Impact of Plasmodium falciparum pfhrp2 and pfhrp3 gene deletions on malaria control worldwide: a systematic review and meta-analysis

Background: Deletion of pfhrp2 and/or pfhrp3 genes cause false negatives in malaria rapid diagnostic test (RDT) and threating malaria control strategies. This systematic review aims to assess the main methodological aspects in the study of pfhrp2 and pfhrp3 gene deletions and its global epidemiological status, with special focus on their distribution in Africa; and its possible impact in RDT. Methods: The systematic review was conducted by examining the principal issues of study design and methodological workflow of studies addressing pfhrp2 deletion. Meta-analysis was applied to represent reported prevalences of pfhrp2 and pfhrp3 single and double deletion in the World Health Organization (WHO) region. Pooled-prevalence of deletions was calculated using DerSimonnian-Laird random effect model. Then, in-deep analysis focused on Africa was performed to assess possible variables related with these deletions. Finally, the impact of these deletions in RDT results was analysed combining reported information about RDT sensitivity and deletion prevalences. Results: 49 articles were included for the systematic review and 37 for the meta-analysis, 13 of them placed in Africa. Study design differs significantly, especially in terms of population sample and information reported, resulting in high heterogeneity between studies that difficulties comparisons and merged conclusions. Reported prevalences vary widely in all the WHO regions, significantly higher deletion were reported in South-Central America, following by Africa and Asia. Pfhrp3 deletion is more prevalent (43% in South-Central America; 3% in Africa; and 1% in Asia) than pfhrp2 deletion (18% in South-Central America; 4% in Africa; and 3% in Asia) worldwide. In Africa, there were not found differences in deletion prevalence by geographical or population origin of samples. The prevalence of deletion among false negatives ranged from 0 to 100% in Africa, but in Asia and South-Central America was only up to 90% and 48%, respectively, showing substantial relation between deletions and false negatives. Conclusion: The concerning prevalence of pfhrp2, pfhrp3 and pfhrp2/3 gene deletions, as its possible implications in malaria control, highlights the importance of regular and systematic surveillance of these deletions. This review has also outlined that a standardized methodology could play a key role to ensure comparability between studies to get global conclusions.I.M.F. received a research fellowship from the University of Alcalá that enables her to develop this study.S

Accessibility and availability of alcohol outlets around schools: An ecological study in the city of madrid, Spain, according to socioeconomic area-level

Neighborhood accessibility and availability of alcohol products has been associated with increased alcohol consumption and harms among adolescents. This availability has been shown to be higher in neighborhoods with lower socio-economic status (SES). The aim of this study was to examine inequalities in alcohol outlet density and proximity around schools by area-level SES in Madrid, Spain. Data on schools, SES, alcohol outlets and population density at census tract level were obtained through public databases from the local government of Madrid. We examined (1) density as the number of alcohol outlets around schools within 3 buffers (i.e. 200 m, 400 m and 800 m) and (2) proximity as the distance from schools to their nearest alcohol outlet. We performed multilevel analyses to examine the associations between alcohol outlet density and proximity and SES, adjusted by population density. Secondary schools (n = 576) located in less deprived areas had lower densities of alcohol outlets at walking distances of 200 and 400 m (50% and 37% lower, respectively p < 0.05). No significant differences were found for the proximity measures. The socioeconomic level of the area in which adolescents go to school is a determinant of their exposure to alcohol, where those who study in high SES areas have lower exposure to alcohol outlets. This study highlights the need to prioritize equity in the design and implementation of policies to limit alcohol accessibility among adolescents, including establishing minimum distances between schools and alcohol outlets or limiting the number of outlets per inhabitant in neighborhoods

Using photovoice to generate policy recommendations to improve the alcohol urban environment: A participatory action research project

The place where we live, work and play may influence our alcohol drinking behaviours. This study aimed to present local policy recommendations on urban determinants for alcohol consumption prevention in a lowincome and a high-income area of Madrid (Spain) using a participatory action research method, with photo voice and nominal group techniques. Participants (n = 26) engaged in a photovoice project initiated a process of critical reflection by discussing and analysing their alcohol environment based on photographs they took themselves. At the end of six week group discussion sessions, participants identified 33 themes related to their alcohol environment. They later met to translate the final categories into urban policy recommendations using a logical framework approach. Then, with a nominal group, they prioritized these recommendations based on time, impact, feasibility, and cost. Finally, participants produced a total of 61 policy recommendations for the improvement of the alcohol environment, highlighting the need for researcher-community collaborations when designing public health interventions

Impairment of several immune functions and redox state in blood cells of Alzheimer's disease patients. Relevant role of neutrophils in oxidative stress

Since aging is considered the most risk factor for sporadic Alzheimer’s Disease (AD), the age-related impairment of the immune system (immunosenescence), based on a chronic oxidative-inflammatory stress situation, could play a key role in the development and progression of AD. Although AD is accompanied by systemic disturbance, reflecting the damage in the brain, the changes in immune response and redox-state in different types of blood cells in AD patients have been scarcely studied. The aim was to analyze the variations in several immune functions and oxidative-inflammatory stress and damage parameters in both isolated peripheral neutrophils and mononuclear blood cells, as well as in whole blood cells, from patients diagnosed with mild (mAD) and severe AD, and of age-matched controls (elderly healthy subjects) as well as of adult controls. The cognitive decline of all subjects was determined by Mini-Mental State Examination (MMSE) test (mAD stage was established at 20 ≤ MMSE ≤ 23 score; AD stage at 27 MMSE). The results showed an impairment of the immune functions of human peripheral blood neutrophils and mononuclear cells of mAD and AD patients in relation to healthy elderly subjects, who showed the typical immunosenescence in comparison with the adult individuals. However, several alterations were only observed in severe AD patients (lower chemotaxis, lipopolysaccharide lymphoproliferation, and interleukin (IL)-10 release; higher basal proliferation, tumor necrosis factor (TNF)-α release, and IL-10/TNF-α ratio), others only in mAD subjects (higher adherence), meanwhile others appeared in both mAD and AD patients (lower phytohemaglutinin lymphoproliferation and higher IL-6 release). This impairment of immune functions could be mediated by: (1) the higher oxidative stress and damage also observed in blood cells from mAD and AD patients and in isolated neutrophils [lower glutathione (GSH) levels, high oxidized glutathione (GSSG)/GSH ratio, and GSSG and malondialdehyde contents], and (2) the higher release of basal pro-inflammatory cytokines (IL-6 and TNF-α) found in AD patients. Because the immune system parameters studied are markers of health and rate of aging, our results supported an accelerated immunosenescence in AD patients

Changes in perceptions of the alcohol environment among participants in a Photovoice project conducted in two districts with different socio-economic status

Perceptions of the alcohol environment may influence alcohol consumption patterns. The purpose of this study was to describe changes in perceptions of the urban alcohol environment as experienced by residents of two districts with different socio-economic status after taking part in a Photovoice study. The study was conducted in Madrid, Spain, in a district with a high socio-economic status (HSES) and another district with a low socio-economic status (LSES). A Photovoice project was conducted with 26 participants divided into four groups based on sex and district. Groups met over five sessions in which they discussed photographs taken by the participants themselves on the subject of alcohol in their neighbourhood. A qualitative, descriptive and thematic analysis of participants' discourses was performed to explore changes in their perceptions of the alcohol environment over the project sessions. Changes in perceptions of the alcohol environment were observed in all groups over the project. The process of change varied by districts' socio-economic characteristics and gender. Greater changes in perceptions of the alcohol environment were observed in HSES, especially among women, as the participants had a much more positive initial view of their alcohol environment. In LSES, participants showed a more critical perception of the alcohol environment from the beginning of the study, and this broadened and intensified over the course of the sessions. Changes in perceptions also varied by thematic categories, including some categories that were discussed from the start (e.g. socialising and alcohol consumption) and categories that only emerged in later sessions (e.g. alcohol advertising). Involvement in a Photovoice project has favoured a shift in the participant's perceptions of their alcohol environment towards more critical positions, widening their scope of perceived elements and raising their awareness of specific problems, such as alcohol advertising and social role of alcohol consumption in relation to alcohol exposure

Residents perceptions of the alcohol environment: A participatory photovoice project in two districts with different socio-economic status in a large city

The purpose of this study was to present the alcohol environment as perceived by its residents in two districts of Madrid using the Photovoice participatory methodology. Secondly, we compared the results according to the socio-economic status of the districts. The study was conducted in the city of Madrid, Spain, in two districts with different socio-economic status. A total of 26 people participated, who took and discussed photographs about their alcohol environment. They grouped them into 33 final categories, such as the socialising role of alcohol or the alcohol advertising. Co-authors further grouped participants final categories into seven general areas. The participants in the Photovoice project have helped to deepen the understanding of the alcohol urban environment. These results may help to design more effective policies to prevent hazardous alcohol consumption.This work was supported by the Plan Nacional sobre Drogas, Spain [grant numbers 2016I047]; The HeartHealthy Hoods project was funded by the European Research Council under the European Union’s Seventh Framework Programme, European Union [FP7/2007–2013/ERC Starting Grant Heart Healthy Hoods Agreement no. 623 336893]; and IM received a research fellowship from the University of Alcala, Spain that enables her to develop this study. Ethics approval We conducted this study in accordance with the Declaration of Helsinki, and received ethical approval by the Ethics Committee of the Universidad de Alcala (CEI/HU/2017/09).S

Availability, Promotion, and Signs of Alcohol Consumption: A Mixed Methods Study of Perceived Exposure and Objective Measures

This study describes the alcohol environment comparing residents' perceptions and objective measures in two different income-level districts. Measures were gathered between 2017 and 2018 in two districts with different income levels in Madrid, Spain. We obtained perceived measures using Photovoice. We procured objective measures through social systematic observation. Data were integrated using triangulation. Perceived and objective measures of the alcohol environment were characterized and compared in terms of alcohol availability, alcohol promotion, and signs of alcohol consumption. The integration was classified as agreement, partial agreement, or dissonance. The results related to alcohol availability and signs of its consumption showed high agreement. Availability was high in both areas, which was recognized by residents. Residents of the high-income district (HID) discussed fewer signs of alcohol consumption, whilst those in the low-income district (LID) reported extensive signs of consumption. Such observations agreed with the objective measures. There were dissonances between the approaches for alcohol promotion. Although the alcohol promotion was higher in HID according to the objective measures, it was deeply discussed by LID residents. Both methodologies helped us deepen the understanding of the alcohol environment. These results may help design more effective interventions to prevent hazardous drinking

Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia

Background: Although rapid diagnostic tests (RDTs) play a key role in malaria-control strategies, their efficacy has been threatened by deletion and genetic variability of the genes pfhrp2/3. This study aims to characterize the deletion, genetic patterns and diversity of these genes and their implication for malaria RDT effectiveness, as well as their genetic evolution in the Amhara region of Ethiopia. Methods: The study included 354 isolates from symptomatic patients from the Amhara region of Ethiopia who tested positive by microscopy. Exon 1-2 and exon 2 of genes pfhrp2 and -3 were amplified, and exon 2 was sequenced to analyse the genetic diversity, phylogenetic relationship and epitope availability. Results: The deletion frequency in exon 1-2 and exon 2 was 22 and 4.6% for pfhrp2, and 68 and 18% for pfhrp3, respectively. Double deletion frequency for pfhrp2 and pfhrp3 was 1.4%. High genetic diversity, lack of clustering by phylogenetic analysis and evidence of positive selection suggested a diversifying selection for both genes. The amino-acid sequences, classified into different haplotypes, varied widely in terms of frequency of repeats, with novel amino-acid changes. Aminoacidic repetition type 2 and type 7 were the most frequent in all the sequences. The most frequent epitopes among protein sequences were those recognized by MAbs 3A4 and C1-13. Conclusion: Deletions and high amino acidic variation in pfhrp2 and pfhrp3 suggest their possible impact on RDT use in the Amhara region, and the high genetic diversity of these genes could be associated with a diversifying selection in Ethiopia. Surveillance of these genes is, therefore, essential to ensure the effectiveness of public health interventions in this region.This work was supported by the project TRPY 111/18 funded by the Institute of Health Carlos III; and IMF received a research fellowship from the University of Alcalá that enables her to develop this study.S

Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia

Background: Although rapid diagnostic tests (RDTs) play a key role in malaria-control strategies, their efficacy has been threatened by deletion and genetic variability of the genes pfhrp2/3. This study aims to characterize the deletion, genetic patterns and diversity of these genes and their implication for malaria RDT effectiveness, as well as their genetic evolution in the Amhara region of Ethiopia. Methods: The study included 354 isolates from symptomatic patients from the Amhara region of Ethiopia who tested positive by microscopy. Exon 1?2 and exon 2 of genes pfhrp2 and -3 were amplified, and exon 2 was sequenced to analyse the genetic diversity, phylogenetic relationship and epitope availability. Results: The deletion frequency in exon 1?2 and exon 2 was 22 and 4.6% for pfhrp2, and 68 and 18% for pfhrp3, respectively. Double deletion frequency for pfhrp2 and pfhrp3 was 1.4%. High genetic diversity, lack of clustering by phylogenetic analysis and evidence of positive selection suggested a diversifying selection for both genes. The amino-acid sequences, classified into different haplotypes, varied widely in terms of frequency of repeats, with novel amino-acid changes. Aminoacidic repetition type 2 and type 7 were the most frequent in all the sequences. The most frequent epitopes among protein sequences were those recognized by MAbs 3A4 and C1-13. Conclusion: Deletions and high amino acidic variation in pfhrp2 and pfhrp3 suggest their possible impact on RDT use in the Amhara region, and the high genetic diversity of these genes could be associated with a diversifying selection in Ethiopia. Surveillance of these genes is, therefore, essential to ensure the effectiveness of public health interventions in this region.Instituto de Salud Carlos II

How patients with COVID-19 managed the disease at home during the first wave in Spain: a cross-sectional study.

Most patients with mild COVID-19 had to stay at home trying to implement an optimal quarantine. The aim of this study was to describe the COVID-19 cases during the first wave of the pandemic in Spain, how they managed the disease at home, focusing on differences by age, as well as differences in knowledge, attitudes and preventive practices, compared with the uninfected population. An online survey was used to conduct a cross-sectional study of individuals who were 14 years or older living in Spain during the COVID-19 lockdown. The main variable was a COVID-19 case. Logistic regression models for COVID-19 cases were obtained using a backward stepwise procedure to assess the association between social variables, disease knowledge, attitudes, prevention practices and emotional impact. 3398 people completed the survey. Participants' mean age was 49.6 (SD=14.3). COVID-19 was significantly more prevalent among married people (5.3%) and those currently doing an on-site work (8.7%). Most of the COVID-19 cases stayed at home (84.0%) during the episode. There were significant age-based differences with regard to self-isolation conditions at home during the disease. COVID-19 cases showed better attitudes, practices and knowledge about disease symptoms and transmission than the uninfected population. COVID-19 cases also felt more depressed (adjusted OR: 3.46, 95% CI 1.45 to 8.26) and had better preventive behaviour than the uninfected population, such as always wearing a mask outside the home (adjusted OR 1.58, 95% CI 1.06 to 2.30). COVID-19 cases found it difficult to comply with recommended home self-isolation conditions, with differences by age group. COVID-19 had an important impact on care dependency in non-hospitalised patients, who were mostly dependent on their families for care. It is necessary to reinforce social and health services and to be ready to meet the care needs of populations during the different waves or in future epidemics.This work was supported by Instituto de Salud Carlos III through the National Tropical Diseases Research Network (RD16CIII/003/001RICET). The funders had no role in study design or in the collection, analysis and interpretation of data, or the decision to submit the article for publication.S