key: cord-0037661-jmifk1q0
authors: Laurens, Matthew B.
title: Infectious Diseases
date: 2019-11-07
journal: Pediatric Board Study Guide
DOI: 10.1007/978-3-030-21267-4_9
sha: ba75a413940054474aaef6e7885355ab759aa904
doc_id: 37661
cord_uid: jmifk1q0

Infectious disease is one of the most common causes of acute care visits to outpatient pediatric clinics, urgent care facilities, and hospital emergency departments.

• Immunization: Required for all enrollees and staff • Assist children with toileting and hand hygiene -Hand washing with soap and water, alcohol-based antiseptic is acceptable if > 24 months old -Careful food preparation and diaper changing -Disinfecting environmental surfaces prevents diarrheal diseases -Respiratory etiquette (sneeze or cough into elbow) • Exclusion and return policies:

-Use gloves when contacting body fluids -Do not exclude because of lice, ringworm, conjunctivitis without fever or behavior change, rash without fever

• Shigella infection -Transmitted from infected feces (personto-person contact) -Do: Stool bacterial cultures for any symptomatic contact -Know: If Shigella infections are confirmed, administer appropriate antibacterial treatment -Return to childcare center if diarrhea has resolved and stool culture is negative • Nontyphoidal Salmonella species -No antibiotic is required except:

• Infants younger than 3 months of age • Immunocompromised host -Infected individuals should be excluded from childcare until symptoms resolve • Salmonella serotype Typhi -Treatment is indicated for infected individuals -Return to childcare center

• 5 years of age or younger: 48 h after antibiotic treatment • Older than 5 years: 24 h after the diarrhea has resolved • Other risk of infection: e.g., Giardia; rotavirus; cryptosporidiosis; respiratory syncytial virus (RSV); parainfluenza virus; adeno, rhino, and corona viruses; Haemophilus influenzae, pneumococcal, hepatitis A, and cytomegalovirus infections

• Standard precautions are indicated in the care of all patients including: -Hand hygiene before and after each patient contact -Protective equipment when needed

• Alcohol-based products preferred because of their superior activity and adherence • Soap and water are preferred when hands are visibly soiled or exposed to a spore-forming organism (Clostridium difficile is the most common), or for norovirus • Gloves, isolation gowns, masks, and goggles for any exposure to body fluids, contaminated materials, and sharps • Strict aseptic technique for all invasive procedures and for catheter care • Separate well and sick children areas in medical offices

• Contact precautions, e.g., RSV, C. difficile, other infectious diarrhea, and Staphylococcus aureus -Gloves and gowns are required when there is direct patient contact • Droplet precautions, e.g., influenza, Neisseria meningitidis, mumps, and Bordetella pertussis -Use of a surgical mask is required -A single room is preferred -Remember all office and hospital staff should receive an annual influenza immunization • Airborne precautions, e.g., Mycobacterium tuberculosis, measles, varicella (with contact precautions), severe acute respiratory syndrome (SARS) -Negative pressure airborne infection isolation room -Room air needs 6-12 changes per hour or recirculation through a high-efficiency particulate air (HEPA) filter -Certified N95 fine particle respirator mask or similar sealing mask

• Exclusive breastfeeding for the first 4-6 months is recommended by American Academy of Pediatrics (AAP) • Interrupt breastfeeding for:

-Breast abscess or cellulitis with direct contact with infant's mouth; can continue on other side -Women with tuberculosis (for first 2 weeks of treatment, then acceptable) -Maternal HIV (except in resource-limited settings) -Maternal human T cell lymphotropic virus (HTLV) types 1 or 2 • Do not interrupt for maternal hepatitis B

• Postpartum colostrum contains high concentrations of antibodies and other infection-protective elements • The actual antibodies against specific microbial agents present in an individual woman's milk depends on her exposure and response to the particular agents • Lactoferrin: Limits bacterial growth by iron chelation • Lysozyme: Bacterial cell wall lysis • Lactalbumin: Enhances Bifidobacterium growth and modulates immune system • Casein: Limits adhesion of bacteria and facilitates the growth of Bifidobacterium • Carbohydrates: Enhance the growth of probiotics • Lipids: Lytic effect on many viruses and are active against Giardia Absolute contraindication of breastfeeding • Maternal HIV infection (except in resourcelimited settings) • HTLV1 and HTLV2 • Tuberculosis (active, untreated pulmonary tuberculosis, until effective maternal treatment for the initial 2 weeks or the infant is receiving isoniazid) • Herpes simplex virus (HSV) infection on a breast (until the lesions are cleared) • Breast abscess or cellulitis with direct contact with infant's mouth; can continue on other side

• Chemoprophylaxis before traveling to endemic areas, e.g., atovaquone/proguanil for malaria should be given before traveling to endemic areas • Use mosquito netting (bed-net) during sleep in tropical areas • Use protective clothing • Repellents, e.g., DEET (> 20%) applied to children should be used to prevent tick and mosquito bites -Insecticide should not be applied to children's hands because of risk of ingestion • Use of occlusive clothing to prevent mosquito and tick bites is effective • Remove tick from skin immediately, then wash with soap and water • Keep pets tick-free • Immunization against disease (e.g., yellow fever, typhoid, cholera, Japanese encephalitis, meningococcus, rabies if high risk) when traveling to endemic area at least 2 weeks before departure

• Exposure to contaminated water can cause diarrhea and other infections, e.g., swimmer's ear • Cryptosporidium is most common cause of recreational water-associated outbreaks; Giardia is second, also Shigella is another cause • Regularly test home pools for pH, free chlorine, or bromine • People with diarrhea should not participate in recreational water activities • Children with diarrhea should avoid swimming for 2 weeks after cessation of diarrhea (for Cryptosporidium) • Avoid water ingestion • Clean the child with soap and water before swimming • Change diapers in the bathroom

• Use of antimicrobials is the most important factor that leads to antimicrobial resistance, including in patients and in agriculture • Diseases for which antibiotics are not appropriate: Nonspecific cough, bronchitis, viral pharyngitis, common cold

• Malnutrition increases susceptibility to infections; repeat or chronic infections contribute to malnutrition. A vicious cycle • Malnutrition increases severity of disease and risk of poor outcomes • Malnutrition increases risk of bacterial versus viral diarrhea • Malnutrition increases risk of pneumonia

• Infants have immature hypothalamic thermoregulatory system and lack a central "control" of temperature, making their body temperature more susceptible to environmental temperature • Infants with CNS infection affecting thermoregulatory system may present with hypothermia

• Example: Sickle cell anemia, congenital or surgical asplenia • Increased risk for bacteremia and meningitis due to encapsulated organisms like Streptococcus pneumoniae, H. influenzae type b (Hib), and N. meningitidis • Consider daily antimicrobial prophylaxis (especially for sickle cell disease) • Special vaccine consideration for asplenia:

-Pneumococcal conjugate (PCV13) and polysaccharide (PPSV23) vaccines are indicated -Following PCV13 series, PPSV23 should be given at 24 months of age and 5 years later -Meningococcal conjugate vaccine (MCV) should be given at 2 months of age (MenACWY-CRM, e.g., Menveo). Revaccinate 3 years later and then every 5 years.

-(MenACWY-D, e.g., Menactra) cannot be given before 2 years of age 

Background • CMV is a double-stranded DNA virus and a member of the Herpesviridae family • At least 60% of the US population has been exposed to CMV • CMV usually causes an asymptomatic infection; afterward, it remains latent throughout life and may reactivate

• Vertical transmission -CMV can be maternally transmitted: (1) transplacentally in utero, (2) at birth through infected maternal genital tract, and (3) postnatally by ingestion of CMVpositive human milk or transfusion -Risk decreased by the use of pasteurized human milk or freezing human milk • Horizontal transmission -Exposure to CMV can occur from almost all body fluids, including:

• Urine, saliva, and tears • Genital secretions, blood transfusion, and transplanted organs -Toddlers infected postnatally with CMV shed the virus in their urine for a mean of 18 months (range 6-40 months) -Healthy adults infected with CMV will shed the virus for up to several weeks -Shedding of CMV in toddlers in childcare centers can be as high as 70% • Transfusion and transplantation -Can be eliminated by CMV-negative donors -Filtration to remove white blood cells (WBCs) -Latent form in tissue and WBCs can be reactivated many years later

• Microcephaly • Periventricular calcifications (intracerebral) • Chorioretinitis, strabismus, microphthalmia, and optic nerve atrophy • Hypotonia, poor feeding, ventriculomegaly, cerebellar hypoplasia • Intrauterine growth restriction • Prematurity • Jaundice • Hepatosplenomegaly • Thrombocytopenia; petechiae and purpura • Later in childhood 7-15% will develop progressive sensorineural hearing loss • Developmental delays

• Perinatally or postnatally: -Confirmed by detection of the virus in urine, blood, saliva or CSF by culture or polymerase chain reaction (PCR) -Congenital CMV: If diagnosed in first 3 weeks of life • Immunocompromised host:

-Test for pp65 antigen (CMV antigenemia assay) or quantitative DNA in blood or plasma Treatment

• Congenital CMV -Treatment modestly improves hearing and neurodevelopmental outcomes for infants -CNS disease is treated with oral valganciclovir (or IV ganciclovir) for 6 months • CMV retinitis in HIV -Ganciclovir and valganciclovir are indicated for induction and maintenance therapy • CMV pneumonitis in bone marrow or stem cell transplant patients -Ganciclovir plus CMV immune globulin are used together

• Epstein-Barr virus (EBV) • HSV1, HSV2 • CMV • VZV • Human herpesvirus type 6 (HHV-6), aka sixth disease • Human herpesvirus type 7 (HHV-7) • HHV-6 and HHV-7 can both cause exanthema subitum, aka roseola • Human herpesvirus type 8 aka Kaposi sarcoma-associated herpesvirus)

• EBV or human herpesvirus-4 is a gammaherpesvirus that infects more than 95% of the world's population • Mode of transmission primarily by oral contact with saliva -EBV is shed in saliva at high concentrations for more than 6 months following acute infection and intermittently at lower concentrations for life -Young children directly or through handling toys -Adolescents due to close contact such as kissing

• EBV infection in healthy person; infectious mononucleosis (EBV is the most common cause) -Fever -Exudative pharyngitis (similar to streptococcal pharyngitis but more painful) -Cervical lymphadenopathy, commonly anterior, and posterior cervical lymph node (may compromise the airway) -Splenomegaly (90%); 2-3 cm below the left costal margin is typical -Hepatomegaly (10%) -Fatigue and malaise -Rash -Typically a benign, self-limited illness in healthy persons, but can cause fatal disseminated infection even in healthy hosts • EBV infection in immunocompromised persons (transplant, HIV) -Fatal disseminated infection -Nonmalignant EBV-associated proliferations, e.g., virus-associated hemophagocytic syndrome -Post-transplant lymphoproliferative disorders -X-linked lymphoproliferative syndrome -Nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin disease, non-Hodgkin lymphoma, gastric carcinoma

• Heterophile antibody test (monospot) -Not recommended for children younger than 5 years of age as the result is not specific for acute mononucleosis -Helpful for older children and adolescents with mono signs and symptoms • EBV viral capsid antigen (VCA) immunoglobulin ( 

• Ampicillin or amoxicillin may cause morbilliform rash • Decrease immunosuppressive therapy in transplant patients if possible • Short courses of corticosteroids for fewer than 2 weeks can be given in the following cases: -Tonsillar inflammation with impending upper airway obstruction -Massive splenomegaly -Myocarditis -Hemolytic anemia -Hemophagocytic lymphohistiocytosis (HLH)

• Splenomegaly: -Avoid strenuous activity and contact sports for 21 days after onset, then limited noncontact aerobic activity if no overt splenomegaly -Contact sports allowed 4-6 weeks after onset if no splenomegaly -Fatigue may persist for 3-6 months or longer Herpes Simplex Virus 1 and 2 (HSV1 and HSV2)

• Characterized by neurovirulence, latency, and reactivation in the area supplied by the ganglia in which latency was established • Reactivation induced by various stimuli (e.g., fever, trauma, emotional stress, sunlight, and menstruation) • Spread by direct contact with lesions or infective secretions 

• Neonatal (3 forms that may overlap): -25%: Disseminated disease affecting mostly liver, lungs, and CNS; "sepsis" clinical picture -30%: CNS disease "meningoencephalitis" -45%: Skin, eye, and mouth (SEM) disease • Children and adolescents:

-Most primary HSV is asymptomatic; reactivation is also mostly asymptomatic -Gingivostomatitis is the most common clinical manifestation; usually HSV1, associated with fever, irritability, submandibular lymphadenopathy and ulcerative gums and buccal mucosa. May recur as "fever blister" or "cold sore" -Genital herpes: Genital vesicles or ulcers of genitalia and/or perineum, HSV1 or HSV2. 

• VZV is herpesvirus family member • Incubation period is 2 weeks • Contagious 1-2 days before rash until all lesions are crusted over • Spreading via airborne or direct contact with mucosa of upper respiratory tract or conjunctiva, and transplacental passage • VZV is the cause of varicella (chickenpox) and herpes zoster (shingles) • Varicella is more contagious than zoster • Immunity to varicella is lifelong; reactivation as zoster infection is possible • Immunocompromised at higher risk for severe disease and disseminated infection

Varicella (Chickenpox) • The prodrome: low-grade fevers, headaches, and malaise • Skin lesions initially appear on the face and trunk • Lesions start as red macules and pass through stages of papules, vesicles with central umbilication, pustules, and then crust over • The vesicle on the erythematous base of a lesion leads to its description as a "pearl" or "dewdrop on a rose petal" • Lesions predominate in central skin areas and proximal upper extremities with relative sparing of distal and lower extremities • Chickenpox generally is a benign self-limited illness, and is more severe in adults, adolescents, and infants compared to older children • Complications include bacterial superinfection, especially with Streptococcus pyogenes, which can progress to cellulitis, myositis, and sepsis • Pneumonia (major cause of morbidity and mortality), hepatitis, and thrombocytopenia are also possible • Immunocompromised patients may experience visceral dissemination, encephalitis, hepatitis • Neonates whose mothers develop varicella 5 days to 2 weeks before delivery have increased risk of death due to diminished maternal antibodies

• Latency establishes in sensory ganglia infected during primary VZV or vaccination • Shingles classically is a unilateral rash consisting of grouped vesicles on an erythematous base, covering 1-3 adjacent dermatomes, often accompanied by pain and pruritus ( Fig. 9 .3) • Postherpetic neuralgia, pain after rash resolves, is uncommon in pediatrics • Discharge or isolate exposed patients without evidence of immunity • VariZIG given to the baby born to mother who develops illness from 5 days before until 2 days after birth • IV acyclovir is indicated for varicella infection in infants born to mothers who experience chickenpox from 5 days before until 2 days after delivery Human Herpesvirus Type 6 (HHV-6) Including Roseola Infantum (Exanthem Subitum)

• Commonly affects children ages 6-18 months old

Clinical presentation ( Fig. 9 .4) • Typically, a nonspecific febrile illness without rash • Very high fever for 3-7 days, followed by maculopapular rash in 20% after fever resolves; rash can last hours to days • They may have lymphadenopathy, vomiting, diarrhea, febrile seizure, or respiratory symptoms (1-2 weeks) and GI tract (3-6 weeks) • Incubation period 3-6 days; paralysis occurs 1-3 weeks after exposure

• Fever and sore throat in 25% • Aseptic meningitis in 1-5% • Flaccid paralysis in a descending manner without reflexes in < 1% -Follows febrile illness -Symmetric paralysis affecting proximal muscles -Cranial nerve and diaphragm/intercostal muscle involvement may affect respiration -33% recover • Affects anterior horn cells in the spinal cord

• Cell culture of pharynx, stool, and CSF obtained as early as possible 

Epidemiology • Transmitted via direct or droplet contact with respiratory secretions • Peak incidence from winter to spring • 25 to 50% asymptomatic • Lifelong immunity • Can transmit 3 days before to 7 days after rash appears • Infants with congenital rubella may shed for 1 year in nasopharyngeal secretions and urine 

Background and epidemiology • S. aureus is the most common cause of skin and soft tissue infection and musculoskeletal infection in healthy children • Second leading cause of healthcare-associated bacteremia (coagulase-negative staphylococci is first) • Leading cause of secondary bacterial pneumonia in children • Most common cause of healthcare-associated surgical site infections • Coagulase positive • Grapelike clusters ( Fig. 9 .8) • S. aureus colonizes the nares and skin in 30-50% of children • Transmitted by direct contact and indirectly from other patients in hospital settings • Can spray short distances into the air • "Vancomycin-intermediately susceptible S.

aureus" related to repeat vancomycin use in individuals. Vancomycin-resistant S. aureus rare • Incubation period can be 12 h for postoperative toxic shock syndrome

• Bullous and crusted impetigo • Skin and soft tissue or lymph node infection • If the organism seeds the bloodstream, dissemination to joints, bones, kidney, liver, muscles, lungs, and heart valves may occur, causing substantial morbidity and potential mortality • S. aureus is the most common cause of osteomyelitis, including sickle cell disease patients (who are also at increased risk for Salmonella osteomyelitis) • Children with cyanotic congenital heart disease are at high risk of staphylococcal brain abscess aureus. • Hot tub folliculitis is usually caused by Gramnegative bacteria (most often P. aeruginosa; self-limited) • Usually the child looks healthy and does not appear ill • Abscess (< 5 cm) drainage alone is curative without antibiotics and should be performed along with a request for culture

• Indication for antibiotics -The child has high fever or other systemic symptom -The abscess is larger than 5 cm -Located in a critical location or in an area difficult to drain -Signs and symptoms persist following incision and drainage • Common oral anti-staphylococcal antibiotics -Trimethoprim-sulfamethoxazole (TMP-SMX) effective against most MRSA -Cephalexin remains a good empiric choice for MSSA and group A Streptococcus (GAS) infections -Clindamycin -Doxycycline (in children older than 8 years of age) -Linezolid (for resistant MRSA infections not susceptible to TMP-SMX or clindamycin) • Recurrent staphylococcal skin infections recommendations -Enhanced hygiene and environmental cleaning -Treatment for anyone in the family who has active disease -Nasal and perianal mupirocin -Skin decolonization (chlorhexidine and/or bleach baths) -Treatment with antibiotic-based decolonization regimens (usually rifampin plus an additional agent) in selected cases

• Production of toxic shock syndrome toxin-1 (TSST-1) • Can be caused by S. aureus or S. pyogenes (aka group A Streptococcus or GAS) 

• Common pneumococcal infections include: -Acute otitis media -Sinusitis -Pneumonia -Bacteremia (most common manifestation of invasive pneumococcal disease) -Meningitis (leading cause of meningitis) • Pneumonia -S. pneumoniae is the most common bacterial cause of community-acquired pneumonia in both children and adults -High fever and ill-appearing -Cough and tachypnea -Respiratory distress -Crackles -Diminished breath sounds -Lobar consolidation may be noted on chest radiography in older children -Know: Infants and young children may have bronchopneumonia with a scattered distribution of parenchymal consolidation -Pleural fluid may be evident in some patients

• Culture from blood or normally sterile body fluids such as CSF, pleural, synovial, or middle ear fluid • PCR on blood or CSF specimen • Positive results should have antimicrobial susceptibility testing for penicillin, cefotaxime or ceftriaxone, and clindamycin.

• Outpatient otitis media: Amoxicillin (80-90 mg/kg/day for < 6 months and 6-23 months with bilateral disease) with watch and wait 48-72 h for older children 

• Group A Streptococcus (GAS) is a Grampositive bacterium that grows in chains ( Fig. 9 .11)

Background and epidemiology • Causes pharyngitis and impetigo • Pharyngitis: Transmits via contact with respiratory tract secretions of infected person • Impetigo: Transmits via direct contact from another person • Increased risk for pharyngitis and impetigo with crowding • Most often in schools, childcare centers, contact sports • Some are chronic pharyngeal carriers • Increased risk of invasive GAS infection in infants and elderly • Like S. aureus, can cause TSS • Rheumatic fever can develop in about 3% of untreated patients with GAS pharyngitis • Incubation period for GAS pharyngitis is 2-5 days; for GAS impetigo is 7-10 days • For TSS, can occur 14 h after inoculation of organism (e.g., trauma)

• Sore throat, fever, headache, and abdominal pain the most classic presentation • Nausea and vomiting may occur • Pharyngeal erythema and palatal petechiae ( Fig. 9 .12) • Inflammation of the uvula • Anterior cervical lymphadenopathy • Tonsillar exudates may or may not be present 

• Rapid antigen detection test is highly recommended to decrease overuse of antibiotics • Testing of asymptomatic household contacts not recommended except when contacts are at increased risk of developing sequelae of GAS infection, e.g., rheumatic fever, post-streptococcal glomerulonephritis, or TSS • If rapid antigen detection test (RADT) positive, treat (specificity of 95%) • If RADT is negative, do throat culture (sensitivity of 65-90%) • Treatment of GAS sore throat as long as 9 days after the onset of symptoms still effectively prevents rheumatic fever; initiation of antibiotics is seldom of urgent importance

• Reduces complications • Decreases the duration of infection • Reduces transmission to others • Oral penicillin VK (250-500 mg twice to three times a day for 10 days) is the antibiotic treatment of choice for GAS pharyngitis • Amoxicillin (50 mg/kg, maximum 1 g, once daily for 10 days) often is used instead of oral penicillin because of its more palatable liquid formulation • Cephalosporins or macrolides may be used as first-line therapy in patients allergic to beta-lactam antibiotics but otherwise are not recommended as first-line therapy • IM benzathine penicillin G 600,000 U for children who weigh < 27 kg and 1.2 million U for heavier children as a single dose (if adherence is a problem but is painful) • Know: Treatment is indicated if a GAS carrier develops an acute illness consistent with GAS pharyngitis Treatment to eradicate GAS carriage indications • History of acute rheumatic fever • Close contact who has a history of rheumatic fever • Families experiencing repeated episodes of GAS pharyngitis • Eradication regimens include clindamycin, cephalosporins, amoxicillin-clavulanate

• Syndrome characterized by exudative pharyngitis, fever, and scarlatiniform rash • Caused by toxin-producing GAS found in secretions and discharge from the nose, ears, throat, and skin

• Fever may be present • Patient usually appears moderately ill • On day 1 or 2, the tongue is heavily coated with a white membrane through which edematous red papillae protrude (classic appearance of white strawberry tongue) ( Fig. 9 .13) • By day 4 or 5, the white membrane sloughs off, revealing a shiny red tongue with prominent papillae (red strawberry tongue) • Red, edematous, exudative tonsillitis • Diffuse, erythematous, blanching, fine papular rash that resembles sandpaper on palpation ( Fig. 9 .14) • The rash is prominent especially in the flexor skin creases of the antecubital fossa and axillae (Pastia lines, which are pathognomonic for scarlet fever) • Circumoral pallor • Desquamation after the rash starts to fade (usually the rash lasts about 1 week) 

• Common (i.e., crusted or nonbullous) impetigo: Initial lesion is a superficial papulovesicular lesion that ruptures easily • The lesion becomes purulent and covered with an amber-colored crust ( Fig. 9 .15) • Bullous impetigo: Superficial fragile bullae containing serous fluid or pus form and then 

Background • Aerobic Gram-negative diplococcus N. meningitidis • Natural commensal organism living in the nasopharynx of humans • Children younger than 2 years of age have a nearly fivefold greater risk of contracting meningococcal disease than the general adult population • Risk of transmission: Crowded living conditions, e.g., college dormitories, military barracks

• Rash -Any rash appearing in the context of a sudden febrile illness should raise concern -Meningococcal rash is typically present within 24 h of any symptomatology -Petechiae may be intraoral or conjunctival or be hidden in skinfolds -Early rash may not be petechial -Aggressive spread of purpura to large areas with ischemic necrosis -Sudden drops in blood pressure -Acute adrenal hemorrhage (Waterhouse-Friderichsen syndrome)

• Culture of the organism from a normally sterile site is the gold standard for bacteriological diagnosis • CSF study:

-CSF WBC counts are elevated in most patients who have meningitis -CSF WBC counts are low or even normal if the disease is severe and rapidly progressive -Markedly low glucose and elevated protein values are associated with the diagnosis of meningitis • All patients with meningococcal disease or meningitis must be tested for CH50 or CH100 assay (20% of children with meningococcal disease will end having a complement deficiency)

• Know: Antibiotics and fluids should not be delayed • Penicillin is effective treatment for both severe meningococcal septicemia (SMS) and meningococcal meningitis if the diagnosis is certain • Broad-spectrum antibiotics effective against N. meningitidis and other potential pathogens are indicated (e.g., ceftriaxone, cefotaxime, and vancomycin) • Emergency care evaluation and preferably transported via emergency medical services to allow for prompt delivery of IV fluids and airway management if the condition is suspected • Large isotonic fluid boluses (20 mL/kg) over the first 5 min • Inotropic/vasoactive agent such as dopamine or dobutamine • Hydrocortisone may be beneficial in children respond poorly to vasopressors

• MenACWY vaccine is routinely recommended at 11-12 years of age; 2 vaccines licensed for children and adults, 1 dose -Can give as young as 2 months as a 4-dose series for high risk (complement deficiency, asplenia, HIV, travel to endemic area) • MenB vaccine is optional and preferred for 16-18 years of age, 2-dose series -Can give as young as 10 years for high risk (complement deficiency, asplenia, outbreak, lab workers); 2-or 3-dose series for high risk • Antibiotic prophylaxis, e.g., rifampin, ciprofloxacin, azithromycin, or ceftriaxone should be used for contacts: -Childcare contact -Direct exposure to oral secretions of individuals with meningococcal disease (such as personnel providing mouth-to-mouth resuscitation) 

• Remember: The organism produces beta lactamase, which makes amoxicillin ineffective • Cefotaxime or ceftriaxone is the antimicrobial of choice • Meropenem or chloramphenicol is another option • Amoxicillin is the drug of choice for noninvasive diseases such as otitis media or sinusitis; if amoxicillin fails, uses antibiotics against beta-lactamase-producing strains, e.g., nontypeable H. influenzae including amoxicillin/ clavulanate, TMP-SMX, azithromycin, cefuroxime axetil, cefixime, and cefpodoxime.

• All members of household who did not receive immunization • Less than 4 years with incomplete immunization • Younger than 12 months who did not complete primary Hib immunization • Immunocompromised child • Nursery school and childcare center if two or more cases within 60 days (outbreak) 

• Small Gram-negative coccobacilli; normal oral flora in animals, e.g., dogs and cats • Dog or cat bite is a common risk

• Erythema, tenderness, and edema usually develop rapidly within 24 h • Regional lymphadenopathy and fever may occur • Infection that occurs days after the bite is usually caused by S. aureus

• Clean wound with soap and water • Treatment should cover potential pathogens, e.g., P. multocida, S. aureus, and anaerobes • Administration of antibiotic within 8-12 h of injury may decrease the risk of infection • Penicillin is the drug of choice for P. multocida alone • Amoxicillin-clavulanate is the drug of choice for suspected polymicrobial wounds, including cat bites • Clindamycin + TMP-SMX is appropriate for children allergic to penicillin

Background • Small Gram-negative coccobacillus that infects only humans • Spreads by aerosol droplets expelled while coughing or sneezing in proximity to others • Incubation period of 7-10 days

• Catarrhal phase -Lasts from 1 to 2 weeks -Mild fever -Cough -The cough worsens as the patient progresses to the paroxysmal phase • Paroxysmal phase -Lasts from 2 to 6 weeks -Rapid fire or staccato cough -5 to 10 uninterrupted coughs occur in succession, followed by a "whoop" as the patient rapidly draws in a breath -May occur several times per hour -Can be associated with cyanosis, salivation, lacrimation, and post tussive emesis -Despite the severe spells, patients often appear relatively well between episodes -Whoop is usually absent in infants less than 6 months of age -Gasping, gagging, and apnea can occur • Convalescent phase -Decreasing frequency and severity of the coughing episodes -Lasts from weeks to months 

• Gram-negative pleomorphic bacillus that causes tularemia or "rabbit fever" • Found in many animals, especially rabbits • Transmitted by ticks and blood-sucking flies • Organism can be ingested or inhaled • Prevalent in the Southwest desert; Arkansas, Missouri, and Oklahoma

• Fever, chills, myalgias, and arthralgias • Irregular ulcers at the site of inoculation • Lymphadenopathy that suppurates and forms an ulcer • Oculoglandular tularemia (unilateral conjunctivitis, corneal ulceration) • Pneumonic tularemia (dry cough, dyspnea, and pleuritic-type chest pain)

• Typhoidal tularemia (fever, chills, myalgias, malaise, and weight loss)

• Serology, e.g., ELISA or PCR Maternal titer low/negative and history of adequate treatment, normal infant physical exam, and infant titer < 4-fold the maternal titer -Less likely: Benzathine penicillin G single dose, no evaluation. Maternal history of adequate treatment > 4 weeks before delivery, normal infant physical exam, and infant titer < 4-fold the maternal titer -Possible: Aqueous crystalline penicillin G for 10 days; analysis of CSF, CBC, long bone radiographs: Mother not treated adequately or treated < 4 weeks before delivery, normal infant physical exam, and infant titer < 4-fold the maternal titer -Proven/highly probable: Aqueous crystalline penicillin G for 10 days; analysis of CSF, CBC, chest and long bone radiographs; transaminase; neuroimaging; ophthalmologic exam. Mother not treated adequately or treated < 4 weeks before delivery, or abnormal infant physical exam, or infant titer 4-fold higher than maternal titer • Treatment with penicillin for acquired syphilis, with doxycycline or tetracycline if allergic to penicillin

Background • M. tuberculosis, a tubercle bacillus, is the causative agent of tuberculosis (TB)

• Mycobacteria, such as M. tuberculosis, are aerobic, non-spore-forming, non-motile, facultative, curved intracellular rods measuring 0.2-0.5 μm by 2-4 μm • Retains many stains after decolorization with acid-alcohol, which is the basis of the acid-fast stains used for pathologic identification • TB spreads most commonly via airborne transmission • TB is unlikely to spread from child < 4 years of age due to limited tussive force • TB is likely to spread from infected adults to children (usually household or childcare center)

• Foreign-born individuals in the USA have TB rates 9.5 times higher than those of persons born in the USA • HIV infection, treatment with TNF-alpha antagonists such as infliximab and etanercept, and other immunocompromising conditions • Recent latent tuberculosis infection (LTBI) • IV drug use • Certain medical conditions such as diabetes and renal failure • Incubation period from exposure to positive test is 2-10 weeks Clinical presentation • Only 5-10% of children older than 3 years of age who have untreated LTBI progress to disease • Most LTBI progress to disease within 1-2 years of initial infection • The most common site of infection is the lung (up to 80%) • Pulmonary disease -Infants and adolescents are more likely to be symptomatic than 5 to 10-year-old children -Cough (usually last 3 weeks or longer) -Hemoptysis -Low-grade fever -Weight loss (rare) -Night sweats -Loss of appetite -Hilar or mediastinal adenopathy may be seen -Cavity lesions • Superficial lymphadenopathy -The most common extrapulmonary form of TB -Children who have TB lymphadenopathy tend to be older than those who have nontuberculous mycobacterial lymphadenopathy -Common locations: Anterior cervical, followed by posterior triangle, submandibular, and supraclavicular -Lymph nodes usually measure 2-4 cm and lack the classic inflammatory findings of pyogenic nodes -There may be overlying violaceous skin discoloration -Surgical node excision is not curative but may be necessary to establish the diagnosis -Most children respond well to a 6-month course of multidrug therapy, but occasionally therapy must be extended to 9 months, based on clinical response • CNS disease -Tuberculomas, occurring in 5% of children who have CNS TB, appear as single rimenhancing lesions ranging from 1 to 5 cm -In TB meningitis, CSF analysis typically demonstrates lymphocytes, a low-glucose concentration, and a high-protein value -The most common findings on CNS imaging:

• Hydrocephalus and basilar enhancement • Vascular lesions involving the basal ganglia and midbrain also are common -TB should be considered in cases of childhood stroke • Pleural TB -Seen more in older child and adolescent -Can occur in isolation or concomitantly with pulmonary parenchymal disease -Symptoms include chest pain, fever, cough, dyspnea, and anorexia. Auscultatory findings mimic those of bacterial pneumonia -Most children have positive tuberculin skin test (TST) results -Effusions are more common on the right and rarely bilateral -The pleural fluid is exudative and lymphocytic -A 6-month course of therapy is recommended • Miliary tuberculosis -Due to lymphohematogenous spread, it is a disease of the young or immunocompromised children -Miliary disease can present shortly after primary infection -Multiorgan involvement is common -Clinical presentation:

• Pyrexia • Hepatomegaly and splenomegaly -TST is insensitive because disseminated disease can produce TST anergy -AFB culture from gastric aspirates can have a yield as high as 50% -A prolonged course of therapy (9-12 months) should be administered to patients who have disseminated disease • Skeletal TB -The most common manifestations of skeletal disease are:

• Spondylitis • Arthritis • Osteomyelitis -Most patients are in the second decade of life -Spinal involvement (Pott disease), which can affect even young children -Skeletal lesions can develop more than 10 years after initial infection -MRI is the preferred imaging choice because it can demonstrate lesions months before plain radiographs -Chest radiographs are positive in 50% of children who have skeletal TB -TST results are usually positive • Other forms of TB include:

-Abdominal -Renal -Cutaneous disease TB testing • Cultures can be obtained by sequential sputum sampling or by gastric aspiration of early morning secretions in the younger child • The bacillus grows slowly -6 to 8 weeks to grow on Lowenstein-Jensen media -2 to 3 weeks to grow in liquid media • AFB stains include Kinyoun, auramine-rhodamine (Truant), and Ziehl-Neelsen • Tuberculin skin test (TST) ( Table 9 .3) -Measured in millimeters of induration (not erythema) -Reading is 48-72 h after placement -Preferred for children < 2 years -Know: If a child returns for TST interpretation after 72 h and has induration meeting the criteria for positivity, the test is considered positive.

-A negative result never eliminates the possibility of TB disease because many disseminated forms of TB, including TB meningitis, can induce TST anergy • False-negative TST results: -Recent measles infection or vaccination -High-dose corticosteroid treatment, irradiation -Immunosuppressive therapy -Immunocompromising medical conditions -Disseminated tuberculosis • False-positive TST result:

-Primarily in children exposed to nontuberculous (environmental) mycobacteria -Children recently received a bacillus Calmette-Guérin vaccine -A boosting phenomenon: Children received multiple sequential TSTs -First screen for exposure risk by history before testing. Do not test all children routinely • Bacillus Calmette-Guérin (BCG) vaccine -TST can be interpreted normally in a child who received a single dose of BCG vaccine as a young child -Having received BCG as an infant may not explain a positive skin test result later in life -The assumption that BCG receipt is the cause of a positive TST could lead to a lack of treatment for high-risk children who potentially could benefit from LTBI therapy • Whole blood interferon-gamma release assays (IGRAs) have several potential advantages: -Only one office visit is required -There is no risk of the boosting phenomenon -More specificity for LTBI because the antigens in the IGRAs is shared less commonly with nontuberculous mycobacteria and are not found on BCG • Chest radiographs -Children who have LTBI usually have normal-appearing chest radiographs Challenging clinical scenarios • Adult in the household has infectious TB -All children in the household should have chest radiographs and TSTs performed -Children younger than 4 years of age should be started empirically on INH and rifampin until the TST is repeated in 2-3 months -If the second TST result is negative and the child is immunocompetent, medication can be discontinued -If the TST result is positive or the child is immunocompromised, INH and rifampin should be continued • Infant whose mother has TB -The TST is helpful only if the result is positive, which is very rare -If the mother has a positive TST result and negative chest radiograph (LTBI), the child needs no evaluation -If the mother has radiographic features consistent with TB, the neonate requires evaluation for congenital TB -If the infant does not have congenital TB, he or she should be separated from the mother until the infant is receiving INH and pyridoxine (if the mother is breastfeeding) and the mother is receiving appropriate multidrug therapy -Once the infant is receiving INH, separation is unnecessary, and breastfeeding should be encouraged unless INH resistance is suspected • Health-care workers (HCWs)

-If positive TST results, they should receive chest radiographs -If the chest radiograph is negative, the HCW may be offered therapy for LTBI after weighing the risks and benefits of latent TB treatment in adults -If the chest radiograph is positive, the HCW needs to be evaluated further 

• Giardiasis is an infection of the small intestine caused by the flagellated protozoan Giardia intestinalis • Mode of transmission -Travelers and hikers who drink water contaminated with stool from infected animals such as beavers, muskrats, and sheep -Outbreaks also may occur from sewage contamination of water supplies -Unprotected anal sex also is a source of transmission -Childcare centers from fecal-oral transmission -Food-associated outbreaks may occur 

• FUO was defined as: -More than 8 days' duration of illness. Temperature greater than 38.3 °C (101 °F) on several occasions -Failure to reach a diagnosis despite 1 week of investigation • Patients with undiagnosed FUO (5-15% of cases) generally have a benign long-term course, especially when the fever is not accompanied by substantial weight loss or other signs of a serious underlying disease • FUO lasting > 6 months is uncommon in children and suggests granulomatous or autoimmune disease (Table 9 .4)

• Age of the patient is helpful: -Children > 6 years of age often have respiratory or genitourinary tract infection, localized infection (abscess, osteomyelitis), JIA, or (rarely) leukemia -Adolescent patients more likely to have TB, inflammatory bowel disease, autoimmune process, or lymphoma in addition to the causes of FUO in younger children • Exposure to wild or domestic animals, and zoonotic infection • History of pica should be elicited; ingestion of dirt is particularly important due to infection with T. canis or T. gondii • Physical examination is essential to find any physical clues to underlying diagnosis, e.g., lymphadenopathy, rash, joint swelling, etc. • Laboratory determined on case-by-case basis • ESR > 30 mm/h indicates inflammation and needs further evaluation 

• Guillain-Barré syndrome remains the predominant neonatal meningitis pathogen • Early-onset disease: Infants typically manifest with signs suggestive of sepsis, often with pneumonia, but less commonly with meningitis • Late-onset disease: Infants typically are 3-4 weeks of age and present with meningitis or bacteremia Neonatal Gram-negative meningitis • Gram-negative bacillary meningitis is rare, E. coli being the most commonly isolated pathogen • Other Gram-negative neonatal meningitis pathogens such as Citrobacter koseri, Enterobacter sakazakii, and Serratia marcescens

• HSV in the newborn can present as isolated skin or mucous membrane lesions, encephalitis, or disseminated process • HSV infection occurs most commonly in infants born to mothers who have active primary infection • Frequently no maternal history or clinical evidence is available to alert the practitioner to this diagnosis • The incubation period is 2 days to 2 weeks, and most infants who develop HSV CNS infection are 2-3 weeks of age

• Common sources:

-Unpasteurized milk -Soft cheese -Prepared ready-to-eat meats -Undercooked poultry -Unwashed raw vegetables • Can precipitate abortion and preterm delivery • Septic appearance in the neonate is typical in cases of early onset • Papular truncal rash has been identified -The patient lies supine and the thigh is flexed at a right angle to the trunk. If knee extension from this position elicits pain, the Kernig sign is positive • Brudzinski sign:

-The patient lies supine and flexes his or her neck -A positive sign occurs if the patient also reflexively flexes the lower extremities, typically at the knees • Absence of Kernig and Brudzinski signs does not exclude meningitis • Exanthems typical for enterovirus, borreliosis (erythema migrans), and invasive meningococcal or pneumococcal disease (petechiae and purpura) may be present

• All children who are suspected of having meningitis should have their CSF examined unless lumbar puncture is contraindicated • Contraindications of lumbar puncture include: -Focal neurologic deficits -Signs of increased ICP -Uncorrected coagulopathy -Cardiopulmonary compromise • CT scan is performed before lumbar puncture if any sign of ICP present • CSF findings in bacterial meningitis (Table 9 .5) -Glucose concentration is usually less than one half of the measured serum value -Protein value often is greater than 100 mg/dL -WBC often greater than 1000/mcL, with a predominance of polymorphonuclear leukocytes -Gram stain is extremely helpful if positive -CSF culture remains the gold standard for diagnosing bacterial meningitis • CSF finding viral meningitis -WBC count of 50-500/mcL -Neutrophil predominance is common early in the course of infection, shifting to lymphocytic predominance quickly during the illness -Glucose and protein concentrations frequently are normal, although the protein value can be slightly elevated. Gram stain is universally negative -In cases of enteroviral meningitis, enteroviral PCR can confirm the diagnosis • Tuberculous meningitis, epidemiologic clue, high protein, and lymphocytosis • SIADH and hyponatremia commonly occur in bacterial meningitis • Leukopenia, thrombocytopenia, and coagulopathy may be present in meningococcal and rickettsial infections

• Therapy should not be delayed if CNS infection is suspected • Appropriate antimicrobials are required in bacterial meningitis, HSV encephalitis, Lyme meningitis, tuberculous meningitis, and rickettsial infection; in all cases, timely diagnosis and correct antimicrobial choice are critical • If the practitioner cannot perform a lumbar puncture or there are contraindications to CSF examination, a blood culture should be obtained and antibiotics administered promptly

• For infants -Ampicillin (300 mg/kg/day divided every 6 h) and cefotaxime (300 mg/kg/day divided every 6 h) is appropriate. Gentamicin can be used instead of cefotaxime -Acyclovir (60 mg/kg/day divided every 8 h) should be added if HSV infection is a concern -Vancomycin (60 mg/kg/day given every 6 h) should be added, if the Gram stain suggests pneumococcus • Children older than 1-2 months of age -Vancomycin (60 mg/kg/day divided every 6 h) plus ceftriaxone (100 mg/kg/day given in one dose or divided into two doses) or cefotaxime (200-300 mg/kg/day divided every 6 h) should be used for empiric coverage -Once culture and susceptibility data are available, definitive therapy can be selected • HSV meningitis -Neonatal HSV CNS infection typically is treated with IV acyclovir (60 mg/kg/day divided every 8 h) for 21 days -The dosing for non-neonates is 30 mg/kg/ day divided every 8 h IV for 14-21 days -Follow-up CSF HSV DNA PCR should be evaluated at day 21 and the course of therapy extended if the result is still positive 

• Adjunctive treatment has reduced rates of mortality, severe hearing loss, and neurologic sequelae, significantly in adults who have community-acquired bacterial meningitis • For children beyond the neonatal age groups, available data suggest that the use of adjunctive corticosteroids may be beneficial for Hib meningitis and could be considered in cases of pneumococcal meningitis • The dose of dexamethasone for bacterial meningitis is 0.6 mg/kg/day divided into four doses and administered IV for 4 days. The first dose should be given before or concurrently with antibiotics

Care of the child exposed to meningitis • Meningococcal and Hib disease create an increased risk for secondary infection in contacts • Rifampin generally is the drug of choice for chemoprophylaxis in children Prognosis for meningitis • Intellectual deficits (intelligence quotient < 70), hydrocephalus, spasticity, blindness, and severe hearing loss are the most common sequelae • Hearing loss occurs in approximately 30% of patients, can be unilateral or bilateral, and is more common in pneumococcal than meningococcal meningitis

• Chronic otitis media • Paranasal sinus infection • Otogenic infections, poor dental hygiene/ complications from dental procedures • Mastoiditis • Metastatic spread, e.g., endocarditis • Right-to-left cardiac or pulmonary shunts, especially in the presence of cyanotic congenital heart disease • Neurosurgical procedures (VP shunt) 

• Little in the laboratory investigation of patients who have brain abscesses is specific to the diagnosis except for culture of the purulent material and antibiotic sensitivity of the responsible organism

• CT scan of the brain -Ill-defined -Low-density change within the parenchyma -Enhancement occurs following administration of contrast material -Classic ring-enhancing lesion with surrounding edema -Calcification is common in abscesses in neonates • MRI

• For abscesses arising as a result of sinusitis in which Streptococci are the most likely organisms, penicillin or cefotaxime and metronidazole • Chronic otitis media or mastoiditis often is associated with P. aeruginosa and Enterobacteriaceae, antibiotics to treat abscesses secondary to these infections should include penicillin, metronidazole, and a third-generation cephalosporin • Metastatic abscesses require a regimen based on the likely site of primary infection • S. aureus is commonly isolated in abscess following trauma

• Provide a specimen of purulent material for bacteriologic analysis and antibiotic sensitivity testing • Remove purulent material, thereby lowering ICP and decreasing the mass effect of the abscess • Decompress and irrigate the ventricular system and debride the abscess in the event of its rupture into the ventricular system Prognosis • Brain abscess is a destructive lesion • Neurologic sequelae: Epilepsy, motor deficits, visual field cuts, learning disability, hydrocephalus requiring VP shunt placement

• Monospot testing for acute mononucleosis is not indicated for children < 5 years of age because results are not reliable in young children.

• For children with multiple ulcerations of buccal mucosa and conjunctival involvement (mucous membranes) with skin rash, think erythema multiforme major (Stevens-Johnson syndrome). • For children with ulcerations of posterior pharynx and painful papules on palms and soles, think enterovirus (especially Coxsackie virus) causing hand, foot, and mouth disease • For a child with pharyngitis and redness of skin creases of anterior cubital fossae (Pastia lines, also called Thompson sign), think Group A Strep (strep throat). • Egg allergy, including anaphylaxis, is not a contraindication to influenza vaccination. Only persons with a previous severe allergic reaction to flu vaccine should not receive flu vaccine. • For returning travelers with fever, obtain malaria testing immediately and begin appropriate therapy (artemether-lumefantrine or atovaquone-proguanil for P. falciparum) if positive. Do not delay! • Children < 2 years old can be colonized with C. difficile and may test positive for the organism. Only patients with C. difficile toxin production should be considered for treatment with first-line oral metronidazole. • Patients with a classic bull's eye rash at the site of a tick bite do not require diagnostic testing. Treat for early localized Lyme disease with doxycycline (amoxicillin or cefuroxime for children < 8 years old). • A positive blood culture for Candida should be acted upon, including repeat blood culture and IV antifungal therapy with central line removal (if associated). A positive sputum culture for Candida may represent colonization and should be taken in the clinical context. • Rash that begins on wrists and ankles, spreading centrally to palms/soles, is likely Rocky Mountain spotted fever. Treat with doxycycline no matter what age. • Children who return from travel to the Middle East or Central America with ulcerative skin lesions and no systemic symptoms may have cutaneous Leishmaniasis.

• Kingella kingae is an etiologic agent of indolent septic arthritis or osteomyelitis in a young child. Can also cause bacteremia in infants and endocarditis in older children. • Uncommon causes of fever in pediatrics include osteomyelitis, intraabdominal abscess, deep venous thrombosis, Still disease, recurrent fever syndromes (periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA), and familial Mediterranean fever).

• CNS complications of HIV include infection (cryptococcal meningitis, toxoplasmosis, CMV encephalitis, neurocysticercosis), lymphoma, progressive multifocal leukoencephalopathy (PML), peripheral neuropathy, and HIV encephalopathy. • Nontuberculous mycobacteria can cause unilateral submandibular lymphadenitis with a violaceous hue in young children. Primary treatment is surgical excision, not antibiotics. Excision prevents fistula formation. • Most mild community-acquired pneumonia can be treated as outpatient with oral amoxicillin as first-line therapy in patients who can tolerate oral fluids. • The most common etiology for osteomyelitis and septic arthritis is S. aureus. Persons with sickle cell disease are at higher risk for Salmonella. • For post-exposure rabies prophylaxis, administer rabies immune globulin at the bite site and rabies vaccine at a contralateral site on days 0, 3, 7, and 14 (four total doses of vaccine). For immunocompromised persons (HIV), a fifth dose of rabies vaccine is given on day 28. • To avoid botulism in the 1st year of life, avoid giving infants prepared cereals that contain honey, as these may also be a potential source. • For TB testing, can use an interferon gamma release assay (IGRA) for children > 2 years of age. Use skin testing for younger children.

Bartonella henselae (cat-scratch disease)

Red book: 2018-2021 report of the committee on infectious diseases

Cytomegalovirus infection, varicella-zoster virus infections

Red book: 2018-2021 report of the committee on infectious diseases

Red book: 2018-2021 report of the committee on infectious diseases

Human immunodeficiency virus infection

Red book: 2018-2021 report of the committee on infectious diseases

HIV testing and prophylaxis to prevent mother-to-child transmission in the United States

National Resource Center for Health and Safety in Child Care and Early Education. CFOC standards online database. www.nrckids.org/CFOC. Aurora: National Resource Center for Health and Safety in Child Care and Early Education

Perianal cellulitis associated with group A streptococci

Herpes simplex

controlled trial of antibiotics in the management of community-acquired skin abscesses in the pediatric patient

Human herpes simplex virus infections: epidemiology, pathogenesis, symptomatology, diagnosis, and management

Ocular complications of congenital infections

Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis

• Traveling to chloroquine resistant areas, e.g., most tropical areas with malaria -Atovaquone-proguanil 1-2 days before and 7 days after travel, or -Doxycycline (> 8 years old) 1 week before until 4 weeks after travel • Traveling to chloroquine sensitive areas, e.g., Central America -Chloroquine 1-2 weeks before and 4 weeks after, or -Atovaquone-proguanil 1-2 days before and 7 days after travel