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Immunological Correlates of Vaccine-Mediated Protection

1 Introduction Today considerable effort is undertaken during vaccine development to identify and measure potential mechanisms of immunological protection. These proposed measurements are then validated by correlation with protection from disease after natural exposure or passive protection, or alternatively related to vaccine efficacy or effectiveness endpoints. The desire to identify correlates of protection, especially early in the development of a vaccine, is more than scientific curiosity.…

How are Vaccines Assessed in Clinical Trials?

1 The vaccine testing paradigm Advances in biotechnology and knowledge of ways to enhance immune responses and immunologic memory have revolutionized the field of human vaccine development, resulting in a vaccine “pipeline” that in recent decades has led to the licensure of many new and improved vaccines. However, a candidate vaccine faces a long, arduous, and expensive road, replete with obstacles, as it commences the journey…

Vaccine Production: Main Steps and Considerations

The vast majority of the more than 1 billion doses of vaccines manufactured worldwide each year are given to perfectly healthy people. It is this fact that drives the requirements for vaccines to be among the most rigorously designed, monitored, and compliant products manufactured today. This chapter provides a high-level overview of typical manufacturing processes for major vaccine types, outlines important considerations in the development and…

Vaccine Adjuvants

The widespread use of effective vaccines against infectious diseases has been one of the most important public health advances in the 20th and 21st centuries. Early vaccines consisting of attenuated or inactivated pathogens or toxins may elicit robust, protective immune responses, but this approach cannot always be used because it is impractical to culture large numbers of organisms, lack of efficacy, or because of safety concerns.…

Vaccine Design in the 21st Century

1 Introduction Vaccines are well-established medical interventions capable of preventing infectious disease. There are many notable vaccine success stories, starting more than 200 years ago with the earliest work by Jenner that led to a cowpox-based immunization to prevent smallpox disease. Subsequent work by Pasteur during the 19th century refined and consolidated the basis of vaccinology through the principles of isolation, inactivation, and administration of key…

How Vaccines Work

1 Introduction Most of the current vaccines are delivered through intramuscular or subcutaneous injection. What happens between the injection, the early reaction, and the induction of protective mechanisms is explained in this chapter. Vaccine responses depend on their interaction with the immune system and understanding the main features of this interaction may help designing vaccines and defining optimal vaccination strategies. Five steps are involved: (1) initial…

Vaccine Basics and the Development and Rollout of COVID-19 Vaccines

Historical Introduction to Vaccines At the end of 2019, a novel human pathogen was first identified in China and resulted in a pandemic that posed the greatest infectious threat that humans had encountered in modern times. The virus responsible for the pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), soon infected hundreds of millions of people, resulting in millions of deaths worldwide. To develop a critical…

Novel Therapeutic Targets for SARS-CoV-2 and COVID-19

Factors That Affect Therapy for Treatment of COVID-19 Symptoms Symptoms of COVID-19 are many , ; some of them are as mild as those of normal influenza and others quite severe. Treatment provided to a patient with mild COVID-19 symptoms may be different from given to one with more serious symptoms such as difficulty of breathing. COVID-19 may lead to a few other manifestations such as…

Therapeutics for COVID-19

Evolution of Therapeutic Approaches The deadly novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), spread like wildfire across the entire world in the first exceptionally severe pandemic of the 21st century. Humanity had last seen a comparable worldwide viral infection in the 20th century, with the 1918 influenza pandemic caused by an H1N1 virus that infected approximately one-third of…

COVID-19: Emergency Medicine Perspectives

OUTLINE Introduction, 268 Clinical Manifestations, 268 History, 269 Physical Examination, 269 Pulmonary, 269 Ear, Nose, and Throat, 269 Neurological, 269 Gastrointestinal, 269 Diagnostic Workup and Investigation, 269 Laboratory Evaluation, 269 Imaging, 271 Consultation, 271 Management, 271 Symptomatic Support, 271 Home Oxygen, 272 Medications, 272 Respiratory Support, 273 Coronavirus Disease–Associated Acute Respiratory Distress Syndrome and Intubation, 273 Invasive Procedures and Hemodynamic Support, 274 Disposition, 274 Admission, 275…

Antiparasitic Agents

In this chapter, antiparasitic therapy is organized into five categories: (1) agents active against luminal protozoans, (2) agents active against the kinetoplastid protozoans, (3) agents active against malarial parasites, (4) antibacterial agents with antiprotozoan activity, and (5) anthelmintics. These divisions are somewhat arbitrary because some drugs are pertinent to more than one category. Appendix 296.1 , which describes the drugs for parasitic infections, is arranged by…

Antiviral Agents

In 1963, idoxuridine became the first antiviral compound to be licensed by the US Food and Drug Administration (FDA) for the topical treatment of herpes simplex virus (HSV) keratitis. This was followed shortly by licensure of amantadine in 1966 as the first systemic antiviral compound for the treatment of influenza A infection. During the 1970s, only vidarabine (1976) received licensure for the systemic treatment of HSV…

Topical Antimicrobial Agents

Topical antimicrobial therapy dates to ancient times when a wide variety of substances such as grease, lint oil, wine, and metallic salts were applied to wounds. Since then, topical antibiotics have been developed. They are most frequently used to treat infections affecting the skin and mucous membranes. Agents include topical preparations of parenterally administered antibiotics and antibiotics and antiseptics not given by any other route because…

Antifungal Agents

Fungal infections in children generally can be divided into superficial infections that affect persons with normal immune systems and invasive infections that occur primarily in children who are immunocompromised. Children can be immunocompromised due to genetic defects, pre-term birth, hematopoietic cell or solid organ transplantation, or following one of the chemotherapeutic regimens used for childhood malignancies. Improved treatments for malignancy and increasing success in the treatment…

Antibacterial Agents

Antibacterial agents, their mechanism of action, spectrum of antibacterial activity, patterns of antibiotic resistance, and current clinical use are presented in this chapter. Fig. 292.1 summarizes the main sites of antibacterial agent activity. Chapter 289 provides the principles regarding the selection of agents based on the characteristics of the patient and co-morbidities, site(s) of infection, likely pathogen(s) and antibiotic susceptibilities, antibiotic tissue exposure, and consideration of…

Pharmacokinetic and Pharmacodynamic Basis of Optimal Antimicrobial Therapy

Acknowledgment The authors acknowledgment contributions of Michael D. Reed to this chapter in previous editions. As clinicians continuously strive to practice evidence-based medicine, the use of antibiotics can be frustratingly empiric. Ethical concerns, multiple confounding variables, and unclear endpoints hamper clinical infectious disease research. This empiricism is clear in most recommendations for antibiotic dosing and duration of therapy, especially in children, because only a fraction of…

Mechanisms and Detection of Antimicrobial Resistance

Microorganisms have survived for millions of years because of their ability to adapt to hostile environments. Since the 1940s, bacteria that cause human infections have been exposed to ever-increasing antimicrobial pressure as a result of appropriate and inappropriate use of these agents. In the US, investigators have estimated that >7 million pounds of antimicrobial agents are consumed annually by humans. Approximately 80% of all antibiotics sold…

Principles of Anti-Infective Therapy

The selection of optimal antibiotic therapy for presumed bacterial infection is based on the assessment of the balance of benefits and risks of specific therapy for each child. Prescribing the right antibiotic(s) early in the course of a serious infection can save a life or avoid substantial morbidity. Antibiotic therapy given to a child without bacterial infection exposes the child needlessly to antibiotic toxicities and other…

Use of Common Clinical Laboratory Tests to Assess Infectious and Inflammatory Diseases

Acute Phase Response Stimuli of many kinds, including infection, trauma, hemorrhage, or ischemia, activate the innate immune system through binding of pathogen-associated molecular patterns (PAMPs) and/or danger-associated molecular patterns (DAMPs) to pattern-recognition receptors (PRRs) on the surface of neutrophils, monocytes, and a variety of other cells. These events lead to the release of multiple proinflammatory cytokines, including interleukin1β (IL-1β), IL-6, IL-8, and tumor necrosis factor (TNF).…