Brucellosis Vaccines: Assessment of Brucella melitensis Lipopolysaccharide Rough Mutants Defective in Core and O-Polysaccharide Synthesis and Export

Background: The brucellae are facultative intracellular bacteria that cause brucellosis, one of the major neglected zoonoses. In endemic areas, vaccination is the only effective way to control this disease. Brucella melitensis Rev 1 is a vaccine effective against the brucellosis of sheep and goat caused by B. melitensis, the commonest source of human infection. However, Rev 1 carries a smooth lipopolysaccharide with an O-polysaccharide that elicits antibodies interfering in serodiagnosis, a major problem in eradication campaigns. Because of this, rough Brucella mutants lacking the O-polysaccharide have been proposed as vaccines. Methodology/Principal Findings: To examine the possibilities of rough vaccines, we screened B. melitensis for lipopolysaccharide genes and obtained mutants representing all main rough phenotypes with regard to core oligosaccharide and O-polysaccharide synthesis and export. Using the mouse model, mutants were classified into four attenuation patterns according to their multiplication and persistence in spleens at different doses. In macrophages, mutants belonging to three of these attenuation patterns reached the Brucella characteristic intracellular niche and multiplied intracellularly, suggesting that they could be suitable vaccine candidates. Virulence patterns, intracellular behavior and lipopolysaccharide defects roughly correlated with the degree of protection afforded by the mutants upon intraperitoneal vaccination of mice. However, when vaccination was applied by the subcutaneous route, only two mutants matched the protection obtained with Rev 1 albeit at doses one thousand fold higher than this reference vaccine. These mutants, which were blocked in O-polysaccharide export and accumulated internal O-polysaccharides, stimulated weak anti-smooth lipopolysaccharide antibodies. Conclusions/Significance: The results demonstrate that no rough mutant is equal to Rev 1 in laboratory models and question the notion that rough vaccines are suitable for the control of brucellosis in endemic areas.This work was funded by the European Commission (Research Contract QLK2-CT-2002-00918) and the Ministerio de Ciencia y Tecnología of Spain (Proyecto AGL2004-01162/GAN)

Biochemistry and physiology of gastrointestinal somatostatin

Somatostatin, a tetradecapeptide initially isolated from the ovine hypothalamus, is widely distributed throughout the gastrointestinal tract where it may act as a hormone, local chemical messenger, or neurotransmitter to elicit many physiological actions. Release of somatostatin from D cells in the gut is regulated by mechanisms that are both dependent on and independent of cAMP. In most cases somatostatin acts to inhibit the function of its target cells. It performs this action in part via pertussis-toxin-sensitive inhibitory guanine nucleotide-binding proteins that regulate adenylate cyclase activity. Other mechanisms may involve sites of action distal to intracellular second messenger systems .Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44411/1/10620_2005_Article_BF01536041.pd

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

Accelerating invasion potential of disease vector Aedes aegypti under climate change

Vector-borne diseases remain a major contributor to the global burden of disease, while climate change is expected to exacerbate their risk. Characterising vector development rate and its spatio-temporal variation under climate change is central to assessing the changing basis of human disease risk. We develop a mechanistic phenology model and apply it to Aedes aegypti, an invasive mosquito vector for arboviruses (e.g. dengue, zika and yellow fever). The model predicts the number of life-cycle completions (LCC) for a given location per unit time based on empirically derived biophysical responses to environmental conditions. Results suggest that the world became ~1.5% more suitable per decade for the development of Ae. aegypti during 1950–2000, while this trend is predicted to accelerate to 3.2–4.4% per decade by 2050. Invasion fronts in North America and China are projected to accelerate from ~2 to 6 km/yr by 2050. An increase in peak LCC combined with extended periods suitable for mosquito development is simulated to accelerate the vector’s global invasion potential

Response to article by Matthew Wasserman et al. (2018): “Modeling the sustained use of the 13-valent pneumococcal conjugate vaccine compared to switching to the 10-valent vaccine in Mexico”

In a recent article, Wasserman et al. estimated and forecasted the health and economic impact of switching from the 13-valent (PCV-13) to the 10-valent (PHiD-CV) pneumococcal conjugate vaccine in Mexico’s national immunization program. In this response letter, we highlight various methodological inconsistencies and model input considerations that potentially bias the results and further recommendations made by the authors

Investigation of ornamental cultivars both Louiseania triloba (Lindl.) Pachom. and its hybrids under the conditions of the South-East of Ukraine

Results of introduction investigations both 9 cultivars of Louiseania triloba (Lindl.) Pachom. and 6 cultivars of Louiseania Carr. × Prunus L. hybrids under the conditions of the South-East of Ukraine have been presented. The new combination ×Prunoseania arnoldiana (Rehder) Mezh. comb. nov. for the hybrids of Louiseania triloba × Prunus cerasifera Ehrh. is proposed

Assessing the Underestimation of Adult Pertussis Disease in Five Latin American Countries

Abstract Introduction Pertussis, a contagious respiratory disease, is underreported in adults. The study objective was to quantify underestimation of pertussis cases in adults aged ≥ 50 years in five Latin American countries (Argentina, Brazil, Chile, Mexico, Peru). Methods A previously published probabilistic model was adapted to adjust the number of pertussis cases reported to national surveillance systems by successive multiplication steps (proportion of pertussis cases seeking healthcare; proportion with a specimen collected; proportion sent for confirmatory testing; proportion positive for pertussis; proportion reported to passive surveillance). The proportions at each step were added in a random effects model to produce a pooled overall proportion, and a final multiplier was calculated as the simple inverse of this proportion. This multiplier was applied to the number of cases reported to surveillance to estimate the number of pertussis cases. Monte Carlo simulation with 10,000 iterations estimated median as well as upper and lower 90% values. Input data were obtained from surveillance systems and published sources. Results The estimated median underestimation factor for pertussis cases in adults ranged from 104 (90% limits 40, 451) in Chile to 114 (90% limits 39, 419) in Argentina. In all five countries, the largest estimated number of cases was in the group aged 50–59 years. The highest number per 100,000 population was in the group aged ≥ 90 years in most countries. The estimated median underestimation factor for pertussis hospitalizations was 2.3 (90% limits 1.8, 3.3) in Brazil and 2.4 (90% limits 1.8, 3.2) in Chile (data not available for other countries). Conclusion This analysis indicates that the number of pertussis cases in adults aged ≥ 50 years in five Latin American countries is approximately 100 times higher than the number captured in surveillance data. These results could support decision-making in the diagnosis, management, and prevention of pertussis disease in adults

How large could the public health impact of introducing recombinant zoster vaccination for people aged ≥50 years in five Latin American countries be?

This study aimed to: (1) estimate the disease burden of herpes zoster (HZ) and (2) assess the potential public health impact of introducing adjuvanted recombinant zoster vaccine (RZV) compared with no vaccination in adults aged ≥50 years in Argentina, Brazil, Mexico, Chile, and Colombia using the ZOster ecoNomic Analysis (ZONA) static multicohort Markov model. The model followed individuals aged ≥50 years from administration of RZV over their remaining lifetime. Inputs were based, most often, on local data. First dose coverage was assumed to be 35%, with 75% second dose compliance. It was predicted that without RZV, there would be 23,558,675 HZ cases, 6,115,981 post-herpetic neuralgia (PHN) cases, and 7,058,779 non-PHN complications in the five countries, but introducing RZV under assumed coverage could avoid 4,583,787 (19%) HZ cases, 1,130,751 (18%) PHN cases, and 1,373,419 (19%) non-PHN complications. Also, 10427,504 (20%) doctor’s office visits and 1,630,201 (19%) days of hospitalization could be averted in the three countries (Argentina, Brazil, and Mexico) with available input data. The numbers needed to be vaccinated to avoid one case of HZ were 9–10 across countries, and to avoid one case of PHN, 35–40. One-way sensitivity analyses showed that the input parameters with the largest impact on the estimated number of HZ cases avoided were first dose coverage, initial HZ incidence, and vaccine efficacy waning. In conclusion, the introduction of RZV for older adults in Latin America could greatly reduce the public health burden of HZ and reduce the related doctor visits and hospitalization days