The term ‘encapsulated bacteria’ refers to bacteria covered with a polysaccharide capsule. Examples of such bacteria include Streptococcus pneumoniae, Klebsiella, Haemophilus influenzae, Neisseria meningitidis, and Pseudomonas aeruginosa. These bacteria belong to different genera but they share in common an important structural and immunological feature, the polysaccharide capsule. The body seems to be especially dependent on splenic function for clearing infections with encapsulated bacteria. Rampant invasive infections with these bacteria, in fact, have been observed in many asplenic states including post surgical splenectomy. Given this observation, medical care has witnessed a considerable shift toward conservative, nonoperative management of splenic injuries. In addition, various spleen-preserving techniques such as partial splenectomy, splenorrhaphy, splenic artery embolization, and splenic autotransplantation have been increasingly utilized in the hope of preserving splenic function. In the present article, we will review the microbiology of encapsulated bacteria, their clinical impact, their role in splenectomized patients, and prevention strategies around the time of and after splenectomy.
The polysaccharide capsule imparts a unique protective and virulence profile that renders encapsulated bacteria especially dangerous to human hosts. For one thing, the polysaccharide capsule functions as an antiphagocytic defense mechanism. Also, the capsule enables these bacteria to evade the adaptive immune response mounted by the host . It does so through many different mechanisms; first, the polysaccharide capsule conceals immunogenic bacterial cell wall components such as lipids, proteins, and lipopolysaccharide (LPS, in Gram negative bacteria). The capsule also prevents phagocytosis and complement-mediated lysis and hinders C reactive protein (CRP) recognition of phosphorylcholine residues in the bacterial cell wall. Because of these factors, encapsulated bacteria represent an especially virulent type of microorganism that poses a unique challenge for the host immune defense system.
Encapsulated bacteria are a significant clinical problem; they are responsible for one third of overall global deaths . S. pneumoniae and H. influenzae are the most common cause of lower respiratory tract infections. Such infections cause a greater burden of disease and death than any other infection, heart disease, or cancer [3,4]. Moreover, despite significant advances in overall and critical medical care, the mortality rate from lower respiratory tract infections has remained stable over the past 5 decades. S. pneumoniae and N. meningitidis account for the vast majority of bacterial meningitis cases in adults [5,6]. The mortality rate among adults with meningitis due to S. pneumoniae alone is reported to reach up to 37% with serious long-term neurological deficits developing in up to 30% [7–10]. In addition, survivors with no serious neurological sequelae have been found to suffer from cognitive impairment in up to 27% cases .
Asplenic patients are at increased risk of infections with encapsulated bacteria and are also at increased risk of death resulting from such infections [12,13]. The clinical condition of severe infection following splenectomy has been termed overwhelming postsplenectomy infection (OPSI). The three organisms most commonly responsible for OPSI are S. pneumoniae, N. meningitidis, and H. influenzae type b (Hib) . The condition is unusually severe with an overall mortality rate of 50% .
Interestingly, the risk of OPSI after splenectomy depends on the underlying condition necessitating splenectomy. Splenectomy performed for trauma has been generally found to be associated with a lower incidence and mortality risk of serious infections compared with splenectomy performed for hematological disorders [16–18]. The exact reasons for these differences in incidence and mortality among the different underlying conditions are unknown. Several explanations for this phenomenon have been put forth, however. Most patients undergoing splenectomy for trauma and immune thrombocytopenic purpura (ITP) are relatively healthy adults. Patients undergoing splenectomy for thalassemia, lymphoma, and sickle cell disease, however, are more likely to be at the extremes of age and have multiple organ systems involvement with disease. It should be noted that those at the extremes of age are known to be at increased risk of infection and death resulting from OPSI. In addition, in contrast to the situation in trauma, many patients undergoing splenectomy for hematological disorders have received some level of corticosteroid therapy; this may in itself predispose to infections around the time of splenectomy depending on the dosage and duration of therapy.
Although OPSI may develop at any age, children have been found to be most susceptible to this condition (especially those younger than 2 years of age) . In addition, although splenectomized patients carry a life-long risk of infection , the risk has been shown to decrease with increased time interval from splenectomy. Several studies have examined the possible explanations behind the relatively increased susceptibility of children to OPSI. The mounting of an effective humoral immune response has been found to be relatively impaired and more dependent on the spleen in those less than 2 years of age. Also, the spleen has several unique immune functions [such as the ability to clear nonopsonized encapsulated bacteria and the production of immunoglobulin M (IgM)] that the children appear to be more heavily dependent on due to their relative immune naivity [21,22].
Mechanism of susceptibility following splenectomy
There are several explanations for the increased susceptibility to infection following splenectomy. It has been demonstrated that both production of anticapsule IgG antibodies and normal complement activation is essential for effective clearance of encapsulated bacteria by the immune system. The postsplenectomy state has been shown to bear a significant impact on both immune functions in the face of infections with encapsulated bacteria. Complement is necessary for the generation of the membrane attack complex that leads to antigen degradation. Properdin produced by the spleen is necessary for the activation of the alternative complement pathway; its deficiency following splenectomy, therefore, may explain, at least partially, the inadequacy of the splenectomized patient's response to infection with encapsulated bacteria. The spleen also produces opsonin; opsonin fixes complement to the capsular polysaccharides and is therefore critical in the immunological defence against encapsulated bacteria.
Any effective antibody response against encapsulated bacteria must be directed specifically toward the outer capsule. This is because the capsule conceals the underlying immunogenic cell wall or membrane antigens rendering a response against such antigens impossible and inconsequential. Splenectomy results in a drastic reduction of marginal zone B cells available in the body. Marginal zone B cells comprise 30% of the B cell population in the spleen but are rare in other lymphoid tissue. Marginal zone B cells have been found to be essential for the generation of an effective antibody response to polysaccharide molecules. Thus, splenectomy results in a hindrance of the body's capacity to generate a specific antibody response to the polysaccharide capsule of encapsulated bacteria.
Prevention strategies for splenectomized patients revolve around three main facets, education, immunization, and prophylaxis. Patient counseling and education are of paramount importance in minimizing the effects of future infections following splenectomy. Despite this, studies have shown that patient education regarding their postsplenectomy state is largely variable and inadequate [23,24]. Patients should be advised of their increased risk of infections and the potential seriousness of infections when they do arise. Patients should have a 7-day supply of antibiotics to take immediately at the first sign of a possible infection. Patients should then seek prompt medical attention and to immediately identify themselves as postsplenectomy patients with a possible new infection. Patients should wear a medical alert bracelet at all times clearly identifying them as postsplenectomy patients so that they can be identified as such in case they fail to communicate this. Splenectomized patients should also be made aware of their increased risk in contracting and dying from travel-related infections and infections following invasive procedures such as surgery, instrumentation, or dental work. Some authorities recommend routine antibiotic prophylaxis during such periods, if the patient is not already on antibiotic prophylaxis; however, firm evidence on the benefits of this approach has yet to emerge.
Immunization is another major cornerstone in preventing serious infections in postsplenectomy patients. The pneumococcal vaccine is uniformly recommended for patients undergoing splenectomy. The vaccine has been shown to be 70% effective in preventing clinically significant pneumococcal infections in healthy adults that have undergone splenectomy . Once again, the compliance rate with routine vaccination for splenectomized patients has been shown to be variable and inadequate . Reimmunization is generally recommended every 3–5 years for splenectomized patients in order to maintain adequate serum antibody levels.
Although the Hib and meningococcal vaccines are recommended by many authorities and routinely administered by many institutions alongside the pneumococcal vaccine, their efficacy and utility are less well defined compared with the pneumococcal vaccine . It is generally agreed that vaccination should be administered two weeks prior to elective splenectomy or at the earliest opportunity thereafter. Patients undergoing emergency splenectomy should be vaccinated two weeks after the procedure. Patients undergoing chemotherapy or radiotherapy should have the vaccination delayed until 6 months after the end of the therapy; prophylactic antibiotics are generally recommended during this interval. The precise value and optimal timing for reimmunization with the Hib and meningococcal vaccines are not yet known.
The third cornerstone in preventing infections in splenectomized patients is long-term antibiotic prophylaxis. This issue is surrounded by a greater deal of controversy compared with patient education and immunization as there is less evidence to support specific recommendations. Given the higher incidence and impact of postsplenectomy infections in children, most authorities agree that antibiotic prophylaxis in this age group is indicated. Although it is generally agreed that such prophylaxis should be administered during the first 2 years following splenectomy (the highest risk period), little agreement or evidence exists on the duration of prophylaxis thereafter, if any. Recommendations have ranged from continued prophylaxis for 5 years, until the age of 18 or 21, to lifelong prophylaxis. Further, the value and duration of antibiotic prophylaxis in adults has yet to be determined.
Encapsulated bacteria are equipped with special immunological advantages because of their surrounding polysaccharide capsule. On this account, these organisms tend to be especially virulent and to have adapted to escape traditional host immune defense mechanisms. Given the unique profile of these organisms and the unique immunological functions of the spleen, the human body is particularly dependent on the spleen for clearance of infections brought on by encapsulated bacteria. Splenectomy, therefore, predisposes to infections with encapsulated bacteria that often go unchecked and result in serious sequalae. Given the developing nature of the child's immune system, children are at the highest risk of developing serious postsplenectomy infections. Several important measures in the form of education, immunization, and antibiotic prophylaxis need to be given extra attention in the splenectomized patient in order to minimize the impact of postsplenectomy sepsis.
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