Microalbuminuria in Perinatally HIV-Infected Children and Adolescents in the United States.

Background: The kidney is a common target for human immunodeficiency virus (HIV), making renal disease a common noninfectious complication of HIV. Microalbuminuria is an important marker that can detect early renal damage. Timely detection of microalbuminuria is important to initiate renal management and stop the progression of renal dysfunction in people with HIV. Limited data are available about renal abnormalities in people with perinatal HIV infection. The objective of this study was to determine the prevalence of microalbuminuria in a cohort of perinatally HIV-infected children and young adults receiving combination antiretroviral therapy and investigate correlations between microalbuminuria and clinical and laboratory findings. Methods: This was a retrospective study of 71 patients with HIV followed in an urban pediatric HIV clinic in Houston, Texas, between October 2007 and August 2016. Demographic, clinical, and laboratory data were compared between subjects with persistent microalbuminuria (PM) and those without. PM is defined as a microalbumin-to-creatinine ratio ≥30 mg/g on at least 2 occasions separated by at least 1 month. Results: Sixteen of 71 patients (23%) met the definition of PM. In univariate analysis, patients with PM had significantly higher CD8+ T-cell activation and lower CD4+ T-cell nadir. Multivariate analysis demonstrated increased microalbuminuria to be independently associated with older age and CD8+ T-cell activation measured as CD8+HLA-DR+ T-cell percentage. Conclusions: Older age and increased activation of CD8+HLA-DR+ on T cells correlate with presence of microalbuminuria in this cohort of HIV-infected patients.

Using Artificial Neural Networks to Predict Intra-Abdominal Abscess Risk Post-Appendectomy.

Objective: To determine if artificial neural networks (ANN) could predict the risk of intra-abdominal abscess (IAA) development post-appendectomy. Background: IAA formation occurs in 13.6% to 14.6% of appendicitis cases with "complicated" appendicitis as the most common cause of IAA. There remains inconsistency in describing the severity of appendicitis with variation in treatment with respect to perforated appendicitis. Methods: Two "reproducible" ANN with different architectures were developed on demographic, clinical, and surgical information from a retrospective surgical dataset of 1574 patients less than 19 years old classified as either negative (n = 1,328) or positive (n = 246) for IAA post-appendectomy for appendicitis. Of 34 independent variables initially, 12 variables with the highest influence on the outcome selected for the final dataset for ANN model training and testing. Results: A total of 1574 patients were used for training and test sets (80%/20% split). Model 1 achieved accuracy of 89.84%, sensitivity of 70%, and specificity of 93.61% on the test set. Model 2 achieved accuracy of 84.13%, sensitivity of 81.63%, and specificity of 84.6%. Conclusions: ANN applied to selected variables can accurately predict patients who will have IAA post-appendectomy. Our reproducible and explainable ANNs potentially represent a state-of-the-art method for optimizing post-appendectomy care.

Extensive Mycobacterium abscessus Pneumonia in an Immunocompetent Infant with No Underlying Lung Pathology.

Pulmonary infection due to Mycobacterium abscessus occurs in patients with cystic fibrosis, but rarely in immunocompetent children without underlying lung pathology. Treatment is complicated by frequent resistance to many antibiotics. We present a case report of a 4-month-old female infant with 2 months of cough, difficulty feeding, and failure to thrive, with extensive culture-confirmed M. abscessus pulmonary infection without identified immunodeficiency or underlying lung pathology following multidisciplinary evaluation. We describe our complete evaluation including immunodeficiency evaluation incorporating whole-exome sequencing, describe our antibiotic selection and treatment duration given complicated susceptibility pattern of the M. abscessus isolate, and review literature for nontuberculous mycobacterial pulmonary disease in immunocompetent children. A complete multidisciplinary evaluation for underlying lung disease and primary and acquired immunodeficiency should be undertaken in pediatric patients with M. abscessus pneumonia. Confirming macrolide susceptibility through erm(41) gene evaluation is clinically important for isolates with complicated susceptibility pattern.

Toxocara species environmental contamination of public spaces in New York City.

Human toxocariasis has been identified as an under-diagnosed parasitic zoonosis and health disparity of significant public health importance in the United States due to its high seropositivity among socioeconomically disadvantaged groups, and possible links to cognitive and developmental delays. Through microscopy and quantitative PCR, we detected that Toxocara eggs are widespread in New York City public spaces, with evidence of significant levels of contamination in all five boroughs. The Bronx had the highest contamination rate (66.7%), while Manhattan had the lowest contamination rate (29.6%). Moreover, infective eggs were only found in the Bronx playgrounds, with over 70% of eggs recovered in embryonic form and the highest egg burden (p = 0.0365). All other boroughs had eggs in the pre-infectious, unembronyated form. Toxocara cati, the cat roundworm, was the predominant species. These results suggest that feral or untreated cats in New York City represent a significant source of environmental contamination. These findings indicate that human toxocariasis has emerged as an important health disparity in New York City, with ongoing risk of acquiring Toxocara infection in public spaces, especially in poorer neighborhoods. There is a need for reducing environmental Toxocara contamination. Additional rigorous public health interventions should explore further approaches to interrupt transmission to humans.

Perinatal HIV-1 Infection in an Extremely Low Birth Weight Infant.

There is limited guidance on how to treat extremely premature infants with HIV infection. This can lead to delay of antiretroviral therapy initiation adversely affecting magnitude of HIV reservoir and disease progression. We report perinatal HIV-1 infection in an extremely low birth weight infant born at 24 5/7 weeks of gestation. Treatment challenges, viral dynamics and clinical outcomes are described.

Plasmodium vivax Infection in Multiple Family Members in Texas, USA.

We report a cluster of 6 pediatric residents of Houston, Texas, USA, who presented with Plasmodium vivax infection within an eight-week period. All had immigrated to the United States from Afghanistan within the previous year. The clustering raises the possibilities of local mosquito vectored infection and/or synchronous relapses. Molecular typing and local mosquito testing are crucial in delineating the source of similar clusters in nonendemic regions. Single-dose hypnozoite eradication treatment may be considered in emigrating children to malaria nonendemic countries.

Imported Congenital Rubella Syndrome, United States, 2017.

Although transmission of rubella virus within the United States is rare, the risk for imported cases persists. We describe a rubella case in a newborn, conceived in Saudi Arabia, in Texas during 2017, highlighting the importance of active surveillance and early diagnosis of this disease.

Angiostrongylus cantonensis Meningitis and Myelitis, Texas, USA.

Infection with Angiostrongylus cantonensis roundworms is endemic in Southeast Asia and the Pacific Basin. A. cantonensis meningitis and myelitis occurred in summer 2013 in a child with no history of travel outside of Texas, USA. Angiostrongyliasis is an emerging neurotropic helminthic disease in Texas and warrants increased awareness among healthcare providers.

Plasma Interferon-Gamma-Inducible Protein 10 Level Associates With Abnormal Memory B Cells Phenotypes in Perinatal HIV Infection.

We demonstrate for perinatally HIV-infected children and adolescents receiving combined antiretroviral therapy and in good clinical status with respect to HIV disease that high concentrations of interferon-gamma-inducible protein 10 associate with increased exhausted memory B cells.

CD31 Expression on CD4+ Cells: A Simple Method for Quantitation of Recent Thymus Emigrant CD4 Cells.

Measurements of CD4+CD31+ cells gave results consistent with those expected for recent thymus emigrant (RTE) CD4+ cells. The method was markedly simpler than established procedures for measurement of CD4+ RTE cells and is usable in locations with limited facilities and budgets.

Recent Thymus Emigrant CD4+ T Cells Predict HIV Disease Progression in Patients With Perinatally Acquired HIV.

BACKGROUND: Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS: In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS: Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS: CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Incidence and predictors of antiretroviral resistance in perinatally HIV-1 infected children and adolescents.

OBJECTIVES: Individuals with perinatally acquired HIV infection have benefited from antiretroviral therapy. However, they often have complex patterns of major resistance mutations that limit the effectiveness of available antiretroviral medications. Knowledge of incidence rates of major antiretroviral resistance mutations should provide a benchmark enabling comparisons of different HIV care delivery modalities. METHODS: We test the hypothesis that incidence rate of major antiretroviral resistance mutations will decline with improvement in HIV care between 1998 and 2009 to NRTI, NNRTI, PI and triple class resistance in perinatally HIV infected individuals. Logistic regression is used to evaluate predictors of single and triple class resistance. RESULTS: Sixty-six individuals are included from a total population of 97 perinatally HIV infected individuals. The incidence rate of NRTI, NNRTI, PI and triple class resistance decreases with decreasing age in parallel with the introduction of new HIV treatment regimens. The youngest children (born 2000-2007) are free of triple class resistance. Mono-therapy associates with major resistance mutations to NRTI (OR 8.7, CI 1.5-50.9, P 0.02); NNRTI exposure associates with major resistance mutations to NNRTI (OR 24.4, CI 5.7-104.5, P 0.01) and triple class resistance (OR 10.7, CI 1.8-67.1, P 0.01). Cumulative viral load is an important predictor of PI resistance (OR 4.0, CI 1.3-12.3, P 0.02). CONCLUSIONS: There is a progressive decrease in the incidence rate of major resistance mutations to antiretroviral drugs and triple class resistance from the oldest to the youngest birth cohort; where adolescents have the highest risk of harboring resistant viruses. The incidence rate of major antiretroviral resistance mutations provides a benchmark for the comparative measurement of effectiveness of different HIV care delivery modalities.

Cardiovascular disease is associated with COPD severity and reduced functional status and quality of life.

INTRODUCTION: Smoking is a major risk factor for both cardiovascular disease (CVD) and chronic obstructive pulmonary disease (COPD). More individuals with COPD die from CVD than respiratory causes and the risk of developing CVD appears to be independent of smoking burden. Although CVD is a common comorbid condition within COPD, the nature of its relationships to COPD affection status and severity, and functional status is not well understood. METHODS: The first 2,500 members of the COPDGene cohort were evaluated. Subjects were current and former smokers with a minimum 10 pack-year history of cigarette smoking. COPD was defined by spirometry as an FEV1/FVC < lower limit of normal (LLN) with further identification of severity by FEV1 percent of predicted (GOLD stages 2, 3, and 4) for the main analysis. The presence of physician-diagnosed self-reported CVD was determined from a medical history questionnaire administered by a trained staff member. RESULTS: A total of 384 (15%) had pre-existing CVD. Self-reported CVD was independently related to COPD (Odds Ratio = 1.61, 95% CI = 1.18-2.20, p = 0.01) after adjustment for covariates with CHF having the greatest association with COPD. Within subjects with COPD, pre-existing self-reported CVD placed subjects at greater risk of hospitalization due to exacerbation, higher BODE index, and greater St. George's questionnaire score. The presence of self-reported CVD was associated with a shorter six-minute walk distance in those with COPD (p < 0.05). CONCLUSIONS: Self-reported CVD was independently related to COPD with presence of both self-reported CVD and COPD associated with a markedly reduced functional status and reduced quality of life. Identification of CVD in those with COPD is an important consideration in determining functional status.

Persistently high perinatal transmission of HIV: assessment of risk factors.

BACKGROUND: Despite dramatic decreases in rates of perinatal mother-to-child-transmission (PMTCT) of HIV in the United States, rates in some groups remain above the national average. Our objective was to examine factors contributing to a high rate of PMTCT of HIV. METHODS: We conducted a retrospective chart review of HIV-exposed infants and their mothers referred to the University of Texas-Houston Pediatric HIV Clinic from January 2000 to June 2007. RESULTS: Of 367 newborns studied, 22 (6%) acquired HIV infection perinatally. Associated risk factors included inadequate prenatal care, failure to receive antiretroviral therapy during pregnancy, detectable viral load and intravenous drug abuse. CONCLUSIONS: The composite rate of PMTCT in this high risk cohort was at least 3-fold higher than expected from the current standard of care. Reduction of rates of PMTCT in our population will require ensuring access to appropriate prenatal care, including delivery of antiretroviral therapy and addressing issues of illicit drug use.

Detection of NH1N1 influenza virus in nonrespiratory sites among children.

Among 20 children admitted with laboratory-confirmed influenza, viral RNA was detected in respiratory secretion, stool and blood in 19, 5 and 1 children, respectively. Gastrointestinal symptoms were common but were not associated with viral RNA in stool. nH1N1 viremia was detected, for the first time, in an immunocompetent child.

Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children.

BACKGROUND: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe). METHODS: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe. RESULTS: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe. CONCLUSIONS: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.

Severe narrowing of left cavernous carotid artery associated with Fusobacterium necrophorum infection.

Severe oropharyngeal infection can result in Lemierre's disease, a syndrome with high mortality secondary to inflammation and thrombosis of cervical and intracranial veins with involvement of contiguous structures; however arterial involvement is rare. We report a case of Lemierre's disease in a 12 year old boy with severe narrowing of the left cavernous carotid artery.

Quantitative computed tomography of the lungs and airways in healthy nonsmoking adults.

OBJECTIVES: The purposes of this study were to evaluate the reference range of quantitative computed tomography (QCT) measures of lung attenuation and airway parameter measurements in healthy nonsmoking adults and to identify sources of variation in those measures and possible means to adjust for them. MATERIALS AND METHODS: Within the COPDGene study, 92 healthy non-Hispanic white nonsmokers (29 men, 63 women; mean [SD] age, 62.7 [9.0] years; mean [SD] body mass index [BMI], 28.1 [5.1] kg/m(2)) underwent volumetric computed tomography (CT) at full inspiration and at the end of a normal expiration. On QCT analysis (Pulmonary Workstation 2, VIDA Diagnostics), inspiratory low-attenuation areas were defined as lung tissue with attenuation values -950 Hounsfield units or less on inspiratory CT (LAA(I-950)). Expiratory low-attenuation areas were defined as lung tissue -856 Hounsfield units or less on expiratory CT (LAA(E-856)). We used simple linear regression to determine the impact of age and sex on QCT parameters and multiple regression to assess the additional impact of total lung capacity and functional residual capacity measured by CT (TLC(CT) and FRC(CT)), scanner type, and mean tracheal air attenuation. Airways were evaluated using measures of airway wall thickness, inner luminal area, wall area percentage (WA%), and standardized thickness of an airway with inner perimeter of 10 mm (Pi10). RESULTS: Mean (SD) %LAA(I-950) was 2.0% (2.7%), and mean (SD) %LAA(E-856) was 9.2% (6.8%). Mean (SD) %LAA(I-950) was 3.6% (3.2%) in men, compared with 1.3% (2.0%) in women (P < 0.001). The %LAA(I-950) did not change significantly with age (P = 0.08) or BMI (P = 0.52). %LAA(E-856) did not show any independent relationship with age (P = 0.33), sex (P = 0.70), or BMI (P = 0.32). On multivariate analysis, %LAA(I-950) showed a direct relationship to TLC(CT) (P = 0.002) and an inverse relationship to mean tracheal air attenuation (P = 0.003), and %LAA(E-856) was related to age (P = 0.001), FRC(CT) (P = 0.007), and scanner type (P < 0.001). Multivariate analysis of segmental airways showed that inner luminal area and WA% were significantly related to TLC(CT) (P < 0.001) and age (0.006). Moreover, WA% was associated with sex (P = 0.05), axial pixel size (P = 0.03), and slice interval (P = 0.04). Lastly, airway wall thickness was strongly influenced by axial pixel size (P < 0.001). CONCLUSIONS: Although the attenuation characteristics of normal lung differ by age and sex, these differences do not persist on multivariate analysis. Potential sources of variation in measurement of attenuation-based QCT parameters include depth of inspiration/expiration and scanner type. Tracheal air attenuation may partially correct variation because of scanner type. Sources of variation in QCT airway measurements may include age, sex, BMI, depth of inspiration, and spatial resolution.