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14.1: Characteristics of Infectious Diseases - Biology

14.1: Characteristics of Infectious Diseases - Biology


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Skills to Develop

  • Distinguish between signs and symptoms of disease
  • Explain the difference between a communicable disease and a noncommunicable disease
  • Compare different types of infectious diseases, including iatrogenic, nosocomial, and zoonotic diseases
  • Identify and describe the stages of an acute infectious disease in terms of number of pathogens present and severity of signs and symptoms

A disease is any condition in which the normal structure or functions of the body are damaged or impaired. Physical injuries or disabilities are not classified as disease, but there can be several causes for disease, including infection by a pathogen, genetics (as in many cancers or deficiencies), noninfectious environmental causes, or inappropriate immune responses. Our focus in this chapter will be on infectious diseases, although when diagnosing infectious diseases, it is always important to consider possible noninfectious causes.

Signs and Symptoms of Disease

An infection is the successful colonization of a host by a microorganism. Infections can lead to disease, which causes signs and symptoms resulting in a deviation from the normal structure or functioning of the host. Microorganisms that can cause disease are known as pathogens.

The signs of disease are objective and measurable, and can be directly observed by a clinician. Vital signs, which are used to measure the body’s basic functions, include body temperature (normally 37 °C [98.6 °F]), heart rate (normally 60–100 beats per minute), breathing rate (normally 12–18 breaths per minute), and blood pressure (normally between 90/60 and 120/80 mm Hg). Changes in any of the body’s vital signs may be indicative of disease. For example, having a fever (a body temperature significantly higher than 37 °C or 98.6 °F) is a sign of disease because it can be measured.

In addition to changes in vital signs, other observable conditions may be considered signs of disease. For example, the presence of antibodies in a patient’s serum (the liquid portion of blood that lacks clotting factors) can be observed and measured through blood tests and, therefore, can be considered a sign. However, it is important to note that the presence of antibodies is not always a sign of an active disease. Antibodies can remain in the body long after an infection has resolved; also, they may develop in response to a pathogen that is in the body but not currently causing disease.

Unlike signs, symptoms of disease are subjective. Symptoms are felt or experienced by the patient, but they cannot be clinically confirmed or objectively measured. Examples of symptoms include nausea, loss of appetite, and pain. Such symptoms are important to consider when diagnosing disease, but they are subject to memory bias and are difficult to measure precisely. Some clinicians attempt to quantify symptoms by asking patients to assign a numerical value to their symptoms. For example, the Wong-Baker Faces pain-rating scale asks patients to rate their pain on a scale of 0–10. An alternative method of quantifying pain is measuring skin conductance fluctuations. These fluctuations reflect sweating due to skin sympathetic nerve activity resulting from the stressor of pain.1

A specific group of signs and symptoms characteristic of a particular disease is called a syndrome. Many syndromes are named using a nomenclature based on signs and symptoms or the location of the disease. Table (PageIndex{1}) lists some of the prefixes and suffixes commonly used in naming syndromes.

Table (PageIndex{1}):Nomenclature of Symptoms
AffixMeaningExample
cyto-cellcytopenia: reduction in the number of blood cells
hepat-of the liverhepatitis: inflammation of the liver
-pathydiseaseneuropathy: a disease affecting nerves
-emiaof the bloodbacteremia: presence of bacteria in blood
-itisinflammationcolitis: inflammation of the colon
-lysisdestructionhemolysis: destruction of red blood cells
-omatumorlymphoma: cancer of the lymphatic system
-osisdiseased or abnormal conditionleukocytosis: abnormally high number of white blood cells
-dermaof the skinkeratoderma: a thickening of the skin

Clinicians must rely on signs and on asking questions about symptoms, medical history, and the patient’s recent activities to identify a particular disease and the potential causative agent. Diagnosis is complicated by the fact that different microorganisms can cause similar signs and symptoms in a patient. For example, an individual presenting with symptoms of diarrhea may have been infected by one of a wide variety of pathogenic microorganisms. Bacterial pathogens associated with diarrheal disease include Vibrio cholerae, Listeria monocytogenes, Campylobacter jejuni, and enteropathogenic Escherichia coli (EPEC). Viral pathogens associated with diarrheal disease include norovirus and rotavirus. Parasitic pathogens associated with diarrhea include Giardia lamblia and Cryptosporidium parvum. Likewise, fever is indicative of many types of infection, from the common cold to the deadly Ebola hemorrhagic fever.

Finally, some diseases may be asymptomatic or subclinical, meaning they do not present any noticeable signs or symptoms. For example, most individual infected with herpes simplex virus remain asymptomatic and are unaware that they have been infected.

Exercise (PageIndex{2})

Explain the difference between signs and symptoms.

Classifications of Disease

The World Health Organization’s (WHO) International Classification of Diseases (ICD) is used in clinical fields to classify diseases and monitor morbidity (the number of cases of a disease) and mortality (the number of deaths due to a disease). In this section, we will introduce terminology used by the ICD (and in health-care professions in general) to describe and categorize various types of disease.

An infectious disease is any disease caused by the direct effect of a pathogen. A pathogen may be cellular (bacteria, parasites, and fungi) or acellular (viruses, viroids, and prions). Some infectious diseases are also communicable, meaning they are capable of being spread from person to person through either direct or indirect mechanisms. Some infectious communicable diseases are also considered contagious diseases, meaning they are easily spread from person to person. Not all contagious diseases are equally so; the degree to which a disease is contagious usually depends on how the pathogen is transmitted. For example, measles is a highly contagious viral disease that can be transmitted when an infected person coughs or sneezes and an uninfected person breathes in droplets containing the virus. Gonorrhea is not as contagious as measles because transmission of the pathogen (Neisseria gonorrhoeae) requires close intimate contact (usually sexual) between an infected person and an uninfected person.

Diseases that are contracted as the result of a medical procedure are known as iatrogenic diseases. Iatrogenic diseases can occur after procedures involving wound treatments, catheterization, or surgery if the wound or surgical site becomes contaminated. For example, an individual treated for a skin wound might acquire necrotizing fasciitis (an aggressive, “flesh-eating” disease) if bandages or other dressings became contaminated by Clostridium perfringens or one of several other bacteria that can cause this condition.

Diseases acquired in hospital settings are known as nosocomial diseases. Several factors contribute to the prevalence and severity of nosocomial diseases. First, sick patients bring numerous pathogens into hospitals, and some of these pathogens can be transmitted easily via improperly sterilized medical equipment, bed sheets, call buttons, door handles, or by clinicians, nurses, or therapists who do not wash their hands before touching a patient. Second, many hospital patients have weakened immune systems, making them more susceptible to infections. Compounding this, the prevalence of antibiotics in hospital settings can select for drug-resistant bacteria that can cause very serious infections that are difficult to treat.

Certain infectious diseases are not transmitted between humans directly but can be transmitted from animals to humans. Such a disease is called zoonotic disease (or zoonosis). According to WHO, a zoonosis is a disease that occurs when a pathogen is transferred from a vertebrate animal to a human; however, sometimes the term is defined more broadly to include diseases transmitted by all animals (including invertebrates). For example, rabies is a viral zoonotic disease spread from animals to humans through bites and contact with infected saliva. Many other zoonotic diseases rely on insects or other arthropods for transmission. Examples include yellow fever (transmitted through the bite of mosquitoes infected with yellow fever virus) and Rocky Mountain spotted fever (transmitted through the bite of ticks infected with Rickettsia rickettsii).

In contrast to communicable infectious diseases, a noncommunicable infectious disease is not spread from one person to another. One example is tetanus, caused by Clostridium tetani, a bacterium that produces endospores that can survive in the soil for many years. This disease is typically only transmitted through contact with a skin wound; it cannot be passed from an infected person to another person. Similarly, Legionnaires disease is caused by Legionella pneumophila, a bacterium that lives within amoebae in moist locations like water-cooling towers. An individual may contract Legionnaires disease via contact with the contaminated water, but once infected, the individual cannot pass the pathogen to other individuals.

In addition to the wide variety of noncommunicable infectious diseases, noninfectious diseases (those not caused by pathogens) are an important cause of morbidity and mortality worldwide. Noninfectious diseases can be caused by a wide variety factors, including genetics, the environment, or immune system dysfunction, to name a few. For example, sickle cell anemia is an inherited disease caused by a genetic mutation that can be passed from parent to offspring (Figure (PageIndex{1})). Other types of noninfectious diseases are listed in Table (PageIndex{2}).

Table (PageIndex{2}): Types of Noninfectious Diseases
TypeDefinitionExample
InheritedA genetic diseaseSickle cell anemia
CongenitalDisease that is present at or before birthDown syndrome
DegenerativeProgressive, irreversible loss of functionParkinson disease (affecting central nervous system)
Nutritional deficiencyImpaired body function due to lack of nutrientsScurvy (vitamin C deficiency)
EndocrineDisease involving malfunction of glands that release hormones to regulate body functionsHypothyroidism – thyroid does not produce enough thyroid hormone, which is important for metabolism
NeoplasticAbnormal growth (benign or malignant)Some forms of cancer
IdiopathicDisease for which the cause is unknownIdiopathic juxtafoveal retinal telangiectasia (dilated, twisted blood vessels in the retina of the eye)


Figure (PageIndex{1}): Blood smears showing two diseases of the blood. (a) Malaria is an infectious, zoonotic disease caused by the protozoan pathogen Plasmodium falciparum (shown here) and several other species of the genus Plasmodium. It is transmitted by mosquitoes to humans. (b) Sickle cell disease is a noninfectious genetic disorder that results in abnormally shaped red blood cells, which can stick together and obstruct the flow of blood through the circulatory system. It is not caused by a pathogen, but rather a genetic mutation. (credit a: modification of work by Centers for Disease Control and Prevention; credit b: modification of work by Ed Uthman)

Lists of common infectious diseases can be found at the following Centers for Disease Control and Prevention (CDC), World Health Organization (WHO), and International Classification of Diseases websites.

Exercise (PageIndex{3})

  1. Describe how a disease can be infectious but not contagious.
  2. Explain the difference between iatrogenic disease and nosocomial disease.

The five periods of disease (sometimes referred to as stages or phases) include the incubation, prodromal, illness, decline, and convalescence periods (Figure (PageIndex{2})). The incubation period occurs in an acute disease after the initial entry of the pathogen into the host (patient). It is during this time the pathogen begins multiplying in the host. However, there are insufficient numbers of pathogen particles (cells or viruses) present to cause signs and symptoms of disease. Incubation periods can vary from a day or two in acute disease to months or years in chronic disease, depending upon the pathogen. Factors involved in determining the length of the incubation period are diverse, and can include strength of the pathogen, strength of the host immune defenses, site of infection, type of infection, and the size infectious dose received. During this incubation period, the patient is unaware that a disease is beginning to develop.

Figure (PageIndex{2}): The progression of an infectious disease can be divided into five periods, which are related to the number of pathogen particles (red) and the severity of signs and symptoms (blue).

The prodromal period occurs after the incubation period. During this phase, the pathogen continues to multiply and the host begins to experience general signs and symptoms of illness, which typically result from activation of the immune system, such as fever, pain, soreness, swelling, or inflammation. Usually, such signs and symptoms are too general to indicate a particular disease. Following the prodromal period is the period of illness, during which the signs and symptoms of disease are most obvious and severe.

The period of illness is followed by the period of decline, during which the number of pathogen particles begins to decrease, and the signs and symptoms of illness begin to decline. However, during the decline period, patients may become susceptible to developing secondary infections because their immune systems have been weakened by the primary infection. The final period is known as the period of convalescence. During this stage, the patient generally returns to normal functions, although some diseases may inflict permanent damage that the body cannot fully repair.

Infectious diseases can be contagious during all five of the periods of disease. Which periods of disease are more likely to associated with transmissibility of an infection depends upon the disease, the pathogen, and the mechanisms by which the disease develops and progresses. For example, with meningitis (infection of the lining of brain), the periods of infectivity depend on the type of pathogen causing the infection. Patients with bacterial meningitis are contagious during the incubation period for up to a week before the onset of the prodromal period, whereas patients with viral meningitis become contagious when the first signs and symptoms of the prodromal period appear. With many viral diseases associated with rashes (e.g., chickenpox, measles, rubella, roseola), patients are contagious during the incubation period up to a week before the rash develops. In contrast, with many respiratory infections (e.g., colds, influenza, diphtheria, strep throat, and pertussis) the patient becomes contagious with the onset of the prodromal period. Depending upon the pathogen, the disease, and the individual infected, transmission can still occur during the periods of decline, convalescence, and even long after signs and symptoms of the disease disappear. For example, an individual recovering from a diarrheal disease may continue to carry and shed the pathogen in feces for some time, posing a risk of transmission to others through direct contact or indirect contact (e.g., through contaminated objects or food).

Exercise (PageIndex{4})

Name some of the factors that can affect the length of the incubation period of a particular disease.

Acute and Chronic Diseases

The duration of the period of illness can vary greatly, depending on the pathogen, effectiveness of the immune response in the host, and any medical treatment received. For an acute disease, pathologic changes occur over a relatively short time (e.g., hours, days, or a few weeks) and involve a rapid onset of disease conditions. For example, influenza (caused by Influenzavirus) is considered an acute disease because the incubation period is approximately 1–2 days. Infected individuals can spread influenza to others for approximately 5 days after becoming ill. After approximately 1 week, individuals enter the period of decline.

For a chronic disease, pathologic changes can occur over longer time spans (e.g., months, years, or a lifetime). For example, chronic gastritis (inflammation of the lining of the stomach) is caused by the gram-negative bacterium Helicobacter pylori. H. pylori is able to colonize the stomach and persist in its highly acidic environment by producing the enzyme urease, which modifies the local acidity, allowing the bacteria to survive indefinitely.2 Consequently, H. pylori infections can recur indefinitely unless the infection is cleared using antibiotics.3 Hepatitis B virus can cause a chronic infection in some patients who do not eliminate the virus after the acute illness. A chronic infection with hepatitis B virus is characterized by the continued production of infectious virus for 6 months or longer after the acute infection, as measured by the presence of viral antigen in blood samples.

In latent diseases, as opposed to chronic infections, the causal pathogen goes dormant for extended periods of time with no active replication. Examples of diseases that go into a latent state after the acute infection include herpes(herpes simplex viruses [HSV-1 and HSV-2]), chickenpox (varicella-zoster virus [VZV]), and mononucleosis (Epstein-Barr virus [EBV]). HSV-1, HSV-2, and VZV evade the host immune system by residing in a latent form within cells of the nervous system for long periods of time, but they can reactivate to become active infections during times of stress and immunosuppression. For example, an initial infection by VZV may result in a case of childhood chickenpox, followed by a long period of latency. The virus may reactivate decades later, causing episodes of shingles in adulthood. EBV goes into latency in B cells of the immune system and possibly epithelial cells; it can reactivate years later to produce B-cell lymphoma.

Exercise (PageIndex{5})

Explain the difference between latent disease and chronic disease.

  • In an infection, a microorganism enters a host and begins to multiply. Some infections cause disease, which is any deviation from the normal function or structure of the host.
  • Signs of a disease are objective and are measured. Symptoms of a disease are subjective and are reported by the patient.
  • Diseases can either be noninfectious (due to genetics and environment) or infectious (due to pathogens). Some infectious diseases are communicable (transmissible between individuals) or contagious (easily transmissible between individuals); others are noncommunicable, but may be contracted via contact with environmental reservoirs or animals (zoonoses)
  • Nosocomial diseases are contracted in hospital settings, whereas iatrogenic disease are the direct result of a medical procedure
  • An acute disease is short in duration, whereas a chronic disease lasts for months or years. Latent diseases last for years, but are distinguished from chronic diseases by the lack of active replication during extended dormant periods.
  • The periods of disease include the incubation period, the prodromal period, the period of illness, the period of decline, and the period of convalescence. These periods are marked by changes in the number of infectious agents and the severity of signs and symptoms.

Footnotes

  1. 1 F. Savino et al. “Pain Assessment in Children Undergoing Venipuncture: The Wong–Baker Faces Scale Versus Skin Conductance Fluctuations.” PeerJ 1 (2013):e37; https://peerj.com/articles/37/
  2. 2 J.G. Kusters et al. Pathogenesis of Helicobacter pylori Infection. Clinical Microbiology Reviews 19 no. 3 (2006):449–490.
  3. 3 N.R. Salama et al. “Life in the Human Stomach: Persistence Strategies of the Bacterial Pathogen Helicobacter pylori.” Nature Reviews Microbiology 11 (2013):385–399.
  4. 4 C. Owens. “P. aeruginosa survives in sinks 10 years after hospital outbreak.” 2015. http://www.healio.com/infectious-dis...pital-outbreak

Contributor

  • Nina Parker, (Shenandoah University), Mark Schneegurt (Wichita State University), Anh-Hue Thi Tu (Georgia Southwestern State University), Philip Lister (Central New Mexico Community College), and Brian M. Forster (Saint Joseph’s University) with many contributing authors. Original content via Openstax (CC BY 4.0; Access for free at https://openstax.org/books/microbiology/pages/1-introduction)


14.1: Characteristics of Infectious Diseases - Biology

As molecular techniques for identifying and detecting microorganisms in the clinical microbiology laboratory have become routine, questions about the cost of these techniques and their contribution to patient care need to be addressed. Molecular diagnosis is most appropriate for infectious agents that are difficult to detect, identify, or test for susceptibility in a timely fashion with conventional methods.

The tools of molecular biology have proven readily adaptable for use in the clinical diagnostic laboratory and promise to be extremely useful in diagnosis, therapy, and epidemiologic investigations and infection control (1,2). Although technical issues such as ease of performance, reproducibility, sensitivity, and specificity of molecular tests are important, cost and potential contribution to patient care are also of concern (3). Molecular methods may be an improvement over conventional microbiologic testing in many ways. Currently, their most practical and useful application is in detecting and identifying infectious agents for which routine growth-based culture and microscopy methods may not be adequate (47).

Nucleic acid-based tests used in diagnosing infectious diseases use standard methods for isolating nucleic acids from organisms and clinical material and restriction endonuclease enzymes, gel electrophoresis, and nucleic acid hybridization techniques to analyze DNA or RNA (6). Because the target DNA or RNA may be present in very small amounts in clinical specimens, various signal amplification and target amplification techniques have been used to detect infectious agents in clinical diagnostic laboratories (5,6). Although mainly a research tool, nucleic acid sequence analysis coupled with target amplification is clinically useful and helps detect and identify previously uncultivatable organisms and characterize antimicrobial resistance gene mutations, thus aiding both diagnosis and treatment of infectious diseases (5,8,9). Automation and high-density oligonucleotide probe arrays (DNA chips) also hold great promise for characterizing microbial pathogens (6).

Although most clinicians and microbiologists enthusiastically welcome the new molecular tests for diagnosing infectious disease, the high cost of these tests is of concern (3). Despite the probability that improved patient outcome and reduced cost of antimicrobial agents and length of hospital stay will outweigh the increased laboratory costs incurred through the use of molecular testing, such savings are difficult to document (3,10,11). Much of the justification for expenditures on molecular testing is speculative (11) however, the cost of equipment, reagents, and trained personnel is real and substantial, and reimbursement issues are problematic (3,11). Given these concerns, a facility's need for molecular diagnostic testing for infectious diseases should be examined critically by the affected clinical and laboratory services. In many instances, careful overseeing of test ordering and prudent use of a reference laboratory may be the most viable options.

Practical Applications of Molecular Methods in the Clinical Microbiology Laboratory

Commercial kits for the molecular detection and identification of infectious pathogens have provided a degree of standardization and ease of use that has facilitated the introduction of molecular diagnostics into the clinical microbiology laboratory (Table 1). The use of nucleic acid probes for identifying cultured organisms and for direct detection of organisms in clinical material was the first exposure that most laboratories had to commercially available molecular tests. Although these probe tests are still widely used, amplification-based methods are increasingly employed for diagnosis, identification and quantitation of pathogens, and characterization of antimicrobial-drug resistance genes. Commercial amplification kits are available for some pathogens (Table 1), but some clinically important pathogens require investigator-designed or "home-brew" methods (Table 2). In addition, molecular strain typing, or genotyping, has proven useful in guiding therapeutic decisions for certain viral pathogens and for epidemiologic investigation and infection control (2,12).

Detection and Identification of Pathogens Without Target Amplification

Commercial kits containing non-isotopically labeled nucleic acid probes are available for direct detection of pathogens in clinical material and identification of organisms after isolation in culture (Table 1). Use of solution-phase hybridization has allowed tests to be performed singly or in batches in a familiar microwell format.

Although direct detection of organisms in clinical specimens by nucleic acid probes is rapid and simple, it suffers from lack of sensitivity. Most direct probe detection assays require at least 10 4 copies of nucleic acid per microliter for reliable detection, a requirement rarely met in clinical samples without some form of amplification. Amplification of the detection signal after probe hybridization improves sensitivity to as low as 500 gene copies per microliter and provides quantitative capabilities. This approach has been used extensively for quantitative assays of viral load (HIV, hepatitis B virus [HBV] and hepatitis C virus [HCV]) (Table 1) but does not match the analytical sensitivity of target amplification-based methods, such as polymerase chain reaction (PCR), for detecting organisms.

The commercial probe systems that use solution-phase hybridization and chemiluminescence for direct detection of infectious agents in clinical material include the PACE2 products of Gen-Probe and the hybrid capture assay systems of Digene and Murex (Table 1). These systems are user friendly, have a long shelf life, and are adaptable to small or large numbers of specimens. The PACE2 products are designed for direct detection of both Neisseria gonorrhoeae and Chlamydia trachomatis in a single specimen (one specimen, two separate probes). The hybrid capture systems detect human papilloma virus (HPV) in cervical scrapings, herpes simplex virus (HSV) in vesicle material, and cytomegalovirus (CMV) in blood and other fluids. All these tests have demonstrated sensitivity exceeding that of culture or immunologic methods for detecting the respective pathogens but are less sensitive than PCR or other target amplification-based methods.

The signal amplification-based probe methods for detection and quantitation of viruses (HBV, HCV, HIV) are presented in an enzyme immunoassay-like format and include branched chain DNA probes (Chiron) and QB replicase (Gene-Trak) methods (Table 1). These methods are not as sensitive as target amplification-based methods for detection of viruses however, the quantitative results have proven useful for determining viral load and prognosis and for monitoring response to therapy (13).

Probe hybridization is useful for identifying slow-growing organisms after isolation in culture using either liquid or solid media. Identification of mycobacteria and other slow-growing organisms such as the dimorphic fungi (Histoplasma capsulatum, Coccidioides immitis, and Blastomyces dermatitidis) has certainly been facilitated by commercially available probes. All commercial probes for identifying organisms are produced by Gen-Probe and use acridinium ester-labeled probes directed at species-specific rRNA sequences (Table 1). Gen-Probe products are available for the culture identification of Mycobacterium tuberculosis, M. avium-intracellulare complex, M. gordonae, M. kansasii, Cryptococcus neoformans, the dimorphic fungi (listed above), N. gonorrhoeae, Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae, Enterococcus spp., S. agalactiae, and Listeria monocytogenes. The sensitivity and specificity of these probes are excellent, and they provide species identification within one working day. Because most of the bacteria listed, plus C. neoformans, can be easily and efficiently identified by conventional methods within 1 to 2 days, many of these probes have not been widely used. The mycobacterial probes, on the other hand, are accepted as mainstays for the identification of M. tuberculosis and related species (7).

Nucleic Acid Amplification

Nucleic acid amplification provides the ability to selectively amplify specific targets present in low concentrations to detectable levels thus, amplification-based methods offer superior performance, in terms of sensitivity, over the direct (non-amplified) probe-based tests. PCR (Roche Molecular Systems, Branchburg, NJ) was the first such technique to be developed and because of its flexibility and ease of performance remains the most widely used molecular diagnostic technique in both research and clinical laboratories. Several different amplification-based strategies have been developed and are available commercially (Table 1). Commercial amplification-based molecular diagnostic systems for infectious diseases have focused largely on systems for detecting N. gonorrhoeae, C. trachomatis, M. tuberculosis, and specific viral infections (HBV, HCV, HIV, CMV, and enterovirus) (Table 1). Given the adaptability of PCR, numerous additional infectious pathogens have been detected by investigator-developed or home-brew PCR assays (5) (Table 2). In many instances, such tests provide important and clinically relevant information that would otherwise be unavailable since commercial interests have been slow to expand the line of products available to clinical laboratories. In addition to qualitative detection of viruses, quantitation of viral load in clinical specimens is now recognized to be of great importance for the diagnosis, prognosis, and therapeutic monitoring for HCV, HIV, HBV, and CMV (13). Both PCR and nucleic acid strand-based amplification systems are available for quantitation of one or more viruses (Table 1).

The adaptation of amplification-based test methods to commercially available kits has served to optimize user acceptability, prevent contamination, standardize reagents and testing conditions, and make automation a possibility. It is not clear to what extent the levels of detection achievable by the different amplification strategies differ. None of the newer methods provides a level of sensitivity greater than that of PCR. In choosing a molecular diagnostic system, one should consider the range of tests available, suitability of the method to workflow, and cost (6). Choosing one amplification-based method that provides testing capabilities for several pathogens is certainly practical.

Amplification-based methods are also valuable for identifying cultured and non-cultivatable organisms (5). Amplification reactions may be designed to rapidly identify an acid-fast organism as M. tuberculosis or may amplify a genus-specific or "universal" target, which then is characterized by using restriction endonuclease digestion, hybridization with multiple probes, or sequence determination to provide species or even subspecies delineation (4,5,14). Although identification was initially applied to slow-growing mycobacteria, it has applications for other pathogens that are difficult or impossible to identify with conventional methods.

Detecting Antimicrobial-Drug Resistance

Molecular methods can rapidly detect antimicrobial-drug resistance in clinical settings and have substantially contributed to our understanding of the spread and genetics of resistance (9). Conventional broth- and agar-based antimicrobial susceptibility testing methods provide a phenotypic profile of the response of a given microbe to an array of agents. Although useful for selecting potentially useful therapeutic agents, conventional methods are slow and fraught with problems. The most common failing is in the detection of methicillin resistance in staphylococci, which may be expressed in a very heterogeneous fashion, making phenotypic characterization of resistance difficult (9,15). Currently, molecular detection of the resistance gene, mec A, is the standard against which phenotypic methods for detection of methicillin resistance are judged (9,15,16).

Molecular methods may be used to detect specific antimicrobial-drug resistance genes (resistance genotyping) in many organisms (Table 3) (8,9). Detection of specific point mutations associated with resistance to antiviral agents is also increasingly important (17,18). Screening for mutations in an amplified product may be facilitated by the use of high-density probe arrays (Gene chips) (6).

Despite its many potential advantages, genotyping will not likely replace phenotypic methods for detecting antimicrobial-drug resistance in the clinical laboratory in the near future. Molecular methods for resistance detection may be applied directly to the clinical specimen, providing simultaneous detection and identification of the pathogen plus resistance characterization (9). Likewise, they are useful in detecting resistance in viruses, slow-growing or nonviable organisms, or organisms with resistance mechanisms that are not reliably detected by phenotypic methods (9,19). However, because of their high specificity, molecular methods will not detect newly emerging resistance mechanisms and are unlikely to be useful in detecting resistance genes in species where the gene has not been observed previously (19). Furthermore, the presence of a resistance gene does not mean that the gene will be expressed, and the absence of a known resistance gene does not exclude the possibility of resistance from another mechanism. Phenotypic antimicrobial susceptibility testing methods allow laboratories to test many organisms and detect newly emerging as well as established resistance patterns.

Molecular Epidemiology

Figure. Pulsed-field gel electrophoresis (PFGE) profiles of Staphylococcus aureus isolates digested with Sma 1. A variety of PFGE profiles are demonstrated in these 23 isolates.

Laboratory characterization of microbial pathogens as biologically or genetically related is frequently useful in investigations (12,20,21). Several different epidemiologic typing methods have been applied in studies of microbial pathogens (Table 4). The phenotypic methods have occasionally been useful in describing the epidemiology of infectious diseases however, they are too variable, slow, and labor-intensive to be of much use in most epidemiologic investigations. Newer DNA-based typing methods have eliminated most of these limitations and are now the preferred techniques for epidemiologic typing. The most widely used molecular typing methods include plasmid profiling, restriction endonuclease analysis of plasmid and genomic DNA, Southern hybridization analysis using specific DNA probes, and chromosomal DNA profiling using either pulsed-field gel electrophoresis (PFGE) or PCR-based methods (12,20). All these methods use electric fields to separate DNA fragments, whole chromosomes, or plasmids into unique patterns or fingerprints that are visualized by staining with ethidium bromide or by nucleic acid probe hybridization (Figure). Molecular typing is performed to determine whether different isolates give the same or different results for one or more tests. Epidemiologically related isolates share the same DNA profile or fingerprint, whereas sporadic or epidemiologically unrelated isolates have distinctly different patterns (Figure). If isolates from different patients share the same fingerprint, they probably originated from the same clone and were transmitted from patient to patient by a common source or mechanism.

Molecular typing methods have allowed investigators to study the relationship between colonizing and infecting isolates in individual patients, distinguish contaminating from infecting strains, document nosocomial transmission in hospitalized patients, evaluate reinfection versus relapse in patients being treated for an infection, and follow the spread of antimicrobial-drug resistant strains within and between hospitals over time (12). Most available DNA-based typing methods may be used in studying nosocomial infections when applied in the context of a careful epidemiologic investigation (12,21). In contrast, even the most powerful and sophisticated typing method, if used indiscriminately in the absence of sound epidemiologic data, may provide conflicting and confusing information.

Financial Considerations

Molecular testing for infectious diseases includes testing for the host's predisposition to disease, screening for infected or colonized persons, diagnosis of clinically important infections, and monitoring the course of infection or the spread of a specific pathogen in a given population. It is often assumed that in addition to improved patient care, major financial benefits may accrue from molecular testing because the tests reduce the use of less sensitive and specific tests, unnecessary diagnostic procedures and therapies, and nosocomial infections (11). However, the inherent costs of molecular testing methods, coupled with variable and inadequate reimbursement by third-party payers and managed-care organizations, have limited the introduction of these tests into the clinical diagnostic laboratory.

Not all molecular diagnostic tests are extremely expensive. Direct costs vary widely, depending on the test's complexity and sophistication. Inexpensive molecular tests are generally kit based and use methods that require little instrumentation or technologist experience. DNA probe methods that detect C. trachomatis or N. gonorrhoeae are examples of low-cost molecular tests. The more complex molecular tests, such as resistance genotyping, often have high labor costs because they require experienced, well-trained technologists. Although the more sophisticated tests may require expensive equipment (e.g., DNA sequencer) and reagents, advances in automation and the production of less-expensive reagents promise to decrease these costs as well as technician time. Major obstacles to establishing a molecular diagnostics laboratory that are often not considered until late in the process are required licenses, existing and pending patents, test selection, and billing and reimbursement (22).

Reimbursement issues are a major source of confusion, frustration, and inconsistency. Reimbursement by third-party payers is confounded by lack of Food and Drug Administration (FDA) approval and Current Procedural Terminology (CPT) codes for many molecular tests. In general, molecular tests for infectious diseases have been more readily accepted for reimbursement however, reimbursement is often on a case-by-case basis and may be slow and cumbersome. FDA approval of a test improves the likelihood that it will be reimbursed but does not ensure that the amount reimbursed will equal the cost of performing the test.

Perhaps more than other laboratory tests, molecular tests may be negatively affected by fee-for-service managed-care contracts and across-the-board discounting of laboratory test fees. Such measures often result in reimbursement that is lower than the cost of providing the test. Although molecular tests may be considered a means of promoting patient wellness, the financial benefits of patient wellness are not easily realized in the short term (11). Health maintenance organizations (HMOs) and managed-care organizations often appear to be operating on shorter time frames, and their administrators may not be interested in the long-term impact of diagnostic testing strategies.

Molecular screening programs for infectious diseases are developed to detect symptomatic and asymptomatic disease in individuals and groups. Persons at high risk, such as immunocompromised patients or those attending family planning or obstetrical clinics, are screened for CMV and Chlamydia, respectively. Likewise, all blood donors are screened for bloodborne pathogens. The financial outcome of such testing is unknown. The cost must be balanced against the benefits of earlier diagnosis and treatment and societal issues such as disease epidemiology and population management.

One of the most highly touted benefits of molecular testing for infectious diseases is the promise of earlier detection of certain pathogens. The rapid detection of M. tuberculosis directly in clinical specimens by PCR or other amplification-based methods is quite likely to be cost-effective in the management of tuberculosis (7). Other examples of infectious disease that are amenable to molecular diagnosis and for which management can be improved by this technology include HSV encephalitis, Helicobacter pylori infection, and neuroborreliosis caused by Borrelia burgdorferi. For HSV encephalitis, detection of HSV in cerebrospinal fluid (CSF) can direct specific therapy and eliminate other tests including brain biopsy. Likewise, detection of H. pylori in gastric fluid can direct therapy and obviate the need for endoscopy and biopsy. PCR detection of B. burgdorferi in CSF is helpful in differentiating neuroborreliosis from other chronic neurologic conditions and chronic fatigue syndrome.

As discussed earlier, molecular tests may be used to predict disease response to specific antimicrobial therapy. Detection of specific resistance genes (mec A, van A) or point mutations resulting in resistance has proven efficacious in managing disease. Molecular-based viral load testing has become standard practice for patients with chronic hepatitis and AIDS. Viral load testing and genotyping of HCV are useful in determining the use of expensive therapy such as interferon and can be used to justify decisions on extent and duration of therapy. With AIDS, viral load determinations plus resistance genotyping have been used to select among the various protease inhibitor drugs available for treatment, improving patient response and decreasing incidence of opportunistic infections.

Pharmacogenomics is the use of molecular-based tests to predict the response to specific therapies and to monitor the response of the disease to the agents administered. The best examples of pharmacogenomics in infectious diseases are the use of viral load and resistance genotyping to select and monitor antiviral therapy of AIDS and chronic hepatitis (17,18). This application improves disease outcome shortens length of hospital stay reduces adverse events and toxicity and facilitates cost-effective therapy by avoiding unnecessary expensive drugs, optimizing doses and timing, and eliminating ineffective drugs.

Molecular strain typing of microorganisms is now well recognized as an essential component of a comprehensive infection control program that also involves the infection control department, the infectious disease division, and pharmacy (10,21). Molecular techniques for establishing presence or absence of clonality are effective in tracking the spread of nosocomial infections and streamlining the activities of the infection control program (21,23). A comprehensive infection control program uses active surveillance by both infection control practitioners and the clinical microbiology laboratory to identify clusters of infections with a common microbial phenotype (same species and antimicrobial susceptibility profile). The isolates are then characterized in the laboratory by using one of a number of molecular typing methods (Table 4) to confirm or refute clonality. Based on available epidemiologic and molecular data, the hospital epidemiologist then develops an intervention strategy. Molecular typing can shorten or prevent an epidemic (23) and reduce the number and cost of nosocomial infections (Table 5) (10). Hacek et al. (10) analyzed the medical and economic benefits of an infection control program that included routine determination of microbial clonality and found that nosocomial infections were significantly decreased and more than $4 million was saved over a 2-year period (Table 5).

The true financial impact of molecular testing will only be realized when testing procedures are integrated into total disease assessment. More expensive testing procedures may be justified if they reduce the use of less-sensitive and less-specific tests and eliminate unnecessary diagnostic procedures and ineffective therapies.

Dr. Pfaller is professor and director of the Molecular Epidemiology and Fungus Testing Laboratory at the University of Iowa College of Medicine and College of Public Health. His research focuses on the epidemiology of nosocomial infections and antimicrobial-drug resistance.


Abstract

Ongoing social, political and ecological changes in the 21st century have placed more people at risk of life-threatening acute and chronic infections than ever before. The development of new diagnostic, prophylactic, therapeutic and curative strategies is critical to address this burden but is predicated on a detailed understanding of the immensely complex relationship between pathogens and their hosts. Traditional, reductionist approaches to investigate this dynamic often lack the scale and/or scope to faithfully model the dual and codependent nature of this relationship, limiting the success of translational efforts. With recent advances in large-scale, quantitative, omics methodologies as well as advances in integrative analytical strategies, systems biology approaches for the study of infectious disease are quickly forming a new paradigm for how we understand and model host–pathogen relationships for translational applications. Here, we delineate a framework for a systems biology approach to infectious disease in three parts: discovery — the design, collection and analysis of omics data representation — iterative modelling, integration and visualization of complex data sets and application — the interpretation and hypothesis-based inquiry towards translational outcomes.

This Review outlines a broad, universal framework for systems biology applied to infectious disease research. From study design, omics data collection, analysis, visualization and interpretation to translational outcomes, the authors illustrate how systems biology can provide insights into host–pathogen relationships for the betterment of human health.


14.1: Characteristics of Infectious Diseases - Biology

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1 About Infectious Disease

The purpose of this reading is to give students a better grasp of the ecology and biology of the Ebola, Measles, and COVID-19 viruses.

This reading will provide you with additional information on the ecology and biology of two viruses that have risen to increased prominence recently — Ebola, Measles, and COVID-19.

In the beginning of your exploration of infectious diseases and their causes, you read stories about three recent epidemics, two about emerging diseases (a disease that has appeared in a population for the first time, or that may have existed previously but is rapidly increasing in incidence or geographic range) and another about a re-emerging disease (a disease that had decreased in incidence in the global population as a result of public health policies and vaccination but has had a resurgence as a public health problem).

Ebola Virus Disease caused by the Ebola virus and Covid-19 caused by a coronavirus are examples of an emerging disease measles (also known as Rubeola) caused by the measles virus is an example of a re-emerging disease. Although the symptoms and the degree of contagiousness (how readily the virus can spread) of the three diseases are different, the viruses are similar in several ways: all are negative strand, category IV RNA viruses two (Ebola and measles) infect cells of the immune system all three exit an infected cell by budding and may spread through the body in circulating infected cells. If these viruses are so similar, why do they differ so dramatically in their symptoms and mortality (death) rates?

To answer this question, you will need to know more about the ecology and biology of each virus. The ecology of a virus involves the interaction that a virus has with the host that serves as its environment and the mechanism by which a virus is transmitted from one host to another. The biology of a virus describes the structure of the virus the mechanisms by which it enters a cell, makes copies of itself (reproduces), and exits the cell and how it causes symptoms of disease in its host.

Many viruses, especially those that cause emerging diseases, are able to infect and reproduce in more than one host species. In some cases, a host may not display disease symptoms (asymptomatic) despite the viral infection. This kind of host species is termed a reservoir host. However, when the virus is transmitted to a different species, it can cause a severe, often fatal, disease. The existence of reservoir hosts makes the eradication of certain kinds of viruses difficult, if not impossible.

Identification of the reservoir host of the Ebola virus has been elusive. Recent evidence has implicated bats as the source of infection but this remains to be proven as, to date, Ebola Virus has never been isolated from a bat. It is speculated that if bats are the reservoir, humans could become infected through contact with bat guano, from a bite, or through using bats as a food source. Once a human is infected, transmission from person to person occurs only by direct contact with blood and body fluids such as saliva, mucus, vomit, feces, sweat, tears, breast milk, urine, and semen.

Ebola virus is made up of a single strand of RNA (negative strand) that is surrounded by proteins and a membrane, which form a long, filamentous structure (see Ebola virus in Table 3). The virus’ first line of attack is infection of cells that make up the immune system, the body’s major defense against infectious agents. The virus binds to the surface of the cell and is taken inside the cell where it releases its genetic material and enzymes needed for virus growth. Inside the cell, the virus makes many copies of itself through the following steps:

  1. Viral RNA polymerase transcribes mRNA from the negative-strand viral RNA.
  2. Using the host protein synthesis machinery, the mRNA directs the synthesis of viral structural proteins and enzymes.
  3. Viral RNA polymerase uses the negative-strand RNA also as a template for the production of a full-length positive-strand RNA as a step in the production of new virus particles (progeny).
  4. Viral RNA polymerase uses the positive-strand RNA (step 3) as a template for the production of full-length negative-strand RNA genomes.
  5. The negative-strand RNA genome, the viral RNA polymerase, and the structural proteins join together to form enormous numbers of viral particles.
  6. The virus exits the cell by budding from the host cell, picking up a coating of host membrane as it leaves.
  7. The host cell then disintegrates because the virus has hijacked its protein making machinery and therefore can no longer survive

Infection of the immune cells by Ebola virus causes havoc in many ways. It inactivates the very cells whose function it is to destroy a viral invader. Other functions of the immune system are activated inappropriately, causing the lining of blood vessels to leak blood and fluids, resulting in the internal bleeding in some Ebola patients. Large numbers of virus particles circulating in the blood can also infect liver cells, producing more particles, killing the liver cells, and leading to organ failure and characteristic symptoms of high fever, muscle aches, malaise, vomiting and diarrhea. Although no treatments were available for past outbreaks and epidemics, testing during the most recent Ebola outbreaks of a vaccine and antiviral drugs have shown promising results.

Measles virus is an example of a virus with no reservoir host. Humans are the only hosts. For this reason, the eradication of measles is possible, provided at least 95% of the population is immune, most reasonably through vaccination.

Measles virus shares many characteristics similar to Ebola virus. It is made up of a single strand of RNA (negative strand) that is surrounded by proteins and a membrane (see measles virus in Table 3). Unlike Ebola, which requires direct contact with body fluids, measles infection occurs when a person inhales virus-laden droplets exhaled from an infected person. The virus particles enter the lungs and, like Ebola, attack immune cells, the body’s first line of defense against infectious agents. The virus binds to the surface of the cell and is taken inside the cell where it releases its genetic material and enzymes needed for virus growth. Inside the cell, the virus makes many copies of itself through steps characteristic of negative-strand RNA viruses:

  1. Viral RNA polymerase transcribes mRNA from the negative-strand viral RNA.
  2. Using the host protein synthesis machinery, the mRNA directs the synthesis of viral structural proteins and enzymes.
  3. Viral RNA polymerase uses the negative-strand RNA also as a template for the production of a full-length positive-strand RNA as a step in the production of new virus particles (progeny).
  4. Viral RNA polymerase uses the positive-strand RNA (step 3) as a template for the production of full-length negative-strand RNA genomes.
  5. The negative-strand RNA genome, the viral RNA polymerase, and the structural proteins join together to form enormous numbers of viral particles.
  6. The virus exits the cell by budding from the host cell, picking up a coating of host membrane as it leaves.
  7. The host cell then disintegrates because the virus has hijacked its protein making machinery and therefore can no longer survive

The infected cells, laden with viral particles, migrate from the lungs to the lymph nodes, infecting more immune cells and spreading the virus to other sites in the body, including the spleen, thymus, and skin. The skin rash characteristic of measles is the result of infection of cells in the skin. In some cases, the virus can reach the brain, where it may cause permanent brain damage.
After several days, the viral-infected cells reach the nasal passages, infecting epithelial cells that line the upper respiratory tract and producing large numbers of viral particles. Infected individuals release clouds of virus-laden droplets from their noses, trachea, tonsils, and lungs. These droplets can remain infectious on surfaces for several hours and can move via air currents to the next susceptible host. This mode of transmission makes the measles virus highly contagious. Besides a rash, other symptoms of measles include coughing, runny nose, and red watery eyes that result from virus infection and cell death and a high fever, a sign of the immune system doing battle. In some instances, measles can lead to more serious symptoms and even death. Prior to the development of an effective vaccine in the early 1960s, 7 to 8 million children died of measles worldwide every year. By 2014 that number was reduced to 145,000.
Because immune cells are a major site of virus reproduction, a bout of measles can leave the victim with an immune system that is somewhat disabled, making that person vulnerable to other infections. Recent studies have indicated that following an infection, a child’s immune system can be weakened for up to three years, leaving the child susceptible to infections that a fully functional immune system would normally fight off.


14.1: Characteristics of Infectious Diseases - Biology

Journal of Immunological Techniques and Infectious Diseases (JIDIT) is a scholarly peer-reviewed academic journal that encourages rigorous research that makes a significant contribution in advancing knowledge for immunological application in the treatment of various infectious diseases. JIDIT includes all major themes pertaining to Immunity, Immunization techniques, Vaccination, Epidemology and treatment of infectious diseases.

Scope of the Journal includes:

  • Epidemology & Pathogenesis of diseases
  • Diagnostic Techniques - Advancements
  • Immunolgy & Microbiology
  • Infectious Diseases & Immune responses
  • Vaccination and Development of Vaccines
  • Clinical & Experimental Immunology

Journal of Immunological Techniques in Infectious Diseases is a peer reviewed scientific Journal that provides a range of options to individuals and university libraries to purchase our articles and also permits unlimited Internet Access to complete Journal content. However, JIDIT has recently started following Hybrid Model of publication of articles. Under hybrid model, journal is giving option to authors to choose their mode of publishing either Open Access (making individual articles freely available online) or Subscription (article access restricted to journal subscribers).

JIDIT accepts wide range of articles including research, review, short communication, case report, rapid communication, letter to the editor, conference proceedings etc. The journal has a sound Editorial Board of experts in their fields. Articles submitted by authors are evaluated by Editors and a group of peer review experts in the field to ensure that the accepted and published articles are of high quality, reflect solid scholarship in their fields, and that the information they contain is accurate, reliable and beneficial to the scientific community. JIDIT uses Editorial Manager System for quality review process. Editorial Manager is an online manuscript submission, review and tracking systems. Authors can submit and track the progress of their articles through the system.

Manuscripts along with cover letters can be submitted to the journal via online submission system or as an e-mail attachment to the Editorial Office at [email protected] Authors can also track the status of their manuscripts post submission through our manuscript tracking system.

Confirmed Special Issues:

Authors can also track the status of their manuscripts post submission through our manuscript tracking system.

Pediatric Infections

There are several pediatric infections which occur commonly in children which can be life threatening. Some of the pediatric infections in children include diarrhea, E. coli infection, chickenpox, common cold, intestinal roundworms, measles, etc

Child immunization and Vaccination

It includes the various child immunization and vaccination techniques to strengthen immune system in children against harmful infectious diseases. The various child immunization and vaccination techniques include Poliovirus, Tetanus, chicken pox vaccine DPT vaccine, Haemophilus influenzae type B vaccine, MMR vaccine etc

New Emerging infectious Diseases

Infectious diseases whose incidence have increased to a great extent or having a threat to increase future are defined as new emerging infectious diseases. HIV, Hepatitis C, Ebola infection, E. coli infections are the most threatening new emerging infectious diseases.

Epidemiology of Infectious Diseases

Epidemiology of Infectious Diseases is the branch of medicine dealing with the incidence, distribution, and possible control of diseases and other various other factors relating to Epidemiology of infectious diseases.

Pathogenesis of Infectious Diseases

Pathogenesis of infectious diseases deals with the manner in which a disease develops and its spread in the body. Pathogenesis of infectious diseases also deals with the cellular reactions and other pathologic mechanisms occurring in the development of disease.

Transmission of Infectious Diseases

Transmission of infectious diseases from person to person occurs by direct or indirect contact. Transmission of Infectious Diseases also occurs by bites from insects or animals. Viruses, bacteria, parasites, and fungi are the major causes of infectious disease.

Diagnostic Techniques

Diagnostic Techniques : Advancements of infectious disease include application of various modern diagnostic techniques for the identification of infectious agent causing the disease and studying the epidemiological considerations and pathogenesis of the disease.

Air Borne Diseases

Airborne diseases are the diseases caused by pathogens which are transmitted through the air. Air borne diseases result from inhalation of contaminated air and also by transfer of pathogen from one person to another using air as the medium.

Water Borne Diseases

Waterborne diseases are caused by pathogenic microorganisms that are transmitted from contaminated fresh water and Water borne infections commonly result from drinking and usage of contaminated water for daily purposes of bathing, cooking, washing etc.

Communicable Diseases

Non-communicable diseases are the diseases that are not transmittable from person to person or from animals to person. These are usually the chronic diseases which last for a longer time. Communicable diseases are the diseases that are transmitted from one person to another through direct contact indirectly through a vector.Communicable & Non Communicable Diseases can be dangerous and fatal.

Pandemic and Epidemic diseases

Epidemic diseases are the diseases which rapidly spread to a large number of people within a short span of time and epidemic diseases are fatal. A pandemic disease is a global outbreak of a particular disease.AIDS is an example of one of the most destructive global pandemic disease.

Pathogenic microorganisms

Pathogenic microorganisms are the organisms which have the capability of causing disease in a particular host. Common examples of pathogenic microorganisms include specific strains of bacteria like Salmonella, Listeria and E. coli, and viruses such as Cryptosporidium and many other types of fungi.

Immunology and Microbiology

Immunology is the branch of science concerned with the various aspects related to immune system, innate and acquired immunity and immunology also deals with laboratory techniques involving the interaction of antigens with specific antibodies. Microbiology is the branch of science dealing with the study of various microorganisms. Microbiology involves the study of their structure and various physical, chemical and biological characteristics pertaining to their capability to cause a disease.

Immune Responses

Infectious Diseases & Immune Responses involves the responses of immune system during the attack of a disease and Infectious Diseases & Immune Responses studies the fighting mechanisms upon the invasion and replication of various microbial agents - bacteria, viruses, fungi, protozoans, and worms as well as reacts in the toxins they produce.

Immunopathology

Immunopathology is the sub discipline of Immunological sciences dealing with the immune responses associated with disease. Immunopathology includes the study of the pathology of an organism, organ system, or disease with respect to the immune system, immunity, and immune responses.

Immunological Sciences

Immunological Sciences deals with the branch of science studying the components of the immune system, immunity from disease, the immune response, and immunological sciences also deals with all the immunologic techniques of analysis.

Clinical Immunology

Clinical immunology deals with the study of diseases caused by disorders of the immune system. Clinical immunology also deals with the diseases where immune reactions play key role in the pathology and clinical features of the disease. Experimental immunology investigates immunological responses to antigens and includes the studies related to detecting and characterizing antibodies and lymphocytes.

Immunization Techniques

Vaccination and immunization techniques are the major ways used for the prevention of several fatal infectious diseases in humans and animals. Vaccination and immunization techniques help in strengthening the immune system and produces antibodies which can fight against the antigens produced by the pathogens causing diseases.

Vaccine Development

Vaccine development is a very long, complicated and tedious procedure including several complex processes usually lasting for 10-15 year. The various stages of vaccine development of a vaccine include exploratory stage, pre-clinical stage, clinical development, regulatory review and approval, manufacturing and Quality control.

Vaccine Testing and Regulation

The developed vaccines undergo a series of vaccine testing and regulation procedures before their final approval and marketing. Several vaccine testing and regulation procedures are involved in all the aspects of vaccine development, manufacturing, and marketing. Regulations pay a key role from the time of vaccine design and clinical testing, manufacturing and to when the final product is marketed worldwide.


Global rise in human infectious disease outbreaks

To characterize the change in frequency of infectious disease outbreaks over time worldwide, we encoded and analysed a novel 33-year dataset (1980–2013) of 12 102 outbreaks of 215 human infectious diseases, comprising more than 44 million cases occuring in 219 nations. We merged these records with ecological characteristics of the causal pathogens to examine global temporal trends in the total number of outbreaks, disease richness (number of unique diseases), disease diversity (richness and outbreak evenness) and per capita cases. Bacteria, viruses, zoonotic diseases (originating in animals) and those caused by pathogens transmitted by vector hosts were responsible for the majority of outbreaks in our dataset. After controlling for disease surveillance, communications, geography and host availability, we find the total number and diversity of outbreaks, and richness of causal diseases increased significantly since 1980 (p < 0.0001). When we incorporate Internet usage into the model to control for biased reporting of outbreaks (starting 1990), the overall number of outbreaks and disease richness still increase significantly with time (p < 0.0001), but per capita cases decrease significantly (p = 0.005). Temporal trends in outbreaks differ based on the causal pathogen's taxonomy, host requirements and transmission mode. We discuss our preliminary findings in the context of global disease emergence and surveillance.

1. Introduction

Understanding the spatial and temporal distribution of novel infectious diseases is among the most important and challenging tasks for the coming century [1–5]. To date, generalizations about global disease trends have primarily been made from two forms of data: counts of endemic diseases present within nations at a single time point (denoted here and in previous studies as ‘disease richness’) [6–8] and records of first-occurrence pathogen emergence events that have occurred globally over time [5]. These past studies have shown that certain pathogens conform to biogeographic trends similar to those exhibited by non-human taxa (e.g. an inverse relationship between disease richness and latitude) [7], that diseases specific to humans (i.e. contagious only between persons) are uniformly distributed around the world, whereas zoonoses (diseases caused by pathogens that spread from animals to humans) are far more localized in their global distribution [6,9,10] and that zoonoses represent the majority of emerging infectious diseases in the human population [5]. However, past studies lack large-scale spatio-temporal data documenting distributions for many pathogens and this has impeded disease biogeographers from fully characterizing the global disease-scape.

Outbreaks occur when the number of cases of disease increases above what would normally be expected in a defined community, geographical area or season [11]. Outbreaks are documented textually and include spatial and temporal attributes, case data, and information about the causal pathogen, and present an opportunity to make new discoveries about global disease trends. However, outbreak records have been largely inaccessible for use in macro-scale analyses as these records are not stored in a manner easily retrievable to the broader research community. The aim of this report is to introduce a new dataset containing data from over 12 000 records of human infectious disease outbreaks and present initial findings from analyses of temporal trends in global outbreaks since the 1980s.

2. Material and methods

We encoded, summarized and analysed a 33-year dataset (1980–2013) of 12 102 outbreaks of 215 human infectious diseases, comprising more than 44 million total cases occurring in 219 nations (table 1). The data are curated as prose records of confirmed outbreaks in the Global Infectious Disease and Epidemiology Online Network (GIDEON) and are accessible via subscription to the site [11]. GIDEON has been used in past macro-scale studies of infectious disease (e.g. [6–8]), but the spatio-temporal data available on outbreaks have not been fully leveraged by researchers because the records are in textual form. We developed a bioinformatics pipeline that automates the parsing and encoding of GIDEON's outbreak records and enables the first macro-scale analyses of global outbreak trends for a suite of unique diseases. We merged these newly encoded records with ecological characteristics of the causal pathogens [6,7] to examine global temporal trends in the total number of outbreaks, richness (total number) of unique causal diseases, diversity (richness in association with outbreak evenness) of causal diseases and per capita cases (total cases caused by an outbreak as a proportion of that nation's population in the outbreak year). Because of inherent biases in global disease data (e.g. electronic supplementary material, figure S1, [3,5–7]), we controlled for the effects of six variables previously identified in the literature as confounding the effects of disease occurrence and reporting at large spatial and temporal scales: latitude, GDP, press freedom, Internet usage, population size and population density all variables were recorded by nation and by year (electronic supplementary material). Using these six confounding variables as the independent variables, we fit quasi-Poisson regression models to identify temporal trends in the number of outbreaks and disease richness. We chose quasi-Poisson models to allow for overdispersion in outbreak occurrences among nation-years. We also used linear regression to model temporal trends in disease diversity and per capita cases. The electronic supplementary material fully describes the nature of the GIDEON outbreak records, the pipeline we built to parse and encode them, the ecological characteristics we used to categorize causal pathogens and our statistical methods.

Table 1. Summary of the human infectious disease outbreak records retrieved by our bioinformatics pipeline. a

a Some diseases could not be assigned to certain sub-categories due to a lack of ecological or epidemiological information [10].

3. Results

Our analyses indicate that the total number of outbreaks and richness of causal diseases have each increased globally since 1980 (figure 1a). Bacteria and viruses represented 70% of the 215 diseases in our dataset and caused 88% of outbreaks over time. Sixty-five per cent of diseases in our dataset were zoonoses that collectively caused 56% of outbreaks (compared to 44% of outbreaks caused by human-specific diseases). Non-vector transmitted pathogens were more common (74% of diseases) and caused more outbreaks (87%) than vector transmitted pathogens (table 1). Salmonellosis caused the most outbreaks of any disease in the dataset (855 outbreaks reported since 1980). However, viral gastroenteritis (typically caused by norovirus) was responsible for the greatest number of recorded cases: more than 15 million globally since 1980.

Figure 1. Global number of human infectious disease outbreaks and richness of causal diseases 1980–2010. Outbreak records are plotted with respect to (a) total global outbreaks (left axis, bars) and total number of diseases causing outbreaks in each year (right axis, dots), (b) host type, (c) pathogen taxonomy and (d) transmission mode. (Online version in colour.)

Previous studies have demonstrated that a nation's likelihood of experiencing, identifying and reporting an outbreak is influenced by its surveillance capabilities, communication infrastructure, geography and availability of hosts for pathogens [5,6–9,12–15]. After controlling for these factors using proxies, by nation and year (electronic supplementary material), the number of outbreaks and richness of causal diseases still exhibit a significant increase since 1980 (p < 0.0001), as do the number of outbreaks and richness of causal diseases for each sub-category of pathogen taxonomy (bacteria, fungi, parasites, protozoa or viruses), pathogen transmission mode (vector transmitted or non-vector transmitted) and host type (human specific or zoonotic figure 1b–d electronic supplementary material, table S1).

The Internet has been shown to significantly improve disease detection and reporting [12–14]. When we add Internet usage as an independent variable to the model (per cent Internet users by nation-year, starting 1990) to control for biased reporting of outbreaks, the overall number of outbreaks and disease richness still increase significantly with time (p < 0.0001 electronic supplementary material, table S2). However, the number of protozoan and fungal disease outbreaks, and richness of human-specific, protozoan and fungal diseases do not increase with time in this model (Internet usage included electronic supplementary material, table S2). Three quarters of the outbreak records reported case data, allowing analysis of global temporal trends in per capita cases. After controlling for Internet usage, overall per capita cases decrease significantly with time, as do human-specific and protozoan disease outbreaks (p = 0.005 electronic supplementary material, table S2).

Measures of disease richness are commonly reported in disease biogeography studies [6–8], but the nature of the outbreak data allows us to quantify, for the first time, global trends in disease diversity. The Shannon diversity index (SDI), common in ecological studies, accounts for both richness or number of unique types (here, unique diseases) and how evenly types are represented in a given dataset (here, across outbreaks) to provide a measure of diversity. Thus, the SDI allows for a new way to examine the global assemblage of infectious diseases (electronic supplementary material). Overall outbreak diversity and the diversity of all sub-categories (by taxonomy, transmission mode and host type) of causal diseases exhibit significant increases since 1980 (figure 2 electronic supplementary material, table S1). After controlling for Internet usage, this trend disappears (p = 0.947), and the diversity of outbreaks caused by human-specific diseases, bacteria, protozoans and fungi exhibit a significant decline since 1990 (p = 0.023, 0.034, 0.002, respectively electronic supplementary material, table S2). By contrast, while diseases caused by pathogens that use non-human hosts to complete their life cycle (e.g. zoonoses and vector transmitted pathogens) exhibit temporal increases in total outbreaks and richness, there is no apparent change in diversity for these diseases (electronic supplementary material, table S2).

Figure 2. Global outbreak diversity for the nations of the world over time. Diversity is calculated for each nation using Shannon's diversity index (SDI) as described in the methods. Nations with the highest diversity of outbreaks are represented by larger values and darker shading. (Online version in colour.)

Rank-abundance distributions shed some light on this finding. The increasingly long tail of the rank-abundance distribution of outbreaks caused by zoonoses (electronic supplementary material, figure S2) reveals that, while the richness of zoonotic diseases is increasing over time, most of these diseases cause only a small fraction of outbreaks. Indeed, a handful of specific zoonoses appear to cause the majority of outbreaks in each decade: from 1980 to 1990, 80% of all zoonotic disease outbreaks were caused by only 25% of potential zoonoses in the dataset, and only 22% and 21% of zoonoses from 1990 to 2000 and from 2000 to 2010, respectively. Thirteen zoonoses represent the top 10 causal diseases in terms of recorded outbreaks in each of the three decades of the dataset (table 2). The rank-abundance distributions of outbreaks caused by human-specific diseases also reveal dominance by a subset of specific diseases. From 1980 to 1990, 80% of outbreaks caused by human-specific diseases were caused by 31% of all potential human-specific diseases in the dataset (32% and 27% of human-specific diseases from 1990 to 2000 and from 2000 to 2010, respectively). Fifteen human-specific diseases represent the top 10 causal diseases in terms of recorded outbreaks in each of the three decades of the dataset (table 2).

Table 2. Top 10 causal diseases in terms of total outbreaks by decade and host type (zoonoses versus human specific).

4. Discussion

Here, we analyse human infectious disease outbreaks across the world, spanning multiple decades. Our results provide new descriptions of the global disease-scape and our new dataset, now available for others to use, will help advance the field of disease biogeography.

While outbreaks represent an increase in the number of disease cases beyond expectations for a given population, emerging human infectious diseases are further characterized by novelty: for example, diseases that have undergone recent evolutionary change, entered the human population for the first time, or have been newly discovered [5,9]. The number of outbreaks, like the number of emerging infectious diseases, appears to be increasing with time in the human population both in total number and richness of causal diseases. Although our finding implies that outbreaks are increasing in impact globally, outbreak cases per capita appear to be declining over time. Our data suggest that, despite an increase in overall outbreaks, global improvements in prevention, early detection, control and treatment are becoming more effective at reducing the number of people infected [13,16–20].

Temporal trends in outbreaks differ for human-specific diseases versus diseases that rely on non-human hosts. Zoonotic disease outbreaks are increasing globally in both total number and richness but not diversity or per capita cases (electronic supplementary material, table S2). Human-specific infectious diseases are also causing an increasing number of outbreaks over time. In contrast to zoonoses, however, human-specific diseases are declining in diversity and in the impact they have through outbreaks (in terms of per capita cases). These findings, along with previous work on emerging infectious disease [5], suggest that zoonoses may be increasingly more novel in the global human population when compared with diseases specific to humans. This novelty may be a function of the various ways in which zoonoses occur for the first time in the human population (e.g. spill-over from animals, evolution or discovery) [5,9]. By contrast, human-specific pathogens appear to be less novel (in terms of diversity) and harmful (in terms of per capita cases) than in the past. We suspect per capita cases for zoonotic outbreaks may indeed be greater than our findings indicate, but this is not detectable due to a lack of communications infrastructure and public health resources in the nations that suffer most from pathogens spilling over to humans from wildlife [5].

The temporal scale of our outbreak dataset allowed us to control for the confounding effects of the Internet (starting in 1990) on the reporting of infectious disease outbreaks. Both the total number of outbreaks and richness of causal diseases increase over time whether we control for Internet usage or not, but temporal trends in diversity and per capita cases change direction and significance once Internet usage is controlled for. It is beyond the scope of this report and our current dataset to determine the role the Internet has played in outbreak detection and reporting, but this has been discussed elsewhere by others (e.g. [12–14]). It is becoming increasingly clear that the Internet can improve disease reporting by supplementing formal surveillance with publicly generated digital disease surveillance [12–14]. Because of this, Internet usage and other proxies for national communication infrastructures are important to incorporate into analyses exploring changes in infectious disease over space and/or time.


Development of Infection

Infectious diseases are usually caused by microorganisms that invade the body and multiply. There are many types of infectious organisms (see also Overview of Infectious Disease).

The following are some examples of how microorganisms can invade the body:

Through the mouth, eyes, or nose

Through contaminated medical devices

People can ingest microorganisms by swallowing contaminated water or eating contaminated food. They may inhale spores or dust or inhale contaminated droplets coughed or sneezed out by another person. People may handle contaminated objects (such as a doorknob) or come into direct contact with a contaminated person and then touch their eyes, nose, or mouth.

Some microorganisms are spread through body fluids such as blood, semen, and stool. Thus, they can invade the body through sexual contact with an infected partner. They also can enter through nonsexual contact with body fluids, such as while providing personal care or medical services.

Human and animal bites and other wounds that break the skin can allow microorganisms to invade the body. Infected insects and ticks can spread diseases when they bite.

Microorganisms can also adhere to medical devices (such as catheters, artificial joints, and artificial heart valves) that are placed in the body. Microorganisms may be present on the device when it is inserted if the device was accidentally contaminated. Or infecting organisms from another site may spread through the bloodstream and lodge on an already implanted device. Because implanted material has no natural defenses, the microorganisms can easily grow and spread, causing disease.

After invading the body, microorganisms must multiply to cause infection. After multiplication begins, one of three things can happen:

Microorganisms continue to multiply and overwhelm the body’s defenses.

A state of balance is achieved, causing chronic infection.

The body—with or without medical treatment—destroys and eliminates the invading microorganism.

Invasion by most microorganisms begins when they adhere to cells in a person’s body. Adherence is a very specific process, involving "lock-and-key" connections between the microorganism and cells in the body. Being able to adhere to the surface of a cell enables microorganisms to establish a base from which to invade tissues.

Whether the microorganism remains near the invasion site or spreads to other sites and how severe the infection is depend on such factors as the following:


IV. Soft Tissue Infections of the Head and Neck

Infection of various spaces and tissues that occur in the head and neck can be divided into those arising from odontogenic, oropharyngeal, or exogenous sources. Odontogenic infections are caused commonly by endogenous periodontal or gingival flora [77]. These infections include peritonsillar and pharyngeal abscesses deep space abscesses, such as those of the retropharyngeal, parapharyngeal, submandibular, and sublingual spaces and cervical lymphadenitis [78, 79]. Complications of odontogenic infection can occur by hematogenous spread or by direct extension resulting in septic jugular vein thrombophlebitis (Lemierre syndrome), bacterial endocarditis, intracranial abscess, or acute mediastinitis [80, 81]. Accurate etiologic diagnosis depends upon collection of an aspirate or biopsy of inflammatory material from affected tissues and tissue spaces while avoiding contamination with mucosal microbiota. The specimen should be placed into an anaerobic transport container to support the recovery of anaerobic bacteria (both aerobic and facultative bacteria survive in anaerobic transport). Requests for Gram-stained smears are standard for all anaerobic cultures because they allow the laboratorian to evaluate the adequacy of the specimen by identifying inflammatory cells, provide an early presumptive etiologic diagnosis, and identify morphologic patterns indicative of mixed aerobic and anaerobic infections [82]. Additionally, spirochetes (often involved in odontogenic infection) cannot be recovered in routine anaerobic cultures but will be seen in the stained smear.

Infections caused by oropharyngeal flora include epiglottitis, mastoiditis, inflammation of salivary tissue, and suppurative parotitis [77, 83]. Because the epiglottis may swell dramatically during epiglottitis, there is a chance of sudden occlusion of the trachea if the epiglottis is disturbed, such as by an attempt to collect a swab specimen. Blood cultures are the preferred sample for the diagnosis of epiglottitis if swabbing is attempted, it should be in a setting with available appropriate emergency response. Oropharyngeal flora also can extend into tissues of the middle ear, mastoid, and nasal sinuses, causing acute infection [77, 84]. Aspirated material, saline lavage of a closed space, and tissue or tissue scrapings are preferred specimens and must be transported in a sterile container. Tissues should be transported under sterile conditions and kept moist by adding a few drops of sterile, nonbacteriostatic saline. Although rarely implicated, if anaerobic bacterial pathogens are suspected, anaerobic transport is required. Note that filamentous fungi are common causes of chronic sinusitis, and they may not be recovered on swabs, even those obtained endoscopically. Endoscopic aspirates or tissue scrapings are the specimens of choice. For microbiology analysis, it is always best to submit the actual specimen, not a swab of the specimen.

Infections caused by exogenous pathogens (not part of the oral flora) include malignant otitis externa, mastoiditis, animal bites and trauma, irradiation burns, and complications of surgical procedures [84, 85]. Mucosal flora may play an etiologic role in these infections, most frequently gram-negative bacilli and staphylococci.

Key points for the laboratory diagnosis of head and neck soft tissue infections:

  • A swab is not the specimen of choice for these specimens. Submit tissue, fluid, or aspirate when possible.
  • Resist swabbing in cases of epiglottitis.
  • Use anaerobic transport containers if anaerobes are suspected.
  • Keep tissue specimens moist during transport.

The following tables include the most common soft tissue and tissue space infections of the head and neck that originate from odontogenic, oropharyngeal, and exogenous sources. The optimum approach to establishing an etiologic diagnosis of each condition is provided

A. Infections of the Oral Cavity and Adjacent Spaces and Tissues Caused by Odontogenic and Oropharyngeal Flora (Table 14)

B. Mastoiditis and Malignant Otitis Externa Caused by Oropharyngeal and Exogenous Pathogens (Table 15)


What You Need To Know About Infectious Disease

A mechanism through which certain cells can increase the rate in which genetic mutations occur, often in response to stress. This mechanism may help explain how bacteria develop resistance to certain antibiotics.

A condition in which there is a deficit in the number of healthy red blood cells in the blood, resulting in fatigue and feelings of weakness.

The process through which pathogenic microorganisms, by way of genetic mutation, develop the ability to withstand exposure to the drugs that had once been successful in eradicating them.

A class of drugs used to kill or inhibit the growth of disease-causing microorganisms. Typically antibiotics are used to treat infections caused by bacteria, but in some cases they are also used against other microorganisms, such as fungi and protozoa.

A class of drugs used to kill or inhibit the growth of disease-causing microorganisms. Typically antibiotics are used to treat infections caused by bacteria, but in some cases they are also used against other microorganisms, such as fungi and protozoa.

An umbrella term for a range of conditions in which the immune system mistakenly attacks healthy tissue in the body.

A taxonomic class of bacteria.

A large group of unicellular microorganisms that lack a cell nucleus. Some bacteria are pathogenic and harmful to humans, some have no effect at all on humans, and some are beneficial.

One of several families of antibiotics, including penicillins, cephalosporins, carbapenems, and monobactams, containing a molecular ring-shaped structure made up of three carbon atoms and one nitrogen atom.

Biological Agent (Terrorism)

A bacterium, virus, or other biological toxin used in bioterrorism or biological warfare.

The deliberate release of a virus, bacterium, or other biological agent to cause illness and death in people, animals, or plants.

A bacterium, virus, or other biological toxin used in bioterrorism or biological warfare.

Large tubes that carry air into smaller branches of the lungs after the air has passed through the mouth, nasal passages, and windpipe.

A class of diseases in which abnormal cells divide without control and are able to invade healthy tissues in various parts of the body.

A class of biological agents that the Centers for Disease Control and Prevention views as posing the highest priority risk to U.S. national security.

The smallest unit of living matter capable of functioning independently.

A semipermeable barrier that separates the interior of a cell from the external environment.

Centers for Disease Control and Prevention (CDC)

A federal agency under the U.S. Department of Health and Human Services that works with partners across the United States to ensure public health&mdashthrough health promotion prevention of disease, injury, and disability and preparedness for new health threats.

An organized structure of DNA and proteins within the nucleus of a cell that contains many genes.

Any disease that is long lasting (3 months or more) or recurrent&mdashas opposed to an acute disease&mdashand cannot be prevented by a vaccine or cured by medication.

A prolonged form of localized immune response to harmful agents and damaged tissue that is characterized by redness, swelling, heat, pain, and/or loss of function.

A condition caused by chronic liver disease characterized by the development of scar tissue leading to a loss of liver function.

The process of shifting from one prevailing state in regional or global climate to another. Climate change is typically the preferred term over &ldquoglobal warming&rdquo because it helps to convey that the characteristics of climate change are not limited to rising temperatures.

A general term for any disease-causing infectious agent spread by direct or indirect contact.

A type of protein secreted by cells in the immune system that carries signals that facilitate cell-to-cell communication and help regulate the way the immune system responds to inflammation and infection.

Any abnormal condition that affects all or part of an organism, resulting in symptoms such as pain or loss of function.

Short for deoxyribonucleic acid, DNA is any of the nucleic acids that contain the genetic instructions necessary for the development and functioning of all living organisms as well as some viruses.

A branch of science that deals with the relation of organisms to one another and their physical environment.

A functional unit that consists of all the living organisms in a particular area, as well as the nonliving, physical components in the environment&mdashsuch as air, soil, water, and sunlight&mdashwith which the organisms interact, and how natural and human-made changes affect these interactions.

The female gamete, or sex cell, which carries the hereditary material of the female parent and unites with the male sperm cell during sexual reproduction.

El Niño-Southern Oscillation Cycle (ENSO)

Inflammation of the brain, often caused by a virus.

The baseline level of disease usually present in a community.

An often sudden increase in the level of disease in a specific population over a given period of time.

The change in heritable traits in a population of organisms over successive generations.

An external skeleton that protects and supports an organism, in contrast to an internal endoskeleton.

Sometimes referred to as a zygote, this is the resulting initial cell formed when a sperm cell unites with an egg cell.

A taxonomic kingdom of spore-forming organisms distinct from plants, animals, and bacteria that includes microorganisms such as yeast and molds, as well as mushrooms.

The structure in the body, beginning with the mouth and extending to the anus, through which food is ingested, broken down, and absorbed to provide the body with nutrients, and waste products are excreted.

The physical and functional unit of heredity made up of DNA. Every individual has two copies of each gene, one inherited from the mother and the other from the father.

A branch of biology that studies heredity and variation in organisms.

In the context of microbiology, a microorganism that causes disease.

A theory in medicine stating that microorganisms are the causative agents of infectious, contagious diseases.

The process by which regional economies, societies, and cultures are becoming integrated through a global network of trade, migration, communication, and the spread of new technology.

The specific geographical area or physical environment that is inhabited by an organism or a population of organisms.

An organism that harbors a parasite or another organism where there is a symbiotic relationship between the two organisms. In some cases, the relationship is commensal, or mutually beneficial, but in the case of a parasite and host, the host may be hurt by the parasite's presence.

The system of biological structures and processes that protects the body from foreign substances, including pathogens.

The process of strengthening the body&rsquos defense against a particular infectious agent, often accomplished by receiving a vaccine.

The period of time between exposure to an infectious agent and the appearance of symptoms of the infection or disease it causes.

The entry, establishment, and replication of pathogens inside a host organism.

A type of illness caused by a pathogenic agent, including viruses, bacteria, fungi, protozoa, parasites, or abnormal proteins known as prions.

A type of protein produced by cells of the immune system that help keep viruses, bacteria, and cancer cells from growing.

The use of veins through which medications and solutions are administered.

An infection that is currently not producing or showing any symptoms but has the potential of being reactivated and then manifesting symptoms.

A broad group of molecules including fats and waxes that are insoluble in water and are an important part of living cells.

An infection of the protective membranes that cover the brain and spinal cord, known collectively as the meninges.

Sometimes referred to as a microorganism, a microbe is an organism that is microscopic and thus invisible to the naked eye.

The relative occurrence of a disease or a condition that causes illness.

The number of deaths in a given time or place.

The moist linings of body passages and internal cavities involved with absorption and secretion of substances.

A change in the sequence of DNA in a cell&rsquos genome that can be caused by radiation, viruses, certain types of chemicals, errors, or environmental factors that occur during cell division and DNA replication.

A unit of length equal to one one-billionth (1 x 10 -9 ) of a meter.

National Institute of Allergy and Infectious Diseases (NIAID)

Part of the U.S. Department of Health and Human Services and the National Institutes of Health, NIAID conducts and supports basic and applied research to better understand, treat, and ultimately prevent infectious, immunologic, and allergic diseases.

The process by which certain heritable traits that contribute to the survival and reproductive success of an organism become more widespread within a population over successive generations.

Also called neurotoxins, these refer to poisonous substances that cause damage to cells in the nervous system.

A living being that can reproduce, grow, react to external stimuli, and maintain its internal equilibrium.

An unexpected increase in the incidence of a particular disease over a given time period and geographic range. A general term that may refer either to an epidemic or a pandemic.

An increase in the occurrence of a particular disease over a very large region, such as a continent or the entire globe, that is greater than what is expected over a given period of time.

A close relationship between two organisms in which one organism, the parasite, benefits at the expense of the host organism.

A biological agent that causes disease.

A ring of DNA usually found in bacteria that is separate from and can replicate independently from DNA in a chromosome and can provide bacteria with some advantages, such as antibiotic resistance.

Large molecules composed of one or more chains of amino acids in a specific order determined by the base sequence of nucleotides in the DNA coding.

A taxonomic group of single-celled microorganisms that live in almost every kind of habitat and include some pathogenic parasites of humans and other animals.

The process that allows technicians to create artificial pieces of DNA in which two or more DNA sequences, often from separate organisms, are combined in ways that would not normally occur naturally.

The process of producing a copy of a strand of DNA.

An organism in which a parasite that is pathogenic for some other organism lives and reproduces without harming its host.

The part of the anatomy that has to do with the passage of air and includes the nose, larynx, trachea, and lungs.

An inflammatory disease that may be caused by an untreated or improperly treated case of strep throat.

A type of virus that is responsible for causing upper respiratory tract infections in humans, otherwise known as the common cold.

Short for ribonucleic acid, RNA is a molecule with long strands of nucleic acids containing a nitrogenous base, a ribose sugar, and a phosphate. RNA is responsible for controlling a number of chemical activities, including protein synthesis, within cells.

A serious mental illness characterized by the presence of hallucinations, delusions, disorganized speech or thinking, a loss of contact with reality, and a noticeable deterioration of functioning in everyday life.

Any abnormal tissue on the skin caused by injury or disease.

One of the most basic units of biological classification, ranking just below the genus and comprising individuals or populations capable of interbreeding.

The male gamete, or sex cell, which carries the hereditary material of the male parent and unites with the female egg cell during sexual reproduction.

An infection caused by any one of several harmful species or subspecies of bacteria of the genus Staphylococcus.

The process of destroying all forms of life, including infectious agents, from a surface, fluid, or biological medium with the use of heat, chemicals, irradiation, high pressure, filtration, or some combination of these methods.

A genetic variant or specific subtype of a microorganism, such as a virus or bacteria.

The process of land conversion and development around the periphery of major cities.

A subjective indication of the presence of disease or a departure from the body&rsquos normal state of functioning.

The process by which tissues are intentionally grown under controlled conditions.

A poisonous substance, often a protein, produced by the metabolic processes of living cells or organisms that can cause disease if introduced into the body.

The main trunk of the network of tubes that carries air to and from the lungs, sometimes referred to as the &ldquowindpipe.&rdquo

The area, sometimes referred to as an ecotone, encompassing the edges of two distinct ecosystems, such as the area where a forest intersects with grassland.

A vaccine that is effective against all forms of the influenza virus.

Disease of the organs involved in the excretion of fluids and reproduction.

A biological preparation that improves the immune system&rsquos ability to recognize and destroy harmful infectious agents.

An organism (usually an arthropod such as a flea, mosquito, or tick) that carries an infectious agent from one host to another.

An infectious agent that is only capable of replicating itself inside the living cells of other organisms.

A special type of cell that works as part of the immune system to defend the body against disease and infection.

World Health Organization (WHO)

The directing and coordinating authority for health within the United Nations system, responsible for providing leadership on global health matters, shaping the health research agenda, setting norms and standards, articulating evidence-based policy options, providing technical support to countries and monitoring and assessing health trends.

A broad group of microscopic fungi that includes harmless forms of yeast used in baking and alcoholic fermentation as well as pathogenic species that can cause disease.