Last data update: May 13, 2024. (Total: 46773 publications since 2009)
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Suspected SARS-CoV-2 Reinfections: Incidence, Predictors, and Healthcare Use among Patients at 238 U.S. Healthcare Facilities, June 1, 2020- February 28, 2021.
Lawandi A , Warner S , Sun J , Demirkale CY , Danner RL , Klompas M , Gundlapalli A , Datta D , Harris AM , Morris SB , Natarajan P , Kadri SS . Clin Infect Dis 2021 74 (8) 1489-1492 In a retrospective cohort study, among 131,773 patients with previous COVID19, reinfection with SARS-CoV-2 was suspected in 253(0.2%) patients at 238 U.S. healthcare facilities between June 1, 2020- February 28, 2021. Women displayed a higher cumulative reinfection risk. Healthcare burden and illness severity were similar between index and reinfection encounters. |
Association Between Caseload Surge and COVID-19 Survival in 558 U.S. Hospitals, March to August 2020.
Kadri SS , Sun J , Lawandi A , Strich JR , Busch LM , Keller M , Babiker A , Yek C , Malik S , Krack J , Dekker JP , Spaulding AB , Ricotta E , Powers Iii JH , Rhee C , Klompas M , Athale J , Boehmer TK , Gundlapalli AV , Bentley W , Datta SD , Danner RL , Demirkale CY , Warner S . Ann Intern Med 2021 174 (9) 1240-1251 BACKGROUND: Several U.S. hospitals had surges in COVID-19 caseload, but their effect on COVID-19 survival rates remains unclear, especially independent of temporal changes in survival. OBJECTIVE: To determine the association between hospitals' severity-weighted COVID-19 caseload and COVID-19 mortality risk and identify effect modifiers of this relationship. DESIGN: Retrospective cohort study. (ClinicalTrials.gov: NCT04688372). SETTING: 558 U.S. hospitals in the Premier Healthcare Database. PARTICIPANTS: Adult COVID-19-coded inpatients admitted from March to August 2020 with discharge dispositions by October 2020. MEASUREMENTS: Each hospital-month was stratified by percentile rank on a surge index (a severity-weighted measure of COVID-19 caseload relative to pre-COVID-19 bed capacity). The effect of surge index on risk-adjusted odds ratio (aOR) of in-hospital mortality or discharge to hospice was calculated using hierarchical modeling; interaction by surge attributes was assessed. RESULTS: Of 144 116 inpatients with COVID-19 at 558 U.S. hospitals, 78 144 (54.2%) were admitted to hospitals in the top surge index decile. Overall, 25 344 (17.6%) died; crude COVID-19 mortality decreased over time across all surge index strata. However, compared with nonsurging (<50th surge index percentile) hospital-months, aORs in the 50th to 75th, 75th to 90th, 90th to 95th, 95th to 99th, and greater than 99th percentiles were 1.11 (95% CI, 1.01 to 1.23), 1.24 (CI, 1.12 to 1.38), 1.42 (CI, 1.27 to 1.60), 1.59 (CI, 1.41 to 1.80), and 2.00 (CI, 1.69 to 2.38), respectively. The surge index was associated with mortality across ward, intensive care unit, and intubated patients. The surge-mortality relationship was stronger in June to August than in March to May (slope difference, 0.10 [CI, 0.033 to 0.16]) despite greater corticosteroid use and more judicious intubation during later and higher-surging months. Nearly 1 in 4 COVID-19 deaths (5868 [CI, 3584 to 8171]; 23.2%) was potentially attributable to hospitals strained by surging caseload. LIMITATION: Residual confounding. CONCLUSION: Despite improvements in COVID-19 survival between March and August 2020, surges in hospital COVID-19 caseload remained detrimental to survival and potentially eroded benefits gained from emerging treatments. Bolstering preventive measures and supporting surging hospitals will save many lives. PRIMARY FUNDING SOURCE: Intramural Research Program of the National Institutes of Health Clinical Center, the National Institute of Allergy and Infectious Diseases, and the National Cancer Institute. |
Equine-like H3 avian influenza viruses in wild birds, Chile
Bravo-Vasquez N , Yao J , Jimenez-Bluhm P , Meliopoulos V , Freiden P , Sharp B , Estrada L , Davis A , Cherry S , Livingston B , Danner A , Schultz-Cherry S , Hamilton-West C . Emerg Infect Dis 2020 26 (12) 2887-2898 Since their discovery in the United States in 1963, outbreaks of infection with equine influenza virus (H3N8) have been associated with serious respiratory disease in horses worldwide. Genomic analysis suggests that equine H3 viruses are of an avian lineage, likely originating in wild birds. Equine-like internal genes have been identified in avian influenza viruses isolated from wild birds in the Southern Cone of South America. However, an equine-like H3 hemagglutinin has not been identified. We isolated 6 distinct H3 viruses from wild birds in Chile that have hemagglutinin, nucleoprotein, nonstructural protein 1, and polymerase acidic genes with high nucleotide homology to the 1963 H3N8 equine influenza virus lineage. Despite the nucleotide similarity, viruses from Chile were antigenically more closely related to avian viruses and transmitted effectively in chickens, suggesting adaptation to the avian host. These studies provide the initial demonstration that equine-like H3 hemagglutinin continues to circulate in a wild bird reservoir. |
Inappropriate empirical antibiotic therapy for bloodstream infections based on discordant in-vitro susceptibilities: a retrospective cohort analysis of prevalence, predictors, and mortality risk in US hospitals
Kadri SS , Lai YL , Warner S , Strich JR , Babiker A , Ricotta EE , Demirkale CY , Dekker JP , Palmore TN , Rhee C , Klompas M , Hooper DC , Powers JH3rd , Srinivasan A , Danner RL , Adjemian J . Lancet Infect Dis 2020 21 (2) 241-251 BACKGROUND: The prevalence and effects of inappropriate empirical antibiotic therapy for bloodstream infections are unclear. We aimed to establish the population-level burden, predictors, and mortality risk of in-vitro susceptibility-discordant empirical antibiotic therapy among patients with bloodstream infections. METHODS: Our retrospective cohort analysis of electronic health record data from 131 hospitals in the USA included patients with suspected-and subsequently confirmed-bloodstream infections who were treated empirically with systemic antibiotics between Jan 1, 2005, and Dec 31, 2014. We included all patients with monomicrobial bacteraemia caused by common bloodstream pathogens who received at least one systemic antibiotic either on the day blood cultures were drawn or the day after, and for whom susceptibility data were available. We calculated the prevalence of discordant empirical antibiotic therapy-which was defined as receiving antibiotics on the day blood culture samples were drawn to which the cultured isolate was not susceptible in vitro-overall and by hospital type by using regression tree analysis. We used generalised estimating equations to identify predictors of receiving discordant empirical antibiotic therapy, and used logistic regression to calculate adjusted odds ratios for the relationship between in-hospital mortality and discordant empirical antibiotic therapy. FINDINGS: 21 608 patients with bloodstream infections received empirical antibiotic therapy on the day of first blood culture collection. Of these patients, 4165 (19%) received discordant empirical antibiotic therapy. Discordant empirical antibiotic therapy was independently associated with increased risk of mortality (adjusted odds ratio 1·46 [95% CI, 1·28-1·66]; p<0·0001), a relationship that was unaffected by the presence or absence of resistance or sepsis or septic shock. Infection with antibiotic-resistant species strongly predicted receiving discordant empirical therapy (adjusted odds ratio 9·09 [95% CI 7·68-10·76]; p<0·0001). Most incidences of discordant empirical antibiotic therapy and associated deaths occurred among patients with bloodstream infections caused by Staphylococcus aureus or Enterobacterales. INTERPRETATION: Approximately one in five patients with bloodstream infections in US hospitals received discordant empirical antibiotic therapy, receipt of which was closely associated with infection with antibiotic-resistant pathogens. Receiving discordant empirical antibiotic therapy was associated with increased odds of mortality overall, even in patients without sepsis. Early identification of bloodstream pathogens and resistance will probably improve population-level outcomes. FUNDING: US National Institutes of Health, US Centers for Disease Control and Prevention, and US Agency for Healthcare Research and Quality. |
Opioid Use Fueling HIV Transmission in an Urban Setting: An Outbreak of HIV Infection Among People Who Inject Drugs-Massachusetts, 2015-2018.
Alpren C , Dawson EL , John B , Cranston K , Panneer N , Fukuda HD , Roosevelt K , Klevens RM , Bryant J , Peters PJ , Lyss SB , Switzer W , Burrage A , Murray A , Agnew-Brune C , Stiles T , McClung P , Campbell EM , Breen C , Randall LM , Dasgupta S , Onofrey S , Bixler D , Hampton K , Jaeger JL , Hsu KK , Adih W , Callis B , Goldman LR , Danner SP , Jia H , Tumpney M , Board A , Brown C , DeMaria A Jr , Buchacz K . Am J Public Health 2019 110 (1) e1-e8 Objectives. To describe and control an outbreak of HIV infection among people who inject drugs (PWID).Methods. The investigation included people diagnosed with HIV infection during 2015 to 2018 linked to 2 cities in northeastern Massachusetts epidemiologically or through molecular analysis. Field activities included qualitative interviews regarding service availability and HIV risk behaviors.Results. We identified 129 people meeting the case definition; 116 (90%) reported injection drug use. Molecular surveillance added 36 cases to the outbreak not otherwise linked. The 2 largest molecular groups contained 56 and 23 cases. Most interviewed PWID were homeless. Control measures, including enhanced field epidemiology, syringe services programming, and community outreach, resulted in a significant decline in new HIV diagnoses.Conclusions. We illustrate difficulties with identification and characterization of an outbreak of HIV infection among a population of PWID and the value of an intensive response.Public Health Implications. Responding to and preventing outbreaks requires ongoing surveillance, with timely detection of increases in HIV diagnoses, community partnerships, and coordinated services, all critical to achieving the goal of the national Ending the HIV Epidemic initiative. (Am J Public Health. Published online ahead of print November 14, 2019: e1-e8. doi:10.2105/AJPH.2019.305366). |
Variation in identifying sepsis and organ dysfunction using administrative versus electronic clinical data and impact on hospital outcome comparisons
Rhee C , Jentzsch MS , Kadri SS , Seymour CW , Angus DC , Murphy DJ , Martin GS , Dantes RB , Epstein L , Fiore AE , Jernigan JA , Danner RL , Warren DK , Septimus EJ , Hickok J , Poland RE , Jin R , Fram D , Schaaf R , Wang R , Klompas M . Crit Care Med 2018 47 (4) 493-500 OBJECTIVES: Administrative claims data are commonly used for sepsis surveillance, research, and quality improvement. However, variations in diagnosis, documentation, and coding practices for sepsis and organ dysfunction may confound efforts to estimate sepsis rates, compare outcomes, and perform risk adjustment. We evaluated hospital variation in the sensitivity of claims data relative to clinical data from electronic health records and its impact on outcome comparisons. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 4.3 million adult encounters at 193 U.S. hospitals in 2013-2014. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sepsis was defined using electronic health record-derived clinical indicators of presumed infection (blood culture draws and antibiotic administrations) and concurrent organ dysfunction (vasopressors, mechanical ventilation, doubling in creatinine, doubling in bilirubin to >/= 2.0 mg/dL, decrease in platelets to < 100 cells/microL, or lactate >/= 2.0 mmol/L). We compared claims for sepsis prevalence and mortality rates between both methods. All estimates were reliability adjusted to account for random variation using hierarchical logistic regression modeling. The sensitivity of hospitals' claims data was low and variable: median 30% (range, 5-54%) for sepsis, 66% (range, 26-84%) for acute kidney injury, 39% (range, 16-60%) for thrombocytopenia, 36% (range, 29-44%) for hepatic injury, and 66% (range, 29-84%) for shock. Correlation between claims and clinical data was moderate for sepsis prevalence (Pearson coefficient, 0.64) and mortality (0.61). Among hospitals in the lowest sepsis mortality quartile by claims, 46% shifted to higher mortality quartiles using clinical data. Using implicit sepsis criteria based on infection and organ dysfunction codes also yielded major differences versus clinical data. CONCLUSIONS: Variation in the accuracy of claims data for identifying sepsis and organ dysfunction limits their use for comparing hospitals' sepsis rates and outcomes. Using objective clinical data may facilitate more meaningful hospital comparisons. |
Difficult-to-treat resistance in gram-negative bacteremia at 173 US hospitals: Retrospective cohort analysis of prevalence, predictors, and outcome of resistance to all first-line agents
Kadri SS , Adjemian J , Lai YL , Spaulding AB , Ricotta E , Prevots DR , Palmore TN , Rhee C , Klompas M , Dekker JP , Powers JH3rd , Suffredini AF , Hooper DC , Fridkin S , Danner RL . Clin Infect Dis 2018 67 (12) 1803-1814 Background: Resistance to all first-line antibiotics necessitates the use of less effective or more toxic "reserve" agents. Gram-negative bloodstream infections (GNBSIs) harboring such difficult-to-treat resistance (DTR) may have higher mortality than phenotypes that allow for >/=1 active first-line antibiotic. Methods: The Premier Database was analyzed for inpatients with select GNBSIs. DTR was defined as intermediate/resistant in vitro to all ss-lactam categories, including carbapenems and fluoroquinolones. Prevalence and aminoglycoside resistance of DTR episodes were compared with carbapenem-resistant, extended-spectrum cephalosporin-resistant, and fluoroquinolone-resistant episodes using CDC definitions. Predictors of DTR were identified. The adjusted relative risk (aRR) of mortality was examined for DTR, CDC-defined phenotypes susceptible to >/=1 first-line agent, and graded loss of active categories. Results: Between 2009-2013, 471 (1%) of 45011 GNBSI episodes at 92 (53.2%) of 173 hospitals exhibited DTR, ranging from 0.04% for Escherichia coli to 18.4% for Acinetobacter baumannii. Among patients with DTR, 79% received parenteral aminoglycosides, tigecycline, or colistin/polymyxin-B; resistance to all aminoglycosides occurred in 33%. Predictors of DTR included urban healthcare and higher baseline illness. Crude mortality for GNBSIs with DTR was 43%; aRR was higher for DTR than for carbapenem-resistant (1.2; 95% confidence interval, 1.0-1.4; P = .02), extended-spectrum cephalosporin-resistant (1.2; 1.1-1.4; P = .001), or fluoroquinolone-resistant (1.2; 1.0-1.4; P = .008) infections. The mortality aRR increased 20% per graded loss of active first-line categories, from 3-5 to 1-2 to 0. Conclusion: Nonsusceptibility to first-line antibiotics is associated with decreased survival in GNBSIs. DTR is a simple bedside prognostic measure of treatment-limiting coresistance. |
Incidence and trends of sepsis in US hospitals using clinical vs claims data, 2009-2014
Rhee C , Dantes R , Epstein L , Murphy DJ , Seymour CW , Iwashyna TJ , Kadri SS , Angus DC , Danner RL , Fiore AE , Jernigan JA , Martin GS , Septimus E , Warren DK , Karcz A , Chan C , Menchaca JT , Wang R , Gruber S , Klompas M . JAMA 2017 318 (13) 1241-1249 Importance: Estimates from claims-based analyses suggest that the incidence of sepsis is increasing and mortality rates from sepsis are decreasing. However, estimates from claims data may lack clinical fidelity and can be affected by changing diagnosis and coding practices over time. Objective: To estimate the US national incidence of sepsis and trends using detailed clinical data from the electronic health record (EHR) systems of diverse hospitals. Design, Setting, and Population: Retrospective cohort study of adult patients admitted to 409 academic, community, and federal hospitals from 2009-2014. Exposures: Sepsis was identified using clinical indicators of presumed infection and concurrent acute organ dysfunction, adapting Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) criteria for objective and consistent EHR-based surveillance. Main Outcomes and Measures: Sepsis incidence, outcomes, and trends from 2009-2014 were calculated using regression models and compared with claims-based estimates using International Classification of Diseases, Ninth Revision, Clinical Modification codes for severe sepsis or septic shock. Case-finding criteria were validated against Sepsis-3 criteria using medical record reviews. Results: A total of 173690 sepsis cases (mean age, 66.5 [SD, 15.5] y; 77660 [42.4%] women) were identified using clinical criteria among 2901019 adults admitted to study hospitals in 2014 (6.0% incidence). Of these, 26061 (15.0%) died in the hospital and 10731 (6.2%) were discharged to hospice. From 2009-2014, sepsis incidence using clinical criteria was stable (+0.6% relative change/y [95% CI, -2.3% to 3.5%], P = .67) whereas incidence per claims increased (+10.3%/y [95% CI, 7.2% to 13.3%], P < .001). In-hospital mortality using clinical criteria declined (-3.3%/y [95% CI, -5.6% to -1.0%], P = .004), but there was no significant change in the combined outcome of death or discharge to hospice (-1.3%/y [95% CI, -3.2% to 0.6%], P = .19). In contrast, mortality using claims declined significantly (-7.0%/y [95% CI, -8.8% to -5.2%], P < .001), as did death or discharge to hospice (-4.5%/y [95% CI, -6.1% to -2.8%], P < .001). Clinical criteria were more sensitive in identifying sepsis than claims (69.7% [95% CI, 52.9% to 92.0%] vs 32.3% [95% CI, 24.4% to 43.0%], P < .001), with comparable positive predictive value (70.4% [95% CI, 64.0% to 76.8%] vs 75.2% [95% CI, 69.8% to 80.6%], P = .23). Conclusions and Relevance: In clinical data from 409 hospitals, sepsis was present in 6% of adult hospitalizations, and in contrast to claims-based analyses, neither the incidence of sepsis nor the combined outcome of death or discharge to hospice changed significantly between 2009-2014. The findings also suggest that EHR-based clinical data provide more objective estimates than claims-based data for sepsis surveillance. |
Premastication as a route of pediatric HIV transmission: case-control and cross-sectional investigations: pediatric HIV risk via premastication
Ivy W 3rd , Dominguez KL , Rakhmanina NY , Iuliano AD , Danner SP , Borkowf CB , Denson AP , Gaur AH , Mitchell CD , Henderson SL , Paul ME , Barton T , Herbert-Grant M , Hader SL , Garcia EP , Malachowski JL , Nesheim SR . J Acquir Immune Defic Syndr 2011 59 (2) 207-12 BACKGROUND: Three cases of pediatric HIV transmission attributed to the feeding practice of premasticating food for children have been reported. The degree of risk that premastication poses for pediatric HIV transmission and the prevalence of this behavior among HIV-infected caregivers is unknown. METHODS: During December 2009-February 2010, we conducted a case-control investigation of late-diagnosed HIV infection in children at six HIV clinics, using in-person and telephone interviews. A cross-sectional investigation of premastication was conducted in concert with this case-control investigation. RESULTS: We compared 11 case-patients to 35 HIV-exposed controls of similar age. Sixteen (35%) of 46 children were fed premasticated food, 10 (22%) by an HIV-infected caregiver. Twenty-seven percent of case-patients received premasticated food from an HIV-infected caregiver compared to 20% of controls (odds ratio = 1.5; 95% confidence interval = 0.3 - 7.1). In the cross-sectional investigation, 48 (31%) of 154 primary caregivers of children aged ≥6 months reported the children received premasticated food from themselves or someone else. The prevalence of premastication decreased with increasing caregiver age, and had been used to feed children aged 1-36 months. CONCLUSIONS: Premastication, a potential route of HIV transmission to children, was a common practice of caregivers. Public health officials and healthcare providers should educate the public about the potential risk of disease transmission via premastication. |
Various viral compartments in HIV-1-infected mothers contribute to in utero transmission of HIV-1
Kourtis AP , Amedee AM , Bulterys M , Danner S , Van Dyke R , O'Sullivan MJ , Maupin R , Jamieson DJ . AIDS Res Hum Retroviruses 2011 27 (4) 421-7 Perinatal HIV transmission occurs in utero or intrapartum. The mechanisms and timing of transmission are not clearly understood. To compare the genetic sequences of the V3 envelope region of infant's plasma HIV to that of the mother's plasma, peripheral blood mononuclear cells (PBMC) and vaginal secretions, and correlate with timing of transmission. All 3 infants had a positive HIV PCR in the first days of life, thus classified as in utero infections. In the first mother-infant pair, two different variants were present in the infant, one correlating with maternal PBMC virus and highly homologous to virus from vaginal secretions and the other identical to sequences in maternal plasma. In the second pair, the infant plasma virus was similar to that of maternal PBMC. In the third pair, the cord blood and infant plasma virus were highly similar to maternal vaginal virus. The presence of more than one HIV variant from the maternal blood and from the vaginal compartment in the cord blood of infants presumably infected in utero could point to more than one episode of transmission or, alternatively, to transmission of PBMC virus. |
Factors associated with declining a rapid human immunodeficiency virus test in labor and delivery
Tan KR , Lampe MA , Danner SP , Kissinger P , Webber MP , Cohen MH , O'Sullivan MJ , Nesheim S , Jamieson DJ . Matern Child Health J 2010 15 (1) 115-21 The Centers for Disease Control and Prevention and the American College of Obstetricians and Gynecologists recommend routine rapid HIV testing in labor and delivery (L&D) for women with undocumented HIV status using an opt-out approach. Identifying factors associated with declining a rapid HIV test in L&D will be helpful in developing strategies to improve rapid HIV testing uptake. Data from the Mother-Infant Rapid Intervention at Delivery study were analyzed. Women ≥24 weeks gestation, in labor, with undocumented HIV status were offered rapid HIV testing using informed consent. Women who declined rapid HIV testing (decliners) but agreed to be interviewed were compared to women who accepted testing (acceptors). 102 decliners and 478 acceptors met inclusion criteria for analysis. Decliners of rapid HIV testing were more likely to have had prenatal care (PNC), after adjusting for age, Hispanic ethnicity, high-school education and city of enrollment (adjusted OR 2.4, 95% CI 1.06-5.58). Having had PNC was collinear with prior HIV education and previous offer of an HIV test during the current pregnancy, so these factors were not part of the model. During PNC, standard informed consent may involve discussions that negatively affect later uptake of testing in L&D. Therefore an opt-out approach to testing may improve testing rates. Furthermore, decliners may have felt that testing in L&D was redundant because of previous testing during PNC; however, if previous testing occurred, this was undocumented at L&D. Documentation and timely communication of HIV status is critical to provide appropriate HIV prophylaxis. |
Guidelines for the Prevention and Treatment of Opportunistic Infections among HIV-exposed and HIV-infected children: recommendations from CDC, the National Institutes of Health, the HIV Medicine Association of the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the American Academy of Pediatrics
Mofenson LM , Brady MT , Danner SP , Dominguez KL , Hazra R , Handelsman E , Havens P , Nesheim S , Read JS , Serchuck L , Van Dyke R . MMWR Recomm Rep 2009 58 1-166 This report updates and combines into one document earlier versions of guidelines for preventing and treating opportunistic infections (OIs) among HIV-exposed and HIV-infected children, last published in 2002 and 2004, respectively. These guidelines are intended for use by clinicians and other health-care workers providing medical care for HIV-exposed and HIV-infected children in the United States. The guidelines discuss opportunistic pathogens that occur in the United States and one that might be acquired during international travel (i.e., malaria). Topic areas covered for each OI include a brief description of the epidemiology, clinical presentation, and diagnosis of the OI in children; prevention of exposure; prevention of disease by chemoprophylaxis and/or vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; and discontinuation of secondary prophylaxis after immune reconstitution. A separate document about preventing and treating of OIs among HIV-infected adults and postpubertal adolescents (Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents) was prepared by a working group of adult HIV and infectious disease specialists. The guidelines were developed by a panel of specialists in pediatric HIV infection and infectious diseases (the Pediatric Opportunistic Infections Working Group) from the U.S. government and academic institutions. For each OI, a pediatric specialist with content-matter expertise reviewed the literature for new information since the last guidelines were published; they then proposed revised recommendations at a meeting at the National Institutes of Health (NIH) in June 2007. After these presentations and discussions, the guidelines underwent further revision, with review and approval by the Working Group, and final endorsement by NIH, CDC, the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Disease Society (PIDS), and the American Academy of Pediatrics (AAP). The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of the evidence supporting the recommendation so readers can ascertain how best to apply the recommendations in their practice environments. An important mode of acquisition of OIs, as well as HIV infection among children, is from their infected mother; HIV-infected women coinfected with opportunistic pathogens might be more likely than women without HIV infection to transmit these infections to their infants. In addition, HIV-infected women or HIV-infected family members coinfected with certain opportunistic pathogens might be more likely to transmit these infections horizontally to their children, resulting in increased likelihood of primary acquisition of such infections in the young child. Therefore, infections with opportunistic pathogens might affect not just HIV-infected infants but also HIV-exposed but uninfected infants who become infected by the pathogen because of transmission from HIV-infected mothers or family members with coinfections. These guidelines for treating OIs in children therefore consider treatment of infections among all children, both HIV-infected and uninfected, born to HIV-infected women. Additionally, HIV infection is increasingly seen among adolescents with perinatal infection now surviving into their teens and among youth with behaviorally acquired HIV infection. Although guidelines for postpubertal adolescents can be found in the adult OI guidelines, drug pharmacokinetics and response to treatment may differ for younger prepubertal or pubertal adolescents. Therefore, these guidelines also apply to treatment of HIV-infected youth who have not yet completed pubertal development. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for preventing and treating OIs, especially those OIs for which no specific therapy exists; 2) information about the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information about managing antiretroviral therapy in children with OIs, including potential drug--drug interactions; 4) new guidance on diagnosing of HIV infection and presumptively excluding HIV infection in infants that affect the need for initiation of prophylaxis to prevent Pneumocystis jirovecii pneumonia (PCP) in neonates; 5) updated immunization recommendations for HIV-exposed and HIV-infected children, including hepatitis A, human papillomavirus, meningococcal, and rotavirus vaccines; 6) addition of sections on aspergillosis; bartonella; human herpes virus-6, -7, and -8; malaria; and progressive multifocal leukodystrophy (PML); and 7) new recommendations on discontinuation of OI prophylaxis after immune reconstitution in children. The report includes six tables pertinent to preventing and treating OIs in children and two figures describing immunization recommendations for children aged 0--6 years and 7--18 years. Because treatment of OIs is an evolving science, and availability of new agents or clinical data on existing agents might change therapeutic options and preferences, these recommendations will be periodically updated and will be available at http://AIDSInfo.nih.gov. |
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