PEDIATRIC INFECTIONS

• ACRONYMS AND DEFINITIONS

• AAP - American Academy of Pediatrics
• AHA - American Heart Association
• EBV - Epstein-Barr virus
• HFMD - Hand, foot, and mouth disease
• OM - Otitis media
• PCR - Polymerase chain reaction
• RSV - Respiratory syncytial virus
• URI - Upper respiratory infection

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• VIRAL INFECTIONS

• Adenovirus
• Epidemiology - adenovirus is a common upper respiratory pathogen that infects people of all ages. Children less than 5 years of age are most commonly affected, and the virus accounts for 5 - 10% of all febrile illnesses in this population. Adenovirus occurs year-round, but infections spike in the winter and early spring. Small outbreaks among children who are confined together (e.g. daycare, camps, school) are common.
• Pathology - the virus is easily spread from person to person through the inhalation of infected air droplets (e.g. coughing, sneezing), direct contact with infected secretions (e.g. kissing, sharing drinks), and touching of infected objects (e.g. doorknobs). Adenovirus is resistant to common disinfectants and can live on surfaces for prolonged periods. It can also be passed through water (e.g. swimming pools, small lakes). Adenovirus typically infects the upper respiratory tract and conjunctiva, where it induces a local inflammatory reaction. In some cases, it may spread to the lower respiratory tract and cause bronchiolitis and pneumonia. Certain subtypes of the virus can also infect the GI tract, bladder, and central nervous system.
• Symptoms - adenovirus infection typically presents with an acute onset of congestion, cough, sore throat, fever, and conjunctivitis. GI symptoms including nausea, vomiting, and diarrhea may also be present but are less common. The incubation period for the virus is 5 days, and most cases resolve within a week. Immunosuppressed patients are at risk for more severe disease.
• Diagnosis - typical symptoms in a child are usually enough to make a clinical diagnosis. Rapid antigen tests are available in clinics that detect the virus in nasal, throat, and conjunctival swabs. Adenovirus PCR testing is performed in laboratories, and the virus is often included in respiratory pathogen panels.
• Treatment - the treatment of adenovirus in immunocompetent patients is supportive. In most cases, the infection resolves within a week.
• Prevention - an adenovirus vaccine does exist, but it is only given to military recruits and is not available to the general public [4,5]

• Croup
• Epidemiology - croup is an upper respiratory illness that mainly affects children between the ages of 6 months and 3 years. The peak incidence occurs during the second year of life, where 5% of children are affected. Croup is most often seen between the months of September and December. Croup outbreaks also follow a biennial pattern, with most cases occurring during odd-numbered years; this mirrors the prevalence of parainfluenza virus, a major cause of croup.
• Pathology - croup occurs when a viral infection leads to significant inflammation of the upper airways. The most common virus implicated in croup is parainfluenza virus. Other pathogens include influenza A and B, adenovirus, RSV, and metapneumovirus. The infection progresses to croup when the larynx, trachea, and bronchi become edematous and inflamed. The swollen subglottic region of the trachea below the vocal cords causes the characteristic "barky" cough and stridor. Epithelial cells necrose, and large amounts of phlegm are produced that contribute to airway obstruction.
• Symptoms - croup may be preceded by 1 - 2 days of nonspecific upper respiratory symptoms (e.g. congestion, low-grade fever). The characteristic "barky" cough (often described as the sound of a seal barking) appears abruptly, and for unknown reasons, is often worse at night. Croup cough typically peaks within 48 hours before resolving over the next 3 - 4 days. Most children have mild cases (> 80%), but a small number of children will have severe cases marked by significant stridor, agitation, increased respiratory effort (e.g. retractions), lethargy, and hypoxia.
• Diagnosis - croup is diagnosed clinically in a child with the characteristic seal-like, barky cough and symptoms
• Treatment - experts recommend a single dose of dexamethasone 0.6 mg/kg given orally or intramuscularly for all patients with croup; some studies have found that lower doses (0.15 and 0.30 mg/kg) are just as effective. Dexamethasone has been shown to decrease the length of symptoms and reduce the need for subsequent medical care. Humidified air, a popular treatment for many years, has not been shown to be beneficial in studies and is not recommended. Sicker patients who are admitted to the hospital are treated with oxygen and nebulized racemic epinephrine. [12,13,14]

• Influenza
• See influenza (flu)

• Mononucleosis
• Epidemiology - mononucleosis is an infectious syndrome primarily caused by the Epstein-Barr virus (EBV), also known as human herpesvirus 4. More than 95% of the world's population is infected with EBV by the time they reach adulthood. Most people are infected in early childhood, where the virus causes mild to no symptoms. After childhood, the highest incidence of infection occurs between the ages of 15 and 24 years. Ten to twenty percent of susceptible people are infected each year, and of these, 30 - 50% will develop a mononucleosis syndrome.
• Pathology - mononucleosis is most often caused by EBV, but it may also be seen with cytomegalovirus, HIV (acute infection), adenovirus, and Toxoplasma gondii. EBV is transmitted through saliva, and teenagers often pass it through kissing and sharing food. The virus infects the epithelial cells of the tonsils, causing necrosis and inflammation. The virus also infects memory B lymphocytes, where it can persist for a lifetime. T lymphocytes sometimes mount a strong response to the virus, and this may worsen symptoms.
• Symptoms - EBV has an incubation period of 30 - 50 days, after which an abrupt onset of fever, lymphadenopathy, pharyngitis, splenomegaly, and lymphocytosis occurs. Splenomegaly may or may not be palpable on exam but is present on ultrasound in most cases. Most symptoms resolve within a month, but some people may experience fatigue for longer periods. Hematologic abnormalities are seen in up to 50% of cases and include lymphocytosis, hemolytic anemia, and thrombocytopenia. Neurologic complications (e.g. Guillain–Barré syndrome, facial nerve palsy, meningoencephalitis) are rare (1 - 5%) but sometimes occur.
• Diagnosis - mononucleosis can be diagnosed clinically in a teenager or young adult with characteristic symptoms and a negative strep test. The heterophile antibody test, also called monospot test, is an assay that detects heterophile antibodies in a sample of blood. Heterophile antibodies are antibodies produced in response to an EBV infection that crossreact with antigens on the erythrocytes of animals (e.g. sheep, horse) and cause agglutination. Monospot tests may be performed on blood from a venous sample or a fingerstick, in which case, rapid tests can give results in minutes. Monospot tests are highly specific but only have a sensitivity of 70 - 90%; in children under 4 years of age, the sensitivity falls to as low as 27%. Heterophile antibodies peak between 2 - 6 weeks after infection, so testing too early may lead to false-negative results. Other testing is not typically necessary but is reviewed here - EBV testing.
• Treatment - mononucleosis is treated symptomatically with fluids, NSAIDs, and rest. Splenic rupture has been reported in 0.5 - 1% of cases, with the highest incidence occurring in the 3 weeks after diagnosis. Because of this, it is recommended that patients avoid contact sports during this time period. [15,16]

• Mumps
• Epidemiology - mumps is an infection caused by the rubulavirus. Mumps used to be a common childhood infection until 1967, when the mumps vaccine was introduced. Since that time, only a small number of outbreaks have occurred among vaccinated populations. In unvaccinated children, the highest incidence of mumps is seen between the ages of 5 and 14 years.
• Pathology - rubulavirus virus, also called the mumps virus, is passed from person to person through infected saliva or respiratory droplets. It can also be transmitted through contaminated surfaces (e.g. doorknobs, tables, etc.). Once the virus gains access to the upper respiratory tract, it invades epithelial cells and replicates. The virus has an affinity for glandular cells, which explains its predilection for the parotid gland. In regional lymph nodes, it infects monocytes, and this allows it to spread systemically. Other organs susceptible to viral invasion include the testis, epididymides, ovaries, pancreas, and CNS.
• Symptoms - the incubation period for the mumps virus is 7 - 21 days. Mumps causes painful swelling of the parotid gland that is typically bilateral (75%). The swelling peaks within 3 days before resolving over the next week. Prodromal symptoms that include low-grade fever, body aches, headache, and malaise are common. Orchitis is uncommon before puberty, but it is seen in 30% of post-pubertal unvaccinated males and around 6% of the vaccinated. It is usually unilateral and may result in testicular atrophy; subsequent infertility is rare. Other complications that are uncommon include oophoritis, mastitis, meningitis, encephalitis, pancreatitis, and hearing loss. Vaccinated individuals can still be infected, but they typically have milder symptoms. (child with mumps)
• Diagnosis - mumps is a clinical diagnosis based on the presence of the characteristic parotid gland swelling. Antibody testing, PCR buccal swab analysis, and viral cultures are available.
• Treatment - mumps is treated symptomatically with fluids, NSAIDs, and rest. Ice or warm packs to swollen parotid glands may help relieve pain. Orchitis can be treated with scrotal support and ice packs.
• Prevention - the MMR (measles, mumps, rubella) vaccine is highly effective at preventing mumps [4,25,26,27]

• Rhinovirus / Coronavirus
• Epidemiology - rhinovirus and coronavirus are the two most common causes of the common cold. From birth to 9 years, children average about 3 - 6 upper respiratory infections per year, and the incidence can run even higher in those who attend daycare and preschool. Rhinovirus infections occur year-round, with a peak incidence between March and October. Coronavirus infections are most prevalent between December and April.
• Pathology - both viruses are passed through contact with infected respiratory particles. Once the virus gains access to the nasal mucosa, it invades epithelial cells and starts to replicate. This elicits a local inflammatory reaction that causes vasodilation, increased vascular permeability, and secretions. The infection typically remains confined to the nasopharynx, but it can spread to include the upper airways (bronchitis), and in rare cases, the lower airways (pneumonia).
• Symptoms - rhinovirus and coronavirus cause the common cold. Symptoms develop 1 - 2 days after infection and peak about 2 - 3 days later. Common symptoms include sinus congestion, runny nose, sore throat, loss of taste/smell, headache, and low-grade fever. If the airways are involved, either directly or from drainage, cough will develop. If eustachian tube function is altered, otitis media may occur. Symptoms usually resolve within 11 days, but up to 25% of patients will still have symptoms 2 weeks after onset.
• Diagnosis - the common cold is a clinical diagnosis and often indistinguishable from other common respiratory infections (e.g. influenza, RSV). Respiratory pathogen panels that detect rhinovirus by PCR are available but are unnecessary in uncomplicated cases.
• Treatment - treatment is supportive and includes antitussives, decongestants, and antihistamines. OTC versions of these medications only provide dosing down to 4 years of age, and the FDA does not recommend their use in children younger than two. Analgesics can be used for fever and pain, and nasal saline sprays are also helpful. Young infants should receive bulb suctioning. Complications such as otitis media may require antibiotics in some cases.

• Rotavirus
• Epidemiology - rotavirus causes a diarrheal illness that was a common childhood disease until the introduction of a vaccine in 2006. Rotavirus still causes significant morbidity and mortality in unvaccinated populations, but in the U.S., cases have dropped dramatically, and serious infections are rare. In unvaccinated populations, the highest incidence is seen in children under 5 years of age. Cases peak in the winter and spring, and in the U.S., the disease has developed a biennial pattern with even-numbered years having a higher prevalence.
• Pathology - rotavirus is spread through the fecal-oral route and is easily passed through touching contaminated surfaces. Once the virus is swallowed and gains access to the small intestine, it invades intestinal villi and inhibits their ability to digest carbohydrates and absorb fluids. This causes osmotically active solutes to pass into the large intestine, where water absorption is impaired, and diarrhea occurs.
• Symptoms - rotavirus has an incubation period of about 2 days, after which an abrupt onset of vomiting, watery diarrhea, abdominal cramping, and low-grade fever occur. Vomiting and diarrhea usually last 3 - 8 days, and in severe cases, significant dehydration can occur.
• Diagnosis - rotavirus infection is often indistinguishable from other causes of viral gastroenteritis, and diagnostic testing does not influence treatment decisions. Rotavirus stool antigen testing is available if diagnostic evaluation is desired.
• Treatment - treatment is supportive and primarily focused on preventing dehydration with oral fluids. Antiemetics and antidiarrheals may benefit older children, but their use in infants and young children is controversial. Patients with significant illness should be admitted for IV hydration.
• Prevention - the first rotavirus vaccine (RotaShield) was introduced in 1999, but it was soon removed from the market because it was associated with rare cases of intussusception. In 2006, a second rotavirus vaccine (RotaTeq) was approved, and in 2008, a third vaccine (Rotarix) was cleared. Rotateq is given at 2, 4, and 6 months of age, and Rotarix is administered at 2 and 4 months. Both vaccines are given orally. [4,35]

• Respiratory syncytial virus (RSV)
• Epidemiology - RSV is by far the most common cause of bronchiolitis in children. Around 90% of children are infected with RSV during the first two years of life, and of these, 40% will have symptomatic infections. The highest incidence of infection occurs between 3 and 6 months of age. RSV is seasonal, with most cases occurring from November to April.
• Pathology - bronchiolitis occurs when viruses infect the epithelial cells of the upper respiratory tract. From there, the virus can spread quickly down the tract until it involves the entire airway. Viral-induced epithelial cell destruction leads to inflammation that produces mucus, bronchiole plugging, and airway collapse. RSV accounts for up to 80% of bronchiolitis infections; other etiologies include rhinovirus, coronavirus, influenza virus, human metapneumovirus, and parainfluenza virus. Secondary bacterial pneumonia is rare, but otitis media is present in about 40% of cases.
• Symptoms - bronchiolitis usually starts with low-grade fever and nasal congestion that progresses over the course of several days to cough, wheezing, rales, increased respiratory effort (e.g. tachypnea, retractions), cyanosis, and in severe cases, hypoxia. In most children, RSV symptoms last for 1 - 3 weeks. Risk factors for severe disease include chronic lung disease, premature birth, congenital heart disease, immunosuppression, and infants < 3 months old.
• Diagnosis - bronchiolitis is typically diagnosed clinically. RSV and influenza antigen tests that can be performed on nasal swabs and produce results within minutes are available in clinics. RSV PCR testing is available in most labs; it is more sensitive, but results take longer to obtain. Respiratory pathogen panels that test for an array of viruses on a single swab (e.g. RSV, influenza, parainfluenza, rhinovirus, metapneumovirus, adenovirus, coronavirus) are increasingly used.
• Treatment - the treatment of bronchiolitis is mostly supportive. Medications including albuterol, epinephrine, and corticosteroids have not been found to be beneficial in trials and are not recommended. Supplemental oxygen is indicated if the oxygen saturation is below 90%. Nebulized hypertonic saline may be beneficial in hospitalized patients.

• Prevention - two monoclonal antibodies, nirsevimab and palivizumab, are approved to prevent RSV infections in infants [1,2,3]


• Nirsevimab (Beyfortus®) - in 2023, the FDA approved nirsevimab, a monoclonal antibody against RSV virus, for the prevention of RSV lower respiratory tract disease in infants. The CDC recommends one dose of nirsevimab for all infants younger than 8 months, born during – or entering – their first RSV season (typically fall through spring). For a small group of children between the ages of 8 and 19 months who are at increased risk of severe RSV disease (e.g., severely immunocompromised), a dose is recommended in their second season. Nirsevimab is given as a single IM injection in the anterolateral aspect of the thigh with dosing based on weight (see below). The effects of nirsevimab on RSV prevention were evaluated in the studies below. [Beyfortus® PI]
• Dosing:
• < 11 lbs (5 kg): 50 mg IM
• ≥ 11 lbs (5 kg): 100 mg IM
• Up to 24 months at increased risk of severe RSV in the second season: 200 mg IM (2 X 100 mg)
• Efficacy:
• Healthy late-preterm and term infants - in the MELODY study, 1490 healthy infants born ≥ 35 weeks gestation were randomized in a 2:1 ratio to nirsevimab or placebo at the beginning of RSV season. The primary outcome of symptomatic RSV infection confirmed by PCR through 150 days occurred in 1.2% of nirsevimab-treated patients and 5% of placebo-treated patients (p<0.001). Hospitalization for RSV occurred in 0.6% and 1.6%, respectively (p=0.07). Three deaths occurred, all in the nirsevimab group; none were determined to be from RSV or related to the vaccine. [PMID 35235726]
• Preterm infants - in a study, 1453 infants born 29 to <35 weeks gestation were randomized in a 2:1 ratio to nirsevimab or placebo at the beginning of RSV season. The primary outcome of symptomatic RSV infection confirmed by PCR through 150 days occurred in 2.6% of nirsevimab-treated patients and 9.5% of placebo-treated patients (p<0.001). Hospitalization for RSV occurred in 0.8% and 4.1%, respectively (p<0.001). Five deaths occurred, two in the nirsevimab group and three in the placebo group; none were determined to be from RSV or related to the vaccine. [PMID 32726528]


• Palivizumab (Synagis®) - palivizumab, a monoclonal antibody with anti-RSV activity, is approved for the prevention of RSV in infants with bronchopulmonary dysplasia, hemodynamically significant congenital heart disease, and those born ≤ 35 weeks gestation who are ≤ 6 months at the beginning of RSV season. It is given as a monthly intramuscular injection (15 mg/kg), starting just before RSV season and continuing throughout. [Synagis® PI]

• Erythema infectiosum (Fifth disease)
• Epidemiology - erythema infectiosum, also called Fifth disease, is a common childhood infection caused by parvovirus B19. Parvovirus B19 infects up to 60% of the population by age 20 years, and most people acquire the virus between the ages of 5 and 15 years. The virus is most active in the winter and early spring, and cyclical community outbreaks occur every 3 - 4 years.
• Pathology - Parvovirus B19 is transmitted through respiratory droplets. Once the virus infects the respiratory tract, it enters the blood and disseminates throughout the body. Parvovirus B19 is different from the parvovirus that infects dogs and cats, and it can not be transmitted to or from animals.
• Symptoms - the incubation period for parvovirus B19 is 7 - 10 days, after which a person may be asymptomatic or develop any of the following: fever (20%), headache (20%), sore throat (15%), itching (15%), congestion (10%), abdominal pain (10%), joint pain (10%). Symptoms last for 2 - 3 days, at which point the rash phase of the illness begins. The first rash appears as intense redness on both cheeks (slapped-cheek rash) that fades over 2 - 4 days. Within 1 - 3 days of the facial rash, a diffuse maculopapular rash that involves the trunk and extremities develops in some. The rash often has a reticular appearance, and it resolves over 1 - 2 weeks. Adults are more likely to have joint pain (up to 50%), and it may be the only symptom of infection. The hands, feet, wrists, and knees are most commonly affected, and symptoms are usually symmetric. The pain typically resolves in 3 weeks but can last for months in some. (erythema infectiosum images)
• Diagnosis - erythema infectiosum is diagnosed clinically in a person who has the characteristic rashes and symptoms. Parvovirus B19 antibodies may be indicated in pregnant women who have been exposed to the virus.
• Treatment - erythema infectiosum typically has a mild course and is treated symptomatically with acetaminophen and NSAIDs. Pregnant women who are acutely infected with parvovirus B19 can pass the virus to the fetus and are at risk for hydrops fetalis; the risk is greatest if infection occurs before week 20 of gestation. Patients with chronic anemic states (e.g. sickle cell disease, thalassemia, leukemia) may develop severe anemia from parvovirus B19 infection because the virus destroys reticulocytes and suppresses erythropoiesis.
• Prevention - patients are contagious during the asymptomatic incubation period and the first 1 - 3 days of symptoms. When the slapped-cheek rash appears, patients are no longer contagious and can return to school. Hand washing should be encouraged. Pregnant women who are exposed to the virus should contact their doctor. [10,11]

• Hand, foot, and mouth disease (HFMD)
• Epidemiology - HFMD is a viral infection that occurs worldwide. People of all ages can be affected, but it most commonly occurs in children under 5 years. Outbreaks in daycares, camps, and schools are common, with the highest incidence occurring in the summer and fall.
• Pathology - in the U.S., HFMD is caused by the coxsackievirus. Coxsackievirus is spread from person to person through oral ingestion, which may occur from contact with infected respiratory droplets, touching an infected person, touching infected surfaces, and the fecal-oral route. Once ingested, the virus infects lymph tissue of the pharynx and lower intestine, and from there, spreads through the blood to involve the skin and other organs.
• Symptoms - the incubation period for HFMD is 3 - 6 days, after which a low-grade fever, decreased appetite, and malaise occur. One to two days later, mouth and throat sores develop that start as red spots and evolve into painful blisters. Soon after, a rash appears on the palms of the hands and soles of the feet; the knees, elbows, buttocks, and genital area may also be affected. The rash may look like flat red spots, or it may form vesicles that are surrounded by a ring of erythema. The vesicles eventually rupture, leaving a yellow base with an erythematous rim. Most symptoms resolve in 7 - 10 days. Affected individuals are most contagious during the first week of symptoms. (hand, foot, and mouth disease images)
• Diagnosis - HFMD is diagnosed clinically by the presence of the characteristic rash and symptoms
• Treatment - HFMD is treated symptomatically. Patients should be encouraged to consume plenty of fluids to prevent dehydration. NSAIDs and acetaminophen can be used for fever and pain. Most symptoms resolve in 7 - 10 days.
• Prevention - HFMD is very contagious. Infected children should be kept away from other children until they are afebrile and skin lesions have dried up. The condition is most contagious during the first week of symptoms; although, the virus is shed in the stool for many weeks. Frequent handwashing can help to prevent the spread. [4,6]

• Herpetic gingivostomatitis
• Epidemiology - herpetic gingivostomatitis is a manifestation of primary HSV-1 infection. Most people acquire the virus in childhood, with the highest incidence occurring between 6 months and 5 years. HSV-1 is ubiquitous, infecting up to 90% of the world's population by age 35.
• Pathology - HSV-1 is acquired through oral secretions. Once the virus gains access to the mouth, it infects mucosal cells and causes them to lyse. Ulcers form that allow the virus to enter the underlying dermis, where it gains access to nerve cells. The virus then ascends nerve axons until it reaches the ganglia, where it can lie dormant for years until reactivation occurs in the form of fever blisters.
• Symptoms - the incubation period for HSV-1 is 3 - 6 days, after which some children remain asymptomatic, but most will develop fever, decreased appetite, and mouth lesions. The lesions start as redness that rapidly evolves into yellow-white vesicles that rupture, ulcerate, and bleed. Lesions can occur anywhere in the mouth and lips, and they are very painful. Acute symptoms usually last 5 - 7 days, and the ulcers take 2 - 3 weeks to heal completely. A third of affected patients will go on to have recurrent fever blisters throughout life. (herpetic gingivostomatitis image)
• Diagnosis - herpetic gingivostomatitis is diagnosed clinically in a child who has the characteristic mouth lesions and symptoms
• Treatment - herpetic gingivostomatitis is primarily treated symptomatically. Patients should be encouraged to consume plenty of fluids to prevent dehydration. NSAIDs and acetaminophen can be used for fever and pain. Topical anesthetics can be applied to mouth lesions. Children who are old enough may benefit from swishing and spitting 2% viscous lidocaine. Acyclovir 15 mg/kg five times a day for 7 days showed benefit in one small trial (N=72) when started within 72 hours of symptom onset. [PMID 9224082] [9]

• Measles (Rubeola)
• Epidemiology - measles, also called rubeola, is a highly contagious viral infection. In 1963, a measles vaccine was introduced that greatly reduced its incidence. In the U.S., most cases occur in unvaccinated people who are exposed to the virus through travelers who bring it back from regions with low vaccination rates (e.g. Africa, India). Measles can infect people of all ages, and in unvaccinated populations, the virus is usually acquired in infancy or early childhood.
• Pathology - measles virus is spread through respiratory droplets, and aerosolized virus can remain infectious up to two hours after an infected person has coughed or sneezed. The virus invades white blood cells (e.g. lymphocytes, dendritic cells, macrophages) in the upper respiratory tract, and from there, it gains access to lymph nodes and disseminates throughout the body, where it can infect epithelial and endothelial cells of almost every organ system.
• Symptoms - the incubation period for measles is about 10 days from the time of exposure to fever and 14 days to the onset of rash. The first symptoms include high-grade fever, cough, coryza (inflammation of the mucous membranes of the nose), and conjunctivitis (the three Cs). About 70% of patients will develop Koplik spots, which are white dots on an erythematous background that occur on the buccal mucosa. (Koplik spot image). Two to four days after the fever starts, an erythematous maculopapular rash appears on the face and hairline; from there, the rash extends downward to cover the entire body. Fever and systemic symptoms usually peak with the onset of the rash, and over the next 7 days, the rash and infection resolve. Patients are considered contagious from 4 days before to 4 days after the rash appears. (measles rash images)
• Diagnosis - in areas where measles is common, the diagnosis can be made based on the characteristic syndrome and rash. In vaccinated populations, the diagnosis may be missed or delayed due to the low incidence of the disease. Measles IgM antibodies are highly sensitive and specific for the condition, but they are undetectable in 25% of patients within 72 hours of rash onset; four days after rash onset, they are almost always present. Measles PCR testing and viral cultures exist, but most labs in the U.S. do not routinely offer them.
• Treatment - high doses of vitamin A have been shown to reduce complications and improve mortality. The WHO recommends that all children diagnosed with measles receive vitamin A (see dosing below). Patients at high risk for severe disease (e.g. immunocompromised, infants < 12 months old, unvaccinated pregnant women) should receive measles immunoglobulin.
• WHO vitamin A dosing recommendations for measles
• < 6 months old: 50,000 IU/day for 2 days
• 6 - 11 months old: 100,000 IU/day for 2 days
• ≥ 12 months old: 200,000 IU/day for 2 days
• Prevention - the MMR (measles, mumps, rubella) vaccine is highly effective at preventing measles. Measles vaccine within 72 hours of exposure and/or measles immunoglobulin within 6 days can help prevent infection in unvaccinated people. [4,28,29]

• Molluscum contagiosum
• Epidemiology - molluscum contagiosum is a benign skin condition that primarily occurs in children 2 - 5 years old and sexually active young adults. In the U.S., it accounts for about 1% of all skin disorders diagnosed each year. It is more common in warm, humid environments, and immunocompromised patients are at greater risk; the prevalence in patients with HIV is as high as 18%.
• Pathology - molluscum contagiosum is caused by a poxvirus that is transmitted through direct skin-to-skin contact and fomites (e.g. towels, razors, toys). The virus only infects keratinocytes in the epidermis and does not spread systemically. Infected epidermal cells enlarge and die, leaving behind remnants that make up the central core of the lesion. The virus is able to persist by producing proteins that inhibit the innate immune response.
• Symptoms - the incubation period for molluscum contagiosum is 2 - 7 weeks. In children, lesions can appear anywhere, but they have a predilection for the groin in young adults. The typical molluscum lesion is a 2 - 5 mm, flesh-colored papule that has an umbilicated center. Inside the umbilicated center is a white core that can be expressed. Lesions may appear in groups or be widely disseminated, and most immunocompetent people have fewer than 20. Molluscum contagiosum infection usually resolves in 6 - 9 months, and individual skin lesions typically disappear within 2 months. Patients with atopic dermatitis may have more severe disease, and they may develop dermatitis around lesions. (molluscum contagiosum images)
• Diagnosis - in children, molluscum contagiosum is a clinical diagnosis based on the presence of the characteristic lesions. In immunocompromised individuals, other conditions must be considered, and a biopsy may be necessary.
• Treatment - molluscum contagiosum is a self-limited condition that resolves spontaneously. Patients often seek treatment for cosmetic reasons. A number of modalities can be used to destroy molluscum lesions. Physical trauma by expressing the central core is the easiest means and makes most lesions go away. Lesions may also be shaved off or frozen. Topical treatments that are effective for warts are also used (e.g. salicylic acid, cantharidin). [20,21]

• Pityriasis rosea
• Epidemiology - pityriasis rosea is an infectious syndrome that is marked by a distinctive rash. The annual incidence of pityriasis rosea is around 0.17%, with most cases occurring in people aged 10 - 35 years. Some studies have found that the condition is more prevalent in the winter months, while others have shown no seasonal variation. Outbreaks have been reported, but the condition does not appear to be highly contagious.
• Pathology - the exact cause of pityriasis rosea is unknown, but it is believed to be caused by a virus, possibly a reactivation of human herpesvirus 6 or 7. On histology, skin lesions show a predominance of T-cells and Langerhans cells, while B cells are lacking.
• Symptoms - pityriasis rosea is a rash that has 2 distinct phases. The first phase occurs in 50 - 90% of patients and is characterized by a solitary patch (herald patch) that appears on the trunk. The patch expands to 2 - 10 cm in diameter over the course of several days, and it exhibits a light-pink center surrounded by a scaly ring of erythema. Within 14 days, a second rash emerges that produces scattered lesions across the chest, abdomen, back, groin, and proximal extremities; the lesions are pink ovals, about 0.5 - 2 cm in size, and they tend to follow skin tension lines (Langer lines), which gives the distinctive "Christmas tree" pattern on the back. The second rash lasts an average of 45 days, and in some people, resolution does not occur for 12 weeks. The rash is itchy in up to 50% of people, and while most people have no residual skin changes, dark-skinned individuals may be left with hyper- or hypopigmentation. Prodromal symptoms (e.g. fatigue, fever, sore throat, arthralgias) are reported in 5 - 70% of patients, depending on the study. (pityriasis rosea images)
• Diagnosis - pityriasis rosea is a clinical diagnosis based on the presence of the characteristic rash
• Treatment - most patients require no treatment. If itching is significant, topical or oral antihistamines can help, as can topical steroids. All patients should take measures to prevent irritating the lesions (e.g. avoiding harsh soaps, sweating, and hot water; wearing loose clothing). Sunlight and/or UV-B phototherapy may speed resolution.
• Recurrence - recurrence is uncommon but has been reported in 2 - 3% of cases [17,18,19]

• Roseola infantum
• Epidemiology - roseola infantum is a common childhood infection that accounts for 10 - 45% of febrile illnesses in U.S. infants. The infection primarily affects children less than 2 years of age, and children between 6 and 12 months have the highest incidence. The virus is most active during the spring and fall seasons, and close to 100% of the world's population has been infected.
• Pathology - roseola infantum is caused by human herpesvirus 6, and to a lesser extent, human herpesvirus 7. The virus is transmitted through respiratory droplets and saliva. Once it gains access to the mouth, the virus infects leukocytes and the salivary glands. From there, it is believed to infect the CNS. After acute infection, the virus remains dormant in monocytes, leukocytes, and other body tissues.
• Symptoms - the average incubation period for roseola infantum is 9 - 10 days, after which a high fever that may exceed 104°F (40°C) occurs; most patients have no other remarkable symptoms. After 3 - 5 days, the fever abruptly resolves, and a diffuse rash characterized by pink confluent papules appears; the rash resolves in 1 - 2 days. Erythematous papules on the soft palate and uvula (Nagayama spots) may develop in up to two-thirds of patients by day 4, and febrile seizures may be seen in up to 15% of children. (roseola infantum images)
• Diagnosis - roseola infantum is diagnosed clinically in an infant with a history of high fever that resolves abruptly before the onset of the characteristic rash
• Treatment - roseola infantum is treated symptomatically. Patients should be encouraged to consume plenty of fluids to prevent dehydration. NSAIDs and acetaminophen can be used for fever. [7,8]

• Rubella
• Epidemiology - rubella, also called German measles, is a viral infection that primarily affects children and young adults. In 1969, a rubella vaccine was introduced that greatly reduced its incidence; less than 10 cases are reported each year in the U.S.. In unvaccinated populations, seasonal outbreaks occur in the spring, and children aged 5 - 9 years have the highest incidence. Rubella epidemics are seen every 3 - 8 years in susceptible populations.
• Pathology - rubella virus is a rubivirus that is passed from person to person through contact with infected respiratory droplets. Once the virus gains access to the upper respiratory tract, it infects epithelial cells and spreads to regional lymph nodes, where it replicates. Viremia occurs next, and during this phase, the virus can be isolated from multiple organ systems. The most feared aspect of the virus is its ability to cross the placenta and damage the developing fetus. Rubella infection during the first trimester increases the risk of miscarriage, fetal death, and a constellation of birth defects known as the congenital rubella syndrome (e.g. cataracts, hearing impairment, heart defects).
• Symptoms - the average incubation period for rubella is 17 days, after which a syndrome of low-grade fever, cervical lymphadenopathy, sore throat, and malaise may occur. A maculopapular rash appears within 5 days of symptom onset in 50 - 80% of infected people. The rash starts on the face and spreads quickly to cover the entire body before disappearing over a median of 3 days. All symptoms typically resolve within a week. Twenty percent of patients develop petechiae on the soft palate called Forchheimer spots (Forchheimer spots image). Asymptomatic infection occurs in up to 50% of children. Infected patients should be considered contagious from 7 days before until 7 days after the rash starts, with the onset of the rash being the most contagious timepoint. (rubella rash image)
• Diagnosis - rubella is challenging to diagnose because it may present with mild, nonspecific symptoms, and it may be overlooked in countries with high vaccination rates. Rubella should be considered in unvaccinated individuals with a febrile rash who recently traveled to a foreign country. Antibody tests are widely available, and IgM is usually detectable 4 days after the onset of rash. PCR testing can be performed on upper respiratory samples and amniotic fluid.
• Treatment - rubella typically causes a mild illness that is treated symptomatically with NSAIDs, fluid, and rest. The greatest concern with the virus is exposure of unvaccinated pregnant women in the first trimester of pregnancy.
• Prevention - the MMR (measles, mumps, rubella) vaccine is highly effective at preventing rubella [4,30,31]

• Varicella (chickenpox)
• Epidemiology - varicella, also called chickenpox, is a common and highly contagious childhood infection. In 1995, a varicella vaccine was introduced that greatly reduced the number of cases. The vaccine is 70 - 90% effective at preventing infection and 95% effective at preventing severe disease. The incidence of varicella is highest in children aged 4 - 10 years, and most cases occur in the winter and spring.
• Pathology - varicella is a herpes virus that is easily passed from person to person through direct contact and inhalation of aerosols from vesicular skin lesions and infected respiratory droplets. The virus infects epithelial cells of the upper respiratory tract, and from there, it gains access to regional lymph nodes, where it multiplies. Four to six days later, the first viremia occurs, which allows the virus to invade the reticuloendothelial system and replicate further. A second viremia occurs 8 - 10 days later that is marked by skin invasion and the characteristic rash. In the epidermis, varicella gains access to local sensory nerves, where it remains dormant in dorsal ganglion cells and can reactivate years later to cause herpes zoster (also called shingles). See herpes zoster for more.
• Symptoms - varicella has an average incubation period of 14 - 16 days, after which low-grade fever and malaise may occur for 1 - 2 days before the onset of the rash; in children, the rash is often the first sign of infection. Varicella rash first appears on the face, back, and trunk before spreading to involve the entire body. Lesions progress from itchy macules to papules to vesicles that crust over. The rash is often accompanied by 2 - 3 days of fever and malaise, and symptoms typically resolve within a week. Breakthrough infections in vaccinated children are usually mild, but up to 30% may have symptoms that are similar to unvaccinated children. Infected persons are considered contagious from 1 - 2 days before rash onset and until all the skin lesions have crusted over. In vaccinated individuals, lesions may not crust; these children are considered contagious until no new lesions have appeared for 24 hours. (varicella images)
• Diagnosis - PCR testing can be performed on swabs from vesicles and other body fluids (e.g. CSF). IgM antibody testing is widely available, but it is less sensitive than PCR and cannot distinguish between primary infection and viral reactivation/re-exposure. Viral cultures take a long time to develop and have low sensitivity. The Tzanck smear that looks for multinucleated giant cells in vesicular fluid is rarely performed anymore.
• Treatment - varicella can be treated with acyclovir or valacyclovir. Maximum benefit is seen when medication is started within 24 hours of rash onset. The AAP recommends treating people who are at high risk for severe disease, which they define as the following:
• Healthy people older than 12 years of age
• People with chronic cutaneous or pulmonary disorders
• People receiving long-term salicylate therapy
• People receiving short, intermittent, or aerosolized courses of corticosteroids
• Prevention - the varicella vaccine, which is given in two doses at 1 year and 4 - 6 years, is 70 - 90% effective at preventing infection. Varicella immune globulin is available to prevent infection in exposed individuals who cannot get the vaccine (e.g. newborns, pregnant women). [4,34]

• Cat scratch disease
• See cat scratch disease

• Diphtheria
• Epidemiology - diphtheria is a bacterial infection that affects the upper airway. Diphtheria was a significant cause of morbidity and mortality among children until the 1930s, when a vaccine against the diphtheria toxin was introduced. Today, only about 1000 cases per year are seen in the U.S.. Susceptible populations include homeless people, unvaccinated, Native Americans, people living in crowded conditions, alcoholics, and lower socioeconomic groups.
• Pathology - diphtheria is caused by a gram-positive bacillus called Corynebacterium diphtheriae. Diphtheria is spread through inhalation of infected respiratory droplets. In rarer cases, it may be transmitted through contact with contaminated fomites (e.g. clothing, doorknobs, etc.). Once the bacteria gains access to the pharynx, it attaches itself to epithelial cells and secretes a toxin. Diphtheria toxin causes a local inflammatory reaction that produces the characteristic grey pseudomembrane over the throat and tonsils. In some people, the toxin is able to spread systemically, where it can affect the myocardium (myocarditis), kidneys, and nervous system (neuropathy). Diphtheria can also infect the skin and cause nonhealing ulcers.
• Symptoms - the average incubation period for diphtheria is 2 - 5 days, after which most patients experience low-grade fever, sore throat, headache, and cervical lymphadenopathy. Within 2 - 3 days, the pseudomembrane appears over the tonsils and throat. The membrane is composed of red blood cells, white blood cells, necrotic tissue, and bacteria; scraping the membrane causes bleeding (pseudomembrane image). If untreated, the membrane can spread to involve the larynx and trachea, leading to airway obstruction and aspiration. It is estimated that untreated, unvaccinated diphtheria has a mortality rate of up to 30%.
• Diagnosis - Corynebacterium diphtheriae can be cultured and isolated from throat and nasal swabs. The isolate is then tested for toxin production using an assay called the Elek test; in the U.S., only the CDC performs this test. Gram staining of culture specimens may reveal nonencapsulated, nonmotile bacilli in clusters. PCR testing exists but is not widely available.
• Treatment - diphtheria is treated with antibiotics and an antitoxin that is derived from horse serum. The antitoxin binds and neutralizes diphtheria toxin, and it is only available from the CDC. The preferred antibiotic is either erythromycin or penicillin G.
• Prevention - the DTaP and TdaP vaccines are highly effective at preventing diphtheria [4,32,33]

• Impetigo
• See impetigo

• Otitis media
• See otitis media

• Pertussis (whooping cough)
• Epidemiology - pertussis was a common childhood infection until the 1940s, when a vaccine was introduced. From there, the incidence steadily declined until the 1980s, when the number of cases started to rise in all age groups. The reason for the reversal is multifactorial and includes the following: (1) increased awareness and surveillance for the disease, (2) better diagnostic methods (e.g. PCR testing), (3) waning vaccine immunity. Protection from the vaccine wanes after 3 - 5 years and is nonexistent after 12. In 2012, the last peak year of pertussis cases, the CDC reported 48,277 cases in the U.S. Worldwide, an estimated 50 million cases occur annually. The incidence of pertussis is highest among infants, but the largest increase in cases has been among adolescents and adults. Pertussis outbreaks typically occur between June and September.
• Pathology - pertussis, also called whooping cough, is caused by Bordetella pertussis, a gram-negative coccobacillus. Pertussis is passed from person to person through infected respiratory droplets that are expelled during coughing, sneezing, and talking. Pertussis attaches itself to ciliated epithelial cells in the upper respiratory tract, where it secretes a toxin that paralyzes cilia; loss of ciliary movement inhibits the clearance of secretions. A purulent exudate forms in the airways that can drain into the lower respiratory tract and compromise oxygen exchange. Young infants (< 6 months old) and people with underlying respiratory, cardiac, or neurologic disease are at greatest risk for severe disease.
• Symptoms - the incubation period for pertussis is 5 - 10 days, after which mild URI symptoms occur (e.g. low-grade fever, mild cough, congestion). One to two weeks later, a second stage begins that is marked by fits of rapid coughing followed by a "whooping" sound. The whooping sound occurs during forced inspiration after repeated coughing. Excessive coughing can also induce vomiting and exhaustion in some patients. The second stage lasts for 1 - 6 weeks in most patients, but some may cough for 10 weeks or more. After the second stage, a convalescent period begins where the cough gradually resolves over 2 - 3 weeks.
• Diagnosis - PCR testing performed on nasopharyngeal swabs is very sensitive for pertussis; however, specificity is highly variable among assays. Testing should be performed 0 - 3 weeks after cough onset, and the CDC has published instructions for using PCR to diagnose pertussis (see CDC pertussis PCR best practices). Pertussis cultures are considered the gold standard for diagnosis, but they are less sensitive than PCR and can take up to 7 days to grow. Antibody testing available at commercial labs is mainly used to confirm past immunization.
• Treatment - most people with pertussis recover fully without treatment. The CDC recommends that persons ≥ 1 year of age be treated within 3 weeks of cough onset and that infants younger than 1 year and pregnant women be treated within 6 weeks. Macrolides and sulfamethoxazole are the preferred antibiotics, and dosing recommendations are available at the links below.
• Azithromycin (preferred drug in infants < 1 month-old)
• Clarithromycin
• Erythromycin
• Sulfamethoxazole / trimethoprim
• Prevention - the DTaP and TdaP vaccines are effective at preventing pertussis, but immunity wanes after 3 - 5 years. The CDC recommends postexposure antibiotic prophylaxis (see antibiotic links above) in all household contacts (within 21 days of onset of cough in the index patient) and high-risk individuals (see CDC high-risk definitions). [4]

• Strep throat
• See strep throat

• Urinary tract infection (UTI)
• See urinary tract infection

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• ASSOCIATED CONDITIONS

• IgA vasculitis (Henoch-Schönlein purpura)
• Epidemiology - IgA vasculitis, formally referred to as Henoch-Schönlein purpura, is an autoimmune syndrome that is sometimes triggered by an infection. IgA vasculitis affects people of all ages, but children have the highest incidence, with about 15 cases per 100,000 per year. Ninety percent of affected individuals are younger than 10 years, and the incidence peaks at 6 years. White males may have a higher risk, and most cases occur in the winter.
• Pathology - the pathology behind IgA vasculitis is not entirely understood, but it is believed to occur when abnormal IgA1 antibodies act as antigens and are bound by IgG and other IgA antibodies. These antibody complexes deposit in blood vessel walls and other organs, where they stimulate the complement pathway and cause inflammation. In greater than 75% of cases, an antecedent upper respiratory tract or GI infection is reported, and it has been hypothesized that antigens from these infections stimulate the IgA production that leads to the syndrome. Other possible stimulating factors include foods, environmental factors, and drugs (e.g. cefuroxime, diclofenac, ampicillin, erythromycin).
• Symptoms - in up to 75% of children, symptoms appear 1 - 3 weeks after an upper respiratory tract or GI infection; group A strep is the most common etiology, and up to 50% of patients with IgA vasculitis have an elevated antistreptolysin O titer. An initial prodromal phase of low-grade fever and malaise may occur before the characteristic rash appears. Other symptoms depend upon the organ systems affected. In most cases, symptoms last an average of 4 weeks before spontaneously resolving.
• Rash (100%) - the rash first appears as macules or urticaria that evolve into papules and eventually, palpable purpura, which are raised, nonblanching lesions caused by blood vessel hemorrhaging into the skin. (IgA vasculitis purpura)
• Arthritis (75%) - arthritis may be the presenting symptom in 15 - 25% of cases. It is marked by swollen, tender joints involving the knees, ankles, and feet. The condition is transient and has no lasting effect.
• Abdominal pain (65%) - colicky abdominal pain occurs about one week after the rash in 65% of cases; however, it may be the presenting symptom in up to 40% of patients. The pain is often accompanied by vomiting, and thirty percent of patients will have GI bleeding that is either occult or gross (e.g. melena, bloody diarrhea). The most concerning complication is intussusception, which is seen in 1- 5% of cases.
• Kidney disease (40%) - kidney disease affects about 40% of patients, and it can occur at any time within 3 months of rash onset. Microscopic hematuria is the most common finding, and gross hematuria is seen in about 25% of patients. Proteinuria accompanies hematuria in 60% of cases. Most patients have complete recovery of kidney function, but 2 - 5% will go on to develop chronic kidney disease.
• Orchitis (35%) - orchitis is seen in up to 35% of male cases
• Diagnosis - there is no definitive lab or imaging test for diagnosing IgA vasculitis. If the condition is suspected, a CBC, CMP, urinalysis, PT, and PTT should be ordered. Diagnostic criteria developed by an international consensus of experts are provided below.
• Palpable purpura in the presence of ≥ 1 of the following:
• Abdominal pain
• Arthritis (acute, any joint) or arthralgia
• Renal involvement (proteinuria, red blood cell casts, or hematuria)
• Proliferative glomerulonephritis or leukocytoclastic vasculitis with predominant deposition of IgA on histology
• Treatment - IgA vasculitis resolves spontaneously in 94% of children and 89% of adults. Treatment is mainly supportive and includes hydration, monitoring for renal and abdominal disease, and use of analgesics; acetaminophen is preferred, and NSAIDs should be avoided if GI bleeding or renal disease is present. Patients with severe disease may need to be monitored as inpatients. Steroids and other immunosuppressants have not been definitively proven to prevent or improve kidney disease but are still used in many cases. ACE inhibitors/ARBs and plasma exchange are other possible treatments.
• Monitoring - patients with IgA vasculitis should be monitored for the development of kidney disease. Urinalysis should be performed weekly while the disease is active and then monthly for 3 months after symptoms have resolved.
• Recurrence - recurrent episodes within the first 6 months of onset occur in up to a third of patients. Patients with initial renal involvement are at greatest risk. [36,37,38]

• Kawasaki disease
• Epidemiology - Kawasaki disease is a vasculitis that affects about 25 per 100,000 children in the U.S. Ninety percent of cases occur in children under the age of five, and the incidence peaks between 18 and 24 months. Males are affected more than females, and Asians have a higher risk than other races.
• Pathology - Kawasaki disease is a vasculitis of medium-sized arteries, particularly the coronary arteries. The etiology of Kawasaki disease is unknown, but it is believed to be related to infections that trigger an abnormal immune response. A long list of common viral and bacterial agents have been implicated, but no definitive link has been found. Once the immune response is triggered, vessel walls are infiltrated by neutrophils, and an inflammatory reaction that includes IgA-producing plasma cells, cytotoxic lymphocytes, and numerous cytokines (e.g. TNF, interleukins) commences. Over the course of weeks to months, the elastic lamina of the vessel wall is destroyed and replaced by fibrous tissue. The scarred and damaged vessel can lead to coronary artery narrowing and aneurysms.
• Symptoms - Kawasaki disease can be broken down into 3 phases
• Acute phase - the acute phase is marked by an abrupt onset of spiking high fevers that last 7 - 14 days and can run longer if untreated. Soon after the fever starts, the following is seen: [1] oral cavity changes that include red, cracked lips and strawberry tongue (97%), [2] generalized maculopapular rash within 5 days of fever onset (96%), [3] bilateral, nonpurulent conjunctivitis (89%), [4] edema and/or erythema of the hands and feet (76%), [5] myocarditis (50 - 70%), [6] cervical lymphadenopathy (63%).
• Subacute phase - the subacute phase begins 2 - 3 weeks after fever onset and is marked by desquamation of the hands and feet, thrombocytosis, arthritis of the large joints (20 - 40%), and the development of coronary artery aneurysms (15 - 25% of untreated patients). The risk of death is highest during this phase.
• Convalescent phase - the convalescent phase begins when clinical symptoms of the disease start to resolve around 6 weeks. Laboratory abnormalities return to normal, and most symptoms are gone within 3 months of presentation. New coronary aneurysms are unusual after 8 weeks, and small coronary aneurysms resolve on their own in 60% of cases.
• Diagnosis - Kawasaki disease is a clinical diagnosis. Diagnostic criteria from the AHA for "classic" Kawasaki disease are presented below. The AHA states that a diagnosis of "incomplete" Kawasaki disease can be made in children with fever for 5 or more days who meet 2 to 3 of the criteria. In these cases, the patient should be evaluated with lab work (e.g. CRP, ESR) and followed clinically.
• Fever of at least 5 days duration and at least 4 of the following:
• Oropharyngeal changes - erythema, cracking lips, strawberry tongue
• Generalized rash - typically maculopapular (Kawasaki disease rash)
• Conjunctivitis - bilateral, nonpurulent, painless, spares the limbus (area immediately surrounding the iris) (limbal-sparing conjunctivitis)
• Extremity changes - edema and/or erythema of the hands and feet that progresses to desquamation in 2 - 3 weeks
• Cervical lymphadenopathy
• Treatment - patients with Kawasaki disease should be admitted to the hospital and given IVIG, which lowers the risk of cardiac abnormalities from around 25% to less than 5%. Aspirin has traditionally been given to reduce inflammation and prevent thrombosis; however, it does not prevent aneurysms, and some have questioned its use. The addition of corticosteroids to IVIG may help to reduce the risk of coronary abnormalities even further; although, results from trials have been mixed.
• Monitoring - patients who develop aneurysms need to be followed with cardiac imaging (e.g. ECHO, stress test, angiography). Antiplatelet therapy and anticoagulants are also recommended in some. [39,40,41]

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