Candida infections | - Oral thrush and diaper dermatitis occur in 50–85% of HIV-infected children
- C. albicans is the most common cause
- Candida esophagitis may be seen in children not responding to HAART
- Disseminated candidiasis is infrequent in HIV+ children
| - Oral thrush may present with angular cheilitis-red, fissured lesions in the corners of the mouth
- Odynophagia, dysphagia, or retrosternal pain may be the presentation of esophageal candidiasis
- Oropharyngeal candidiasis may be absent in children on HAART who have esophageal candidiasis
- Barium swallow in esophageal candidiasis reveals classic cobblestoning appearance
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Coccidiodomycosis | - Caused by Coccidioides immitis, which is endemic in southwestern US, northern Mexico, and Central and South America
- In utero and perinatal transmission occur
| - Common symptoms include fever and dyspnea as well as weight loss, lymphadenopathy, headache, and chest pain
- Pulmonary disease may present with bilateral diffuse reticulonodular infiltrates, persistent nodules, or thin-walled cavities
- Features of disseminated disease are rash including but not limited to erythema nodosum, arthralgias, bone, joint, or CNS disease
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Cryptococcosis | - Less frequent infection in HIV-infected children (1%) than in HIV+ adults
- Most frequent in children aged 6–18 years and with CD4%<15%
| - Initially, meningitis is most frequent presentation-indolent course of fever, headache, and altered mental status
- Disseminated cryptococcosis may involve the skin and has a varied presentation including umbilicated papules indistinguishable from molluscum contagiosum
- Pulmonary disease may be clinically subtle—recurrent fever with pulmonary nodules, dry cough, intrathoracic lymphadenopathy, or pulmonary infiltrates (focal or diffuse)
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Cryptosporidiosis | - Highly infectious parasite transmitted by ingested oocytes
- Predilection for the jejunum and terminal ileum
| - Severe profuse, nonbloody, persistent, watery diarrhea with abdominal cramps
- Can be chronic in immunocompromised children and complicated by malnutrition
- Migration into the biliary system may cause acalculous cholecystitis and sclerosing cholangitis
- Pulmonary or disseminated infection occurs rarely
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CMV | - The commonest perinatal infection in the United States (incidence of 0.2–2.2% of live-born infants)—this rate is probably even higher is infants with perinatal HIV exposure
- Rate of congenital infection is 30–40% in mothers with primary CMV infection during pregnancy
- The rate of congenital CMV is lower (0.15–1.0%) after recurrent maternal CMV during pregnancy caused by reactivation or by infection with a different strain of CMV
- 50–80% of US women of childbearing age are seropositive for CMV
- 90% of HIV-infected pregnant women are co-infected with CMV
- HIV-infected children are at higher risk of acquiring CMV infection, particularly in first 4 years of life
- Overall, a third of HIV-infected children shed CMV (up to 60% in those with AIDS)
- CMV causes 8–10% of pediatric AIDS-defining illness with CMV retinitis accounting for 25% of these
| - Only 10% of infants with in utero infection are symptomatic at birth
- Features of newborns with symptomatic CMV disease include small for gestational age, microcephaly, intracranial calcifications, impaired hearing, purpura/petechiae, jaundice, chorioretinitis, and hepatosplenomegaly
- Long-term sequelae of congenital infection are seen in 90% of those with symptomatic infection at birth-hearing loss, mental retardation, chorioretinitis, optic atrophy, seizures, or learning disabilities
- Of the 90% of infants with in utero infection who are asymptomatic at birth, 10–15% develop long-term sequelae such as hearing loss
- In HIV-infected children, CMV co-infection doubles the rate of progression of HIV disease
- CMV retinitis: frequently asymptomatic in young HIV-infected children; may be discovered on screening eye examination; older children present with floaters, loss of peripheral, or reduced central vision
- Extraocular disease may involve lungs (interstitial pneumonia with nonproductive cough), GI tract, sinuses, or CNS (20% have normal CSF)
- GI manifestations include colitis (most commonly), oral or esophageal ulcers, hepatitis, ascending cholangitis, or gastritis
- CNS manifestations include myelitis, subacute encephalopathy, and polyradiculopathy
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Herpes simplex virus | - Risk for neonatal HSV is greatest (30–50%) with primary maternal HSV infection
- Maternal reactivation of HSV is associated with a lower risk (0%–5%) of neonatal infection
- 75% of neonatal infection in the United States are caused by HSV type 2
- HIV-infected women more commonly shed HSV from the vulva and cervix than HIV uninfected women
- The risk for maternal genital HSV reactivation and shedding increases with decreasing CD4 count
- In 6% of pediatric AIDS cases, recurrent or persistent HSV infection is the AIDS-indicator condition
| - Neonatal HSV may present as disseminated multiorgan disease (25%), localized CNS disease (35%) or diseases localized to the skin, eyes, and mouth (40%)
- Orolabial HSV is the most common presentation outside of the neonatal period and may be severe in HIV-infected children
- Rarely, primary orolabial HSV disseminates with visceral and generalized skin involvement
- Other sites of HSV in severely immunocompromised children include esophagus, CNS, genitalia or dissemination to the liver, adrenals, kidney, spleen, lung, and brain
- HSV proctitis may be seen in sexually active children or adolescents
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Histoplasmosis | - Incidence is 0.4% in United States HIV-infected children but is higher in HIV-infected children in Latin America (2.7–3.8%)
- No evidence for congenital disease
| - Disseminated disease most frequently presents with prolonged fever
- Other symptoms include malaise, nonproductive cough and weight loss
- Interstitial pneumonitis is rare in children but a primary pulmonary focus may lead to dissemination in HIV+ children
- Signs of dissemination include hepatosplenomegaly (89% of infants), skin lesions, anemia, thrombocytopenia, elevated transaminases
- Disseminated histoplasmosis is fatal if not treated
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Human papillomavirus | - Transmission occurs by close person-to-person contact e.g., sexual intercourse or passage through an infected birth canal
- HPV DNA detection rates may be as high as 95% in nonpregnant HIV+ women
- Predominant risk factors for HPV in adolescents are number of lifetime and recent sexual partners
- Persistent HPV infection, particularly with types 16, 18, 31, or 33 is associated with a high risk of developing carcinoma
| - Wart lesions occur most frequently on the cutaneous and mucosal squamous epithelium of hands, feet, face, and genitalia
- Other sites include skin and mucus membranes of the anus, nose, conjunctiva, gastrointestinal, and respiratory systems
- Warts may be smooth and flat or pedunculated
- HPV immunization should still be given to those with HPV lesions—this is because the vaccine may protect them from acquiring HPV infection with a second or third serotype
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MAC | - Acquired through inhalation, inoculation or ingestion
- Respiratory and GI colonization may act as portal for dissemination
- Frequency of pediatric disseminated MAC increases with age and falling CD4%, particularly with CD4%<50%
| - Disseminated MAC: recurrent fever, weight loss, night sweats, fatigue, abdominal pain, anemia, leucopenia, thrombocytopenia, occasionally elevated alkaline phosphatase
- Less commonly: pulmonary MAC or cutaneous disease, including lymphadenitis
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Mycobacterium tuberculosis | - Incidence of TB may be as much as 100-fold higher in HIV-infected vs uninfected children in the United States
- Infection usually represents primary TB rather than reactivation disease
- Identify and treat the source patient-usually an adult in the child's home
| - Congenital TB has nonspecific signs: poor feeding, failure to thrive, enlarged liver/spleen, fever, occasionally progressive pneumonia, meningitis
- Pediatric pulmonary TB often presents in a nonspecific way: weight loss, fever, pulmonary infiltrate with hilar adenopathy
- Common extrapulmonary sites include lymph nodes, military (via hematogenous), CNS, bone, pericardium, pleura, and peritoneum
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Pneumocystis jiroveci pneumonia | - Highest incidence in first year of life, peak age is 3–6 months
- CD4 counts are not a good indicator of risk for PCP in infants <1 year old
| - Tachypnea, dyspnea, and cough
- Fever in some
- Bibasilar rales and hypoxia
- Extrapulmonary disease is rare
- Coinfection with CMV is a poor prognostic feature
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Serious and recurrent bacterial infections | - S. pneumoniae is the most prominent invasive pathogen in HIV-infected children
- Pseudomonas and Salmonella species are the most common causes of gram-negative bacteremia
- S. aureus is the most commonly isolated pathogen in catheter-related infections
| - Acute presentation with fever is most common
- Leukocytosis may be absent in severely immunocompromised children
- Recurrence of a previous infection is more likely
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Syphilis | - Can be transmitted from mother to child at any stage of pregnancy
- Rate of congenital syphilis may be 50 times greater among infants of HIV+ women in the United States
- Of HIV+ adolescents, 9% girls and 6% boys have syphilis
| - Sixty percent of infants with congenital syphilis are asymptomatic
- Early features of congenital syphilis hepatosplenomegaly, peeling rash on palms and soles, jaundice, bloody nasal discharge, pseudoparalysis, bone marrow suppression
- Late features of congenital syphilis: abnormalities of CNS, bone, teeth, eyes, and skin
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Toxoplasmosis | - Major mode of transmission is congenital
- Infection of the fetus in early gestation results in more severe disease
- Older children acquire disease through eating poorly cooked meat containing parasitic cysts or by ingesting sporulated oocysts in soil, food or water
| - Majority of newborns are asymptomatic
- When symptoms occur, they are localized to the neurologic system (calcifications, hydrocephalus, retinitis, seizures, microcephaly) or a generalized disease (rash, hepatosplenomegaly, bone marrow suppression, jaundice, lymphadenopathy)
- Reactivated chronic toxoplasmosis may present as pneumonitis, hepatitis, and cardiomyopathy/myocarditis.
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Varicella zoster virus | - Mortality and morbidity is higher in HIV+ immunocompromised children than HIV- children
- Congenital VZV: it is unknown whether this occurs more frequently in the newborns of HIV+ women
- Zoster is unusual among HIV+ children who had primary VZV when their CD4% was normal
- Zoster is common (rate of up to 70%) among HIV+ children who had primary VZV when their CD4% was <15%
- This high rate of zoster is decreased when these children are exposed to HAART and VZV immunization
| - Congenital infection is characterized by skin scarring, limb hypoplasia, microcephaly, cortical atrophy, seizures, mental retardation, ocular damage (chorioretinitis, microopthalmia, cataracts), renal anomalies, swallowing dysfunction, and aspiration pneumonia
- Primary VZV classically presents with fever and a generalized pruritic vesicular rash
- Persistent lesions may be atypical and lack a vesicular component
- Chronic VZV (appearance of new lesions for >1 month after primary or recurrent VZV infection) is associated with low CD4%
- Viral isolates may become acyclovir resistant during prolonged therapy
- Typically, zoster presents with a frequently painful vesicular eruption in a dermatomal distribution but atypical forms occur in this population
- VZV retinitis: a rare complication in HIV+ children, which may be confused with CMV retinitis
- Rarely may present as a progressive encephalitis
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