Infections associated with diseases are those infections that are associated with possible infectious etiologies that meet the requirements of Koch's postulates. Other methods of causation are described by the Bradford Hill criteria and evidence-based medicine.
Koch's postulates have been modified by some epidemiologists, based on the sequence-based detection of distinctive pathogenic nucleic acid sequences in tissue samples. When using this method, absolute statements regarding causation are not always possible. Higher amounts of distinctive pathogenic nucleic acid sequences should be in those exhibiting disease, compared to controls. In addition, the DNA load should become lower with the resolution of the disease. The distinctive pathogenic nucleic acid sequences load should also increase upon recurrence.
Other conditions are met to establish cause or association including studies in disease transmission. This means that there should be a high disease occurrence in those carrying a pathogen, evidence of a serological response to the pathogen, and the success of vaccination prevention. Direct visualization of the pathogen, the identification of different strains, immunological responses in the host, how the infection is spread and, the combination of these should all be taken into account to determine the probability that an infectious agent is the cause of the disease. A conclusive determination of a causal role of an infectious agent for in a particular disease using Koch's postulates is desired yet this might not be possible. [1]
The leading cause of death worldwide is cardiovascular disease, but infectious diseases are the second leading cause of death worldwide and the leading cause of death in infants and children. [2]
Other causes or associations of disease are: a compromised immune system, environmental toxins, radiation exposure, diet and other lifestyle choices, stress, and genetics. Diseases may also be multifactorial, requiring multiple factors to induce disease. For example: in a murine model, Crohn's disease can be precipitated by a norovirus, but only when both a specific gene variant is present and a certain toxin has damaged the gut. [3]
A list of the more common and well-known diseases associated with infectious pathogens is provided and is not intended to be a complete listing.
Asthma | Mycoplasma pneumoniae [4] and Chlamydia pneumoniae infections are associated with the onset and symptoms of asthma. [5] |
Autoimmune diseases | Autoimmune diseases are associated with Neoehrlichia mikurensis infection, and Borrelia miyamotoi infection, [1] and HIV, [6] and the bacterium Mycobacterium tuberculosis . [7] Autoimmune thyroid disease is associated with Epstein-Barr virus. [8] |
Cancer | Anal cancer is associated with human papillomaviruses. [9] Bladder cancer Schistosoma helminths can cause cancer. [10] |
Chronic fatigue syndrome | Chronic fatigue syndrome (also known as myalgic encephalomyelitis) is associated with enteroviruses (such as Coxsackie B virus), [31] [32] human herpesvirus 6 variant A, [33] human herpesvirus 7, [34] and parvovirus B19. [35] [36] The bacteria Coxiella burnetii [37] and Chlamydia pneumoniae [38] are known causes of chronic fatigue syndrome (antibiotics can cure these bacterial forms of chronic fatigue syndrome). |
Common cold | The common cold is also known as Acute rhinosinusitis (ARS) and is caused by a viral infection. [39] Efforts to develop vaccines are ongoing. [2] |
Crohn's disease | One study found ileocecal Crohn's disease is associated with viral species from the enterovirus genus (but note that all the study cohort with ileocecal Crohn's disease had disease-associated mutations in either their NOD2 or ATG16L1 genes). [40] Crohn's disease is associated with Mycobacterium avium subspecies paratuberculosis. [41] In a murine model, Crohn's disease is precipitated by the norovirus CR6 strain, [3] [42] but only in combination with a variant of the Crohn's susceptibility gene ATG16L1, and chemical toxic damage to the gut. In other words, in this mouse model, Crohn's is precipitated only when these three causal factors (virus, gene, and toxin) act in combination. |
Coronary heart disease | Coronary heart disease is associated with herpes simplex virus 1 and the bacterium Chlamydia pneumoniae . [43] |
Dementia | Dementia is associated with herpes simplex virus type 1, herpes simplex virus type 2, cytomegalovirus, West Nile virus, bornavirus, and HIV. Dementia is also associated with the helminth Taenia solium (pork tapeworm), and with Borrelia species bacteria. [44] |
Depression | Depression is associated with cytomegalovirus [45] and West Nile virus, [46] and the protozoan parasite Toxoplasma gondii. [47] It is thought that depression may be precipitated by the effect of immune signals (such as pro-inflammatory cytokines) reaching the brain from infections located in the peripheries of the body. [48] [49] Major depressive disorder is associated with bornavirus, [50] as well as Bartonella [51] and Borrelia [44] species bacteria. |
Diabetes mellitus type 1 | Diabetes mellitus type 1 is associated with viral species from the enterovirus genus, [53] [54] specifically echovirus 4 [55] and Coxsackie B virus (the latter it is thought may infect and destroy the insulin producing beta-cells in the pancreas and also damage these cells via indirect autoimmune mechanisms). [56] [57] One study found Coxsackie B1 virus associated with a higher risk of the beta cell autoimmunity that portends type 1 diabetes; though Coxsackie B3 and B6 viruses were found to be associated with a reduced risk of such autoimmunity (possibly due to immune cross-protection against Coxsackie B1 virus). [58] In boys, human parechovirus infection has been linked to a subsequent appearance of diabetes-associated autoantibodies. [59] |
Diabetes mellitus type 2 | Diabetes mellitus type 2 is associated with cytomegalovirus, [60] hepatitis C virus, [61] enteroviruses, [54] Ljungan virus [62] |
Dilated cardiomyopathy | Dilated cardiomyopathy is associated with enteroviruses such as Coxsackie B virus. [63] |
Epilepsy | Epilepsy is associated with human herpesvirus 6. [64] |
Gonorrhea | Men who have had a gonorrhea infection have a risk of having prostate cancer. [65] |
Guillain–Barré syndrome | Guillain–Barré syndrome is associated with the bacterium Campylobacter jejuni , and with the viruses cytomegalovirus [66] and enterovirus. [67] |
Irritable bowel syndrome | Irritable bowel syndrome (IBS) is associated with the bacteria enteroaggregative Escherichia coli [68] and Mycobacterium avium subspecies paratuberculosis, [69] the protozoan parasite Giardia lamblia , [70] and pathogenic strains of the protozoan parasite Blastocystis hominis . [71] Irritable bowel syndrome in those with HIV is associated with the protozoan Dientamoeba fragilis . [72] |
Low back pain | Lower back pain is associated with a spinal disc infection with anaerobic bacteria, especially the bacterium Cutibacterium acnes . [73] [74] |
Lupus | Lupus is associated with the viruses parvovirus B19, [75] Epstein-Barr virus, [76] and cytomegalovirus. [77] |
Lyme disease | Lyme disease is associated with infection by Borrelia miyamotoi , and Rickettsia species. [1] |
Metabolic syndrome | Metabolic syndrome is associated with the bacteria Chlamydia pneumoniae [78] and Helicobacter pylori , as well as the viruses cytomegalovirus and herpes simplex virus 1. [79] |
Multiple sclerosis | Multiple sclerosis, a demyelinating disease, is associated with Epstein-Barr virus [80] (and strongly associated with certain genetic variants of this virus), [81] human herpesvirus 6, [82] varicella zoster virus, [83] and the bacterium Chlamydia pneumoniae . [84] |
Myocardial infarction | Myocardial infarction (heart attack) is associated with Chlamydia pneumoniae , [85] cytomegalovirus [86] and Coxsackie B virus (an enterovirus). [87] (Coxsackie B virus is also associated with sudden unexpected death due to myocarditis). [88] |
Obesity | Obesity is associated with adenovirus 36, which is found in 30% of obese people, but only in 11% of non-obese people. [89] [90] It has further been demonstrated that animals experimentally infected with adenovirus 36 (or adenovirus 5, or adenovirus 37) will develop increased obesity. [91] Adenovirus 36 induces obesity by infecting fat cells (adipocytes), wherein the expression of the adenovirus E4orf1 gene turns on both the cell's fat producing enzymes and also instigates the generation of new fat cells. [92] Evidence suggests that obesity can be a viral disease, and that the worldwide obesity epidemic that began in the 1980s may be in part due to viral infection. [93] [94] Obesity is also associated with higher gut levels of certain Bacillota bacteria in relation to Bacteroidota bacteria. Overweight individuals tend have more Bacillota bacteria (such as Clostridium , Staphylococcus , Streptococcus , and Helicobacter pylori ) in their gut, whereas normal weight individuals tend have more Bacteroidota bacteria. [95] |
Obsessive–compulsive disorder | Obsessive–compulsive disorder is associated with Streptococcus [96] and Borrelia [44] species bacteria. |
Panic disorder | Panic disorder is associated with Borrelia [44] and Bartonella [51] species bacteria. [51] |
Parkinson's disease | Parkinson's disease is associated with influenza A virus, [97] as well as the protozoan parasite Toxoplasma gondii . [98] |
Psoriasis | Psoriasis is associated with a Helicobacter pylori trigger. [99] |
Rheumatoid arthritis | Rheumatoid arthritis is associated with parvovirus B19. [75] |
Sarcoidosis | Sarcoidosis is associated with Mycobacteria [100] species and the bacterium Helicobacter pylori [101] |
Schizophrenia | Schizophrenia is associated with bornavirus, [50] the bacterium Chlamydia trachomatis , [102] as well as Borrelia species bacteria. [44] Schizophrenia is also linked to neonatal infection with Coxsackie B virus (an enterovirus), which one study found carries an increased risk of adult onset schizophrenia. [103] Prenatal exposure to influenza virus in the first trimester of pregnancy increases the risk of schizophrenia by 7-fold. [104] |
Severe acute respiratory syndrome | Severe acute respiratory syndrome is a viral disease. Efforts to develop a vaccine are ongoing. [2] |
Stroke | Stroke is associated with the bacteria Chlamydia pneumoniae , [105] Helicobacter pylori , [106] Mycobacterium tuberculosis , [107] and Mycoplasma pneumoniae , [108] as well as the virus varicella zoster virus [109] and Histoplasma species fungi. [110] |
Thromboangiitis obliterans | Thromboangiitis obliterans is associated with Rickettsia species bacteria. [111] |
Tourette syndrome | Tourette syndrome is associated with Streptococcus species bacteria. [112] Aggravating or contributory microbes in Tourette's may include the bacteria Mycoplasma pneumoniae , [113] Chlamydia pneumoniae , Chlamydia trachomatis , and the protozoan parasite Toxoplasma gondii . [114] |
Vasculitis | Vasculitis is associated with HIV, parvovirus B19, [75] and hepatitis B virus. The hepatitis C virus is an established cause of vasculitis. |
Infectious pathogen-associated diseases include many of the most common and costly chronic illnesses. The treatment of chronic diseases accounts for 75% of all US healthcare costs (amounting to $1.7 trillion in 2009). [115]
One of first examples of systematic study of disease causation was Avicenna, in the tenth century. The history of infection and disease were observed in the 1800s and related to the one of the tick-borne diseases, Rocky Mountain spotted fever. The cause of viral encephalitis was discovered in Russia based upon epidemiological clustering of cases. The virus causing this illness was isolated in 1937. The rash typical of Lyme borreliosis was identified the early 1900s. [1] Historically, some chronic diseases were linked or associated with infectious pathogens. [116] [117] [118]
Pneumonia is an inflammatory condition of the lung primarily affecting the small air sacs known as alveoli. Symptoms typically include some combination of productive or dry cough, chest pain, fever, and difficulty breathing. The severity of the condition is variable.
Infectious mononucleosis, also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adults, the disease often results in fever, sore throat, enlarged lymph nodes in the neck, and fatigue. Most people recover in two to four weeks; however, feeling tired may last for months. The liver or spleen may also become swollen, and in less than one percent of cases splenic rupture may occur.
The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. Epstein–Barr virus (EBV) is the first identified oncogenic virus, that is a virus that can cause cancer. EBV establishes permanent infection in humans. It causes infectious mononucleosis and is also tightly linked to many malignant diseases (cancers). Various vaccine formulations underwent testing in different animals or in humans. However, none of them were able to prevent EBV infection and no vaccine has been approved to date.
Neutropenia is an abnormally low concentration of neutrophils in the blood. Neutrophils make up the majority of circulating white blood cells and serve as the primary defense against infections by destroying bacteria, bacterial fragments and immunoglobulin-bound viruses in the blood. People with neutropenia are more susceptible to bacterial infections and, without prompt medical attention, the condition may become life-threatening.
Coxsackie B is a group of six serotypes of coxsackievirus (CVB1-CVB6), a pathogenic enterovirus, that trigger illness ranging from gastrointestinal distress to full-fledged pericarditis and myocarditis.
Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form, typically progressing from a long-lasting asymptomatic condition up to a decompensated hepatic disease and hepatocellular carcinoma (HCC).
Enterovirus is a genus of positive-sense single-stranded RNA viruses associated with several human and mammalian diseases. Enteroviruses are named by their transmission-route through the intestine.
Chlamydia pneumoniae is a species of Chlamydia, an obligate intracellular bacterium that infects humans and is a major cause of pneumonia. It was known as the Taiwan acute respiratory agent (TWAR) from the names of the two original isolates – Taiwan (TW-183) and an acute respiratory isolate designated AR-39. Briefly, it was known as Chlamydophila pneumoniae, and that name is used as an alternate in some sources. In some cases, to avoid confusion, both names are given.
An opportunistic infection is an infection caused by pathogens that take advantage of an opportunity not normally available. These opportunities can stem from a variety of sources, such as a weakened immune system, an altered microbiome, or breached integumentary barriers. Many of these pathogens do not necessarily cause disease in a healthy host that has a non-compromised immune system, and can, in some cases, act as commensals until the balance of the immune system is disrupted. Opportunistic infections can also be attributed to pathogens which cause mild illness in healthy individuals but lead to more serious illness when given the opportunity to take advantage of an immunocompromised host.
Community-acquired pneumonia (CAP) refers to pneumonia contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited a hospital or who live in long-term care facilities. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling with fluid. This inhibits lung function, causing dyspnea, fever, chest pains and cough.
Virus latency is the ability of a pathogenic virus to lie dormant within a cell, denoted as the lysogenic part of the viral life cycle. A latent viral infection is a type of persistent viral infection which is distinguished from a chronic viral infection. Latency is the phase in certain viruses' life cycles in which, after initial infection, proliferation of virus particles ceases. However, the viral genome is not eradicated. The virus can reactivate and begin producing large amounts of viral progeny without the host becoming reinfected by new outside virus, and stays within the host indefinitely.
Human herpesvirus 6 (HHV-6) is the common collective name for human betaherpesvirus 6A (HHV-6A) and human betaherpesvirus 6B (HHV-6B). These closely related viruses are two of the nine known herpesviruses that have humans as their primary host.
Herpesviridae is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ἕρπειν, referring to spreading cutaneous lesions, usually involving blisters, seen in flares of herpes simplex 1, herpes simplex 2 and herpes zoster (shingles). In 1971, the International Committee on the Taxonomy of Viruses (ICTV) established Herpesvirus as a genus with 23 viruses among four groups. As of 2020, 115 species are recognized, all but one of which are in one of the three subfamilies. Herpesviruses can cause both latent and lytic infections.
Paroxysmal cold hemoglobinuria (PCH) or Donath–Landsteiner hemolytic anemia (DLHA) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder.
A subclinical infection—sometimes called a preinfection or inapparent infection—is an infection by a pathogen that causes few or no signs or symptoms of infection in the host. Subclinical infections can occur in both humans and animals. Depending on the pathogen, which can be a virus or intestinal parasite, the host may be infectious and able to transmit the pathogen without ever developing symptoms; such a host is called an asymptomatic carrier. Many pathogens, including HIV, typhoid fever, and coronaviruses such as COVID-19 spread in their host populations through subclinical infection.
Human betaherpesvirus 5, also called human cytomegalovirus (HCMV,HHV-5), is a species of virus in the genus Cytomegalovirus, which in turn is a member of the viral family known as Herpesviridae or herpesviruses. It is also commonly called CMV. Within Herpesviridae, HCMV belongs to the Betaherpesvirinae subfamily, which also includes cytomegaloviruses from other mammals. CMV is a double-stranded DNA virus.
Owl's eye appearance, also known as owl's eye sign, is a pattern used in the medical field to describe cells that resemble the shape of an actual owl's eye. Using the techniques of histology and radiology, microscopes and other medical imaging are used to locate this pattern of "owl's eye" shaped cells. The term may be applied to the appearance of the cells themselves, or to aspects of their morphology, such as reference to an "owl eye nucleus". The presence of "owl's eye" cells has been linked to a variety of conditions, such as in the pathology of Hodgkin's lymphoma, a form of cancer. In particular, owl's eye appearance has been used to indicate the presence of cytomegalovirus (CMV), a genus of virus found in humans and other primates.
Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand.
The stages of HIV infection are acute infection, latency, and AIDS. Acute infection lasts for several weeks and may include symptoms such as fever, swollen lymph nodes, inflammation of the throat, rash, muscle pain, malaise, and mouth and esophageal sores. The latency stage involves few or no symptoms and can last anywhere from two weeks to twenty years or more, depending on the individual. AIDS, the final stage of HIV infection, is defined by low CD4+ T cell counts, various opportunistic infections, cancers, and other conditions.