Elizabeth Secord

Newborn Screening for Severe Combined Immunodeficiency in 11 Screening Programs in the United States

IMPORTANCE Newborn screening for severe combined immunodeficiency (SCID) using assays to detect T-cell receptor excision circles (TRECs) began in Wisconsin in 2008, and SCID was added to the national recommended uniform panel for newborn screened disorders in 2010. Currently 23 states, the District of Columbia, and the Navajo Nation conduct population-wide newborn screening for SCID. The incidence of SCID is estimated at 1 in 100,000 births. OBJECTIVES To present data from a spectrum of SCID newborn screening programs, establish population-based incidence for SCID and other conditions with T-cell lymphopenia, and document early institution of effective treatments. DESIGN Epidemiological and retrospective observational study. SETTING Representatives in states conducting SCID newborn screening were invited to submit their SCID screening algorithms, test performance data, and deidentified clinical and laboratory information regarding infants screened and cases with nonnormal results. Infants born from the start of each participating program from January 2008 through the most recent evaluable date prior to July 2013 were included. Representatives from 10 states plus the Navajo Area Indian Health Service contributed data from 3,030,083 newborns screened with a TREC test. MAIN OUTCOMES AND MEASURES Infants with SCID and other diagnoses of T-cell lymphopenia were classified. Incidence and, where possible, etiologies were determined. Interventions and survival were tracked. RESULTS Screening detected 52 cases of typical SCID, leaky SCID, and Omenn syndrome, affecting 1 in 58,000 infants (95% CI, 1/46,000-1/80,000). Survival of SCID-affected infants through their diagnosis and immune reconstitution was 87% (45/52), 92% (45/49) for infants who received transplantation, enzyme replacement, and/or gene therapy. Additional interventions for SCID and non-SCID T-cell lymphopenia included immunoglobulin infusions, preventive antibiotics, and avoidance of live vaccines. Variations in definitions and follow-up practices influenced the rates of detection of non-SCID T-cell lymphopenia. CONCLUSIONS AND RELEVANCE Newborn screening in 11 programs in the United States identified SCID in 1 in 58,000 infants, with high survival. The usefulness of detection of non-SCID T-cell lymphopenias by the same screening remains to be determined.

Using motivational interviewing in HIV field outreach with young african american men who have sex with men: A randomized clinical trial

OBJECTIVES We sought to determine whether field outreach with motivational interviewing, as compared with traditional field outreach, leads to increases in HIV counseling and testing and rates of return for test results among young African American men who have sex with men (MSM). METHODS In a randomized, 2-group, repeated-measures design, 96 young African American MSM completed a motivational interviewing-based field outreach session and 92 young African American MSM completed a traditional field outreach session. The percentages of participants agreeing to traditional HIV counseling and testing (an oral swab of the cheek) and returning for test results were the primary outcome measures. RESULTS More of the participants in the motivational interviewing condition than the control condition received HIV counseling and testing (49% versus 20%; chi(2)(1) = 17.94; P = .000) and returned for test results (98% versus 72%; chi(2)(1) = 10.22; P = .001). CONCLUSIONS The addition of motivational interviewing to field outreach is effective in encouraging high-risk young African American MSM to learn their HIV status. Also, peer outreach workers can be effectively trained to reduce health disparities by providing evidence-based brief counseling approaches targeting high-risk minority populations.

Update on the use of immunoglobulin in human disease: A review of evidence.

&NA; Human immunoglobulin preparations for intravenous or subcutaneous administration are the cornerstone of treatment in patients with primary immunodeficiency diseases affecting the humoral immune system. Intravenous preparations have a number of important uses in the treatment of other diseases in humans as well, some for which acceptable treatment alternatives do not exist. We provide an update of the evidence‐based guideline on immunoglobulin therapy, last published in 2006. Given the potential risks and inherent scarcity of human immunoglobulin, careful consideration of its indications and administration is warranted.

IgE against HIV proteins in clinically healthy children with HIV disease

Elevated serum Ige was detected in 26% (7 of 30) of children with HIV infection. The majority of children with elevated IgE were of one ethnic group (Puerto Rican) (4 of 7), compared with only 9% (2 of 23) in the normal to low IgE group (p = 0.02). Most of the children with elevated IgE had decreased circulating CD4+ T cells (5 of 7 or 71%); but none had opportunistic infections, and none failed to thrive. Although similar numbers of children with normal to low IgE had decreased circulating CD4+ T cells (19 of 23 or 83%), this group had opportunistic infections (6 of 23 or 26%) and failure to thrive (7 of 30 or 30%). There was no difference in incidence of allergic symptoms between groups. IgE antibody against HIV protein was detected by Western blot technique in the sera of three children with elevated serum IgE. Thus we have identified a group of children with HIV infection and elevated serum IgE of predominantly one ethnic group, who are without opportunistic infections or failure to thrive, some of whom produce HIV-specific IgE. This suggests that IgE may play a protective (perhaps late compensatory) role in HIV disease in genetically predisposed individuals.

Atypical expiratory flow volume curve in an asthmatic patient with vocal cord dysfunction.

BACKGROUND Vocal cord dysfunction can coexist with or masquerade as asthma. Vocal cord dysfunction, when coexistent with asthma, contributes substantially to the refractory nature of the respiratory problem. OBJECTIVE To report a case of an asthmatic patient with vocal cord dysfunction and a previously unreported unique expiratory flow volume curve. RESULTS A 16-year-old female, known to have asthma, developed increased frequency of her asthma exacerbations. Spirometry, during symptoms, showed an extrathoracic airway obstruction with a reproducible unique abrupt drop and rise in the expiratory flow volume loop. Laryngoscopy showed adduction of the vocal cords during inspiration and expiration. CONCLUSIONS We report a unique expiratory flow volume curve in an asthmatic with vocal cord dysfunction that resolved with panting maneuvers. Speech and psychological counseling helped prevent future attacks.

Multisystemic therapy for high-risk African American adolescents with asthma: a randomized clinical trial.

OBJECTIVE The primary purpose of the study was to determine whether Multisystemic Therapy adapted for health care settings (MST-HC) improved asthma management and health outcomes in high-risk African American adolescents with asthma. METHOD Eligibility included self-reported African American ethnicity, ages 12 to 16, moderate to severe asthma, and an inpatient hospitalization or at least 2 emergency department visits for asthma in the last 12 months. Adolescents and their families (N = 170) were randomized to MST-HC or in-home family support. Data were collected at baseline and posttreatment (7 months) based on an asthma management interview, medication adherence phone diary, and lung function biomarker (forced expiratory volume in 1 s [FEV1]). Analyses were conducted using linear mixed modeling for continuous outcomes and generalized linear mixed modeling for binary outcomes. RESULTS In intent-to-treat analyses, adolescents randomized to MST-HC were more likely to improve on 2 of the measures of medication adherence and FEV1. Per-protocol analysis demonstrated that MST-HC had a medium effect on adherence measures and had a small to medium effect on lung function and the adolescents response to asthma exacerbations. CONCLUSION There are few interventions that have been shown to successfully improve asthma management in minority youth at highest risk for poor morbidity and mortality. MST, a home-based psychotherapy originally developed to target behavior problems in youth, improved asthma management and lung function compared to a strong comparison condition. Further follow-up is necessary to determine whether MST-HC reduces health care utilization accounting for seasonal variability. A limitation to the study is that a greater number of participants in the control group came from single-parent families than in the MST group.

ASTHMA IN IMMUNE-COMPETENT CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS

ASTHMA IN IMMUNE-COMPETENT CHILDREN WITH HUMAN IMMUNODEFICIENCY VIRUS Elevations of serum IgE and drug hypersensitivities have been commonly reported in patients with human immunodeficiency virus (HIV).1–6 Asthma, however, was rarely reported to occur in HIVinfected persons in the pre–antiretroviral therapy (ART) era.7 In the era of ART and immune reconstitution in HIV-infected individuals, there have been reports of increased incidence of asthma in patients with HIV.8 We report an overall increase in the incidence of asthma in our children infected with HIV and a correlation of asthma diagnosis with reconstitution of CD4 T cells after ART therapy in HIV-infected children. These findings are of interest to HIV practitioners who will be treating patients with increased asthma symptoms and who will be concerned about the competence of newly reconstituted T cells. The findings are of interest to allergists because of the implication that CD4 T cells are necessary for the localized inflammatory response in asthma. Patients were recruited from the Pediatric HIV Clinic at Children’s Hospital of Michigan, Detroit. The study was approved by the Human Investigation Committee of Wayne State University, Detroit, and written consent was obtained from all families. Patients were recruited, and their medical records were reviewed for any evidence of asthma by symptom and/or treatment history. Those with asthma had detailed medical record reviews starting at the time of HIV diagnosis. Data were collected on asthma exacerbations based on emergency department visits, hospitalizations, and steroid bursts. Pulmonary function data were reviewed to confirm diagnosis. CD4 T-cell percentages and absolute counts were recorded. The asthma severity was evaluated by the recommendations of the National Heart, Lung, and Blood Institute/National Asthma Education and Prevention Program guidelines. Differences in T-cell numbers and percentages were analyzed by the Mann-Whitney U test. A total of 85 HIV-infected children (aged 3–16 years) were recruited for the study; 24 (28%) had persistent asthma (12 girls and 12 boys). Six of the asthmatic patients had a history of intermittent wheeze without need for inhaled corticosteroid in infancy. At the time of persistent asthma diagnosis, the CD4 T cells of all asthmatic patients were within acceptable limits for age. Twenty patients had never had a significant decrease in T cells, and 4 had decreases in T-cell percentage and/or absolute count below Pneumocystis carinii or Pneumocystis jiroveci prophylaxis level before starting HIV therapy (nadirs of absolute CD4 T-cell counts: 204, 32, 23, and 24 cells/ L). The T cells of these 4 patients were subsequently reconstituted. A previous review of our pediatric HIV medical records from the pre-ART era revealed no persistent asthmatic patients (0 of 148 patients receiving treatment for persistent asthma) compared with the 28% at the time of the study. The 4 children with reconstituted T cells showed significant differences in T-cell percentage (nadir/diagnosis values, 12%/23%, 2%/24%, 1%/29%, and 4%/20%; P .02) and absolute values (nadir/diagnosis values, 204/736, 32/816, 23/812, and 24/440 cells/ L; P .02) between nadir of T-cell count (preasthma) and values at the time of diagnosis with persistent asthma. Interestingly, the CD4 T-cell levels decreased transiently below the level recommended for P carinii/jiroveci prophylaxis in 2 patients whose T cells had never been reconstituted (previously persistent adequacy of CD4 T-cell counts), and the decrease in each case coincided with improvement in asthma (persistent to intermittent). This study highlights the ability of reconstituted CD4 cells (in HIV-infected children receiving ART) to assist in asthmatic inflammation. It also introduces a new population of asthmatic children (whose T cells were reconstituted or never immune depleted): immune-competent HIV-infected children.

Alu-repeat-induced deletions within the NCF2 gene causing p67-phox-deficient chronic granulomatous Disease (CGD)

Mutations that impair expression or function of the components of the phagocyte NADPH oxidase complex cause chronic granulomatous disease (CGD), which is associated with life‐threatening infections and dysregulated granulomatous inflammation. In five CGD patients from four consanguineous families of two different ethnic backgrounds, we found similar genomic homozygous deletions of 1,380 bp comprising exon 5 of NCF2, which could be traced to Alu‐mediated recombination events. cDNA sequencing showed in‐frame deletions of phase zero exon 5, which encodes one of the tandem repeat motifs in the tetratricopeptide (TPR4) domain of p67‐phox. The resulting shortened protein (p67Δ5) had a 10‐fold reduced intracellular half‐life and was unable to form a functional NADPH oxidase complex. No dominant negative inhibition of oxidase activity by p67Δ5 was observed. We conclude that Alu‐induced deletion of the TPR4 domain of p67‐phox leads to loss of function and accelerated degradation of the protein, and thus represents a new mechanism causing p67‐phox–deficient CGD. Hum Mutat 30:1–8, 2009.

Achieving adherence to antiretroviral medications for pediatric HIV disease using an empirically supported treatment : A case report

Adherence to antiretroviral medication regimens among human immunodeficiency virus positive-children is influenced by a number of psychosocial factors including characteristics of the child, the caregiver, the medical team, and the medications. To address these factors requires treatment approaches that are flexible and comprehensive. One such treatment approach is multisystemic therapy (MST), an empirically supported intensive home-based treatment approach that has been proven effective with other chronic pediatric conditions. This case report describes the use of MST with a poorly adherent, perinatally infected adolescent.

Panhypopituitarism in a child with common variable immunodeficiency

BACKGROUND Common variable immunodeficiency (CVID) represents a group of heterogeneous, still undifferentiated, syndromes that are all characterized by defective antibody formation. It is often associated with autoimmune disease. METHODS An African-American girl was diagnosed with CVID at age 3 years. She was seen during an adrenal crisis precipitated by pneumonia at the age of 8 years and 10 months. The diagnosis of panhypopituitarism was established soon after. RESULTS Panhypopituitarism in this patient was believed to be the result of the autoimmune process known as lymphocytic hypophysitis. This hypothesis was suggested by the results of magnetic resonance imaging. CONCLUSIONS Awareness of the possibility of this process in children or adults with CVID may lead to earlier diagnosis of panhypopituitarism. These patients also have failure to thrive, and earlier diagnosis may avoid a life-threatening event.