Center-Based Experiences Implementing Strategies to Reduce Risk of Horizontal Transmission of SARS-Cov-2: Potential for Compromise of Neonatal Microbiome Assemblage.

Perinatal transmission of COVID-19 is poorly understood and many neonatal intensive care units' (NICU) policies minimize mother-infant contact to prevent transmission. We present our unit's approach and ways it may impact neonatal microbiome acquisition. We attended COVID-19 positive mothers' deliveries from March-August 2020. Delayed cord clamping and skin-to-skin were avoided and infants were admitted to the NICU. No parents' visits were allowed and discharge was arranged with COVID-19 negative family members. Maternal breast milk was restricted in the NICU. All twenty-one infants tested negative at 24 and 48 hours and had average hospital stays of nine days. 40% of mothers expressed breastmilk and 60% of infants were discharged with COVID-19 negative caregivers. Extended hospital stays, no skin-to-skin contact, limited maternal milk use, and discharge to caregivers outside primary residences, potentially affect the neonatal microbiome. Future studies are warranted to explore how ours and other centers' similar policies influence this outcome.

Prolonged chronic phase of greater than 10 years of chronic myelogenous leukemia in a patient with congenital human immunodefeciency virus infection.

A 15-year-old male with congenital HIV infection was diagnosed with chronic myelogenous leukemia (CML) at age 4 years 9 months. HIV was initially treated with zidovudine. For the last >10 years he has received didanosine, lamivudine, and nelfinavir. CML was treated with Interferon alfa (INF-alpha) for >10 years and a brief course of hydroxyurea (HU). He remained in chronic phase CML since diagnosis however recent molecular monitoring revealed increased BCR/ABL transcripts necessitating a change in therapy to imatinib. The very prolonged chronic phase of CML in this patient has been unexpected especially in light of the underlying congenital HIV infection.

Pediatric primary cutaneous blastomycosis clinically responsive to itraconazole.

Primary cutaneous blastomycosis is a rare infection, especially among children. We present the case of a 16-year-old immunocompetent adolescent boy with primary cutaneous blastomycosis arising after falling into a flowerbed in a region where the fungus Blastomyces dermatitidis is hyperendemic. Following treatment with itraconazole 200 mg 3 times daily for 3 days, followed by 200 mg 2 times daily for 6 months, the lesion healed with only residual dyschromia.

Meningitis.

Meningitis is defined as inflammation of the meninges, in almost all cases identified by an abnormal number of white blood cells in the cerebrospinal fluid and specific clinical signs/symptoms. Onset may be acute or chronic, and clinical symptoms of acute disease develop over hours to days. This article reviews the epidemiology, pathophysiology, clinical manifestations, diagnosis, and management of acute meningitis, and provides a list of key points for primary care practitioners. Aseptic and bacterial meningitis vary significantly and are discussed separately.

Effect of perinatal antiretroviral drug exposure on hematologic values in HIV-uninfected children: An analysis of the women and infants transmission study.

BACKGROUND: With the increasing use of antiretroviral (ARV) drugs to prevent mother-to-child transmission of human immunodeficiency virus (HIV), large numbers of infants are exposed, with possible consequent toxicity. METHODS: Hematologic values in 1820 uninfected HIV- and ARV-exposed children were compared with those in 351 ARV-unexposed children from the Women and Infants Transmission Study. Hemoglobin concentrations and platelet, neutrophil, lymphocyte, and CD4+ and CD8+ cell counts were analyzed at birth and ages 2, 6, 12, 18, and 24 months. Multivariate analysis was conducted age 0-2 and 6-24 months, with adjustment for multiple cofactors. RESULTS: Hemoglobin concentrations and neutrophil, lymphocyte, and CD4+ cell counts were significantly lower at age 0-2 months in infants exposed to ARV drugs than in those who were not. At 6-24 months, differences in hemoglobin concentrations and neutrophil counts were no longer significant, whereas differences in platelet, lymphocyte, and CD4+ cell counts persisted and CD8+ cell counts became significantly lower. In comparison with ARV monotherapy, combination therapy was associated with larger decreases in neutrophil, lymphocyte, and CD8+ cell counts at age 0-2 months but with only differences in CD8+ cell counts at age 6-24 months. Clinically significant abnormalities were rare and did not differ by exposure to ARV drugs. CONCLUSION: Infants exposed to ARV drugs have small but significant differences in several hematologic parameters for the first 24 months of life. These results indicate the need for long-term follow-up of uninfected infants with ARV exposure.

Predictors of immunologic long-term nonprogression in HIV-infected children: implications for initiating therapy.

BACKGROUND: Early markers that predict immunologic long-term nonprogression in infants with perinatally acquired HIV infection might assist in subsequent antiretroviral treatment decisions. OBJECTIVES: We sought to identify early markers of immunologic long-term HIV disease nonprogression. METHODS: We analyzed immunologic and virologic characteristics at 1 and 2 months of age in HIV-infected children who were enrolled in the Women and Infants Transmission Study and born before 1995, comparing immunologic long-term nonprogressors (ILTNPs; n = 10) with non-ILTNPs (n = 127). ILTNPs were children who survived to 8 years or older with CD4 percentages of 25% or greater and counts of 500 cells/mm 3 or more without receiving highly active antiretroviral therapy. Non-ILTNPs were defined as all other HIV-infected children. Receiver operating characteristic curve analysis was used to assess combined sensitivity and specificity for each of these characteristics and to determine potential threshold values to discriminate between ILTNPs and non-ILTNPs. RESULTS: Characteristics in the first 2 months of life associated with ILTNP status in univariate analysis included higher CD4 percentages, lower CD8 + percentages, lower CD8 + HLA-DR + percentages, and lower HIV-1 RNA PCR values. In receiver operating characteristic analysis CD8 + HLA-DR + percentage had the best combined sensitivity and specificity for discriminating between ILTNPs and non-ILTNPs. CD8 + HLA-DR + percentages of 5% or less predicted ILTNP status with 80% sensitivity and 80% specificity. In multivariate analysis CD8 + HLA-DR+ percentage of 5% or less remained a significant predictor of ILTNP status after adjusting for CD3 + CD4 + percentage and HIV-1 RNA PCR value (odds ratio, 15.4; 95% CI, 1.9-124.7). CONCLUSION: CD8 + HLA-DR + T-lymphocyte percentage of less than 5% at 1 to 2 months of age might be predictive for ILTNP status but should not be used at this time to make treatment-deferral decisions. Immune activation in HIV-infected infants might herald more disease progression. Further study of the use of this subpopulation in early infancy to predict ILTNP status is warranted.

Combination antiretroviral strategies for the treatment of pregnant HIV-1-infected women and prevention of perinatal HIV-1 transmission.

CONTEXT: The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. OBJECTIVE: To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. DESIGN: Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. MAIN OUTCOME MEASURE: HIV-1 status of the infant. RESULTS: HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. CONCLUSION: Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.