Actionable diagnosis of neuroleptospirosis by next-generation sequencing.

A 14-year-old boy with severe combined immunodeficiency presented three times to a medical facility over a period of 4 months with fever and headache that progressed to hydrocephalus and status epilepticus necessitating a medically induced coma. Diagnostic workup including brain biopsy was unrevealing. Unbiased next-generation sequencing of the cerebrospinal fluid identified 475 of 3,063,784 sequence reads (0.016%) corresponding to leptospira infection. Clinical assays for leptospirosis were negative. Targeted antimicrobial agents were administered, and the patient was discharged home 32 days later with a status close to his premorbid condition. Polymerase-chain-reaction (PCR) and serologic testing at the Centers for Disease Control and Prevention (CDC) subsequently confirmed evidence of Leptospira santarosai infection.

Safety and Treatment Outcomes of Infants and Children Treated With Daptomycin: Six-Year Experience From a Pediatric Academic Medical Center.

Daptomycin is a common treatment for serious infections caused by gram-positive bacteria in adult patients; however, data regarding its safety and efficacy in the pediatric population are limited. This was a retrospective chart review of adverse reactions and treatment outcomes associated with daptomycin use in children <13 years old who received at least 1 dose of daptomycin. At least 1 dose of daptomycin was received by 147 patients. Seventy-two patients received daptomycin for 5 or more days. New-onset loose stools on daptomycin initiation were reported for 14 (9.5%) patients, elevations in creatine kinase in 3 (2%) patients, and elevated aspartate transaminase and alanine transaminase in 13 (8.8%) and 9 (6.1%) patients, respectively. Two patients (1.4%) had daptomycin discontinued due to specific concerns for adverse drug reactions. Daptomycin was found to be safe and effective in this pediatric cohort that included young children and infants with a variety of types and severities of infections.

Remdesivir Use in Pediatric Patients for SARS-CoV-2 Treatment: Single Academic Center Study.

BACKGROUND: Millions of children in the United States have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with many infections leading to hospitalization. For pediatric patients, especially younger children, treatment options are limited. Remdesivir has demonstrated a positive safety and efficacy profile in adults, but little data is published regarding remdesivir use in pediatric patients. Additional data for SARS-CoV-2 treatments in pediatric patients is required to prevent further SARS-CoV-2-related morbidity and mortality. At a single pediatric academic medical center, the safety and efficacy of remdesivir was evaluated. METHODS: A retrospective review of patients admitted to a pediatric academic medical center who received remdesivir over a 17-month period was completed. All pediatric patients who received at least 1 dose of remdesivir were included. Safety and efficacy were assessed using national organization's definitions of clinical improvement, bradycardia, hypertension, acute kidney injury and drug-induced liver injury. RESULTS: There were 48 pediatric patients included in this study with 29% of patients admitted to the pediatric intensive care unit. Less than one-third of patients received the full treatment course of remdesivir, with over half of patients not completing therapy due to symptomatic improvement or hospital discharge. Majority of patients required some level of supplemental oxygen support. The median World Health Organization score was consistent throughout all 5 days of therapy. No patients experienced significant bradycardia, hypertension, acute kidney injury, or drug-induced liver injury. CONCLUSIONS: Remdesivir may correlate with clinical stability or improvement and demonstrates safety when used in pediatric patients. A randomized controlled trial is needed to confirm these findings.

Comprehensive Care Improvement for Oncologic Fever and Neutropenia from a Pediatric Emergency Department.

Introduction: Rapid time to antibiotics (TTA) for pediatric patients with fever and neutropenia in an emergency department decreases in-hospital mortality. Additionally, national guidelines recommend outpatient antibiotic management strategies for low-risk fever and neutropenia (LRFN). This study had two specific aims: (1) improve the percent of patients with suspected fever and neutropenia who receive antibiotics within 60 minutes of arrival from 55% to 90%, and (2) develop and operationalize a process for outpatient management of LRFN patients by October 2018. Methods: Using Lean methodologies, we implemented Plan-Do-Check-Act cycles focused on guideline development, electronic medical record reminders, order-set development, and a LRFN pathway as root causes for improvements. We used statistical process control charts to assess results. Results: The project conducted from July 2016 to October 2018 showed special cause improvement in December 2016 on a G-chart. Monthly Xbar-chart showed improvement in average TTA from 68.5 minutes to 42.5 minutes. A P-chart showed improvement in patients receiving antibiotics within 60 minutes, from 55% to 86.4%. A LRFN guideline and workflow was developed and implemented in October 2017. Conclusions: Implementation of guidelines, electronic medical record reminders, and order sets are useful tools to improve TTA for suspected fever and neutropenia. Utilizing more sensitive statistical process control charts early in projects with fewer patients can help recognize and guide process improvement. The development of workflows for outpatient management of LRFN may be possible, though it requires further study.

The HIV-Infected Adolescent.

HIV-infected adolescents represent a unique, yet diverse, population requiring specialized medical and psychosocial HIV care. Perinatally infected and behaviorally infected adolescents often have differing therapeutic needs, but may share common difficulties, including medication nonadherence, high-risk sexual behavior, psychosocial stressors, and concomitant psychiatric disorders. Addressing these needs within a culturally sensitive framework and in the context of a population-specific approach to treatment is paramount to optimizing care. Harm reduction for this group to maximize their health and limit HIV transmission to others is also critical with respect to the rising incidence of newly diagnosed HIV-positive adolescents. Implementing a formal, multidisciplinary program that involves individual youths and their families for improved transition to adult HIV care will afford such adolescents a better chance for a healthy adulthood.

Assessing Medical Neglect in HIV-Exposed or Infected Children.

Human Immunodeficiency Virus (HIV) causes a chronic illness requiring lifelong medical care to prevent opportunistic infections and death. It is important to identify medical neglect in children that are perinatally exposed to or living with human immunodeficiency virus and to take steps to prevent it. Diagnosis of medical neglect must be considered in the context of the caregivers' understanding of the risks of harm, and the logistical, cultural and social factors that may influence their actions or non-actions. When medical neglect as failure of treatment or prevention of infection is suspected, medical providers should work collaboratively with caregivers to assess and address barriers to adherence and to provide resources and support. Medical neglect may be diagnosed if repeated preventive efforts fail.

Vaccine-Strain Herpes Zoster Ophthalmicus in a 14-month-old Boy Prompting an Immunodeficiency Workup: Case Report and Review of Vaccine-strain Herpes Zoster.

We present a case of herpes zoster ophthalmicus in an otherwise healthy 14-month-old male associated with vaccine-strain varicella-zoster virus 11 weeks after monovalent varicella vaccine administration. Herpes zoster ophthalmicus, especially in the setting of familial immunoglobulin A deficiency, prompted further immunologic workup. A high index of suspicion is necessary for timely diagnosis and treatment of vaccine-strain herpes zoster.

Defective IL-2 production by HIV-1-specific CD4 and CD8 T cells in an adolescent/young adult cohort.

Here we investigate the effect of viremia and the influence of HAART on the frequency and quality of HIVspecfic T cells in an adolescent/young adult cohort. Measurements of viral loads and the magnitude and quality of antiviral cellular immune responses were performed on 14 HAART-naive and 8 treated HIV-1-infected adolescents. Cross-sectional correlations between viral load and cellular immune responses were determined and data were analyzed by viral load (<4000, 4000-40,000, and >40,000 copies/ml plasma) and patient treatment status. All 22 patients showed a broad IFN-gamma ELISPOT response that was proportional to viral load (r = 0.53, p = 0.02), recognizing an average of five to eight peptide pools throughout Gag, Pol, Env, Tat, Rev, and Nef. Intracellular cytokine staining was performed with pools of overlapping peptides corresponding to HIV Gag to distinguish CD8 response from CD4 response. Among untreated patients with increased viral load there was a constant IFN-gamma CD8 response but a declining IFN-gamma CD4 response. HIV-specific IL-2 production was consistently low in CD8 cells but inversely related to viral load in CD4 cells (r = -0.52, p = 0.02). In this crosssectional analysis, time on HAART was associated with an increased frequency of antiviral IFN-gamma- and IL-2-coproducing CD4 cells (r = 0.98, p <0.001), but not of antiviral CD8 cells. Our results suggest that T cells coproducing IL-2 and IFN-gamma are a better marker for immunological competence than T cells producing IFN-gamma alone. They also suggest that HAART may be associated with an improved capacity for IL-2 production by antiviral CD4 T cells in a time-dependent manner. Longitudinal studies are clearly necessary to assess the impact of HAART on these parameters.

Rapid review of liquid-based smears as a quality control measure.

The objective of this study was to investigate the effectiveness of a standardized method of rapid review (RR) of monolayer preparations for the identification of abnormalities, the presence of an endocervical component and infectious agents. A total of 200 ThinPrep (Cytyc, Boxborough, MA) slides representing the spectrum of abnormalities commonly encountered in cervical/vaginal cytologic specimens was retrieved from archive. The study set comprised 129 cases within normal limits (WNL); 36 low-grade epithelial abnormalities (LGEA); 28 high-grade epithelial abnormalities (HGEA), including 2 endocervical adenocarcinomas in situ (AIS) and 7 carcinomas. Eighteen false negative (FN) cases were also included for study. Originally missed on initial review, these cases were found to be abnormal on quality control review (17 LGEA; 1 AIS). Commonly encountered infectious agents were represented and included Candida albicans, Trichomonas vaginalis, herpes simplex virus, and Actinomyces. The slides were reviewed using a standardized method of RR (turret technique, for 60 sec) by three experienced screeners masked to the original reference diagnosis. Median sensitivity for LGEA was 70% (range, 67-72%); HGEA, 69% (range, 54-80%); and FN, 65% (range, 56-78%). Specificity remained high, median specificity for LGEA was 95%; HGEA, 97%; and FN, 100%. There was no significant overcalling of any diagnostic category. The chi-square test at P < 0.05 showed no significant difference between RR and full manual rescreen of the ThinPrep smears in this study. While no statistical difference was proven, the sensitivity measurements for all categories of abnormality were moderate due to the high proportion of atypical cases included into the study set. Abnormalities on the monolayer preparations frequently displayed fewer, smaller groups of disaggregated cells with rounded cytoplasmic outlines that were difficult to discern on RR. Interobserver variation was noted. Monolayers with a paucity of diagnostic cells and those displaying subtle nuclear atypia were often overlooked.

Premastication as a route of pediatric HIV transmission: case-control and cross-sectional investigations.

BACKGROUND: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown. METHODS: During December 2009 to February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at 6 HIV clinics using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation. RESULTS: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared with 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 to 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age and had been used to feed children aged 1-36 months. CONCLUSIONS: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and health care providers should educate the public about the potential risk of disease transmission via premastication.

Reasons for testing and clinical and demographic profile of adolescents with non-perinatally acquired HIV infection.

OBJECTIVES: We sought to examine the demographic, clinical, and behavioral characteristics; reasons for HIV testing; and factors that contribute to delays in entry into specialized HIV care after diagnosis of HIV infection among adolescents in an urban clinic in Georgia. METHODS: All of the data for this study were obtained solely by medical chart review. Demographic, clinical, behavioral, and HIV testing data were abstracted from medical charts of 59 non-perinatally HIV-infected adolescents who were aged 13 to 18 years and entered care at the pediatric and adolescent HIV clinic of a Georgia hospital during 1999-2002. HIV-infected adolescents were compared by demographic, clinical, and behavioral characteristics as well as by circumstances surrounding HIV testing. Recent seroconversion was defined as having a documented negative or indeterminate HIV antibody test (confirmed) or a self-reported negative HIV test (probable) < or =6 months before HIV diagnosis. RESULTS: Of 59 HIV-infected adolescents, 35 (59%) were female and 56 (95%) were black/African American. Fifteen (25%) had > or =1 sexually transmitted infection when they entered care. All female (vs 38% male) adolescents were infected through heterosexual sexual intercourse; 9 (26%) were pregnant at the time of HIV diagnosis. Adolescents whose HIV was diagnosed at non-health care facilities entered HIV care much later than adolescents whose HIV was diagnosed at health care facilities (median: 108 vs 25 days). Approximately one half of adolescents had CD4+ T-cell counts <350 cells per microL and/or HIV-1 viral loads >55,000 copies per mL at entry into care. Twenty-seven (46%) adolescents had a previous negative HIV test; 7 had confirmed recent seroconversion, and 3 had probable recent seroconversion. Among adolescents with a documented reason for testing, routine medical screening was the most frequent reason for HIV testing; few adolescents were documented as having self-initiated HIV testing. CONCLUSIONS: Strategies are needed to implement timely linkage to medical services of adolescents who receive a diagnosis of HIV infection at non-health care facilities and to increase HIV testing, prevention efforts, and recognition of recent HIV infection among sexually active adolescents.