Asymptomatic carrier

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Typhoid Mary in a 1909 newspaper illustration. Mary Mallon was an asymptomatic carrier of Salmonella typhi who is thought to have infected 53 others with typhoid fever while continuing her work as a cook. Mallon-Mary 01.jpg
Typhoid Mary in a 1909 newspaper illustration. Mary Mallon was an asymptomatic carrier of Salmonella typhi who is thought to have infected 53 others with typhoid fever while continuing her work as a cook.

An asymptomatic carrier is a person or other organism that has become infected with a pathogen, but shows no signs or symptoms. [1]

Contents

Although unaffected by the pathogen, carriers can transmit it to others or develop symptoms in later stages of the disease. Asymptomatic carriers play a critical role in the transmission of common infectious diseases such as typhoid, HIV, C. difficile , influenzas, cholera, tuberculosis, and COVID-19, [2] although the latter is often associated with "robust T-cell immunity" in more than a quarter of patients studied. [3] While the mechanism of disease-carrying is still unknown, researchers have made progress towards understanding how certain pathogens can remain dormant in a human for a period of time. [4] A better understanding of asymptomatic disease carriers is crucial to the fields of medicine and public health as they work towards mitigating the spread of common infectious diseases.

Types of asymptomatic carriers

Asymptomatic carriers can be categorized by their current disease state. [5] When an individual transmits pathogens immediately following infection but prior to developing symptoms, they are known as an incubatory carrier. Humans are also capable of spreading disease following a period of illness. Typically thinking themselves cured of the disease, these individuals are known as convalescent carriers. Viral diseases such as hepatitis and poliomyelitis are frequently transmitted in this manner. "Healthy carriers" never exhibit signs or symptoms of the disease, yet are capable of infecting others, and are often considered to be the "classic" asymptomatic carriers. [5] While the mechanism of disease carrying is still unknown, researchers have made progress towards understanding how certain pathogens can remain dormant in a human for a period of time. [4]

Significance in disease transmission

The limited information on the prevalence of asymptomatic carriers creates a considerable difficulty when planning public health initiatives. Given that disease surveillance is dependent on estimates for both the asymptomatic rates and symptomatic rates of disease, the lack of information on the prevalence of carriers can lead to insufficient initiatives for the mitigation of common public health concerns such as C. difficile or influenza. [6] [7]

Researchers have expressed the desire to better predict transmission methods in order to determine the appropriate public health response. [8] For example, a disease with a known low asymptomatic rate may lead to increased surveillance of symptomatic cases, whereas a higher asymptomatic rate could lead to more aggressive methods such as travel bans and compulsory quarantines, since the number of infectious, asymptomatic cases would be unknown. [6]

Possible explanations

While an exact explanation for asymptomatic carriage is unknown, researchers have been dedicating their efforts towards understanding how specific bacteria thrive in human hosts in the hopes of determining a universal understanding of asymptomatic transmission. [9] [10]

A biological mechanism utilizing Salmonella

Numerous research publications have demonstrated how salmonella is able to remain in immune cells and alter their metabolic systems in order to further transmit the disease. [11] Utilizing a closely related strand of bacterium (S. typhimurium), scientists have been able to create a mouse model that mimics the persistent salmonella cases seen in carriers of typhoid. Knowing that the bacterium can reside in mice for their entire lives, researchers have been able to determine that the bacterium tends to reside in macrophages. Further examination of the gut lymph nodes of the mice reveals that S. typhimurium changes the inflammatory response of the macrophages. [12] Instead of eliciting an inflammatory response from the attack cells, the bacterium is able to convert them into an anti-inflammatory macrophage, allowing for optimal survival conditions. In the words of lead scientist Denise Monack, "It wasn't that inflammatory macrophages were invulnerable to infection, but rather that, having infected a macrophage, S. typhimurium was much more able to replicate in the anti-inflammatory type". [12]

Investigators have also found that the presence of peroxisome proliferator-activated receptors (PPARs) correlated to the presence of salmonella bacterium. PPARs, thought of as roaming genetic switches, are responsible for the fat metabolism needed to sustain anti-inflammatory macrophages in which S. typhimurium hides. [11]

Asymptomatic bacteriuria

Asymptomatic bacteriuria is a condition that typically impacts 3–5% of women, with the most vulnerable populations being the elderly and those diagnosed with diabetes. [13] Within the female population, the risk of bacteriuria increases with age. Escherichia coli is the most common organism found during urine analysis, though the variety of potentially infectious organisms is diverse and can include Enterobacteriaceae, Pseudomonas aeruginosa, Enterococcus species, and group B streptococcus. [14] The Agency for Healthcare Research and Quality has issued a set of screening recommendations as well as offered some insight into the mechanism of bacteriuria. [14] Results of the meta-analysis produced no clear explanation for asymptomatic carriage, but did yield new evidence that strengthened the support for screening for asymptomatic bacteriuria in pregnant women only. [14]

Infectious diseases

Asymptomatic carriers have furthered the spread of many infectious diseases. A common principle in epidemiology, the 80–20 rule, speculates that 80% of the disease transmission is conducted by only 20% of people in a population. [15]

Typhoid fever

Typhoid fever is an ailment caused by the bacterium Salmonella enterica ser. Typhi. An individual can acquire this infection from consuming risky foods or drinks, or by consuming foods or drinks prepared by an infected individual. Those who recover from this infection can still carry the bacteria in their cells, and therefore be asymptomatic. [16]

Typhoid Mary

Typhoid Mary in a New York Hospital Mary Mallon (Typhoid Mary).jpg
Typhoid Mary in a New York Hospital

Mary Mallon, known as "Typhoid Mary", was an asymptomatic carrier of Salmonella enterica serovar typhi, the causative agent of typhoid fever. [11] She was a cook for several families and soldiers in New York City during the late 1800s, and several cases of typhoid fever were traced to her by the Health Department. At the time, there was no way of eradicating the disease, and it was spread primarily through fecal-oral transmission. Most of Mary Mallon's transmission risk was thought to arise from her continued involvement in occupations involving food preparation and handling. New York City's public health officials initially sought to merely restrict her from such employment rather than permanently quarantining her. When she continued to be non-compliant, the Health Commission ordered that she be quarantined on one of the islands surrounding Manhattan. She remained there until her death. [17]

Despite appearing perfectly healthy, it is estimated that Mallon infected about 50 people before she was quarantined on North Brother Island. [18] Scientists calculate that between 1% and 6% of individuals infected with Salmonella typhi become chronic, asymptomatic carriers like Mary. [11]

HIV

HIV infection has a long period during which the person is asymptomatic. [19] Although the host may not be experiencing symptoms, the virus can still be passed on to others. It is also possible for the infection to become symptomatic after this incubation period. Whether the host is showing symptoms or not, opportunistic infections can take advantage of the weakened immune system and cause further complications. [20]

Epstein–Barr virus

Many carriers are infected with persistent viruses such as Epstein–Barr virus (EBV), a member of the herpes virus family. Studies show that about 95% of adults have antibodies against EBV, which means they were infected with the virus at some point in their life. [21]

Clostridioides difficile

Clostridioides difficile has also been shown to be spread by asymptomatic carriers, and poses significant problems in home-care settings. [6] Reports indicating that over 50% of long-term patients present with fecal contamination despite a lack of symptoms have led many hospitals to extend the period of contact precautions until discharge. [6]

Cholera

For cholera the estimates of the ratio of asymptomatic to symptomatic infections have ranged from 3 to 100. [22]

Chlamydia

Chlamydia, an STI that affects both men and women, can also be asymptomatic in most individuals. Although the infection may not yield any obvious symptoms, it can still damage the reproductive system. If the infection goes unnoticed for a long time, infected individuals are at risk of developing pelvic inflammatory disease (PID). Like chlamydia, PID can also be asymptomatic. [23]

Poliomyelitis

A small number of asymptomatic carriers of polio (referred to as chronic excretors) continue to produce active virus for years (or even decades) after their initial exposure to the oral Sabin vaccine. [24] Carriers of the attenuated virus unintentionally spread the attenuated virus, inoculating others, giving them contact immunity; however some adults with weak immune systems have contracted paralytic polio from contact with recently immunized children. Carriers of virulent strains spread polio, increasing the difficulty of poliomyelitis eradication. [25]

Tuberculosis

Tuberculosis (TB) is an infectious disease usually caused by the bacterium Mycobacterium tuberculosis (MTB). Tuberculosis generally affects the lungs, but can also affect other parts of the body. [26] Active or symptomatic tuberculosis is spread from person to person through the air through bacterium spores that are released into the air following a cough or sneeze. Some individuals may be infected with the tuberculosis mycobacterium but never display symptoms. [27] Called latent tuberculosis, these cases, while uncontagious, are particularly problematic from a public health perspective, since approximately 10% of those diagnosed with latent TB will go on to develop an active (and contagious) case. [27]

COVID-19

A 2021 paper estimated that at least 50% of SARS-CoV-2 infections were a result of exposure to asymptomatic carriers. [28]

See also

Related Research Articles

A human pathogen is a pathogen that causes disease in humans.

<span class="mw-page-title-main">Typhoid fever</span> Disease caused by the bacteria Salmonella Typhi

Typhoid fever, also known simply as typhoid, is a disease caused by Salmonella enterica serotype Typhi bacteria, also called Salmonella typhi. Symptoms vary from mild to severe, and usually begin six to 30 days after exposure. Often there is a gradual onset of a high fever over several days. This is commonly accompanied by weakness, abdominal pain, constipation, headaches, and mild vomiting. Some people develop a skin rash with rose colored spots. In severe cases, people may experience confusion. Without treatment, symptoms may last weeks or months. Diarrhea may be severe, but is uncommon. Other people may carry it without being affected, but are still contagious. Typhoid fever is a type of enteric fever, along with paratyphoid fever. Salmonella enterica Typhi is believed to infect and replicate only within humans.

<span class="mw-page-title-main">Infection</span> Invasion of an organisms body by pathogenic agents

An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable disease, is an illness resulting from an infection.

<span class="mw-page-title-main">Koch's postulates</span> Four criteria showing a causal relationship between a causative microbe and a disease

Koch's postulates are four criteria designed to establish a causal relationship between a microbe and a disease. The postulates were formulated by Robert Koch and Friedrich Loeffler in 1884, based on earlier concepts described by Jakob Henle, and the statements were refined and published by Koch in 1890. Koch applied the postulates to describe the etiology of cholera and tuberculosis, both of which are now ascribed to bacteria. The postulates have been controversially generalized to other diseases. More modern concepts in microbial pathogenesis cannot be examined using Koch's postulates, including viruses and asymptomatic carriers. They have largely been supplanted by other criteria such as the Bradford Hill criteria for infectious disease causality in modern public health and the Molecular Koch's postulates for microbial pathogenesis.

Paratuberculosis is a contagious, chronic and sometimes fatal infection that primarily affects the small intestine of ruminants. It is caused by the bacterium Mycobacterium avium subspecies paratuberculosis. Infections normally affect ruminants, but have also been seen in a variety of nonruminant species, including rabbits, foxes, and birds. Horses, dogs, and nonhuman primates have been infected experimentally. Paratuberculosis is found worldwide, with some states in Australia being the only areas proven to be free of the disease. At least in Canada, the signs of BJD usually start when cattle are four to seven years of age, and then usually only are diagnosed in one animal at a time. Cattle "with signs of Johne’s disease shed billions of bacteria through their manure and serve as a major source of infection for future calves."

<span class="mw-page-title-main">Salmonellosis</span> Infection caused by Salmonella bacteria

Salmonellosis is a symptomatic infection caused by bacteria of the Salmonella type. It is the most common disease to be known as food poisoning, these are defined as diseases, usually either infectious or toxic in nature, caused by agents that enter the body through the ingestion of food. In humans, the most common symptoms are diarrhea, fever, abdominal cramps, and vomiting. Symptoms typically occur between 12 hours and 36 hours after exposure, and last from two to seven days. Occasionally more significant disease can result in dehydration. The old, young, and others with a weakened immune system are more likely to develop severe disease. Specific types of Salmonella can result in typhoid fever or paratyphoid fever. Typhoid fever and paratyphoid fever are specific types of salmonellosis, known collectively as enteric fever, and are, respectively, caused by salmonella typhi & paratyphi bacteria, which are only found in humans. Most commonly, salmonellosis cases arise from salmonella bacteria from animals, and chicken is a major source for these infections.

<span class="mw-page-title-main">Natural reservoir</span> Type of population in infectious disease ecology

In infectious disease ecology and epidemiology, a natural reservoir, also known as a disease reservoir or a reservoir of infection, is the population of organisms or the specific environment in which an infectious pathogen naturally lives and reproduces, or upon which the pathogen primarily depends for its survival. A reservoir is usually a living host of a certain species, such as an animal or a plant, inside of which a pathogen survives, often without causing disease for the reservoir itself. By some definitions a reservoir may also be an environment external to an organism, such as a volume of contaminated air or water.

<span class="mw-page-title-main">Opportunistic infection</span> Infection caused by pathogens that take advantage of an opportunity not normally available

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.

WHO Disease Staging System for HIV Infection and Disease in Adults and Adolescents was first produced in 1990 by the World Health Organization and updated in September 2005. It is an approach for use in resource limited settings and is widely used in Africa and Asia and has been a useful research tool in studies of progression to symptomatic HIV disease.

<span class="mw-page-title-main">Viral encephalitis</span> Medical condition

Viral encephalitis is inflammation of the brain parenchyma, called encephalitis, by a virus. The different forms of viral encephalitis are called viral encephalitides. It is the most common type of encephalitis and often occurs with viral meningitis. Encephalitic viruses first cause infection and replicate outside of the central nervous system (CNS), most reaching the CNS through the circulatory system and a minority from nerve endings toward the CNS. Once in the brain, the virus and the host's inflammatory response disrupt neural function, leading to illness and complications, many of which frequently are neurological in nature, such as impaired motor skills and altered behavior.

Immune reconstitution inflammatory syndrome (IRIS) is a condition seen in some cases of HIV/AIDS or immunosuppression, in which the immune system begins to recover, but then responds to a previously acquired opportunistic infection with an overwhelming inflammatory response that paradoxically makes the symptoms of infection worse.

<span class="mw-page-title-main">Paratyphoid fever</span> Bacterial infection caused by one of the three types of Salmonella enterica

Paratyphoid fever, also known simply as paratyphoid, is a bacterial infection caused by one of three types of Salmonella enterica. Symptoms usually begin 6–30 days after exposure and are the same as those of typhoid fever. Often, a gradual onset of a high fever occurs over several days. Weakness, loss of appetite, and headaches also commonly occur. Some people develop a skin rash with rose-colored spots. Without treatment, symptoms may last weeks or months. Other people may carry the bacteria without being affected; however, they are still able to spread the disease to others. Typhoid and paratyphoid are of similar severity. Paratyphoid and typhoid fever are types of enteric fever.

<span class="mw-page-title-main">Subclinical infection</span> Nearly or completely asymptomatic infection

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.

<span class="mw-page-title-main">Bacteriuria</span> Medical condition

Bacteriuria is the presence of bacteria in urine. Bacteriuria accompanied by symptoms is a urinary tract infection while that without is known as asymptomatic bacteriuria. Diagnosis is by urinalysis or urine culture. Escherichia coli is the most common bacterium found. People without symptoms should generally not be tested for the condition. Differential diagnosis include contamination.

<span class="mw-page-title-main">Sexually transmitted infection</span> Infection transmitted through human sexual behavior

A sexually transmitted infection (STI), also referred to as a sexually transmitted disease (STD) and the older term venereal disease (VD), is an infection that is spread by sexual activity, especially vaginal intercourse, anal sex, oral sex, or sometimes manual sex. STIs often do not initially cause symptoms, which results in a risk of passing the infection on to others. Symptoms and signs of STIs may include vaginal discharge, penile discharge, ulcers on or around the genitals, and pelvic pain. Some STIs can cause infertility.

The co-epidemic of tuberculosis (TB) and human immunodeficiency virus (HIV) is one of the major global health challenges in the present time. The World Health Organization (WHO) reports 9.2 million new cases of TB in 2006 of whom 7.7% were HIV-infected. Tuberculosis is the most common contagious infection in HIV-Immunocompromised patients leading to death. These diseases act in combination as HIV drives a decline in immunity while tuberculosis progresses due to defective immune status. This condition becomes more severe in case of multi-drug (MDRTB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Tuberculosis can occur at any stage of HIV infection. The risk and severity of tuberculosis increases soon after infection with HIV. A study on gold miners of South Africa revealed that the risk of TB was doubled during the first year after HIV seroconversion. Although tuberculosis can be a relatively early manifestation of HIV infection, it is important to note that the risk of tuberculosis progresses as the CD4 cell count decreases along with the progression of HIV infection. The risk of TB generally remains high in HIV-infected patients, remaining above the background risk of the general population even with effective immune reconstitution and high CD4 cell counts with antiretroviral therapy.

<span class="mw-page-title-main">Superspreading event</span> Event in which 3 or more people attend and an infectious disease is spread much more than usual

A superspreading event (SSEV) is an event in which an infectious disease is spread much more than usual, while an unusually contagious organism infected with a disease is known as a superspreader. In the context of a human-borne illness, a superspreader is an individual who is more likely to infect others, compared with a typical infected person. Such superspreaders are of particular concern in epidemiology.

<span class="mw-page-title-main">Feline zoonosis</span> Medical condition

A feline zoonosis is a viral, bacterial, fungal, protozoan, nematode or arthropod infection that can be transmitted to humans from the domesticated cat, Felis catus. Some of these diseases are reemerging and newly emerging infections or infestations caused by zoonotic pathogens transmitted by cats. In some instances, the cat can display symptoms of infection and sometimes the cat remains asymptomatic. There can be serious illnesses and clinical manifestations in people who become infected. This is dependent on the immune status and age of the person. Those who live in close association with cats are more prone to these infections, but those that do not keep cats as pets can also acquire these infections as the transmission can be from cat feces and the parasites that leave their bodies.

<span class="mw-page-title-main">Latent period (epidemiology)</span> Time interval between infection by a pathogen and the individual becoming infectious

In epidemiology, particularly in the discussion of infectious disease dynamics (modeling), the latent period is the time interval between when an individual or host is infected by a pathogen and when that individual becomes infectious, i.e. capable of transmitting pathogens to other susceptible individuals.

<span class="mw-page-title-main">Transmission of COVID-19</span> Mechanisms that spread coronavirus disease 2019

The transmission of COVID-19 is the passing of coronavirus disease 2019 from person to person. COVID-19 is mainly transmitted when people breathe in air contaminated by droplets/aerosols and small airborne particles containing the virus. Infected people exhale those particles as they breathe, talk, cough, sneeze, or sing. Transmission is more likely the closer people are. However, infection can occur over longer distances, particularly indoors.

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