Infectious disease

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

An infectious disease is a clinically evident disease resulting from the presence of pathogenic microbial agents, including viruses, bacteria, fungi, protozoa, multicellular parasites, and aberrant proteins known as prions. These pathogens are able to cause disease in animals and/or plants.

Infectious pathologies are usually qualified as contagious diseases (also called communicable diseases) due to their potentiality of transmission from one person or species to another. ^[1] Transmission of an infectious disease may occur through one or more of diverse pathways, including physical contact with infected individuals. These infecting agents may also be transmitted through liquids, foods, body fluids, contaminated objects, aerocole particles, or by vectors.

The term infectivity describes the ability of an organism to enter, survive and multiply in the host; while the infectiousness of a disease indicates the comparative ease with which the disease is transmitted to other hosts.^[2] An infection, however, is not synonymous with an infectious disease, as an infection may not cause important clinical symptoms or impair host function.

Epidemiology is an important tool used to study disease in a population. For infectious diseases it helps to determine if a disease outbreak is sporadic (occasional occurrence), endemic (regular occurrence in a region), epidemic (unusually high number of cases in a region), or pandemic (global epidemic).

Diagnosis of infectious disease sometimes involves identifying an infectious agent either directly or indirectly. In practice most minor infectious diseases such aswarts,cutaneous abscesses, respiratory system infections and diarrheal diseases are diagnosed by their clinical presentation. Conclusions about the cause of the disease are based upon the likelihood that a patient came in contact with a particular agent, the presence of a microbe in a community, and other epidemiological considerations. Given sufficient effort, all known infectious agents can be specifically identified.

Diagnosis of infectious disease is nearly always initiated by medical history and physical examination. More detailed identification techniques involve the culture of infectious agents isolated from a patient. Culture allows identification of infectious organisms by examining their microscopic features, by detecting the presence of substances produced by pathogens, and by directly identifying an organism by its genotype. The benefits of identification, however, are often greatly outweighed by the cost, as often there is no specific treatment, the cause is obvious, or the outcome of an infection is benign.

Techniques (such as X-rays, CT scans, PET scans or NMR) are used to produce images of internal abnormalities resulting from the growth of an infectious agent. The images are useful in detection of, for example, a bone abscess or a spongiform encephalopathy produced by a prion.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

• Abū Alī ibn Sīnā (Avicenna) discovered the contagious nature of infectious diseases in the early 11th century, for which he is considered the father of modern medicine. He introduced quarantine as a means of limiting the spread of contagious and infectious diseases in The Canon of Medicine, circa 1020. He also stated that bodily secretion is contaminated by foul foreign earthly bodies before being infected, but he did not view them as primary causes of disease.

• When the Black Death bubonic plague reached al-Andalus in the 14th century, Ibn Khatima and Ibn al-Khatib hypothesized that infectious diseases are caused by microorganisms which enter the human body. Such ideas became more popular in Europe during the renaissance, particularly through the writing of the Italian monk Girolamo Fracastoro.^[1]

• Anton van Leeuwenhoek (1632-1723) advanced the science of microscopy, allowing for easy visualization of bacteria.

• Louis Pasteur proved beyond doubt that certain diseases are caused by infectious agents, and developed a vaccine for rabies.

• Robert Koch, provided the study of infectious diseases with a scientific basis known as Koch’s postulates.

• Edward Jenner, Jonas Salk and Albert Sabin developed effective vaccines for smallpox and polio, which would later result in the eradication and near-eradication of these diseases, respectively.

• Alexander Fleming discovered the world’s first antibiotic Penicillin.

• Gerhard Domagk develops Sulphonamides, the first broad spectrum synthetic antibacterial drugs.

A pandemic (or global epidemic) is a disease that affects people over an extensive geographical area.

• Plague of Justinian, from 541 to 750, killed between 50 and 60 percent of Europe’s population.^[2]
• The Black Death of 1347 to 1352 killed 25 million in Europe over 5 years (estimated to be between 25 and 50% of the populations of Europe, Asia, and Africa – the world population at the time was 500 million).
• The introduction of smallpox, measles and typhus to the areas of Central and South America by European explorers during the 15th and 16th centuries caused pandemics among the native inhabitants. Between 1518 and 1568 disease pandemics are said to have caused the population of Mexico to fall from 20 million to 3 million.^[3]
• The first European influenza epidemic occurred between 1556 and 1560, with an estimated mortality rate of 20%.^[3]
• Smallpox killed an estimated 60 million Europeans in the 18th century alone. Up to 30% percent of those infected, including 80% of the children under 5 years of age, died from the disease, and one third of the survivors went blind. ^[4]
• The Influenza Pandemic of 1918 (or the Spanish Flu) killed 25-50 million people (about 2% of world population of 1.7 billion).^[5] Today Influenza kills about 250,000 to 500,000 worldwide each year.

In most cases, microorganisms live in harmony with their hosts. Such is the case for many tropical viruses and the insects, monkeys, or other animals in which they have lived and reproduced. Because the microbes and their hosts have co-evolved, the hosts gradually become resistant to the microorganisms. When a microbe jumps from a long-time animal host to a human being, it may cease to be a harmless parasite and become pathogenic.

With most new infectious diseases, some human action is involved, changing the environment so that an existing microbe can take up residence in a new niche. When that happens, a pathogen that had been confined to a remote habitat appears in a new or wider region, or a microbe that had infected only animals suddenly begins to cause human disease.

Several human activities have led to the emergence and spread of new diseases, see also Globalization and Disease:

• Encroachment on wildlife habitats. The construction of new villages and housing developments in rural areas brings people into contact with animals–and the microbes they harbor.
• Changes in agriculture. The introduction of new crops attracts new crop pests and the microbes they carry to farming communities, exposing people to unfamiliar diseases.
• The destruction of rain forests. As countries make use of their rain forests, by building roads through forests and clearing areas for settlement or commercial ventures, people encounter insects and other animals harboring previously unknown microorganisms.
• Uncontrolled urbanization. The rapid growth of cities in many developing countries tends to concentrate large numbers of people into crowded areas with poor sanitation. These conditions foster transmission of contagious diseases.
• Modern transport. Ships and other cargo carriers often harbor unintended “passengers”, that can spread diseases to faraway destinations. While with international jet-airplane travel, people infected with a disease can carry it to distant lands, or home to their families, before their first symptoms appear.

The medical treatment of infectious diseases falls into the medical field of Infectiology and in some cases the study of propagation pertains to the field of Epidemiology. Generally, infections are initially diagnosed by primary care physicians or internal medicine specialists. For example, an “uncomplicated”pneumonia will generally be treated by the internist or the pulmonologist (lung physician).The work of the infectiologist therefore entails working with both patients and general practitioners, as well as laboratory scientists, immunologists, bacteriologists and other specialists..

An infectious disease team may be alerted when:

• The disease has not been definitively diagnosed after an initial workup
• The patient is immunocompromised (for example, in AIDS or after chemotherapy);
• The infectious agent is of an uncommon nature (e.g. tropical diseases);
• The disease has not responded to first line antibiotics;
• The disease might be dangerous to other patients, and the patient might have to be isolated.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

Among the almost infinite varieties of microorganisms, relatively few cause disease in otherwise healthy individuals.^[1] Infectious disease results from the interplay between those few pathogens and the defenses of the hosts they infect. The appearance and severity of disease resulting from any pathogen depends upon the ability of that pathogen to damage the host as well as the ability of the host to resist the pathogen. Infectious microorganisms, or microbes, are therefore classified as either primary pathogens or as opportunistic pathogens according to the status of host defenses.

Infectious disease are caused by pathogenic microorganisms. These disease can be categorized into 4 main categories:

• Bacterial infections
• Viral infecions
• Fungal infections
• Parasitic infections

Bacterial infections can be classified based on their cellular features and specificities including:

• Cellular wall thickness: Gram staining mathod
  • Gram positive bacteria
  • Gram negative bacteria
• Microscopic shape
  • Bacillus shaped bacteria
  • Branchig shaped bacteria
  • Coccus shaped bacteria
  • Coma shaped bacteria
• Use an O2-dependent system to generate ATP
  • Aerobics
  • Anaerobics
• Oxidative damage susceptibility=Catalase enzyme
  • Catalase positive bacteria
  • Catalase negative bacteria
• Oxidase containing method
  • Oxidase positive bacteria
  • Oxidase negative bacteria
• Lactose fermenting method
  • Lactose fermenting bacteria
  • Non-lactose fermenting bacteria
• Coagulase containing method
  • Coagulase positive bacteria
  • Coagulase negative bacteria

Viral classification:

• Genetic material
  • DNA virus
  • RNA virus
• Number of genetic copies in the virus
  • Single stranded genome
  • Double stranded genome

RNA viruses themselves can be categorized based on their ability to use host cell polymerizes or need to bring their own polymerizes with themselves into 2 categories:

• Positive stranded viruses
• Negative stranded viruses

Bacteria

Gram staining

Gram positive

Aerobic

Anerobic

Bacillus shaped bacteria

Branching shaped bacteria

Bacillus shaped bacteria

Coccus shaped bacteria

Branching shaped bacteria

Listeria Bacillus Corynebacterium

Nocardia

Clostridium Propionibacterium

Staphylococcus Streptococcus

Actinomyces

Gram negative

Coccus shaped bacteria

Bacillus shaped bacteria

Comma shaped bacteria

Campylobacter jejuni Vibrio cholerae Helicobacter pylori

Diplococcus shaped gram negative bacteria

Coccobacillus shaped gram negative bacteria

Neisseria gonorrhoaea Neisseia meningtidis Moraxella

Haemophilus influenzae Pasteurella Brucella Bordetella pertussis Francisella tularensis

Lactose fermentation

Positive

Negative

Klebsiella Escherichia coli Enterobacter Citrobacter Serratia

Pseudomonas Shigella Salmonella Yersinia Proteus

Virus classification

Viral genome type

DNA viruses

RNA viruses

ssDNA

dsDNA

ssRNA

dsRNA

Parvovirus

Reoviridae

Linear genome

Circular genome

Positive strand

Negative strand

Herpes virus Adenovirus Poxvirus Parvovirus

Papillomavirus Polyomavirus Hepadnavirus

Picornaviruses Hepevirus Caliciviruses Flaviviruses Togaviruses Retroviruses Coronaviruses Arenaviruses

Arenavirus Bunyavirus Paramyxovirus Orthomyxoviruses Filoviruses Rhabdoviruses

Mycology classification

Main infectious sites and methods

Systemic mycoses

Cutaneous mycoses

Histoplasma Blastomyces Coccidioidomyces Paracoccidioidomyces

Opportunistic fungal infections

Candida albicans Aspergillus fumigatus Cryptococcus neoformans Mucor spp. Rhizopus spp. Pneumocystis jirovecii Sporothrix schenckii

Tinea dermatophytes

Tinea pityriasis versicolor

Tinea capitis Tinea corporis Tinea cruris Tinea pedis Tinea unguium

Malassezia spp. (a Pityrosporum spp.)

Parasites classification

Main categories

Ectoparasites

Protozoa

Worms

Sarcoptes scabiei Pediculus humanus Phthirus pubis

gastrointestinal infections

CNS infections

hematologic infections

Visceral infections and Sexual transmitted diseases

Nematodes (roundworms)

Cestodes (tapeworms)

Trematodes (flukes)

Giardia lamblia Entamoeba histolytica Cryptosporidium

Toxoplasma gondii Naegleria fowleri Trypanosoma brucei

Plasmodium vivax Plasmodium ovale Plasmodium falciparum Plasmodium malariae Babesia

Trypanosoma cruzi Leishmania donovani Trichomonas vaginalis

Enterobius vermicularis (pinworm) Ascaris lumbricoides (giant roundworm) Strongyloides stercoralis (threadworm) Ancylostoma duodenale Necator americanus (hookworms) Trichinella spiralis Trichuris trichiura (whipworm) Toxocara canis Onchocerca volvulus Loa loa Wuchereria bancrofti

Taenia solium Diphyllobothrium latum Echinococcus granulosus

Schistosoma Clonorchis sinensis

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• Primary Pathogens cause disease as a result of their presence or activity within the normal, healthy host, and their intrinsic virulence (the severity of the disease they cause) is, in part, a necessary consequence of their need to reproduce and spread. Many of the most common primary pathogens of humans only infect humans, however many serious diseases are caused by organisms acquired from the environment or which infect non-human hosts.

• Opportunistic Pathogens are organisms which cause an infectious disease in a host with depressed resistance are classified as opportunistic pathogens. Opportunistic disease may be caused by microbes that are ordinarily in contact with the host, such as bacteria or fungi in the gastrointestinal or the upper respiratory tract, and they may also result from (otherwise innocuous) microbes acquired from other hosts (as in Clostridium difficile enterocolitis) or from the environment as a result of traumatic introduction (as in surgical wound infections or compound fractures). An opportunistic disease requires impairment of host defenses, which may occur as a result of genetic defects (such as Chronic granulomatous disease), exposure to antimicrobial drugs or immunosuppressive chemicals (as might occur following poisoning or cancer chemotherapy), exposure to ionizing radiation, or as a result of an infectious disease with immunosuppressive activity (such as with measles, malaria or HIV disease). Primary pathogens may also cause more severe disease in a host with depressed resistance than would normally occur in an immunosufficient host.

One way of proving that a given disease is “infectious”, is to satisfy Koch’s postulates (first proposed by Robert Koch), which demands that the infectious agentbe identified only in patients and not in healthy controls, and that patients who contract the agent also develop the disease. These postulates were first used in the discovery that Mycobacteria species cause tuberculosis. Koch’s postulates cannot be met ethically for many human diseases because they require experimental infection of a healthy individual with a pathogen produced as a pure culture. Often, even diseases that are quite clearly infectious do not meet the infectious criteria. For example,Treponema pallidum, the causative spirochete of syphilis, cannot be cultured in vitro – however the organism can be cultured in rabbit testes. It is less clear that a pure culture comes from an animal source serving as host than it is when derived from microbes derived from plate culture.

One of the main infectious diseases pathogenesis is due to antigens, which can be classified into:

• Exogenous antigens: Natural invaders, such as infectious pathogens and animal venoms, are exogenous proteins that are toxic to host cells and consist of protein complexes of variable size expressing different levels of virulence. Endogenous proteins that are released from activated or destroyed cells, and those produced in an immune response, including proinflammatory cytokines and proteolytic enzymes from immune cells such as macrophage or granulocytes, could also be toxic to the host cells.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

Infectious disease are caused by pathogenic microorganisms. These disease can be categorized into 4 main categories:

• Bacterial infections
• Viral infecions
• Fungal infections
• Parasitic infections

• Anthrax

• Botulism

• Diptheria

• Gas Gangrene and other Clostridial Infections

• Listeria monocytogenes and Eryspelothrix Rhusiopathiae

• Mixed Anaerobic Infections

• Pneumococcal Infections

• Staphylococcal Infections

• Streptococcal Infections

• Tetanus

• Bartonellosis

• Brucellosis

• Chancroid

• Cholera

• Donovanosis (Granuloma Inguinale)

• Enteric Bacilli

• Gonococcal Infections

• Haemophilus Infections

• Legionella Infections

• Melioidosis and Glanders

• Meningococcal Infections

• Salmonellosis

• Shigellosis

• Tularemia

• Yersinia enterocolitica Infection (Yersiniosis)

• Yersinia Pestis Infection

• Whooping Cough
• Anthrax

• Botulism

• Diptheria

• Gas Gangrene and other Clostridial Infections

• Listeria monocytogenes and Eryspelothrix Rhusiopathiae

• Mixed Anaerobic Infections

• Pneumococcal Infections

• Staphylococcal Infections

• Streptococcal Infections

• Tetanus

• Tuberculosis
• Leprosy (Hansen’s disease)
• Other Mycobacterial Infections

• Syphilis
• Non-venereal Treponematosis: Yaws, Pinta, and Endemic Syphilis
• Leptospirosis
• Relapsing Fever
• Lyme disease (Borreliosis)

• Arbovirus Infections

• Arenavirus Infections

• The Biology of Viruses

• Cytomegalovirus Infection

• Enteroviruses and Reoviruses

• Epstein-Barr Virus Infections, Including Infectious Mononucleosis

• Herpes Simplex Viruses

• Human Papillomavirus Infections

• Influenza

• Measles (Rubeola)

• Mumps

• Rabies, Rhabdovirus, and Marburg-like Agents

• Common Viral Respiratory Infections

• The Human Retroviruses

• Rubella (“German Measles“) and Other Viral Exanthems

• Smallpox, Vaccinia and Other Poxviruses

• Varicella-Zoster Virus Infections

• Viral Gastroenteritis

• West Nile Virus

• Yellow Fever Virus

• Actinomycosis and Nocardiosis
• Fungal infections

• Rickettsial diseases

• Mycoplasma Infections

• Chlamydial Infections

• Amebiasis

• Babesiosis

• Cryptosporidiosis

• Filariasis

• Giardiasis

• Leishmaniasis

• Malaria

• Nematodes, Cestodes, and Hermaphroditic Trematodes

• Pneumocystis Carinii pneumonia

• Scabies, Chiggers, and other ectoparasites

• Schistosomiasis

• Toxoplasmosis

• Trichinosis

• Trypanosomiasis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

Epidemiology is an important tool used to study disease in a population. For infectious diseases it helps to determine if a disease outbreak is sporadic (occasional occurrence), endemic (regular cases often occurring in a region), epidemic (an unusually high number of cases in a region), or pandemic (a global epidemic).

The World Health Organization collects information on global deaths by International Classification of Disease (ICD) code categories. The following table lists the top infectious disease killers which caused more than 100,000 deaths in 2002 (estimated). 1993 data is included for comparison.

Worldwide mortality due to infectious diseases^[1]

Rank	Cause of death	Deaths 2002	Percentage of all deaths	Deaths 1993	1993 Rank
N/A	All infectious diseases	14.7 million	25.9%	16.4 million	32.2%
1	Lower respiratory infections[2]	3.9 million	6.9%	4.1 million	1
2	HIV/AIDS	2.8 million	4.9%	0.7 million	7
3	Diarrheal diseases[3]	1.8 million	3.2%	3.0 million	2
4	Tuberculosis (TB)	1.6 million	2.7%	2.7 million	3
5	Malaria	1.3 million	2.2%	2.0 million	4
6	Measles	0.6 million	1.1%	1.1 million	5
7	Pertussis	0.29 million	0.5%	0.36 million	7
8	Tetanus	0.21 million	0.4%	0.15 million	12
9	Meningitis	0.17 million	0.3%	0.25 million	8
10	Syphilis	0.16 million	0.3%	0.19 million	11
11	Hepatitis B	0.10 million	0.2%	0.93 million	6
12-17	Tropical diseases (6)[4]	0.13 million	0.2%	0.53 million	9, 10, 16-18
Note: Other causes of death include maternal and perinatal conditions (5.2%), nutritional deficiencies (0.9%), noncommunicable conditions (58.8%), and injuries (9.1%).

The top three single agent/disease killers are HIV/AIDS, TB and malaria. While the number of deaths due to nearly every disease have decreased, deaths due to HIV/AIDS have increased fourfold. Childhood diseases include pertussis, poliomyelitis, diphtheria, measles and tetanus. Children also make up a large percentage of lower respiratory and diarrheal deaths.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]

An infectious disease is transmitted from some source. Defining the means of transmission plays an important part in understanding the biology of an infectious agent, and in addressing the disease it causes. Transmission may occur through several different mechanisms. Respiratory diseases and meningitis are commonly acquired by contact with aerosolized droplets, spread by sneezing, coughing, talking or even singing. Gastrointestinal diseases are often acquired by ingesting contaminated food and water. Sexually transmitted diseases are acquired through contact with bodily fluids, generally as a result of sexual activity. Some infectious agents may be spread as a result of contact with a contaminated, inanimate object (known as a fomite), such as a coin passed from one person to another, while other diseases penetrate the skin directly.

Transmission of infectious diseases may also involve a “vector“. Vectors may be mechanical or biological. A mechanical vector picks up an infectious agent on the outside of its body and transmits it in a passive manner. An example of a mechanical vector is a housefly, which lands on cow dung, contaminating its appendages with bacteria from the feces, and then lands on food prior to consumption. The pathogen never enters the body of the fly.

In contrast, biological vectors harbor pathogens within their bodies and deliver pathogens to new hosts in an active manner, usually a bite. Biological vectors are often responsible for serious blood-borne diseases, such as malaria,viral encephalitis, Chagas disease and African sleeping sickness. Biological vectors are usually, though not exclusively, arthropods, such as mosquitoes, ticks, fleas and lice. Vectors are often required in the life cycle of a pathogen. A common strategy, used to control vector borne infectious diseases, is to interrupt the life cycle of a pathogen, by killing the vector.

The relationship between virulence and transmission is complex, and has important consequences for the long term evolution of a pathogen. Since it takes time for a microbe and a new host species to co-evolve, an emerging pathogen may hit its earliest victims especially hard. It is usually in the first wave of a new disease that death rates are highest. If a disease is rapidly fatal, the host may die before the microbe can get passed along to another host. However, this cost may be overwhelmed by the short term benefit of higher infectiousness if transmission is linked to virulence, as it is for instance in the case of cholera (the explosive diarrhea aids the bacterium in finding new hosts) or many respiratory infections (sneezing and coughing create infectious aerosols).

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