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61-570: Quellung is the German word for "swelling" and describes the microscopic appearance of pneumococcal or other bacterial capsules after their polysaccharide antigen has combined with a specific antibody. The antibody usually comes from serum taken from an immunized laboratory animal. As a result of this combination, and precipitation of the large, complex molecule formed, the capsule appears to swell, because of increased surface tension, and its outlines become demarcated. The pneumococcal quellung reaction

122-421: A polysaccharide capsule that acts as a virulence factor for the organism; more than 100 different serotypes are known, and these types differ in virulence , prevalence , and extent of drug resistance . The capsular polysaccharide (CPS) serves as a critical defense mechanism against the host immune system. It composes the outermost layer of encapsulated strains of S. pneumoniae and is commonly attached to

183-620: A cause of neonatal infections . Streptococcus pneumoniae is the main cause of community acquired pneumonia and meningitis in children and the elderly, and of sepsis in those infected with HIV . The organism also causes many types of pneumococcal infections other than pneumonia . These invasive pneumococcal diseases include bronchitis , rhinitis , acute sinusitis , otitis media , conjunctivitis , meningitis , sepsis, osteomyelitis , septic arthritis , endocarditis , peritonitis , pericarditis , cellulitis , and brain abscess . Streptococcus pneumoniae can be differentiated from

244-511: A characteristic, staccato cough. CAP in older infants reflects increased exposure to microorganisms, with common bacterial causes including Streptococcus pneumoniae , Escherichia coli , Klebsiella pneumoniae , Moraxella catarrhalis and Staphylococcus aureus . Maternally-derived syphilis is also a cause of CAP in infants. Viral causes include human respiratory syncytial virus (RSV), human metapneumovirus , adenovirus, human parainfluenza viruses , influenza and rhinovirus , and RSV

305-654: A diagnosis of CAP. The diagnostic tools employed will depend on the severity of illness, local practices and concern about complications of the infection. All patients with CAP should have their blood oxygen monitored with pulse oximetry . In some cases, arterial blood gas analysis may be required to determine the amount of oxygen in the blood. A complete blood count (CBC) may reveal extra white blood cells , indicating infection. CAP may be prevented by treating underlying illnesses that increases its risk, by smoking cessation , and by vaccination . Vaccination against Haemophilus influenzae and Streptococcus pneumoniae in

366-409: A group of bacteria that typically live in the large intestine ; contamination of food and water by these bacteria can result in outbreaks of pneumonia. Pseudomonas aeruginosa , an uncommon cause of CAP, is a difficult bacteria to treat. Bacteria and fungi typically enter the lungs by inhalation of water droplets, although they can reach the lung through the bloodstream if an infection is present. In

427-454: A hospital or who live in long-term care facilities. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung ( alveoli ) filling with fluid. This inhibits lung function, causing dyspnea , fever , chest pains and cough . CAP, the most common type of pneumonia, is a leading cause of illness and death worldwide . Its causes include bacteria , viruses , fungi and parasites . CAP

488-580: A humoral immune response targeting the CPS present on the bacterial surface. PPSV23 offers T-cell -independent immunity and requires revaccination 5 years after the first vaccination because of its temporary nature. PCV13 was developed when determining its low efficacy in children and infants. PCV13 elicits a T-cell-dependent response and provides enduring immunity by promoting interaction between B and T cells, leading to an enhanced and prolonged immune response. Components from S. pneumoniae have been harnessed for

549-424: A noninvasive phenotype . Genetic information can vary up to 10% between strains. The pneumococcal genome is known to contain a large and diverse repertoire of antimicrobial peptides, including 11 different lantibiotics . Natural bacterial transformation involves the transfer of DNA from one bacterium to another through the surrounding medium. Transformation is a complex developmental process requiring energy and

610-542: A range of applications in biotechnology. Through engineering of surface molecules from this bacterium, proteins can be irreversibly linked using the sortase enzyme or using the SnoopTag/SnoopCatcher reaction. Various glycoside hydrolases have also been cloned from S. pneumoniae to help analysis of cell glycosylation . Historically, Haemophilus influenzae has been a significant cause of infection, and both H. influenzae and S. pneumoniae can be found in

671-659: A three-day course of antibiotics seems sufficient for most mild-to-moderate CAP in children. In 2001 the American Thoracic Society , drawing on the work of the British and Canadian Thoracic Societies , established guidelines for the management of adult CAP by dividing patients into four categories based on common organisms: For mild-to-moderate CAP, shorter courses of antibiotics (3–7 days) seem to be sufficient. Some patients with CAP will be at increased risk of death despite antimicrobial treatment. A key reason for this

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732-419: A treatment complication, inappropriate antibiotics for the causative organism, a previously unsuspected microorganism (such as tuberculosis ) or a condition mimicking CAP (such as granuloma with polyangiitis). Additional tests include X-ray computed tomography , bronchoscopy or lung biopsy . CAP is common worldwide, and is a major cause of death in all age groups. In children, most deaths (over two million

793-405: A virus enters the lungs through the inhalation of water droplets and invades the cells lining the airways and the alveoli. This leads to cell death; the cells are killed by the virus or they self-destruct . Further lung damage occurs when the immune system responds to the infection. White blood cells , particularly lymphocytes , activate chemicals known as cytokines which cause fluid to leak into

854-496: Is a Gram-positive , spherical bacteria, alpha-hemolytic member of the genus Streptococcus . S. pneumoniae cells are usually found in pairs ( diplococci ) and do not form spores and are non motile. As a significant human pathogenic bacterium S. pneumoniae was recognized as a major cause of pneumonia in the late 19th century, and is the subject of many humoral immunity studies. Streptococcus pneumoniae resides asymptomatically in healthy carriers typically colonizing

915-607: Is a common source of illness and hospitalization in infants. CAP caused by fungi or parasites is not usually seen in otherwise-healthy infants. Although children older than one month tend to be at risk for the same microorganisms as adults, children under five years of age are much less likely to have pneumonia caused by Mycoplasma pneumoniae , Chlamydophila pneumoniae or Legionella pneumophila than older children. In contrast, older children and teenagers are more likely to acquire Mycoplasma pneumoniae and Chlamydophila pneumoniae than adults. A full spectrum of microorganisms

976-492: Is caused by overwhelming response to an infection and leads to tissue damage, organ failure , and even death. The symptoms include confusion, shortness of breath, elevated heart rate, pain or discomfort, over-perspiration, fever, shivering, or feeling cold. Due to the importance of disease caused by S. pneumoniae , several vaccines have been developed to protect against invasive infection. The World Health Organization recommends routine childhood pneumococcal vaccination; it

1037-521: Is dependent on expression of numerous genes. In S. pneumoniae , at least 23 genes are required for transformation. For a bacterium to bind, take up, and recombine exogenous DNA into its chromosome , it must enter a special physiological state called competence . Competence in S. pneumoniae is induced by DNA-damaging agents such as mitomycin C , fluoroquinolone antibiotics ( norfloxacin , levofloxacin and moxifloxacin ), and topoisomerase inhibitors . Transformation protects S. pneumoniae against

1098-438: Is diagnosed by assessing symptoms, performing a physical examination, by x-ray or by sputum examination. Patients with CAP sometimes require hospitalization, and it is treated primarily with antibiotics , antipyretics and cough medicine . Some forms of CAP can be prevented by vaccination and by abstaining from tobacco products. Major complications of CAP include: Many different microorganisms can cause CAP. However,

1159-451: Is generally made based on clinical suspicion along with a positive culture from a sample from virtually any place in the body. S. pneumoniae is, in general, optochin sensitive, although optochin resistance has been observed. The recent advances in next-generation sequencing and comparative genomics have enabled the development of robust and reliable molecular methods for the detection and identification of S. pneumoniae . For instance,

1220-532: Is given to the treatment setting; most patients are cured by oral medication, while others must be hospitalized for intravenous therapy or intensive care . Current treatment guidelines recommend a beta-lactam, like amoxicillin, and a macrolide, like azithromycin or clarithromycin, or a quinolone , such as levofloxacin . Doxycycline is the antibiotic of choice in the UK for atypical bacteria, due to increased Clostridioides difficile infection in hospital patients linked to

1281-446: Is identified in only half the cases. It is possible for a fetus to develop a lung infection before birth by aspirating infected amniotic fluid or through a blood-borne infection which crossed the placenta . Infants can also inhale contaminated fluid from the vagina at birth. The most prevalent pathogen causing CAP in newborns is Streptococcus agalactiae , also known as group-B streptococcus (GBS). GBS causes more than half of CAP in

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1342-649: Is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, the United States, Greece, and South Africa. Currently, there are two vaccines available for S. pneumoniae: the pneumococcal polysaccharide vaccine (PPV23) and the pneumococcal conjugate vaccine (PCV13). PPV23 functions by utilizing CPS to stimulate the production of type-specific antibodies, initiating processes such as complement activation, opsonization, and phagocytosis to combat bacterial infections. It elicits

1403-489: Is made clinically, rather than on the basis of a particular test. Evaluation begins with a physical examination by a health provider, which may reveal fever, an increased respiratory rate ( tachypnea ), low blood pressure ( hypotension ), a fast heart rate ( tachycardia ) and changes in the amount of oxygen in the blood. Palpating the chest as it expands and tapping the chest wall to identify dull, non-resonant areas can identify stiffness and fluid, signs of CAP. Listening to

1464-415: Is often prescribed, with co-trimaxazole as an alternative when there is allergy to penicillins. Further studies are needed to confirm the efficacy of newer antibiotics. With the increase in drug-resistant Streptococcus pneumoniae , antibiotics such as cefpodoxime may become more popular. Hospitalized children receive intravenous ampicillin , ceftriaxone or cefotaxime , and a recent study found that

1525-411: Is part of the normal upper respiratory tract flora . As with many natural flora, it can become pathogenic under the right conditions, typically when the immune system of the host is suppressed . Invasins , such as pneumolysin , an anti phagocytic capsule , various adhesins , and immunogenic cell wall components are all major virulence factors . After S. pneumoniae colonizes the air sacs of

1586-436: Is potentially lethal to the bacteria. The ability of S. pneumoniae to repair oxidative DNA damage in its genome caused by this host defense likely contributes to the pathogen's virulence. Consistent with this premise, Li et al. reported that, among different highly transformable S. pneumoniae isolates, nasal colonization fitness and virulence (lung infectivity) depend on an intact competence system. Streptococcus pneumoniae

1647-532: Is responsible for CAP in adults, and patients with certain risk factors are more susceptible to infections by certain groups of microorganisms. Identifying people at risk for infection by these organisms aids in appropriate treatment. Many less-common organisms can cause CAP in adults; these may be determined by identifying specific risk factors, or when treatment for more common causes fails. Some patients have an underlying problem which increases their risk of infection. Some risk factors are: The symptoms of CAP are

1708-549: Is the host's exaggerated inflammatory response. There is a tension between controlling the infection on one hand and minimizing damage to other tissues on the other. Some recent research focuses on immunomodulatory therapy that can modulate the immune response in order to reduce injury to the lung and other affected organs such as the heart. Although the evidence for these agents has not resulted in their routine use, their potential benefits are promising. Some CAP patients require intensive care, with clinical prediction rules such as

1769-460: Is the most prevalent disease caused by Streptococcus pneumoniae , characterized by symptoms such as fever, chills, coughing, rapid or labored breathing, and chest pain. For the elderly, they may include confusion, low alertness, and the former listed symptoms to a lesser degree. Pneumococcal meningitis is an infection of the tissue covering the brain and spinal cord. Symptoms include stiff neck, fever, headache, confusion, and photophobia . Sepsis

1830-414: Is treated with an antibiotic that kills the infecting microorganism; treatment also aims at managing complications. If the causative microorganism is unidentified, which is often the case, the laboratory identifies the most effective antibiotic; this may take several days. Health professionals consider a person's risk factors for various organisms when choosing an initial antibiotic. Additional consideration

1891-667: The Xisco gene was recently described as a biomarker for PCR-based detection of S. pneumoniae and differentiation from closely related species. Atromentin and leucomelone possess antibacterial activity, inhibiting the enzyme enoyl-acyl carrier protein reductase , (essential for the biosynthesis of fatty acids ) in S. pneumoniae . Resistant pneumococcal strains are called penicillin-resistant pneumococci ( PRP ), penicillin-resistant Streptococcus pneumoniae ( PRSP ), Streptococcus pneumoniae penicillin resistant ( SPPR ) or drug-resistant Strepotococcus pneumoniae ( DRSP ). In 2015, in

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1952-461: The lungs , the body responds by stimulating the inflammatory response, causing plasma, blood, and white blood cells to fill the alveoli. This condition is called bacterial pneumonia. S. pneumoniae undergoes spontaneous phase variation , changing between transparent and opaque colony phenotypes. The transparent phenotype has a thinner capsule and expresses large amounts of phosphorylcholine (ChoP) and choline-binding protein A (CbpA), contributing to

2013-426: The pneumonia severity index and CURB-65 guiding the decision whether or not to hospitalize. Factors increasing the need for hospitalization include: Laboratory results indicating hospitalization include: X-ray findings indicating hospitalization include: The CAP outpatient mortality rate is less than one percent, with fever typically responding within the first two days of therapy, and other symptoms abating in

2074-402: The viridans streptococci , some of which are also alpha-hemolytic , using an optochin test, as S. pneumoniae is optochin-sensitive. S. pneumoniae can also be distinguished based on its sensitivity to lysis by bile , the so-called "bile solubility test". The encapsulated , Gram-positive, coccoid bacteria have a distinctive morphology on Gram stain, lancet -shaped diplococci. They have

2135-456: The 93 known capsular serotypes of Streptococcus pneumoniae in diagnostic settings, but in recent years it has been challenged by the latex agglutination method , and further by molecular typing techniques such as the polymerase chain reaction , which detect DNA and therefore target genetic differences between serotypes. Currently, there are 100 known capsular serotypes. Pneumococcus Streptococcus pneumoniae , or pneumococcus ,

2196-570: The CPS inhibits phagocytosis by preventing granulocytes ' access to the cell wall. In 1881, the organism, known later in 1886 as the pneumococcus for its role as a cause of pneumonia, was first isolated simultaneously and independently by the U.S. Army physician George Sternberg and the French chemist Louis Pasteur . The organism was termed Diplococcus pneumoniae from 1920 because of its characteristic appearance in Gram-stained sputum . It

2257-450: The US, there were an estimated 30,000 cases, and in 30% of them the strains were resistant to one or more antibiotics. Community acquired pneumonia Community-acquired pneumonia (CAP) refers to pneumonia (any of several lung diseases) contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited

2318-432: The advent of serum therapy to treat certain types of pneumococcal pneumonia in the 1920s because selection of the proper antiserum to treat an individual patient required correct identification of the infecting pneumococcal serotype, and the quellung reaction was the only method available to do this. Dr. Albert Sabin made modifications to Neufeld's technique so that it could be done more rapidly, and other scientists expanded

2379-525: The alveoli, bacteria and fungi travel into the spaces between cells and adjacent alveoli through connecting pores. The immune system responds by releasing neutrophil granulocytes , white blood cells responsible for attacking microorganisms, into the lungs. The neutrophils engulf and kill the microorganisms, releasing cytokines which activate the entire immune system. This response causes fever, chills and fatigue, common symptoms of CAP. The neutrophils, bacteria and fluids leaked from surrounding blood vessels fill

2440-515: The alveoli, impairing oxygen transport. Bacteria may travel from the lung to the bloodstream, causing septic shock (very low blood pressure which damages the brain, kidney, and heart). A variety of parasites can affect the lungs, generally entering the body through the skin or by being swallowed. They then travel to the lungs through the blood, where the combination of cell destruction and immune response disrupts oxygen transport. Patients with symptoms of CAP require evaluation. Diagnosis of pneumonia

2501-672: The alveoli. The combination of cell destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream. In addition to their effects on the lungs, many viruses affect other organs. Viral infections weaken the immune system, making the body more susceptible to bacterial infection, including bacterial pneumonia. Although most cases of bacterial pneumonia are caused by Streptococcus pneumoniae , infections by atypical bacteria such as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila can also cause CAP. Enteric gram-negative bacteria , such as Escherichia coli and Klebsiella pneumoniae , are

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2562-431: The bacteria's ability to adhere and colonize in the nasopharynx. The opaque phenotype is characterized by a thicker capsule, resulting in increased resistance to host clearance. It expresses large amounts of capsule and pneumococcal surface protein A (PspA) which help the bacteria survive in the blood. Phase-variation between these two phenotypes allows S. pneumoniae to survive in different human body systems. Pneumonia

2623-602: The bactericidal effect of mitomycin C. Michod et al. summarized evidence that induction of competence in S. pneumoniae is associated with increased resistance to oxidative stress and increased expression of the RecA protein, a key component of the recombinational repair machinery for removing DNA damage . On the basis of these findings, they suggested that transformation is an adaptation for repairing oxidative DNA damage. S. pneumoniae infection stimulates polymorphonuclear leukocytes (granulocytes) to produce an oxidative burst that

2684-436: The bloodstream. Sputum Gram staining and culture can also reveal the causative microorganism. In severe cases, bronchoscopy can collect fluid for culture. Special tests, such as urinalysis, can be performed if an uncommon microorganism is suspected. Chest X-rays and X-ray computed tomography (CT) can reveal areas of opacity (seen as white), indicating consolidation. CAP does not always appear on x-rays, sometimes because

2745-416: The common causative agents Streptococcus agalactiae , Listeria monocytogenes and Escherichia coli . To treat the herpes simplex virus , IV acyclovir is administered for 21 days. Treatment of CAP in children depends on the child's age and the severity of illness. Children under five are not usually treated for atypical bacteria. If hospitalization is not required, a seven-day course of amoxicillin

2806-419: The disease is in its initial stages or involves a part of the lung not clearly visible on x-ray. In some cases, chest CT can reveal pneumonia not seen on x-rays. However, congestive heart failure or other types of lung damage can mimic CAP on x-ray. When signs of pneumonia are discovered during evaluation, chest X-rays and examination of the blood and sputum for infectious microorganisms may be done to support

2867-522: The first week after birth. Other bacterial causes of neonatal CAP include Listeria monocytogenes and a variety of mycobacteria . CAP-causing viruses may also be transferred from mother to child; herpes simplex virus , the most common, is life-threatening, and adenoviridae , mumps and enterovirus can also cause pneumonia. Another cause of neonatal CAP is Chlamydia trachomatis , which, though acquired at birth, does not cause pneumonia until two to four weeks later. It usually presents with no fever and

2928-432: The first week. However, X-rays may remain abnormal for at least a month. Hospitalized patients have an average mortality rate of 12 percent, with the rate rising to 40 percent for patients with bloodstream infections or those who require intensive care. Factors increasing mortality are identical to those indicating hospitalization. When CAP does not respond to treatment, this may indicate a previously unknown health problem,

2989-724: The first year of life has been protective against childhood CAP. A vaccine against Streptococcus pneumoniae , available for adults, is recommended for healthy individuals over 65 and all adults with COPD, heart failure , diabetes mellitus , cirrhosis , alcoholism , cerebrospinal fluid leaks or who have had a splenectomy . Re-vaccination may be required after five or ten years. Patients who have been vaccinated against Streptococcus pneumoniae , health professionals, nursing-home residents and pregnant women should be vaccinated annually against influenza . During an outbreak, drugs such as amantadine , rimantadine , zanamivir and oseltamivir have been demonstrated to prevent influenza. CAP

3050-547: The human upper respiratory system. A study of competition in vitro revealed S. pneumoniae overpowered H. influenzae by attacking it with hydrogen peroxide . There is also evidence that S. pneumoniae uses hydrogen peroxide as a virulence factor. However, in a study adding both bacteria to the nasal cavity of a mouse within two weeks, only H. influenzae survives; further analysis showed that neutrophils (a type of phagocyte) exposed to dead H. influenzae were more aggressive in attacking S. pneumoniae . Diagnosis

3111-405: The increased use of clarithromycin . Ceftriaxone and azithromycin are often used to treat community-acquired pneumonia, which usually presents with a few days of cough, fever, and shortness of breath. Chest x-ray typically reveals a lobar infiltrate (rather than diffuse). Most newborn infants with CAP are hospitalized, receiving IV ampicillin and gentamicin for at least ten days to treat

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3172-458: The lungs with a stethoscope ( auscultation ) can also reveal signs associated with CAP. A lack of normal breath sounds or the presence of crackles can indicate fluid consolidation. Increased vibration of the chest when speaking, known as tactile fremitus, and increased volume of whispered speech during auscultation can also indicate the presence of fluid. Several tests can identify the cause of CAP. Blood cultures can isolate bacteria or fungi in

3233-413: The most common cause is Streptococcus pneumoniae . Certain groups of people are more susceptible to CAP-causing pathogens - infants , adults with chronic conditions (such as chronic obstructive pulmonary disease ), and senior citizens. Alcoholics and others with compromised immune systems are more likely to develop CAP from Haemophilus influenzae or Pneumocystis jirovecii . A definitive cause

3294-567: The peptidoglycan of the cell wall. It consists of a viscous substance derived from a high-molecular-weight polymer composed of repeating oligosaccharide units linked by covalent bonds to the cell wall. The virulence and invasiveness of various strains of S. pneumoniae vary according to their serotypes, determined by their chemical composition and the quantity of CPS they produce. Variations among different S. pneumoniae strains significantly influence pathogenesis , determining bacterial survival and likelihood of causing invasive disease. Additionally,

3355-420: The respiratory tract, sinuses, and nasal cavity . However, in susceptible individuals with weaker immune systems , such as the elderly and young children, the bacterium may become pathogenic and spread to other locations to cause disease. It spreads by direct person-to-person contact via respiratory droplets and by auto inoculation in persons carrying the bacteria in their upper respiratory tracts. It can be

3416-502: The result of lung infection by microorganisms and the response of the immune system to the infection. Mechanisms of infection are different for viruses and other microorganisms. Up to 20 percent of CAP cases can be attributed to viruses. The most common viral causes are influenza, parainfluenza, human respiratory syncytial virus, human metapneumovirus and adenovirus. Less common viruses which may cause serious illness include chickenpox , SARS , avian flu and hantavirus . Typically,

3477-466: The technique to identify 29 additional serotypes. Application of Neufeld’s discoveries to other important areas of research came when Fred Griffith showed that pneumococci could transfer information to transform one serotype into another. Oswald Avery , Colin MacLeod , and Maclyn McCarty later showed that the transforming factor was deoxyribonucleic acid, or DNA . Serum therapy for infectious diseases

3538-511: The transforming factor in Griffith's experiment was not protein , as was widely believed at the time, but DNA. Avery's work marked the birth of the molecular era of genetics . The genome of S. pneumoniae is a closed, circular DNA structure that contains between 2.0 and 2.1 million base pairs depending on the strain . It has a core set of 1553 genes , plus 154 genes in its virulome , which contribute to virulence and 176 genes that maintain

3599-510: Was displaced by antibiotics in the 1940s, but identification of specific serotypes remained important as the understanding of the epidemiology of pneumococcal infections still required their identification to determine where different serotypes spread, as well as the variable invasiveness of different serotypes. Understanding the prevalence of various serotypes was also critical to the development of pneumococcal vaccines to prevent invasive infections. The quellung reaction has been used to identify

3660-418: Was first described in 1902 by the scientist Fred Neufeld , and applied only to Streptococcus pneumoniae , both as microscopic capsular swelling and macroscopic agglutination (clumping visible with the naked eye). It was initially an intellectual curiosity more than anything else, and could distinguish only the three pneumococcal serotypes known at that time. However, it acquired an important practical use with

3721-504: Was renamed Streptococcus pneumoniae in 1974 because it was very similar to streptococci . Streptococcus pneumoniae played a central role in demonstrating that genetic material consists of DNA . In 1928, Frederick Griffith demonstrated transformation of life turning harmless pneumococcus into a lethal form by co-inoculating the live pneumococci into a mouse along with heat-killed virulent pneumococci. In 1944, Oswald Avery , Colin MacLeod , and Maclyn McCarty demonstrated that

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