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Background. The epidemiologic trends of hepatitis B virus (HBV) infection in human immunodeficiency virus (HIV)-infected patients over the past 20 years are largely unknown. Methods. Prevalence and risk factors for HBV infection overall, at the time of HIV infection, and after HIV infection were examined in an ongoing observational HIV cohort study. Risk factors for HBV infection at the time of diagnosis of HIV infection were evaluated using logistic regression, and risk of incident HBV infection after diagnosis of HIV infection was evaluated using Cox proportional hazards models. Results. Of the 2769 evaluable participants, 1078 (39%) had HBV infection, of whom 117 (11%) had chronic HBV infection. The yearly cross-sectional prevalence of HBV infection decreased from a peak of 49% in 1995 to 36% in 2008 (P< .001). The prevalence of HBV infection at the time of diagnosis of HIV infection decreased during 1989-2008 from 34% to 9% (P<.001). The incidence of HBV infection after diagnosis of HIV infection decreased from 4.0 cases per 100 person-years during the pre-highly active antiretroviral therapy (HAART) era to 1.1 cases per 100 person-years during the HAART era (P< .001); however, this incidence remained unchanged during 2000-2008 (P=.49), with 120% of HBV infections occurring after HIV infection being chronic. Decreased risk of HBV infection after diagnosis of HIV infection was associated with higher CD4 cell count and the use of HBV-active HAART. Receipt of ⩾1 dose of HBV vaccine was not associated with reduced risk of HBV infection after diagnosis of HIV infection. Conclusions. Although the burden of HBV infection overall is slowly decreasing among HIV-infected individuals, the persistent rate of HBV infection after diagnosis of HIV infection raises concern that more-effective prevention strategies may be needed to significantly reduce the prevalence of HBV infection in this patient population. [ABSTRACT FROM AUTHOR]

We conducted a retrospective cohort study that tested 2,000 US military personnel for Coccidioides antibodies in a disease-endemic region. The overall incidence of seroconversion was 0.5 cases/100 person-years; 12.5% of persons who seroconverted had illnesses requiring medical care. No significant association was found between demographic characteristics and seroconversion or disease.

Objective: To evaluate changing Clostridioides difficile infection (CDI) testing among inpatients with indeterminate enzyme immunoassay (EIA) results (antigen+/toxin-) from reflexive polymerase chain reaction (PCR) testing to clinician-ordered PCR testing., Design: Multicenter, before-and-after, quasi-experimental study., Setting: Four large urban tertiary-care hospitals., Methods: We evaluated two 6-month periods before and after an intervention. The primary study outcome was the change in the number of CDI diagnoses between periods. Secondary outcomes included the number of PCR tests performed, adverse events, and healthcare cost savings., Results: In total, 500 EIA-indeterminate C. difficile test results were evaluated: 281 before the intervention and 219 thereafter. CDI was diagnosed by PCR among EIA-indeterminate cases in 182 in the preintervention period versus 94 patients in the postintervention period (48% reduction; P < .01). PCR testing was performed in 99.6% of indeterminate cases (280 of 281; 1 not performed due to an inhibitor) in the preintervention period versus 66% (144 of 219) in the postintervention period (34% reduction; P < .01). We observed no differences between study periods in 30-day all-cause (P = .96), GI-related (P = .93), or C. difficile (P = .47) readmissions, nor in 30-day C. difficile infections (P > .99). No patient without a PCR test in the postintervention period and not treated was later diagnosed with CDI. Each reflexive PCR test not performed led to a cost savings of $4,498 per patient., Conclusions: Applying diagnostic stewardship to C. difficile PCR testing in the inpatient setting led to significant reductions in both testing and cases. Changing the C. difficile PCR testing algorithm for EIA-indeterminate cases from reflexive to clinician-required ordering resulted in valuable cost savings without associated adverse events.

Introduction: Capnocytophaga canimorsus infections are associated with dog bites, especially in asplenic or immunocompromised patients, and typically manifest as sepsis and/or bacteremia. Meningitis has been rarely described, and its diagnosis may be delayed due to poor or slow growth using traditional culture techniques. We provide our experience using polymerase chain reaction (PCR) to establish the diagnosis and perform a comprehensive review of C. canimorsus meningitis cases to provide summary data on the clinical manifestations, diagnosis, and outcomes of this unusual infection., Methods: A systematic review of the peer-reviewed English literature (PubMed, Embase, Ovid Medline) from January 1966 to March 2018 was conducted to identify cases of C. canimorsus meningitis. Data collected included demographics, risk factors, cerebrospinal fluid (CSF) findings, PCR results, treatments, and outcomes. Descriptive statistics are presented as numbers (percentages) and medians (ranges)., Results: A total of 37 patients were reviewed with a median age of 63 years (12 days to 83 years) with a male predominance (76%). A relatively low proportion had an immunocompromised state (16% splenectomy and 5% steroid use); the most common risk factor was alcoholism (19%). Fifty-nine percent reported a dog bite (all within ≤ 14 days prior to presentation), while 22% reported a non-bite dog exposure, 3% reported cat bite, and 3% reported both dog and cat exposures; 11% reported no animal contact. CSF parameters included a median white count of 1024 cells/mm 3 , 81% had neutrophilic predominance, median protein of 190 mg/dl, and median glucose CSF/serum ratio 0.23. In 54% of cases, blood cultures were positive for C. canimorsus (median, 4 days) and 70% had positive CSF cultures (median, 5 days). PCR established the diagnosis in eight (22%) cases. Antibiotic therapy was given for a median of 15 days (range, 7 to 42 days). Prognosis was overall favorable with only one (3%) death reported and adverse neurologic and/or physical sequelae in 19% of the survivors., Conclusion: C. canimorsus meningitis is a rare but increasingly important clinical entity occurring in patients of all ages, typically after dog exposure. While classically considered an infection among immunocompromised patients, most cases have occurred in previously healthy, immunocompetent persons. Diagnosis may be rapidly established by PCR, and this test should be considered in culture-negative cases with associated exposures. Outcome was generally favorable after a median antibiotic duration of 15 days.

Background: Spinal epidural abscesses are uncommon but potentially devastating infections that often elude early diagnosis. An increasing incidence has been suggested; however, few contemporary data are available regarding risk factors and epidemiologic trends over time., Methods: A retrospective study of spinal epidural abscesses from 2004 to 2014 at a large academic hospital was conducted. Cases were identified using International Classification of Diseases, Ninth Revision (ICD-9) code 324.1, and a review of medical and radiographic records was performed to confirm each case. Data collected included sociodemographics, medical history, suspected route of infection, treatments, and outcome., Results: The incidence was 5.1 cases for each 10,000 admissions, with no significant changes during the study period. The route of infection was identified in 52% of cases, with bacteremia as the most common (26%), followed by recent surgery/procedure (21%) and spinal injection (6%). An identifiable underlying risk factor was present in 84% of cases, most commonly diabetes and intravenous drug use. A causative organism was identified in 84% of cases, most commonly Staphylococcus aureus; methicillin-resistant isolates accounted for 25% of S. aureus cases. All cases received intravenous antibiotic therapy, and 73% underwent a drainage procedure. Fifteen percent had an adverse outcome (8% paralysis and 7% death)., Conclusions: The incidence of spinal epidural abscesses may be increasing, with the present study demonstrating a ≥5-fold higher rate compared with historical data. Although the outcome in most cases was favorable, spinal epidural abscesses continue to cause substantial morbidity and mortality and should remain a "not to be missed diagnosis.", (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: This study was to compare B and T memory cells elicited by a single dose monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009 H1N1) in HIV + and HIV - groups, and to analyze the impact of the prior seasonal vaccines to the immunogenicity of this vaccine., Methods: Blood samples were collected before vaccination (day 0) and at days 28 and 180. Participants were categorized into HIV - /LAIV, HIV - /TIV and HIV + /TIV subgroups according to the trivalent live-attenuated or inactivated (LAIV or TIV) seasonal influenza vaccines they received previously. The IgG + memory B cells (B Mem ) and IFNγ + T cells were measured against antigens including the H1N1 vaccine, the hemagglutinin (HA) and neuraminidase (NA) proteins or peptide pools of the pandemic and the seasonal H1N1 strains, respectively., Results: Overall B Mem responses increased significantly at day 28 but returned to baseline by day 180 in all three subgroups. The average frequency of the H1N1-specific B Mem at day 28 for the HIV - /LAIV, HIV - /TIV and HIV + /TIV groups was 2.14%, 1.26% and 1.67%, respectively, and the average fold change was 14.39, 3.81 and 3.93, respectively. The differences of B Mem between HIV - /LAIV and the two TIV subgroups were significant. For the IFNγ response, the overall spot counts ranged widely between 0 and 958/10 6 PBMCs. The group average spot counts to H1N1 vaccine was 89, 102, and 30 at day 28 for HIV - /LAIV, HIV - /TIV and HIV + /TIV subgroups, respectively. The average increase of IFNγ response at day 28 vs day 0 in all three subgroups did not reach 2-fold., Conclusion: Participants with a prior LAIV seasonal vaccine, as compared to a TIV seasonal vaccine, responded significantly better to the monovalent H1N1 vaccine. Excluding LAIV participants, no difference was seen between the HIV + and HIV - subject groups in terms of B Mem . The B Mem response declined at 6months., (Copyright © 2017. Published by Elsevier Ltd.)

Vaccination is a critical component for ensuring the ongoing health HIV-infected adults. Since this group may have reduced immune responses and shorter durations of protection post-vaccination, HIV-specific guidelines have been published. This review article provides a comprehensive discussion of the current guidelines and evidence-based data for vaccinating HIV-infected adults, including data on dosing schedules, immunogenicity studies, and safety. In the current paper, part II of the review, live vaccines, as well as vaccines for travelers and specific occupational groups, will be discussed.

Background: Vaccination is the most important preventive strategy against influenza, however post-vaccination antibody responses are often inadequate especially among HIV-infected persons. Vitamin D deficiency has been suggested to adversely influence immune responses and is highly prevalent among HIV-infected adults. Therefore, we evaluated the association between 25-hydroxyvitamin D [25(OH)D] levels and post-influenza vaccination responses., Methods: We conducted a prospective cohort study evaluating the immunogenicity of monovalent influenza A (H1N1) vaccination among both HIV-infected and HIV-uninfected adults (18-50years of age) during the 2009-2010 influenza season. Antibody titers were evaluated at baseline, day 28, and 6months post-vaccination using hemagluttination inhibition assays. Serum 25(OH)D levels were measured at day 28. Univariate and multivariate regression analyses examined the association between 25(OH)D levels [categorized as <20ng/ml (deficiency) vs. ⩾20ng/ml] with the primary outcome of seroconversion. Secondary outcomes included seroprotection; a ⩾4-fold increase in titers; and geometric mean titers post-vaccination. Analyses were repeated using 25(OH)D levels as a continuous variable., Results: A total of 128 adults [64 HIV-infected (median CD4 count 580cells/mm(3)) and 64 HIV-uninfected] were included. Seroconversion at day 28 post-vaccination was achieved in fewer HIV-infected participants compared with HIV-uninfected participants (56% vs. 74%, p=0.03). Vitamin D deficiency was more prevalent among HIV-infected persons vs. HIV-uninfected persons (25% vs. 17%), although not significantly different (p=0.39). There were no associations found between lower 25(OH)D levels and poorer antibody responses at day 28 or 6months for any of the study outcomes among either HIV-infected or HIV-uninfected adults., Conclusion: Vitamin D deficiency was common among both HIV-infected and HIV-uninfected adults, but lower levels did not predict antibody responses after H1N1 (2009) influenza vaccination. Low 25(OH)D levels do not explain poorer post-vaccination responses among HIV-infected persons., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Necrotizing fasciitis is a severe, life-threatening infection.  Serratia marcescens, a Gram-negative bacterium, is an extremely rare cause of necrotizing fasciitis., Methods: A case of S. marcescens necrotizing fasciitis is described, and a comprehensive review of the literature (1966-2015) of monomicrobial cases due to this organism performed., Results: We report the first case of S. marcescens necrotizing fasciitis in the setting of calciphylaxis associated with end-stage renal disease.  A comprehensive review of the literature of S. marcescens necrotizing fasciitis is provided to enhance the awareness of this increasingly recognized infection, and to provide a concise summary of risk factors, treatment, and outcome., Conclusions: Our case and review highlight the potential risk factors for S. marcescens necrotizing fasciitis, including underlying renal disease and open wounds, and demonstrate the emergence of this organism as a cause of severe, life-threatening soft tissue infections.

The need to understand the impact of war on military families has never been greater than during the past decade, with more than three million military spouses and children affected by deployments to Operations Iraqi Freedom and Enduring Freedom. Understanding the impact of the recent conflicts on families is a national priority, however, most studies have examined spouses and children individually, rather than concurrently as families. The Department of Defense (DoD) has recently initiated the largest study of military families in US military history (the Millennium Cohort Family Study), which includes dyads of military service members and their spouses (n > 10,000). This study includes US military families across the globe with planned follow-up for 21+ years to evaluate the impact of military experiences on families, including both during and after military service time. This review provides a comprehensive description of this landmark study including details on the research objectives, methodology, survey instrument, ancillary data sets, and analytic plans. The Millennium Cohort Family Study offers a unique opportunity to define the challenges that military families experience, and to advance the understanding of protective and vulnerability factors for designing training and treatment programs that will benefit military families today and into the future., (Copyright © 2014 John Wiley & Sons, Ltd.)

Vaccines are critical components for protecting HIV-infected adults from an increasing number of preventable diseases. However, missed opportunities for vaccination among HIV-infected persons persist, likely due to concerns regarding the safety and efficacy of vaccines, as well as the changing nature of vaccine guidelines. In addition, the optimal timing of vaccination among HIV-infected adults in regards to HIV stage and receipt of antiretroviral therapy remain important questions. This article provides a review of the current recommendations regarding vaccines among HIV-infected adults and a comprehensive summary of the evidence-based literature of the benefits and risks of vaccines among this vulnerable population.

Despite the marked expansion of roles for women in the US military over the last decade, whether differences by gender exist in regard to the development of mental health conditions postdeployment is unclear. This comprehensive review of the literature (2001-2012) examined whether US servicewomen were more likely than men to experience post-traumatic stress disorder (PTSD) after returning from deployments to the Iraq and Afghanistan conflicts. Findings from 18 studies from 8 unique study populations were reviewed. Seven studies found that women had a higher risk for screening positive for PTSD compared with men, including prospectively designed studies that evaluated new-onset PTSD among members from all service branches. Although results from studies with Veterans Affairs samples found women at decreased risk in 4 analyses, these studies used the same source databases, were conducted in treatment-seeking populations, and were mostly unable to account for combat experience. Seven studies detected no differences by gender. In summary, women appeared to have a moderately higher risk for postdeployment PTSD, although there was a lack of consensus among the studies, and even those with the most rigorous methods were not designed specifically to evaluate potential gender differences. Given the limitations of the published literature, further research should use longitudinal study designs and comprehensive evaluations of deployment experiences while adjusting for predeployment factors to confirm that gender differences exist with regard to postdeployment PTSD.

Background: Sleep disturbances are reportedly common among persons infected with human immunodeficiency virus (HIV), but recent data, including comparisons with HIV-uninfected persons, are limited., Methods: We performed a cross-sectional study among early-treated HIV-infected military beneficiaries (n = 193) to determine the prevalence and factors associated with insomnia (Pittsburgh Sleep Quality Index [PSQI]) and daytime sleepiness (Epworth Sleepiness Scale [ESS]). Data were compared with HIV-uninfected persons (n = 50) matched by age, sex, race or ethnicity, and military rank., Results: Forty-six percent of HIV-infected persons had insomnia (PSQI >5), and 30% reported daytime drowsiness (ESS ≥10). The prevalence of insomnia and daytime sleepiness was not significantly higher compared with the HIV-uninfected group (38% [P = .30] and 20% [P = .18], respectively). In the multivariate model, factors associated with insomnia among HIV infected patients included depression (odds ratio [OR], 16.8; 95% confidence interval [CI], 2.0-142.1; P = .01), increased waist size (OR, 2.7; 95% CI, 1.4-5.1; P = .002), and fewer years of education (OR, 0.8; 95% CI, .7-.95; P = .006). Neurocognitive impairment (diagnosed in 19% of HIV-infected participants) was not associated with insomnia; however, HIV-infected persons with insomnia were 3.1-fold more likely to have a decline in activities of daily living than those without insomnia (23% vs 9%; P = .01). Only 18% of HIV-infected persons reported using a sleep medication at least weekly., Conclusions: HIV-infected persons have a high prevalence of insomnia, but among an early-treated cohort this rate was not significantly higher compared with HIV-uninfected persons. Factors associated with insomnia among HIV-infected patients include depression and increased waist size. Prompt diagnosis and treatment of sleep disturbances are advocated and may improve quality of life.

Background: Although highly active antiretroviral therapy (HAART) has improved HIV survival, some patients receiving therapy are still dying. This analysis was conducted to identify factors associated with increased risk of post-HAART mortality., Methods: We evaluated baseline (prior to HAART initiation) clinical, demographic and laboratory factors (including CD4+ count and HIV RNA level) for associations with subsequent mortality in 1,600 patients who began HAART in a prospective observational cohort of HIV-infected U.S. military personnel., Results: Cumulative mortality was 5%, 10% and 18% at 4, 8 and 12 years post-HAART. Mortality was highest (6.23 deaths/100 person-years [PY]) in those with ≤ 50 CD4+ cells/mm3 before HAART initiation, and became progressively lower as CD4+ counts increased (0.70/100 PY with ≥ 500 CD4+ cells/mm3). In multivariate analysis, factors significantly (p < 0.05) associated with post-HAART mortality included: increasing age among those ≥ 40 years (Hazard ratio [HR] = 1.32 per 5 year increase), clinical AIDS events before HAART (HR = 1.93), ≤ 50 CD4+ cells/mm3 (vs. CD4+ ≥ 500, HR = 2.97), greater HIV RNA level (HR = 1.36 per one log10 increase), hepatitis C antibody or chronic hepatitis B (HR = 1.96), and HIV diagnosis before 1996 (HR = 2.44). Baseline CD4+ = 51-200 cells (HR = 1.74, p = 0.06), and hemoglobin < 12 gm/dL for women or < 13.5 for men (HR = 1.36, p = 0.07) were borderline significant., Conclusions: Although treatment has improved HIV survival, defining those at greatest risk for death after HAART initiation, including demographic, clinical and laboratory correlates of poorer prognoses, can help identify a subset of patients for whom more intensive monitoring, counseling, and care interventions may improve clinical outcomes and post-HAART survival.

Background: With improved survival after the introduction of highly active antiretroviral therapy (HAART), non-AIDS-related morbidity and mortality have come to the forefront in the management of HIV patients. HAART has been linked to the development of several risk factors for cardiovascular disease including insulin resistance and hyperlipidemia, but its influence on hypertension requires further study., Methods: We performed a cross-sectional study of HIV-infected persons at two large HIV clinics to evaluate the prevalence and factors associated with hypertension. Hypertension was defined by at least two blood pressure measurements >140/90 mmHg or the use of an antihypertensive medication. Statistical analyses included multivariate logistic regression models., Results: We studied 707 HIV-infected adults with a median age of 41 years (IQR 36-46), 92% were male, 49% were Caucasian, and 72% were receiving HAART. The overall prevalence of hypertension was 31% and was similar among those receiving and not receiving HAART (32% vs. 29%, p = 0.47). Factors associated with hypertension in the multivariate model included increasing age, longer duration of HIV, higher body mass index, and diabetes, with a trend for African American ethnicity., Conclusions: Hypertension is common among HIV-infected persons and is associated with established risk factors, but not with HAART use. Given the high prevalence of hypertension and its association with duration of HIV infection, other factors such as virally-mediated endothelial changes or immune activation may play a role. Further investigations are needed.

Changes in serologic status in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infected individuals with either isolated anti-HBc or resolved HBV infection have been reported, but the frequency of clinically meaningful long-term serologic changes is not well-defined. This study therefore, examined longitudinal serologic status for hepatitis B surface antigen (HBsAg)-negative HIV/HBV co-infected participants in a large cohort. Among 5,222 cohort participants, 347 (7%) were initially isolated anti-HBc positive, and 1,073 (21%) had resolved HBV infection (concurrently reactive for anti-HBc and anti-HBs). Thirty-three (10%) of the 347 participants with isolated anti-HBc were later positive for HBsAg at least once, compared with 3 (0.3%) of those with resolved HBV (P < 0.001). A total of 14 participants became persistently positive for HBsAg and were thus classified as having late-onset chronic HBV infection at a median of 3.7 years after initial HBV diagnosis. For those initially with HBsAg-negative HIV/HBV co-infection, the rate of late-onset chronic HBV infection was 1.39/1,000 person-years. Those with late-onset chronic HBV infection experienced significant decreases in CD4 cell counts (P = 0.002) with a mean of 132 cells/µl at the time of late-onset chronic HBV infection, but no factor distinguished those who were positive for HBsAg only once from those that developed late-onset chronic HBV infection. Over a median of 2.9 years following late-onset chronic HBV infection, 3 of 14 subsequently lost HBsAg. The occurrence of late-onset chronic HBV infection in HBsAg negative HIV/HBV co-infected adults appears to be one important, albeit rare, clinical event seen almost exclusively in those with isolated anti-HBc and low CD4 cell count., (Copyright © 2011 Wiley-Liss, Inc.)

Background: Limited data exist on the immunogenicity of the 2009 influenza A (H1N1) vaccine among immunocompromised persons, including those with human immunodeficiency virus (HIV) infection., Methods: We compared the immunogenicity and tolerability of a single dose of the monovalent 2009 influenza A (H1N1) vaccine (strain A/California/7/2009H1N1) between HIV-infected and HIV-uninfected adults 18-50 years of age. The primary end point was an antibody titer of ≥ 1:40 at day 28 after vaccination in those with a prevaccination level of ≤ 1:10, as measured by hemagglutination-inhibition assay. Geometric mean titers, influenza-like illnesses, and tolerability were also evaluated., Results: One hundred thirty-one participants were evaluated (65 HIV-infected and 66 HIV-uninfected patients), with a median age of 35 years (interquartile range, 27-42 years). HIV-infected persons had a median CD4 cell count of 581 cells/mm(3) (interquartile range, 476-814 cells/mm(3)) , and 82% were receiving antiretroviral medications. At baseline, 35 patients (27%) had antibody titers of >1:10. HIV-infected patients (29 [56%] of 52), compared with HIV-uninfected persons (35 [80%] of 44), were significantly less likely to develop an antibody response (odds ratio, .20; P = .003). Changes in the median geometric mean titer from baseline to day 28 were also significantly lower in HIV-infected patients than in HIV-uninfected persons (75 vs 153; P = .001). Five influenza-like illnesses occurred (2 cases in HIV-infected persons), but none was attributable to the 2009 influenza H1N1 virus. The vaccine was well tolerated in both groups., Conclusions: Despite high CD4 cell counts and receipt of antiretroviral medications, HIV-infected adults generated significantly poorer antibody responses, compared with HIV-uninfected persons. Future studies evaluating a 2-dose series or more-immunogenic influenza A (H1N1) vaccines among HIV-infected adults are needed (ClinicalTrials.gov NCT00996970).

Background: The risk of pneumococcal disease persists, and antibody responses to revaccination with the 23-valent polysaccharide vaccine (PPV) are low among human immunodeficiency virus (HIV)-infected adults. We determined whether revaccination with the 7-valent pneumococcal conjugate vaccine (PCV) would enhance these responses., Methods: In a randomized clinical trial, we compared the immunogenicity of revaccination with PCV ( n = 131) or PPV (n = 73) among HIV-infected adults (median CD4 cell count, 533 cells/mm(3)) who had been vaccinated with PPV 3-8 years earlier. HIV-uninfected adults (n = 25) without prior pneumococcal vaccination received 1 dose of PCV. A positive response was defined as a >or=2-fold increase (from baseline to day 60) in capsule-specific immunoglobulin G, with a postvaccination level >or=1000 ng/mL for at least 2 of the 4 serotypes., Results: HIV-infected persons demonstrated a higher frequency of positive antibody responses to PCV than to PPV (57% vs 36%) (P = .004) and greater mean changes in the immunoglobulin G concentration from baseline to day 60 for serotypes 4, 9V, and 19F (P < .05, for all), but not for serotype 14. However, by day 180, both outcomes were similar. Responses to PCV were greater in frequency and magnitude for all serotypes in HIV-uninfected adults, compared with those in HIV-infected adults., Conclusions: Among persons with HIV infection, revaccination with PCV was only transiently more immunogenic than PPV, and responses were inferior to those in HIV-uninfected subjects with primary vaccination. Pneumococcal vaccines with more robust and sustained immunogenicity are needed for HIV-infected adults. Clinical trial registration. ClinicalTrials.gov identifier NCT00622843.

Infectious myositis is defined as an infection of a skeletal muscle. Infectious myositis is most commonly caused by bacteria; however, a variety of viral, parasitic, and fungal agents may also cause myositis. The pathogenesis of nonbacterial infectious myositis is via direct or hematogenous infection of the musculature or immune mechanisms. Symptoms typically include muscular pain, tenderness, swelling, and/or weakness. The diagnosis of the specific microbe is often suggested by the presence of concordant clinical signs and symptoms, a detailed medical and travel history, and laboratory data. For example, immunocompromised hosts have a heightened risk of fungal myositis, whereas the presence of a travel history to an endemic location and/or eosinophilia may suggest a parasitic cause. Definitive diagnosis requires detecting the organism by specific laboratory testing including serologies, histopathology, and/or cultures. Treatment entails antimicrobial agents against the pathogen, with consideration for surgical drainage for focal purulent collections within the musculature.

Ileitis, or inflammation of the ileum, is often caused by Crohn's disease. However, ileitis may be caused by a wide variety of other diseases. These include infectious diseases, spondyloarthropathies, vasculitides, ischemia, neoplasms, medication-induced, eosinophilic enteritis, and others. The clinical presentation of ileitis may vary from an acute and self-limited form of right lower quadrant pain and/or diarrhea, as in the majority of cases of bacterial ileitis, but some conditions (ie, vasculitis or Mycobacterium tuberculosis) follow a chronic and debilitating course complicated by obstructive symptoms, hemorrhage, and/or extraintestinal manifestations. Ileitis associated with spondylarthropathy or nonsteroidal anti-inflammatory drugs is typically subclinical and often escapes detection unless further testing is warranted by symptoms. In a minority of patients with long-standing Crohn's ileitis, the recrudescence of symptoms may represent a neoplasm involving the ileum. Distinguishing between the various forms of ileitis remains a test of clinical acumen. The diagnosis of the specific etiology is suggested by a detailed history and physical examination, laboratory testing, and ileocolonoscopy and/or radiologic data.

Background: Declining rates of hospitalizations occurred shortly after the availability of highly active antiretroviral therapy (HAART). However, trends in the late HAART era are less defined, and data on the impact of CD4 counts and HAART use on hospitalizations are needed., Methods: We evaluated hospitalization rates from 1999 to 2007 among HIV-infected persons enrolled in a large US military cohort. Poisson regression was used to compare hospitalization rates per year and to examine factors associated with hospitalization., Results: Of the 2429 participants, 822 (34%) were hospitalized at least once with 1770 separate hospital admissions. The rate of hospitalizations (137 per 1000 person-years) was constant over the study period [relative rate (RR) 1.00 per year change, 95% confidence interval: 0.98 to 1.02]. The hospitalization rates due to skin infections (RR: 1.50, P = 0.02), methicillin-resistant staphylococcus aureus (RR: 3.19, P = 0.03), liver disease (RR: 1.71, P = 0.04), and surgery (RR: 1.17, P = 0.04) significantly increased over time, whereas psychological causes (RR: 0.60, P < 0.01) and trauma (RR: 0.54, P < 0.01) decreased. In the multivariate model, higher nadir CD4 (RR: 0.92 per 50 cells, P < 0.01) and higher proximal CD4 counts (RR of 0.71 for 350-499 vs. <350 cells/mm(3) and RR 0.67 for > or = 500 vs. 350 cells/mm(3), both P < 0.01) were associated with lower risk of hospitalization. Risk of hospitalization was constant for proximal CD4 levels above 350 (RR: 0.94 P = 0.51, CD4 > or = 500 vs. 350-499). HAART was associated with a reduced risk of hospitalization among those with a CD4 <350 (RR: 0.72, P = 0.02) but had smaller estimated and nonsignificant effects at higher CD4 levels (RR: 0.81, P = 0.33 and 1.06, P = 0.71 for CD4 350-499 and > or = 500, respectively)., Conclusions: Hospitalizations continue to occur at high rates among HIV-infected persons with increasing rates for skin infections, methicillin-resistant staphylococcus aureus, liver disease, and surgeries. Factors associated with a reduced risk of hospitalization include CD4 counts >350 cells per cubic millimeter and HAART use among patients with a CD4 count <350 cells per cubic millimeter.

To assess the effect of obesity on CD4 cell counts, we estimated the association of time-updated BMI categories with CD4 changes among 1001 documented HIV seroconverters. During the pre-highly active antiretroviral therapy (HAART) era, a higher BMI was associated with less reduction in CD4 cell counts over time. However during the HAART era, obese versus normal weight patients had smaller increases in CD4 cell counts (+69 versus +116 cells, P = 0.01). Lower CD4 cell counts may now be another adverse consequence of obesity.

Objective: To evaluate the incidence rates of anal cancer over the HIV epidemic and assess the impact of HAART use on anal cancer events., Methods: We evaluated the incidence of and factors associated with anal cancer using longitudinal data from the prospective U.S. Military Natural History Study (1985-2008). Poisson regression and Cox proportional hazard models were utilized., Results: Among 4506 HIV-infected men with 37 806 person-years of follow-up, anal cancer rates (per 100 000 person-years) increased five-fold, from 11 in the pre-HAART to 55 in the HAART era (P = 0.02). Rates continued to increase, reaching 128 in 2006-2008. Persons with HIV infection for more than 15 years had a 12-fold higher rate than those with less than 5 years (348 vs. 28, P < 0.01). At cancer diagnosis (n = 19), median age was 42 years, median CD4 cell count was 432 cells/microl, 74% had a CD4 nadir cell count less than 200 cells/microl, 42% had a prior AIDS event, and 74% had received HAART. From separate models, prior AIDS event (hazard ratio 3.88, P = 0.01) and lower CD4 nadir (hazard ratio 0.85 per 50 cell, P = 0.03) were associated with anal cancer, with a trend for a history of gonorrhea (hazard ratio 2.43, P = 0.07). Duration of HAART use was not associated with a reduced risk of anal cancer (hazard ratio 0.94, P = 0.42)., Conclusion: Incidence rates of anal cancer have progressively increased during the HIV epidemic. Persons with a longer duration of HIV infection have a substantially higher rate of anal cancer. As HIV-infected persons are experiencing longer life expectancies and HAART does not appear protective of anal cancer, studies on preventive strategies are needed.

Objective: To assess the association of hepatitis B virus (HBV) vaccination with risk of HBV infection among HIV-infected patients and HBV infection risk factors among vaccinees., Design: Observational cohort study., Methods: Participants enrolled from 1986 through 2004, unvaccinated and serologically negative for HBV infection at the time of HIV diagnosis, were followed longitudinally through 2007 for the occurrence of HBV infection. Risk factors for HBV infection were evaluated using time to event methods, including Kaplan-Meier survival curves and Cox proportional hazards models., Results: During 11 632 person-years of follow-up, the rate of HBV infection was 2.01 (95% CI 1.75-2.27)/100 person-years. Receipt of at least one dose of vaccine was not associated with reduced risk of HBV (unadjusted hazard ratio 0.86, 95% CI 0.7-1.1; adjusted hazard ratio 1.08, 95% CI 0.8-1.4). Receipt of three or more doses of vaccine was also not associated with reduced risk (hazard ratio 0.96; 95% CI 0.56-1.64). Among 409 vaccinees with HBsAb less than 10 IU/l, 46 (11.2%) developed HBV infection compared with 11 of 217 (5.1%) vaccinees with HBsAb > or =10 IU/l (hazard ratio 0.51; 95% CI 0.3-1.0). In participants with initial HBsAb less than 10 IU/l, 16 of 46 (35%) infections were chronic, compared with none of 11 in those with initial HBsAb at least 10 IU/l (P = 0.02)., Conclusion: Overall, HBV vaccination was not associated with reduced risk of HBV infection in our cohort of HIV-infected individuals. However, the small subset of vaccinees with a positive vaccine response may have had reduced HBV infection risk, including chronic disease. Improvements in vaccine delivery and immunogenicity are needed to increase HBV vaccine effectiveness in HIV-infected patients.

Background: A novel swine-origin influenza A (H1N1) virus was identified in March 2009 and subsequently caused worldwide outbreaks. The San Diego region was an early focal point of the emerging pandemic. We describe the clinical and epidemiologic characteristics of this novel strain in a military population to assist in future outbreak prevention and control efforts., Methods: We performed an epidemiologic evaluation of novel H1N1 virus infections diagnosed in San Diego County among 96,258 local US military beneficiaries. The structured military medical system afforded the ability to obtain precise epidemiologic information on the impact on H1N1 virus infection in a population. The novel H1N1 virus was confirmed using real-time reverse transcriptase polymerase chain reaction (rRT-PCR)., Results: From 21 April through 8 May 2009, 761 patients presented with influenza-like illness and underwent rRT-PCR testing. Of these patients, 97 had confirmed novel H1N1 virus infection, with an incidence rate of 101 cases per 100,000 persons. The median age of H1N1 patients with H1N1 virus infection was 21 years (interquartile range, 15-25 years). Fever was a universal symptom in patients with H1N1 virus infection; other symptoms included cough (present in 96% of patients), myalgia or arthralgia (57%), and sore throat (51%). Sixty-eight (70%) of our patients had an identifiable epidemiologic link to another confirmed patient. The largest cluster of cases of H1N1 virus infection occurred on a Navy ship and involved 32 (8%) of 402 crew members; the secondary attack rate was 6%-14%. The rapid influenza testing that was used during this outbreak had a sensitivity of 51% and specificity of 98%, compared with rRT-PCR. Only 1 patient was hospitalized, and there were no deaths., Conclusions: A novel H1N1 influenza A virus caused a significant outbreak among military beneficiaries in San Diego County, including a significant cluster of cases onboard a Navy ship. The outbreak described here primarily affected adolescents and young adults and resulted in a febrile illness without sequelae.

Background: Preclinical studies suggest that the antiretroviral agent, nelfinavir mesylate (NFV), may have antineoplastic properties. The relationship between NFV and cancer incidence among HIV-infected patients is unknown., Methods: We evaluated the impact of NFV on cancer development in a large cohort of HIV-infected persons with 108 cancer events during 13,421 person-years of follow-up. Using multivariate time-updated Cox proportional hazard models, the risk of cancer among those receiving NFV were compared to those on non-NFV antiretroviral regimens., Results: The risk of cancer among those receiving NFV was similar to those on non-NFV antiretroviral regimens (hazard ratio 1.0, 95% confidence interval 0.5, 1.7, P = 0.90). We also examined AIDS-defining and non-AIDS-defining cancers separately and found no significant associations between NFV use and cancer risk. Antiretroviral use, with or without a protease inhibitor (PI) component, was associated with a reduced risk of AIDS-defining cancers compared with no antiretroviral therapy; however, the risk of cancer was the same among those using PI or PI-sparing regimens., Discussion: Despite reports that NFV may have tumoricidal activity, we found no significant relationship between NFV or PI use compared with other antiretrovirals and the risk of developing cancer among a large cohort of HIV-infected persons.

Venous thrombotic events (VTEs) may occur at higher rates among patients with HIV; some studies suggest that highly active antiretroviral therapy (HAART) may increase the risk for these potentially life-threatening events. We performed a retrospective study among patients with HIV to evaluate the incidence and risk factors for VTEs during the HAART era. A literature review was performed examining VTEs in the pre- and post-HAART eras. Seventeen (3.7%) of 465 patients with HIV experienced a VTE. The overall incidence rate of deep VTEs among HIV-positive persons was 377 cases per 100,000 person-years, a fourfold higher rate compared to age-matched males in the general population. The median age at VTE was 36 years (range, 27-68). Patients with a thrombosis compared to those without had significantly lower current CD4 (153 versus 520 cells/mm(3), p < 0.001) and nadir (76 versus 276 cells/mm(3), p < 0.001) CD4 counts, higher viral loads (3.6 versus 1.7 log(10) copies per milliliter, p = 0.003), and more likely to have a diagnosis of AIDS (76% versus 32%, p < 0.001); there were no differences in demographics, hyperlipidemia, current use of HAART, the duration of HAART or protease inhibitor (PI) exposure. A review of the literature noted 129 VTE cases; mean age was 40 years, mean CD4 count was 181 cells/mm(3), the majority of patients were not receiving HAART, and the most common risk factor was an ongoing infection. Thrombotic events are occurring among patients with HIV despite their relatively young ages. Advanced HIV disease is a risk factor for development of thromboses, possibly due to an increased inflammatory state or the presence of concurrent comorbidities such as infections. HAART or PI therapy does not appear to play a significant role in the occurrence of VTEs.

Nontyphoidal salmonellosis is the leading cause of foodborne illness in the United States, causing about 1.4 million infections annually. Most cases of salmonellosis are due to ingestion of contaminated food items such as eggs, dairy products, and meats, but almost any foodstuff can be implicated, including peanut butter, as seen during a recent outbreak of more than 600 Salmonella infections. Although outbreaks often gain national media attention, the majority of nontyphoidal Salmonella infections in the United States occur sporadically. Risk factors for salmonellosis include gastric hypoacidity, recent use of antibiotics, extremes of age, and immunosuppressive conditions. Clinical manifestations of the infection most commonly involve self-limited gastroenteritis, but bacteremia and endovascular and localized infections may occur. Most cases of gastrointestinal involvement are self-limited, and antibiotic therapy is reserved for persons at risk for complicated disease. Preventive strategies by both industry and consumers are advocated to further reduce the occurrence of nontyphoidal salmonellosis.

Coccidioidomycosis has had an impact on the military since the discovery of the causative agent, Coccidioides immitis, over a century ago. The first reports of Coccidioides outbreaks affecting U.S. military personnel were reported by Smith and others during World War II. Since that time, numerous outbreaks and sporadic cases have occurred, affecting both the health and readiness of our armed forces. This article summarizes the impact of Coccidioides sp. on our military troops with a review of the literature, a description of the experience at a tertiary referral hospital treating the disease, and a synopsis of incidence studies conducted at bases in the southwestern United States. The substantial effect that coccidioidomycosis has had on the military supports the development of both newer and more effective treatments as well as a Valley Fever vaccine for prevention of this disease.

Community-acquired (CA) methicillin-resistant Staphylococcus aureus (MRSA) rates have rapidly increased in the general population; however, little data on recent incidence rates and risk factors of CA-MRSA infections among HIV patients appear in the literature. A retrospective study was conducted from 1993 through 2005 among patients at a large HIV clinic. Trends in CA-MRSA infection incidence rates, clinical characteristics and risk factors for CA-MRSA were evaluated. Seven percent of our cohort developed a CA-MRSA infection during the study period. The rate of CA-MRSA infections among HIV-infected population significantly increased since 2003, with an incidence of 40.3 cases/1000 person-years in 2005, which was 18-fold higher than the general population served at our facility. In all, 90% of infections were skin/soft tissue infections with a predilection for buttock or scrotal abscess formation; 21% of patients experienced a recurrent infection. Risk factors included a low CD4 count at the time of infection (odds ratio [OR] per 100 CD4 cells 0.84, P = 0.03), high maximum log(10) HIV viral load (OR 4.54, P<0.001), recent use of beta-lactam antibiotics (OR 6.0 for receipt of two prescriptions, P<0.001) and a history of syphilis (OR 4.55, P = 0.01). No patient receiving trimethoprim-sulfamethoxazole prophylaxis developed a CA-MRSA infection. Over the study period, CA-MRSA accounted for an increasing percentage of positive wound cultures and Staphylococcus aureus isolates, 37% and 65%, respectively, during 2005. In conclusion, CA-MRSA infections have rapidly increased among HIV-infected patients, a group which has a higher rate of these infections than the general population. Risk factors for CA-MRSA among HIV-infected patients include low current CD4 cell count, recent beta-lactam antibiotic use and potentially high-risk sexual activity as demonstrated by a history of syphilis infection.

Erectile dysfunction (ED) and hypogonadism are increasingly recognized conditions, however, the prevalence and etiologies of these conditions among HIV-infected men remain unclear. We studied 300 HIV-infected men who completed standardized questionnaires regarding sexual function and hypogonadal symptoms. An early morning testosterone test was performed; patients with a low serum testosterone level (defined by <300 ng/dL), underwent additional blood tests to determine the etiology of the hypogonadism. The participants' mean age was 39 years (range, 19-72); 61% were Caucasian; 24%, African American; 9%, Hispanic; and 5% other. Participants had been HIV-positive for a mean of 9 years (range, 0.5-20) with a mean CD4 count of 522 cells/mm(3) (range, 1-1531). Sixty percent were receiving antiretroviral therapy. ED was reported by 61.4%; of those with ED, 32% did not have a rigid enough erection for penetration, and 46% were unable to sustain an erection for the completion of intercourse. In the multivariate analysis, increasing age (odds ratio [OR] 1.4 for a 5-year increment, p < 0.001) and depression (OR 2.64, p < 0.0001) were associated with ED. A higher current CD4 count was protective (OR 0.80 for each 100 cells/mm(3), p = 0.004). Only 25% of patients with ED had utilized a phosphodiesterase-5-inhibitor for treatment. Seventeen percent of the 300 men were hypogonadal; there was no correlation between hypogonadism and ED. Increasing age and a higher body mass index (BMI) were positively associated with hypogonadism, while smoking was negatively associated (OR 0.44, p = 0.02). All patients with low testosterone had secondary hypogonadism. There was no association between ED or hypogonadism with the current, past, or cumulative use of HIV medications.

Infectious myositis, an infection of the skeletal muscle(s), is uncommon. This clinical entity may be caused by viral, bacterial, fungal, and parasitic pathogens. Viral etiologies typically cause diffuse myalgias and/or myositis, whereas bacteria and fungi usually lead to a local myositis which may be associated with sites compromised by trauma or surgery and are more common among immunocompromised patients. Localized collections within the muscles are referred to as pyomyositis. Other pyogenic causes of myositis include gas gangrene, group A streptococcal myonecrosis, and other types of non-clostridial myonecrosis. Early recognition and treatment of these conditions are necessary as they may rapidly become life-threatening.