When compared to chest X-rays, thoracic ultrasounds identified Lung ultrasound has been tested for its diagnostic potential and it was found to be a sensitive tool for confirming CAP in children Chest computed tomography is not used for children due to radiation Recently, a computer-aided differential diagnosis system was tested for distinguishing types of pneumonia, using high-resolution computed tomography.
For example, high levels of CRP and procalcitonin accompanied by unilateral hyperventilation and grunting were associated with pneumonia On the other hand, children with no clinical signs of pneumonia and low CRP results were at a lower risk for pneumonia. The use of PCR for diagnosis is also being developed.
A positive blood pneumococcal PCR can more accurately confirm the diagnosis of pneumonia PCR has been used to detect pneumolysin in whole blood samples By contrast, assessment of quantitative real-time PCR indicated that it is more successful in achieving greater speed, specificity, and sensitivity compared to multiplex PCR The two main modes of preventing pneumococcal infections are using antibiotics and vaccinations against pneumococcus Antibiotics are essential in reducing bacterial load Such treatment can work by killing the bacteria or hindering their growth The first antibiotic to be created was penicillin which was discovered in by Alexander Fleming , and antibiotics have been used widely since.
However, misuse of antibiotics can cause bacteria to become resistant 39 , , Resistant bacteria are then able to survive post antibiotic treatment and they can grow, multiply, and share antibiotic-resistant genes with each other.
Pneumococcal strains that were penicillin-resistant were first recorded in the s Currently, penicillin-resistant strains have spread worldwide with pneumococcus also being resistant to other types of antibiotics: erythromycin, tetracycline, and chloramphenicol Mutations in penicillin-binding proteins pbp affect binding of penicillin which acts by blocking cell wall synthesis Erythromycin resistance gene erm B blocks the binding of macrolides antibiotics targeting protein synthesis and mefA and mefE genes produce an efflux pump which regulates entry of the antibiotics — Resistant S.
This resistance increases the number of doctor visits and hospitalizations For example, the CDC reports that the resistance can lead to 1,, more illness and 7, deaths annually This reduction in ability to treat and clear the pathogen led to the development of vaccines that would provide protection prior to infection and thus reduce the need for antibiotics Currently, there are two types of inactivated vaccinations that protect against S.
The pneumococcal polysaccharide vaccine 23 PPSV23 uses purified capsular polysaccharides and is routinely given to adults who are 65 and older — It protects against 23 serotypes of S. This vaccine works in a T-cell independent manner.
The polysaccharide antigens are recognized by B cells which differentiate into plasma cells that produce antibodies specific for the polysaccharide antigens PPSV23 provides T-cell-independent immunity and requires revaccination 5 years after the first vaccination because the immunity is transient , The pneumococcal conjugate vaccine PCV was developed after noticing the low efficacy and poor immunogenicity of PPSV23 in infants and young children 91 , In the conjugate vaccine, the purified polysaccharides covalently conjugated to a carrier protein, specifically CRM , This elicits a T-cell-dependent response which provides mucosal immunity and immunologic memory in children PCV13 provides long-lasting immunity by causing B and T cells to interact B cells recognize and process the carrier protein The MHCII needed for antigen-presentation to T cells, binds to the peptide produced following B cell breakdown of the carrier protein When it comes to high-risk individuals, the CDC recommends the prime-boost method of vaccination.
This involves priming the immune system to a specific antigen, and enhancing this antigen-specific immune response by re-administering the antigen The prime-boost strategy increases immunity to antigens and is recommended for high-risk individuals , There are two ways to prime and boost the immune system: homologous, in which the same vaccine is received twice, and heterologous, which utilizes different types of vaccines The heterologous method has been shown to be more immunogenic Currently, children and adults who are at high risk for pneumococcal disease and have pre-existing conditions undergo the prime-boost strategy prevention by receiving the PCV13 followed by the PPSV23 , Prime-boost vaccinated HIV-infected groups have been shown to be more likely to display a twofold increase in IgG geometric mean concentrations PCV13 provides a longer and stronger level of protection against S.
Despite the availability of pneumococcal vaccines, it is important to note that these vaccinations are both serotype and age dependent 23 , 91 , — , Understanding the role that age plays in host immune system activation is essential for better prognosis and treatment of diseases. As stated previously, young children and the elderly are at higher risk for contracting pneumococcal diseases This is due to immunosenescence within the elderly population, whereas for infants, it is due to their underdeveloped immune systems In addition to age recommendations, the CDC also recommends the use of either vaccine in high-risk individuals with pre-existing health conditions.
For example, both vaccines are recommended in young children and adults ages 19—64 with pre-existing health conditions 23 , 24 , These vaccine recommendations are reevaluated regularly based on vaccine efficacy and changes within the bacteria serotypes , Vaccines have drastically reduced invasive pneumococcal diseases, especially CAP in young children and adults Table 2 However, these vaccines have pitfalls.
The current vaccines only protect against S. Some studies suggest that there is little evidence that PPSV23 protects against non-invasive pneumococcal diseases, which are more prevalent in adults Weinberger et al. These researchers argue that PPSV23 does not show a real benefit to the elderly As for, PCV13 they argue that it is already used in children and thus adults should be partially protected from serotypes in PCV13 due to herd immunity They also state that herd immunity should provide partial protection and thus will lead to reduction of efficacy of PCV13 Other studies also discuss herd immunity from PCV13 due to infants and toddlers being vaccinated , This becomes a problem because of serotype replacement.
The serotypes that are not in the vaccine can colonize young children and spread to adults , In addition, with serotype vaccines, the serotypes that are popular and commonly cause CAP and other diseases may not necessarily do so in the future and so these vaccines would need to be reevaluated. Recently researchers at Merck Sharp and Dohme Corp.
Current vaccines are ineffective against non-encapsulated S. Further developments of vaccinations are vital for eliminating the burden of S. Following pneumococcal diseases such as pneumonia, high-risk individuals may experience longer recovery times and complications due to the disease 1 , , About 1. According to the CDC, there were over 50, deaths within the US during 29 and the majority of these deaths were seen in the elderly Older adults have lower survival rates than other age groups 94 , The elderly may recover from pneumococcal diseases such as CAP, but they face higher death rates due to the high possibility of developing other health problems and the reoccurrence of the disease 1 , 94 , Infants and young children who recover from CAP have an increased risk for developing respiratory problems For example, research indicates that young children face a greater risk for reduced lung function and developing chronic obstructive pulmonary disease 44 , In some cases, increased death rates and complications are due to delays in diagnosis.
Such delays in turn hamper timely treatment, which also increases the severity of the disease. For example, meningitis can progress quickly and cause permanent disabilities such as brain damage, hearing loss, and seizures 24 , 52 , Timely treatment can reduce the risk of neurological damage and death due to this infection In addition, ear and sinus infections can lead to hearing loss and respiratory problems respectively The environment also plays a role in affecting recovery rates and reoccurrence of the disease especially for smokers and those residing in nursing homes and crowded areas 1.
Furthermore, Tiewsoh et al. Nutrition also plays a vital role in how well someone will recover from these diseases Some complications due to pneumococcal pneumonia include respiratory failure, lowered oxygen levels, and collapsed lungs 4.
It is also possible for the lungs to fill with fluid and this fluid can become infected. This is called bacteremia which is the most common complication for pneumonia 4 , Pneumonia and other pneumococcal diseases are classified as invasive if the bacteria migrate to the blood. In addition, individuals with this disease can develop pericarditis which is inflammation of the sac around the heart, lung abscess, empyema, and blockage of airways 4 , It is also highly probable for coinfections to occur when suffering with pneumonia.
Most of these health complications are seen in elderly subjects, and this also points to the increasing importance of improved diagnostics, treatments, and vaccinations for this age group.
Pneumococcal diseases cause millions of deaths worldwide 36 , In this review, we have characterized S. We have discussed the host defenses against S.
We have also indicated that young children, elders, and individuals who are immunocompromised all have an increased risk for contracting pneumococcal diseases. The majority of previous efforts have provided an extensive characterization of S.
However, in terms of treatment and prevention there remain substantial open questions that need to be addressed as discussed below. There are a variety of methods available for pneumococcal disease diagnostics.
Many of the current tests needed to confirm S. Culture-independent methods that take advantage of the latest technologies are being developed, such as the use of a lung ultrasound to assess pneumonia Chavez et al.
Similarly, the use of mass spectrometry to examine metabolites from the saliva , breath , and urine , of patients being tested for pneumococcal diseases is under development. The urine antigen test discussed above also provides rapid results that will allow for quicker diagnosis and treatment once S.
With diagnostic methods improving, pneumococcal disease treatments are also being updated. Antibiotics are available to reduce the colonization of S. Broad-spectrum antibiotics are no longer as effective , Inhaled therapeutics are underdeveloped but can be beneficial for treating pneumonia and other pneumococcal diseases.
This method can provide a mode of delivering antibiotics and antimicrobials in a more targeted manner, improve mucociliary clearance via hypertonic saline solutions and inhalation of cytokines to stimulate the immune system On the other hand, to also reduce the effect of antibiotic resistance, S.
Treatment and prevention of pneumonia and other pneumococcal diseases are of major concern for the clinical field due to the high death rates and low efficacy of current vaccines due to aging differences and serotype replacement.
Some alternative vaccination methods have been proposed and are also being developed. For instance, Weinberger et al. Some researchers have proposed creating a conjugate vaccine that targets all or more of the identified serotypes of S. However, the impact on the immune system and immunogenicity of this vaccine would need to be thoroughly investigated This vaccine would also need to demonstrate better efficacy than existing vaccines In addition, observing how pneumococcal disease incidence rates are changing as more and more people are getting vaccinated will lead to accurate assessment of pneumococcal disease burden and vaccine efficacy Vaccination policies and cost-effect analyses can benefit from information on vaccine disease reduction Serotype-independent vaccines are also being investigated.
These include protein, protein and polysaccharide combination, and whole cell vaccines , , , Protein vaccines would contain surface proteins that are highly conserved in S.
For example, PspA and inactivated pneumolysin have been tested in phase 1 clinical trials as protein antigens PspA is considered an ideal protein candidate because reports indicate that PspA family 2 is commonly found in S.
For example, in Pakistan most strains of pneumococci have PspA genes These protein vaccines can provide an extra preventative method once developed and will require thorough analysis of regulation and what regulatory issues may be faced In addition, as a form of combination therapy, a vaccine with protein antigens as well as conjugated polysaccharide antigens may also provide a broader range of protection against pneumococcal diseases , On the other hand, whole cell vaccinations would introduce a dead S.
HogenEsch et al. This exposed the host to multiple parts of S. They found that the vaccine led to the productions of antibodies and IL which defend against S. Researchers have also started developing live attenuated pneumococcal vaccines , The SPY1 strain is a live attenuated strain of pneumococci that does not have a capsule Xu et al.
More recently, Zhang et al. This modified SPY1 vaccine led to higher stability, more production of IgG, and an overall increase in protection when compared to the SPY1 vaccine Additional concerns of serotype-independent vaccines include determining if the vaccines will be immunogenic in all ages, whether or not the vaccines would elicit a strong immune response, and ensuring that they can induce a pro-inflammatory state while not leading to an over activation of the immune system.
All of these novel methods show great promise, but they require further assessments. Overall, there has been progress in our understanding of pneumococcal diseases over the last three decades, however, the diseases still constitute a big burden on health care. There has been a great decrease in pneumococcal diseases since the implementation of purified polysaccharide and polysaccharide conjugate vaccines, but over time due to serotype replacement, antibiotic resistance, and changes in immunity with age, the treatments, and vaccines in place may prove ineffective.
Therefore, ongoing research to improve vaccinations and treatments must continue toward alleviating the ill effects of S. All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. GM is funded by Jean P. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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