Community transmission of rotavirus infection in a vaccinated population in Blantyre, Malawi: a prospective household cohort study.

BACKGROUND: Rotavirus vaccine effectiveness is reduced among children in low-income countries. Indirect (transmission-mediated) effects of rotavirus vaccine might contribute to the total population effect of vaccination. We aimed to examine risk factors for transmission of rotavirus to household contacts in Blantyre, Malawi, and estimated the effectiveness of rotavirus vaccine in preventing transmission of infection to household contacts. METHODS: In this prospective household cohort study, we recruited children born after Sept 17, 2012, and aged at least 6 weeks (vaccine-eligible children) with acute rotavirus gastroenteritis and their household contacts, in four government health facilities in Blantyre, Malawi. Clinical data, a bulk stool sample, and 1-2 mL of serum were collected from case children at presentation. Clinical data and stool samples were also prospectively collected from household contacts over 14 days from presentation. A single stool sample was collected from control households containing asymptomatic children who were frequency age-matched to case children. Samples were tested for rotavirus using semi-quantitative real-time PCR and for anti-rotavirus IgA using a semi-quantitative sandwich ELISA. Risk factors for household transmission of rotavirus infection and clinical disease, including disease severity and faecal shedding density, were identified using mixed effects logistic regression. Vaccine effectiveness against transmission was estimated as 1 minus the ratio of secondary attack rates in vaccinated and counterfactual unvaccinated populations, using vaccine effectiveness estimates from the associated diarrhoeal surveillance platform to estimate the counterfactual secondary attack rate without vaccination. FINDINGS: Between Feb 16, 2015, and Nov 11, 2016, we recruited 196 case households (705 members) and 55 control households (153 members). Household secondary attack rate for rotavirus infection was high (434 [65%] of 665 individuals) and secondary attack rate for clinical disease was much lower (37 [5%] of 698). Asymptomatic infection in control households was common (40 [28%] of 144). Increasing disease severity in an index child (as measured by Vesikari score) was associated with increased risk of transmission of infection (odds ratio 1·17 [95% CI 1·06-1·30) and disease (1·28 [1·08-1·52]) to household contacts. Estimated vaccine effectiveness against transmission was 39% (95% CI 16-57). INTERPRETATION: Rotavirus vaccine has the potential to substantially reduce household rotavirus transmission. This finding should be considered in clinical and health economic assessments of vaccine effectiveness. FUNDING: Wellcome Trust, US National Institutes of Health, and US National Institute of Allergy and Infectious Diseases

Etiology of Diarrhea Among Hospitalized Children in Blantyre, Malawi, Following Rotavirus Vaccine Introduction: A Case-Control Study.

Despite rotavirus vaccination, diarrhea remains a leading cause of child mortality. We collected stool specimens from 684 children <5 years of age hospitalized with diarrhea (cases) and 527 asymptomatic community controls for 4 years after rotavirus vaccine introduction in Malawi. Specimens were tested for 29 pathogens, using polymerase chain reaction analysis. Three or more pathogens were detected in 71% of cases and 48% of controls. Pathogens significantly associated with diarrhea included rotavirus (in 34.7% of cases and 1.5% of controls), enteric adenovirus (in 29.1% and 2.7%, respectively), Cryptosporidium (in 27.8% and 8.2%, respectively), heat-stable enterotoxin-producing Escherichia coli (in 21.2% and 8.5%, respectively), typical enteropathogenic E. coli (in 18.0% and 8.3%, respectively), and Shigella/enteroinvasive E. coli (in 15.8% and 5.7%, respectively). Additional interventions are required to prevent diarrhea due to rotavirus and other common causal pathogens

Direct and possible indirect effects of vaccination on rotavirus hospitalisations among children in Malawi four years after programmatic introduction.

IntroductionDespite increased use of vaccine in routine immunisation, rotavirus remains a major cause of acute gastroenteritis (AGE) in low-income countries. We describe rotavirus prevalence and hospitalisation in Malawi pre and four years post vaccine introduction; provide updated vaccine effectiveness (VE) estimates; and assess rotavirus vaccine indirect effects.MethodsChildren under five years of age presenting to a referral hospital in Blantyre with AGE were recruited. Stool samples were tested for rotavirus using Enzyme Immunoassay. The change in rotavirus prevalence was evaluated using Poisson regression. Time series analysis was used to further investigate trends in prevalence over time. VE against rotavirus diarrhoea of any severity was estimated using logistic regression. Indirect effects were estimated by evaluating rotavirus prevalence in unvaccinated children over time, and by comparing observed reductions in incidence of rotavirus hospitalisation to those expected based on vaccine coverage and trial efficacy estimates.Results2320 children were included. Prevalence of rotavirus in hospitalised infants (ConclusionsFollowing rotavirus vaccine introduction in Malawi, prevalence of rotavirus in hospitalised children with AGE has declined significantly, with some evidence of an indirect effect in infants. Despite this, rotavirus remains an important cause of severe diarrhoea in Malawian children, particularly in the second year of life

Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) in the early stages of Alzheimer’s disease

Alzheimer’s disease (AD) is one of the most common causes of dementia in the world. Patients with AD frequently complain of vision disturbances that do not manifest as changes in routine ophthalmological examination findings. The main causes of these disturbances are neuropathological changes in the visual cortex, although abnormalities in the retina and optic nerve cannot be excluded. Pattern electroretinogram (PERG) and pattern visual evoked potential (PVEP) tests are commonly used in ophthalmology to estimate bioelectrical function of the retina and optic nerve. The aim of this study was to determine whether retinal and optic nerve function, measured by PERG and PVEP tests, is changed in individuals in the early stages of AD with normal routine ophthalmological examination results. Standard PERG and PVEP tests were performed in 30 eyes of 30 patients with the early stages of AD. The results were compared to 30 eyes of 30 normal healthy controls. PERG and PVEP tests were recorded in accordance with the International Society for Clinical Electrophysiology of Vision (ISCEV) standards. Additionally, neural conduction was measured using retinocortical time (RCT)—the difference between P100-wave latency in PVEP and P50-wave implicit time in PERG. In PERG test, PVEP test, and RCT, statistically significant changes were detected. In PERG examination, increased implicit time of P50-wave (P < 0.03) and amplitudes reductions in P50- and N95-waves (P < 0.0001) were observed. In PVEP examination, increased latency of P100-wave (P < 0.0001) was found. A significant increase in RCT (P < 0.0001) was observed. The most prevalent features were amplitude reduction in N95-wave and increased latency of P100-wave which were seen in 56.7% (17/30) of the AD eyes. In patients with the early stages of AD and normal routine ophthalmological examination results, dysfunction of the retinal ganglion cells as well as of the optic nerve is present, as detected by PERG and PVEP tests. These dysfunctions, at least partially, explain the cause of visual disturbances observed in patients with the early stages of AD

Quantitative EEG findings in patients with acute, brief depression combined with other fluctuating psychiatric symptoms: a controlled study from an acute psychiatric department

<p>Abstract</p> <p>Background</p> <p>Patients with brief depressive episodes and concurrent rapidly fluctuating psychiatric symptoms do not fit current diagnostic criteria and they can be difficult to diagnose and treat in an acute psychiatric setting. We wanted to study whether these patients had signs of more epileptic or organic brain dysfunction than patients with depression without additional symptomatology.</p> <p>Methods</p> <p>Sixteen acutely admitted patients diagnosed with a brief depressive episode as well as another concurrent psychiatric diagnosis were included. Sixteen patients with major depression served as controls. Three electroencephalographic studies (EEG) were visually interpreted and the background activity was also analysed with quantitative electroencephalography (QEEG).</p> <p>Results</p> <p>The group with brief depression and concurrent symptoms had multiple abnormal features in their standard EEG compared to patients with major depression, but they did not show significantly more epileptiform activity. They also had significantly higher temporal QEEG delta amplitude and interhemispheric temporal delta asymmetry.</p> <p>Conclusion</p> <p>Organic brain dysfunction may be involved in the pathogenesis of patients with brief depressive episodes mixed with rapidly fluctuating psychiatric symptoms. This subgroup of depressed patients should be investigated further in order to clarify the pathophysiology and to establish the optimal evaluation scheme and treatment in an acute psychiatric setting.</p

NADPH Phagocyte Oxidase Knockout Mice Control Trypanosoma cruzi Proliferation, but Develop Circulatory Collapse and Succumb to Infection

•NO is considered to be a key macrophage-derived cytotoxic effector during Trypanosoma cruzi infection. On the other hand, the microbicidal properties of reactive oxygen species (ROS) are well recognized, but little importance has been attributed to them during in vivo infection with T. cruzi. In order to investigate the role of ROS in T. cruzi infection, mice deficient in NADPH phagocyte oxidase (gp91phox−/− or phox KO) were infected with Y strain of T. cruzi and the course of infection was followed. phox KO mice had similar parasitemia, similar tissue parasitism and similar levels of IFN-γ and TNF in serum and spleen cell culture supernatants, when compared to wild-type controls. However, all phox KO mice succumbed to infection between day 15 and 21 after inoculation with the parasite, while 60% of wild-type mice were alive 50 days after infection. Further investigation demonstrated increased serum levels of nitrite and nitrate (NOx) at day 15 of infection in phox KO animals, associated with a drop in blood pressure. Treatment with a NOS2 inhibitor corrected the blood pressure, implicating NOS2 in this phenomenon. We postulate that superoxide reacts with •NO in vivo, preventing blood pressure drops in wild type mice. Hence, whilst superoxide from phagocytes did not play a critical role in parasite control in the phox KO animals, its production would have an important protective effect against blood pressure decline during infection with T. cruzi

Competitive Tendering In The Netherlands: Central Planning Or Functional Specifications?

Institute of Transport and Logistics Studies. Faculty of Economics and Business. The University of Sydne

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease