The effect of malaria control on Plasmodium falciparum in Africa between 2000 and 2015.

Since the year 2000, a concerted campaign against malaria has led to unprecedented levels of intervention coverage across sub-Saharan Africa. Understanding the effect of this control effort is vital to inform future control planning. However, the effect of malaria interventions across the varied epidemiological settings of Africa remains poorly understood owing to the absence of reliable surveillance data and the simplistic approaches underlying current disease estimates. Here we link a large database of malaria field surveys with detailed reconstructions of changing intervention coverage to directly evaluate trends from 2000 to 2015, and quantify the attributable effect of malaria disease control efforts. We found that Plasmodium falciparum infection prevalence in endemic Africa halved and the incidence of clinical disease fell by 40% between 2000 and 2015. We estimate that interventions have averted 663 (542-753 credible interval) million clinical cases since 2000. Insecticide-treated nets, the most widespread intervention, were by far the largest contributor (68% of cases averted). Although still below target levels, current malaria interventions have substantially reduced malaria disease incidence across the continent. Increasing access to these interventions, and maintaining their effectiveness in the face of insecticide and drug resistance, should form a cornerstone of post-2015 control strategies.

Weight-of-evidence evaluation of associations between particulate matter exposure and biomarkers of lung cancer.

Research suggests that exposure to ambient particulate matter (PM) may be associated with lung cancer; however, no mode of action (MoA) for this has been established. We applied a weight-of-evidence (WoE) approach to evaluate recent evidence from four realms of research (controlled human exposure, epidemiology, animal, and in vitro) to determine whether the overall evidence supports one or more MoAs by which PM could cause lung cancer. We evaluated three general MoAs: DNA damage and repair; other genotoxic effects, including mutagenicity and clastogenicity; and gene expression, protein expression, and DNA methylation. After assessing individual study quality, we evaluated the strength of the evidence within as well as across disciplines using a modified set of Bradford Hill considerations. We conclude that the overall WoE indicates it is plausible that PM of various size fractions may cause direct DNA damage, but the evidence is insufficient regarding the alternative MoAs we evaluated. More research is needed to determine whether DNA damage can lead to downstream events and, ultimately, lung cancer.

Does the weather play a role in the spread of pandemic influenza? A study of H1N1pdm09 infections in France during 2009-2010.

Understanding patterns of influenza spread and persistence is crucial for pandemic preparedness. The H1N1pdm09 virus caused the first influenza pandemic of the 21st century which resulted in at least 18500 deaths. Based on laboratory-confirmed primary-care case reports we investigated the role of weather conditions and socio-demographic variables in its initial spread and subsequent presence in France. Our findings suggest that low relative humidity and high population density were determinants in shaping the early spread of the virus at the national level. Those conditions also favoured the persistence of viral presence throughout the first 33 weeks of the pandemic. Additionally this persistence was significantly favoured by low insolation. These results confirm the increasingly recognized role of humidity in influenza dynamics and underlie the concomitant effect of insolation. Therefore climatic factors should be taken into account when designing influenza control and prevention measures.

Small-for-gestational-age birth and maternal plasma antioxidant levels in mid-gestation: a nested case-control study.

OBJECTIVE: To assess whether maternal plasma antioxidant levels in mid-pregnancy are associated with small-for-gestational-age (SGA) birth. DESIGN: Case-control study nested within a population-based cohort study. SETTING: Four hospitals in Montreal, Canada. POPULATION: Pregnant women recruited before 24 weeks of gestation, whose pregnancies were not complicated by pre-eclampsia or preterm delivery. METHODS: Blood samples were obtained at 24-26 weeks and assayed for nutritionally derived antioxidant levels in SGA cases (n = 324) and randomly selected controls with birthweights between the 25th and 75th centiles (n = 672). We performed logistic regression analyses using the standardised z-score of each antioxidant as the main independent variable, after summing highly correlated antioxidants or combining via principle component analysis. We adjusted for risk factors for SGA that were associated with antioxidant levels. MAIN OUTCOME MEASURES: SGA, birthweight <10th centile for gestational age and sex. RESULTS: Retinol was positively associated with risk of SGA (adjusted odds ratio [OR] 1.41; 95% confidence interval [95% CI] 1.22-1.63, per SD increase). Carotenoids (log of the sum of ß-carotene, lutein/zeaxanthin, α- and ß-cryptoxanthin) were negatively associated with SGA (adjusted OR 0.64; 95% CI 0.54-0.78, per SD increase). We found no significant associations between SGA and lycopene or any of the forms of vitamin E assessed, including α-tocopherol, corrected α-tocopherol (per nmol/l of low-density lipoprotein articles), or γ-tocopherol. CONCLUSIONS: Elevated retinol may be associated with an increased risk of SGA, whereas elevated carotenoid levels may reduce the risk. A better understanding of the nature of these associations is required, however, before recommending specific nutritional interventions in an attempt to prevent SGA birth.

Risk stratification in extramammary Paget disease.

Extramammary Paget disease (EMPD) is an uncommon intraepithelial adenocarcinoma that involves body sites with apocrine glands such as the genital, perineal and perianal regions. Risk stratification and treatment planning for EMPD can be challenging. This review presents important prognostic information in EMPD to assist physicians with risk stratification of patients with EMPD. The best-understood prognostic factors are depth of invasion and involvement of extracutaneous sites. Tumours that invade into the reticular dermis or have a depth of > 1 mm are associated with poorer prognosis. Additionally, tumours spreading outside the skin into lymph nodes or other tissues are higher risk. There is an emerging understanding of the importance of tumour genetics in risk stratification, and we review the data on Ki-67, cyclin D1, Mucin 5AC and E-cadherin. There is less evidence supporting the importance of lesion site and patient age in risk stratification. This succinct review will be helpful in clinical practice and in EMPD research.

Influenza vaccine effectiveness estimates in Europe in a season with three influenza type/subtypes circulating: the I-MOVE multicentre case-control study, influenza season 2012/13.

In the fifth season of Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE), we undertook a multicentre case-control study (MCCS) in seven European Union (EU) Member States to measure 2012/13 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory confirmed as influenza. The season was characterised by substantial co-circulation of influenza B, A(H1N1)pdm09 and A(H3N2) viruses. Practitioners systematically selected ILI patients to swab ≤7 days of symptom onset. We compared influenza-positive by type/subtype to influenza-negative patients among those who met the EU ILI case definition. We conducted a complete case analysis using logistic regression with study as fixed effect and calculated adjusted vaccine effectiveness (AVE), controlling for potential confounders (age, sex, symptom onset week and presence of chronic conditions). We calculated AVE by type/subtype. Study sites sent 7,954 ILI/acute respiratory infection records for analysis. After applying exclusion criteria, we included 4,627 ILI patients in the analysis of VE against influenza B (1,937 cases), 3,516 for A(H1N1)pdm09 (1,068 cases) and 3,340 for influenza A(H3N2) (730 cases). AVE was 49.3% (95% confidence interval (CI): 32.4 to 62.0) against influenza B, 50.4% (95% CI: 28.4 to 65.6) against A(H1N1)pdm09 and 42.2% (95% CI: 14.9 to 60.7) against A(H3N2). Our results suggest an overall low to moderate AVE against influenza B, A(H1N1)pdm09 and A(H3N2), between 42 and 50%. In this season with many co-circulating viruses, the high sample size enabled stratified AVE by type/subtype. The low estimates indicate seasonal influenza vaccines should be improved to achieve acceptable protection levels.

Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study.

Within the Influenza Monitoring Vaccine Effectiveness in Europe (I-MOVE) project we conducted a multicentre case­control study in eight European Union (EU) Member States to estimate the 2011/12 influenza vaccine effectiveness against medically attended influenza-like illness (ILI) laboratory-confirmed as influenza A(H3) among the vaccination target groups. Practitioners systematically selected ILI / acute respiratory infection patients to swab within seven days of symptom onset. We restricted the study population to those meeting the EU ILI case definition and compared influenza A(H3) positive to influenza laboratory-negative patients. We used logistic regression with study site as fixed effect and calculated adjusted influenza vaccine effectiveness (IVE), controlling for potential confounders (age group, sex, month of symptom onset, chronic diseases and related hospitalisations, number of practitioner visits in the previous year). Adjusted IVE was 25% (95% confidence intervals (CI): -6 to 47) among all ages (n=1,014), 63% (95% CI: 26 to 82) in adults aged between 15 and 59 years and 15% (95% CI: -33 to 46) among those aged 60 years and above. Adjusted IVE was 38% (95%CI: -8 to 65) in the early influenza season (up to week 6 of 2012) and -1% (95% CI: -60 to 37) in the late phase. The results suggested a low adjusted IVE in 2011/12. The lower IVE in the late season could be due to virus changes through the season or waning immunity. Virological surveillance should be enhanced to quantify change over time and understand its relation with duration of immunological protection. Seasonal influenza vaccines should be improved to achieve acceptable levels of protection.

Paediatric TB care in the United Kingdom.

BACKGROUND: Care of patients with paediatric TB is delivered in a variety of settings by different clinicians in the United Kingdom. Paediatric practices vary in size. Guidelines on managing children with TB differ in recommendations. These factors contribute to variations in practice.OBJECTIVE: To describe practice among UK professionals caring for children exposed to or infected with TB, and their investigation and treatment.METHODS: From 81 NHS (National Health Service) clinical services, 114 individuals responded to a web-based questionnaire.RESULTS: We describe variation in several areas of practice, with important differences between smaller and larger centres. Most respondents go beyond National Institute for Health & Care Excellence guidance and screen child contacts of extrapulmonary TB. Most respondents would presume pulmonary TB exposed children aged under 2 years to be infected. They would not rely on immunological investigations to rule out infection. There was wide variety in approaches to microbiological diagnosis, and in the use of laboratory investigations to monitor treatment. Many respondents felt unclear on how to manage newborns exposed to TB, or children exposed to multidrug-resistant TB.CONCLUSION: These findings support the case for further developing regional networks providing evidence and consensus-based care for children with TB.

Influence of ultrasound-to-delivery interval and maternal-fetal characteristics on validity of estimated fetal weight.

OBJECTIVES: To explore the effects of ultrasound-to-delivery interval and maternal-fetal characteristics on the distribution of measurement error in estimated fetal weights (EFWs), and to determine the predictive ability of EFW for diagnosis of small-for-gestational age (SGA) and large-for-gestational age (LGA) among infants delivered within 1 day of an ultrasound examination. METHODS: Percentage differences between EFW and birth weights were calculated in 3697 pregnancies. Linear regression was used to compare the accuracy of EFW for births on each of the 6 days after an ultrasound scan with the accuracy observed among births on the same day. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value for diagnosis of SGA and LGA according to EFW was assessed. RESULTS: The mean +/- SD percentage difference among deliveries within 1 day of the last ultrasound scan was 0.2 +/- 9.0%. Mean percentage differences were not significantly different from day 0 on days 1, 2 and 3; however, combining the data from these 4 days obscured a slight bias towards an overestimation of weight evident on day 0 and day 1. Among deliveries within 1 day of an ultrasound scan, the PPV was 61% for SGA diagnosis and 54% for LGA diagnosis. CONCLUSION: Combining data from births > 1 day after the last ultrasound examination may lead to a false conclusion that there is systematic underestimation of weight. EFW tended to underestimate the weight of macrosomic fetuses and overestimate that of small fetuses which limited sensitivity and PPV. Maternal-fetal characteristics are weak predictors of individual errors in EFW.

Flu vaccine coverage for recommended populations in France.

OBJECTIVES: To estimate the size of the populations targeted by the French recommendations of the High Council for Public Health (French acronym HCSP) regarding vaccination against seasonal flu and to estimate vaccination coverage rates in these populations. PATIENTS AND METHODS: The analysis was conducted on a representative sample of patients retrieved from the French Health Insurance databases during three influenza seasons (2012-2013, 2013-2014, 2014-2015). Patients targeted by the influenza vaccination recommendations were identified based on their sociodemographic characteristics and disease identification algorithms during each season. Vaccine coverage rates were estimated based on reimbursed influenza vaccines. Results were extrapolated using indirect standardization to the overall French population. RESULTS: Populations targeted by the recommendations were estimated after extrapolation to 17.6, 17.8, and 18.0 million for the 2012-13, 2013-14, and 2014-15 influenza seasons, respectively. The vaccination coverage rates in these target populations were respectively estimated at 32.1%, 31.9%, and 32.1%; i.e. 44.2%, 43.1%, and 42.7% for individuals aged ≥65 years and 12.9%, 13.2%, and 13.7% for individuals ˂65 years of age presenting a risk justifying vaccination. CONCLUSIONS: Immunization coverage against influenza in France remains well below the target of 75% set by the World Health Organization. Multiple strategies combining communication, education, access program, and professional engagement could be implemented to improve this situation.

Non-invasive in vivo quantification of human skin tension lines.

Human skin is a composite tissue that exhibits anisotropic mechanical properties. This anisotropy arises primarily from the alignment of collagen and elastin fibers in the dermis, which causes the skin to exhibit greater tension in one direction, making it appear stiffer. A diverse number of skin tension guidelines have been developed to assist surgeons in making incisions that produce the least conspicuous scars. However, skin anisotropy is believed to vary from subject to subject, and no single guideline is universally recognized as the best to implement for surgical applications. To date, no system exists that can rapidly and non-invasively measure lines of skin tension in vivo. In this article, we evaluate the ability of a new aspiration system to measure the anisotropy of human skin. The device painlessly applies a radial stress of 17 kPa to a region of skin, and captures radially asymmetric skin deformations via a dermal camera. These deformations are used to quantify orientations of strain extrema and the direction of greatest skin stiffness. The ratio of these asymmetric strains varies between 1 and -0.75. A simple 2D transverse isotropic model captures this behavior for multiple anatomical sites. Clinical trials reveal that skin tension line orientations are comparable with existing skin tension maps and generally agree across subjects, however orientations statistically differ between individuals. As such, existing guidelines appear to provide only approximate estimates of skin tension orientation. STATEMENT OF SIGNIFICANCE: Skin tension lines (STL) in human skin arise primarily from collagen fiber alignment in the dermis. These lines are used by surgeons to guide incisions that produce the least conspicuous scars. While numerous anatomical STL maps exist, no single guideline is universally recognized as the most reliable. Moreover, manual methods of quantifying STL are imprecise. For the first time, we have developed a device capable of rapidly and non-invasively measuring STL orientations in vivo, using a single test. Our results are used to establish a simple constitutive model of mechanical skin anisotropy. Clinical trials further reveal STL orientations are comparable with existing maps, but statistically differ between individuals. Existing guidelines therefore appear to provide only approximate estimates of STL orientation.

[Respiratory tract infections in institutions for elderly people: the GROG Géronto-Alsace, strategy of surveillance and alert]. / Infections respiratoires aiguës dans les collectivités de personnes âgées: le GROG Géronto-Alsace, une démarche expérimentale de surveillance et d'alerte.

OBJECTIVE: Outbreaks of respiratory tract infections are common in institutions for elderly people. The objective of our study was the implementation of a network including 11 institutions to determine the frequency of such outbreaks. Using the collected data, criteria and alert levels are defined to assess the level of respiratory tract infections and develop appropriate interventions. METHODOLOGY: Prospective surveillance for respiratory tract infection was conducted in 11 institutions in Alsace for 2 years. Clinical definitions were used to identify the infected residents. For the identification of influenza virus, nasopharyngeal samples using swabs were obtained and rapid tests (immunoassay) were performed. RESULTS: During the surveillance, outbreaks were identified in institutions. The same observations occurred in all institutions at the same time. Alert levels were defined in order to characterize the outbreak period and to improve detection and control of outbreaks of respiratory tract infections. CONCLUSION: Ours findings show the importance of an adequate surveillance and networks improve the impact of such measures.

Influenza B burden during seasonal influenza epidemics in France.

CONTEXT: Seasonal flu outbreaks are linked to the circulation of influenza virus type A or B. Special attention has always been paid to influenza A epidemics; but recently, several studies have investigated the impact of influenza B virus epidemics, particularly as, since the 1980s, two antigenically different influenza B lineages co-circulate, raising the issue of vaccine matching. OBJECTIVES: We present the results of influenza B burden during nine influenza seasons (2003-2013) and vaccine matching of the circulating lineages. PATIENTS AND METHODS: Clinical and virological influenza surveillance data, collected by the Regional Groups for Influenza Surveillance Network in France, allows for studying the burden of influenza in the practice of the population of ambulatory care physicians. RESULTS AND CONCLUSION: Our analysis is based on 37,801 samples, of which 12,036 were virologically confirmed influenza cases (31.8%), including 3576 cases of influenza B (29.7% of influenza cases). Influenza B viruses significantly circulated during six seasons. For each season, the influenza B epidemic peaked later than the influenza A epidemic. Influenza B is very common in children of school age but also affects other age groups. Finally, more than one-third of the analyzed influenza B viruses belonged to a different lineage than the one used in the composition of the trivalent vaccine. Our results are comparable to those described in other countries.

Prevalence of mitral valve prolapse in normal children.

Although echocardiography has become the standard noninvasive method of diagnosing mitral valve prolapse, the diagnostic criteria have been established without clearly defining the range of normal patterns for mitral valve closure. The current study reports the analysis of mitral valve closure patterns in 193 children (aged 5 days to 18 years) making scheduled visits for well child care who were screened by history and physical examination to exclude structural heart disease. Mitral valve systolic leaflet position was analyzed for the appearance of any portion of either leaflet superior to the plane of the anulus. Superior systolic motion was noted in 13% of the overall study group; this pattern was uncommon in infants but more frequent in older children, with a prevalence of 35% in the 10 to 18 year age group. There was no statistically significant difference between male and female children at any age. The prevalence of superior systolic motion decreased markedly if consideration was given to its presence in more than one echocardiographic view (1%) or to displacement of the coaptation point of the mitral valve leaflets (0.5%). Superior systolic motion occurs with such frequency in normal children as to call into question the reliability of this pattern of mitral valve closure as a standard for the diagnosis of mitral valve prolapse. More restrictive diagnostic criteria which consider the degree of leaflet displacement or its presence in multiple echocardiographic views may be necessary to identify those subjects whose mitral valve closure patterns truly fall outside the range of normal.