Recent publications from TDC authors

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NCBI: db=pubmed; Term=(Yansouni C[Author]) OR (Iqbal A[Author] parasitology) OR (Ndao M[Author]) OR (Ward BJ[Author]) OR (Semret M[Author]) OR (Libman M[Author]) OR (Greenaway C[author]) OR (Barkati S[Author])
Updated: 2 hours 19 min ago

Fecal sludge as a fuel: characterization, cofire limits, and evaluation of quality improvement measures.

Sun, 02/17/2019 - 00:49
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Fecal sludge as a fuel: characterization, cofire limits, and evaluation of quality improvement measures.

Water Sci Technol. 2018 Dec;78(12):2437-2448

Authors: Hafford LM, Ward BJ, Weimer AW, Linden K

Abstract
In many low-income cities, a high proportion of fecal sludge, the excreta and blackwater collected from onsite sanitation systems such as pit latrines, is not safely managed. This constitutes a major danger to environmental and human health. The water, sanitation, and hygiene sector has recognized that valorization of treated fecal sludge could offset the upfront cost of treatment by using it as a fuel source. The few quantitative studies on fecal sludge fuel published to date have focused on heating value, moisture, ash fraction, and heavy metals. However, other factors impacting fuel utility, specifically ash speciation, have not been adequately quantified for fecal sludge. This study contributes to closing that gap and shows the value of more detailed quantification. It first characterizes fecal sludge samples from Colorado and Uganda, confirms that the fuel is better if cofired with other biomass, and outlines a framework for determining safe cofire ratios. Second, the study evaluates two methods for improving fecal sludge as a fuel: carbonization and ash leaching. Carbonization of fecal sludge did not improve fuel quality, but leaching showed promise in ash reduction.

PMID: 30767909 [PubMed - in process]

Embracing the challenges of migration medicine.

Fri, 02/08/2019 - 00:12
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Embracing the challenges of migration medicine.

J Travel Med. 2019 Feb 06;:

Authors: Greenaway C, Castelli F

PMID: 30726955 [PubMed - as supplied by publisher]

Infectious diseases at different stages of migration: an expert review.

Fri, 02/08/2019 - 00:12
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Infectious diseases at different stages of migration: an expert review.

J Travel Med. 2019 Feb 06;:

Authors: Greenaway C, Castelli F

Abstract
Background: Human migration is increasing in magnitude and scope. The majority of migrants arriving in high income countries originate from countries with a high prevalence of infectious diseases. The risk and burden of infectious diseases are not equally distributed among migrant groups and varies with migration stage.
Methods: A broad literature review on the drivers for infectious diseases and associated health outcomes among migrants across different stages of migration was conducted. The aim was to provide practitioners with an overview of the key infectious disease risks at each stage to guide health promotion strategies.
Results: A complex interaction of factors lead to infectious diseases and associated poor health outcomes among migrants. The most important drivers are the epidemiology of infectious diseases in their countries of origin, the circumstances and conditions of the migration journey, and barriers accessing health care post arrival. During the recent large waves of forced migration into Europe the primary health concerns on arrival were, psychological, traumatic and chronic non-communicable diseases. In the early settlement period, crowded and unhygienic living conditions in reception camps facilitated outbreaks of respiratory, gastrointestinal, skin infections and vaccine preventable diseases. After re-settlement, undetected and untreated latent infections due to tuberculosis, viral hepatitis, HIV, chronic helminthiasis and Chagas disease lead to poor health outcomes. Migrants are disproportionally affected by preventable travel related diseases such as malaria, typhoid and hepatitis due to poor uptake of pre-travel prophylaxis and vaccination. Infectious diseases among migrants can be decreased at all migration stages with health promotion strategies adapted to their specific needs and delivered in a linguistically and culturally sensitive manner.
Conclusions: Tailored health promotion and screening approaches and accessible and responsive health systems, regardless of legal status, will be needed at all migration stages to limit the burden and transmission of infectious diseases in the migrant population.

PMID: 30726941 [PubMed - as supplied by publisher]

What's in a Name and Why "Tropical Medicine" Matters in 2019.

Wed, 02/06/2019 - 00:04
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What's in a Name and Why "Tropical Medicine" Matters in 2019.

Infect Dis Clin North Am. 2019 Mar;33(1):xiii-xiv

Authors: Libman M, Yansouni CP

PMID: 30712770 [PubMed - in process]

Migration Medicine.

Wed, 02/06/2019 - 00:04
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Migration Medicine.

Infect Dis Clin North Am. 2019 Mar;33(1):265-287

Authors: Greenaway C, Castelli F

Abstract
Migration is increasing and practitioners need to be aware of the unique health needs of this population. The prevalence of infectious diseases among migrants varies and generally mirrors that of their countries of origin, but is modified by the circumstance of migration, the presence of pre-arrival screening programs and post arrival access to health care. To optimize the health of migrants practitioners; (1) should take all opportunities to screen migrants at risk for latent infections such as tuberculosis, chronic hepatitis B and C, HIV, strongyloidiasis, schistosomiasis and Chagas disease, (2) update routine vaccines in all age groups and, (3) be aware of "rare and tropical infections" related to migration and return travel.

PMID: 30712766 [PubMed - in process]

Antimicrobial Resistance in the Tropics.

Wed, 02/06/2019 - 00:04
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Antimicrobial Resistance in the Tropics.

Infect Dis Clin North Am. 2019 Mar;33(1):231-245

Authors: Semret M, Haraoui LP

Abstract
Antimicrobial resistance (AMR) is on the rise and spreading rapidly worldwide. Low- and middle-income countries, because of weak health systems, are particularly vulnerable to this increase. Population mobility further fuels the globalization of AMR, with travelers and migrants at significant risk of harboring drug-resistant organisms. This article provides an overview of the factors that contribute to the emergence, spread, and persistence of AMR, particularly antibiotic-resistance, in the tropics. Also addressed are clinical implications of this emergent global crisis for migrants and travelers, using specific scenarios commonly encountered in those populations.

PMID: 30712764 [PubMed - in process]

New Tools to Test Stool: Managing Travelers' Diarrhea in the Era of Molecular Diagnostics.

Wed, 02/06/2019 - 00:04
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New Tools to Test Stool: Managing Travelers' Diarrhea in the Era of Molecular Diagnostics.

Infect Dis Clin North Am. 2019 Mar;33(1):197-212

Authors: Eckbo EJ, Yansouni CP, Pernica JM, Goldfarb DM

Abstract
Travelers' diarrhea affects up to 60% of visitors to tropical and subtropical regions. Although symptoms are generally self-limited, some infections are associated with significant morbidity and occasional mortality. Newer molecular diagnostic techniques allow for highly sensitive, specific, and expeditious testing of a wide range of potential pathogens. Identification of the causative pathogen of travelers' diarrhea allows for targeted therapy and management and a reduction in empiric broad-spectrum coverage.

PMID: 30712762 [PubMed - in process]

Toxoplasma gondii infection in stranded St. Lawrence Estuary beluga Delphinapterus leucas in Quebec, Canada.

Wed, 02/06/2019 - 00:04
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Toxoplasma gondii infection in stranded St. Lawrence Estuary beluga Delphinapterus leucas in Quebec, Canada.

Dis Aquat Organ. 2018 09 27;130(3):165-175

Authors: Iqbal A, Measures L, Lair S, Dixon B

Abstract
The St. Lawrence Estuary (SLE) beluga Delphinapterus leucas in Quebec, Canada, is endangered due to intensive hunting in the 19th and 20th centuries and subsequent anthropogenic contamination and human activities in the region. Infectious disease is a primary cause of death in this population. The protozoan parasite Toxoplasma gondii is reported in numerous marine mammal species, including beluga. In the present study, 55 tissue samples (heart and brain) collected from 34 stranded SLE beluga were analysed by PCR followed by DNA sequencing and restriction fragment length polymorphism analysis (RFLP) to determine the PCR prevalence and genotypes of T. gondii in these beluga. Of 34 beluga tested, 44% were positive for T. gondii by PCR, with males having a higher prevalence of infection than females and with more infected neonates and juveniles than adults. Molecular analyses indicated that all T. gondii infecting stranded SLE beluga grouped into genotype II, which predominates in humans. While our results indicate that a high prevalence of stranded beluga are PCR-positive for T. gondii infection, very few deaths are attributed to toxoplasmosis based on published necropsy results. Toxoplasma gondii can cause a range of diseases, including neurological deficits, and more data are needed to investigate this parasite's effect on population recovery.

PMID: 30259869 [PubMed - indexed for MEDLINE]

Needle-free delivery of influenza vaccine using the Med-Jet® H4 is efficient and elicits the same humoral and cellular responses as standard IM injection: A randomized trial.

Mon, 02/04/2019 - 00:36

Needle-free delivery of influenza vaccine using the Med-Jet® H4 is efficient and elicits the same humoral and cellular responses as standard IM injection: A randomized trial.

Vaccine. 2019 Jan 29;:

Authors: Shapiro JR, Hodgins B, Hendin HE, Patel A, Menassa K, Menassa C, Menassa M, Pereira JA, Ward BJ

Abstract
BACKGROUND: Needle-free vaccine delivery systems have many potential advantages including increased vaccine compliance and decreased risk of needlestick injuries and syringe reuse. The Med-Jet® H4 is a gas-powered, auto-disabling disposable syringe jet injector. The Med-Jet family of products are currently being used in dermatology, podiatry, pain management and veterinary practices. The objectives of this study were to assess patient attitudes, time-efficiency, safety and immunogenicity of the seasonal influenza vaccine delivered by Med-Jet compared to the traditional needle-and-syringe.
METHODS: A total of 80 patients were randomized 2:1:1 to receive a commercial trivalent vaccine by Med-Jet or needle injection from a single-dose or multi-dose vial. Patient attitudes were assessed pre-randomization and post-immunization. Safety data were collected for 21 days post-immunization. Efficiency of vaccine administration was measured through a time-and-motion study. Humoral and cellular responses were assessed on Days 0 and 21.
RESULTS: Overall, the participants readily accepted Med-Jet vaccination despite greater frequency of transient local reactions (eg: redness, swelling) immediately following immunization. Vaccine administration took slightly longer with the Med-Jet, but this difference decreased over time. Geometric mean hemagglutination inhibition titers, seroconversion and seroprotection rates in the Med-Jet and needle groups were equivalent for all influenza strains in the vaccine. Microneutralization responses were also essentially identical. There were no significant differences between the groups in the frequency of functional CD4 + T cells, memory subset distribution or poly-functionality.
CONCLUSIONS: These data suggest that the Med-Jet is an acceptable means of delivering seasonal influenza vaccine. The system was attractive to subjects, rapidly learned by skilled vaccine nurses and elicited both humoral and cellular responses that were indistinguishable from those elicited with needle injection. While other studies have assessed the humoral response to jet injection of influenza vaccine, to our knowledge, this study is the first to assess the cellular aspect of this response. (ClinTrials.gov-NCT03150537).

PMID: 30709725 [PubMed - as supplied by publisher]

Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network.

Thu, 01/31/2019 - 01:08
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Resource utilization and cost of influenza requiring hospitalization in Canadian adults: A study from the serious outcomes surveillance network of the Canadian Immunization Research Network.

Influenza Other Respir Viruses. 2018 03;12(2):232-240

Authors: Ng C, Ye L, Noorduyn SG, Hux M, Thommes E, Goeree R, Ambrose A, Andrew MK, Hatchette T, Boivin G, Bowie W, ElSherif M, Green K, Johnstone J, Katz K, Leblanc J, Loeb M, MacKinnon-Cameron D, McCarthy A, McElhaney J, McGeer A, Poirier A, Powis J, Richardson D, Sharma R, Semret M, Smith S, Smyth D, Stiver G, Trottier S, Valiquette L, Webster D, McNeil SA, Serious Outcomes Surveillance Network of the Canadian Immunization Research Network (CIRN) Investigators, Toronto Invasive Bacterial Diseases Network (TIBDN) Investigators

Abstract
BACKGROUND: Consideration of cost determinants is crucial to inform delivery of public vaccination programs.
OBJECTIVES: To estimate the average total cost of laboratory-confirmed influenza requiring hospitalization in Canadians prior to, during, and 30 days following discharge. To analyze effects of patient/disease characteristics, treatment, and regional differences in costs.
METHODS: Study utilized previously recorded clinical characteristics, resource use, and outcomes of laboratory-confirmed influenza patients admitted to hospitals in the Serious Outcomes Surveillance (SOS), Canadian Immunization Research Network (CIRN), from 2010/11 to 2012/13. Unit costs including hospital overheads were linked to inpatient/outpatient resource utilization before and after admissions.
RESULTS: Dataset included 2943 adult admissions to 17 SOS Network hospitals and 24 Toronto Invasive Bacterial Disease Network hospitals. Mean age was 69.5 years. Average hospital stay was 10.8 days (95% CI: 10.3, 11.3), general ward stays were 9.4 days (95% CI: 9.0, 9.8), and ICU stays were 9.8 days (95% CI: 8.6, 11.1) for the 14% of patients admitted to the ICU. Average cost per case was $14 612 CAD (95% CI: $13 852, $15 372) including $133 (95% CI: $116, $150) for medical care prior to admission, $14 031 (95% CI: $13 295, $14 768) during initial hospital stay, $447 (95% CI: $271, $624) post-discharge, including readmission within 30 days.
CONCLUSION: The cost of laboratory-confirmed influenza was higher than previous estimates, driven mostly by length of stay and analyzing only laboratory-confirmed influenza cases. The true per-patient cost of influenza-related hospitalization has been underestimated, and prevention programs should be evaluated in this context.

PMID: 29125689 [PubMed - indexed for MEDLINE]

The Effectiveness and Cost-Effectiveness of Hepatitis C Screening for Migrants in the EU/EEA: A Systematic Review.

Wed, 01/30/2019 - 01:13
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The Effectiveness and Cost-Effectiveness of Hepatitis C Screening for Migrants in the EU/EEA: A Systematic Review.

Int J Environ Res Public Health. 2018 09 14;15(9):

Authors: Greenaway C, Makarenko I, Chakra CNA, Alabdulkarim B, Christensen R, Palayew A, Tran A, Staub L, Pareek M, Meerpohl JJ, Noori T, Veldhuijzen I, Pottie K, Castelli F, Morton RL

Abstract
Chronic hepatitis C (HCV) is a public health priority in the European Union/European Economic Area (EU/EEA) and is a leading cause of chronic liver disease and liver cancer. Migrants account for a disproportionate number of HCV cases in the EU/EEA (mean 14% of cases and >50% of cases in some countries). We conducted two systematic reviews (SR) to estimate the effectiveness and cost-effectiveness of HCV screening for migrants living in the EU/EEA. We found that screening tests for HCV are highly sensitive and specific. Clinical trials report direct acting antiviral (DAA) therapies are well-tolerated in a wide range of populations and cure almost all cases (>95%) and lead to an 85% lower risk of developing hepatocellular carcinoma and an 80% lower risk of all-cause mortality. At 2015 costs, DAA based regimens were only moderately cost-effective and as a result less than 30% of people with HCV had been screened and less 5% of all HCV cases had been treated in the EU/EEA in 2015. Migrants face additional barriers in linkage to care and treatment due to several patient, practitioner, and health system barriers. Although decreasing HCV costs have made treatment more accessible in the EU/EEA, HCV elimination will only be possible in the region if health systems include and treat migrants for HCV.

PMID: 30223539 [PubMed - indexed for MEDLINE]

Prevalence of strongyloidiasis and schistosomiasis among migrants: a systematic review and meta-analysis.

Mon, 01/28/2019 - 00:04
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Prevalence of strongyloidiasis and schistosomiasis among migrants: a systematic review and meta-analysis.

Lancet Glob Health. 2019 Feb;7(2):e236-e248

Authors: Asundi A, Beliavsky A, Liu XJ, Akaberi A, Schwarzer G, Bisoffi Z, Requena-Méndez A, Shrier I, Greenaway C

Abstract
BACKGROUND: Global migration from regions where strongyloidiasis and schistosomiasis are endemic to non-endemic countries has increased the potential individual and public health effect of these parasitic diseases. We aimed to estimate the prevalence of these infections among migrants to establish which groups are at highest risk and who could benefit from screening.
METHODS: We did a systematic review and meta-analysis of strongyloidiasis and schistosomiasis prevalence among migrants born in endemic countries. Original studies that included data for the prevalence of Strongyloides or Schistosoma antibodies in serum or the prevalence of larvae or eggs in stool or urine samples among migrants originating from countries endemic for these parasites and arriving or living in host countries with low endemicity-specifically the USA, Canada, Australia, New Zealand, Israel, and 23 western European countries-were eligible for inclusion. Pooled estimates of the prevalence of strongyloidiasis and schistosomiasis by stool or urine microscopy for larvae or eggs or serum antibodies were calculated with a random-effects model. Heterogeneity was explored by stratification by age, region of origin, migrant class, period of study, and type of serological antigen used.
FINDINGS: 88 studies were included. Pooled strongyloidiasis seroprevalence was 12·2% (95% CI 9·0-15·9%; I2 96%) and stool-based prevalence was 1·8% (1·2-2·6%; 98%). Migrants from east Asia and the Pacific (17·3% [95% CI 4·1-37·0]), sub-Saharan Africa (14·6% [7·1-24·2]), and Latin America and the Caribbean (11·4% [7·8-15·7]) had the highest seroprevalence. Pooled schistosomiasis seroprevalence was 18·4% (95% CI 13·1-24·5; I2 97%) and stool-based prevalence was 0·9% (0·2-1·9; 99%). Sub-Saharan African migrants had the highest seroprevalence (24·1·% [95% CI 16·4-32·7]).
INTERPRETATION: Strongyloidiasis affects migrants from all global regions, whereas schistosomiasis is focused in specific regions and most common among sub-Saharan African migrants. Serological prevalence estimates were several times higher than stool estimates for both parasites. These data can be used to inform screening decisions for migrants and support the use of serological screening, which is more sensitive and easier than stool testing.
FUNDING: None.

PMID: 30683241 [PubMed - in process]

Author response: Progressive multifocal leukoencephalopathy after fingolimod treatment.

Thu, 01/17/2019 - 01:46
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Author response: Progressive multifocal leukoencephalopathy after fingolimod treatment.

Neurology. 2019 Jan 15;92(3):151

Authors: Berger JR, Cree BA, Greenberg B, Hemmer B, Ward BJ, Dong VM, Merschhemke M

PMID: 30643034 [PubMed - in process]

A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities.

Sat, 01/12/2019 - 01:35
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A plant-derived VLP influenza vaccine elicits a balanced immune response even in very old mice with co-morbidities.

PLoS One. 2019;14(1):e0210009

Authors: Hodgins B, Pillet S, Landry N, Ward BJ

Abstract
BACKGROUND: The elderly are at high risk from influenza, in part because immunity wanes with age and through the accumulation of comorbidities. A novel plant-derived virus-like-particle (VLP) vaccine bearing influenza hemagglutinin can induce a balanced humoral and cellular response in old mice (16-18 months) while split virion vaccines elicit mostly antibodies. Because mice also collect comorbidities and lose immune competence as they age, we wished to determine how the plant-derived VLP vaccine would perform in animals approaching the end of their life-span.
MATERIALS AND METHODS: Old (24-26 months) female BALB/c mice received two intramuscular doses of H1-VLP vaccine, an inactivated H1N1 vaccine (IIV) (both based on A/H1N1/California/07/09) (3μg each) or PBS. Serum was collected on day 42 and humoral responses were measured by enzyme-linked immunosorbent assay (ELISA), microneutralization (MN) and hemagglutination inhibition (HI) assays. Influenza-specific splenocyte CD4+ & CD8+ T cell responses were measured by flow cytometry. Full body computed tomography (CT) and structured necropsies were performed on day 42. Comorbidities including reduced lung volume (kyphosis), masses, abscesses, etc. were assessed using a standard scoring system (1-21) and mice with scores ≥5 were considered to have important comorbidities.
RESULTS: Overall, 53.3% of the animals had significant comorbidities. Three weeks post-boost, HI and MN titres were mostly undetectable but ELISA titres were significantly higher in the H1-VLP animals compared to the IIV group (GMT (95% CI): 961 (427, 2163) vs 425 (200, 903): p = 0.03). Both CD4+(TNFα, IFNγ) and CD8+ (IFNγ) T cell responses were also greater in the H1-VLP group than the IIV.
CONCLUSIONS: Even in very old mice with comorbidities, the plant-made H1-VLP vaccine elicited a stronger and more balanced immune response than IIV. Animals with fewer comorbidities tended to have the better composite (humoral and cellular) responses. These novel vaccines have the potential to address some of the limitations of current vaccines in the elderly.

PMID: 30629622 [PubMed - in process]

Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD.

Thu, 01/10/2019 - 00:28
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Effectiveness of Influenza Vaccination on Hospitalizations and Risk Factors for Severe Outcomes in Hospitalized Patients With COPD.

Chest. 2019 Jan;155(1):69-78

Authors: Mulpuru S, Li L, Ye L, Hatchette T, Andrew MK, Ambrose A, Boivin G, Bowie W, Chit A, Dos Santos G, ElSherif M, Green K, Haguinet F, Halperin SA, Ibarguchi B, Johnstone J, Katz K, Langley JM, LeBlanc J, Loeb M, MacKinnon-Cameron D, McCarthy A, McElhaney JE, McGeer A, Powis J, Richardson D, Semret M, Shinde V, Smyth D, Trottier S, Valiquette L, Webster D, McNeil SA, Serious Outcomes Surveillance (SOS) Network of the Canadian Immunization Research Network (CIRN)

Abstract
BACKGROUND: The effectiveness of influenza vaccination in reducing influenza-related hospitalizations among patients with COPD is not well described, and influenza vaccination uptake remains suboptimal.
METHODS: Data were analyzed from a national, prospective, multicenter cohort study including patients with COPD, hospitalized with any acute respiratory illness or exacerbation between 2011 and 2015. All patients underwent nasopharyngeal swab screening with polymerase chain reaction (PCR) testing for influenza. The primary outcome was an influenza-related hospitalization. We identified influenza-positive cases and negative control subjects and used multivariable logistic regression with a standard test-negative design to estimate the vaccine effectiveness for preventing influenza-related hospitalizations.
RESULTS: Among 4,755 hospitalized patients with COPD, 4,198 (88.3%) patients with known vaccination status were analyzed. The adjusted analysis showed a 38% reduction in influenza-related hospitalizations in vaccinated vs unvaccinated individuals. Influenza-positive patients (n = 1,833 [38.5%]) experienced higher crude mortality (9.7% vs 7.9%; P = .047) and critical illness (17.2% vs 12.1%; P < .001) compared with influenza-negative patients. Risk factors for mortality in influenza-positive patients included age > 75 years (OR, 3.7 [95% CI, 0.4-30.3]), cardiac comorbidity (OR, 2.0 [95% CI, 1.3-3.2]), residence in long-term care (OR, 2.6 [95% CI, 1.5-4.5]), and home oxygen use (OR, 2.9 [95% CI, 1.6-5.1]).
CONCLUSIONS: Influenza vaccination significantly reduced influenza-related hospitalization among patients with COPD. Initiatives to increase vaccination uptake and early use of antiviral agents among patients with COPD could reduce influenza-related hospitalization and critical illness and improve health-care costs in this vulnerable population.
TRIAL REGISTRY: ClinicalTrials.govNo.:NCT01517191; URL www.clinicaltrials.gov.

PMID: 30616737 [PubMed - in process]

The establishment of surrogates and correlates of protection: Useful tools for the licensure of effective influenza vaccines?

Fri, 01/04/2019 - 00:48
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The establishment of surrogates and correlates of protection: Useful tools for the licensure of effective influenza vaccines?

Hum Vaccin Immunother. 2018 03 04;14(3):647-656

Authors: Ward BJ, Pillet S, Charland N, Trepanier S, Couillard J, Landry N

Abstract
The search for a test that can predict vaccine efficacy is an important part of any vaccine development program. Although regulators hesitate to acknowledge any test as a true 'correlate of protection', there are many precedents for defining 'surrogate' assays. Surrogates can be powerful tools for vaccine optimization, licensure, comparisons between products and development of improved products. When such tests achieve 'reference' status however, they can inadvertently become barriers to new technologies that do not work the same way as existing vaccines. This is particularly true when these tests are based upon circularly-defined 'reference' or, even worse, proprietary reagents. The situation with inactivated influenza vaccines is a good example of this phenomenon. The most frequently used tests to define vaccine-induced immunity are all serologic assays: hemagglutination inhibition (HI), single radial hemolysis (SRH) and microneutralization (MN). The first two, and particularly the HI assay, have achieved reference status and criteria have been established in many jurisdictions for their use in licensing new vaccines and to compare the performance of different vaccines. However, all of these assays are based on biological reagents that are notoriously difficult to standardize and can vary substantially by geography, by chance (i.e. developing reagents in eggs that may not antigenitically match wild-type viruses) and by intention (ie: choosing reagents that yield the most favorable results). This review describes attempts to standardize these assays to improve their performance as surrogates, the dangers of over-reliance on 'reference' serologic assays, the ways that manufacturers can exploit the existing regulatory framework to make their products 'look good' and the implications of this long-established system for the introduction of novel influenza vaccines.

PMID: 29252098 [PubMed - indexed for MEDLINE]

Cysteine proteases in protozoan parasites.

Fri, 12/28/2018 - 01:44
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Cysteine proteases in protozoan parasites.

PLoS Negl Trop Dis. 2018 08;12(8):e0006512

Authors: Siqueira-Neto JL, Debnath A, McCall LI, Bernatchez JA, Ndao M, Reed SL, Rosenthal PJ

Abstract
Cysteine proteases (CPs) play key roles in the pathogenesis of protozoan parasites, including cell/tissue penetration, hydrolysis of host or parasite proteins, autophagy, and evasion or modulation of the host immune response, making them attractive chemotherapeutic and vaccine targets. This review highlights current knowledge on clan CA cysteine proteases, the best-characterized group of cysteine proteases, from 7 protozoan organisms causing human diseases with significant impact: Entamoeba histolytica, Leishmania species (sp.), Trypanosoma brucei, T. cruzi, Cryptosporidium sp., Plasmodium sp., and Toxoplasma gondii. Clan CA proteases from three organisms (T. brucei, T. cruzi, and Plasmodium sp.) are well characterized as druggable targets based on in vitro and in vivo models. A number of candidate inhibitors are under development. CPs from these organisms and from other protozoan parasites should be further characterized to improve our understanding of their biological functions and identify novel targets for chemotherapy.

PMID: 30138453 [PubMed - indexed for MEDLINE]

Effectiveness of Screening and Treatment Approaches for Schistosomiasis and Strongyloidiasis in Newly-Arrived Migrants from Endemic Countries in the EU/EEA: A Systematic Review.

Tue, 12/25/2018 - 00:59
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Effectiveness of Screening and Treatment Approaches for Schistosomiasis and Strongyloidiasis in Newly-Arrived Migrants from Endemic Countries in the EU/EEA: A Systematic Review.

Int J Environ Res Public Health. 2018 Dec 20;16(1):

Authors: Agbata EN, Morton RL, Bisoffi Z, Bottieau E, Greenaway C, Biggs BA, Montero N, Tran A, Rowbotham N, Arevalo-Rodriguez I, Myran DT, Noori T, Alonso-Coello P, Pottie K, Requena-Méndez A

Abstract
We aimed to evaluate the evidence on screening and treatment for two parasitic infections-schistosomiasis and strongyloidiasis-among migrants from endemic countries arriving in the European Union and European Economic Area (EU/EEA). We conducted a systematic search of multiple databases to identify systematic reviews and meta-analyses published between 1 January 1993 and 30 May 2016 presenting evidence on diagnostic and treatment efficacy and cost-effectiveness. We conducted additional systematic search for individual studies published between 2010 and 2017. We assessed the methodological quality of reviews and studies using the AMSTAR, Newcastle⁻Ottawa Scale and QUADAS-II tools. Study synthesis and assessment of the certainty of the evidence was performed using GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. We included 28 systematic reviews and individual studies in this review. The GRADE certainty of evidence was low for the effectiveness of screening techniques and moderate to high for treatment efficacy. Antibody-detecting serological tests are the most effective screening tests for detection of both schistosomiasis and strongyloidiasis in low-endemicity settings, because they have higher sensitivity than conventional parasitological methods. Short courses of praziquantel and ivermectin were safe and highly effective and cost-effective in treating schistosomiasis and strongyloidiasis, respectively. Economic modelling suggests presumptive single-dose treatment of strongyloidiasis with ivermectin for all migrants is likely cost-effective, but feasibility of this strategy has yet to be demonstrated in clinical studies. The evidence supports screening and treatment for schistosomiasis and strongyloidiasis in migrants from endemic countries, to reduce morbidity and mortality.

PMID: 30577567 [PubMed - in process]

Opportunities and barriers to implementing antibiotic stewardship in low and middle-income countries: Lessons from a mixed-methods study in a tertiary care hospital in Ethiopia.

Sat, 12/22/2018 - 00:29
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Opportunities and barriers to implementing antibiotic stewardship in low and middle-income countries: Lessons from a mixed-methods study in a tertiary care hospital in Ethiopia.

PLoS One. 2018;13(12):e0208447

Authors: Gebretekle GB, Haile Mariam D, Abebe W, Amogne W, Tenna A, Fenta TG, Libman M, Yansouni CP, Semret M

Abstract
BACKGROUND: Global action plans to tackle antimicrobial resistance (AMR) include implementation of antimicrobial stewardship (AMS), but few studies have directly addressed the challenges faced by low and middle-income countries (LMICs). Our aim was to explore healthcare providers' knowledge and perceptions on AMR, and barriers/facilitators to successful implementation of a pharmacist-led AMS intervention in a referral hospital in Ethiopia.
METHODS: Tikur Anbessa Specialized Hospital (TASH) is an 800-bed tertiary center in Addis Ababa, and the site of an ongoing 4-year study on AMR. Between May and July 2017, using a mixed approach of quantitative and qualitative methods, we performed a cross-sectional survey of pharmacists and physicians using a pre-tested questionnaire and semi-structured interviews of purposively selected respondents until thematic saturation. We analyzed differences in proportions of agreement between physicians and pharmacists using χ2 and fisher exact tests. Qualitative data was analyzed thematically.
FINDINGS: A total of 406 survey respondents (358 physicians, 48 pharmacists), and 35 key informants (21 physicians and 14 pharmacists) were enrolled. The majority of survey respondents (>90%) strongly agreed with statements regarding the global scope of AMR, the need for stewardship, surveillance and education, but their perceptions on factors contributing to AMR and their knowledge of institutional resistance profiles for common bacteria were less uniform. Close to 60% stated that a significant proportion of S. aureus infections were caused by methicillin-resistant strains (an incorrect statement), while only 48% thought a large proportion of gram-negative infections were caused by cephalosporin-resistant strains (a true statement). Differences were noted between physicians and pharmacists: more pharmacists agreed with statements on links between use of broad-spectrum antibiotics and AMR (p<0.022), but physicians were more aware that lack of diagnostic tests led to antibiotic overuse (p<0.01). More than cost, fear of treatment failure and of retribution from senior physicians were major drivers of antibiotic prescription behavior particularly among junior physicians. All respondents identified high turnover of pharmacists, poor communication between the laboratory, pharmacists and clinicians as potential challenges; but the existing hierarchical culture and academic setting were touted as opportunities to implement AMS in Ethiopia.
CONCLUSIONS: This knowledge and perceptions survey identified specific educational priorities and implementation strategies for AMS in our setting. This is likely also true in other LMICs, where expertise and infrastructure may be lacking.

PMID: 30571688 [PubMed - in process]

Clinical Pearls in Travellers and Migrants.

Thu, 12/13/2018 - 00:10
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Clinical Pearls in Travellers and Migrants.

J Travel Med. 2018 Dec 10;:

Authors: Wilder-Smith A, van Genderen PJ, Barkati S, Coyle C, Staehelin C, Richter J, Bottieau E

PMID: 30535197 [PubMed - as supplied by publisher]

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