Category: Infection

Introduction

Traditionally, sexually transmitted infections (STI) have been seen as a concern for young and adult populations that are more sexually active. However, researchers note that in high-income countries, STIs are becoming more prevalent among people over 60 (Lyons et al., 2017). At the current time, a significant proportion of older people in the West already have progressive views on sex and even have experience using mobile dating apps. At the same time, the older generation is also at risk of becoming exposed to infections that could have a devastating impact on their health. This paper explores and analyzes older people’s awareness of the STI danger and safer sexual practices, and provides evidence that the older generation is at increased risk in this regard. It also suggests possible solutions to address the above issues.

Factors of Increased STI Risk

It should be mentioned that the prevalence of STIs among older persons is a problem that is becoming global. Currently, it is not only acute in Europe and the United States, but also affects countries such as Brazil, Australia and Canada (Lyons et al., 2017; Malaquias et al., 2017; Spring, 2015). There are specific factors that put older individuals at greater risk in this regard. It is primarily due to the fact that the older generation is becoming more sexually active. In a study involving 1,652 respondents over the age of 60, more than 75 percent of men and women reported they had had a sexual experience in the past five years (Lyons et al., 2017). Another study also reveals a demographic characteristic, according to which out of 457 surveyed elders, more than 55 percent of women and only about 7 percent of men had inactive sex life (Malaquias et al., 2017). Thus, the proportion of older people engaged in sexual activity is quite high.

Lack of awareness of the characteristics of these infections and the necessary precautions remain significant risk factors. Research generally indicates that elders are aware of the STI danger and the mechanism of infection transmission (Lyons et al., 2017; Malaquias et al., 2017). At the same time, they are demonstrated to have a limited understanding of specific STIs. The most significant concern is the very high percentage of respondents who are unaware of the protection afforded by sexual protection measures (Lyons et al., 2017). Moreover, according to a study, over 85 percent of female elders and 50 percent of male elders reported never using a condom during their sexual activity (Malaquias et al., 2017). It should be noted that this high percentage demonstrates that people who know about the danger of getting infected still choose unsafe sex. Researchers state that older women engaging in sexual intercourse may be “at a greater risk of developing STIs because they lack sufficient awareness about safer sex or are unable to assert themselves in the relationship” (Spring, 2015, p. 6). Thus, not only ignorance but also hesitation can lead to adverse health outcomes.

In addition to the high levels of sexual activity and non-use of protection measures by older persons, the characteristics of infection are also an increased risk factor. According to Lyons et al. (2017), STI risk does not “decrease with age,” and “STIs could be present without obvious symptoms” (p. 260). Moreover, STIs, including HIV/AIDS, can be much more dangerous for older persons than for their young counterparts (Malaquias et al., 2017). Thus, the factor of sexual activity that is common to all population groups is complemented by the factor of increased health risk and the factor of condom non-use by the older generation.

Recommendations for Action

Primarily, informing is associated with the prevention of STIs among older people. According to Smith and Angarone (2015), it “begins with recognizing the risk behaviors of individual patients and counseling on changing these behaviors to prevent the acquisition of STIs” (p. 508). This counseling will be particularly effective in institutions and hospitals frequently visited by older people. The main objective of these measures is to demonstrate more clearly the consequences of dangerous behavior on the health of the individual and his or her partner, even if they are prone to disregard them. Given that older people are less likely to use condoms, it makes sense to distribute them free of charge, for example, at STIs treatment centers.

Preliminary medical examinations and early treatment are also important objectives. Researchers note that “partner notification and treatment is an effective tool in identifying cases of STI,” and “treatment of sexual partners reduces the rate at which the index case becomes reinfected” (Smith & Angarone, 2015, p. 516). Therefore, appropriate healthcare facilities can provide older people and their partners with the opportunity to be tested for STI as part of social programs. Another possible measure is to include a regular STI test in health insurance. Particular emphasis should be placed on developing a culture of partner notification and testing, as this is the most effective way to break the chain of infection.

Conclusion

It may be concluded that the older generation is now becoming more sexually active and, at the same time, is not inclined to use sexual protection means. Given this and the fact that STIs can develop without noticeable symptoms, and some of these diseases are particularly devastating for the health of older people, they are at high risk. Adequate and mass informing about the consequences of STI, as well as about the need for regular testing, can reduce the risk of infection. Opportunities for testing and obtaining sexual protection measures should be made available to elders.

References

Lyons, A., Heywood, W., Fileborn, B., Minichiello, V., Barrett, C., Brown, G., Hinchliff, S., Malta, S., & Crameri, P. (2017). Sexually active older Australian’s knowledge of sexually transmitted infections and safer sexual practices. Australian and New Zealand Journal of Public Health, 41(3), 259-261.

Malaquias, B. S. S., Nardelli, G. G., Azevedo, N. F., Ledic, C. S., Gaudenci, E. M., & da Silva Santos, Á. (2017). Sexuality and knowledge about hiv/aids in elders who participate in a social center for the elderly. Bioscience Journal, 33(2), 465-475.

Smith, L., & Angarone, M. P. (2015). Sexually transmitted infections. Urologic Clinics, 42(4), 507-518.

Spring, L. (2015). Older women and sexuality–are we still just talking lube? Sexual and Relationship Therapy, 30(1), 4-9.

Categories of Antimicrobial Agents

Different types of organisms (fungi, bacteria, viruses, etc.) cause different diseases, which implies that each one requires a particular antimicrobial agent to be successfully treated. Antimicrobial agents are used to preventing infections caused by pathogens and can be categorized as follows:

1. Antibacterial drugs. These drugs are meant to stop the pathogenic action of various kinds of bacteria.
2. Antiviral drugs. They are used to stop the pathogenic action of viruses.
3. Antifungal drugs. Such agents are needed to prevent the fungal action in the host.
4. Antiparasitic drugs. They are intended to hinder the growth of pathogenic parasites (Kelesidis & Falagas, 2015).

However, this is not the only possible way of classification. Antimicrobials can also be categorized by their ability to kill bacteria or inhibit their growth:

1. Bactericidal drugs kill harmful organisms (penicillins, quinolones, cephalosporins, aminoglycosides, etc.).
2. Bacteriostatic drugs delay or inhibit bacteria growth or hinder their replication (sulfonamides, tetracyclines, macrolides, etc.).
3. Some drugs can be referred to both groups since they act differently depending on the state of bacteria, duration of exposure, dosage, and other factors (aminoglycosides, metronidazole, fluoroquinolones, etc.) (Khurshid et al., 2016).

Another way to categorize antibacterials is by the spectrum of bacteria that react to them:

1. Narrow-spectrum drugs are used only against particular species of bacteria since their activity is highly limited (polymixins, nitroimidazoles, glycopeptides, aminoglycosides, etc.).
2. Intermediate-spectrum antibacterials are also limited inactivity but can affect several types of microorganisms simultaneously (ticarcillin, carbenicillin, ceftiofur, cephalosporins, etc.).
3. Broad-spectrum drugs are active both against Gram-positive and Gram-negative bacteria (fluoroquinolones, tetracyclines, 4^th-generation cephalosporins, phenols, etc.) (Kelesidis & Falagas, 2015).

Finally, antibacterials may be divided by the site of their activity:

1. inhibitors of cell wall synthesis;
2. inhibitors of cell membrane function;
3. inhibitors of protein synthesis;
4. inhibitors of nucleic acid synthesis;
5. inhibitors of other metabolic processes (Cansizoglu & Toprak, 2017).

Viral and Bacterial Infections

Table 1. Bacterial vs. Viral Infections.

Bacterial infection (caused by bacteria pathogenic in nature). They typically lead to skin infections, sore throat, pneumonia, urinary tract infections, bacterial pneumonia, and suchlike diseases. They are typically more severe than viral infections (Sweeney, Wong, & Khatri, 2016). If they are left untreated, their consequences can be deplorable for the patient.

On the contrary, viral infections are caused by viruses that typically hide in cells and attack the body when the immune system is weakened. They include common colds, viral meningitis, viral pneumonia, measles, AIDS, and other diseases (Silasi et al., 2015).

Why Proper Identification is Important

It is crucial to find out whether the disease is caused by a viral or bacterial infections since their treatments are considerably different. The situation is complicated by the fact that both types of infections may have the same symptoms. Bacterial infections are to be treated with antibiotics, which kill bacteria or hinder their reduplication. For viral infections, antiviral drugs are implemented; however, prevention is the key measure as some viral infections are incurable (such as AIDS). Antibiotics do not work for this type of infection (Talaro & Chess, 2018).

References

Cansizoglu, M. F., & Toprak, E. (2017). Fighting against evolution of antibiotic resistance by utilizing evolvable antimicrobial drugs. Current Genetics, 63(6), 973-976.

Kelesidis, T., & Falagas, M. E. (2015). Substandard/counterfeit antimicrobial drugs. Clinical Microbiology Reviews, 28(2), 443-464.

Khurshid, Z., Naseem, M., Sheikh, Z., Najeeb, S., Shahab, S., & Zafar, M. S. (2016). Oral antimicrobial peptides: Types and role in the oral cavity. Saudi Pharmaceutical Journal, 24(5), 515-524.

Silasi, M., Cardenas, I., Kwon, J. Y., Racicot, K., Aldo, P., & Mor, G. (2015). Viral infections during pregnancy. American Journal of Reproductive Immunology, 73(3), 199-213.

Sweeney, T. E., Wong, H. R., & Khatri, P. (2016). Robust classification of bacterial and viral infections via integrated host gene expression diagnostics. Science Translational Medicine, 8(346), 346ra91-346ra91.

Talaro, K. P., & Chess, B. (2018). Foundations in microbiology. New York, NY: McGraw-Hill.

The ongoing global MERS-CoV outbreak presents several dangers to the hospital and the radiology department, specifically. First and foremost, there is a possibility that infected patients will enter the location, potentially spreading the disease to workers or other residents. To that end, a reinforcement of the standard prevention measures to further reduce the danger is necessary. Second, there is an expectation that the flow of patients to the radiology department is going to increase, possibly doubling. As such, the workers there have to be prepared to continue providing essential services at a high pace while maintaining sanitary conditions. As the director of the radiology department that is also responsible for ED, inpatient floors, and OR, all of these matters are the author’s concern. As such, they have prepared this report to elaborate on the changes in staffing, infection control, and supply distribution they intend to implement.

Staffing

Due to the expectation of the arrival of infected patients, who can contaminate the surfaces they touch, the department will limit itself to essential operations. Seear and Ezezika (2017) define these as X-rays, ultrasounds, and technician training. All of the other practices will be suspended, and the staff responsible for them will be partially furloughed. These operations will only be performed if there is an immediate and urgent need, and the staff on duty should be able to handle them. The number of workers who handle the essential operations will be increased based on the patient flow projections weighted against the department’s current capacity. Moreover, technician training will also be stopped for the duration of the outbreak because it is unsafe, and there will likely be no time for it.

Infection Control

Generally, radiographic instruments tend not to penetrate the patient’s tissues or touch them directly. As such, infection control procedures tend to be laxer there than in departments such as surgery. However, as Iannucci and Howerton (2017) note, there are still opportunities for cross-contamination. As such, due to the outbreak, controls will be intensified, and instruments will be disinfected after each use. With that said, due to the high throughput, it is not feasible to use high-intensity procedures because of the time and cost involved. As such, the department will engage in medium-intensity disinfection after each usage of its services. The staff will be using personal protection equipment such as masks and gloves and be instructed to wash their hands regularly. In doing so, it should be able to reduce the incidence of infection for both the staff and the patients.

The other settings under the management of the author require more stringent measures. The ED and the OR will be subject to strict disinfection measures after each usage. Moreover, the inpatient floors are particularly concerning because of the constant risk that they represent. Regular cleaning and disinfection will take place wherever possible, and patient monitoring and isolation will take place. Bearman et al. (2018) recommend the usage of safe injection practices and respiratory hygiene alongside cough etiquette. The staff will be reminded to wear PPE at all times and handle all surfaces that they touch carefully and safely. Additional caution will be applied when dealing with patients who cannot move, as their surroundings cannot be disinfected thoroughly. With these measures, the danger of infection should become less pressing, though the chance always exists, and vigilance will be required.

Supply Distribution

The primary problem in the handling of increased hospital demand during an outbreak of an infection is the limited amount of available supplies. They will be distributed based on the danger of each area for which the author is responsible. The inpatient floors are the most problematic because of the high concentration of potentially infected people there and the need for close interaction with them. As such, they will receive the highest proportion of supplies of every kind. Many of the same considerations apply to the ED, and it will also have a high priority, though its smaller size will mean it receives less total equipment. The radiology department and the OR will receive a smaller amount of supplies because they represent smaller dangers and do not undergo the same sterilization procedures. However, the author will try to ensure that the needs of each area under their oversight are met.

Conclusion

The emergence of the MERS-CoV outbreak is going to change the priorities of the hospital to an increased focus on infection control. All non-essential activities will be suspended, and some of the workers who handle them will be reassigned to X-rays and ultrasounds to handle the increased demand. Disinfection procedures will happen more often and be more thorough, even with equipment that does not touch the patients. Staff will wear personal protective equipment and handle surfaces carefully at all times, and patients will be asked to observe cough etiquette. In terms of supply distribution priorities, the inpatient floors and the ED will take priority, though the management will also attempt to satisfy the needs of the other departments. The prevention of infections is a significant concern, and it is critical to address them with all possible attention.

Educational Materials

• Hand Hygiene 101. Web.
• Infection Prevention for Patients. Web.
• Safe Injection Practice. Web.
• Precautions for Potentially Infected Patients. Web.
• Disinfection and Sterilization Guideline. Web.
• Updates to the Guideline. Web.

References

Bearman, G., Munoz-Price, S., Morgan, D. J., & Murthy, R. K. (eds.). (2018). Infection prevention: New perspectives and controversies. Springer.

Iannucci, J. M., & Howerton, L. J. (2017). Dental radiography: A workbook and laboratory manual (5^th ed.). Elsevier.

Seear, M., & Ezezika, O. (2017). An introduction to global health (3^rd ed.). Canadian Scholars.

Chlamydia

This is a bacterial infection which is passed over in the course of sexual contact. Among the adults, about five percent of them are infected with this disease. Among the females who are adolescents, 10 percent of this group of people is infected with the disease. Generally, the groups of people who are most vulnerable to the infection include the young adults, the people who stay in urban areas, the African Americans, and those people having lower social economic status (“Chlamydia” 1).

Causes

This infection is caused by a bacterium referred to as Chlamydia trachomatis. One of the ways of transmission, as considered earlier on, is by having intimate contact such as sexual intercourse. Another way through which this disease can be passed over is transmission from mother to baby during birth. This disease can cause pneumonia in a new born baby and even severe eye infections among those babies that are born by the mothers who are infected with the disease.

Symptoms

The symptoms for this disease vary depending on whether the infected person is a man or a woman. The symptoms portrayed in men are not similar to those in women. In Women, no symptoms are seen in about 80 percent of the infected people. One of the symptoms that are seen is bleeding after one having sexual intercourse and also during the period between the menstrual cycles. Another symptom in women is having discharge from the vagina and also having lower abdominal pain in the course of urinating. In men, just as it is the case in the women, those who might be infected may not show any signs. Among the symptoms are; “a discharge coming from the penis during urination, one may experience a burning pain, and duct inflammation in the testicles or having pain in the testicles” (“Chlamydia” Para 5).

Treatment

This disease can be treated using antibiotics. Prescription may be given by a physician of a single dose of such a drug as azithromycin which is taken as a pill. More so, the doctor may recommend that such an antibiotic as doxyclycline be taken two times each day for a period of one week. Boskey (Para 1) points out that the most appropriate treatment for an individual having Chlamydia is dependent on a number of factors. She points out that if one feels that he or she may have difficulty remembering to take a peel every day at some specified time in the course of the day for a whole week, he or she may suggest to the doctor for he or she be given treatment by giving a single dose. However, it may be a little bit expensive to be given a single dose as compared to taking pills very day for a whole week. It is important to point out that a large percentage of those people using the antibiotics will be healed (about 95 percent of them).

Prevention

This infection can be avoided by when people engaging in protected sex where they use condoms. More so, it can be prevented by one trying to avoid as much as possible to have sex with those partners that might be high-risk partners. More so, prevention might be through offering treatment to those sexual partners that might be infected or ensuring that these partners have been tested before having sexual intercourse with them. About twenty five percent of the sexual partners will once again be infected for the reason that treatment was not given to the other partner (“Chlamydia”).

Prognosis

When treatment of this infection is carried out using antibiotics, the infected people can be cured (up to 95 percent of these cases). However, there arise complications in the cases where no treatment is done. Among these complications is that there will be development of “pelvic inflammatory disease” in between ten to forty percent of the infected women. Among those females who might develop the “pelvic inflammatory disease”, 5 percent of them will acquire perihepatitis and is a kind of the disease of the liver.

Still considering women, they may grow chronic pelvic pain and turn out to be sterile and this will come about as a result of the fallopian tubes blocking, hindering transportation of the egg from the ovary to reach the uterus. Considering the case for men, among them, there can be those who might grow reactive arthritis that is sexually acquired. More so, they may experience swelling of the testicles that is painful.

References

Boskey, Elizabeth, How is Chlamydia treated? 2008. Web.

“Chlamydia”, emedicidnehealth. eMedicineHealth. 2010. Web.

Introduciton

Bacterial infections are the most frequent human diseases throughout life. In particular, E. coli is a type of gram-negative rod-shaped bacteria that is widespread in the lower intestines of warm-blooded animals. Escherichia coli represents the most abundant aerobic commensals in the colon. Most strains of E. coli are harmless, but serotype O157: H7 can cause severe food poisoning in humans and animals.

Description of E. coli

E. coli is a gram-negative bacterium, facultative anaerobic; it does not form endospores. The cells are rod-shaped, with slightly rounded ends, 0.4-0.8 × 1-3 μm in size, and the cell volume is about 0.6-0.7 μm3 (Frankel & Ron, 2018). E. coli can live on different substrates; under anaerobic conditions, it forms lactate, succinate, ethanol, acetate, and carbon dioxide as a waste product. This often produces molecular hydrogen, which interferes with the formation of the above metabolites; therefore, E. coli often coexists with microorganisms that consume hydrogen, such as methanogens or bacteria that reduce sulfate (Sperandio & Bonach, 2015). E. coli cells have pili (fimbria) and are motile due to the peritrichial flagella.

Escherichia coli is a classical object of molecular genetics; 87.8% of the genome is occupied by real and probable protein-coding genes, or cistrons (Sperandio & Bonach, 2015). This type of bacteria can be examined using a light microscope or atomic force microscopy. According to the Gram method, Escherichias are colored pink (gram-negative); the smears under the microscope are randomly arranged.

Virulence Factors

ExPEC E. coli are characterized by a wide range of virulence-associated factors, in particular, toxins, adhesins, iron acquisition factors, polysaccharide capsules, lipopolysaccharides, and invasins, plasmids, as well as other genetic elements of mobile nature. Diseases caused by E. coli are called coli infections, or Escherichiosis (Rojas-Lopez et al., 2017). Intestinal infections, occupying a leading position in the structure of Escherichiosis, are associated with four different groups: E. coli-enterotoxigenic (ETCP), enteroinvasive (EICP), enteropathogenic (EPEC), and enterohemorrhagic (EHEC).

Immunity

The key factor in the mechanism of innate immunity of the mucous membranes is TLR4, which recognizes pathogens, promotes the induction of the production of cytokines, interferons, antimicrobial peptides. The microbiocidal molecules of the mucous membrane – antimicrobial peptides, defensins, cathelicidins, lactoferrin – are also mediators of the innate immune response. Uropathogenic Escherichia coli triggers an inflammatory response via virulence factors that mediate adhesion to the urothelium.

Primary ligand-binding receptors, represented by chemokine receptors, are involved in the recognition of pathogen-associated molecular patterns (PAMP). The second receptors, represented by TLR-4, provide a transmembrane signal (Rojas-Lopez et al., 2017). This is followed by the release of mediators of inflammation, immunity, differentiation of cytokine cells, recruitment of neutrophils from the vessels into the blood, and their penetration into the bladder cavity (Rojas-Lopez et al., 2017). As a result, bacteria are cleared and urine cleansed; this is the scheme of an acute inflammatory process in the bladder mucosa. According to the researchers, the impaired immune response is possible at any level and may be associated with insufficient expression of defensins, TLRs, as well as with an imbalance in the cytokine profile (Torres, 2016). Usually, the disease begins with abdominal pain, diarrhea, vomiting, and fever, flowing in the form of enteritis.

Infectious disease information

Escherichiosis refers to acute intestinal diseases with a fecal-oral transmission mechanism. Each of the classes of pathogenic E. coli is characterized by certain differences in the disease course, which in its symptoms may resemble cholera or dysentery. The incubation period lasts 3-6 days (usually 4-5 days). Most commonly, E. coli causes urinary tract infection, which is often an ascending infection (for example, from the perineum through the urethra). E. coli can also lead to prostatitis and pelvic inflammatory disease. As a whole, E. Coli diseases can be listed as follows (Frankel & Ron, 2018):

• Urinary tract infections (most common);
• Intestinal infection (some strains);
• Invasive infection (rare, except in newborns);
• Infections of other organs and tissues.

Epidemiology

The reservoir and source of infection is a sick person or a carrier. The most dangerous are patients with Escherichiosis caused by EPEC and EIKP, less – patients with Escherichiosis caused by ETCP, EHEC, and EACP (Frankel & Ron, 2018). The period of contagiousness of the source depends on the properties of the pathogen. With escherichiosis caused by ETCP and EHEC, the patient is contagious only in the first days of the disease, with diseases caused by EICP and EHEC, 1-2 weeks (sometimes up to 3 weeks) (Frankel & Ron, 2018). The mechanism of transmission of the pathogen is fecal-oral; transmission routes can be food, water, home (through contaminated hands, toys, etc.). The main sources of STEC outbreaks are raw or undercooked minced meat products, raw milk, and fecal-contaminated vegetables; below, the transmission mechanism is presented schematically.

Prevention

Preventive measures are reduced to the observance of the sanitary-hygienic regime and the rules of personal hygiene; no specific prophylaxis is performed. A childhood vaccine is not applied to the general population; however, the vaccine was created. The efficacy of the E. coli Escherichia coli (ETEC) vaccine developed by Swedish researchers has been confirmed in clinical trials, and now it is in the process of further trials (Erjavec, 2019). For now, to prevent infection, control measures must be followed at all stages of the food chain – from agricultural production on farms to processing and preparation of food, both in commercial enterprises and at home. On the household level, it is recommended to use chlorine-based disinfectant cleaners when cleaning plumbing fixtures and all surfaces.

Treatment

Treatment should be started empirically based on the location and severity of the infection and then modified based on antibiotic susceptibility testing. The agents cause violation of cell wall synthesis or damage to the cytoplasmic membrane. Many strains are resistant to ampicillin and tetracyclines, so other drugs must be used; these include ticarcillin, piperacillin, cephalosporins, carbapenems, fosfomycin, nitrofurantoin, aminoglycosides, trimethoprim/sulfamethoxazole (TMP/SMX), and fluoroquinolones (Frankel & Ron, 2018). Surgery may be required to debride the source of infection (to drain pus, debride necrotic lesions, or remove foreign bodies). EHEC infections of the gastrointestinal tract are not treated with antibiotics.

Critical Relevance

In addition to resistance to ampicillin and tetracycline, E. coli is becoming increasingly resistant to TMP/SMC and fluoroquinolones. Moreover, multidrug-resistant strains that produce extended-spectrum beta-lactamases (ESBLs) are often a major important cause of community-acquired (domestic) urinary tract infections and sepsis. ESBLs can hydrolyze most beta-lactams, including penicillins and broad-spectrum cephalosporins, and monobactams, but not carbapenems (imipenem, meropenem, doripenem, ertapenem); they should be used to treat E. coli infections that produce ESBLs (Frankel & Ron, 2018). Fosfomycin is active against multidrug-resistant strains and is an alternative oral drug for lower urinary tract infections.

Conclusion

Urinary tract infections are among the most common infectious diseases that occur widely in both outpatient and inpatient practice. This is one of the most pressing problems in most countries of the world. Uropathogenic strains of E. coli are able to form biofilms (microcolonies) on the mucous membrane of the bladder and inside epithelial cells. Due to the widespread prevalence of diseases caused by E. coli, the study of the characteristics of this microorganism and the dissemination of knowledge about methods of treatment and prevention are of particular importance.

References

Erjavec, M. (2019). The Universe of Escherichia coli. IntechOpen.

Frankel, G., & Ron, E. (Eds.). (2018). Escherichia coli, a versatile pathogen. Springer.

Rojas-Lopez, M., Monterio, R., Pizza, M., Desvaux, M., Rosin, R. (2017). Intestinal pathogenic Escherichia coli: Insights for vaccine development. Frontiers of Microbiology, 9, 1–14. Web.

Sperandio, V., & Bonach, C. H. (2015). Enterohemorrhagic Eecherichia coli and other shiga toxin-producing E. coli (1^st ed.). ASM Press.

Torres, A. G. (Ed.). (2016). Escherichia coli in the Americas. Springer.

For effective control of viral infections, the bodies of infected persons often mount both adaptive or specific, and innate immune responses (Markine-Goriaynoff, Hulhoven and Cambiaso 2709, par. 1). Cytolytic responses may be initiated by the natural killer (NK) cells or T lymphocytes, but this depends on the infecting pathogen. Other responses to viral infection may be in the form of antibody production, or release of molecules that inhibit replication of the infecting virus. A number of viruses have been able to evade the immune responses and therefore persist in immune-compromised hosts. A good example is the “lactate dehydrogenase-elevating virus (LDV), which persists indefinitely in the circulation of infected mice” (Markine-Goriaynoff, Hulhoven and Cambiaso 2709, par. 1). The LDV virus persists in the mice “despite the production of neutralizing antibodies and the induction of effective helper and cytolytic T lymphocytes” (Markine-Goriainoff, Hulhoven and Cambiaso 2709, par. 2). These immune responses are not effective in controlling viral replication, their specificity not withstanding. However, there is no sufficient data on the innate responses that are triggered by LDV. Responses such as the “NK activation have not been analyzed extensively” (Markine-Goriaynoff, Hulhoven and Cambiaso 2709, par. 4). Therefore, this study was conducted to examine if LDV infection leads to the activation of Natural killer (NK) cells and their resultant IFN-y secretion.

Methods

Pathogen free female mice; “CBA/Ht, DBA/2, BALB/c, BALB/c nu/nu and BALB/cBy-SCID (SCID) and isolator-reared 129/Sv mice were raised at the Ludwig Institute for Cancer Research (Brussels, Belgium) and used when 8±13 weeks old”, Infection by LDV was done via an intra-peritoneal injection (Markine-Goriaynoff, Hulhoven and Cambiaso 2710, par. 1). The monoclonal antibodies for the recognition of the VP3 protein found in the LDV were made available. Suitable antibodies for the inhibition of NK cell activity were prepared in a rabbit using incomplete Freund’s adjuvant and purified asialoganglioside –GMI (Markine-Goriaynoff, Hulhoven and Cambiaso 2710, par. 2). Titration of “LDV was done using the new sensitive particle counting immunoassay based on agglutination of latex beads coated with two different anti-LDV m Abs by virus” particles (Markine-Goriaynoff, Hulhoven and Cambiaso 2710, par. 4). Flow cytometry testing was performed using FACScan flow cytometer which showed the results as a percentage (Markine-Goriaynoff, Hulhoven and Cambiaso 2710, par. 5). The RNA was extracted and gene expression evaluated using RT-PCR protocols.

Results

The effect of LDV on NK cells was initially analyzed by examining the ratio of spleen ad peritoneal cells recognized by DX5 antibody at varying times following infection (Markine-Goriaynoff, Hulhoven and Cambiaso 2711, par. 1). 4 days after the infection with LDV a pronounced rise in the spleen cell population was witnessed in the 129/Sv mice. A similar rise in cell population was also seen in the spleen of BALB/c mice (Markine-Goriaynoff, Hulhoven and Cambiaso 2711, par. 1).

The lytic activity of the spleen and the peritoneal cells from the LDV-infected mice was examined to further investigate NK cell activation following LDV infection (Markine-Goriaynoff, Hulhoven and Cambiaso 2711, par. 2). “NK-sensitive target YAC-1 cells were used to test the lytic activity and against the TEPC.1033 cells” which are known to be resistant to NK mediated lysis (Markine-Goriaynoff, Hulhoven and Cambiaso 2711, par. 2). Significant YAC-1 lysis did not take place in the peritoneal cells that were derived from uninfected mice. However efficient YAC-1 lysis was observed in the cells that were harvested from infected mice. In addition, “TEPC.1033 failed to lyse indicating that the NK cells were the lytic effectors” (Markine-Goriaynoff, Hulhoven and Cambiaso 2711, par. 2). Peak lysis occurred one to two days following mice inoculation with LDV virus. When SCID mice, “which lack ctyolytic T lymphocytes were infected with LDV, the increase in the lytic activity of the peritoneal cells against YAC-1 was also observed” (Markine-Goriaynoff, Hulhoven and Cambiaso 2712, par. 2). Furthermore, the addition of “anti-ASGM1 polyclonal antibody, which usually eliminates NK cells in-vivo, inhibited most of the anti-YAC-1 lytic activity from bulb or SCID” animals infected with LDV (Markine-Goriaynoff, Hulhoven and Cambiaso 2712, par. 2).

The study also revealed that LDV triggered the release of IFN-y gene expression and IFN-y production by NK cells (Markine-Goriaynoff, Hulhoven and Cambiaso 2712, par. 3). The LDV’s effects on NK production were determined by measurements the cytokine level in the mice serum after varying periods of time. The effect was additionally tested by RT-PCR to determine the level of expression. It was established that expression of the gene occurred a short duration after the spleen or peritoneal cells were infected with LDV and peaked in 12 hours. Similar observations were made when “nude mice (treated with depleting anti-CD4 or anti-CD8 mAbs) were used and thus indicating that the message expression and production of this cytokine were independent from T lymphocytes” (Markine-Goriaynoff, Hulhoven and Cambiaso 2712, par. 3). Investigations for the effects NK cells and IFN-y on LDV showed that the two cannot inhibit early LDV replication (Markine-Goriaynoff, Hulhoven and Cambiaso 2712, par. 3).

Discussion

The activation of NK cell and the subsequent cell mediated cytoxicity and IFN-y production is common in many viral infections, “including lymphocytic choriomenengitis virus (LCMV), mouse hepatitis virus (MHV) and murine cytomegalovirus (MCMV)” (Markine-Goriaynoff, Hulhoven and Cambiaso 2713, par. 1). Therefore it does not come as a surprise to observe similar cytolysis following LDV inoculation, although LDV was chiefly known for enhancing humoral immune response while decreasing cellular responses (Markine-Goriaynoff, Hulhoven and Cambiaso 2714, par. 1). This indicates that the increased cytolytic activity following infection with LDV may actually be credited to the virus. Furthermore, the inhibition of the cytolytic effects when anti-ASGM1 antibody is administered indicates that NK cells played a roll in this effect. The results of this study show the diverse processes in the activation different NK cell function triggered LDV inoculation, “with very early IFN-y production rapidly followed by an increase in cytolytic activity and finally a slight delayed of CD49b+ cells” (Markine-Goriaynoff, Hulhoven and Cambiaso 2714, par. 2). Explanation for this occurrence can be linked to the sequential activity facilitated by different cytokines. Cytokines such as the IL-12, IL-15 and growth factor may be responsible for the NK activities as they are usually produced following LDV infection. Previous studies have shown that “LDV varaemia usually persists despite the development of T and B cell mediated anti-viral immune responses and little is known about the effects of NK cells on the replication of this virus” (Markine-Goriaynoff, Hulhoven and Cambiaso 2714, par. 3). Data obtained by this study show that the initial rapid replication phase exhibited LDV virus is not controlled by NK cells. In addition, “the inability of G129 mice to respond to IFN-y did not modify the viral titres” (Markine-Goriaynoff, Hulhoven and Cambiaso 2714, par. 3). This finding validates previous results that showed the inability of IFN-y to inhibit LDV viral replication though it may confer protection against polioencephalomyelitis that is induced by LDV (Markine-Goriaynoff, Hulhoven and Cambiaso 2714, par. 4). In most mouse strains, LDV does not cause any pathological manifestations, however, it affects the immune response leading to enhanced humoral responses are triggered. The virus triggers activation of the immune system to produce the inflammatory responses that are characteristic of its infection (Markine-Goriaynoff, Hulhoven and Cambiaso 2715, par. 1).

Reference

Markine-Goriaynoff, Dominique, et al. “Natural killer cell activation after infection with lactate dehydrogenase-elevating virus.” Journal of General Virology (2002): 83, 2709–2716. Web.

Introduction

Bloodstream infections are one of the most serious health conditions. They can be defined as the inflammatory response caused by the invasion of the bloodstream by bacterial or fungal microorganisms. The important task of the microbiology laboratory is to timely detect and test blood-borne pathogens. Additionally, nurses, who are generally in direct contact with patients, need to follow preventive measures, for example, handwashing, to avoid blood infections. Even though BSIs have always been a significant medical issue, the current problems are connected with the resistance of infecting organisms to antibiotics.

Goals and Solutions

In order to decrease the number of BSIs cases, it is necessary to set short- and long-term goals. The short-term solution includes educating nurses, healthcare givers, patients, and caregivers. The long-term goal is to sustain change after the initial education of the medical personnel and patients. Even though handwashing is a simple preventive measure, educating medical staff and patients about its importance may reduce the risk of BSIs. Another example is proper catheter management, which is an effective way to decrease BSIs cases in oncological settings. Members of management, educators, nurses, and patients all play a significant role in achieving long-term results.

Data Collection

Data can be collected through laboratories and from frontline nurses who are in direct contact with patients. Laboratories can assist in identifying the source of the infection and the way blood cultures are acquired, while nurses may explain the barriers to hand hygiene and other preventive measures. Finally, it would be appropriate to consult infection prevention teams. For example, The Centers for Disease Control and Prevention aims to develop strategies to prevent BSIs. According to their recommendations, the major solution is to properly train the staff in terms of hygiene at the workplace. Therefore, the ideal benchmark is to decrease the BSIs occurrence by providing high-quality personnel education.

Data Analysis

The data analysis showed that a third of mortalities are associated with bloodstream infections. Other negative outcomes include prolonged hospital stay, reduced patient satisfaction, and high hospital costs. Figure 1 demonstrates that bacteria play a more significant role in causing blood infections compared to fungi, viruses, and other microorganisms. Impaired skin integrity is the major cause of implications since it facilitates the invasion of microorganisms into the blood system. BSIs are estimated at 15% of real cases, and the prognosis for patients with blood infections is usually poor.

Improvement of Proposed Solutions and the Preferred Solution

BSIs, or sepsis, can be a threat to a patient’s life, and therefore, timely recognition and intervention are required. The major cause is connected with the use of invasive devices in patient care, such as intravenous cannulas, central lines, and urinary catheters. An unsafe clinical environment and various psychological factors also increase the risk of infection.

Therefore, care providers should be taught to conduct all invasive procedures in a safe way. It is also necessary to provide healthcare institutions with enough equipment and resources required to reduce the risk of BSIs. Moreover, research activities aimed to improve the quality of care may contribute to solving the problem of frequent BSIs occurrence. Research is the preferred solution since it addresses functional challenges and helps determine the root cause of the problem and necessary preventive measures.

Conclusion

In order to sustain the change, it is necessary to make it a part of the corporate culture. Medical institutions need to develop regulations and guidelines aimed to solve the problem of BSIs. The main measures should include research activities, implementation of findings, and evaluation of the outcomes. Moreover, it is important to understand that combatting BSIs is teamwork, where all stakeholders, including nurses and patients, play an important role.

In conclusion, bloodstream infections are one of the major problems in the field of healthcare. They are associated with poor medical prognosis and a high level of mortalities. Therefore, sterility of invasive devices, nurses’ and patients’ education, and research activities are the most effective ways of reducing the rate of BSIs occurrence.

References

Aliyu, S., Cohen, B., Liu, J., & Larson, E. (2018). Prevalence and risk factors for bloodstream infection present on hospital admission. Journal of Infection Prevention, 19(1), 37 – 42.

Bell, T., & O’Grady, N. (2017). Prevention of central line–associated bloodstream infections. Infectious Disease Clinics of North America, 31(3), 551-559.

Centers for Disease Control and Prevention (CDC). (2015). BSI. Web.

Hallam, C., Jackson, T., Rajgopal, A., & Russell, B. (2018). Establishing catheter-related bloodstream infection surveillance to drive improvement. Journal of infection prevention, 19(4), 160 – 66.

Kell, D. B., & Pretorius, E. (2015). On the translocation of bacteria and their lipopolysaccharides between blood and peripheral locations in chronic, inflammatory diseases: The central roles of LPS and LPS-induced cell death. Integrative Biology, 7(11), 1339-1377.

McLaws, M. L. (2015). The relationship between hand hygienge and healthcare-associated infections: its complicated. Infection and Drug Resistance, 8(1), 7-18.

Vijayan, A., & Boyce, J. M. (2018). 100% use of infection control procedures in hemodialysis facilities: Call to action. Clinical Journal of the American Society of Nephrology, 13(4), 671-673.

Viscoli, C. (2016). Bloodstream infections: The peak of the iceberg. Virulence, 7(3), 248-251.

Infections that occur while the provision of medical care has severe consequences, such as complications of diseases, and social and moral damage to both patients and medical personnel. One of the most urgent of such problems is urinary tract infections (UTIs). Consequences that these conditions can lead to include severe purulent septic complications, bacteremia, and other issues. Some aspects may complicate the course of infections, such as the presence of foreign bodies in the urinary tract. Bladder catheterization is among the primary sources of pathogenic spread. Catheter-associated urinary tract infections (CAUTIs) represent a considerable proportion of complications and are one of the most common in-hospital infections (De la Cruz et al., 2020). The relevance of these issues is the reason to choose a presentation’s theme.

At our workplace, we often deal with patients with urinal infections. In the case of complications, the hospital incurs additional expenses on patient retention, and the patients themselves can also receive a more significant bill. Sick people stay longer in the hospital, and medical staff needs to plan the time they usually lack to meet all patients. More importantly, although widespread, such incidents negatively affect the image of the hospital – patients may accuse staff of unprofessionalism. In such a situation, staff morale is deteriorating, and respectively efficiency and productivity fall.

The presented plan of implementation of new policies regarding the use of indwelling urinary catheters in the hospital can become a reality on conditions managers and staff are highly motivated. A possible incentive to begin implementation may be assessing the costs that the hospital carries due to CAUTIs and the possibility of preventing them. This stimulus requires additional research that will provide data to hospital managers. Their desire to change the situation could be the beginning of a new policy. However, there are many obstacles at various levels that the institution may face.

First of all, the obstacle to any changes in the receipt of funding is necessary to conduct research, find coaches, and give staff incentives. Other barriers are the time and motivation of medical staff. On the one hand, reducing the number of patients with infection is an incentive, but, on the other, the prospect is only potential and requires evidence to attract staff’s attention. Moreover, in the hospital, people work in conditions of a very limited amount of time, and training, the effectiveness of which is not apparent, will harm patients’ care. The productivity of the educational program depends on the trainer, materials, implementation strategy. If they are not good enough, there will be an additional obstacle to the implementation of the plan.

In conclusion, the severity of the consequences and the prevalence of Catheter-associated urinary tract infection (CAUTI) suggest the need for action. Patients, hospitals, and the entire healthcare sector incur additional costs due to the appearance of these infections. Moreover, any complications during treatment are dangerous to the patient and pose a threat to the hospital’s image. The measures proposed in the presentation to introduce a new policy about the use of indwelling urinary catheters are possible in our institution but require a high motivation for action from all employees. Obstacles that may appear during the implementation of changes include the search for the funding necessary for research and incentives. Moreover, the plan requires the allocation of additional staff time, the development of a clear implementation strategy, which will attract staff’s attention, and the search for a competent coach.

Reference

De la Cruz, J., Locke, M., Schmeling, S., Stump, C., & Thompson, D. (2020). CAUTI reduction. [PowerPoint slides].

Introduction

The origin of acquired immune against infectious diseases was discovered almost two thousand year earlier. In 430 BC Thucydides observed that the great plague in Athens never attacked the one who ailed once; they were either killed or recovered and were never to be tormented twice. By the end of the 18^th century, Jenner observed that immunization for small pox could be provided through a vaccination with cowpox virus, which became the basic idea behind all vaccination literature.

Today vaccination is used worldwide to provide immunity against many infectious and fatal diseases. The concept behind this vaccine which has made it so successful is that behind all viral or bacterial diseases, primary protection is though t to be provided by a long-lived biological immune response of the human body through production of antibodies in the body. This was the basis for all vaccines throughout medical history.

Tuberculosis (TB) disease is not infected by ninety percent of the people infected with Mycobacterium tuberculosis. This implies that human beings are inherently immune to TB. The people who do get infected are those who have low-immunity because of their infection with HIV or due to their low socio-economic background that characterize many TB patients. Thus, it is believed that “immune suppression, rather than an inherently inadequate immune system, is the most important determinant of predisposition to disease.” (Hanekom et al, 2007) It is further believed that an immunocompetent person may still be infected by TB, although less frequently, and the virulence nature of the infecting pathogen may transform eh scenario into a confusing one.

Presently TB vaccine research and development has been undergoing an era of renaissance. This, though, is in sharp contrast to the limited development of BCG in the first two decades of the 20^th century. This is so because after almost seventy years of development of BCG, it is the only TB vaccine available to medical science. Mostly the researches in the field have been operational which tried to innumerate areas like expanding the delivery program of BCG through Expanded Programme on Immunization, holding field trials in various geographical locations using different BCG strains (Ferguson & Simes, 1949; Aronson et al, 1958; Rosenthal et al, 1961; Vandiviere et al, 1973; Hart & Sutherland, 1977).

A meta-analysis of these studies shows that the effectiveness of the BCG vaccine varies greatly (<0% to >80%) (Colditz et al, 1994; Colditz et al, 1995) and there are various opinions regarding the effectiveness of BCG vaccine today (Rahman et al, 2001; Fine, 2001).

Research has shown that the incidence of TB in Great Britain has increased over the years (Rose et al, 2001; Nursing Times, 2007). According to statistics the reported cases of TB increased by 2 percent in England and Northern Ireland in 2007 (Nursing Times, 2007).

But research has also proven that there has been a dramatic decline in cases of TB in developed countries (Vynnycky & Fine, 1999). Given these two contradictory views, it is safe to assume that the death toll and rate of infection due to Tb has drastically gone down in developed countries like the US and the UK where proper immunization is provided to the mass. But does this indicate that TB can be eradicated completely and there would be no need for TB vaccine? This is an area that requires proper understanding regarding the present researches of TB and search for new vaccines.

In this paper, we will critically analyze the vaccination developed for tuberculosis (TB) and how the process of immunization for the bacteria takes place. Then we will try to ascertain that if TB vaccines are required in the UK with the decreased number of incidents of TB. The main aim of this paper is to facilitate an understanding of how pathogen (e.g. TB) interacts with the host producing metabolic and immunological events. In this paper we will discuss how vaccinations work to immunize human body from fatal and infectious diseases. The vaccinations which are used to prevent TB like BCG and discuss them critically. Further, this paper will try to ascertain if TB vaccination can be or should be removed from UK.

Role of Vaccine

The immune system of all humans has two distinct arms but they are interactive viz. innate and adaptive (Hanekom et al, 2007). ‘Innate’ immunity is the response that the host gives when it has its first encounter with a pathogen. This immunity is capable of providing immunity against a broad variety of microbial challenges in non-specific nature. The different cell types which belong to the innate system comprise of macrophages, which form the front line in defence against TB.

But in contrast, ‘adaptive’ immunity is pathogen specific. This is why it is also called ‘specific’ immunity. In case of ‘innate’ immunity, once the system identifies the approach of a pathogen, it tries to control its initial spread, and adaptive immunity grows within the system to deal with the specific challenge. This primary tackling of the pathogen by the adaptive design within the system is called the ‘immunological memory’, which implies that the infection is remembered by the system, which enables it to react more rapidly and vigorously when there occurs a case of re-infection with the same pathogen. For example, in case of TB, the T lymphocyte is a key example of an adaptive immune cell.

Is a TB vaccine possible?

TB Vaccine

History of TB in the UK

TB has been around in the European continent since 8000 BC (this can be said due to the presence of skeletal deformities caused due to TB has been identified). The disease reached epidemic proportions in the early 19^th century when there was a rapid growth of urban poor population due to industrialization. Historians have estimated that one-third of all the deaths in London during the period were due to TB from 1800 to 1840 (Storey, 2004). Although the disease attacked mostly the underprivileged, but its occurrence among the affluent class could not be negated.

In the early times, TB was known as “the white plague”, was not completely understood by medical science. Theories of the disease, then, were attributed to moral turpitude, to drinking of contaminated water, air and soil or to socio-economic causes particular to the locality. It was not until 1882; Robert Koch identified tubercle bacillus that the realization doomed on medical science that it could be transmitted.

This led to the confinement of the patient in his home, hospitals, or sanatoriums for such patients. Radical surgical methods were tried to remove the affected areas, other than phrenicolysis (dividing the phrenic nerve), plombage (a process of extrapleural insertion of fat, soft paraffin wax, sponge, and Lucite shpheres) and scalenectomy (process by which scalene muscle is divided) were attempted as treatments of TB.

Even though proper modern day treatment was absent in the UK along with chemotherapy, the incidence of the disease declined in the UK, mainly due to public health policy reforms and improved “nutritional status and social and physical environment of the urban poor” (Storey, 2004, p.291) in the early 20^th century. Such reforms had its origin from the belief that insanity caused this epidemic proportion disease. In 1913 it was made a law that all TB infections are to be informed to the authorities according to the National Public Health Tuberculosis Act.

The arrival of proper and effective drug therapy helped in declining the onset of TB in the UK. The introduction of radiology to be used to screen, improve surveillance, pasteurize milk, treat the contact individuals, and widespread use do BCG vaccine declined the rate of TB considerably. But in the 1980s there was a relapse of TB in the UK and reasons were more due to rise in social deprivation, HIV co-infection and a failure to control the spread of the disease.

Vaccination

In order to understand how the TB vaccines work it is important to understand the natural history of TB. When a healthy uninfected person is exposed to the source case it may lead to primary infection with Mycobacterium tuberculosis. This infection with M. tuberculosis may lead to primary TB or to a persistent asymptomatic infection, which is difficult to be diagnosed, as it remains silent throughout the person’s life.

But in case of 10 percent of immunocompetent people and 8 percent of HIV-positive individuals that such a latent infection may go undiagnosed which leads to TB. This history of TB provides avenues for three possible ways of vaccination for TB, which are “one that would prevent primary infection and disease following exposure; a second that would prevent reactivation in those already infected; and a third, an immunotherapeutic adjunct to standard TB treatment, which would speed and enhance standard TB treatment in those already ill from TB.” (Ginsberg, 2002, p.483) These different forms of immunizations are discussed in greater detail later.

Types of vaccine for TB

There are four basic types of vaccine for TB. The first comprises of one or more mycobacterial components which are thought to produce protective immunity, and comprises of almost 50 percent of the people who are identified as contracts (Ginsberg, 2002). These individuals who were given this vaccine were tested and were found to be composed of protein subunits, while a few use lipid or carbohydrate subunits. The second form of immunization is an unalloyed DNA vaccine.

And the third, is based on “love, accentuated mycobacteria, including recombinant BCGs (rBCGs) expressing immunodominant antigens and/or cytokines, attenuated strains of M. tuberculosis, and nonpathogenic mycobacteria (e.g. M. vaccae, M. smegmatis, M. microti, and M. habana)” (Ginsberg, 2002, p.484). And the fourth vaccine was made based upon live, attenuated, nonmycobacterial vectors, such as Salmonella or vaccinia virus.” (Ginsberg, 2002, p.484)

The vaccine that is currently used against TB is called bacille Calmette-Guérin (BCG), was developed by the French scientists Calmette and Guérin in the early 20^th century. BCG has been effectively used around the globe for over 80 years and has been provided to more people than any other vaccine. It has minimal side effects and is used to prevent miliary and meningeal TB in children and infants to a certain degree. But BCG fails to prevent any immunization from the most prevalent from of the disease i.e. pulmonary TB in adults. Actually, the efficacy of BCG in adults ranges from 0 to 80 percent depending on the geographic location and other socio-economic conditions (Fine, 1995).

Though a meta-analysis of the vaccination, data available shows that it has a theoretical effectiveness of 50 percent; it is prevalent knowledge that only 5 percent of the vaccine-preventable deaths caused by TB could have been prevented by BCG. Hence, it can be concluded that BCG is not a satisfactory vaccination to prevent TB. But there are still arguments regarding the need of a new vaccine to prevent TB (Kaufmann, 2000).

Kauffman even question the necessity of a vaccine when chemotherapy can completely cure TB. But the reason a preventive measure is required is due to the nature of the drugs which need to be taken for a long period of time (usually 6 months or more) and a combination of three specific drugs have to be taken to develop drug resistance. Studies have shown that compliance to the drug regime is very high and a patient suffering to chronic TB cannot be properly treated using this strategy (Kaufmann, 2000). Moreover, such therapy is expensive and cannot be accessed by the mass. Hence, there is a need to develop an effective but less costly medical prevention or treatment to fight TB.

The feasibility of TB vaccination usually receives support from the fact that less than 10 percent of the candidates infected by M. tuberculosis develop acute TB. The main cause of TB, as is believed, is due to the weakening of the immune system, which keeps the bacteria under check till the time its active. This fact is re-established due to the infection of TB to HIV positive individuals. But experiments with mice after been treated with chemotherapy show that the mice are not immune to M. tuberculosis, which shows that there is a need for vaccine against TB. Thus, the immune system fails to control the pathogen in the long run, and it gets weakened due to exogenous interventions, thus allowing reactivation of the bacteria. This explains the triggering of acute TB in BCG expressed candidates.

Even though there are a number of vaccinations available, why BCG is the most commonly used vaccine? First, even though there are a number of available vaccinations against TB, all these strains of BCG work effectively in combating TB. This is a sure prevention due to the “low dose, aerosol challenge models in mice and guinea pigs, currently considered the standard for such experiments, most closely mimic primary TB disease in a naive host” (Ginsberg, 2002, p.484). BCG helps in prevention of children and infants who are “immunologically naïve hosts” from getting infected.

Second reason behind this is that only a few animal vaccines models have provided protection as well as BCG. A few of them have provided better protection than control BCGs, which is measured by the “number of colony forming units in lung, liver, and spleen, and clinical features such as weight change and survival” (Ginsberg, 2002, p.484). Now testing of these candidates are being done for safety and immunogenicity testing in humans.

Improvement of BCG

Research is being conducted to improve BCG. Strategies being followed by a small number of researchers involve testing the effectiveness of BCG at lower doses and in a prime-boost protocol. This strategy follows the data from the deer infection model which indicates that double vaccinations delivered as a prime, followed by a booster dose are more effective than single vaccines to protect against infection and disease (Griffin et al, 1999; Griffin et al, 2001). Hoft et al. have investigated the human system’s response to BCG when delivered in various methods, to see if BCG may become more effective if the delivery method is altered (Hoft et al, 2000; Hoft & Worku, 2000). For instance, oral delivery, which was the initial method used provide better mucosal immunity then the present method of intradermal route.

Further researches are being conducted to improve using the prime-boost strategy that combines BCG (either as a boost/prime vaccine) along with a new candidate vaccine. It is expected that the two vaccines will act additively and maybe even synergistically to improve the effectiveness of BCG (Feng et al, 2001; McShane et al, 2001; Brooks et al, 2001). If BCG vaccine could be improved or be used with another vaccine then the administrative problem of commissioning a completely new vaccine could be eliminated. This would make the acceptability and usability easier and will provide better immunity.

New Vaccines

There are various new vaccines which have been introduced as substitutes of BCG. The first new candidate vaccine to enter the first phase of trials for safety and immunogenicity was an immunodominant protective antigen called Ag85A. This was made from M. tuberculosis which is expressed in individuals in the same process as vaccinia virus (MVA-Ag85A) (McShane et al, 2001). McShane and Hill have tested MVA-Ag85A in a few tuberculin skin test-positive candidates.

They expect that in order to investigate the “safety, immunogenicity, and efficacy of a BCG prime/MVA-Ag85A boost strategy” in both case of skin test positive and negative individuals will provide the desired result. They further intend to test, in similar fashion o f a prime-boost strategy, a poxvirus called FP9 while expressing Ag85A in candidates.

There are other tests which are being conducted in the UK to provide a substitute of BCG or to provide BCG along with a new vaccine following the prime-boost strategy. These have been mentioned by Ginsberg:

“Other candidates being readied for human testing in the next 6 months–2 years include: a recombinant BCG over expressing Ag85B (M. Horwitz, personal communication, 2002), in a collaborative effort with the Sequella Global TB Foundation

and the United States National Institute of Allergy and Infectious Disease; a subunit vaccine composed of M. tuberculosis-derived immunodominant fusion proteins, Ag72f+/-Ag85 (S. Reed, personal communication, 2002); a multi-epitope subunit vaccine/adjuvant combination developed by InterCell Corporation; and, potentially, attenuated mutants of M. tuberculosis being developed at Albert Einstein College of Medicine, New York, USA, and the Howard Hughes Medical Institute, New York, USA, by William Jacobs Jr (W.R. Jacobs Jr, personal communication, 2002). These attenuated strains of M. tuberculosis lack the ability to make key amino acids or vitamins and cannot survive in the host for long. The hope is this will render them safe for use, even in immunocompromised individuals.” (Ginsberg, 2002, p.485)

Jacobs et al. have made new M. tuberculosis which is said to be the inventive attenuating transmutation of M. bovis, following the same process of RD1 deletion that helped in the making of BCG (Behr et al, 1999). This process of RD1 deletion in M. tuberculosis will be helpful to test the working hypothesis that by deletion of RD1, the strain will be attenuated, but will remain in the human system for a long enough time to make the system immune and self-protective response, which would be stronger than the protection provided by BCG. This experimentation is being furthered by exploring M. tuberculosis virulence by comparing the genomes of virulent mycobacteria, and also various strains of BCG to each other and the virulent mycobacteria.

An environmental bacterium called M. vaccae is also being tested on humans. This experimentation includes a heat-inactivated investigation as a preventive vaccine in a form of 5 doses expressed in HIV-positive individuals (Waddell et al, 2000).

An alternative to BCG vaccine is required, as it has been found through research that the effectiveness of BCG vaccine differs greatly in different population. The underlying hypothesis to this effect is due to the interaction of the vaccine and microbacteria which is commonly found in the environment. But no precise mechanism as to how this affects the vaccine is yet to be found. This study was conducted on mice who were priory given BCG. The study revealed that BCG enabled only a transient immune response with low frequency of microbacterium cells and no immunity against TB (Brandt et al, 2002). The test also showed that the TB subunit vaccines had no effect after exposure to environmental microbacterium and hence provided a better protection against TB (Brandt et al, 2002).

DNA vaccines are presently being tested experimentally as an alternative to BCG (20). DNA vaccines are expected to have higher responsiveness due to their ability to induce persistent, cell emanated immune responses to antibodies isolated from various viruses, bacteria, and parasitic pathogens. In animals, DNA vaccines have been used to provide protective immunization against HIV, influenza, bovine herpesvirus, rabies, leishmaniasis, malaria, herpes simplex virus, and tuberculosis (Chattergoon et al, 1997; Donnelly et al, 1997; Huygen, 1998). So it has been tested to see its effectiveness as prevention against TB in humans.

Another new vaccine tested as TB vaccine is DNA vaccines encoding native ESAT-6, MPT-64, KatG, or HBHA mycrobacterial proteins or similar protein fused in the tissue plasminogen activator (TPA) signal sequences were tested for their capacity to combat “elicit, humoral, cell-mediated, and protective immune responses in vaccinated mice” (Li et al, 1999, p.4780). All the eight induced plasmids produced specific humoral responses, the constructs of TPA fusions created a higher antibody in vaccinated individuals.

Even though the DNA vaccines induced in vaccinated individuals created a substantial gamma interferon response in spleen, the antigen-specific response of the lung was 2 to 10 times lower than the spleen’s response during the time of infection. But the research showed that “DNA vaccines encoding the ESAT-6, MPT-64, and KatG antigens fused to TPA signal sequences evoked significant protective responses in mice aerogenically challenged with low doses of Mycobacterium tuberculosis Erdman 17 to 21 days after the final immunization.” (Li et al, 1999, p.4780) The research further indicates that the response of BCG to M. tuberculosis has greater than that of the DNA vaccines tested; the authors believe further research in the area could produce alternative results.

T cells are central to the protection of the system against TB; further development of vaccines should be focused on T-lymphocyte populations. All the vaccines which are in use today work through antibodies rather than T-cells. Moreover, most of the vaccines do not prevent infection, but try to prevent the disease but they allow the entering and settling of the pathogen in the host but simply prevent its harmful effects initially.

Further, vaccines are given in an early date when infection did not occur, which shows that vaccinations by nature are preventive rather than therapeutic. This is effective for other disease, but TB, when these tissues need to be considered. Since a large group o people who are living with the infection, a post-infection vaccine strategy must be developed. Moreover, due to the increasing concern of co-infection of HIV and MDR-TB, therapeutic vaccines need special attention.

DNA vaccination has been developed as an alternative as has been done by many researchers, who have tried a successful therapy of TB on mice by treating them with DNA construct encoding HSP60 (Lowrie & al., 1999) and ESAT-6, MPT-64, and KatG (Li et al, 1999). Thus, a vaccine which could prevent the infection with M. tuberculosis would be ideal to prevent TB as because at the time of infection the host usually encounters small number of bacterium. Thus, a theoretical experiment to prevent infection of TB exists.

In another strain, if an antibody successfully prevented and eliminated the eliminate M. tuberculosis in the alveolar stage before they reach macrophages, would provide a solution to the problem. But this possibility is yet to be conceptualized.

Vaccine induced immunity is a more likely prospect. This vaccine induced immunity will attack the pathogen once it establishes itself in the macrophages, which is exclusively done by T lymphocytes.

Table 1 show that current vaccines available. The subunit approach relies on the axiom that a few antigens are enough to trigger a protective immune response of the system. Recent research in the area of M. tuberculosis genome and due to the availability of increased information regarding gene introduced from transcriptome and proteome analyses, the availability of protective antigens is a lot (Cole & al., 1998; Jungblut & al., 1999; Behr et al, 1999). The DNA technique showed 129 types of M. tuberculosis –which are specific open reading frames unavailable in the BCG vaccine strains (Behr et al, 1999). Evidently, the M. tuberculosis genes absent in BCG are the causes for the virulence factors, but also decrease the protective antigens. This development has triggered the interest for the hunt for M. tuberculosis genes which are of interest for the development of a vaccine, as destroyers or as protective antigens.

Table 1: TB vaccine candidates.

Even though there is a plethora of literature regarding genomics and proteomics, there are no clear parameters that define protective antigens. The question that arises is if there are M. tuberculosis-specific antigens that are missing in BCG? Are they antigens which are unseen or cell-bound? Or do they possess certain unique functions? Maybe they are most profusely expressed proteins? The present research do not provide any clear understanding of all these questions or any plan of action which leaves the researchers to screen every single antigen as a possible candidate for vaccine. This is most likely best attained with naked DNA constructs, because they are easy to make and have a proven history of vaccine efficiency.

Protective antigens has been identified to belong to the antigen 85 family and hsp60 (Huygen & al., 1996; Tascon et al, 1996) and both have shown that this could protect mouse more this way than by BCG. Researchers who have been working for Malaria vaccine have identified that protective antigens with a vaccinomics approach which is a term for immunization free of the biological features of the candidate’s antigens (Hoffman et al, 1998).

On identifying the protective antigens, synthetic polypeptides uniting promiscuous defensive epitopes from numerous antigens can easily be done. The success of a protein vaccine will depends on the identification of a protective antigen and potent adjuvant which develops its immunogenicity. Even though naked DNA vaccines have substantial immunogenicity, additional developments are required in the area. Recombinant carriers comprise of attenuated salmonella and vaccination virus. The advantage of the former is that that it can be given orally and thus rouses a mucosal immune response, while the latter is a potent stimulator of CD8+ T cells. Both are equally feasible mainly in other systems.

The bacterial vaccine approach is based on the assumption that numerous antigens – proteinaceous and non-proteinaceous – naturally act together to provide maximum protection (Table 1). Additionally, entire bacterial vaccines yield from integral adjuvanticity. The methods to establish deletion of mutants in M. tuberculosis has been developed and the evidence of standard has been recognized i.e. if a single gene is deleted it can cause adequate attenuation (Berthet & al., 1998).

Assuming M. tuberculosis damages the immune reaction and thus stimulates inadequate protection, which is targeted for deletion, would comprise of classical virulence factors and immunosuppressive components. These consist of inhibitors of macrophage activation since the preeminent T cell fails when macrophages is not fully activated. Similarly, efforts have been made to develop the immunogenicity of BCG by two ways:

• by developing the CD8+ T cell stimulating capacity,
• by providing it with Th1 cell-evoking cytokines.

Another method is through engineering BCG to over-express discrete antigens, mainly due to its lack of the encoding gene and since it creates the antigen in inadequate amount.

The third method, i.e. the combination-vaccine strategy intends to unite both the approaches. According to this theory, both BCG and M. tuberculosis may be improved by merging both the options. On the other hand, as discussed earlier, prime-boost strategies, have already established their effectiveness in the investigational malaria model, are being used to make TB vaccination (Sedegah & al., 1998).

All the approaches discussed above are presently at the stage of animal experimentation or have just passed Phase I. but none have attained the efficiency of BCG. Thus, it is difficult to find a way to set a benchmark for a vaccine for TB. Here the question arises if a vaccine that provides protection equal to BCG, should it be considered inadequate? Or there should be a vaccine that can provide immunization in both pre- and post-infection stages?

It is often argued that a subunit vaccine which is as effective as BCG and provides higher degree of safety as compared to particularly in immune-compromised hosts, which provides the possibility to indentify a vaccinated and an infected candidate. Contrarily, a bacterial vaccine has to be much better than BCG if it is to be used further. In practicality, any vaccine has to prove its efficiency greater than BCG, to be accepted as a human vaccination.

Are they required in UK?

The BCG vaccine in the UK was initially provided to all children in schools within the age group of 10-14 years. But in 2005 the Department of Health made changes in its previous policy due to the fact that children in schools are not affected by TB. But the vaccination program was shifted to infants aged 0 to 12 months in areas which have high incidents of TB or whose parents or grandparents belonged to areas where there was high degree of TB. Research has shown that there is very low infection left in the country and the risk of the infection has lowered considerably (Batty, 6 July 2005; Department of Health, 2005).

So the authorities have decided that the universal vaccination programme should be stopped and the focus must shift to the areas, such as London, where the incidence of the infection is still high. Regarding this it can be said that areas which were once prone to TB infections should not be avoided too as these areas were primarily vaccinated with BCG. Research in the area shows that BCG is only helpful in preventing the infection from spreading but it does not terminate it neither does it prevent contamination of a non-infected person. So it may be possible that the infection may spread through the primary contact. So there remains chances of the infection to spread from individual to the other, if not assume the size of an acute disease in an individual. Thus, it is important to vaccinate the areas where the TB was earlier prevalent.

Another argument that must be posed in this respect is that even though it unanimous knowledge that BCG does not provide complete immunity against TB, it does not provide complete immunity. Experts are of the view that it provides immunity only to three-quarter of the people vaccinated with BCG. Thus, even the effectiveness of the vaccine is under scrutiny.

Due to the decreased trend of TB in the UK, this has gone down from 50000 cases in 1950s to 7000 per annum in the 21st century (Scottish Government, 6 July 2005). The concentration of the disease is more in urban areas and large cities. Thus, there seems to be no need to vaccinate infants in non-TB areas. But complete withdrawal of the TB vaccination program is not an option. This is because it will trigger the need to immediately develop a vaccine which will eradicate TB completely.

So as long as a new vaccine is not developed which will be able to eradicate the infection from the candidate systems, removing the vaccination program in the UK cannot be an option. This is because even though BCG is not a complete solution for TB, it does provide some benefit in terms of prevention of spreading of the disease in a system. Thus, removing of the vaccination program is a possibility only if there is a vaccine that proves to be successful in eradicating TB from the roots.

Conclusion

TB has been a scary name to all till the early 20^th century. But with the development of BCG in the 1950s there was expected to be a solution that prevents the spreading the disease and reducing fatality caused by it. This provided a clear demarcation for the use of the vaccination which was safe and reduced the incidence considerably. But with the increased incidence of HIV infections in the 1980s, the incidence of TB increased. This was so because BCG vaccinated systems helped to grow immunity against M. Tuberculosis but as the immune system grew weaker due to HIV, the infection which was still present in the system starts to spread. This increases the cases of death due to TB.

So there arose a need to develop another vaccine which could provide immunity against TB and also do away with the infection. This triggered the numerous researches which were conducted in the area to develop a vaccine which could provide better immunity to candidates than BCG. But till date such vaccination has not been developed. Some of these researches tried to make a vaccination which could be expressed in combination with BCG increasing its efficacy while others have tried to travel through a different road altogether. This latter strategy is to make a DNA vaccine which could be effectively eradicate M. Tuberculosis.

But all these researches have not passed phase I of vaccination research where the vaccines have just been tested on animals like rats or guinea pigs. Clearly there is a need for a new vaccine to be developed which could eradicate the disease.

The public health policy in the UK has changed in the UK due to the decreased incidence of TB in the country. But there are still cases of TB found in select areas. The policy presently followed is to immunize small children within the age group of 0 to 12 months with BCG vaccine. This would help them not to get infected with the bacterium.

Clearly neither the policy stance of the UK government as well as the medical research scenario provides the signal that TB could be completely eradicated from the UK in the near future. This vaccination can be done away only if there is developed a vaccination which completely kills the bacteria.

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Introduction

Medicines of plant origin have been used by man in different cultures along history. Recently plant medicines have gained popularity because of safety, biological medicinal activity, and less cost. Urinary tract infection is a term that points to infection anywhere in the urinary tract although commonly linked to cystitis. Urinary tract infection is the second common type of infection caused in 80% of cases by gram-negat bacillus E. coli. Medicinal plants play a significant role in treating and preventing urinary tract infections as disinfectants, analgesics, and diuretics (Bag and colleagues, 2008). Cranberry is a low-lying evergreen vine that grows widely in the US and was first documented in 1614 by Captain John Smith, known as the admiral of New England. By 1686 it became popular to be considered with codfish and corn as the most prized American food (Cappelloni, 2002).

Recent evidence suggests that cranberry is effective in preventing urinary tract infection as it prevents E. coli from adherence to the walls of the urinary bladder (Bag and colleagues, 2008). The aim of this essay is to provide a brief review on the use of cranberry in preventing urinary tract infection.

Cranberry: pharmacology and mechanisms of action

Early research on cranberry use to prevent urinary tract infections suggested that its action in acidifying the urine is the main pharmacologic advantage (Lynch, 2004). However, current research centers on the role played by proanthocyanidins (cranberry falvonoids) to inhibit bacterial adherence to host tissues (Duguoa and others, 2008). Harkins (2000, pp. 9-12) suggested the fructose in cranberry contributes to its antibacterial action. Research suggested that proanthocyanidins are effective against many other microorganisms like P. aeuroginosa, K. pneumonia, P. mirabilis, and S. aureus. Evidence suggests that proanthocyanidins are effective also against H. pylori in the stomach, as well as against poliovirus (Duguoa and others, 2008). Evidence from recent studies suggests high level of antioxidants and anticarcinogenic effect of cranberry (Duguoa and others, 2008).

There are two E. coli strains responsible for urinary tract infection (UTI), a non-fimbriated and P-fimbriated type; the latter is responsible for the more serious UTI (acute pyelonephritis). Since the first step in developing infection is adherence of bacteria to target tissue surface, Liu and colleagues (2006, pp. 297-305) used Atomic Force Microscopy to study P-fimbriated strain bacterial adhesion and the effects of cranberry. Their results suggested that cranberry juice block the bacterial adhesive action after exposure period less than three hours. Not only that their finding suggested acidic medium is not needed to achieve such a block, which still occurs in PH 7. However, they did not show any effect of cranberry juice on fimbriae expression although evidence suggests there maybe interaction with bacterial DNA to inhibit fimbriae expression. They concluded that cranberry juice has an immediate effect on E. coli making the organism less adhesive and thus preventing infection (Liu and colleagues, 2006).

Greenberg and others (2005, p. 875) compared the antibacterial effect of dried cranberry raisins to that of the juice or sweetened juice cocktail in a pilot study. Data from this study showed a difference in bacterial anti-adhesion activity in human urine on using a single serving of sweetened dried cranberry and raisins where there was no effect. They suggested, because of the small sample, further investigation is needed, which may further enlighten the mechanism of cranberry action.

Uses and efficacy of cranberry juice

There is evidence suggesting cranberry juice is effective against Helicobacter pylori spiral organism blamed for nearly half the cases of gastric or duodenal ulcer, and is also effective against plaque bacteria causing periodontal disease. However, there is significant research pointing to its effectiveness in prevention of urinary tract infection (Lynch, 2004).

Raz and others (2004, p. 1417) reviewed the clinical studies on cranberry juice in urinary tract infection and inferred there is no enough evidence to suggest the fruit can be used in treating UTI. However, for prevention of UTI, evidence suggested the benefit of cranberry juice in prophylaxis from UTI, with sexually active adult females showing the strongest evidence. This group is followed by elderly group where using cranberry juice is successful in reducing bacteruria. They also noticed that clinical studies on patients with high risk of UTI (like patients with neurogenic bladder) are not enough to draw conclusions.

Females are at higher risk of having UTI than males, and the risk increases during pregnancy. Given the high safety profile of cranberry juice on the mother and the fetus makes it a suitable choice for prevention of UTI for females especially during pregnancy and lactation (Duguoa and others, 2008).

Kontiokari and others (2001, p.1) studied three groups of females with urinary tract infection caused by E. coli, the first group received cranberry ­ lingonberry juice, the second received Lactobacillus GG drink, and the third control group received no intervention. Their results pointed to a significant difference in UTI recurrence rate among the three groups in favor of the first group. They inferred regular consumption of cranberry juice reduces the recurrence rate of UTI.

Wing et al (2008, p. 1367) studied the effects of cranberry juice on pregnant females with asymptomatic bacteruria. Results showed reduced frequency of recurrent asymptomatic bacteruria and UTI on daily drinking of cranberry juice. Thus, they inferred the juice has a preventive effect against UTI during pregnancy.

Older people are the second common group to suffer from UTI (Raz et al, 2004). McMurdo et al (2005, p. 256) examined the potential of cranberry juice in preventing UTI in hospitalized elderly. Results suggested significant reduction of UTI caused by E. coli in the group receiving cranberry juice compared to control; however, the overall rate of UTI showed no significant difference between the two groups.

Cranberry juice: Evidence of efficacy

Cranberry juice or in tablet forms with increased fluid intake was found more effective than increased fluid intake alone in preventing UTI in sexually active females. Stothers (2002, p.1561) inferred if cranberry juice or products are added to the conservative measure of increased fluid intake to prevent UTI in this group, this would result in 10 to 15% lesser incidence of recurrent UTI. Di Martino and colleagues (2006, pp.21-27) tested the in vitro anti adherence activity of cranberry juice on E. coli strains. They reported the resulting decrease in bacterial adherence is dose-dependent and occurs unlinked to gene encoding or antibiotic resistance phenotype. Besides, they report that cranberry juice affects adherence of E. coli strains. McMurdo and colleagues compare cranberry extract to small doses of trimethoprim for prophylaxis of urinary tract infection in elderly females. Their results suggested a narrow advantage of low doses of trimethoprim over cranberry extracts in preventing recurrent UTI in older females. Given the higher safety, lack of resistance, and absent fungus superimposed infection, they inferred cranberry extract can be a successful measure to prevent recurrent UTI in this group of patients.

Tong and others (2006, p. 1417) examined the potential of cranberry juice in the treatment of UTI by examining the antibacterial activity of cranberry juice in urine. The result showed that urine collected after drinking cranberry juice does not have either bactericidal or bacteriostatic activity against E. coli. They inferred that efficacy of cranberry juice in UTI prevention is because of its anti adherence effect combined with factors other than antibiotic like effect. Therefore, they could not recommend therapeutic use of cranberry juice in UTI treatment.

Contraindications, drug interaction and side effects of cranberry juice Cranberry fruit (processed or not) has good safety profile despite the lack of long-term safety data as a drug. Cranberry use is reported to increase the absorption of vitamin B12 in patients receiving proton pump inhibitors for the treatment of gastric ulcers. Because of it its effect acidifying the urine, cranberry may cause the kidneys to excrete weakly alkaline drugs (like antidepressants) more quickly; thus reducing their effectiveness (Lynch, 2004).

Cranberry may cause significant rise in the urinary oxalate level; therefore with excessive use (around four liters a day), individuals with tendency to form urinary tract stones may be at increased risk. Excessive use may also be associated with gastrointestinal upsets like diarrhea especially in children and young adults (Duguoa and others, 2008).

Cranberry is not known to interact with drugs; however, there are reports of interaction with warfarin. These reports point to increased antithrombotic effects of warfarin when administered in patients receiving cranberry fruits. This may be because the juice inhibits the activity of cytochrome P450-2C9 enzyme responsible for metabolism of S-warfarin (metabolized derivative responsible for anticoagulant effect) resulting in higher plasma levels and accordingly increased anticoagulant effect (Greenblatt and von Moltke, 2005).

Conclusion

There is evidence that cranberry juice is useful to prevent urinary tract infections especially in adult sexually active females. However there is no clear evidence about the amount and concentration to be takes, therefore further research is needed to determine its efficacy in prevention of UTI in susceptible population. There is a need to study the effect of other forms of cranberry as capsules, tablets or other products.

References

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