Hepatitis viruses Leishmaniasis Leptospirosis Malaria disseminated other arboviruses in intravascular coagulation the same class) Serology testing Serology testing Acute hepatitis A and B: supportive Chronic hepatitis C: Ledipasvir, sofosub specific antiviral agents, +/– ribavirin Direct visualization of Visualization of Consultation with CDC should be perfor protozoa from bone protozoa from bone Standard treatment involves pentavalent marrow aspirate marrow or splenic sodium stibogluconate; miltefosine an aspiration Serology if other diagnostic also been used tests unavailable Serology not useful for cutaneous form Ancillary for visceral form: marrow suppression, elevated hepatic transaminases, hypoalbuminemia, hypergammaglobulinemia PCR, culture, or PCR is sensitive and Penicillin or ampicillin for severe diseas immunohistochemical continues to be Doxycycline or amoxicillin for mild dise staining (culture is positive even after also recommended for prophylaxis sensitive and slow) initiation of therapy Need to monitor for Jarisch–Herxheimer Ancillary: can see Serology (microscopic initiation of therapy lymphocytic agglutination test, cerebrospinal fluid MAT) pleocytosis with elevated If sending blood protein and opening cultures, need to pressure; elevated hepatic notify laboratory to transaminases and hold culture for 2–4 bilirubin; urinalysis mo showing pyuria, proteinuria, and hematuria; elevated creatinine, creatine kinase, and amylase Thick, thin smear Thick smear: quantify Check CDC site for regions level of parasitemia (https://www.cdc.gov/malaria/traveler Anemia, thrombocytopenia, ) where parasites retain chloroquine su hypoglycemia, metabolic Thin smear: allows for acidosis, elevated speciation; presence P falciparum: creatinine, bilirubin, and of >1 ring form in a Atovaquone/Proguanil (Malarone) × d serum transaminases erythrocyte suggests Artemether-lumefantrine (Coartem) × Obtain type and screen P falciparum, the Quinine + (clindamycin or doxycycline) and G6PD level (need to species responsible Mefloquine (Larium) × doses know status before for most deaths Severe/complicated malaria: quinine + c treating with primaquine globally exchange transfusion considered for c for the hypnozoite form high-grade parasitemia seen in P vivax and ovale For vivax/ovale: atovaquone Proguanil ) If strongly suspect malaria, not withhold treatment if initial smears negative, simply repeat smears in 12–24 hrs Measles In a malaria-endemic region, low-grade parasitemia may not explain all a child’s symptoms Serology for IgM antibody Mumps Clinical diagnosis PCR and serology testing Neurocysticercosis CSF serology, characteristic neuroimaging: hypodense cysts with well-defined edges; can see edema as parasites die Ancillary: CSF eosinophilia Polio Culture of throat or stool (obtain two or more for enterovirus isolation obtained at least 24 hrs apart) Rabies Serology Ancillary tests of minimal value, except to exclude other causes of meningoencephalitis Salmonella typhi Stool culture for gastroenteritis Bone marrow culture or blood culture for those with enteric fever Salmonella, nontyphi Schistosomiasis Shigella Strongyloides Tuberculosis Serology for IgM antibody Supportive treatment Vitamin A once daily for days associat morbidity and mortality (WHO recom PCR and serology testing Supportive treatment Serology in CSF (serum serology cross-reacts with Echinococcus ) Utility of treatment if cysts is controvers associated with acute inflammation Use of albendazole or praziquantel with Culture of throat or stool Supportive Serology Supportive care, but prognosis dismal on Visualization of Negri bodies on cerebellar or nape of neck biopsies Stool culture Supportive if asymptomatic or uncompli gastroenteritis Ampicillin, amoxicillin, or trimethoprim susceptible strains For invasive disease, empiric treatment w spectrum cephalosporin, azithromycin Conventional stool culture Stool culture Ceftriaxone or azithromycin if need trea mo old, immunocompromised host (in hemoglobinopathies) Identification of eggs in Identification of eggs Praziquantel (most effective against adul stool (S mansoni or immature stages, so retreatment after Serology does not japonicum ) or urine (S differentiate acute hematobium ) and chronic Eosinophilia infection Conventional stool culture Stool culture Fluid resuscitation Ancillary: leukocytosis with Azithromycin or Ceftriaxone daily for bandemia is common Stool to detect larvae (often Visualization of larvae Ivermectin is treatment of choice by WH need to obtain multiple in stool Also used: mebendazole stool samples) Watch for anaphylaxis during treatment patients Respiratory specimen (expectorated sputum, induced sputum, or Most children will have negative cultures, and Multidrug therapy (isoniazid, rifampin, p ethambutol) administered via directly gastric aspirate) for acidfast culture; additional cultures if extrapulmonary TB is suspected Ancillary: tuberculin skin test, interferon gamma release assay (IGRA), chest radiograph; check for HIV Yellow fever Serology Ancillary: thrombocytopenia, elevated PT, PTT, hyperbilirubinemia, prolonged elevation of hepatic transaminases diagnosis is made on Consultation with specialists in pediatric the basis of (1) given infrequency of diagnosis in chil consistent clinical States and radiographic findings, (2) epidemiologic link to a source case, (3) immunologic evidence of TB (skin test, IGRA), and exclusion of other diagnoses Serology Supportive Patients who received Avoid nonsteroidal anti-inflammatories yellow fever vaccine can have an elevated IgM for several years; cross-reaction with other flaviviruses can be seen CDC, Centers for Disease Control and Prevention; PCR, polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; CSF, cerebrospinal fluid; EKG, electrocardiogram; TB, tuberculosis; HIV, human immunodeficiency virus; DIC, disseminated intravascular coagulation; G6PD, glucose-6phosphate dehydrogenase; WHO, World Health Organization In the next section, six major diseases or syndromes will be reviewed: malaria, tuberculosis, typhoid, dengue, chikungunya, and diarrheal diseases Other infections will then be organized based on the primary organ system involved HIV will be covered at the end of this chapter Malaria CLINICAL PEARLS AND PITFALLS Persons returning to their native countries (VFRs) are at particular risk for malaria, since many fail to take the necessary precautions either to avoid insect exposure or to take prophylaxis Malaria should be considered in the differential diagnosis of any febrile child who has returned from a malaria-endemic region in the preceding month; one negative blood smear should not lead the PEM provider to rule out malaria Chloroquine resistance is widespread, and this drug should not be used as empiric therapy for the ill child with suspected malaria Current Evidence Malaria is the most important parasitic disease of man with prevalence estimated to be over 200 million with almost 500,000 deaths each year, most of whom are children The majority of morbidity and mortality is due to Plasmodium falciparum Malaria is endemic throughout tropical regions worldwide; in 2017, 90 countries were malaria-endemic, and over billion persons were at risk of malaria The most common species worldwide are Plasmodium vivax, prevalent on the Indian subcontinent and in Central America, and P falciparum, prevalent in Africa and in Papua New Guinea High-risk regions include sub-Saharan Africa, Papua New Guinea, the Solomon Islands, and Vanuatu Approximately 40% of the reported cases of malaria in the United States are from foreign travelers Infections with P falciparum can progress rapidly, some fatally, and must be considered in the differential diagnosis in all febrile children who have recently visited an endemic region Approximately 90% of P falciparum infections are acquired in sub-Saharan Africa, and up to 90% of travelers who are infected begin to have symptoms within month after their return In contrast to P falciparum infections, travelers infected with P vivax and Plasmodium ovale may show symptoms several months to years after exposure Seventy percent of P vivax infections are acquired in Asia or Latin America Chloroquine-sensitive malaria exists in Central America as well as the Caribbean and limited parts of South America There are regions that have developed chloroquine and mefloquine (Lariam) resistance, specifically in Southeast Asia It is vital for the clinician to ask about not only if malaria prophylaxis was taken but also the medication and how it was administered Both chloroquine and mefloquine kill the parasite only in the hematogenous phase; it is thus vital to take these medications for weeks upon leaving the endemic region Early termination of these medications could result in malaria even in someone who was “taking prophylaxis.” Bed nets are effective as the mosquito vector is a night-time feeder Goals of Treatment The goal of treatment is for the clinician to rapidly recognize that the febrile child returning from a malariaendemic region should be evaluated for plasmodial infection and that empiric antimalarial therapy, even in the absence of a positive blood smear, should be initiated for the toxic-appearing child Clinical Considerations Clinical recognition: The most common symptoms of malaria are fever, malaise, headache, myalgia, vomiting, and diarrhea Signs include pyrexia, tachycardia, tachypnea, dehydration, pallor, splenomegaly, and icterus While the frequency and spectrum of complications differ among the plasmodial species ( e-Table 94.15 ), signs and symptoms cannot differentiate between species The malaria species and degree of parasitemia will affect the types and degree of symptoms that are displayed Severe malaria is defined as shock, acidosis, hypoglycemia, end-organ involvement (e.g., CNS, renal), and/or parasitemia exceeding 5% of erythrocytes Triage considerations: Given the constellation of symptoms, malaria should be considered in all febrile travelers almost regardless of their clinical presentation Clinical assessment: The blood smear is considered the diagnostic reference standard Both thick and thin smears should be obtained Thick smears allow for a much larger volume of blood to be examined and thus for the detection of smaller numbers of parasites (leading to increased sensitivity), while the thin smear will allow for the identification of the species and the percentage of affected red blood cells If the initial blood films are negative for malaria and the disease is still clinically suspected, examination of the thick and thin smears should be repeated at least once within 12 to 24 hours after the initial evaluation One negative blood smear should not cause the clinician to exclude malaria from the differential diagnosis In malaria-endemic areas, many children have lowlevel parasitemia It is therefore important to consider other pathogens when children are found to have low-grade parasitemia on blood smear Thrombocytopenia without leukocytosis is a characteristic feature of malaria, as is splenomegaly Rapid assays for malaria are also available In laboratories where personnel may be less familiar with performing blood smears, these rapid assays may be far superior to blood smears Management: Malaria is a reportable disease to the U.S CDC Empiric treatment should be decided upon in consultation with an ID specialist Most children with malaria treated in the United States are admitted for treatment Empiric therapy is based upon the disease severity, the species, and data regarding drug resistance in different geographic regions Children with severe malaria should be admitted to an intensive care unit for monitoring and because some children will require exchange transfusion (if parasitemia exceeds 10% or there is evidence of cerebral or renal involvement) These children should receive parenteral therapy (clindamycin with either IV quinine or quinidine; artesunate is a newer parenteral regimen and is likely to be used more frequently as IV quinidine becomes less available) Blood smears should be repeated after therapy is initiated to evaluate response to therapy and need for additional interventions Primaquine is needed to kill the dormant phase seen in P vivax and P ovale infections to prevent relapse Prior to use of primaquine, patients need to be screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency (primaquine can cause hemolytic anemia in patients with G6PD); women of child-bearing age also need to be screened for pregnancy (primaquine is a potential teratogen) Both chloroquine and quinidine are available in intravenous preparations from the CDC Standard precautions are used for patients with malaria Tuberculosis CLINICAL PEARLS AND PITFALLS ... prolonged elevation of hepatic transaminases diagnosis is made on Consultation with specialists in pediatric the basis of (1) given infrequency of diagnosis in chil consistent clinical States and