Background

The optimum strategy for stopping treatment with drugs that have different half-lives in a combination regimen to minimize the risk of selecting drug-resistant viruses remains unknown. We evaluated drug concentrations in plasma, human immunodeficiency virus (HIV) load, and development of drug resistance after a planned treatment interruption of a nonnucleoside reverse-transcriptase inhibitor (NNRTI)–containing regimen in HIV type 1–infected children.

Methods

Children with viral loads <50 copies/mL and CD4 cell percentages ≥30% (for children aged 2–6 years) or CD4 cell percentages ≥25% and CD4 cell counts ≥500 cells/μL (for children aged 7–15 years) were randomized to either a planned treatment interruption or to continuous therapy. In the planned treatment interruption arm, either (1) treatment with nevirapine or efavirenz was stopped, and treatment with the remaining drugs was continued for 7–14 days, or (2) nevirapine or efavirenz were replaced by a protease inhibitor, and all drugs were stopped after 7–14 days. Sampling for determination of plasma drug concentrations, measurement of viral load, and drug resistance testing was scheduled at day 0, day 7 (drug concentrations only), day 14, and day 28 after interruption of treatment with an NNRTI.

Results

Treatment with an NNRTI was interrupted for 35 children (20 were receiving nevirapine, and 15 were receiving efavirenz). Median time from NNRTI cessation to stopping all drugs was 9 days (range, 6–15 days) for nevirapine and 14 days (range, 6–18 days) for efavirenz. At 7 days, 1 (5%) of 19 and 4 (50%) of 8 children had detectable nevirapine and efavirenz concentrations, respectively; efavirenz remained detectable in 3 (25%) of 12 children at 14 days. At 14 days, viral load was ≥50 copies/mL in 6 of 16 children interrupting treatment with nevirapine (range, 52–7000 copies/mL) and in 2 of 12 children interrupting treatment with efavirenz (range, 120–1600 copies/mL). No new NNRTI mutations were observed.

Conclusions

In children with virological suppression who experienced interruption of treatment with an NNRTI, staggered or replacement stopping strategies for a median of 9 days for nevirapine and 14 days for efavirenz were not associated with the selection of NNRTI resistance mutations.

Consecutive missed doses may differentially impact the efficacy of antiretroviral therapy associated with the use of a nonnucleoside reverse-transcriptase inhibitor (NNRTI) and a ritonavir-boosted protease inhibitor (PI). In a cohort of 72 subjects receiving a boosted PI, average adherence to dosage was a better predictor of human immunodeficiency virus (HIV) replication than was the duration or frequency of treatment interruption. In contrast with an NNRTI, consecutive missed doses of a boosted PI did not emerge as a major risk factor for HIV replication.

Background

Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in patients hospitalized in intensive care units. Recent studies suggest that dental plaque biofilms serve as a reservoir for respiratory pathogens. The goal of this study was to determine the genetic relationship between strains of respiratory pathogens first isolated from the oral cavity and later isolated from bronchoalveolar lavage fluid from the same patient undergoing mechanical ventilation with suspected VAP.

Methods

Plaque and tracheal secretion samples were obtained on the day of hospital admission and every other day thereafter until discharge from the intensive care unit from 100 patients who underwent mechanical ventilation. Bronchoalveolar lavage was performed for 30 patients with suspected VAP. Pulse-field gel electrophoresis and multilocus sequence typing were used to determine the genetic relatedness of strains obtained from oral, tracheal, and bronchoalveolar lavage samples.

Results

Isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter species, and enteric species recovered from plaque from most patients were indistinguishable from isolates recovered from bronchoalveolar lavage fluid (i.e., had >95% similarity of pulse-field gel electrophoresis patterns). Nearly one-half of the Pseudomonas strains showed identical genetic profiles between patients, which suggested a common environmental source of infection.

Conclusions

Respiratory pathogens isolated from the lung are often genetically indistinguishable from strains of the same species isolated from the oral cavity in patients who receive mechanical ventilation who are admitted to the hospital from the community. Thus, dental plaque serves as an important reservoir for respiratory pathogens in patients who undergo mechanical ventilation.

Trial registration

ClinicalTrials.gov identifier: NCT00123123

The United Nations is committed to achieving universal access to HIV care, treatment, and prevention. Although the gateway to HIV care and secondary prevention is knowledge of serostatus, use of voluntary counseling and testing in resource-limited settings with the highest burden of HIV/AIDS has been limited. Based on evidence of increased patient uptake and the opportunity to avoid missed HIV testing opportunities in health care facilities, in 2007 the World Health Organization recommended provider-initiated HIV testing as a standard part of medical care in settings of generalized HIV epidemics. While provider-initiated testing has shown promise, optimal implementation strategies which ensure broad coverage, while preserving human rights, remain an active area of research. We review the benefits of knowledge of HIV serostatus and evidence from multiple countries surrounding the successes and pitfalls of provider-initiated testing in health care and home-based settings.

Objective

We compared differences in the hospital charges, length of hospital stay, and mortality between patients with healthcare- and community-associated bloodstream infections, urinary tract infections, and pneumonia due to antimicrobial-resistant versus -susceptible bacterial strains.

Methods

A retrospective analysis of an electronic database compiled from laboratory, pharmacy, surgery, financial, and patient location and device utilization sources was undertaken on 5699 inpatients who developed healthcare-or community-associated infections between 2006 and 2008 from 4 hospitals (1 community, 1 pediatric, 2 tertiary/quaternary care) in Manhattan. The main outcome measures were hospital charges, length of stay, and mortality among patients with antimicrobial-resistant and -susceptible infections caused by Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii.

Results

Controlling for multiple confounders using linear regression and nearest neighbor matching based on propensity score estimates, resistant healthcare- and community-associated infections, when compared with susceptible strains of the same organism, were associated with significantly higher charges ($15 626; confidence interval [CI], $4339–$26 913 and $25 573; CI, $9331–$41 816, respectively) and longer hospital stays for community-associated infections (3.3; CI, 1.5–5.4). Patients with resistant healthcare-associated infections also had a significantly higher death rate (0.04; CI, 0.01–0.08).

Conclusions

With careful matching of patients infected with the same organism, antimicrobial resistance was associated with higher charges, length of stay, and death rates. The difference in estimates after accounting for censoring for death highlight divergent social and hospital incentives in reducing patient risk for antimicrobial resistant infections.

Background

Role of serum cryptococcal antigen in the diagnosis and determinants of antigen positivity in solid organ transplant (SOT) recipients with pulmonary cryptococcosis has not been fully defined.

Methods

Study population included SOT recipients with pulmonary cryptococcosis in a prospective, multicenter study conducted between 1999 and 2006.

Results

Cryptococcal antigen was positive in 83% (40/48) of the patients with pulmonary cryptococcosis. Patients with concomitant extrapulmonary disease were more likely to have a positive antigen (p=0.018), and antigen titers were higher in those with extrapulmonary disease (p=0.003) or fungemia (p=0.045). Patients with single nodules were less likely to have a positive antigen than those with all other radiographic presentations (p=0.053). Among patients with isolated pulmonary cryptococcosis, lung transplant recipients were less likely to have positive cryptococcal antigen than other types of SOT recipients (p=0.003). In all, 38% of the patients were asymptomatic or had pulmonary cryptococcosis detected as an incidental finding. Nodular densities or mass lesions were more likely to present as asymptomatic or incidentally detected pulmonary cryptococcosis than pleural effusions and infiltrates (p=0.008).

Conclusions

A positive serum cryptococcal antigen in SOT recipients with pulmonary cryptococcosis appears to reflect extrapulmonary or more advanced radiographic disease.

Background

The Centers for Disease Control and Prevention recently recommended the expansion of human immunodeficiency virus (HIV) antibody testing. However, antibody tests have longer “window periods” after HIV acquisition than do nucleic acid amplification tests (NAATs).

Methods

Public Health–Seattle & King County offered HIV antibody testing to men who have sex with men (MSM) using the OraQuick Advance Rapid HIV-1/2 Antibody Test (OraQuick; OraSure Technologies) on oral fluid or finger-stick blood specimens or using a first- or second-generation enzyme immunoassay. The enzyme immunoassay was also used to confirm reactive rapid test results and to screen specimens from OraQuick-negative MSM prior to pooling for HIV NAAT. Serum specimens obtained from subsets of HIV-infected persons were retrospectively evaluated by use of other HIV tests, including a fourth-generation antigen-antibody combination assay.

Results

From September 2003 through June 2008, a total of 328 (2.3%) of 14,005 specimens were HIV antibody positive, and 36 (0.3%) of 13,677 antibody-negative specimens were NAAT positive (indicating acute HIV infection). Among 6811 specimens obtained from MSM who were initially screened by rapid testing, OraQuick detected only 153 (91%) of 169 antibody-positive MSM and 80% of the 192 HIV-infected MSM detected by the HIV NAAT program. HIV was detected in serum samples obtained from 15 of 16 MSM with acute HIV infection that were retrospectively tested using the antigen-antibody combination assay.

Conclusions

OraQuick may be less sensitive than enzyme immunoassays during early HIV infection. NAAT should be integrated into HIV testing programs that serve populations that undergo frequent testing and that have high rates of HIV acquisition, particularly if rapid HIV antibody testing is employed. Antigen-antibody combination assays may be a reasonably sensitive alternative to HIV NAAT.

Background

We sought to characterize the clinical and molecular epidemiologic characteristics of Staphylococcus aureus colonization (especially extranasal colonization) and to determine the extent to which community-associated methicillin-resistant S. aureus (MRSA) has emerged in community nursing homes.

Methods

The study enrolled a total of 213 residents, with or without an indwelling device, from 14 nursing homes in southeastern Michigan. Samples were obtained from the nares, oropharynx, groin, perianal area, wounds, and enteral feeding tube site. Standard microbiologic methods were used to identify methicillin-susceptible S. aureus and MRSA. Molecular epidemiologic methods included pulsed-field gel electrophoresis, PCR detection of Panton-Valentine leukocidin, and SCCmec and agr typing.

Results

One hundred thirty-one residents (62%) were colonized with S. aureus (MRSA colonization in 86). S. aureus colonization occurred in 80 (76%) of 105 residents with indwelling devices and in 51 (47%) of 108 residents without indwelling devices (P < .001). Of the 86 residents who were colonized with MRSA, nares culture results were positive for only 56 (65%). Residents with devices in place were more likely to be colonized at multiple sites. Eleven different strains of MRSA were identified by pulsed-field gel electrophoresis. Seventy-three residents (85%) were colonized with hospital-associated SCCmec II strains, and 8 (9%) were colonized with community-associated SCCmec IV strains, 2 of which carried Panton-Valentine leukocidin.

Conclusions

Extranasal colonization with MRSA is common among nursing home residents—particularly among residents with an indwelling device. We documented the emergence of community-associated SCCmec IV MRSA strains in the community nursing home setting in southeastern Michigan.

Mupirocin has been used in nursing homes to prevent the spread of methicillin-resistant Staphylococcus aureus (MRSA), despite the lack of controlled trials. In this double-blind, randomized study, the efficacy of intranasal mupirocin ointment versus that of placebo in reducing colonization and preventing infection was assessed among persistent carriers of S. aureus. Twice-daily treatment was given for 2 weeks, with a follow-up period of 6 months. Staphylococcal colonization rates were similar between residents at the Ann Arbor Veterans Affairs (VA) Extended Care Center, Michigan (33%), and residents at a community-based long-term care facility in Ann Arbor (36%), although those at the VA Center carried MRSA more often (58% vs. 35%; P = .017). After treatment, mupirocin had eradicated colonization in 93% of residents, whereas 85% of residents who received placebo remained colonized (P < .001). At day 90 after study entry, 61% of the residents in the mupirocin group remained decolonized. Four patients did not respond to mupirocin therapy; 3 of the 4 had mupirocin-resistant S. aureus strains. Thirteen (86%) of 14 residents who became recolonized had the same pretherapy strain; no strain recovered during relapse was resistant to mupirocin. A trend toward reduction in infections was seen with mupirocin treatment.

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-α) inhibitors for rheumatologic disorders. Although TNF-α inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti–TNF-α drugs and herpes simplex virus encephalitis has not been previously described.

Background

Clinical signs and symptoms of acute human immunodeficiency virus (HIV) infection in infants are not well characterized.

Methods

Serial clinical assessments and HIV PCR assays were conducted in a cohort of children born to HIV-seropositive mothers from birth to 2 years of age. Acute HIV infection visits were defined as those up to 3 months prior to and including the visit at which HIV DNA was first detected. Noninfection visits included all visits at which the child had test results negative for HIV, including the last visit at which a test result negative for HIV DNA was obtained in children who later acquired HIV infection. Differences in the prevalence of symptoms at acute infection versus noninfection visits were determined overall and were stratified by age at infection (<2 months vs. ≥2 months). HIV RNA was measured serially in infected infants and was compared between infants with and infants without symptoms of acute HIV infection.

Results

There were 125 acute infection visits (among 56 infants) and 3491 noninfection visits (among 306 infants). Acute HIV infection was associated with rash (odds ratio [OR], 1.8; 95% confidence interval [CI], 1.1–2.8), failure to thrive (OR, 1.9; 95% CI, 1.0–3.5), and lymphadenopathy (OR, 2.5; 95% CI, 1.4–4.8). Acute HIV infection was associated with lymphadenopathy (OR, 2.6; 95% CI, 1.3–5.0) in infants <2 months of age and with pneumonia (OR, 3.2; 95% CI, 1.1–9.3) and dehydration (OR, 6.0; 95% CI, 1.9–18.5) in infants ≥2 months of age. Infant peak viral load and mortality were not associated with symptoms of acute HIV infection. However, infants with symptoms had higher viral levels later in the course of infection than did those without symptoms (P = .05).

Conclusions

Infants may manifest symptoms early during the course of HIV infection, and symptoms of acute HIV infection may correlate with poor viral control. Rash, failure to thrive, lymphadenopathy, pneumonia, and dehydration may signify acute HIV infection in infants.

Prevention of mother-to-child transmission of HIV-1 (MTCT) remains a challenge in most resource-limited settings, particularly in Africa. Single-dose and short-course antiretroviral (ARV) regimens are only partially effective and have failed to achieve wide coverage despite their apparent simplicity. More potent ARV combinations are restricted to pregnant women who need treatment for themselves but are also infrequently used. Furthermore, postnatal transmission via breastfeeding is a serious additional threat. Modifications of infant feeding practices aim to reduce breast-milk HIV transmission: replacement feeding is neither affordable nor safe for the majority of African women, and early breastfeeding cessation (e.g. prior to 6 months of life) requires substantial care and nutritional counselling to be practised safely. The recent roll out of ARV treatment has changed the paradigm of prevention of MTCT. To date, postnatal ARV interventions that have been evaluated target either maternal ARV treatment to selected breastfeeding women, with good efficacy, or single-drug post-exposure prophylaxis for short periods of time to their neonates, with a partial efficacy and at the expense of acquisition of drug-related viral resistance. We hypothesize that a viable solution to eliminate paediatric AIDS lies in the universal provision of fully suppressive ARV regimens to all HIV-infected women through pregnancy, delivery, and covering the entire breastfeeding period. Based on the available evidence, we suggest translating into practice the recently available evidence on this matter without any further delay.

Infections in skilled nursing facilities (SNFs) are common and result in frequent hospital transfers, functional decline, and death. Colonization with multidrug-resistant organisms (MDROs) – including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacilli (R-GNB) – is also increasingly prevalent in SNFs. Antimicrobial resistance among common bacteria can adversely affect clinical outcomes and increase health care costs. Recognizing a need for action, legislators, policy-makers, and consumer groups are advocating for surveillance cultures to identify asymptomatic patients with MDROs, particularly MRSA in hospitals and SNFs. Implementing this policy for all SNF residents may be costly, impractical, and ineffective. Such a policy may result in a large increase in the number of SNF residents placed in isolation precautions with the potential for reduced attention by health care workers, isolation, and functional decline. Detection of colonization and subsequent attempts to eradicate selected MDROs can also lead to more strains with drug resistance. We propose an alternative strategy that uses a focused multicomponent bundle approach that targets residents at a higher risk of colonization and infection with MDROs, specifically those who have an indwelling device. If this strategy is effective, similar strategies can be studied and implemented for other high-risk groups.

Infections in skilled nursing facilities (SNFs) are common and result in frequent hospital transfers, functional decline, and death. Colonization with multidrug-resistant organisms (MDROs) – including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and multidrug-resistant gram-negative bacilli (R-GNB) – is also increasingly prevalent in SNFs. Antimicrobial resistance among common bacteria can adversely affect clinical outcomes and increase health care costs. Recognizing a need for action, legislators, policy-makers, and consumer groups are advocating for surveillance cultures to identify asymptomatic patients with MDROs, particularly MRSA in hospitals and SNFs. Implementing this policy for all SNF residents may be costly, impractical, and ineffective. Such a policy may result in a large increase in the number of SNF residents placed in isolation precautions with the potential for reduced attention by health care workers, isolation, and functional decline. Detection of colonization and subsequent attempts to eradicate selected MDROs can also lead to more strains with drug resistance. We propose an alternative strategy that uses a focused multicomponent bundle approach that targets residents at a higher risk of colonization and infection with MDROs, specifically those who have an indwelling device. If this strategy is effective, similar strategies can be studied and implemented for other high-risk groups.

We revealed that treatment of seasonal influenza virus-infected pediatric patients with zanamivir resulted in the emergence of fewer drug-resistant influenza viruses and less virus shedding than did treatment with oseltamivir.

(See editorial commentary by Dolan on pages 438-439.)

Background. Although influenza virus resistance to the neuraminidase inhibitor zanamivir is reported less frequently than is resistance to the neuraminidase inhibitor oseltamivir in clinical settings, it is unknown whether this difference is due to the limited use of zanamivir or to an inherent property of the drug. We therefore compared the prevalence of drug-resistant viruses and virus shedding in seasonal influenza virus–infected children treated with either oseltamivir or zanamivir.

Methods. Clinical specimens (throat or nasal swab) were collected from a total of 144 pediatric influenza patients during the 2005–2006, 2006–2007, 2007–2008, and 2008–2009 influenza seasons. Neuraminidase inhibitor–resistant mutants were detected among the isolated viruses by sequencing the viral hemagglutinin and neuraminidase genes. Sensitivity of the viruses to neuraminidase inhibitors was tested by neuraminidase inhibition assay.

Results. In oseltamivir- or zanamivir-treated influenza patients who were statistically comparable in their age distribution, vaccination history, and type or subtype of virus isolates, the virus-shedding period in zanamivir-treated patients was significantly shorter than that in oseltamivir-treated patients. Furthermore, the frequency of zanamivir-resistant viruses was significantly lower than that of oseltamivir-resistant viruses.

Conclusion. In comparison with treatment with oseltamivir, treatment of pediatric patients with zanamivir resulted in the emergence of fewer drug-resistant influenza viruses and a shorter virus-shedding period. We conclude that zanamivir shows promise as a better therapy for pediatric influenza patients.

Background

Many resource-limited countries rely on clinical and immunologic monitoring without routine virologic monitoring of HIV-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV viral load (VL) had independent predictive value in the presence of immunologic and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (WHO events) among HIV-infected children receiving HAART in Latin America.

Methods

The NICHD International Site Development Initiative (NISDI) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes in infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess the time to new WHO events as a function of immunological status, VL, hemoglobin and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors.

Results

The mean follow-up was 2.5 years; new WHO events occurred in 16% of 584 children. In proportional hazards modeling, most recent VL > 5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio=1.81, 95% CI 1.05–3.11; p=0.033), even after adjustment for CD4-defined immunosuppression, hemoglobin level, age and body mass index.

Conclusions

Routine virologic monitoring, using the WHO virologic failure threshold of 5,000 copies/mL, adds independent predictive value to immunologic and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virologic monitoring should be considered for all settings providing HAART to children.

Background. Many resource-limited countries rely on clinical and immunological monitoring without routine virological monitoring for human immunodeficiency virus (HIV)-infected children receiving highly active antiretroviral therapy (HAART). We assessed whether HIV load had independent predictive value in the presence of immunological and clinical data for the occurrence of new World Health Organization (WHO) stage 3 or 4 events (hereafter, WHO events) among HIV-infected children receiving HAART in Latin America.

Methods. The NISDI (Eunice Kennedy Shriver National Institute of Child Health and Human Development International Site Development Initiative) Pediatric Protocol is an observational cohort study designed to describe HIV-related outcomes among infected children. Eligibility criteria for this analysis included perinatal infection, age <15 years, and continuous HAART for ≥6 months. Cox proportional hazards modeling was used to assess time to new WHO events as a function of immunological status, viral load, hemoglobin level, and potential confounding variables; laboratory tests repeated during the study were treated as time-varying predictors.

Results. The mean duration of follow-up was 2.5 years; new WHO events occurred in 92 (15.8%) of 584 children. In proportional hazards modeling, most recent viral load >5000 copies/mL was associated with a nearly doubled risk of developing a WHO event (adjusted hazard ratio, 1.81; 95% confidence interval, 1.05–3.11; P = .033), even after adjustment for immunological status defined on the basis of CD4 T lymphocyte value, hemoglobin level, age, and body mass index.

Conclusions. Routine virological monitoring using the WHO virological failure threshold of 5000 copies/mL adds independent predictive value to immunological and clinical assessments for identification of children receiving HAART who are at risk for significant HIV-related illness. To provide optimal care, periodic virological monitoring should be considered for all settings that provide HAART to children.

Background

World Health Organization guidelines for antiretroviral treatment (ART) in resource-limited settings recommend either stavudine or tenofovir as part of initial therapy. We evaluated the clinical outcomes and cost-effectiveness of first-line ART using tenofovir in India, compared to current practice using stavudine or zidovudine.

Methods

We used a state-transition model of HIV disease to examine strategies using different nucleoside reverse transcriptase inhibitors, combined with lamivudine and nevirapine, compared to no ART: 1) stavudine; 2) stavudine, with substitution by zidovudine after six months; 3) zidovudine; 4) tenofovir. Data were from the Y.R. Gaitonde Centre for AIDS Research and Education in Chennai, India and published studies.

Results

Discounted mean per person survival was 36.9 months (40.1 months undiscounted) with no ART, 115.5 months (145.3) with stavudine-containing ART, 115.6 months (145.5) with stavudine and six-month zidovudine substitution, 115.7 months (145.6) with zidovudine-containing ART, and 125.9 months (162.2) with initial tenofovir. Discounted lifetime medical costs were $610 with no ART and ranged from $5,560 with stavudine-containing ART to $5,720 with zidovudine-containing ART. Initial tenofovir had an incremental cost-effectiveness ratio of $670/year of life saved compared to no ART and was more economically efficient than the other regimens. Results were most sensitive to variations in the costs of first-line tenofovir, access to additional ART after failure, mean initial CD4 count, and quality of life adjustment.

Conclusions

Using tenofovir as part of first-line ART in India will improve survival, is cost-effective by international standards, and should be considered for initial therapy for HIV-infected patients in India.

Background

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) expressing Panton-Valentine Leukocidin (PVL) cause severe skin and soft tissue infections (SSTI), necrotizing pneumonia and other invasive infections. PVL toxin has been implicated as a virulence factor and antibody to a component of this toxin is under investigation as a vaccine candidate. The role of PVL in pathogenesis remains controversial and it is unknown if human serum antibody to PVL modulates infection.

Methods

We determined antibody levels to PVL in sera from children aged 0-18 years presenting with PCR-confirmed PVL-positive MRSA SSTI with or without prior MRSA infection or SSTI, PVL-positive MRSA invasive infections, PVL-negative MRSA infections and uninfected controls. We also measured antibody-mediated neutralization of PVL-induced lysis of human polymorphonuclear cells.

Results

Antibody to PVL was present in healthy children reaching adult levels by 4-6 years with a nadir at 4-6 months likely due to loss of maternal antibody. Children with a primary PVL-positive MRSA infection had moderate levels of antibody to PVL that increased following infection. Children with prior MRSA or SSTI infections had high levels of antibody to PVL at the onset of infection. There was no increase in antibody to PVL in this populations’ sera after the onset of infection. Sera from children with PVL-positive MRSA SSTIs, particularly those with prior MRSA or SSTI, and convalescent sera from children with invasive PVL-positive MRSA infection, potently inhibited PVL-induced lysis of PMNs.

Conclusions

Neutralizing antibody to PVL does not protect children against primary or recurrent CA-MRSA SSTI.

There are currently seven approved therapies for chronic hepatitis B infection, an increase from just three agents five years ago. This review will focus on the pharmacology, potency, and adverse events associated with immunomodulatory agents and nucleos(t)ide analogs, with an emphasis on targets of therapy within the hepatitis B lifecycle. We will also offer guidelines for the use of available anti-HBV agents and review the emerging challenges in hepatitis B management, including HBV drug resistance, its management, and the potential role of combination therapy.

Background

Serial cross-sectional data on antibody levels to 2009 pandemic influenza A (H1N1) virus from a population can be used to estimate the infection attack rates and immunity against future infection in the community.

Methods

Between April and December 2009, we obtained 12,217 serum specimens from blood donors (16–59 yo), 2,520 from hospital outpatients (5–59yo), and 917 from subjects of a community pediatric cohort study (5–14yo). We estimated infection attack rates by comparing the proportions of specimens with antibody titers ≥1:40 by viral microneutralization before and after the first wave of the pandemic. Estimates were validated using paired sera from 324 individuals that spanned the first wave. Combining these estimates with epidemiologic surveillance data, we calculated the proportion of infections that led to hospitalization, intensive care admission, and death.

Results

We found that 3.3% and 14% of 5–59 yo had antibody titers ≥1:40 before and after the first wave. The overall attack rate was 10.7% with the following age-stratification: 43.4% in 5–14 yo, 15.8% in 15–19 yo, 11.8% in 20–29 yo, and 4–4.6% in 30–59 yo. Case-hospitalization rates were 0.47%–0.87% among 5–59 yo. Case-ICU and case-fatality rates increased from 7.9 and 0.4 per 100,000 infections in 5–14 yo to 75 and 26.5 per 100,000 infections in 50–59 yo.

Conclusions

Almost half of all school-children in Hong Kong were infected during the first wave. Compared to school-children aged 5–14, older adults aged 50–59 had 9.5 and 66 times higher risk of ICU admission and death if infected.

Previously, we found that 4 weeks of treatment with lopinavir-ritonavir did not decrease insulin sensitivity but did increase adiponectin levels. In the present study, a single dose of lopinavir-ritonavir decreases insulin sensitivity but does not alter adiponectin levels. Insulin resistance from protease inhibitors may decrease with prolonged use; an increase in adiponectin levels may mediate this effect.