Cost-Effectiveness of Pre-exposure HIV Prophylaxis During Pregnancy and Breastfeeding in Sub-Saharan Africa

Antiretroviral pre-exposure prophylaxis (PrEP) for the prevention of HIV acquisition is cost-effective when delivered to those at substantial risk. Despite a high incidence of HIV infection among pregnant and breastfeeding women in sub-Saharan Africa (SSA), a theoretical increased risk of preterm birth on PrEP could outweigh the HIV prevention benefit

Decline in CD4 T lymphocytes with monotherapy bridging strategy for non-adherent adolescents living with HIV infection: Results of the IMPAACT P1094 randomized trial

Introduction Management of persistently non-adherent youth living with HIV (YLHIV) with virologic failure (VF) on combination antiretroviral therapy (cART) remains challenging. One strategy has been using 3TC/ FTC monotherapy (3TC/FTC), which in the presence of the M184V resistance mutation, does not suppress viral replication nor select for additional drug resistance mutations, and reduces viral fitness with limited side effects. P1094 compared the immunologic outcome of continuing failing cART vs. switching to 3TC/FTC as a “bridging strategy” to subsequent suppressive cART for non-adherent YLHIV with pre-existing M184V resistance. Materials & methods Participants with documented nonadherence, M184V mutation, CD4+ T cell count ≥100 cells/mm3 and VF (HIV-1 plasma RNA ≥400 copies/mL (2.6 log10 HIV-1 RNA) were enrolled and randomized to continue failing cART vs. switch to 3TC/FTC. The primary endpoint (time to ≥30% CD4+ T cell decline or development of CDC class C events) at 28-weeks were assessed by Kaplan-Meier (K-M) curves in an intent-to-treat analysis. Results Thirty-three perinatally acquired YLHIV participants (16 continuing cART and 17 3TC/FTC) enrolled in the study. The median age, entry CD4+ T cell count, and viral load were 15 years (Inter-quartile range (IQR) 14–20), 472 cells/mm3 (IQR 384–651), and 4.0 log10HIV-1 RNA copies/ml (IQR 3.2–4.5), respectively. Five participants, all in the 3TC/FTC arm, reached the primary endpoint for absolute CD4+ T cell decline (p = 0.02, exact log-rank test comparing monotherapy to cART). The Kaplan-Meier estimate of probability of primary endpoint on 3TC/FTC at 28 weeks was 0.41 (standard error 0.14). There were no CDC class C events or deaths and no statistically significant difference in frequencies of adverse events between the arms. Conclusions Non-adherent participants randomized to 3TC/FTC were more likely than those maintained on failing cART to experience a confirmed decline in CD4+ count of ≥30%. Although this study suffers from limitations of small sample size and premature discontinuation, the randomized comparison to continuing failing cART indicates that 3TC/FTC provides inferior protection from immunologic deterioration for non-adherent youth with M184V resistance. Better alternatives to 3TC/FTC such as ART with higher barriers to resistance and novel adherence and treatment strategies for nonadherent youth are urgently needed

Epidemiology of community-onset Staphylococcus aureus infections in pediatric patients: an experience at a Children's Hospital in central Illinois

<p>Abstract</p> <p>Background</p> <p>The nation-wide concern over methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) has prompted many clinicians to use vancomycin when approaching patients with suspected staphylococcal infections. We sought to characterize the epidemiology of community-onset <it>S. aureus </it>infections in hospitalized children to assist local clinicians in providing appropriate empiric antimicrobial therapy.</p> <p>Methods</p> <p>From January 2005–June 2008, children (0–18 years old) admitted to the Children's Hospital of Illinois with community-onset <it>S. aureus </it>infections were identified by a computer-assisted laboratory-based surveillance and medical record review.</p> <p>Results</p> <p>Of 199 patients, 67 (34%) had invasive infections, and 132 (66%) had skin and soft tissue infections (SSTIs). Among patients with invasive infections, <it>S. aureus </it>isolates were more likely to be susceptible to methicillin (MSSA 63% vs. MRSA 37%), whereas patients with SSTIs, <it>S. aureus </it>isolates were more likely to be resistant to methicillin (MRSA 64% vs. MSSA 36%). Bacteremia and musculoskeletal infections were the most common invasive infections in both groups of <it>S. aureus</it>. Pneumonia with empyema was more likely to be caused by MRSA (<it>P </it>= 0.02). The majority (~90%) of MRSA isolates were non-multidrug resistant, even in the presence of healthcare-associated risk factors.</p> <p>Conclusion</p> <p>Epidemiological data at the local level is important for antimicrobial decision-making. MSSA remains an important pathogen causing invasive community-onset <it>S. aureus </it>infections among hospitalized children. In our hospital, nafcillin in combination with vancomycin is recommended empiric therapy in critically ill patients with suspected invasive staphylococcal infections. Because up to 25% of MSSA circulating in our area are clindamycin-resistant, clindamycin should be used cautiously as empiric monotherapy in patients with suspected invasive staphylococcal infections.</p

Zinc adjunct therapy reduces case fatality in severe childhood pneumonia: a randomized double blind placebo-controlled trial

<p>Abstract</p> <p>Background</p> <p>Pneumonia is a leading cause of children's deaths in developing countries and hinders achievement of the fourth Millennium Development Goal. This goal aims to reduce the under-five mortality rate, by two thirds, between 1990 and 2015.</p> <p>Few studies have examined the impact of zinc adjunct therapy on the outcome of childhood pneumonia. We determined the effect of zinc as adjunct therapy on time to normalization of respiratory rate, temperature and oxygen saturation. We also studied the effect of zinc adjunct therapy on case fatality of severe childhood pneumonia (as a secondary outcome) in Mulago Hospital, Uganda.</p> <p>Methods</p> <p>In this double blind, randomized, placebo-controlled clinical trial, 352 children aged 6 to 59 months, with severe pneumonia were randomized to zinc (20 mg for children ≥12 months, and 10 mg for those < 12 months) or a placebo once daily for seven days, in addition to standard antibiotics for severe pneumonia. Children were assessed every six hours. Oxygen saturation was normal if it was above 92% (breathing room air) for more than 15 minutes. The respiratory rate was normal if it was consistently (more than 24 hours) below 50 breaths per minute in infants and 40 breaths per minute in children above 12 months of age. Temperature was normal if consistently below 37.5°C. The difference in case fatality was expressed by the risk ratio between the two groups.</p> <p>Results</p> <p>Time to normalization of the respiratory rate, temperature and oxygen saturation was not significantly different between the two arms.</p> <p>Case fatality was 7/176 (4.0%) in the zinc group and 21/176 (11.9%) in the placebo group: Relative Risk 0.33 (95% CI 0.15 to 0.76). Relative Risk Reduction was 0.67 (95% CI 0.24 to 0.85), while the number needed to treat was 13. Among HIV infected children, case fatality was higher in the placebo (7/27) than in the zinc (0/28) group; RR 0.1 (95% CI 0.0, 1.0).</p> <p>Among 127 HIV uninfected children receiving the placebo, case fatality was 7/127 (5.5%); versus 5/129 (3.9%) among HIV uninfected group receiving zinc: RR 0.7 (95% CI 0.2, 2.2). The excess risk of death attributable to the placebo arm (Absolute Risk Reduction or ARR) was 8/100 (95% CI: 2/100, 14/100) children. This excess risk was substantially greater among HIV positive children than in HIV negative children (ARR: 26 (95% CI: 9, 42) per 100 versus 2 (95% CI: -4, 7) per 100); <it>P</it>-value for homogeneity of risk differences = 0.006.</p> <p>Conclusion</p> <p>Zinc adjunct therapy for severe pneumonia had no significant effect on time to normalization of the respiratory rate, temperature and oxygen saturation. However, zinc supplementation in these children significantly decreased case fatality.</p> <p>The difference in case fatality attributable to the protective effect of zinc therapy was greater among HIV infected than HIV uninfected children. Given these results, zinc could be considered for use as adjunct therapy for severe pneumonia, especially among Highly Active Antiretroviral Therapy</p> <p>naïve HIV infected children in our environment.</p> <p>Clinical trials registration number</p> <p>clinicaltrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT00373100">NCT00373100</a></p

Fusidic acid and clindamycin resistance in community-associated, methicillin-resistant Staphylococcus aureus infections in children of Central Greece

<p>Abstract</p> <p>Introduction</p> <p>In Greece, fusidic acid and clindamycin are commonly used for the empiric therapy of suspected staphylococcal infections.</p> <p>Methods</p> <p>The medical records of children examined at the outpatient clinics or admitted to the pediatric wards of the University General Hospital of Larissa, Central Greece, with community-associated staphylococcal infections from January 2003 to December 2009 were reviewed.</p> <p>Results</p> <p>Of 309 children (0-14 years old), 21 (6.8%) had invasive infections and 288 (93.2%) skin and soft tissue infections (SSTIs). Thirty-five patients were ≤30 days of age. The proportion of staphylococcal infections caused by a community-associated methicillin-resistant <it>Staphylococcus aureus </it>(CA-MRSA) isolate increased from 51.5% (69 of 134) in 2003-2006 to 63.4% (111 of 175) in 2007-2009 (<it>P </it>= 0.037). Among the CA-MRSA isolates, 88.9% were resistant to fusidic acid, 77.6% to tetracycline, and 21.1% to clindamycin. Clindamycin resistance increased from 0% (2003) to 31.2% (2009) among the CA-MRSA isolates (<it>P </it>= 0.011). Over the 7-year period, an increase in multidrug-resistant CA-MRSA isolates was observed (<it>P </it>= 0.004). One hundred and thirty-one (93.6%) of the 140 tested MRSA isolates were Panton-Valentine leukocidin-positive. Multilocus sequence typing of 72 CA-MRSA isolates revealed that they belonged to ST80 (n = 61), ST30 (n = 6), ST377 (n = 3), ST22 (n = 1), and ST152 (n = 1). Resistance to fusidic acid was observed in ST80 (58/61), ST30 (1/6), and ST22 (1/1) isolates.</p> <p>Conclusion</p> <p>In areas with high rate of infections caused by multidrug-resistant CA-MRSA isolates, predominantly belonging to the European ST80 clone, fusidic acid and clindamycin should be used cautiously as empiric therapy in patients with suspected severe staphylococcal infections.</p

Medium-size-vessel vasculitis

Medium-size-artery vasculitides do occur in childhood and manifest, in the main, as polyarteritis nodosa (PAN), cutaneous PAN and Kawasaki disease. Of these, PAN is the most serious, with high morbidity and not inconsequential mortality rates. New classification criteria for PAN have been validated that will have value in epidemiological studies and clinical trials. Renal involvement is common and recent therapeutic advances may result in improved treatment options. Cutaneous PAN is a milder disease characterised by periodic exacerbations and often associated with streptococcal infection. There is controversy as to whether this is a separate entity or part of the systemic PAN spectrum. Kawasaki disease is an acute self-limiting systemic vasculitis, the second commonest vasculitis in childhood and the commonest cause of childhood-acquired heart disease. Renal manifestations occur and include tubulointerstitial nephritis and renal failure. An infectious trigger and a genetic predisposition seem likely. Intravenous immunoglobulin (IV-Ig) and aspirin are effective therapeutically, but in resistant cases, either steroid or infliximab have a role. Greater understanding of the pathogenetic mechanisms involved in these three types of vasculitis and better long-term follow-up data will lead to improved therapy and prediction of prognosis

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

Alendronate improves bone mineral density in perinatally HIV-infected children and adolescents with low bone mineral density for age

BACKGROUND: Perinatally HIV-infected (PHIV) children and adolescents with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in HIV-infected youth. METHODS: Fifty-two PHIV 11- \u3c 25 years of age with low lumbar spine (LS) BMD (Z-score \u3c -1.5) were randomized to receive once-weekly alendronate or placebo in a double-blind cross-over study designed to assess the safety and efficacy of 48 and 96 weeks of alendronate in the US and Brazil (ClinicalTrials.gov # NCT000921557). All participants received daily calcium carbonate and vitamin D supplementation and were asked to engage in regular weight-bearing exercise. Safety and efficacy are summarized for the initial 48 weeks of the trial. RESULTS: Grade \u3e /= 3 abnormal laboratory values, signs, or symptoms developed in 5 of 32 (16%) participants on alendronate and 2 of 18 (11%) on placebo (p \u3e 0.99). No cases of jaw osteonecrosis, atrial fibrillation, or non-healing fractures were reported. Mean increases (95% confidence interval) in LS BMD over 48 weeks were significantly larger on alendronate [20% (14%, 25%)] than placebo [7% (5%, 9%), p \u3c 0.001]. Similar improvements were seen for whole body BMD. CONCLUSIONS: In this small study in PHIV children and adolescents with low LS BMD, 48 weeks of alendronate was well-tolerated, showed no safety concerns, and significantly improved LS and whole body BMD compared to participants on vitamin D/calcium supplementation and exercise alone