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Work 1-10 of 61

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Article

HIV-1 non-macrophage-tropic R5 envelope glycoproteins are not more tropic for entry into primary CD4+T-cells than envelopes highly adapted for macrophages

by Thomas Musich; Olivia O'Connell; Maria Paz Gonzalez-Perez; Cynthia Derdeyn; Paul J. Peters; Paul R. Clapham

2015

Subjects
  • Biology, Virology
  • Biology, Microbiology
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Non-mac-tropic HIV-1 R5 viruses are predominantly transmitted and persist in immune tissue even in AIDS patients who carry highly mac-tropic variants in the brain. Non-mac-tropic R5 envelopes (Envs) require high CD4 levels for infection contrasting with highly mac-tropic Envs, which interact more efficiently with CD4 and mediate infection of macrophages that express low CD4. Non-mac-tropic R5 Envs predominantly target T-cells during transmission and in immune tissue where they must outcompete mac-tropic variants. Here, we investigated whether Env+ pseudoviruses bearing transmitted/founder (T/F), early and late disease non-mac-tropic R5 envelopes mediated more efficient infection of CD4+ T-cells compared to those with highly mac-tropic Envs. Results: Highly mac-tropic Envs mediated highest infectivity for primary T-cells, Jurkat/CCR5 cells, myeloid dendritic cells, macrophages, and HeLa TZM-bl cells, although this was most dramatic on macrophages. Infection of primary T-cells mediated by all Envs was low. However, infection of T-cells was greatly enhanced by increasing virus attachment with DEAE dextran and spinoculation, which enhanced the three Env+virus groups to similar extents. Dendritic cell capture of viruses and trans-infection also greatly enhanced infection of primary T-cells. In trans-infection assays, non-mac-tropic R5 Envs were preferentially enhanced and those from late disease mediated levels of T-cell infection that were equivalent to those mediated by mac-tropic Envs. Conclusions: Our results demonstrate that T/F, early or late disease non-mac-tropic R5 Envs do not preferentially mediate infection of primary CD4+ T-cells compared to highly mac-tropic Envs from brain tissue. We conclude that non-macrophage-tropism of HIV-1 R5 Envs in vitro is determined predominantly by a reduced capacity to target myeloid cells via low CD4 rather than a specific adaptation for T-cells entry that precludes macrophage infection.

Article

Prevention and Control of Youth Camp-Associated Acute Gastroenteritis Outbreaks

by Anita K Kambhampati; Zachary A Marsh; Michele C Hlavsa; Virginia A Roberts; Antonio R Vieira; Jonathan S Yoder; Aron J Hall

2019

Subjects
  • Health Sciences, Public Health
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Background: Approximately 14 million children attend more than 14000 US camps every year. Shared accommodations and activities can facilitate acute gastroenteritis (AGE) outbreaks. Methods: We analyzed data from the National Outbreak Reporting System on US youth camp-associated AGE outbreaks that occurred between 2009 and 2016. We also conducted a systematic literature search of youth camp-associated AGE outbreaks that have occurred around the world and a gray literature search for existing recommendations on outbreak prevention and control at camps worldwide. Results: Thirty-nine US jurisdictions reported a total of 229 youth camp-associated AGE outbreaks to the National Outbreak Reporting System. Of the 226 outbreaks included in our analyses, 120 (53%) were reported to have resulted from person-to-person transmission, 42 (19%) from an unknown transmission mode, 38 (17%) from foodborne transmission, 19 (8%) from waterborne transmission, 5 (2%) from animal contact, and 2 (<1%) from environmental contamination. Among 170 (75%) outbreaks with a single suspected or confirmed etiology, norovirus (107 [63%] outbreaks), Salmonella spp (16 [9%]), and Shiga-toxin producing Escherichia coli (12 [7%]) were implicated most frequently. We identified 43 additional youth camp-associated AGE outbreaks in the literature that occurred in various countries between 1938 and 2014. Control measures identified through the literature search included camp closure, separation of ill campers, environmental disinfection, and education on food preparation and hand hygiene. Conclusions: Youth camp-associated AGE outbreaks are caused by numerous pathogens every year. These outbreaks are facilitated by factors that include improper food preparation, inadequate cleaning and disinfection, shared accommodations, and contact with animals. Health education focused on proper hygiene and preventing disease transmission could help control or prevent these outbreaks.

Article

Estimating tuberculosis cases and their economic costs averted in the United States over the past two decades

by Kenneth Castro; S.M. Marks; M.P. Chen; A.N. Hill; J.E. Becerra; R Miramontes; C.A. Winston; T.R. Navin; R.H. Pratt; K.H. Young; P.A. LoBue

2016

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Public Health
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BACKGROUND: Following a concerted public health response to the resurgence of tuberculosis (TB) in the United States in the late 1980s, annual TB incidence decreased substantially. However, no estimates exist of the number and cost savings of TB cases averted. METHODS : TB cases averted in the United States during 1995-2014 were estimated: Scenario 1 used a static 1992 case rate; Scenario 2 applied the 1992 rate to foreign-born cases, and a pre-resurgence 5.1% annual decline to US-born cases; and a statistical model assessed human immunodeficiency virus and TB program indices. We applied the cost of illness to estimate the societal benefits (costs averted) in 2014 dollars. RESULT S : During 1992-2014, 368 184 incident TB cases were reported, and cases decreased by two thirds during that period. In the scenarios and statistical model, TB cases averted during 1995-2014 ranged from approximately 145 000 to 319 000. The societal benefits of averted TB cases ranged from US3.1 to US6.7 billion, excluding deaths, and from US6.7 to US14.5 billion, including deaths. CONCLUS IONS : Coordinated efforts in TB control and prevention in the United States yielded a remarkable number of TB cases averted and societal economic benefits. We illustrate the value of concerted action and targeted public health funding.

Article

Exploring water, sanitation, and hygiene coverage targets for reaching and sustaining trachoma elimination: G-computation analysis

by Matthew Freeman; Kristin M Sullivan; Emma M Harding-Esch; Alexander P Keil; Wilfrid E Batcho; Amadou A Bio Issifou; Victor Bucumi; Assumpta L Bella; Emilienne Epee; Segni Bobo Barkesa; Fikre Seife Gebretsadik; Salimato Sanha; Khumbo M Kalua; Michael P Masika; Abdallahi O Minnih; Mariamo Abdala; Marília E Massangaie; Abdou Amza; Boubacar Kadri; Beido Nassirou; Caleb D Mpyet; Nicholas Olobio; Mouctar D Badiane; Balgesa E Elshafie; Gilbert Baayenda; George E Kabona; Oscar Kaitaba; Alistidia Simon; Tawfik Q Al-Khateeb; Consity Mwale; Ana Bakhtiari; Daniel Westreich; Anthony W Solomon; Emily W Gower

2023

Subjects
  • Health Sciences, Epidemiology
  • Health Sciences, Medicine and Surgery
  • Health Sciences, Opthamology
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Abstract:Close

Background Trachoma is the leading infectious cause of blindness. To reduce transmission, water, sani-tation, and hygiene (WaSH) improvements are promoted through a comprehensive public health strategy. Evidence supporting the role of WaSH in trachoma elimination is mixed and it remains unknown what WaSH coverages are needed to effectively reduce transmission. Methods/Findings We used g-computation to estimate the impact on the prevalence of trachomatous inflam-mation—follicular among children aged 1–9 years (TF1-9) when hypothetical WaSH interventions raised the minimum coverages from 5% to 100% for “nearby” face-washing water (<30 minutes roundtrip collection time) and adult latrine use in an evaluation unit (EU). For each scenario, we estimated the generalized prevalence difference as the TF1-9 prevalence under the intervention scenarios minus the observed prevalence. Data from 574 cross-sec-tional surveys conducted in 16 African and Eastern Mediterranean countries were included. Surveys were conducted from 2015–2019 with support from the Global Trachoma Mapping Project and Tropical Data. When modeling interventions among EUs that had not yet met the TF1-9 elimination tar-get, increasing nearby face-washing water and latrine use coverages above 30% was gen-erally associated with consistent decreases in TF1-9. For nearby face-washing water, we estimated a 25% decrease in TF1-9 at 65% coverage, with a plateau upon reaching 85% coverage. For latrine use, the estimated decrease in TF1-9 accelerated from 80% coverage upward, with a 25% decrease in TF1-9 by 85% coverage. Among EUs that had previously met the elimination target, results were inconclusive. Conclusions Our results support Sustainable Development Goal 6 and provide insight into potential WaSH-related coverage targets for trachoma elimination. Targets can be tested in future tri-als to improve evidence-based WaSH guidance for trachoma.

Article

Obesity, Diabetes, and the Risk of Invasive Group B Streptococcal Disease in Nonpregnant Adults in the United States

by Samantha I Pitts; Nisa M Maruthur; Gayle E Langley; Tracy Pondo; Kathleen A Shutt; Rosemary Hollick; Stephanie J Schrag; Ann Thomas; Megin Nichols; Monica Farley; James P Watt; Lisa Miller; William Schaffner; Corinne Holtzman; Lee H Harrison

2018

Subjects
  • Health Sciences, Public Health
  • Health Sciences, Epidemiology
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Background. Rates of invasive group B Streptococcus (GBS) disease, obesity, and diabetes have increased in US adults. We hypothesized that obesity would be independently associated with an increased risk of invasive GBS disease. Methods. We identified adults with invasive GBS disease within Active Bacterial Core surveillance during 2010-2012 and used population estimates from the Behavioral Risk Factor Surveillance System to calculate invasive GBS incidence rates. We estimated relative risks (RRs) of invasive GBS using Poisson analysis with offset denominators, with obesity categorized as class I/II (body mass index [BMI] = 30-39.9 kg/m2) and class III (BMI ≥ 40.0 kg/m2). Results. In multivariable analysis of 4281 cases, the adjusted RRs of invasive GBS disease were increased for obesity (class I/ II: RR, 1.52; 95% confidence interval [CI], 1.14-2.02; and class III: RR, 4.87; 95% CI, 3.50-6.77; reference overweight) and diabetes (RR, 6.04; 95% CI, 4.77-7.65). The adjusted RR associated with class III obesity was 3-fold among persons with diabetes (95% CI, 1.38-6.61) and nearly 9-fold among persons without diabetes (95% CI, 6.41-12.46), compared with overweight. The adjusted RRs associated with diabetes varied by age and BMI, with the highest RR in young populations without obesity. Population attributable risks of invasive GBS disease were 27.2% for obesity and 40.1% for diabetes. Conclusions. Obesity and diabetes were associated with substantially increased risk of infection from invasive GBS. Given the population attributable risks of obesity and diabetes, interventions that reduce the prevalence of these conditions would likely reduce the burden of invasive GBS infection.

Article

Editorial: Emerging and Re-emerging Vector-borne and Zoonotic Diseases

by Alfonso J Rodriguez-Morales; Jaime A Cardona-Ospina; Matthew Collins

2021

Subjects
  • Health Sciences, Medicine and Surgery
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The Colombian Nobel laureate Gabriel Garcia Marquez stated in his last will, “la muerte no llega con la vejez, sino con el olvido” (“death does not come with old age, but with oblivion”). Indeed, how many deaths due to tropical diseases can be avoided? How can investment in these neglected diseases significantly change the course of the disease? Even in a macro vision, how could the socioeconomic condition of those affected by these diseases be changed to avoid transmission, morbidity, and mortality? We must rescue tropical and emerging global diseases from oblivion, and the rescue begins with us.

Article

Closing the book on Category II: time for individualized regimens for patients with recurrent tuberculosis

by Sara Auld; Neel Gandhi; N. Sarita Shah

2018

Subjects
  • Health Sciences, Public Health
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FOLLOWING THE CLINICAL TRIALS by the Singapore Tuberculosis Service and the British Medical Research Council in the 1970s, the 6-month ‘short-course’ tuberculosis (TB) regimen, based on isoniazid, rifampicin, and pyrazinamide, was widely adopted in the 1980s.1,2 However, for patients undergoing retreatment for TB disease, there was no clear evidence-based treatment regimen. In an effort to fill this gap, in 1991 the World Health Organization (WHO) endorsed the ‘Category II’ regimen, an 8-month regimen with the addition of streptomycin, as a retreatment regimen for patients with TB disease relapse, treatment failure, or treatment after an interruption of at least 2 months.3 Despite this endorsement, it was already recognized that the addition of a single drug to a failing regimen set the stage for the amplification of drug resistance and poor clinical outcomes.4–6 Nearly two decades later, in the face of mounting data pointing to its ineffectiveness, in 2010 the WHO recommended against using the Category II regimen.7 This reversal remains highly relevant for the 19% of retreatment cases estimated to have drug resistance in the context of relapsed or recurrent disease in 2016.

Article

Tackling the unknowns of short-course rifapentine-based treatment for active tuberculosis: a decision analysis

by David Holland; CD Hamilton; JE Stout

2016

Subjects
  • Health Sciences, Medicine and Surgery
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BACKGROUND: Shorter treatment regimens for tuberculosis (TB) are deemed vital for advancing TB control. Murine studies have suggested potential new regimens; however, Phase II human studies of these drug combinations have not shown clear improvement in 2-month culture conversion over current therapy. Nevertheless, drugs such as rifapentine (RPT) may have additional sterilizing effects after 2 months that are difficult to measure in current Phase II studies. OBJECTIVES : To model potential bactericidal effects of RPT in a Phase III trial of a 4-month anti-tuberculosis regimen. METHODS : We developed a Markov model of antituberculosis treatment to compare two regimens for treating TB: a 6-month standard (rifampin-based) treatment and a 4-month regimen using high-dose RPT. The primary outcome was the number of relapses. RESULT S : In the base-case scenario, standard therapy resulted in fewer relapses; improvement in 2-month culture conversion rates in the RPT arm did not change this result. However, while RPT has better sterilizing ability during months 3 and 4 (as observed in the mouse model), the 4-month regimen results in fewer relapses. CONCLUS IONS : Higher 2-month culture conversion rates are neither sufficient nor necessary for making a theoretical 4-month anti-tuberculosis treatment regimen advantageous.

Article

Conserved Oligopeptide Permeases Modulate Sporulation Initiation in Clostridium difficile

by Adrianne Edwards; Kathryn L. Nawrocki; Shonna McBride

2014

Subjects
  • Health Sciences, Immunology
  • Health Sciences, General
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The anaerobic gastrointestinal pathogen Clostridium difficile must form a metabolically dormant spore to survive in oxygenic environments and be transmitted from host to host. The regulatory factors by which C. difficile initiates and controls the early stages of sporulation in C. difficile are not highly conserved in other Clostridium or Bacillus species. Here, we investigated the role of two conserved oligopeptide permeases, Opp and App, in the regulation of sporulation in C. difficile. These permeases are known to positively affect sporulation in Bacillus species through the import of sporulation-specific quorum-sensing peptides. In contrast to other spore-forming bacteria, we discovered that inactivating these permeases in C. difficile resulted in the earlier expression of early sporulation genes and increased sporulation in vitro. Furthermore, disruption of opp and app resulted in greater virulence and increased the amounts of spores recovered from feces in the hamster model of C. difficile infection. Our data suggest that Opp and App indirectly inhibit sporulation, likely through the activities of the transcriptional regulator SinR and its inhibitor, SinI. Taken together, these results indicate that the Opp and App transporters serve a different function in controlling sporulation and virulence in C. difficile than in Bacillus subtilis and suggest that nutrient availability plays a significant role in pathogenesis and sporulation in vivo. This study suggests a link between the nutritional status of the environment and sporulation initiation in C. difficile.

Article

The Intracellular Environment of Human Macrophages That Produce Nitric Oxide Promotes Growth of Mycobacteria

by Joo-Yong Jung; Ranjna Madan Lala; Maria Georgieva; Jyothi Rengarajan; Charles D. Sohaskey; Franz-Christoph Bange; Cory M. Robinson

2013

Subjects
  • Biology, Microbiology
  • Health Sciences, Medicine and Surgery
  • File Download
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Nitric oxide (NO) is a diffusible radical gas produced from the activity of nitric oxide synthase (NOS). NOS activity in murine macrophages has a protective role against mycobacteria through generation of reactive nitrogen intermediates (RNIs). However, the production of NO by human macrophages has remained unclear due to the lack of sensitive reagents to detect NO directly. The purpose of this study was to investigate NO production and the consequence to mycobacteria in primary human macrophages. We found that Mycobacterium bovis BCG or Mycobacterium tuberculosis infection of human macrophages induced expression of NOS2 and NOS3 that resulted in detectable production of NO. Treatment with gamma interferon (IFN-γ), L-arginine, and tetrahydrobiopterin enhanced expression of NOS2 and NOS3 isoforms, as well as NO production. Both of these enzymes were shown to contribute to NO production. The maximal level of NO produced by human macrophages was not bactericidal or bacteriostatic to M. tuberculosis or BCG. The number of viable mycobacteria was increased in macrophages that produced NO, and this requires expression of nitrate reductase. An narG mutant of M. tuberculosis persisted but was unable to grow in human macrophages. Taken together, these data (i) enhance our understanding of primary human macrophage potential to produce NO, (ii) demonstrate that the level of RNIs produced in response to IFN-γ in vitro is not sufficient to limit intracellular mycobacterial growth, and (iii) suggest that mycobacteria may use RNIs to enhance their survival in human macrophages.
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