926–32 |year=2008 |month=March |pmid=18260752 |doi=10.1086/528798 |url=http://www.journals.uchicago.edu/doi/full/10.1086/528798}}</ref>
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| Pneumococcal antigen (cell wall C polysaccharide) may be detected in various body fluids. Older detection kits, based on latex agglutination, added little value above Gram staining and were occasionally [[Type I and type II errors|false-positive]]. Better results are achieved with rapid immunochromatography, which has a sensitivity (identifies the cause) of 70-80% and >90% specificity (when positive identifies the actual cause) in pneumococcal infections. The test was initially validated on urine samples, but has been applied succesfully to other body fluids.<ref name=Werno/> | | [[Pneumococcal infections history and symptoms|History and Symptoms]] | [[Pneumococcal infections physical examination|Physical Examination]] | [[Pneumococcal infections laboratory findings|Laboratory Findings]] | [[Pneumococcal infections chest x ray|Chest X Ray]] | [[Pneumococcal infections imaging findings|Other Imaging Findings]] | [[Pneumococcal infections other diagnostic studies|Other Diagnostic Studies]] |
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| == Treatment == | | ==Treatment== |
| Historically, treatment relied primarily on β-lactam antibiotics. In the 1960s, nearly all strains of ''S. pneumoniae'' were susceptible to [[penicillin]], but since that time, there has been an increasing prevalence of penicillin [[antibiotic resistance|resistance]], especially in areas of high [[antibiotic]] use. A varying proportion of strains may also be resistant to [[cephalosporin]]s, [[macrolide]]s (such as erythromycin), [[tetracycline]], [[clindamycin]] and the [[quinolone]]s. Penicillin-resistant strains are more likely to be resistant to other antibiotics. Most isolates remain susceptible to [[vancomycin]], though its use in a β-lactam-susceptible isolate is less desirable because of tissue distribution of the drug and concerns of development of vancomycin resistance. More advanced beta-lactam antibiotics ([[cephalosporins]]) are commonly used in combination with other drugs to treat meningitis and community-acquired pneumonia. In adults, recently developed fluoroquinolones such as [[levofloxacin]] and [[moxifloxacin]] are often used to provide empiric coverage for patients with pneumonia. [[Susceptibility testing]] should be routine, with empiric antibiotic treatment guided by resistance patterns in the community in which the organism was acquired, pending the results. There is currently debate as to how relevant the results of susceptibility testing are to clinical outcome.<ref name="ClinInfectDis2006-Peterson">{{cite journal | author=Peterson LR | title=Penicillins for treatment of pneumococcal pneumonia: does in vitro resistance really matter? | journal=Clin Infect Dis | year=2006 | pages=224–33 | volume=42 | issue=2 | pmid=16355333 | doi=10.1086/497594}}</ref><ref name="ClinInfectDis2006-Tleyjeh">{{cite journal | author=Tleyjeh IM, Tlaygeh HM, Hejal R, Montori VM, Baddour LM | title=The impact of penicillin resistance on short-term mortality in hospitalized adults with pneumococcal pneumonia: a systematic review and meta-analysis | journal=Clin Infect Dis | year=2006 | pages=788–97 | volume=42 | issue=6 | pmid=16477555 | doi=10.1086/500140}}</ref> There is slight clinical evidence that penicillins may act synergistically with macrolides to improve outcomes.<ref>{{cite journal | title=Addition of a Macrolide to a β-Lactam based empirical antibiotic regimen is associated with lower in-hospital mortality for patients with bacteremic pneumococcal pneumonia | author=Martínez JA, Horcajada JP, Almela M, ''et al.'' | journal=Clin Infect Dis | volume=36 | year=2003 | pages=389–395 | doi=10.1086/367541 | pmid=12567294}}</ref>
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| == Prevention ==
| | [[Pneumococcal infections medical therapy|Medical Therapy]] | [[Pneumococcal infections prevention|Prevention]] | [[Pneumococcal infections cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Pneumococcal infections future or investigational therapies|Future or Investigational Therapies]] |
| ===Vaccination in the USA===
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| In the USA, a heptavalent pneumococcal [[conjugate vaccine]] vaccine (PCV 7) (e.g. Prevenar<ref>E.M.E.A.:[http://www.emea.europa.eu/humandocs/PDFs/EPAR/Prevenar/H-323-PI-en.pdf Prevenar - Annex I: Summary of Product Characteristics]</ref>) is recommended since 2000 for all children aged 2–23 months and for at-risk children aged 24–59 months. The normally 4-doses series is given at 2, 4, 6 & 12–14 months of age. Protection is good against deep pneumococcal infections (especially septicemia and meningitis). Similar 9- and 13-valent vaccines are being tested. Yet, if the child is exposed to a serotype of pneumococcus that is not contained in the vaccine, he/she is not afforded any protection. This limitation, and the ability of capsular-polysaccharide conjugate vaccines to promote the spread of non-covered serotypes, has led to research into vaccines that would provide species-wide protection.
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| [[Pneumococcal polysaccharide vaccine]] (Pneumovax is one brand) gives at least 85% protection in those under 55 years of age for five years or longer. Immunization is suggested for those at highest risk of infection, including those 65 years or older; generally the vaccine should be a single lifetime dose, as there is a high risk of side effects if repeated. The standard 23-valent vaccines are ineffective for children under two years old.
| | ==Case Studies== |
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| The current guidelines of the [[American College of Physicians]] call for administration of the immunization between ages 2 and 65 when indicated, or at age 65. If someone received the immunization before age 60, the guidelines call for a one-time revaccination.
| | [[Pneumococcal infections case study one|Case #1]] |
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| ''Revaccination'' at periodic intervals is also indicated for those with other conditions such as [[asplenia]] or [[nephrotic syndrome]].
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| ===Vaccination in the UK===
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| It was announced in February 2006 that the UK government would introduce vaccination with the conjugate vaccine in children aged 2, 4 and 13 months.<ref name="BBCVac">[http://news.bbc.co.uk/1/hi/health/4692908.stm "Children to be given new vaccine"] ''BBC News'', February 08, 2006, retrieved August 25, 2006</ref><ref name="DoHPress">[http://www.dh.gov.uk/PublicationsAndStatistics/PressReleases/PressReleasesNotices/fs/en?CONTENT_ID=4128036&chk=PI8e57 "Pneumococcal vaccine added to the childhood immunisation programme"] February 08, 2006</ref> This is expected to start on September 4, 2006 and is to include changes to the immunisation programme in general.<ref name="MRF">[http://www.meningitis.org/disease-info/vaccines/change-to-the-immunisation-programme-in-the-uk "Changes to the immunisation programme in the UK"] ''Meningitis Research Foundation'', retrieved August 25, 2006</ref>
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| ===Vaccination worldwide===
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| [[PneumoADIP|Pneumococcal vaccines Accelerated Development and Introduction Plan (PnemoADIP)]] is a program to accelerate the evaluation and access to new pneumococcal vaccines in the developing world. PneumoADIP is funded by the [[Global Alliance for Vaccines and Immunization|Global Alliance for Vaccines and Immunization (GAVI)]]. Thirty GAVI countries have expressed interest in participating by 2010. PneumoADIP aims to save 5.4 million children by 2030.<ref name="PneumoADIP website">[http://www.pneumoadip.com "PneumoADIP website"]</ref>
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| ===Vaccine research===
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| There is currently research into producing vaccines than can be given into the nose rather than by injection.<ref>{{cite journal | title=Intranasal immunization with killed unencapsulated whole cells prevents colonization and invasive disease by capsulated pneumococci| author= Malley R. Lipsitch M, Stack A, Saladino R, Fleisher G, Pelton S, Thompson C, Briles D, Anderson P. | journal=Infect Immun | year=2001 | volume=69 | pages=4870–4873 | url=http://iai.asm.org/cgi/content/full/69/8/4870 | doi=10.1128/IAI.69.8.4870-4873.2001 | pmid=11447162}}</ref> It is believed that this improves vaccine efficacy and also avoids the need for injection.
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| The development of serotype-specific anticapsular monoclonal antibodies has also been researched in recent years. These antibodies have been shown to prolong survival in a mouse model of pneumococcal infection characterized by a reduction in bacterial loads and a suppression of the host inflammatory response.<ref>{{cite journal |author=Burns T, Abadi M, Pirofski L |title=Modulation of the lung inflammatory response to serotype 8 pneumococcal infection by a human immunoglobulin m monoclonal antibody to serotype 8 capsular polysaccharide |journal=Infect Immun |volume=73 |issue=8 |pages=4530–8 |year=2005 |pmid=16040964 |doi=10.1128/IAI.73.8.4530-4538.2005}}</ref><ref>{{cite journal |author=Fabrizio K, Groner A, Boes M, Pirofski L |title=A Human Monoclonal IgM Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal Infection |journal=Clin Vaccine Immunol |volume= |issue= |pages= |year= |pmid=17301214}}</ref>
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| ==References==
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| {{reflist|2}}
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| {{Gram-positive bacterial diseases}} | | {{Gram-positive bacterial diseases}} |
| {{CNS diseases of the nervous system}} | | {{CNS diseases of the nervous system}} |
| {{Respiratory pathology}} | | {{Respiratory pathology}} |
| {{SIB}}
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