Enteropathogenic Escherichia coli (EPEC)

Enteropathogenic Escherichia coli (EPEC) is a type of E. coli that causes diarrhea by adhering to intestinal cells and injecting effector proteins. It is a major cause of infantile diarrhea in developing and developed countries, and it does not produce toxin. EPEC is different from enterotoxigenic E. coli (ETEC), which is the leading cause of travelers` diarrhea and produces toxin.

EPEC can be classified into typical EPEC (tEPEC) and atypical EPEC (aEPEC) based on the presence of certain genes and plasmids. Typical EPEC have a plasmid called EAF (E. coli adherence factor) that encodes for bundle-forming pili (BFP), which are hair-like structures that help the bacteria to form microcolonies on the intestinal surface. Atypical EPEC lack this plasmid but have other adhesins that mediate attachment.

Both types of EPEC have a chromosomal pathogenicity island called LEE (locus of enterocyte effacement), which contains genes that encode for a type III secretion system (T3SS) and an adhesin called intimin. The T3SS allows the bacteria to inject proteins into the host cells, one of which is Tir (translocated intimin receptor), which acts as a receptor for intimin on the cell membrane. The binding of intimin to Tir leads to the formation of attaching and effacing (A/E) lesions, which are characterized by the destruction of the microvilli and the accumulation of actin beneath the bacteria. This results in malabsorption and diarrhea.

EPEC infection is mainly transmitted through the fecal-oral route, with contaminated hands, food, water or fomites as vehicles. Humans are the only source of typical EPEC, whereas atypical EPEC can also be found in animals. Person-to-person spread is common, especially among children in daycare centers or households.

EPEC infection affects primarily children younger than 2 years old, but can also cause sporadic diarrhea in adults. The symptoms include watery diarrhea, non-bloody stools, vomiting, fever and dehydration. The onset of disease may be as rapid as a few hours after ingestion of EPEC, and the duration may vary from a few days to several weeks. In some cases, persistent diarrhea may lead to malnutrition, growth retardation or death.

The diagnosis of EPEC infection is based on phenotypic or genotypic methods. Phenotypic methods involve detecting the A/E histopathology in intestinal biopsy specimens or cell cultures using fluorescence microscopy. Genotypic methods involve detecting the presence of specific genes or plasmids using DNA hybridization or PCR.

The treatment of EPEC infection consists of preventing dehydration by correcting fluid and electrolyte imbalances with oral or intravenous rehydration. Antibiotics may be useful in some cases, but resistance is common among EPEC strains. Other therapies such as bismuth subsalicylate or bovine anti-EPEC antibodies may also be helpful. There is no vaccine available for EPEC infection.

In conclusion, EPEC is an important cause of diarrhea in children and adults worldwide. It causes disease by attaching to intestinal cells and destroying their surface structure. It is transmitted through fecal-oral route and can cause severe dehydration and complications. It can be diagnosed by phenotypic or genotypic methods and treated by rehydration and antibiotics. Prevention of dehydration and correction of fluid and electrolyte imbalances are essential for managing EPEC infection.

EPEC as a common cause of diarrhea in children under 5 years old in developing countries

Diarrhea is one of the major causes of death and morbidity in children under 5 years old, especially in developing countries. According to the World Health Organization, diarrhea accounts for about 525,000 deaths per year in this age group. Among the various pathogens that can cause diarrhea, enteropathogenic Escherichia coli (EPEC) are important because of their high prevalence and association with persistent diarrhea.

EPEC are classified into two groups based on the presence or absence of a plasmid-encoded bundle-forming pilus (BFP): typical EPEC (tEPEC) and atypical EPEC (aEPEC). Both groups share the ability to produce attaching and effacing (A/E) lesions on the intestinal epithelium, mediated by genes located on a chromosomal pathogenicity island called the locus of enterocyte effacement (LEE). However, tEPEC also carry the EPEC adherence factor (EAF) plasmid that encodes BFP, which facilitates the initial attachment and microcolony formation on the host cells.

Recent epidemiological studies have shown that aEPEC are more prevalent than tEPEC in both developed and developing countries, and that they can cause both endemic and outbreak diarrhea in children. Therefore, it is important to further characterize the pathogenicity and diversity of these emerging strains.

The exact mechanisms of diarrhea caused by EPEC are not fully understood, but they involve the disruption of the normal microvillus structure, the alteration of cellular signaling pathways, and the induction of inflammatory responses by the A/E lesions. These effects result in malabsorption and secretion of water and electrolytes, leading to watery diarrhea.

The incidence of EPEC infection varies depending on the geographic region, the socioeconomic status, and the diagnostic methods used. In general, EPEC are more common in low-income countries, where children under 5 years old experience an average of 3 to 7 episodes of diarrhea per year. After rotavirus infections, EPEC are one of the leading causes of death in children in developing countries. EPEC infection is also associated with growth faltering, malnutrition, and impaired cognitive development in children.

The diagnosis of EPEC infection is based on molecular methods that detect the presence of LEE genes or BFP genes in stool samples. However, these methods are not widely available or affordable in resource-limited settings. Therefore, there is a need for fast, easy, and inexpensive diagnostic tools that can identify EPEC infection and guide appropriate treatment and prevention strategies.

The treatment of EPEC infection consists mainly of oral or intravenous rehydration therapy to correct fluid and electrolyte imbalances. Antibiotics may be useful in some cases, but their use is limited by the emergence of resistance among EPEC strains. Other therapies such as zinc supplementation, probiotics, or immunoglobulins may also have some beneficial effects. However, the best way to prevent EPEC infection is to improve access to safe drinking water, sanitation, and hygiene practices, as well as to promote exclusive breastfeeding and adequate nutrition for young children.

In conclusion, EPEC are a common cause of diarrhea in children under 5 years old in developing countries, with significant impacts on their health and development. More research is needed to understand the pathogenesis and diversity of EPEC strains, as well as to develop better diagnostic and therapeutic options. Meanwhile, preventive measures such as improving water quality and sanitation, enhancing hygiene behaviors, and supporting breastfeeding and nutrition should be implemented to reduce the burden of EPEC infection.

EPEC is transmitted through the fecal-oral route, which means that the bacteria in the feces of an infected person can enter the mouth of another person and cause infection. This can happen through various ways, such as:

• Drinking water contaminated with human or animal waste that contains EPEC
• Eating food that has been prepared or handled by someone who did not wash their hands properly after using the toilet or changing a diaper
• Eating raw or undercooked shellfish that have been harvested from polluted water sources
• Having oral contact with the anus of an infected person, either directly or indirectly through objects or fingers
• Swimming in pools or lakes that are not adequately disinfected and contain EPEC

The fecal-oral route of transmission can be prevented by practicing good hygiene and sanitation measures, such as:

• Washing hands thoroughly with soap and water before eating, preparing food, and after using the toilet or handling feces
• Boiling or treating water before drinking or using it for cooking
• Cooking food well and avoiding cross-contamination between raw and cooked food
• Avoiding contact with the feces of infected people or animals
• Using condoms or dental dams during oral-anal sex

EPEC is a non-toxigenic and non-invasive pathogen that causes diarrhea by disrupting the normal structure and function of the small intestine. The main mechanism of EPEC pathogenesis is the formation of attaching and effacing (A/E) lesions on the epithelial cells of the small intestine. A/E lesions are characterized by the loss of microvilli, the intimate attachment of bacteria to the cell membrane, and the accumulation of cytoskeletal proteins beneath the bacteria.

The formation of A/E lesions involves several steps that are mediated by different virulence factors of EPEC. First, EPEC adheres to the epithelial cells by using plasmid-encoded bundle-forming pili (BFP), which facilitate the aggregation of bacteria into microcolonies on the cell surface. However, BFP are only present in typical EPEC (tEPEC) strains, while atypical EPEC (aEPEC) strains lack this plasmid and may use other adhesins to attach to the cells.

Second, EPEC injects several proteins into the host cells by using a type III secretion system (T3SS), which is encoded by a chromosomal pathogenicity island called locus of enterocyte effacement (LEE). One of these proteins is translocated intimin receptor (Tir), which inserts into the cell membrane and acts as a receptor for another bacterial protein called intimin, which is located on the outer membrane of EPEC. The binding of intimin to Tir triggers the rearrangement of actin and other cytoskeletal elements beneath the attached bacteria, forming a pedestal-like structure.

Third, EPEC also injects other proteins that interfere with various cellular processes, such as signal transduction, membrane trafficking, apoptosis, and innate immunity. For example, EspF and Map induce membrane ruffling and loss of microvilli, EspG and EspH disrupt microtubule dynamics and vesicle transport, EspZ inhibits apoptosis and cytokine production, and NleB and NleE block NF-κB activation and inflammatory responses.

The effect of EPEC infection on the small intestine is multifactorial and depends on several factors, such as the strain type, the host susceptibility, and the duration of infection. In general, EPEC infection causes watery diarrhea by impairing the absorption and secretion of water and electrolytes in the small intestine. This is mainly due to the destruction of microvilli, which reduces the surface area for nutrient absorption and enzyme activity. Moreover, EPEC infection may also alter the expression and function of various transporters involved in water and electrolyte homeostasis, such as SLC26A3 (a chloride-bicarbonate exchanger) and NHE3 (a sodium-hydrogen exchanger).

In addition to diarrhea, EPEC infection may also cause other clinical manifestations, such as vomiting, fever, abdominal pain, dehydration, malnutrition, growth retardation, and even death in severe cases. The severity of EPEC infection may be influenced by factors such as bacterial load, virulence profile, co-infection with other pathogens, host immunity, nutritional status, and environmental conditions.

EPEC infection in children is mainly characterized by watery diarrhea, which may be severe and protracted, lasting for more than 14 days. The diarrhea is usually non-bloody, but may contain mucus. Other symptoms include vomiting, fever, abdominal cramps, and dehydration. The onset of disease may be as rapid as a few hours after ingestion of EPEC.

EPEC infection can cause serious complications in children, especially in developing countries where malnutrition, poor sanitation, and lack of health care are prevalent. Some of the possible complications are:

• Growth retardation due to chronic diarrhea and malabsorption.
• Hemolytic uremic syndrome (HUS) due to atypical EPEC strains that produce Shiga toxin. HUS is a life-threatening condition that causes hemolytic anemia, thrombocytopenia, and acute renal failure.
• Necrotizing enterocolitis (NEC) due to severe intestinal inflammation and necrosis. NEC is a surgical emergency that affects mainly premature infants and can lead to perforation, peritonitis, and sepsis.
• Sepsis due to bacterial translocation across the damaged intestinal mucosa. Sepsis is a systemic inflammatory response syndrome that can cause organ failure and death.

EPEC infection in children is a major public health problem that requires prompt diagnosis and treatment to prevent dehydration and complications. Prevention measures include improving hygiene, sanitation, and nutrition, as well as promoting breastfeeding and vaccination.

Given that EPEC strains, as with other diarrheagenic E. coli strains, are defined on the basis of virulence properties, there are two approaches to the detection of EPEC in the laboratory: phenotypic and genotypic.

Phenotypic approach

The phenotypic approach requires the use of cell cultures and fluorescence microscopy, and is based on the observation of the attaching-and-effacing (A/E) histopathology, which is the hallmark of infections due to EPEC. This method involves inoculating a monolayer of cultured epithelial cells with a stool sample or an isolated bacterial strain, and then staining the cells with fluorescent antibodies to detect the presence of bacteria and the characteristic A/E lesions. This method is sensitive and specific, but it is also labor-intensive, time-consuming, and requires specialized equipment and expertise.

Genotypic approach

The genotypic approach requires the use of DNA hybridization or PCR, and is based on the detection of specific genes that encode the virulence factors of EPEC. The most commonly used gene targets are:

• The eae gene, which encodes intimin, an outer membrane protein that mediates the intimate attachment of EPEC to the epithelial cells and the formation of A/E lesions.
• The bfpA gene, which encodes bundle-forming pilus (BFP), a plasmid-encoded fimbrial adhesin that mediates the initial aggregation of EPEC on the epithelial cell surface. This gene is present only in typical EPEC strains, whereas atypical EPEC strains lack this gene.
• The LEE pathogenicity island, which is a chromosomal region that contains more than 40 genes involved in the secretion and translocation of bacterial proteins into the host cells, including eae and tir (translocated intimin receptor).

The genotypic approach is faster, simpler, and more widely available than the phenotypic approach, but it may not detect all EPEC strains, especially those that have lost or acquired virulence genes by horizontal gene transfer. Moreover, some genes may be shared by other diarrheagenic E. coli pathotypes, such as enterohemorrhagic E. coli (EHEC) or enteroaggregative E. coli (EAEC), which may cause cross-reactions or false positives.

Therefore, a combination of phenotypic and genotypic methods may be necessary to achieve an accurate diagnosis of EPEC infection in clinical settings. Additionally, other laboratory tests may be useful to assess the inflammatory and immunological response of the host to EPEC infection, such as fecal leukocytes, lactoferrin, or anti-EPEC antibodies.

As with other diarrheal pathogens, the primary goal of treatment of EPEC diarrhea is to prevent dehydration by correcting fluid and electrolyte imbalances. Oral rehydration may be sufficient for milder cases, but more severe cases require parenteral rehydration. Correction of nutritional imbalance with lactose-free formula or breast milk may be insufficient for some severely ill patients, and total parenteral nutrition may be required.

A variety of antibiotics have been used to treat EPEC and have proved useful in many cases, but multiple antibiotic resistances are common for EPEC. Antibiotics are not generally recommended for adults with mild to moderate symptoms who are appropriate for outpatient management. However, they may be considered for patients with severe infections (including those requiring hospitalization), immunocompromised hosts, and those with risk factors for complicated disease (such as age >50 years, valvular or endovascular cardiac disease, inflammatory bowel disease, or pregnancy). The choice of antibiotic should be based on the local susceptibility patterns and the clinical scenario.

Other therapies such as bismuth subsalicylate and specific bovine anti-EPEC milk immunoglobulins have also proven useful in some studies. There are no vaccines currently available or in clinical trials to prevent disease due to EPEC.

The best way to prevent EPEC infection is to avoid exposure to contaminated food, water, or objects that may have been in contact with fecal matter. Some preventive measures include:

• Washing hands thoroughly with soap and water before eating, preparing food, or feeding children
• Using clean water for drinking, cooking, and washing dishes
• Boiling or treating water with chlorine or iodine if the source is uncertain
• Avoiding raw or undercooked meat, poultry, eggs, seafood, or dairy products
• Peeling or washing fruits and vegetables before eating
• Storing food at appropriate temperatures and discarding leftovers after 2 hours
• Cleaning and sanitizing utensils, cutting boards, and countertops after use
• Avoiding contact with sick animals or their feces
• Disposing of human and animal waste properly

People with an EPEC infection who work in food handling, provide patient care or child care, or who attend a child care facility should stay home while they have symptoms and until they have been free from diarrhea for 24 hours. They should also wash their hands frequently and avoid sharing personal items such as towels, cups, or utensils.

There are no vaccines currently available or in clinical trials to prevent disease due to EPEC. However, some research has suggested that a synthetic peptide that blocks the binding site of a bacterial protein called Nck may protect intestine cells from EPEC infection and diarrhea. More studies are needed to confirm the safety and efficacy of this potential therapy.

In conclusion, EPEC is a common cause of diarrhea in children under 5 years old in developing countries and can lead to serious complications such as dehydration, malnutrition, and growth impairment. Prevention of EPEC infection depends on good hygiene practices and avoiding exposure to contaminated sources. Treatment of EPEC infection involves rehydration and antibiotics, as well as correcting fluid and electrolyte imbalances. Early diagnosis and prompt management of EPEC infection can reduce morbidity and mortality in affected populations.

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