John J. Manaloor

Travel-Related Infections in Children

Malaria, diarrhea, respiratory infections, and cutaneous larva migrans are common travel-related infections observed in children and adolescents returning from trips to developing countries. Children visiting friends and relatives are at the highest risk because few visit travel clinics before travel, their stays are longer, and the sites they visit are more rural. Clinicians must be able to prepare their pediatric-age travelers before departure with preventive education, prophylactic and self-treating medications, and vaccinations. Familiarity with the clinical manifestations and treatment of travel-related infections will secure prompt and effective therapy.

Malassezia Pneumonia: A Rare Complication of Parenteral Nutrition Therapy.

Malassezia species (formerly known as Pityrosporum) are part of normal human skin flora and have been associated with benign dermatologic conditions, such as seborrheic dermatitis and tinea versicolor. In rare cases, however, Malassezia has been associated with systemic disease in immunocompromised patients and infants in the neonatal intensive care unit. Malassezia species require long-chain fatty acids for growth and therefore have a known predilection for individuals receiving lipid containing intravenous parenteral nutrition (PN). Systemic infections are characterized by prolonged fevers and illness but can include nonspecific signs and symptoms. We present the diagnosis and management of a rare case of an immunocompetent, nonneonatal, PN-dependent child with Malassezia furfur pneumonia.

Success With Extended-Infusion Meropenem After Recurrence of Baclofen Pump-Related Achromobacter Xylosoxidans Meningitis in an Adolescent

A 13-year-old female experienced a recurrence of baclofen pump-related central nervous system (CNS) infection caused by Achromobacter, despite absence of retained foreign material. Due to the failure of meropenem (120 mg/kg/d in divided doses every 8 hours and infused over 30 minutes) in the initial infection, the dose was infused over 4 hours during the recurrence. Meropenem is an antibiotic for which efficacy is time dependent, and 4-hour versus 30-minute infusions have been shown to prolong the time the concentration of the antibiotic exceeds the minimum inhibitory concentration (MIC) of the organism at the site of infection (T>MIC). Meropenem serum concentrations were obtained and indicated that T>MIC was at least 75% of the dosing interval. Our patient improved with no noted recurrences or adverse effects on the extended-infusion meropenem regimen. Utilization of extended-infusion beta-lactam dosing whenever possible in the treatment of serious infections caused by gram-negative organisms should be considered, as this dosing appears to be safe and improves the probability of achieving pharmacokinetic/pharmacodynamic goals.

Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady

Background. Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum. Methods. A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV+ subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data. Results. Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis. Conclusions. This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD.

Photo Quiz: Diarrhea and Fever in a Child Returning from Africa

A previously healthy 22-month-old African-American female presented with a 5-day history of diarrhea and fever that had begun immediately upon return from a 2.5-month-long stay in Niger. She had been evaluated at an outpatient clinic, where she was found to be dehydrated, so she was given

16S rRNA deep sequencing identifies Actinotignum schaalii as the major component of a polymicrobial intra-abdominal infection and implicates a urinary source

Introduction. It can be difficult to catalogue the individual organisms comprising polymicrobial patient infections, both because conventional clinical microbiological culture does not facilitate the isolation and enumeration of all members of a complex microbial community, and because fastidious organisms may be mixed with organisms that grow rapidly in vitro. Empiric antimicrobial treatment is frequently employed based on the anatomical site and the suspected source of the infection, especially when an appropriately collected surgical specimen is not obtained. Case presentation. We present a case of an intra-abdominal infection in a patient with complex anatomy and recurrent urinary tract infections. Imaging did not reveal a clear source of infection, no growth was obtained from urine cultures and initial abdominal fluid cultures were also negative. In contrast, 16S rRNA deep sequencing of abdominal fluid samples revealed mixed bacterial populations with abundant anaerobes, including Actinotignum schaalii (Actinobaculum schaalii). Ultimately, only Enterobacter cloacae complex and meticillin-resistant Staphylococcus aureus, both of which were identified by sequencing, were recovered by culture. Conclusion. The clinical application of 16S rRNA deep sequencing can more comprehensively and accurately define the organisms present in an individual patients polymicrobial infection than conventional microbiological culture, detecting species that are not recovered under standard culture conditions or that are otherwise unexpected. These results can facilitate effective antimicrobial stewardship and help elucidate the possible origins of infections.

Hepatitis A, B, and C

1. John C. Christenson, MD* 2. John J. Manaloor, MD* 1. *Ryan White Center for Pediatric Infectious Disease and Global Health, Indiana University School of Medicine, Riley Hospital for Children, Indianapolis, IN. Because hepatitis A, B, and C viruses are responsible for substantial morbidity and mortality, clinicians must learn to recognize, treat and prevent infections caused by these viruses. After completing this article, readers should be able to: 1. Describe the epidemiology of hepatitis A, B, and C virus infections. 2. Recognize the clinical features of hepatitis A infection. 3. Appropriately administer vaccines for the prevention of hepatitis A and B infection. 4. Recognize the various antiviral regimens used for the treatment of hepatitis B and C liver disease. 5. Order the most appropriate tests for the diagnosis of hepatitis virus infections. During the past 30 years, the understanding of hepatitis viruses has greatly expanded. Knowledge of hepatitis has progressed from merely describing the various clinical syndromes to a greater understanding of the pathogenesis of disease caused by these viruses and the development of chronic infection that eventually leads to cirrhosis or hepatocellular carcinoma. Expanded understanding also has led to the development of effective vaccines against hepatitis A virus (HAV) and hepatitis B virus (HBV) and antiviral therapies against hepatitis C virus (HCV). The introduction of routine vaccination against HAV and HBV starting in early childhood in the United States has resulted in a substantial decrease in both of these infections in children and the subsequent complications of HBV-related chronic liver disease. Effective screening of mothers during pregnancy and the administration of HBV vaccine soon after birth, along with administration of hepatitis B immune globulin (HBIG) to infants born to women who have HBV infection, has led to near eradication of perinatally acquired HBV disease in the United States and other countries with effective screening programs. The introduction …

Case 2: Shoulder Pain in 7-year-old Girl

1. Ashley L. Scheffer, MD* 2. Palka R. Patel, MD† 3. John J. Manaloor, MD‡ 1. *Department of Child Health, University of Arizona College of Medicine-Phoenix; Department of Pediatric Critical Care, Phoenix Childrens Hospital, Phoenix, AZ 2. †Uganda Site Director, Global Primary Care Program, MGH Global Health, Massachusetts General Hospital, Boston, MA 3. ‡Clinical Pediatrics; Pediatric Antimicrobial Stewardship Program, Ryan White Center for Pediatric Infectious Diseases and Global Health, Riley Hospital for Children, Indiana University School of Medicine, Indianapolis, IN A previously healthy, fully vaccinated 7-year-old girl presents with a 3-day history of pain in her right shoulder, refusal to move her right arm, and temperature to 39.4°C (103°F). She complains of pain at the superior and posterior areas of her right shoulder, over her right scapula, and at the right lateral chest in the mid-axillary area. She maintains her neck in a slightly flexed and laterally rotated position. The review of systems is otherwise negative. She is eating and drinking well and denies sweats, chills, malaise, or antecedent viral respiratory tract infection. She was evaluated 2 days earlier for the same symptoms. At that time, the right shoulder and arm had no abnormalities and she had full range of motion of the right shoulder. The radiograph of the right shoulder was read as normal. She was discharged from the urgent care facility with a diagnosis of muscle strain and a recommendation to use ibuprofen as needed for pain. On physical examination today, her temperature is 39.4°C (102.9° F), heart rate is 130 beats per minute, and respiratory rate is 14 breaths per minute. She appears anxious and remains very still on the examination table. She maintains a rigid posture when sitting up, keeping her neck slightly flexed and rotated to the right. She refuses to move her shoulder. One hour after provision of acetaminophen, clinicians elicit full passive range of motion of her right shoulder but she continues to refuse active range of motion. Upon examination of the neck, 5 to 10 degrees of active motion in any direction is elicited. Her gait is normal. Aside from tachycardia, …

Pediatric Kawasaki Disease and Adult HIV Kawasaki-like Syndrome Are Likely the Same Malady

Background. Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum. Methods. A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV+ subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data. Results. Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis. Conclusions. This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD.

Editor's choice: Pediatric Kawasaki Disease and Adult Human Immunodeficiency Virus Kawasaki-Like Syndrome Are Likely the Same Malady

Background. Pediatric Kawasaki disease (KD) and human immunodeficiency virus (HIV)+ adult Kawasaki-like syndrome (KLS) are dramatic vasculitides with similar physical findings. Both syndromes include unusual arterial histopathology with immunoglobulin (Ig)A+ plasma cells, and both impressively respond to pooled Ig therapy. Their distinctive presentations, histopathology, and therapeutic response suggest a common etiology. Because blood is in immediate contact with inflamed arteries, we investigated whether KD and KLS share an inflammatory signature in serum. Methods. A custom multiplex enzyme-linked immunosorbent assay (ELISA) defined the serum cytokine milieu in 2 adults with KLS during acute and convalescent phases, with asymptomatic HIV+ subjects not taking antiretroviral therapy serving as controls. We then prospectively collected serum and plasma samples from children hospitalized with KD, unrelated febrile illnesses, and noninfectious conditions, analyzing them with a custom multiplex ELISA based on the KLS data. Results. Patients with KLS and KD subjects shared an inflammatory signature including acute-phase reactants reflecting tumor necrosis factor (TNF)-α biologic activity (soluble TNF receptor I/II) and endothelial/smooth muscle chemokines Ccl1 (Th2), Ccl2 (vascular inflammation), and Cxcl11 (plasma cell recruitment). Ccl1 was specifically elevated in KD versus febrile controls, suggesting a unique relationship between Ccl1 and KD/KLS pathogenesis. Conclusions. This study defines a KD/KLS inflammatory signature mirroring a dysfunctional response likely to a common etiologic agent. The KD/KLS inflammatory signature based on elevated acute-phase reactants and specific endothelial/smooth muscle chemokines was able to identify KD subjects versus febrile controls, and it may serve as a practicable diagnostic test for KD.