Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreac-tivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD.
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Michael T. Yin;
Stephanie Shiau;
David Rimland;
Cynthia L. Gibert;
Roger J. Bedimo;
Maria C. Rodriguez-Barradas;
Katherine Harwood;
Josh Aschheim;
Amy C. Justice;
Julie A. Womack
Background: FRAX is a validated, computer-based clinical fracture risk calculator that estimates the 10-year risk of major osteoporotic (clinical spine, forearm, hip, or shoulder) fracture, and hip fracture alone. It is widely used for decision making in fracture prevention, but it may underestimate the risk in HIV-infected individuals. Some experts recommend considering HIV as a cause of secondary osteoporosis when calculating FRAX in HIV-infected individuals. Methods: From the Veterans Aging Cohort Study Virtual Cohort, we included 24,451 HIV-infected and uninfected men aged 50-70 years with complete data in the year 2000 to approximate all but 2 factors (ie, history of secondary osteoporosis and parental hip fracture) for modified-FRAX calculation without bone density and 10-year observational data for incident fragility fracture. The accuracy of the modified-FRAX calculation was compared by the observed/estimated (O/E) ratios of fracture by HIV status. Results: The accuracy of modified-FRAX was less for HIV-infected [O/E 1.62, 95% confidence interval (CI) 1.45 to 1.81] than uninfected men (O/E 1.29, 95% CI: 1.19 to 1.40), but improved when HIV was included as a cause of secondary osteoporosis (O/E 1.20, 95% CI: 1.08 to 1.34). However, only 3%-6% of men with incident fractures were correctly identified by the modified-FRAX using accepted FRAX thresholds for pharmacologic therapy. Conclusions: Modified-FRAX underestimated the fracture rates more in older HIV-infected than in otherwise similar uninfected men. The accuracy improved when HIV was included as a cause of secondary osteoporosis, but it still performed poorly for case finding. Further studies are necessary to determine how to use FRAX or define an HIV-specific index to risk stratify for screening and treatment in older HIV-infected individuals.
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Tamil Kendall;
Isabella Danel;
Diane Cooper;
Sophie Dilmitis;
Angela Kaida;
Athena Kourtis;
Ana Langer;
Ilana Lapidos-Salaiz;
Eva Lathrop;
Allisyn Moran;
Hannah Sebitloane;
Janet M. Turan;
D. Heather Watts;
Mary Nell Wegner
Introduction: HIV makes a significant contribution to maternal mortality, and women living in sub-Saharan Africa are most affected. International commitments to eliminate preventable maternal mortality and reduce HIV-related deaths among pregnant and postpartum women by 50% will not be achieved without a better understanding of the links between HIV and poor maternal health outcomes and improved health services for the care of women living with HIV (WLWH) during pregnancy, childbirth, and postpartum.Methods: This article summarizes priorities for research and evaluation identified through consultation with 30 international researchers and policymakers with experience in maternal health and HIV in sub-Saharan Africa and a review of the published literature.Results: Priorities for improving the evidence about effective interventions to reduce maternal mortality and improve maternal health among WLWH include better quality data about causes of maternal death among WLWH, enhanced and harmonized program monitoring, and research and evaluation that contributes to improving: (1) clinical management of pregnant and postpartum WLWH, including assessment of the impact of expanded antiretroviral therapy on maternal mortality and morbidity, (2) integrated service delivery models, and (3) interventions to create an enabling social environment for women to begin and remain in care.Conclusions: As the global community evaluates progress and prepares for new maternal mortality and HIV targets, addressing the needs of WLWH must be a priority now and after 2015. Research and evaluation on maternal health and HIV can increase collaboration on these 2 global priorities, strengthen political constituencies and communities of practice, and accelerate progress toward achievement of goals in both areas.
Background: The use of valve surgery for infective endocarditis (IE) in end-stage renal disease (ESRD) patients may be different than in the general population. We assessed predictors of early surgery in ESRD patients with IE. Methods: We conducted a retrospective cohort study among dialysis patients with left-sided IE between 2005 and 2015. Indications for surgery were based on current endocarditis guidelines. Patients were categorized as early valve replacement surgery or delayed/no surgery. We used logistic regression to determine independent predictors of early surgery. Results: Among 229 patients, 67 (29.3%) underwent early surgery. New congestive heart failure was the only high level of evidence indication independently associated with early surgery (odds ratio [OR], 12.1; 95% confidence interval [CI], 3.4-43.6). Transfer from outside hospital (OR, 5.4; 95% CI, 2.2-13.3), valve rupture (OR, 6.9; 95% CI, 2.6-17.9), coagulase-negative staphylococcus etiology (OR, 3.8; 95% CI, 1.4-10.6), and presence of any low level of evidence indication (OR, 5.9; 95% CI, 2.2-15.5) predicted early surgery. Preexisting valve disease (OR, 0.31; 95% CI, 0.12-0.82) and surgical contraindications (OR, 0.05; 95% CI, 0.005-0.4) predicted nonsurgical treatment. Conclusions: Among ESRD patients with IE, most surgical indications are not predictive of early surgery.
Objectives: To determine risk factors for poor outcomes among patients with pulmonary multidrug- or extensively drug-resistant (M/XDR) tuberculosis (TB) in Georgia. Methods: This was a prospective, population-based observational cohort study. Results: Among 380M/XDR-TB patients (mean age 38 years), 179 (47%) had a poor outcome: 59 (16%) died, 37 (10%) failed, and 83 (22%) defaulted. Newly diagnosed M/XDR-TB cases were significantly more likely to have a favorable outcome than retreatment cases (odds ratio (OR) 4.26, 95% confidence interval (CI) 1.99-9.10, p<0.001). In the multivariable analysis, independent risk factors for a poor treatment outcome included previous treatment history (OR 2.92, 95% CI 1.29-6.58), bilateral disease (OR 1.90, 95% CI 1.20-3.01), body mass index (BMI, kg/m2) ≤18.5 (OR 1.91, 95% CI 1.11-3.29), and XDR-TB (OR 2.28, 95% CI 1.11-4.71). Patients who underwent surgical resection (OR 0.27, 95% CI 0.11-0.64) and had sputum culture conversion by 4 months (OR 0.33, 95% CI 0.21-0.52) were significantly less likely to have poor treatment outcomes. Conclusions: Adjunctive surgery appeared to be beneficial in treating patients with M/XDR-TB. Retreatment cases, XDR-TB, bilateral disease, and low BMI were associated with a poor outcome. Additional studies are needed to further define the apparent beneficial role of surgery in the treatment of M/XDR-TB.
We describe a pilot study that attempted to infect human volunteers with Cyclospora cayetanensis. Seven healthy volunteers ingested an inoculum of Cyclospora oocysts (approximately 200-49,000 oocysts). The volunteers did not experience symptoms of gastroenteritis, and no oocysts were detected in any stool samples during the 16 weeks volunteers were monitored.
In 2008, an outbreak of isoniazid-resistant tuberculosis was identified among residents of homeless shelters in Atlanta, Georgia, USA. When initial control efforts involving standard targeted testing failed, a comprehensive approach that involved all providers of services for the homeless successfully interrupted the outbreak.
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Conrad P. Quinn;
Carol L. Sabourin;
Nancy A. Niemuth;
Han Li;
Vera A. Semenova;
Thomas L. Rudge;
Heather J. Mayfield;
Jarad Schiffer;
Robert S. Mittler;
Chris Ibegbu;
Jens Wrammert;
Rafi Ahmed;
April M. Brys;
Robert E. Hunt;
Denyse Levesque;
James E. Estep;
Roy E. Barnewall;
David M. Robinson;
Brian D. Plikaytis;
Nina Marano
A 3-dose (0, 1, and 6 months) intramuscular (3-IM) priming series of a human dose (HuAVA) and dilutions of up to 1:10 of anthrax vaccine adsorbed (AVA) provided statistically significant levels of protection (60 to 100%) against inhalation anthrax for up to 4 years in rhesus macaques. Serum anti-protective antigen (anti-PA) IgG and lethal toxin neutralization activity (TNA) were detectable following a single injection of HuAVA or 1:5 AVA or following two injections of diluted vaccine (1:10, 1:20, or 1:40 AVA). Anti-PA and TNA were highly correlated (overall r 2 =0.89 for log10-transformed data). Peak responses were seen at 6.5 months. In general , with the exception of animals receiving 1:40 AVA, serum anti-PA and TNA responses remained significantly above control levels at 28.5 months (the last time point measured for 1:20 AVA), and through 50.5 months for the HuAVA and 1:5 and 1:10 AVA groups (P < 0.05). PA-specific gamma interferon (IFN-γ) and interleukin-4 (IL-4) CD4 + cell frequencies and T cell stimulation indices were sustained through 50.5 months (the last time point measured). PA-specific memory B cell frequencies were highly variable but, in general, were detectable in peripheral blood mononuclear cells (PBMC) by 2 months, were significantly above control levels by 7 months, and remained detectable in the HuAVA and 1:5 and 1:20 AVA groups through 42 months (the last time point measured). HuAVA and diluted AVA elicited a combined Th1/Th2 response and robust immunological priming, with sustained production of high-avidity PA-specific functional antibody, long-term immune cell competence, and immunological memory (30 months for 1:20 AVA and 52 months for 1:10 AVA). Vaccinated animals surviving inhalation anthrax developed high-magnitude anamnestic anti-PA IgG and TNA responses. Copyright
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Nila J. Dharan;
Leslie Z. Sokolow;
Po-Yung Cheng;
Paul Gargiullo;
Ken Gershman;
Ruth Lynfield;
Craig Morin;
Ann Thomas;
James Meek;
Monica Farley;
Katherine E. Arnold;
Art Reingold;
Allen S. Craig;
William Schaffner;
Nancy M. Bennett;
Shelley Zansky;
Joan Baumbach;
Sarah Lathrop;
Laurie Kamimoto;
David K. Shay
BACKGROUND: Young children are at increased risk of severe outcomes from influenza illness, including hospitalization. We conducted a case-control study to identify risk factors for influenza-associated hospitalizations among children in US Emerging Infections Program sites.
METHODS: Cases were children 6-59 months of age hospitalized for laboratory-confirmed influenza infections during 2005-2008. Age- and zip-code-matched controls were enrolled. Data on child, caregiver and household characteristics were collected from parents and medical records. Conditional logistic regression was used to identify independent risk factors for hospitalization.
RESULTS: We enrolled 290 (64%) of 454 eligible cases and 1089 (49%) of 2204 eligible controls. Risk for influenza hospitalization increased with maternal age < 26 years [odds ratio (OR): 1.8, 95% confidence interval (CI): 1.1-2.9]; household income below the poverty threshold (OR: 2.2, 95% CI: 1.4-3.6); smoking by > 50% of household members (OR: 2.9, 95% CI: 1.4-6.6); lack of household influenza vaccination (OR: 1.8, 95% CI: 1.2-2.5) and presence of chronic illnesses, including hematologic/oncologic (OR: 11.8, 95% CI: 4.5-31.0), pulmonary (OR: 2.9, 95% CI: 1.9-4.4) and neurologic (OR: 3.8, 95% CI: 1.6-9.2) conditions. Full influenza immunization decreased the risk among children 6-23 months of age (OR: 0.5, 95% CI: 0.3-0.9) but not among those 24-59 months of age (OR: 1.5, 95% CI: 0.8-3.0; P value for difference = 0.01).
CONCLUSIONS: Chronic illnesses, young maternal age, poverty, household smoking and lack of household influenza vaccination increased the risk of influenza hospitalization. These characteristics may help providers to identify young children who are at greatest risk for severe outcomes from influenza illness.