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.

Human Rabies - Texas, 2021.

In late August 2021, a boy aged 7 years was bitten by a bat while he was playing outside his apartment home in Medina County, Texas. He informed his parents; however, no rabies postexposure prophylaxis (PEP) was sought because there were no visible bite marks, and the family was unaware that contact with a bat, including in the absence of visible bite marks, might cause rabies. Approximately 2 months later, the child was hospitalized for altered mental status, seizures, and hypersalivation and ultimately received a diagnosis of rabies. Experimental therapies were attempted; however, the child died 22 days after symptom onset. Fifty-seven persons who met criteria for suspected or known exposure to infectious secretions in this case were advised to consult with a medical provider about the need for rabies PEP in accordance with Advisory Committee on Immunization Practices (ACIP) guidelines (1). Rabies, an acute, progressive neuroencephalitis, is nearly always fatal. Although dogs are the most common source of human rabies deaths worldwide and account for an estimated 59,000 annual cases of human rabies globally (2), bats are the most common source of domestically acquired rabies in the United States and have been implicated in 31 (81.6%) of 38 human infections since 2000 (3). Attempts to prevent death or poor neurologic outcomes once rabies symptoms develop have been largely unsuccessful (4). Administration of rabies PEP, comprising rabies immunoglobulin and a series of doses of rabies vaccine, is critical to preventing rabies after an exposure; enhanced public education about the risk posed by bats, and the availability of PEP to prevent rabies, is needed.

SARS-CoV-2 and Streptococcus pneumoniae Coinfection in a Previously Healthy Child.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported in December 2019 in Wuhan, China. This novel coronavirus has been responsible for a pandemic that continues to devastate nations worldwide. COVID-19, like other viruses, causes pneumonia. However, unlike other viral respiratory tract infections such as influenza, bacterial coinfection in COVID-19 patients has uncommonly been described in adult and pediatric patients. We report a case of Streptococcus pneumoniae and COVID-19 coinfection in a previously healthy 4-year-old child.

Antibiotic Safety and Effectiveness in Premature Infants With Complicated Intraabdominal Infections.

BACKGROUND: In premature infants, complicated intraabdominal infections (cIAIs) are a leading cause of morbidity and mortality. Although universally prescribed, the safety and effectiveness of commonly used antibiotic regimens have not been established in this population. METHODS: Infants ≤33 weeks gestational age and <121 days postnatal age with cIAI were randomized to ≤10 days of ampicillin, gentamicin, and metronidazole (group 1); ampicillin, gentamicin, and clindamycin (group 2); or piperacillin-tazobactam and gentamicin (group 3) at doses stratified by postmenstrual age. Due to slow enrollment, a protocol amendment allowed eligible infants already receiving study regimens to enroll without randomization. The primary outcome was mortality within 30 days of study drug completion. Secondary outcomes included adverse events, outcomes of special interest, and therapeutic success (absence of death, negative cultures, and clinical cure score >4) 30 days after study drug completion. RESULTS: One hundred eighty infants [128 randomized (R), 52 nonrandomized (NR)] were enrolled: 63 in group 1 (45 R, 18 NR), 47 in group 2 (41 R, 6 NR), and 70 in group 3 (42 R, 28 NR). Thirty-day mortality was 8%, 7%, and 9% in groups 1, 2, and 3, respectively. There were no differences in safety outcomes between antibiotic regimens. After adjusting for treatment group and gestational age, mortality rates through end of follow-up were 4.22 [95% confidence interval (CI): 1.39-12.13], 4.53 (95% CI: 1.21-15.50), and 4.07 (95% CI: 1.22-12.70) for groups 1, 2, and 3, respectively. CONCLUSIONS: Each of the antibiotic regimens are safe in premature infants with cIAI. CLINICAL TRIAL REGISTRATION: NCT0199499.

Murine Typhus Outbreak Presenting as Multisystem Inflammatory Syndrome in Children During SARS-CoV-2 Pandemic.

Multisystem inflammatory syndrome in children is a severe illness associated with the SARS-CoV-2 pandemic that possesses features overlapping with other pediatric diseases causing systemic inflammation. Significant diagnostic and treatment uncertainty remain, and clinicians should maintain a broad differential when evaluating patients for multisystem inflammatory syndrome in children, as antibiotic-susceptible infections such as murine typhus may present similarly.

Safety of Metronidazole in Late Pre-term and Term Infants with Complicated Intra-abdominal Infections.

BACKGROUND: Metronidazole is frequently used off-label in infants with complicated intra-abdominal infections (cIAI) to provide coverage against anaerobic organisms, but its safety and efficacy in this indication are unknown. METHODS: In the Antibiotic Safety in Infants with Complicated Intra-Abdominal Infections open-label multicenter trial infants ≥34 weeks gestation at birth and <121 days postnatal age with cIAIs were administered metronidazole as part of multimodal therapy. Metronidazole safety was evaluated by reporting of adverse events (AEs) and safety events of special interest. Cure from disease was determined by blood cultures and a clinical cure score >4. A blinded adjudication committee reviewed all safety events of special interest. RESULTS: Fifty-five infants were included, median gestational age was 36 weeks (range: 34-41) and postnatal age was 7 days (0-63). The most common additional antibiotics received included gentamicin, piperacillin-tazobactam, ampicillin and vancomycin. Only one AE, a candidal rash, was identified to be potentially caused by metronidazole administration. One infant died of cardiopulmonary failure, which was deemed unrelated to metronidazole. The most common events of special interest included feeding intolerance in 18 (33%) infants, and exploratory laparotomy in 10 (18%) requiring intestinal anastomosis in 7 (13%) infants. There was 1 (2%) intestinal stricture. Fifty-three infants (96%) achieved overall therapeutic success, 54 (98%) were alive through 30 days post-study therapy, and 54 (98%) had 30-day clinical cure score >4. CONCLUSIONS: In a cohort of late pre-term and term infants with cIAIs, combination antibiotic therapy that included metronidazole was safe, and therapeutic success was high.

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.

Severe emm89 Group A Streptococcal Disease Characterized by Toxic Shock and Endocarditis.

Invasive group A Streptococcus infections are associated with diverse presentations. We report a severe, rare case of GAS infection with dissemination including endocarditis and STSS. While whole genome sequencing of blood and pharyngeal isolates did not reveal any unique features attributable to the severe presentation, our approach serves as a template for investigation of severe manifestations of common infections.

Transverse Myelitis and Guillain-Barré Syndrome Associated with Cat-Scratch Disease, Texas, USA, 2011.

We describe a case of coexisting transverse myelitis and Guillain-Barré syndrome related to infection with Bartonella henselae proteobacterium and review similar serology-proven cases. B. henselae infection might be emerging as a cause of myelitis and Guillain-Barré syndrome and should be considered as an etiologic factor in patients with such clinical presentations.

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.

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.

Use of nucleoside reverse transcriptase inhibitor-only regimens in HIV-infected children and adolescents.

OBJECTIVE: In adults, nucleoside reverse transcriptase inhibitor-only antiretroviral regimens (NOARs) with ≥3 nucleoside reverse transcriptase inhibitors are less potent than highly active antiretroviral therapy (HAART). Published pediatric experience with NOARs is limited; thus, we wished to better define the virological, immunological and toxicological effects of NOARs in children and adolescents. METHODS: We analyzed data from NOAR-treated participants in LEGACY, a multicenter observational cohort study of HIV-infected children and adolescents. NOAR-treated case-participants were matched to participants without prior NOAR who initiated HAART during the same year for comparison. RESULTS: Of 575 participants with data from time of HIV diagnosis through 2006, 67 (12%) received NOARs for at least 24 weeks; most (46%) received the fixed dose combination of zidovudine/lamivudine/abacavir. NOAR use peaked in 2001 to 2002. NOAR-treated participants were significantly older and more treatment experienced than HAART-treated participants. Virologic outcomes, including the percentage of participants with a plasma HIV RNA viral load <400 copies/mL at week 24 (47% versus 34%) and the mean 24-week change in log10 plasma HIV RNA viral load from baseline (-0.63 versus -1.02), were similar between NOAR- and HAART-treated participants, but virologic rebound was more likely in NOAR-treated participants (77% versus 54%, P = 0.02). Increase in CD4 percentage points from baseline to 24 weeks was negligible in NOAR-treated participants compared with HAART-treated participants (0.95% versus 10.1%, P < 0.001). Anemia and leukopenia were more commonly reported with NOARs than HAART. DISCUSSION: Week 24 virologic outcomes were similar between NOAR- and HAART-treated participants, but NOAR durability was poorer and their use was associated with less immunologic reconstitution. NOARs should play a limited role in pediatric and adolescent antiretroviral therapy.