Safety, Tolerability, and Pharmacokinetics of a Long-Acting Broadly Neutralizing Human Immunodeficiency Virus Type 1 (HIV-1) Monoclonal Antibody VRC01LS in HIV-1-Exposed Newborn Infants.

BACKGROUND: Perinatal human immunodeficiency virus type 1 (HIV-1) continues to occur due to barriers to effective antiretroviral prevention that might be mitigated by long-acting broadly neutralizing monoclonal antibodies (bNAbs). METHODS: An extended half-life bNAb, VRC01LS, was administered subcutaneously at 80 mg/dose after birth to HIV-1-exposed, nonbreastfed (cohort 1, n = 10) and breastfed (cohort 2, n = 11) infants. Cohort 2 received a second dose (100 mg) at 12 weeks. All received antiretroviral prophylaxis. VRC01LS levels were compared to VRC01 levels determined in a prior cohort. RESULTS: Local reactions (all grade ≤2) occurred in 67% and 20% after dose 1 and dose 2, respectively. The weight-banded dose (mean 28.8 mg/kg) of VRC01LS administered subcutaneously achieved a mean (standard deviation) plasma level of 222.3 (71.6) µg/mL by 24 hours and 44.0 (11.6) µg/mL at week 12, prior to dose 2. The preestablished target of ≥50 µg/mL was attained in 95% and 32% at weeks 8 and 12, respectively. The terminal half-life was 37-41 days. VRC01LS level after 1 dose was significantly greater (P <.002) than after a VRC01 dose (20 mg/kg). No infants acquired HIV-1. CONCLUSIONS: VRC01LS was well tolerated with pharmacokinetics that support further studies of more potent long-acting bNAbs as adjunct treatment with antiretrovirals to prevent infant HIV-1 transmission.

Infections after Natural Disasters.

Natural disasters, particularly flooding, are associated with many environmental changes, and the chances of infections after a disaster increase. Dead bodies are not associated with increased infections, but many other factors contribute to the increase in infections and possible outbreaks. This article discusses the factors associated with increased risk of infections and the types of infections that may occur after a natural disaster. This article also presents a brief discussion of infection prevention and mitigation after a natural disaster.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America (IDSA) to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

2018 Infectious Diseases Society of America Clinical Practice Guideline for the Management of Outpatient Parenteral Antimicrobial Therapy.

A panel of experts was convened by the Infectious Diseases Society of America to update the 2004 clinical practice guideline on outpatient parenteral antimicrobial therapy (OPAT) [1]. This guideline is intended to provide insight for healthcare professionals who prescribe and oversee the provision of OPAT. It considers various patient features, infusion catheter issues, monitoring questions, and antimicrobial stewardship concerns. It does not offer recommendations on the treatment of specific infections. The reader is referred to disease- or organism-specific guidelines for such support.

Evolutionarily conserved epitopes on human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus reverse transcriptases detected by HIV-1-infected subjects.

Anti-human immunodeficiency virus (HIV) cytotoxic T lymphocyte (CTL)-associated epitopes, evolutionarily conserved on both HIV type 1 (HIV-1) and feline immunodeficiency virus (FIV) reverse transcriptases (RT), were identified using gamma interferon (IFN-γ) enzyme-linked immunosorbent spot (ELISpot) and carboxyfluorescein diacetate succinimide ester (CFSE) proliferation assays followed by CTL-associated cytotoxin analysis. The peripheral blood mononuclear cells (PBMC) or T cells from HIV-1-seropositive (HIV(+)) subjects were stimulated with overlapping RT peptide pools. The PBMC from the HIV(+) subjects had more robust IFN-γ responses to the HIV-1 peptide pools than to the FIV peptide pools, except for peptide-pool F3. In contrast, much higher and more frequent CD8(+) T-cell proliferation responses were observed with the FIV peptide pools than with the HIV peptide pools. HIV-1-seronegative subjects had no proliferation or IFN-γ responses to the HIV and FIV peptide pools. A total of 24% (40 of 166) of the IFN-γ responses to HIV pools and 43% (23 of 53) of the CD8(+) T-cell proliferation responses also correlated to responses to their counterpart FIV pools. Thus, more evolutionarily conserved functional epitopes were identified by T-cell proliferation than by IFN-γ responses. In the HIV(+) subjects, peptide-pool F3, but not the HIV H3 counterpart, induced the most IFN-γ and proliferation responses. These reactions to peptide-pool F3 were highly reproducible and persisted over the 1 to 2 years of testing. All five individual peptides and epitopes of peptide-pool F3 induced IFN-γ and/or proliferation responses in addition to inducing CTL-associated cytotoxin responses (perforin, granzyme A, granzyme B). The epitopes inducing polyfunctional T-cell activities were highly conserved among human, simian, feline, and ungulate lentiviruses, which indicated that these epitopes are evolutionarily conserved. These results suggest that FIV peptides could be used in an HIV-1 vaccine.

The Many Faces of Neurological Neonatal Herpes Simplex Virus Infection.

This case series explores the various manifestations of central nervous system (CNS) involvement in neonatal herpes simplex virus (HSV) infection and highlights the challenges involved in their diagnosis and treatment. Neonatal HSV infection is a rare but serious condition that can have significant neurological consequences. The article presents three cases of neonatal HSV infection, all involving the CNS, each characterized by distinct clinical features and outcomes. Case 1 describes a three-week-old male with severe HSV meningoencephalitis resulting in poor response to treatment and death. Cases 2 and 3 describe younger neonates who presented early in the disease course with disseminated infection and skin, eye, and mouth (SEM) lesions. Although both patients had CNS involvement, their outcomes were remarkably favorable. The wide range of clinical presentations of CNS manifestations in neonatal HSV infection, ranging from nonspecific to evident neurological symptoms, underscores the need for a high index of suspicion and comprehensive evaluation to ensure early diagnosis and appropriate treatment. However, it also notes that even with timely treatment, some cases may still have a poor prognosis.

Neuroimaging in Tick Paralysis: Looking Outside the Box.

Tick paralysis is a rare but potentially deadly form of muscle paralysis caused by a neurotoxin transmitted through the saliva of gravid, engorged female ticks of various species. Often, there is an initial misdiagnosis or delay in diagnosis due to the rarity of the diagnosis, the obscure location of the tick, and the disease's clinical similarity to Guillain-Barre syndrome. We report the case of a 4-year-old girl with tick paralysis in whom the tick was not found until 2 days after hospital admission. Upon the review of the imaging, it was discovered that the tick was visible on the MRI of the brain that had been reported as normal.

Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity.

PURPOSE: The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies. METHODS: A population PK model was developed using opportunistically collected plasma samples. For each dosing strategy, model-based probability of target attainment (PTA) estimates were computed for study participants using empirical Bayes estimates. In addition, the effects of body size and renal function on PTA were evaluated using stochastic model simulations with virtually generated subjects. RESULTS: Twenty-nine participants, 24 of whom were obese, contributed data towards the analysis. The median (range) age, body weight, and body mass index of participants were 12.2 years (2.3-20.6), 59.2 kg (8.4-121), and 25.2 kg/m2 (13.8-42.9), respectively. Administration of 50 mg/kg intravenously (IV) every 8 hours (q8h; max 6 g/day) or 40 mg/kg IV q6h (max 6 g/day) resulted in PTA values of ≥ 90% (minimum inhibitory concentration 8 mg/L) for the subset of obese participants with estimated glomerular filtration rates (GFR) ≥ ~ 80 mL/min/1.73 m2. However, for both regimens, stochastic model simulations denoted lower PTA values (< 90%) with increasing body weight for virtual subjects with GFR ≥ 120 mL/min/1.73 m2. Alternatively, permitting for a maximum daily dose of 8 g/day using a 40 mg/kg IV q6h regimen provided PTA values that were near or above target (90%) for virtual subjects between 10 to 120 kg with GFR ≥ 80 mL/min/1.73 m2. CONCLUSION: Our analysis suggests administration of 40 mg/kg IV q6h (max 8 g/day) maximizes PTA in children and adolescents with obesity and GFR ≥ 80 mL/min/1.73 m2. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01431326.

The unique issues of outpatient parenteral antimicrobial therapy in children and adolescents.

The decision to discharge a hospitalized child or adolescent to receive outpatient parenteral antimicrobial therapy (OPAT) is based on criteria very different from those concerning adults. Clinical studies of pediatric OPAT are sparse, as are pharmacokinetic data for antimicrobial agents in children. Other issues unique to children are requirements for special nursing and intravenous infusion skills, as well as the increase of complications. The psychological disadvantage of hospitalization in children, compared with adults, is great, and both populations are equally vulnerable to nosocomial infection, increasingly augmented by multidrug-resistant organisms. Although the relatively few clinical studies involving OPAT in children attest to its efficacy and safety, well-designed prospective trials and comprehensive cost-benefit analyses are still needed.

Immunogenicity and Efficacy of a Novel Multi-Antigenic Peptide Vaccine Based on Cross-Reactivity between Feline and Human Immunodeficiency Viruses.

For the development of an effective HIV-1 vaccine, evolutionarily conserved epitopes between feline and human immunodeficiency viruses (FIV and HIV-1) were determined by analyzing overlapping peptides from retroviral genomes that induced both anti-FIV/HIV T cell-immunity in the peripheral blood mononuclear cells from the FIV-vaccinated cats and the HIV-infected humans. The conserved T-cell epitopes on p24 and reverse transcriptase were selected based on their robust FIV/HIV-specific CD8⁺ cytotoxic T lymphocyte (CTL), CD4⁺ CTL, and polyfunctional T-cell activities. Four such evolutionarily conserved epitopes were formulated into four multiple antigen peptides (MAPs), mixed with an adjuvant, to be tested as FIV vaccine in cats. The immunogenicity and protective efficacy were evaluated against a pathogenic FIV. More MAP/peptide-specific CD4⁺ than CD8⁺ T-cell responses were initially observed. By post-third vaccination, half of the MAP/peptide-specific CD8⁺ T-cell responses were higher or equivalent to those of CD4⁺ T-cell responses. Upon challenge, 15/19 (78.9%) vaccinated cats were protected, whereas 6/16 (37.5%) control cats remained uninfected, resulting in a protection rate of 66.3% preventable fraction (p = 0.0180). Thus, the selection method used to identify the protective FIV peptides should be useful in identifying protective HIV-1 peptides needed for a highly protective HIV-1 vaccine in humans.

Influenza vaccine: awareness and barriers to immunization in families of children with chronic medical conditions other than asthma.

OBJECTIVES: Children with chronic medical conditions (CMCs) are considered to be at increased risk for influenza and its related complications. Despite this, influenza immunization rates in the United States for children with CMCs in the primary care setting remain between 7-10%. This was a survey study looking at the barriers to influenza immunization among children with CMCs other than asthma. We examined caregiver knowledge and perceptions regarding influenza vaccine in addition to assessing other barriers, such as availability and perceived safety of the vaccine. METHODS: The study was conducted during the fall-winter influenza seasons of 2002-2003 and 2003-2004 at five academic institutions across the southeastern US. Convenience samples of 100-150 families attending pediatric subspecialty clinics were surveyed. RESULTS: A total of 794 surveys were completed. Controlling for disease, failure to recommend vaccination was significantly associated with failure to get the vaccine (P < 0.0001). Of the children who did not receive the vaccine, 61% of their parents believed that the vaccine itself could give influenza, 54% cited other safety concerns, and 30% thought it did not work. Among vaccine recipients, 163 (43%) reported that the primary care provider had given the vaccine, whereas 171 (45%) reported that the vaccine had been given at the subspecialty clinic. CONCLUSION: This study highlights the importance of physician recommendation, as well as parental education, as some of the key elements crucial to the receipt of influenza vaccination in children with CMCs.

Throat culture is necessary after negative rapid antigen detection tests.

This study was conducted to determine if culture confirmation is needed for a negative rapid antigen detection test. Data on 18,509 tests done in patients younger than 18 years old were reviewed. Of the 14,167 (76.5%) that were negative, 968 (6.8%) were associated with positive cultures. No significant seasonal variation was noted. Significant differences were found between hospital and pediatric practices in the percentage of patients with a negative rapid antigen detection test who actually had group A beta-hemolytic streptococcus (3.5% to 9.8%). This study supports the recommendation of culture confirmation of a negative rapid antigen detection test and validation of results within an individual practice if confirmatory cultures are not being performed. This study showed a high false-negative rate of the negative rapid antigen detection test and variation among hospital and pediatric practices for rates of positive culture after a negative rapid antigen detection test.

Survival times and complications of catheters used for outpatient parenteral antibiotic therapy in children.

Outpatient parenteral antibiotic therapy is routinely used in pediatrics, but few data are available on catheter-associated complications and survival times. Catheter-associated complications, defined as mechanical or nonmechanical, and survival times in peripherally inserted central catheters and central venous catheters used for outpatient parenteral antibiotic therapy in childhood were compared. The life test procedure was performed to determine survival time. Cox proportional hazards model was used to compare the independent effect of variables such as age and gender on catheter survival. There were 104 peripheral and 130 central venous catheters, of which 28 peripheral and 19 central catheters had mechanical complications, and 13 peripheral and 17 central catheters had nonmechanical complications. Peripheral catheters are more likely to develop mechanical complications and have a shorter survival time than central venous catheters. For outpatient parenteral antibiotic therapy longer than 6 weeks, central venous catheters appear to be a better choice.

Immunization update.

Although the development and licensure of new vaccines over the last 2 years has generated a lot of excitement as well as debate, there is a lot more to come. Not discussed in this article. licensure of another long-awaited vaccine albeit for use in adults was that for herpes zoster. The second HPV and rotavirus vaccines are awaiting approval in the US. Next in line are the vaccines both prophylactic as well as therapeutic against HIV. Topics of debate over the new vaccines include discussions amongst practices as to the affordability and cost of the new vaccines as well as the ethical debate amongst lawmakers and the general public regarding the rights and wrongs of compulsory vaccination against HPV. Another ongoing discussion is regarding the availability of approved vaccines. Shortages have been seen with several of the childhood vaccines including heptavalent pneumococcal conjugate vaccine, tetravalent meningococcal conjugate vaccine, hepatitis A vaccine, as well as the ongoing saga with influenza vaccines. Across the globe while the struggle against polio continues, there is encouraging news regarding the reduction in measles-related deaths, particularly in Africa. The last few years have indeed been landmark years in infectious disease research as the search continues for better and safer vaccines globally.

Infection Prevention and Control in Pediatric Ambulatory Settings.

Since the American Academy of Pediatrics published its statement titled "Infection Prevention and Control in Pediatric Ambulatory Settings" in 2007, there have been significant changes that prompted this updated statement. Infection prevention and control is an integral part of pediatric practice in ambulatory medical settings as well as in hospitals. Infection prevention and control practices should begin at the time the ambulatory visit is scheduled. All health care personnel should be educated regarding the routes of transmission and techniques used to prevent the transmission of infectious agents. Policies for infection prevention and control should be written, readily available, updated every 2 years, and enforced. Many of the recommendations for infection control and prevention from the Centers for Disease Control and Prevention for hospitalized patients are also applicable in the ambulatory setting. These recommendations include requirements for pediatricians to take precautions to identify and protect employees likely to be exposed to blood or other potentially infectious materials while on the job. In addition to emphasizing the key principles of infection prevention and control in this policy, we update those that are relevant to the ambulatory care patient. These guidelines emphasize the role of hand hygiene and the implementation of diagnosis- and syndrome-specific isolation precautions, with the exemption of the use of gloves for routine diaper changes and wiping a well child's nose or tears for most patient encounters. Additional topics include respiratory hygiene and cough etiquette strategies for patients with a respiratory tract infection, including those relevant for special populations like patients with cystic fibrosis or those in short-term residential facilities; separation of infected, contagious children from uninfected children when feasible; safe handling and disposal of needles and other sharp medical devices; appropriate use of personal protective equipment, such as gloves, gowns, masks, and eye protection; and appropriate use of sterilization, disinfection, and antisepsis. Lastly, in this policy, we emphasize the importance of public health interventions, including vaccination for patients and health care personnel, and outline the responsibilities of the health care provider related to prompt public health notification for specific reportable diseases and communication with colleagues who may be providing subsequent care of an infected patient to optimize the use of isolation precautions and limit the spread of contagions.