Pediatrics_Nelson

Pediatrics_Nelson. Zoonoses are infections that are transmitted in nature between vertebrate animals and humans. Many zoonotic pathogens are maintained in nature by means of an enzootic cycle, in which mammalian hosts and arthropod vectors reinfect each other. Humans frequently are only incidentally infected. Of the more than 150 different human zoonotic diseases that have been described (Table 122-1), Lyme disease (Borrelia burgdorferi)accounts for 90% of reported vector-borne infections in the United States. Other common pathogens include Rickettsia rickettsii (Rocky Mountain spotted fever), ehrlichiosis (Ehrlichia chaffeensis), West Nile virus, and anaplasmosis (Anaplasma phagocytophilum). The epidemiology of zoonoses is related to the geographic distribution of the hosts and, if vector-borne, the distribution and seasonal life cycle of the vector.


Pediatrics_Nelson

Pediatrics_Nelson. Many zoonoses are spread by ticks including Lyme disease, Rocky Mountain spotted fever, ehrlichiosis, tularemia, tick typhus,and babesiosis. Mosquitoes transmit the arboviral encephalitides (see Chapter 101), dengue fever, malaria, and yellow fever. Preventive measures to avoid tick-borne and mosquito-borne diseases include using insect repellants that contain DEET (N,N-diethyl-m-toluamide) on skin and insect repellants that contain permethrin on clothing; avoiding tick-infested habitats(thick scrub oak, briar, poison ivy sites); avoiding excretory products of wild animals; wearing appropriate protective clothing(closed-toe shoes, long pants, etc.); and promptly removing ticks.


Pediatrics_Nelson

Pediatrics_Nelson. Ticks are best removed using blunt forceps or tweezers to grasp the tick as close to the skin as possible to pull the tick steadily outward. Squeezing, twisting, or crushing the tick should be avoided because the tick’s bloated abdomen can act like a syringe if squeezed. Transmission of infection seems to bemost efficient after 30 to 36 hours of nymphal tick attachment forhuman granulocytic ehrlichiosis, after 36 to 48 hours for B. burgdorferi, and after 56 to 60 hours for Babesia. Prophylactic antimicrobial therapy after a tick bite or exposure is not recommended.


Pediatrics_Nelson

Pediatrics_Nelson. Lyme disease is a tick-borne infection caused by the spirochete, B. burgdorferi. The vector in the eastern and midwestern United States is Ixodes scapularis, the black-legged tick that is commonly known as the deer tick. The vector on the Pacific Coast is Ixodes pacificus, the western black-legged tick. Ticks usually become infected by feeding on the white-footed mouse (Peromyscus leucopus), which is a natural reservoir for B. burgdorferi. The larvae are dormant over winter and emerge the following spring in the nymphal stage, the stage of the tick that is most likely to transmit the infection to humans. Over 20,000 cases are reported annually in the United States, with 96% of cases reported from New England, the eastern parts of the Middle Atlantic states, and the upper Midwest


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Pediatrics_Nelson. Figure 122-1 The geographic distribution of 24,364 confirmed cases of Lyme disease in the United States in 2011. The risk for acquiring Lyme disease varies by the distribution of Ixodes scapularis and Ixodes pacificas, the proportion of infected ticks for each species at each stage of the tick’s life cycle, and the presence of grassy or wooded locations favored by white-tailed deer. (From Centers for Disease Control and Prevention: Lyme Disease—United States, 2011, available from the CDC website: http://www.cdc.gov/lyme/stats/ maps/map2011.html (Fig. 122-1). In Europe most cases occur in Scandinavian countries and central Europe. Because exposure to ticks is more common in warm months, Lyme disease is noted predominantly in summer. The incidence is highest among children 5 to 10 years old, at almost twice the incidence among adolescents and adults. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com The clinical manifestations are divided into early and late stages. Early infection may be localized or disseminated. Early localized disease develops 7 to 14 days after a tick bite as the site forms an erythematous papule that expands to form a red, raised border, often with central clearing. The lesion, erythema migrans, harbors B. burgdorferi and may be 15 cm wide, pruritic, or painful. Systemic manifestations may include malaise, lethargy, fever, headache, arthralgias, stiff neck, myalgias, and lymphadenopathy. The skin lesions and early manifestations resolve without treatment over 2 to 4 weeks. Not all patients with Lyme disease recall a tick bite or develop erythema migrans.


Pediatrics_Nelson

Pediatrics_Nelson. Approximately 20% of patients develop early disseminated disease with multiple secondary skin lesions, aseptic meningitis, pseudotumor, papilledema, cranioneuropathies including Bell palsy, polyradiculitis, peripheral neuropathy, mononeuritis multiplex, or transverse myelitis. Carditis with various degrees of heart block rarely may develop during this stage. Neurologic manifestations usually resolve by 3 months but may recur or become chronic.


Pediatrics_Nelson

Pediatrics_Nelson. Late disease begins weeks to months after infection. Arthritis is the usual manifestation and may develop in 50% to 60% of untreated patients. The male to female ratio is 7:1. The knee is involved in greater than 90% of cases, but any joint may be affected. Symptoms may resolve over 1 to 2 weeks but often recur in other joints. If untreated most cases resolve, but chronic erosive arthritis persists in 10% of patients as the episodes increase in duration and severity. Cardiac abnormalities occur in approximately 10% of untreated patients. Neuroborreliosis, the late manifestations of Lyme disease involving the central nervous system (CNS), is rarely reported in children.


Pediatrics_Nelson

Pediatrics_Nelson. Antibody tests during early, localized Lyme disease may be negative and are not useful. The diagnosis of late disease is confirmed by serologic tests specific for B. burgdorferi. Thesensitivity and specificity of serologic tests for Lyme disease vary substantially. A positive enzyme-linked immunosorbent assay or immunofluorescence assay result must be confirmed by immunoblot showing antibodies against at least either two to three (for IgM) or five (for IgG) proteins of B. burgdorferi(at least one of which is one of the more specific, low-molecular-weight, outer-surface proteins).


Pediatrics_Nelson

Pediatrics_Nelson. In late disease, the erythrocyte sedimentation rate is elevated and complement may be reduced. The joint fluid shows an inflammatory response with total white blood cell count of 25,000 to 125,000 cells/mm3, often with a polymorphonuclear predominance (see Table 118-2). The rheumatoid factor and antinuclear antibody are negative, but the Venereal Disease Research Laboratory test may be falsely positive. With CNS involvement, the cerebrospinal fluid shows a lymphocytic pleocytosis with normal glucose and slightly elevated protein.


Pediatrics_Nelson

Pediatrics_Nelson. A history of a tick bite and the classic rash is helpful but is not always present. Erythema migrans of early, localized disease may be confused with nummular eczema, tinea corporis, granuloma annulare, an insect bite, or cellulitis. Southern tick-associated rash illness, which is similar to erythema migrans, occurs in southeastern and south central states and is associated with the bite of Amblyomma americanum, the lone star tick, and infection with Borrelia lonestari.


Pediatrics_Nelson

Pediatrics_Nelson. During early, disseminated Lyme disease, multiple lesions may appear as erythema multiforme or urticaria. The aseptic meningitis is similar to viral meningitis, and the seventh nerve palsy is indistinguishable from herpetic or idiopathic Bell palsy. Lyme carditis is similar to viral myocarditis. Monarticular or pauciarticular arthritis of late Lyme disease may mimic suppurative arthritis, juvenile idiopathic arthritis, or rheumatic fever (see Chapter 89). The differential diagnosis of neuroborreliosis includes degenerative neurologic illness, encephalitis, and depression. Early localized disease and early disseminated disease, including facial nerve palsy (or other cranial nerve palsy) and carditis with first-degree or second-degree heart block, is treated with doxycycline or amoxicillin for 14 to 21 days. Early disease with carditis with third-degree heart block or meningitis and Cat-scratch disease Bartonella henselae Cats, dogs Bites and scratches United States


Pediatrics_Nelson

Pediatrics_Nelson. Cat-scratch disease Bartonella henselae Cats, dogs Bites and scratches United States Erysipeloid Erysipelothrix rhusiopathiae Sheep, swine, turkeys, Direct contact Worldwide ducks, fish Wound infection Mycobacterium marinum, Fish, aquarium Direct contact, scratches Worldwide Mycobacterium fortuitum, Mycobacterium kansasii Leptospirosis Leptospira interrogans Dogs, rodents, livestock Direct contact, contact Worldwide with water or soil contaminated by urine of infected animals Relapsing fever Borrelia Rodents, fleas Louse bite, flea bite, Western and southern transplacental transmission United States Southern tick-associated Borrelia lonestari Deer, rodents Tick bite (I. scapularis) Southeastern and rash illness south-central U.S. African tick-bite fever Rickettsia africae Cattle, goats (?) Tick bite Sub-Saharan Africa, Caribbean Rickettsialpox Rickettsia akari Mice Mite bite North America, Russia, Ukraine, Adriatic region, Korea, South Africa


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Pediatrics_Nelson. Rickettsialpox Rickettsia akari Mice Mite bite North America, Russia, Ukraine, Adriatic region, Korea, South Africa Murine typhus–like illness Rickettsia felis Opossums, cats, dogs Flea bite Western hemisphere, Europe Epidemic typhus Rickettsia prowazekii Humans Louse feces Africa, South America, Central America, Mexico, Asia Flying squirrel (sylvatic) R. prowazekii Flying squirrels Lice or fleas of flying United States typhus Scrub typhus Orientia tsutsugamushi Rodents (?) Chigger bite Southern Asia, Japan, Indonesia, Australia, Korea, Asiatic Russia, India, China Human Ehrlichia chaffeensis Deer, dogs Tick bite (Amblyomma United States, Europe, monocytic ehrlichiosis Anaplasmosis (human Anaplasma Rodents, deer, Tick bite (I. scapularis) United States, Europe granulocytic ehrlichiosis) phagocytophilum ruminants Sennetsu ehrlichiosis Neorickettsia sennetsu Unknown Ingestion of helminth-Japan, Malaysia contaminated fish (?)


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Pediatrics_Nelson. Sennetsu ehrlichiosis Neorickettsia sennetsu Unknown Ingestion of helminth-Japan, Malaysia contaminated fish (?) Table 122-1 Major Zoonotic and Vector-Borne Infections*—cont’d DISEASE CAUSATIVE AGENT COMMON ANIMAL RESERVOIRS VECTORS/MODES OF TRANSMISSION GEOGRAPHIC DISTRIBUTION Hantavirus cardiopulmonary syndrome Hantavirus Rodents, mice, cats Aerosol inhalation Southwestern United States Lymphocytic Lymphocytic Rodents, hamsters, mice Aerosol inhalation, direct Worldwide choriomeningitis choriomeningitis virus contact, bite Rabies Rabies virus Dogs, skunks, bats, Bites and scratches Worldwide raccoons, foxes, cats Vesicular stomatitis Vesicular stomatitis virus Horses, cattle, swine Direct contact Americas Babesiosis Babesia Cattle, wild and Tick bite (I. scapularis), Worldwide domestic rodents blood transfusion Leishmaniasis, Leishmania Domestic and wild dogs Sandfly bite Tropics mucocutaneous and cutaneous


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Pediatrics_Nelson. Leishmaniasis, Leishmania Domestic and wild dogs Sandfly bite Tropics mucocutaneous and cutaneous Leishmaniasis, visceral Leishmania donovani Domestic and wild dogs Sandfly bite Tropics complex Malaria Plasmodium Humans Mosquito bite (Anopheles) Usually imported to the United States, Southern California Toxoplasmosis Toxoplasma gondii Cats, livestock, pigs Ingestion of oocysts in Worldwide fecally contaminated material or ingestion of tissue cysts in undercooked meat Adapted from Christenson JC: Epidemiology of infectious diseases. In Jenson HB, Baltimore RS, editors: Pediatric Infectious Diseases: Principles and Practice, ed 2, Philadelphia, 2002, Saunders, pp 18−20. *Many helminths are also zoonotic (see Tables 123-4 and 123-5).


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Pediatrics_Nelson. Philadelphia, 2002, Saunders, pp 18−20. *Many helminths are also zoonotic (see Tables 123-4 and 123-5). late neurologic disease (other than facial nerve or other cranial nerve palsy) are treated with intravenous or intramuscular ceftriaxone or intravenous penicillin G for 14 to 28 days. Arthritis is treated with doxycycline (for children >9 years of age) or amoxicillin for 28 days. If there is recurrence, treatment should be with a repeated oral regimen or with the regimen for late neurologic disease. Carditis, especially conduction disturbances, and arthritis are the major complications of Lyme disease. Even untreated, most cases eventually resolve without sequelae. Lyme disease is readily treatable and curable. The long-term prognosis is excellent for early and late disease. Early treatment may prevent progression to carditis and meningitis. Recurrences of arthritis are rare after recommended treatment.


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Pediatrics_Nelson. A community-based study of children with Lyme disease found no evidence of impairment 4 to 11 years later. Measures to minimize exposure to tick-borne diseases are the most reasonable means of preventing Lyme disease. Postexposure prophylaxis is not routinely recommended because the overall risk of acquiring Lyme disease after a tick bite is only 1% to 2% even in endemic areas, and treatment of the infection, if it develops, is highly effective. Nymphal stage ticks must feed for 36 to 48 hours, and adult ticks must feed for 48 to 72 hours before the risk of transmission of B. burgdorferi from infected ticks becomes substantial. In hyperendemic regions, prophylaxis of adults with doxycycline, 200 mg as a single dose, within 72 hours of a nymphal tick bite is effective in preventing Lyme disease.


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Pediatrics_Nelson. The cause of Rocky Mountain spotted fever is R. rickettsii, gram-negative coccobacillary organisms that resemble bacteria but have incomplete cell walls and require an intracellular site for replication. The organism invades and proliferates within the endothelial cells of blood vessels, causing vasculitis and resulting in increased vascular permeability, edema, and, eventually, decreased vascular volume, altered tissue perfusion, and widespread organ failure. Many tick species are capable of transmitting R. rickettsii. The principal ticks are the American dog tick (Dermacentor variabilis) in the eastern United States and Canada, the wood tick (Dermacentor andersoni) in the western United States and Canada, the brown dog tick (Rhipicephalus sanguineus) in Mexico, and Amblyomma cajennense in Central and South America.


Pediatrics_Nelson

Pediatrics_Nelson. Rocky Mountain spotted fever is the most common rickettsial illness in the United States, occurring primarily in the eastern coastal, southeastern, and western states. Most cases occur from May to October after outdoor activity in wooded areas, with peak incidence among children 1 to 14 years of age. Approximately 40% of infected persons are unable to recall a tick bite. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com The incubation period of Rocky Mountain spotted fever is 2 to 14 days, with an average of 7 days. The onset is nonspecific with headache, malaise, and fever. A pale, rose-red macular or maculopapular rash appears in 90% of cases. The rash begins peripherally and spreads to involve the entire body, including palms and soles. The early rash blanches on pressure and is accentuated by warmth. It progresses over hours or days to a petechial and purpuric eruption that appears first on the feet and ankles, then the wrists and hands, and progresses centripetally to the trunk and head. Myalgias, especially of the lower extremities, and intractable headaches are common. Severe cases progress with splenomegaly, myocarditis, renal impairment, pneumonitis, and shock.


Pediatrics_Nelson

Pediatrics_Nelson. Thrombocytopenia (usually <100,000 cells/mm3), anemia, hyponatremia, and elevated hepatic transaminase levels are common laboratory findings. Organisms can be detected in skin biopsy specimens by fluorescent antibodies or polymerase chain reaction, although this test is not widely available. Serologic testing is used to confirm the diagnosis, although treatment is begun before confirmation.


Pediatrics_Nelson

Pediatrics_Nelson. The differential diagnosis includes meningococcemia, bacterial sepsis, toxic shock syndrome, leptospirosis, ehrlichiosis, measles, enteroviruses, infectious mononucleosis, collagen vascular diseases, Henoch-Schönlein purpura, and idiopathic thrombocytopenic purpura. The diagnosis of Rocky Mountain spotted fever should be suspected with fever and petechial rash, especially with a history of a tick bite or outdoor activities during spring and summer in endemic regions. Fever, headache, and myalgias lasting more than 1 week in patients in endemic areas indicate Rocky Mountain spotted fever. Delayed diagnosis and late treatment usually result from atypical initial symptoms and late appearance of the rash.


Pediatrics_Nelson

Pediatrics_Nelson. Therapy for suspected Rocky Mountain spotted fever should not be postponed pending results of diagnostic tests. Doxycycline is the drug of choice, even for young children, despite the theoretical risk of dental staining in children younger than 9 years of age. Fluoroquinolones also are active against R. rickettsii and may be an alternative treatment. In severe infections, capillary leakage results in noncardiogenic pulmonary edema (acute respiratory distress syndrome), hypotension, disseminated intravascular coagulation, circulatory collapse, and multiple organ failure, including encephalitis, myocarditis, hepatitis, and renal failure. Untreated illness may persist for 3 weeks before progressing to multisystem involvement. The mortality rate is 25% without treatment, which is reduced to 3.4% with treatment. Permanent sequelae are common after severe disease. Preventive measures to avoid tick-borne infections and careful removal of ticks are recommended.


Pediatrics_Nelson

Pediatrics_Nelson. Preventive measures to avoid tick-borne infections and careful removal of ticks are recommended. The term ehrlichiosis often is used to refer to all forms of infection with Ehrlichia. Human monocytic ehrlichiosis is caused by E. chaffeensis, which infects predominantly monocytic cells andis transmitted by the tick A. americanum. Disease may also be caused by Ehrlichia ewingii. Human anaplasmosis is caused by A. phagocytophilum and is transmitted by the tick I. scapularis. Ehrlichiosis occurs commonly in the United States. Human monocytic ehrlichiosis occurs in broad areas across the southeastern, south central, and Mid-Atlantic United States in a distribution that parallels that of Rocky Mountain spotted fever. Anaplasmosis is found mostly in the northeastern and upper midwestern United States, but infections have now been identified in northern California, the Mid-Atlantic states, and broadly across Europe.


Pediatrics_Nelson

Pediatrics_Nelson. Human monocytic ehrlichiosis, anaplasmosis, and Ehrlichiosis ewingii cause similar acute febrile illness characterized by fever, malaise, headache, myalgias, anorexia, and nausea, but often without a rash. In contrast to adult patients, nearly two thirds of children with human monocytic ehrlichiosis present with a macular or maculopapular rash, although petechial lesions may occur. Symptoms usually last for 4 to 12 days. Characteristic laboratory findings include leukopenia, lymphocytopenia, thrombocytopenia, anemia, and elevated hepatic transaminases. Morulae are found infrequently in circulating monocytes of persons with human monocytic ehrlichiosis but are found in 40% of circulating neutrophils in 20% to 60% of persons with anaplasmosis (Fig. 122-2). Seroconversion or fourfold rise in antibody titer confirms the diagnosis.


Pediatrics_Nelson

Pediatrics_Nelson. Ehrlichiosis is clinically similar to other arthropod-borne infections, including Rocky Mountain spotted fever, tularemia, babesiosis, early Lyme disease, murine typhus, relapsing fever, and Colorado tick fever. The differential diagnosis also includes infectious mononucleosis, Kawasaki disease, endocarditis, viral infections, hepatitis, leptospirosis, Q fever, collagen vascular diseases, and leukemia. As with Rocky Mountain spotted fever, therapy for suspected ehrlichiosis should not be postponed pending results of diagnostic tests. Ehrlichiosis and anaplasmosis are treated with doxycycline.


Pediatrics_Nelson

Pediatrics_Nelson. As with Rocky Mountain spotted fever, therapy for suspected ehrlichiosis should not be postponed pending results of diagnostic tests. Ehrlichiosis and anaplasmosis are treated with doxycycline. Figure 122-2 A morula (arrowhead) containing Anaplasma phagocytophilum in a neutrophil. Ehrlichia chaffeensis and A. phagocytophilum have similar morphologies but are serologically and genetically distinct. (Wright stain, original magnification X 1200.) (From Walker DH, Dumler JS: Ehrlichia chaffeensis (human monocytotropic ehrlichiosis), Anaplasma phagocytophilum (human granulocytotropic anaplasmosis), and other ehrlichieae. In Mandell GL, Bennett JE, Dolin R, editors: Principles and Practice of Infectious Diseases, ed 6, Philadelphia, 2005, Churchill Livingstone, Fig. 190-2, p 2315.)


Pediatrics_Nelson

Pediatrics_Nelson. Severe pulmonary involvement with acute respiratory distress syndrome has been reported in several cases. Other reported severe complications include meningoencephalitis and myocarditis. Most patients improve within 48 hours. Preventive measures to avoid tick-borne infections and careful removal of ticks are recommended. Protozoa are the simplest organisms of the animal kingdom. They are unicellular. Most are free living, but some have a commensal or parasitic existence. Protozoal diseases include malaria, toxoplasmosis, babesiosis, and the intestinal protozoal diseases, amebiasis, cryptosporidiosis, and giardiasis.


Pediatrics_Nelson

Pediatrics_Nelson. Malaria is caused by obligate intracellular protozoa of the genus Plasmodium, including P. falciparum, P. malariae, P. ovale, P. vivax, and P. knowlesi. Plasmodium has a complex life cycle that enables survival in different cellular environments in the human host and in the mosquito vector. There are two major phases in the life cycle, an asexual phase (schizogony) in humans and a sexual phase (sporogony) in mosquitoes. The erythrocytic phase of Plasmodium asexual development begins when the merozoites released from exoerythrocytic schizonts in the liver penetrate erythrocytes. When inside the erythrocyte, the parasite transforms into the ring form, which enlarges to become a trophozoite. These latter two forms can be identified with Giemsa stain on blood smear, which is the primary means of confirming the diagnosis of malaria.


Pediatrics_Nelson

Pediatrics_Nelson. The parasites usually are transmitted to humans by female Anopheles mosquitoes. Malaria also can be transmitted through blood transfusion via contaminated needles and transplacentally to a fetus. Malaria is a worldwide problem with transmission in more than 100 countries with a combined population of more than 1.6 billion people. Malaria is an important cause of fever and morbidity in the tropical world. The principal areas of transmission are sub-Saharan Africa, southern Asia, Southeast Asia, Mexico, Haiti, the Dominican Republic, Central and South America, Papua New Guinea, and the Solomon Islands. Approximately 1000 to 2000 imported cases are recognized annually in the United States, with most cases occurring among infected foreign civilians from endemic areas who travel to the United States and among U.S. citizens who travel to endemic areas without appropriate chemoprophylaxis. Available @ StudentConsult.com Fever of Unknown Origin


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Pediatrics_Nelson. Available @ StudentConsult.com Fever of Unknown Origin The clinical manifestations of malaria range from asymptomatic infection to fulminant illness and death, depending on the virulence of the infecting malaria species and the host immune response. The incubation period ranges from 6 to 30 days, depending on the Plasmodium species (Table 123-1).The most characteristic clinical feature of malaria, which is seldom noted with other infectious diseases, is febrile paroxysms alternating with periods of fatigue but otherwise relative wellness. The classic symptoms of the febrile paroxysms of malaria include high fever, rigors, sweats, and headache. Paroxysms coincide with the rupture of schizonts that occur every 48 hours with P. vivax and P. ovale (tertian periodicity) and every 72 hours with P. malariae (quartan periodicity).


Pediatrics_Nelson

Pediatrics_Nelson. Short-term relapse describes the recurrence of symptoms after a primary attack that is due to the survival of erythrocyte forms in the bloodstream. Long-term relapse describes the renewal of symptoms long after the primary attack, usually due to the release of merozoites from an exoerythrocytic source in the liver. Long-term relapse occurs with P. vivax and P. ovale because of persistence in the liver and with P. malariae because of persistence in the erythrocyte.


Pediatrics_Nelson

Pediatrics_Nelson. The diagnosis of malaria is established by the identification oforganisms on stained smears of peripheral blood. In nonimmune persons, symptoms typically occur 1 to 2 days beforeparasites are detectable on blood smear. Although P. falciparumis most likely to be identified from blood during a febrile paroxysm, the timing of the smears is less important than obtainingsmears several times each day over 3 successive days. Both thickand thin blood smears should be examined. The concentration of erythrocytes on a thick smear is approximately 20 to 40 times greater than that on a thin smear. Thick smears are used to scan large numbers of erythrocytes quickly. Thin smears allow for positive identification of the malaria species and determinationof the percentage of infected erythrocytes, which also is usefulin following the response to therapy. Rapid diagnostic tests mayemerge as point of care tests in the near future.


Pediatrics_Nelson

Pediatrics_Nelson. The most important aspect of diagnosing malaria in children isto consider the possibility of malaria in any child who has fever,chills, splenomegaly, anemia, or decreased level of consciousness with a history of recent travel or residence in an endemicarea, regardless of the use of chemoprophylaxis. The differential diagnosis is broad and includes many infectious diseases,such as typhoid fever, tuberculosis, brucellosis, relapsing fever,infective endocarditis, influenza, poliomyelitis, yellow fever,trypanosomiasis, kala-azar, and amebic liver abscess. Table 123-1 Characteristics of Plasmodium Species Causing Malaria CHARACTERISTIC P. FALCIPARUM P. VIVAX P. OVALE P. MALARIAE P. KNOWLESI Exoerythrocytic cycle 5.5–7 days 6–8 days 9 days 12–16 days 8-9 days Erythrocytic cycle 48 hours 42–48 hours 49–50 hours 72 hours 24 hours Erythrocyte Young erythrocytes, Reticulocytes Reticulocytes Older erythrocytes Older erythrocytes preference but can infect all


Pediatrics_Nelson

Pediatrics_Nelson. Erythrocyte Young erythrocytes, Reticulocytes Reticulocytes Older erythrocytes Older erythrocytes preference but can infect all Duration of untreated 1–2 years 1.5–4 years (includes 1.5–4 years (includes 3–50 years Unknown infection Usual periodicity of None 48 hours 48 hours 72 hours 24 hours febrile attacks Duration of febrile 16–36 hours (may be 8–12 hours 8–12 hours 8–10 hours Unknown paroxysm longer) Adapted from Strickland GT: Malaria. In Strickland GT, editor: Hunter’s Tropical Medicine, ed 7, Philadelphia, 1991, WB Saunders, p 589.


Pediatrics_Nelson

Pediatrics_Nelson. Adapted from Strickland GT: Malaria. In Strickland GT, editor: Hunter’s Tropical Medicine, ed 7, Philadelphia, 1991, WB Saunders, p 589. Oral chloroquine is the recommended treatment except for chloroquine-resistant P. falciparum. Either atovaquone-proguanil (Malarone) or artemether-lumefantrine (Coartem) is an appropriate first-line therapy for malaria acquired in areas of chloroquine resistance. Specific treatment should be guided by where the patient acquired the infection and the local resistance patterns. Patients with malaria usually require hospitalization and may require intensive care unit admission. Quinidine gluconate is the only drug available in the United States that is used for parenteral treatment.


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Pediatrics_Nelson. Cerebral malaria is a complication of P. falciparum infection and a frequent cause of death (20% to 40% of cases), especially among children and nonimmune adults. Similar to other complications, cerebral malaria is more likely to occur among patients with intense parasitemia (>5%). Other complications include splenic rupture, renal failure, severe hemolysis (blackwater fever), pulmonary edema, hypoglycemia, thrombocytopenia, and algid malaria (sepsis syndrome with vascular collapse). Death may occur with any of the malarial species but is most frequent with complicated P. falciparum malaria. The likelihood of death is increased in children with preexisting health problems, such as measles, intestinal parasites, schistosomiasis, anemia, and malnutrition. Death is much more common in developing countries.


Pediatrics_Nelson

Pediatrics_Nelson. There are two components of malaria prevention: reduction of exposure to infected mosquitoes and chemoprophylaxis. Mosquito protection is necessary because no prophylactic regimen can guarantee protection in every instance due to the widespread development of resistant organisms. Chemoprophylaxis is necessary for all visitors to and residents of the tropics who have not lived there since infancy. Children of nonimmune women should have chemoprophylaxis from birth. Children of women from endemic areas have passive immunity until 3 to 6 months of age, after which they are increasingly likely to acquire malaria. Specific chemoprophylaxis should be guided by the distribution of resistance pattern and determined before making specific recommendations ( http://www.cdc.gov/malaria/travelers/country_table/a.html ).Mefloquine, doxycycline, chloroquine, and Malarone are commonly prescribed medications. Available @ StudentConsult.com


Pediatrics_Nelson

Pediatrics_Nelson. Available @ StudentConsult.com Splenomegaly Lymphadenopathy Petechiae/Purpura Fever of Unknown Origin Toxoplasmosis is a zoonosis caused by Toxoplasma gondii, an intracellular protozoan parasite. Infection is acquired by infectious oocysts, such as those excreted by newly infected cats, which play an important role in amplifying the organism in nature, or from ingesting cysts in contaminated, undercooked meat. Less commonly, transmission occurs transplacentally during acute infection of pregnant women. In the United States, the incidence of congenital infection is 1 to 2 per 1000 live births.


Pediatrics_Nelson

Pediatrics_Nelson. Acquired toxoplasmosis is usually asymptomatic. Symptomatic infection is typically a heterophile-negative mononucleosis syndrome that includes lymphadenopathy, fever,and hepatosplenomegaly. Disseminated infection, includingmyocarditis, pneumonia, and central nervous system (CNS)toxoplasmosis, is more common among immunocompromised persons, especially persons with acquired immunodeficiency syndrome (AIDS). Among women infected duringpregnancy, 40% to 60% give birth to an infected infant. Thelater in pregnancy that infection occurs, the more likely it isthat the fetus will be infected, but the less severe the illness (see Chapter 66). Serologic diagnosis can be established by afourfold increase in antibody titer or seroconversion, a positive IgM antibody titer, or positive polymerase chain reactionfor T. gondii in peripheral white blood cells, cerebrospinalfluid (CSF), serum, or amniotic fluid.


Pediatrics_Nelson

Pediatrics_Nelson. Treatment includes pyrimethamine and sulfadiazine, which act synergistically against Toxoplasma. Because these compounds are folic acid inhibitors, they are used in conjunction with folinic acid. Spiramycin, which is not licensed in the United States, also is used in therapy of pregnant women with toxoplasmosis. Corticosteroids are reserved for patients with acute CNS or ocular infection. Ingesting only well-cooked meat and avoiding cats orsoil in areas where cats defecate are prudent measures forpregnant or immunocompromised persons. Administration of spiramycin to infected pregnant women has beenassociated with lower risks of congenital infection in theiroffspring. Helminths are divided into three groups: roundworms, or nematodes, and two groups of flatworms, the trematodes (flukes) and the cestodes (tapeworms).


Pediatrics_Nelson

Pediatrics_Nelson. Hookworm infection is caused by several species of hookworms, with Ancylostoma duodenale and Necator americanus being the most important (Table 123-2). There are more than 9 million humans worldwide infected with hookworms. Ancylostoma duodenale is the predominant species in Europe, the Mediterranean region, northern Asia, and the west coast of South America. N. americanus predominates in the Western hemisphere, sub-Saharan Africa, Southeast Asia, and the Pacific Islands. Optimal soil conditions and fecal contamination are found in many agrarian tropical countries and in the southeastern United States. Infection typically occurs in young children, especially during the first decade of life. The larvae are found in warm, damp soil and infect humans by penetrating the skin. They migrate to the lungs, ascend the trachea, are swallowed, and reside in the intestine. The worms mature and attach to the intestinal wall, where they suck blood and shed eggs.


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Pediatrics_Nelson. Cutaneous larva migrans Ancylostoma braziliense Larval penetration Albendazole or ivermectin or (azoonotic hookworm) (and failure to migrate) thiabendazole topically Infant ancylostomiasis A. duodenale Perinatal (?) Albendazole or mebendazole or pyrantel pamoate Intestinal ascariasis Ascaris lumbricoides Ingestion of Ascaris eggs Albendazole or mebendazole or pyrantel pamoate Diarrhea, malabsorption Strongyloides stercoralis Larval penetration Ivermectin or thiabendazole (celiac-like) Pinworm Enterobius vermicularis Ingestion of embryonated eggs Albendazole or mebendazole or pyrantel pamoate Abdominal angiostrongyliasis Angiostrongylus costaricensis Ingestion of contaminated food Mebendazole or thiabendazole Eosinophilic meningitis Angiostrongylus cantonensis (rat Ingestion of undercooked Mebendazole lungworm) contaminated seafood


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Pediatrics_Nelson. Eosinophilic meningitis Angiostrongylus cantonensis (rat Ingestion of undercooked Mebendazole lungworm) contaminated seafood Infections are usually asymptomatic. Intense pruritus (ground itch) occurs at the site of larval penetration, usually the soles of the feet or between the toes, and may include papules and vesicles. Migration of larvae through the lungs usually is asymptomatic. Symptoms of abdominal pain, anorexia, indigestion, fullness, and diarrhea occur with hookworm infestation. The major manifestation of infection is anemia. Examination of fresh stool for hookworm eggs is diagnostic. Therapy includes anthelmintic treatment with albendazole, mebendazole, or pyrantel pamoate and treatment for anemia. Eradication depends on sanitation of the patient’s environment and chemotherapy.


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Pediatrics_Nelson. Ascariasis is caused by Ascaris lumbricoides, a large nematode. It is the most prevalent helminthiasis, affecting 1 billion people (see Table 123-2). After humans ingest the eggs, larvae are released and penetrate the intestine, migrate to the lungs, ascend the trachea, and are swallowed. On entering the intestines again, they mature and produce eggs that are excreted in the stool and are deposited in the soil, where they survive for prolonged periods. Manifestations may be the result of migration of the larvae to other sites of the body or the presence of adult worms in the intestine. Pulmonary ascariasis occurs as the larvae migrate through the lung, producing cough, blood-stained sputum, eosinophilia, and transient infiltrates on chest x-ray films.


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Pediatrics_Nelson. Adult larvae in the small intestine may cause abdominal pain and distention. Intestinal obstruction from adult worms rarely occurs. Migration of worms into the bile duct may rarely cause acute biliary obstruction. Examination of fresh stool for characteristic eggs is diagnostic. Effective control depends on adequate sanitary treatment and disposal of infected human feces. Visceral larva migrans is a systemic nematodiasis caused by ingestion of the eggs of the dog tapeworm, Toxocara canis, or, less commonly, the cat tapeworm, Toxocara cati, or the raccoon tapeworm, Baylisascaris procyonis (see Table 123-2).These organisms also cause ocular larva migrans.


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Pediatrics_Nelson. Visceral larva migrans is most common in young children with pica who have dogs or cats as pets. Ocular toxocariasis occurs in older children. The eggs of these roundworms are produced by adult worms residing in the dog and cat intestine. Ingested eggs hatch into larvae that penetrate the gastrointestinal tract and migrate to the liver, lung, eye, CNS, and heart, where they die and calcify. Symptoms of visceral larva migrans are the result of the number of migrating worms and the associated immune response. Light infections are often asymptomatic. Symptoms include fever, cough, wheezing, and seizures. Physical findings may include hepatomegaly, crackles, rash, and lymphadenopathy. Visual symptoms may include decreased acuity, strabismus, periorbital edema, or blindness. Eye examination Parasitoses due to other Ingestion of raw or inadequately Paragonimiasis Paragonimus westermani, P. Praziquantel or bithionol miyazaki, P. mexicanus, P. kellicotti,


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Pediatrics_Nelson. Parasitoses due to other Ingestion of raw or inadequately Paragonimiasis Paragonimus westermani, P. Praziquantel or bithionol miyazaki, P. mexicanus, P. kellicotti, P. uterobilateralis, P. skjabini, P. hueitungensis, P. heterotrema, P. africanus (lung flukes) may reveal granulomatous lesions near the macula or disc. Ocular larva migrans is characterized by isolated, unilateral ocular disease and no systemic findings. Larvae probably enter the anterior vitreous of the eye from a peripheral branch of the retinal artery and elicit granulomas in the posterior and peripheral poles that cause vision loss.


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Pediatrics_Nelson. Eosinophilia and hypergammaglobulinemia associated with elevated isohemagglutinin levels suggest the diagnosis, which is confirmed by serology (enzyme-linked immunosorbent assay) or, less commonly, by biopsy. This is usually a self-limited illness. In severe disease, albendazole or mebendazole is used. Deworming puppies and kittens, major excreters of eggs, decreases the risk of infection. Available @ StudentConsult.com Pinworm is caused by Enterobius vermicularis, a nematode that is distributed worldwide. Enterobiasis affects individuals at all socioeconomic levels, especially children. Crowded living conditions predispose to infection. Humans ingest the eggs carried on hands, present in house dust or on bedclothes. The eggs hatch in the stomach, and the larvae migrate to the cecum and mature. At night the females migrate to the perianal area to lay their eggs, which are viable for 2 days.


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Pediatrics_Nelson. The most common symptoms are nocturnal anal pruritus (pruritus ani) and sleeplessness, presumably resulting from the migratory female worms. Vaginitis and salpingitis may develop secondary to aberrant worm migration. The eggs are detected by microscopically examining adhesive cellophane tape pressed against the anus in the morning to collect eggs. Less commonly, a worm may be seen in the perianal region. Treatment is with albendazole (400 mg), mebendazole (100 mg), or pyrantel pamoate (11 mg/kg, maximum 1 g) each given as a single oral dose and repeated in 2 weeks. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com Schistosomiasis (bilharziasis) is caused by flukes that parasitize the bloodstream, including Schistosoma haematobium, Schistosoma mansoni, Schistosoma japonicum, and, rarely, Schistosoma intercalatum and Schistosoma mekongi (Table 123-3). Schistosomiasis affects more than 2 million people, mainly children and young adults with a peak age range of 10 to 20 years. Humans are infected by cercariae in contaminated water that emerge in an infectious form from snails and penetrate intact skin. Each adult worm migrates to specific sites: S. haematobium to the bladder plexus and S. intercalatum and S. mekongi to the mesenteric vessels. The eggs are deposited by the adult flukes in urine (S. haematobium) or stool (S. mansoni Echinococcosis Echinococcus granulosus var. Alveolar echinococcosis Echinococcus multilocularis Surgical resection is only reliable means of treatment; some reports suggest adjunct use of albendazole or mebendazole


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Pediatrics_Nelson. Alveolar echinococcosis Echinococcus multilocularis Surgical resection is only reliable means of treatment; some reports suggest adjunct use of albendazole or mebendazole Neurocysticercosis Larval stage of Taenia solium Ingestion of infected raw/ Albendazole or praziquantel (cysticerci) undercooked pork Adult tapeworm infections T. solium (pork tapeworm) Ingestion of contaminated raw/ Praziquantel undercooked pork and S. japonicum). S. haematobium is prevalent in Africa and the Middle East; S. mansoni in Africa, the Middle East, the Caribbean, and South America; S. japonicum in China, the Philippines, and Indonesia; S. mekongi in the Far East; and S. intercalatum in West Africa.


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Pediatrics_Nelson. The manifestations of schistosomiasis result from eggs that are trapped at the site of deposition or at metastatic locations. Within 3 to 12 weeks of infection, while the worms are maturing, a syndrome of fever, malaise, cough, abdominal pain, and rash can occur. This syndrome is followed by a resultant inflammatory response that leads to further symptoms. Katayama fever is an acute condition, with fever, weight loss, hepatosplenomegaly, and eosinophilia. Eggs may be found in the urine (S. haematobium) or stool (S. mansoni and S. japonicum)of infected individuals. Sanitary measures, molluscacides, and therapy for infected individuals may help control the illness.


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Pediatrics_Nelson. Echinococcosis includes hydatid or unilocular cyst disease, caused by Echinococcus granulosus (the minute dog tapeworm) or Echinococcus vogeli, and alveolar cyst disease, caused by Echinococcus multilocularis (Table 123-4). Dogs become infected with tapeworms by eating infected sheep or cattle viscera and excrete eggs in their stools. Humans acquire echinococcosis by ingesting eggs and become an intermediate host. The eggs hatch in the intestinal tract, and the larva (oncospheres) penetrate the mucosa and enter the circulation to pass to the liver and other visceral organs, forming cysts 2 cm in diameter.


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Pediatrics_Nelson. E. granulosus has a worldwide distribution and is endemic in sheep-raising and cattle-raising areas of Australia, South America, South Africa, the former Soviet Union, and the Mediterranean region. The prevalence is highest in children. Symptoms caused by E. granulosus result from space-occupyingcysts. Pulmonary cysts may cause hemoptysis, cough, dyspnea,and respiratory distress. Brain cysts appear as tumors; livercysts cause problems as they compress and obstruct blood flow.Ultrasonography identifies cystic lesions, and the diagnosis isconfirmed by serologic testing. Large or asymptomatic granulosa cysts are removed surgically. Treatment with albendazolehas shown some benefit.


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Pediatrics_Nelson. Neurocysticercosis is caused by infection with the larval stages (cysticerci) of the pork tapeworm, Taenia solium, and is the most frequent helminthic infection of the CNS (see Table 1234). Humans are infected after consuming cysticerci in raw or undercooked larva-containing pork. T. solium is endemic in Asia, Africa, and Central and South Americas. Cysts typically enlarge slowly, causing no or minimal symptoms for years or decades until the organism begins to die. The cyst then begins to swell, and leakage of antigen incites an inflammatory response, resulting in the presenting signs of focal or generalized seizures and calcified cerebral cysts identified by computed tomography or magnetic resonance imaging. The CSF shows lymphocytic or eosinophilic pleocytosis. The diagnosis is confirmed by serologic testing. Neurocysticercosis is treated with albendazole or praziquantel, corticosteroids for concomitant cerebral inflammation from cyst death, and anticonvulsant drugs.


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Pediatrics_Nelson. Mycobacterium tuberculosis are pleomorphic, weakly gram-positive curved rods. Mycobacteria are acid fast, which is the capacity to form stable mycolate complexes with arylmethane dyes. Mycobacteria grow slowly; culture from clinical specimens on solid synthetic media usually takes 3 to 6 weeks. Drug-susceptibility testing requires an additional 4 weeks. Growth can be detected in 1 to 3 weeks in selective liquid media using radiolabeled nutrients. Polymerase chain reaction (PCR) of clinical specimens allows rapid diagnosis in many laboratories.


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Pediatrics_Nelson. An estimated 10 to 15 million persons in the United States have latent tuberculosis infection (infection with M. tuberculosis and no disease). Without treatment, tuberculosis disease develops in 5% to 10% of immunologically normal adults with tuberculosis infection at some time during their lives; the risk is higher in infants. An estimated 8 million new cases of tuberculosis occur each year among adults worldwide. Three million deaths are attributed to the disease annually. In developing countries, 1.3 million new cases of the disease occur in children under 15 years of age, and 450,000 children die each year of tuberculosis. Most children with tuberculosis infection and disease acquire M. tuberculosis from an infectious adult.


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Pediatrics_Nelson. Transmission of M. tuberculosis is from person to person, usually by respiratory droplets that become airborne when the ill individual coughs, sneezes, laughs, sighs, or breathes. Infected droplets dry and become droplet nuclei, which may remain suspended in the air for hours, long after the infectious person has left the environment.


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Pediatrics_Nelson. Several patient-related factors are associated with an increased chance of transmission. Of these a positive acid-fast smear of the sputum most closely correlates with infectivity. Children with primary pulmonary tuberculosis disease rarely, if ever, infect other children or adults. Tubercle bacilli are relatively sparse in the endobronchial secretions of children with primary pulmonary tuberculosis, and a significant cough is usually lacking. When young children cough, they rarely produce sputum, lacking the tussive force necessary to project and suspend infectious particles of the requisite size. Hospitalized children with suspected pulmonary tuberculosis are placed initially in respiratory isolation. Most infectious patients become noninfectious within 2 weeks of starting effective treatment, and many become noninfectious within several days.


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Pediatrics_Nelson. In North America, tuberculosis rates are highest in for-eign-born persons from high-prevalence countries, residents of prisons, residents of nursing homes, homeless persons, users of illegal drugs, persons who are poor and medically indigent, health care workers, and children exposed to adults in high-risk groups. Among U.S. urban dwellers with tuberculosis, persons with acquired immunodeficiency syndrome (AIDS) and racial minorities are overrepresented. Most children are infected with M. tuberculosis from household contacts, but outbreaks of childhood tuberculosis centered in elementary and high schools, nursery schools, family day care homes, churches, school buses, and stores still occur. A high-risk adult working in the area has been the source of the outbreak in most cases. Available @ StudentConsult.com Cough Hemoptysis Back Pain Fever and Rash Lymphadenopathy Fever of Unknown Origin


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Pediatrics_Nelson. Available @ StudentConsult.com Cough Hemoptysis Back Pain Fever and Rash Lymphadenopathy Fever of Unknown Origin Latent tuberculosis describes the asymptomatic stage of infection with M. tuberculosis. The tuberculin skin test (TST) is positive, but the chest radiograph is normal, and there are no signs or symptoms of illness. Tuberculosis disease occurs when there are clinical signs and symptoms or an abnormal chest radiograph. The term tuberculosis usually refers to the disease. The interval between latent tuberculosis and the onset of disease may be several weeks or many decades in adults. In young children, tuberculosis usually develops as an immediate complication of the primary infection, and the distinction between infection and disease may be less obvious.


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Pediatrics_Nelson. Primary pulmonary tuberculosis in older infants and children is usually an asymptomatic infection. Often the disease is manifested by a positive TST with minimal abnormalities on the chest radiograph, such as an infiltrate with hilar lymphadenopathy or Ghon complex. Hilar lymphadenopathy may compress the bronchi or trachea malaise, low-grade fever, erythema nodosum, or symptoms resulting from lymph node enlargement may occur after the development of delayed hypersensitivity. Lymphadenopathy is common in primary pulmonary disease. Hilar lymphadenopathy may compress the bronchi or trachea. The most common extrathoracic sites of lymphadenitis are the cervical, supraclavicular, and submandibular areas (scrofula).


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Pediatrics_Nelson. Progressive primary disease is characterized by a primary pneumonia that develops shortly after initial infection. Progression to pulmonary disease, disseminated miliary disease, or progression of central nervous system (CNS) granulomas to meningitis occurs most commonly in the first year of life. Tuberculous pleural effusion, which may accompany primary infection, generally represents the immune response to the organisms and most commonly occurs in older children or adolescents. Pleurocentesis reveals lymphocytes and an increased protein level, but the pleural fluid usually does not contain bacilli.


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Pediatrics_Nelson. Reactivation pulmonary tuberculosis, common in adolescents and typical in adults, usually is confined to apical segments of upper lobes or superior segments of lower lobes. There is usually little lymphadenopathy and no extrathoracic infection because of established hypersensitivity. This is a manifestation of a secondary expansion of infection at a site seeded years previously during primary infection. Advanced disease is associated with cavitation and endobronchial spread of bacilli. Symptoms include fever, night sweats, malaise, and weight loss. A productive cough and hemoptysis often herald cavitation and bronchial erosion.


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Pediatrics_Nelson. Miliary tuberculosis refers to widespread hematogenous dissemination to multiple organs. The lesions are of roughly the same size as a millet seed, from which the name miliary is derived. Miliary tuberculosis is characterized by fever, general malaise, weight loss, lymphadenopathy, night sweats, and hepatosplenomegaly. Diffuse bilateral pneumonitis is common, and meningitis may be present. The chest radiograph reveals bilateral miliary infiltrates, showing overwhelming infection. The TST may be nonreactive as a result of anergy. Liver or bone marrow biopsy is useful for the diagnosis.


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Pediatrics_Nelson. Tuberculous meningitis most commonly occurs in children under 5 years old and often within 6 months of primary infection. Tubercle bacilli that seed the meninges during the primary infection replicate, triggering an inflammatory response. This condition may have an insidious onset, initially characterized by low-grade fever, headache, and subtle personality change. Progression of the infection results in basilar meningitis with impingement of the cranial nerves and is manifested by meningeal irritation and, eventually, increased intracranial pressure, deterioration of mental status, and coma. Computed tomography (CT) scans show hydrocephalus, edema, periventricular lucencies, and infarctions. Cerebrospinal fluid (CSF) analysis reveals pleocytosis (50 to 500 leukocytes/mm3), which early in the course of disease may be either lymphocytes or polymorphonuclear leukocytes. Glucose is low, and protein is significantly elevated. Acid-fast bacilli are not detected frequently in the CSF by


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Pediatrics_Nelson. in the course of disease may be either lymphocytes or polymorphonuclear leukocytes. Glucose is low, and protein is significantly elevated. Acid-fast bacilli are not detected frequently in the CSF by either routine or fluorescent staining procedures. Although culture is the standard for diagnosis, PCR for M. tuberculosis is useful to confirm meningitis.


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Pediatrics_Nelson. Skeletal tuberculosis results from either hematogenous seeding or direct extension from a caseous lymph node. This is usually a chronic disease with an insidious onset that may be mistaken for chronic osteomyelitis caused by Staphylococcus aureus. Radiographs reveal cortical destruction. Biopsy and culture are essential for proper diagnosis. Tuberculosis of the spine, Pott’s disease, is the most common skeletal site followed by the hip as well as fingers and toes (dactylitis).


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Pediatrics_Nelson. Other forms of tuberculosis include abdominal tuberculosis that occurs from swallowing infected material. This is a relatively uncommon complication in developed nations where dairy herds are inspected for bovine tuberculosis. Tuberculous peritonitis is associated with abdominal tuberculosis and presents as fever, anorexia, ascites, and abdominal pain. Urogenital tuberculosis is a late reactivation complication and is rare in children. Symptomatic illness presents as dysuria, frequency, urgency, hematuria, and sterile pyuria.


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Pediatrics_Nelson. Two types of tests are used to detect the immune response to M. tuberculosis and are used to screen patients for latent tuberculosis and investigation of active tuberculosis. The TST response to tuberculin antigen is a manifestation of a T cell−mediated delayed hypersensitivity. The Mantoux test, an intradermal injection of 5 TU (tuberculin units) of purified protein derivative standard (PPD-S), usually on the volar surface of the forearm, is the standard TST. It is usually positive 2 to 6 weeks after onset of infection (occasionally 3 months) and at the time of symptomatic illness. This test is preferred in children less than 5 years of age. It may also be used in other settings such as contact investigations or in older patients. Only persons at high risk should be offered a Mantoux test (Table 124-1). False-negative responses may occur early in the illness, with use of inactivated antigen (as a result of poor storage practice or inadequate administration), or as a result of


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Pediatrics_Nelson. test (Table 124-1). False-negative responses may occur early in the illness, with use of inactivated antigen (as a result of poor storage practice or inadequate administration), or as a result of immunosuppression (secondary to underlying illness, AIDS, malnutrition, or overwhelming tuberculosis). Tests with questionable results should be repeated after several weeks of therapy and adequate nutrition. Because of poor nutrition, a high proportion of internationally adopted children arriving in the United States have an initial false-positive TST. All internationally adopted children with an initially negative TST should have a repeat TST after 3 months in the United States. The TST is interpreted based on the host status and size of induration (Table 124-2).


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Pediatrics_Nelson. Table 124-1 Tuberculin Skin Test (TST) Recommendations for Infants, Children, and Adolescents* CHILDREN FOR WHOM IMMEDIATE TST OR IGRA IS INDICATED:† Contacts of people with confirmed or suspected contagious tuberculosis (contact investigation) Children with radiographic or clinical findings suggesting tuberculosis disease Children immigrating from countries with endemic infection (e.g., Asia, Middle East, Africa, Latin America, countries of the former Soviet Union), including international adoptees Children with travel histories to countries with endemic infection and substantial contact with indigenous people from such countries Children infected with HIV infection (TST only)


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Pediatrics_Nelson. Children infected with HIV infection (TST only) Children with other medical conditions, including diabetes mellitus, chronic renal failure, malnutrition, and congenital or acquired immunodeficiencies deserve special consideration. Without recent exposure, these people are not at increased risk of acquiring tuberculosis infection. Underlying immune deficiencies associated with these conditions theoretically would enhance the possibility for progression to severe disease. Initial histories of potential exposure to tuberculosis should be included for all of these patients. If these histories or local epidemiologic factors suggest a possibility of exposure, immediate and periodic TST or IGRA should be considered. An initial TST or IGRA should be performed before initiation of immunosuppressive therapy, including prolonged steroid administration, use of tumor necrosis factor-alpha antagonists, or other immunosuppressive therapy in any child requiring these treatments.


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Pediatrics_Nelson. Recommendations from American Academy of Pediatrics: Tuberculosis. In Pickering LK, Baker CJ, Kimberlin DW, et al, editors. Red Book: 2012 Report of the Committee on Infectious Diseases, ed 29, Elk Grove Village, IL, 2012, American Academy of Pediatrics. HIV, Human immunodeficiency virus; IGRA, interferon-gamma release assay; LTBI, latent tuberculosis infection. *Bacille Calmette-Guérin immunization is not a contraindication to a TST. †Beginning as early as 3 months of age. ‡If the child is well, the TST or IGRA should be delayed for up to 10 weeks after return. A whole blood test of interferon-gamma (INF-γ) release assay (IGRA), a cytokine elaborated by lymphocytes in response to tuberculosis antigens, is the recommended diagnostic test for persons older than 5 years of age in the United States. It has similar sensitivity as the TST but improved specificity because it is unaffected by prior bacille Calmette-Guérin vaccination.


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Pediatrics_Nelson. The ultimate diagnostic confirmation relies on culture of the organism, a process that usually is more successful with tissue, such as pleura or pericardial membrane from biopsy, rather than pleural or pericardial fluid. Sputum is an excellent source for diagnosis in adults but is difficult to obtain in young children. Induced sputum or gastric fluid obtained via an indwelling nasogastric tube with samples taken before or immediately on waking contains swallowed sputum and provides appropriate samples in young children. Large volumes of fluid (CSF, pericardial fluid) yield a higher rate of recovery of organisms, Induration ≥5 mm Children in close contact with persons with known or suspected contagious tuberculosis disease Children suspected to have tuberculosis disease Findings on chest radiograph consistent with active or previously active tuberculosis Clinical evidence of tuberculosis disease†


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Pediatrics_Nelson. Children suspected to have tuberculosis disease Findings on chest radiograph consistent with active or previously active tuberculosis Clinical evidence of tuberculosis disease† Children receiving immunosuppressive therapy‡ or with immunosuppressive conditions, including HIV infection Children <4 years of age Children with other medical conditions, including Hodgkin disease, lymphoma, diabetes mellitus, chronic renal failure, and malnutrition Children with increased exposure to tuberculosis disease Children born, or whose parents were born, in high-prevalence regions of the world Children frequently exposed to adults who are HIV-infected, homeless, users of illicit drugs, residents of nursing homes, incarcerated or institutionalized, or migrant farm workers Children who travel to high-prevalence regions of the world


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Pediatrics_Nelson. Induration ≥15 mm Children ≥4 years of age without any risk factors *These criteria apply regardless of previous bacille Calmette-Guérin immunization. Erythema at tuberculin skin test site does not indicate a positive test result. Tuberculin reactions should be read at 48 to 72 hours after placement. †Evidence by physical examination or laboratory assessment that would include tuberculosis in the working differential diagnosis (e.g., meningitis). ‡Including immunosuppressive doses of corticosteroids. but slow growth of the mycobacteria makes culture less helpful in very ill children. When the organism is grown, drug susceptibilities should be determined because of the increasing incidence of resistant organisms. Antigen detection and DNA probes have expedited diagnosis, especially with CNS disease.


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Pediatrics_Nelson. Antigen detection and DNA probes have expedited diagnosis, especially with CNS disease. Because many cases of pulmonary tuberculosis in children are clinically relatively silent, radiography is a cornerstone for the diagnosis of disease. All lobar segments of the lung are at equal risk of being the focus of the initial infection. In 25% of cases, two or more lobes of the lungs are involved, although disease usually occurs at one site only. Spread of infection to regional lymph nodes occurs early.


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Pediatrics_Nelson. The hallmark of childhood pulmonary tuberculosis is the relatively large size and importance of the hilar lymphadenitis compared with the less significant size of the initial parenchymal focus, together historically referred to as the Ghon complex (with or without calcification of the lymph nodes). Hilar lymphadenopathy is inevitably present with childhood tuberculosis. Partial bronchial obstruction caused by external compression from the enlarging nodes can cause air trapping, hyperinflation, and lobar emphysema. Occasionally children have a picture of lobar pneumonia without impressive hilar lymphadenopathy. If the infection is progressively destructive, liquefaction of the lung parenchyma leads to formation of a thin-walled primary tuberculous cavity. Adolescents with pulmonary tuberculosis may develop segmental lesions with hilar lymphadenopathy or the apical infiltrates, with or without cavitation, that are typical of adult reactivation tuberculosis.


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Pediatrics_Nelson. Radiographic studies aid greatly in the diagnosis of extrapulmonary tuberculosis in children. Plain radiographs, CT, and magnetic resonance imaging (MRI) of the tuberculous spine usually show collapse and destruction of the vertebral body with narrowing of the involved disk spaces. Radiographic findings in bone and joint tuberculosis range from mild joint effusions and small lytic lesions to massive destruction of the bone. In tuberculosis of the CNS, CT or MRI of the brains of patients with tuberculous meningitis may be normal during early stages of the infection. As disease progresses, basilar enhancement and communicating hydrocephalus with signs of cerebral edema or early focal ischemia are the most common findings.


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Pediatrics_Nelson. The differential diagnosis of tuberculosis includes a multitude of diagnoses because tuberculosis may affect any organ, and in early disease the symptoms and signs may be nonspecific. In pulmonary disease, tuberculosis may appear similar to pneumonia, malignancy, and any systemic disease in which generalized lymphadenopathy occurs. The diagnosis of tuberculosis should be suspected if the TST or IGRA is positive or if there is history of tuberculosis in a close contact. The differential diagnosis of tuberculous lymphadenopathy includes infections caused by atypical mycobacteria, cat-scratch disease, fungal infection, viral or bacterial disease, toxoplasmosis, sarcoidosis, drug reactions, and malignancy. The diagnosis may be confirmed by fine-needle aspiration but may necessitate excisional biopsy accompanied by appropriate histologic and microbiologic studies.


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Pediatrics_Nelson. The treatment of tuberculosis is affected by the presence of naturally occurring drug-resistant organisms in large bacterial populations, even before therapy is initiated, and the fact that mycobacteria replicate slowly and can remain dormant in the body for prolonged periods. Although a population of bacilli as a whole may be considered drug susceptible, a subpopulation of drug-resistant organisms occurs at fairly predictable frequencies of 105 to 107, depending on the drug. Cavities may contain 109 tubercle bacilli with thousands of organisms resistant to any one drug, but only rare organisms are resistant to multiple drugs. Patients with latent tuberculosis infection have small bacterial populations and a single drug, such as isoniazid, can be Table 124-3 Recommended Treatment Regimens for Drug-Susceptible Tuberculosis in Infants, Children, and Adolescents INFECTION OR DISEASE CATEGORY REGIMEN COMMENTS LATENT TUBERCULOSIS INFECTION (POSITIVE TST RESULT, NO DISEASE)


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Pediatrics_Nelson. Isoniazid-susceptible 9 months of isoniazid, once a day If daily therapy is not possible, DOT twice a week can be used for 9 months. Isoniazid-resistant 6 months of rifampin, once a day Isoniazid-rifampin–resistant Consult a tuberculosis specialist. If hilar lymphadenopathy only, a 6-month course of isoniazid and rifampin is sufficient. Drugs can be given 2 or 3 times per week under DOT in the initial phase if nonadherence is likely. rifampin, once a day or twice a week For patients who may have acquired tuberculosis in (9–12 months total) geographic areas where resistance to streptomycin is common, capreomycin, kanamycin, or amikacin may be used instead of streptomycin. Recommendations from Pickering LK, Baker CJ, Long SS, et al: Red Book: 2012 Report of the Committee on Infectious Diseases, ed 27, Elk Grove Village, IL, 2012, American Academy of Pediatrics. DOT, Directly observed therapy; TST, tuberculin skin test.


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Pediatrics_Nelson. given. Therapy for latent infection is aimed at eradicating thepresumably small inoculum of organisms sequestered withinmacrophages and suppressed by normal T cell activity. Toprevent reactivation of these latent bacilli, therapy with a single agent (usually isoniazid for 9 months) is suggested. Children with primary pulmonary tuberculosis and patients withextrapulmonary tuberculosis have medium-sized populationsin which significant numbers of drug-resistant organisms mayor may not be present. In general these patients are treated withat least two drugs (Table 124-3) for a prolonged course, typically6 to 9, depending on the type of disease. Isoniazid and rifampinare bactericidal for M. tuberculosis and are effective against allpopulations of mycobacteria. Along with pyrazinamide, theyform the backbone of the antimicrobial treatment of tuberculosis. Other drugs are used in special circumstances, such astuberculous meningitis and antibiotic-resistant tuberculosis.


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Pediatrics_Nelson. A 9-month regimen of isoniazid and rifampin cures greater than 98% of cases of drug-susceptible pulmonary tuberculosis. After daily administration for the first 1 to 2 months, both drugs can be given daily or twice weekly for the remaining 7 to 8 months, with equivalent results and low rates of adverse reactions. The addition of pyrazinamide for the first 2 months of the regimen reduces the total duration of treatment to 6 months and has similar efficacy. Noncompliance, or nonadherence, is a major problem in tuberculosis control because of the long-term nature of treatment and the sometimes difficult social circumstances of the patients. As treatment regimens become shorter, adherence assumes an even greater importance. Improvement in compliance occurs with directly observed therapy, which means that the health care worker is physically present when the medications are administered, and is the standard of care in most settings.


Pediatrics_Nelson

Pediatrics_Nelson. The prognosis of tuberculosis in infants, children, and adolescents is excellent with early recognition and effective chemotherapy. In most children with pulmonary tuberculosis, the disease completely resolves, and ultimately radiographic findings are normal. The prognosis for children with bone and joint tuberculosis and tuberculous meningitis depends directly on the stage of disease at the time antituberculosis medications are started. Tuberculosis of the spine may result in angulation or gibbus formation that requires surgical correction after the infection is cured. Most childhood tuberculous meningitis occurs in developing countries, where the prognosis is poor. Tuberculosis control programs involve case finding and treatment, which interrupts secondary transmission of infection from close contacts. Infected close contacts are identified by positive TST reactions and can be started on appropriate treatment to prevent transmission.


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Pediatrics_Nelson. Prevention of transmission in health care settings involves appropriate physical ventilation of the air around the source case. Offices, clinics, and hospital rooms used by adults with possible tuberculosis should have adequate ventilation, with air exhausted to the outside (negative-pressure ventilation).Health care providers should have annual TSTs.


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Pediatrics_Nelson. The only available vaccine against tuberculosis is the bacille Calmette-Guérin vaccine. The original vaccine organism was a strain of Mycobacterium bovis attenuated by subculture every 3 weeks for 13 years. The preferred route of administration is intradermal injection with a syringe and needle because this is the only method that permits accurate measurement of an individual dose. The official recommendation of the World Health Organization is a single dose administered during infancy. This vaccine is not routinely used in the United States. Some studies show bacille Calmette-Guérin to provide 80% to 90% protection from tuberculosis, and other studies show no protective efficacy at all. Many infants who receive bacille Calmette-Guérin vaccine never have a positive TST reaction. When a reaction does occur, the induration size is usually less than 10 mm, and the reaction wanes after several years.


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Pediatrics_Nelson. The cause of acquired immunodeficiency syndrome (AIDS) is the human immunodeficiency virus (HIV), a single-stranded RNA virus of the retrovirus family that produces a reverse transcriptase enabling the viral RNA to act as a template for DNA transcription and integration into the host genome. HIV-1 causes 99% of all human cases. HIV-2, which is less virulent, causes 1% to 9% of cases in parts of Africa and is very rare in the United States.


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Pediatrics_Nelson. HIV infects helper T cells (CD4 cells) and cells of monocyte-macrophage lineage via interaction of viral protein gp120 with the CD4 molecule and chemokines (CXCR4 on T cells and CCR5 on dendritic cells and macrophages) that serve as coreceptors. Interaction with these molecules facilitates membrane fusion and cell entry by the virus. HIV infection directly and indirectly depletes CD4 T cells. Because helper T cells are important for delayed hypersensitivity, T cell–dependent B cell antibody production, and T cell–mediated lymphokine activation of macrophages, their destruction produces a profound combined (B and T cell) immunodeficiency. A lack of T cell regulation and unrestrained antigenic stimulation result in polyclonal hypergammaglobulinemia with nonspecific and ineffective globulins. Other cells bearing CD4, such as microglia, astrocytes, oligodendroglia, and placental tissues also may be infected with HIV.


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Pediatrics_Nelson. HIV infection is a continuously progressive process with a variable period of clinical latency before development of AIDS-defining conditions. All untreated patients have evidence of ongoing viral replication and progressive CD4 lymphocyte depletion. There are no overt manifestations of immunodeficiency until CD4 cell numbers decline to critical threshold levels. Quantitation of the viral load has become an important parameter in management.


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Pediatrics_Nelson. Horizontal transmission of HIV is by sexual contact (vaginal, anal, or orogenital), percutaneous contact (from contaminated needles or other sharp objects), or mucous membrane exposure to contaminated blood or body fluid. Transmission by contaminated blood and blood products has been eliminated in developed countries but still occurs in developing countries. Vertical transmission of HIV from mother to infant may occur transplacentally in utero, during birth, or by breastfeeding. Risk factors for perinatal transmission include prematurity, rupture of membranes more than 4 hours, and high maternal circulating levels of HIV at delivery. Perinatal transmission can be decreased from approximately 25% to less than 8% with antiretroviral treatment of the mother before and during delivery and postnatal treatment of the infant. Breastfeeding by HIV-infected mothers increases the risk of vertical transmission by 30% to 50%. In untreated infants, the mean incubation interval for development of


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Pediatrics_Nelson. treatment of the infant. Breastfeeding by HIV-infected mothers increases the risk of vertical transmission by 30% to 50%. In untreated infants, the mean incubation interval for development of an AIDS-defining condition after vertical transmission is 5 months (range, 1 to 24 months) compared with a longer incubation period after horizontal transmission of 7 to 10 years.


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Pediatrics_Nelson. Worldwide, as of 2010, approximately 34 million persons are living with HIV and 3.4 million of them are children. Therewere 2.7 million new infections in 2010 with approximately390,000 new infections in children. Roughly 70% of all people living with HIV reside in sub-Saharan Africa. Worldwide, 1.8 million people died from HIV-related illnesses in 2010. In2010 the estimated number of people over the age of 13 yearsand living with HIV in the United States was 1.1 million, and approximately 9800 children are infected. Vertical transmission is much less common than previously, and approximately50 infants are born with HIV infection each year in the UnitedStates. Most pediatric cases now occur in adolescents whoengage in unprotected sexual activities. Worldwide the numberof deaths related to HIV and the number of children infected with HIV have steadily decreased in large part due to treatmentwith antiretroviral therapy. Available @ StudentConsult.com


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Pediatrics_Nelson. Available @ StudentConsult.com Neck Masses Hoarseness Diarrhea Arthritis Fever and Rash Lymphadenopathy Anemia Petechiae/Purpura Failure to Thrive In adolescents and adults, primary infection results in the acute retroviral syndrome that develops after an incubation period of 2 to 6 weeks and consists of fever, malaise, weight loss, pharyngitis, lymphadenopathy, and often a maculopapular rash. The risk of opportunistic infections and other AIDS-defining conditions is related to the depletion of CD4 T cells. A combination of CD4 cell count and percentage and clinical manifestations is used to classify HIV infection in children (Tables 125-1 and 125-2). Initial symptoms with vertical transmission vary and may include failure to thrive, neurodevelopmental delay, lymphadenopathy, hepatosplenomegaly, chronic or recurrent diarrhea, interstitial pneumonia, or oral thrush. These findings may be subtle and remarkable only by their persistence.


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Pediatrics_Nelson. From Centers for Disease Control and Prevention: 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age, MMWR 43(RR-12):1–10, 1994. Manifestations that are more common in children than adults with HIV infection include recurrent bacterial infections, lymphoid hyperplasia, chronic parotid swelling, lymphocytic interstitial pneumonitis, and earlier onset of progressive neurologic deterioration. Pulmonary manifestations of HIV infection are common and include Pneumocystis jirovecipneumonia, which can present early in infancy as a primary pneumonia characterized by hypoxia, tachypnea, retractions, elevated serum lactate dehydrogenase, and fever.


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Pediatrics_Nelson. In the United States, most pregnant women are screened and, if indicated, treated for HIV infection. Infants born to HIV-infected mothers receive prophylaxis and are prospectively tested for infection. The diagnosis of HIV infection in most infants born in the United States is confirmed before development of clinical signs of infection. HIV infection can be diagnosed definitively by 1 month of age and in virtually all infected infants by 6 months of age using viral diagnostic assays (RNA polymerase chain reaction [PCR], DNA PCR, or virus culture). Maternal antibodies may be detectable until 12 to 15 months of age, and a positive serologic test is not considered diagnostic until 18 months of age.


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Pediatrics_Nelson. HIV DNA PCR is the preferred virologic method for diagnosing HIV infection during infancy and identifies 38% of infected infants at 48 hours and 96% at 28 days. Diagnostic viral testing should be performed by 48 hours of age, at 1 to 2 months of age, and at 3 to 6 months of age. An additional test at 14 days of age is often performed because the diagnostic sensitivity increases rapidly by 2 weeks of age. HIV RNA PCR has 25% to 40% sensitivity during the first weeks of life, increasing to 90% to 100% by 2 to 3 months of age. However a negative HIV RNA PCR cannot be used to exclude infection and, thus, is not recommended as first-line testing.


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Pediatrics_Nelson. HIV infection of an exposed infant is confirmed if virologic tests are positive on two separate occasions. HIV infection can be reasonably excluded in nonbreastfed infants with at least two virologic tests performed at older than 1 month of age, with one test being performed after 4 months of age, or at least two negative antibody tests performed after 6 months of age, with an interval of at least 1 month between the tests. Loss of HIV antibody combined with negative HIV DNA PCR confirms absence of HIV infection. Persistence of a positive HIV antibody test after 18 months of age indicates HIV infection. The differential diagnosis of AIDS in infants includes primary immunodeficiency syndromes and intrauterine infections with cytomegalovirus (CMV) and syphilis. Prominenceof individual symptoms, such as diarrhea, may suggest otheretiologies.


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Pediatrics_Nelson. Management of HIV infection in children and adolescents is rapidly evolving and becoming increasingly complex. It should be directed by a specialist in the treatment of HIV infection. Therapy is initiated based on the severity of HIV disease, as indicated by AIDS-defining conditions, and the risk of disease progression, as indicated by CD4 cell count and plasma HIV RNA level (Table 125-3). Initiation of antiretroviral therapy while the patient is still asymptomatic may preserve immune function and prevent clinical progression but incurs the adverse effects of therapy and may facilitate emergence of drug-resistant virus. Because the risk of HIV progression is fourfold to sixfold greater in infants and very young children, treatment recommendations for children are more aggressive than for adults. All age groups show rapid increases in risk as CD4 cell percentage declines to less than 15%.


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Pediatrics_Nelson. Initiation of therapy (see Table 125-3) is recommended for infants less than 12 months of age regardless of symptoms of HIV disease or HIV RNA level. Initiation of therapy is recommended for all children 1 to 5 years of age with AIDS or significant HIV-related symptoms or CD4 below 25% (clinical category C or most clinical category B) regardless of symptoms or HIV RNA level. For children older than 5 years with AIDS or significant HIV-related symptoms, CD4 count below 350/mm3 should be treated. Indications for treatment of adolescents and adults include CD4 cell count less than 200 to 350/mm3 or plasma HIV RNA levels above 55,000 copies/mL. Combination therapy with highly active antiretroviral therapy (HAART) is recommended based on the risk of disease progression as determined by CD4 percentage or count and plasma HIV RNA copy number; the potential benefits


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Pediatrics_Nelson. Children who have no signs or symptoms considered to be the result of HIV infection or who have only one of the conditions listed in category A Children with two or more of the following conditions, but none of the conditions listed in categories B and C: Lymphadenopathy (nodal tissue enlargement of ≥0.5 cm palpable at more than two sites; bilateral = one site) Recurrent or persistent upper respiratory infection, sinusitis, or Children who have symptomatic conditions, other than those listed for category A or category C, that are attributed to HIV infection. Examples of conditions in clinical category B include, but are not limited to, the following: Anemia (<8 g/dL), neutropenia (<1000/mm3), or thrombocytopenia (<100,000/mm3) persisting ≥30 days Bacterial meningitis, pneumonia, or sepsis (single episode) Candidiasis, oropharyngeal (i.e., thrush) persisting for >2 months in children younger than 6 months of age


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Pediatrics_Nelson. Bacterial meningitis, pneumonia, or sepsis (single episode) Candidiasis, oropharyngeal (i.e., thrush) persisting for >2 months in children younger than 6 months of age Cardiomyopathy Cytomegalovirus infection with onset before the age of 1 month Diarrhea, recurrent or chronic Hepatitis HSV stomatitis, recurrent (i.e., more than two episodes within 1 HSV bronchitis, pneumonitis, or esophagitis with onset before the age of 1 month Herpes zoster (i.e., shingles) involving at least two distinct episodes or more than one dermatome Leiomyosarcoma LIP or pulmonary lymphoid hyperplasia complex Nephropathy Nocardiosis Fever lasting >1 month Varicella, disseminated (i.e., complicated chickenpox)


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Pediatrics_Nelson. Serious bacterial infections, multiple or recurrent (i.e., any combination of at least two culture-confirmed infections within a 2-year period), of the following types: septicemia, pneumonia, meningitis, bone or joint infection, or abscess of an internal organ or body cavity (excluding otitis media, superficial skin or mucosal abscesses, and indwelling catheter-related infections) Candidiasis, esophageal or pulmonary (bronchi, trachea, lungs) Coccidioidomycosis, disseminated (at site other than or in addition to lungs or cervical or hilar lymph nodes) Cryptococcosis, extrapulmonary Cryptosporidiosis or isosporiasis with diarrhea persisting >1 month Cytomegalovirus disease with onset of symptoms before the age of 1 month (other than liver, spleen, or lymph nodes)


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Pediatrics_Nelson. Cryptosporidiosis or isosporiasis with diarrhea persisting >1 month Cytomegalovirus disease with onset of symptoms before the age of 1 month (other than liver, spleen, or lymph nodes) Encephalopathy (at least one progressive deficit present for at least 2 months in the absence of a concurrent illness): (a) failure to attain or loss of developmental milestones/intellectual ability, verified by standard scale or tests; (b) impaired brain growth or acquired microcephaly; (c) acquired symmetric motor deficit manifested by two or more of the following: paresis, pathologic reflexes, ataxia, or gait disturbance Herpes simplex virus infection (mucocutaneous ulcer persisting for >1 month; bronchitis, pneumonitis, or esophagitis affecting a child younger than 1 month of age Histoplasmosis, disseminated (other than or in addition to lungs or cervical or hilar lymph nodes) Kaposi sarcoma


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Pediatrics_Nelson. Histoplasmosis, disseminated (other than or in addition to lungs or cervical or hilar lymph nodes) Kaposi sarcoma Lymphoma (primary tumor, in brain; Burkitt lymphoma; immunoblastic or large cell lymphoma of B cell or unknown immunologic phenotype) Mycobacterium tuberculosis, disseminated or extrapulmonary Mycobacterium, other species or unidentified species, disseminated (other than or in addition to lungs, skin, or cervical or hilar lymph nodes) Mycobacterium avium complex or Mycobacterium kansasii, disseminated (other than or in addition to lungs, skin, or cervical or hilar lymph nodes) Salmonella (nontyphoid) septicemia, recurrent Toxoplasmosis of the brain with onset before the age of 1 month


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Pediatrics_Nelson. Salmonella (nontyphoid) septicemia, recurrent Toxoplasmosis of the brain with onset before the age of 1 month Wasting syndrome in the absence of a concurrent illness could explain the following findings: (a) persistent weight loss >10% of baseline or (b) downward crossing of at least two percentile lines on the weight-for-age chart or (c) below the 5th percentile on the weight-for-height chart on two consecutive measurements, ≥30 days apart, plus (1) chronic diarrhea (i.e., two or more loose stools per day for >30 days) or (2) documented fever (for ≥30 days, intermittent or constant)


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Pediatrics_Nelson. From the Working Group on Antiretroviral Therapy and Medical Management of HIV-infected Children: Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Department of Health and Human Services. February 23, 2009. Available at http://aidsinfo.nih.gov/contentfiles/PediatricGuidelines.pdf . Updated from Centers for Disease Control and Prevention: 1994 revised classification system for human immunodeficiency virus infection in children less than 13 years of age, MMWR 43(RR-12):1–10, 1994. HIV, Human immunodeficiency virus infection; HSV, herpes simplex virus; LIP, lymphoid interstitial pneumonia. <12 months • Regardless of clinical Treat symptoms, immune status, or viral load


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Pediatrics_Nelson. HIV, Human immunodeficiency virus infection; HSV, herpes simplex virus; LIP, lymphoid interstitial pneumonia. <12 months • Regardless of clinical Treat symptoms, immune status, or viral load CD4 <25%, regardless of Treat symptoms or HIV RNA level† ◯ HIV RNA ≥100,000 copies/mL ◯ HIV RNA < 100,000 copies/mL ◯ HIV RNA < 100,000 copies/mL ◯ HIV RNA < 100,000 copies/mL *CDC clinical categories C and B (except for the following category B conditions: single episode of serious bacterial infection or lymphoid interstitial pneumonitis). †The data supporting this recommendation are stronger for those with CD4 percentage <20% than for those with CD4 percentage of 20% to 24%.


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Pediatrics_Nelson. †The data supporting this recommendation are stronger for those with CD4 percentage <20% than for those with CD4 percentage of 20% to 24%. ‡CDC clinical category A or N or the following category B conditions: single episode of serious bacterial infection or lymphoid interstitial pneumonitis. §Clinical and laboratory data should be re-evaluated every 3 to 4 months. ‖The data supporting this recommendation are stronger for those with CD4 count <200 than for those with CD4 counts of 200 to 350 cells/mm3.


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Pediatrics_Nelson. and risks of therapy; and the ability of the caregiver to adhere to administration of the therapeutic regimen. Effective combination therapy significantly reduces viral loads and leads to the amelioration of clinical symptoms and opportunistic infections. Combination therapy that includes either a non-nucleoside reverse transcriptase inhibitor or a protease inhibitor (PI) plus a dual–nucleoside/nucleotide reverse transcriptase inhibitor backbone is recommended for initial treatment of all HIV infected children. The goal of therapy is to reduce the plasma HIV RNA to below the level of detection and normalize or preserve the patient’s immune status. The most recent specific recommendations for treatment regimens ( http://aidsinfo.nih.gov/guidelines/ ) should be consulted before initiating therapy for any patient.


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Pediatrics_Nelson. The ability of HIV to develop resistance to antiretroviral agents rapidly and the development of cross-resistance to several classes of agents simultaneously are major problems. Determination of HIV RNA, CD4 cell count, and HIV phenotype and genotype is essential for monitoring and modifying antiretroviral treatment.


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Pediatrics_Nelson. Routine immunizations are recommended to prevent vaccine-preventable infections but may result in suboptimal immune responses. In addition to heptavalent pneumococcal conjugate vaccine, 23-valent pneumococcal polysaccharide vaccine is recommended for HIV-infected children at 2 years of age and adolescents and adults with CD4 counts at or above 200/mm3. Because of the risk of fatal measles in children with AIDS, children without severe immunosuppression should receive their first dose of MMR at 12 months of age and may receive the booster as soon as 4 weeks later. Varicella zoster virus (VZV) vaccine should be given only to asymptomatic, nonimmunosuppressed children beginning at 12 months of age as two doses of vaccine at least 3 months apart. Inactivated split influenza virus vaccine should be administered annually to all HIV-infected children at or after 6 months of age. HIV-infected children exposed to varicella or measles should receive varicella zoster immune globulin or


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Pediatrics_Nelson. should be administered annually to all HIV-infected children at or after 6 months of age. HIV-infected children exposed to varicella or measles should receive varicella zoster immune globulin or immunoglobulin prophylaxis.


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Pediatrics_Nelson. The approach to the numerous opportunistic infections in HIV-infected patients involves treatment and prophylaxis for infections likely to occur as CD4 cells are depleted. With potent antiretroviral therapy and immune reconstitution, routine prophylaxis for common opportunistic infections depends on the child’s age and CD4 count. Infants born to HIV-infected mothers receive prophylaxis for P. jiroveci pneumonia with trimethoprim-sulfamethoxazole (TMP-SMZ) beginning at 4 to 6 weeks of age and continued for the first year of life or discontinued if HIV infection is subsequently excluded. TMP-SMZ prophylaxis for P. jiroveci pneumonia for older children and adolescents is provided if CD4 cell counts are less than 200/ mm3 or there is history of oropharyngeal candidiasis. Clarithromycin prophylaxis for Mycobacterium avium-complexinfection is provided if CD4 cell counts are below 50/mm3.


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Pediatrics_Nelson. P. jiroveci pneumonia is treated with high-dose TMP-SMZ and corticosteroids. Oral and gastrointestinal candidiasis is common in children and usually responds to imidazole therapy. VZV infection may be severe and should be treated with acyclovir or other antivirals. Recurrent herpes simplex virus (HSV) infections also may require long-term antiviral prophylaxis. Other common infections in HIV-infected patients include toxoplasmosis, CMV, Epstein-Barr virus infection, salmonellosis, and tuberculosis. Children and adults with HIV are prone to malignancies, especially non-Hodgkin lymphomas, with the gastrointestinal tract being the most common site. Leiomyosarcomas are the second most common tumors among HIV-infected children. Kaposi sarcoma, caused by HHV-8, is distinctly rare in children with HIV. It was once common among adults with AIDS and is now infrequent with HAART.


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Pediatrics_Nelson. The availability of HAART has improved the prognosis for HIV and AIDS dramatically. Risk of death is directly related to the degree of immunosuppression, viral load, and young age. Children less than 1 year of age with very low CD4 percentiles and high viral loads have the poorest prognosis. Identification of HIV-infected women before or during pregnancy is crucial to providing optimal therapy for infected women and their infants and to preventing perinatal transmission. Prenatal HIV counseling and testing with consent should be provided for all pregnant women in the United States.


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Pediatrics_Nelson. The rate of vertical transmission is reduced to less than 8% by chemoprophylaxis with a regimen of zidovudine to the mother (100 mg five times/24 hours orally) started by 4 weeks gestation, continued during delivery (2 mg/kg loading dose intravenously followed by 1 mg/kg/hour intravenously), and then administered to the newborn for the first 6 weeks of life (2 mg/kg every 6 hours orally). Other regimens incorporating single-dose nevirapine for infants have been shown to be similarly effective and are used in developing countries. The current recommendations for the United States include a 6-week prophylactic with zidovudine for the infant in combination with maternal intrapartum therapy. The maternal regimen includes continuation of antiretroviral therapy (if appropriate) and intravenous zidovudine if the mother’s viral load is >400 copies/mL or is unknown ( http://aidsinfo.nih.gov/ contentfiles/lvguidelines/peri_recommendations.pdf ). Scheduled cesarean section at 38 weeks to prevent


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Pediatrics_Nelson. if the mother’s viral load is >400 copies/mL or is unknown ( http://aidsinfo.nih.gov/ contentfiles/lvguidelines/peri_recommendations.pdf ). Scheduled cesarean section at 38 weeks to prevent vertical transmission is recommended for women with HIV RNA levels greater than 1000 copies/mL, but it is unclear whether cesarean section is beneficial when viral load is less than 1000 copies/mL or when membranes have already ruptured.


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Pediatrics_Nelson. Preventing HIV infection in adults decreases the incidence of infection in children. Adult prevention results from behavior changes such as safe-sex practices, decrease in intravenous drug use, and needle exchange programs. Prevention of pediatric AIDS includes avoidance of pregnancy and breastfeeding (in developed countries) in high-risk women. Screening of blood donors has almost eliminated the risk of HIV transmission from blood products. HIV infection almost never is transmitted in a casual or nonsexual household setting. Feigin RD, Cherry J, Demmler GJ, et al: Textbook of Pediatric Infectious Diseases, ed 6, Philadelphia, 2009, Saunders Isaacs D: Evidence-based Pediatric Infectious Disease, Malden, MA, 2007, Kliegman RM, Stanton BF, Behrman RE, et al: Nelson Textbook of Pediatrics, ed 19, Philadelphia, 2007, Saunders Long SS, Pickering LK, Prober CG: Principles and Practice of Pediatric Infec tious Diseases, ed 4, Philadelphia, 2012, Churchill Livingstone


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Pediatrics_Nelson. Long SS, Pickering LK, Prober CG: Principles and Practice of Pediatric Infec tious Diseases, ed 4, Philadelphia, 2012, Churchill Livingstone Pickering LK, Baker CJ, Long SS, et al: Red Book: 2012 Report of the Com mittee on Infectious Diseases, ed 27, Elk Grove Village, IL, 2012, American Academy of Pediatrics Plotkin SA, Orenstein WA, Offit PA: Vaccines, ed 5, Philadelphia, 2008, The Digestive System Warren P. Bishop and Dawn R. Ebach 17 After identifying the major gastrointestinal (GI) symptom, onset and progression should be determined (improved, unchanged, worsening). Characterization of signs and symptoms should identify factors such as triggers; actions that alleviate the symptom; timing, frequency and duration of symptoms; relationship to meals and defecation; and associated symptoms (e.g., fever or weight loss). Other key history includes exposures to others (family, school contacts), travel, environmental exposure, and impact of illness on the child (school absences).


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Pediatrics_Nelson. The history may suggest a diagnosis and direct the evaluation, which should include a full examination as well as a thorough abdominal examination. Extraintestinal disorders may produce GI manifestations (e.g., emesis with group A streptococcal pharyngitis, abdominal pain with lower lobe pneumonia). The examination should begin with a careful external inspection for abdominal distention, bruising or discoloration, abnormal veins, jaundice, surgical scars, and ostomies. Abnormalities of intensity and pitch of bowel sounds can occur with bowel obstruction. When palpating for tenderness, the examiner should note location, facial expression, guarding, and rebound tenderness. Palpation can also detect enlargement of the liver or spleen as well as feces and masses. If detected, organomegaly should be measured (with a tape measure), noting abnormal firmness or contour. A rectal examination, including inspection for fissures, skin tags, abscesses, and fistulous openings, should be performed


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Pediatrics_Nelson. be measured (with a tape measure), noting abnormal firmness or contour. A rectal examination, including inspection for fissures, skin tags, abscesses, and fistulous openings, should be performed for children with history suggesting constipation, GI bleeding, abdominal pain, chronic diarrhea, and suspicion of inflammatory bowel disease (IBD). Digital rectal examination should include assessment of anal sphincter tone, anal canal size and elasticity, tenderness, extrinsic masses, presence of fecal impaction, and caliber of the rectum. Stool should be tested for occult blood.