69832 research outputs found
Sort by
Complete attenuation of Plasmodium falciparum sporozoites by atovaquone-proguanil.
Get PDFTo develop a Plasmodium falciparum (Pf) vaccine that precludes replication inside the host for improved vaccine safety, we tested chemo-attenuation (CVac) of sporozoites (SPZ) with atovaquone-proguanil (AP). In mice, P. berghei sporozoites administered with AP invaded hepatocytes, arrested early, and induced robust protection, which correlated with parasite-specific effector-memory CD8+ T cell responses. In a clinical trial of PfSPZ-CVac (AP), in which three doses of 5.12 × 104 or 1.5 × 105 PfSPZ were administered by direct venous inoculation combined with oral single-dose AP (1000/400 mg), blood stage infections were fully prevented during immunisation. 2/8 and 2/10 of vaccinees, respectively, were protected when challenged with 3.2 × 103 PfSPZ 10 weeks later, inferior to PfSPZ-CVac (chloroquine/CQ) that allows in-host replication. Comparative analysis of responses to 228 Pf proteins revealed that protection with PfSPZ-CVac (CQ) was associated with antibodies to two liver-stage antigens (LISP2, LSA1) and a multi-stage antigen (PfMSP5), but not to the major surface protein PfCSP. The complete arrest of high numbers of Pf sporozoites by single-dose AP should allow a significant dose-frequency reduction of the current daily AP malaria chemoprophylaxis regimen
The prevalence of trachoma, ocular Chlamydia trachomatis infection and anti-Pgp3 antibodies in Choiseul Province, Solomon Islands.
Get PDFTrachoma, caused by repeated ocular infection with Chlamydia trachomatis, remains a leading infectious cause of blindness globally, with significant implications for public health. The World Health Organization and partners aim to eliminate trachoma as a public health problem by 2030, targeting specific prevalence thresholds for trachomatous trichiasis (TT) and trachomatous inflammation-follicular (TF). Diagnosis is primarily clinical. Studies have shown discrepancies between prevalence estimates of TF and C. trachomatis infection. This study, undertaken in Choiseul, Solomon Islands, evaluated TF, evidence of current C. trachomatis infection (by polymerase chain reaction (PCR) on conjunctival swabs), and evidence of past exposure to that bacterium (using anti-Pgp3 serology on dried blood spots). Among 645 1-9-year-old children, TF prevalence was 17.5% and C. trachomatis prevalence was 8.5%. These findings suggest transmission of sufficient intensity to pose a public health problem. Notably, 59% of children with TF had evidence of neither current nor previous C. trachomatis infection. Increasing age was associated with TF and evidence of past infection, but not current infection. The community had poor water, sanitation, and hygiene conditions. This study highlights the benefit of integrating laboratory testing for guiding effective trachoma elimination as a public health problem. Although our work was limited by imperfect enrolment of resident children and the logistical challenges of collecting samples in a remote region, we believe our data justify continued public health interventions against trachoma in Choiseul
Efficacy and effectiveness of hand hygiene-related practices used in community settings for removal of organisms from hands: a systematic review.
Get PDFBACKGROUND: This systematic review collected and synthesised evidence on the efficacy and effectiveness of commonly used hand hygiene materials and methods for removing or inactivating pathogens on hands in community settings. The evidence was generated to support the development of the WHO Guidelines for Hand Hygiene in Community Settings.
METHODS: We searched PubMed, Web of Science, EMBASE, CINAHL, Global Health, Cochrane Library, Global Index Medicus, Scopus, PAIS Index, WHO IRIS, UN Digital Library and World Bank eLibrary, and consulted experts in March 2023 for studies published between 1 January 1980 and 29 March 2023. Eligible studies included laboratory and field studies measuring reduction in organisms on hands after washing as intended in community settings; healthcare settings were excluded. Two reviewers independently extracted data from each study; risk of bias was assessed using the Mixed Method Appraisal Tool and a laboratory-based quality assessment tool. Summary results in terms of log10 reduction in organisms on hands were calculated for categories with five or more data points from two or more studies.
RESULTS: Of 177 studies that met inclusion criteria, the majority focused on alcohol-based hand sanitiser (111, 63%) and handwashing with soap and water (110, 62%). Most evidence (119, 67%) assessed bacterial reductions and only 7 (4%) studies addressed enveloped viruses. Across studies, there was a >2 log10 reduction in bacteria after handwashing with soap and water (2.19 (95% CI 1.5 to 2.87)) or alcohol-based sanitisers (3.13 (95% CI 2.7 to 3.56)), and for viruses after handwashing with soap and water (2.03 (95% CI 1.45 to 2.62)). However, there was a <2 log10 reduction for viruses with alcohol-based sanitisers (1.86 (95% CI 1.37 to 2.35)).
CONCLUSIONS: The ability to compare efficacy across materials and methods was limited due to the focus on bacteria and soap and water and alcohol-based sanitisers. Additional evidence quantifying the impact of handwashing on viruses (especially enveloped viruses), handwashing alternatives other than alcohol-based sanitisers, drying methods and microbial water quality, as well as the effectiveness of many of these products in the field would support more evidence-based recommendations.
PROSPERO REGISTRATION NUMBER: CRD42023429145
Highly conserved Plasmodium vivax genomes in Duffy-negative individuals from Sudan.
No full textDuffy-negatives were previously thought to be immune to Plasmodium vivax infections due to Duffy binding protein's (PvDBP1) inability to invade erythrocytes lacking Duffy antigen receptor for chemokines (DARC) expression. Nevertheless, reports of P. vivax cases are growing throughout Africa and among Duffy-negative people. Although there are alternative invasion mechanisms by P. vivax, the exact mechanisms in Duffy-negative individuals are unclear. Sudan, with a mixed Duffy-negative and Duffy-positive population, is ideal to study differences between these infections on epidemiological and genetic scales. The goal of this study was to compare Duffy-positive and Duffy-negative infections in Sudanese individuals on epidemiological and genomic scales. We collected epidemiological data and sequenced parasite genomes and found that Duffy-positive individuals had significantly higher parasitemia than Duffy-negatives (p=0.0000132). Furthermore, Duffy-positive infected P. vivax genomes were much more diverse than Duffy-negatives, across all 14 chromosomes and 44 specific erythrocyte binding gene candidates. Genes of the merozoite surface protein family account for much of the genetic diversity found. Many erythrocyte binding gene candidates are under selection pressure, both positive and negative. Finally, in genes currently implicated in binding, we have found amino acids that have undergone mutations to a structurally different residue, potentially affecting binding and antigenic conformation
Burden of cardiovascular diseases in England (2020-24): a national cohort using electronic health records data.
Get PDFBACKGROUND: The COVID-19 pandemic led to substantial health services disruption in England. Health-care policy makers need reliable national-level information on disease burden to plan services. Whole-population individual-level data, which are routinely collected and linked across multiple sources, provide comprehensive estimates that can be regularly updated at low cost. We aimed to measure the burden of cardiovascular diseases in the whole population of England from 2020 to 2024.
METHODS: Using linked National Health Service England hospital, primary care, death, and specialist registers between Jan 1, 2020, and May 31, 2024, we defined 79 common and rare cardiovascular diseases, and estimated incidence, prevalence, 30-day case fatality, and post-diagnosis rates of myocardial infarction and ischaemic stroke, focusing on five common conditions (myocardial infarction, ischaemic stroke, heart failure, atrial fibrillation, and peripheral vascular disease), as well as pulmonary embolism, myocarditis, and intracranial venous thrombosis. We conducted subgroup analyses based on and adjusted for age, sex, ethnicity, long-term conditions, deprivation, and geographical area.
FINDINGS: Analysis of data for 57 406 990 people in England between 2020 and 2024 revealed changes in cardiovascular disease burden. Although incidences after the pandemic were generally stable for the five common diagnoses, myocardial infarction (events per 100 000 person-years: 245·2 vs 216·9; -12%, 95% CI -17 to -6; p=0·0003) and peripheral vascular disease (97·9 vs 86·5; -12%, -21 to -1; p=0·032) showed decreases compared with January to February, 2020. Prevalence increased for ischaemic stroke (1·5% vs 1·8%; +16%, 10 to 21; p<0·0001), heart failure (0·9% vs 1·2%; +25%, 17 to 34; p<0·0001), and atrial fibrillation (2·8% vs 2·9%; +3%; 2 to 5; p=0·0001). There was little change in 30-day case fatality for most common diagnoses before and after the pandemic. Post-diagnosis myocardial infarction and stroke rates from 30 days to 1 year increased for myocardial infarction (events per 100 000 person-years: 18 850 vs 21 289; +13%, 5 to 22; p=0·0023), ischaemic stroke (11 849 vs 13 574; +15%, 7 to 23; p=0·0008), and heart failure (5821 vs 6393; +10%, 1 to 19; p=0·031) after the pandemic. Subgroup analyses indicated higher burdens among older adults, males, deprived populations, people with multiple long-term conditions, and Asian or Black ethnicities. There were clear regional variations in the incidence of stroke, myocardial infarction, heart failure, atrial fibrillation, and peripheral vascular disease.
INTERPRETATION: Our study offers new insights into recent cardiovascular disease patterns and reveals important health inequalities at a whole-population scale for multiple cardiovascular diseases, during and after the COVID-19 pandemic. These inequalities are targets for the improvement of cardiovascular health.
FUNDING: British Heart Foundation Data Science Centre (Health Data Research UK)
'It makes us sick': experiences of air pollution among children with asthma and their caregivers in African countries.
Get PDFBACKGROUND: This study was carried out to document experiences and perceptions of air pollution among adolescents with asthma symptoms, and their caregivers.
METHOD: A qualitative study among children with symptoms of asthma (aged 12-16 years) and their caregivers was conducted in seven African countries (Ghana, Nigeria, Malawi, South Africa, Tanzania, Uganda and Zimbabwe). Focus group discussions were used to collect data from children and caregivers and a total of 41 sessions (children 21, caregivers 20) were held. Analysis of the data gave rise to two major themes (perception of air pollution and mitigation against air pollution) from which subthemes were derived.
RESULTS: Participants identified causes of air pollution as cigarette smoking, use of wood for cooking, burning of garbage, generator, presence of industries in residential areas; and that these worsened asthma symptoms. The experiences the children had encountered were at home, while commuting to school and in school. Personal mitigation measures and governmental measures were suggested.
CONCLUSION: It is recommended that governments implement policies to mitigate air pollution and to encourage individuals to adopt personal measures to mitigate its impact
Maternal and perinatal mortality: geospatial analysis of inequality in pregnancy related and perinatal mortality in Ethiopia.
Get PDFWhile there is ample evidence of the overall reduction in perinatal and pregnancy-related mortality in Ethiopia, it remains uncertain if geographic disparities have diminished. This study aimed to investigate perinatal and pregnancy-related mortality spatial distributions, trends over time, and factors associated with the distribution in Ethiopia. We used data from Ethiopian Demographic and Health Surveys conducted in 2000, 2005, 2011, and 2016. In each survey, around 15 500 women aged 15-49 years were interviewed from about 550 neighborhoods randomly sampled from across the country. Perinatal and pregnancy-related mortality were used as outcome variables. We carried out an optimized hotspot analysis using the Getis-Ord Gi* statistic in ArcGIS Pro to identify the time trend of geographical clusters with high (hot spot) and low (cold spot) perinatal and pregnancy-related mortality. In addition, we conducted a geographically weighted Poisson regression in R to examine the factors associated with the spatial distribution of perinatal and pregnancy-related mortality. Perinatal and pregnancy-related mortality exhibited a clustering pattern, indicating the presence of geographic inequality, with a decreasing pattern from 2000 to 2016. We detected hotspot areas in developed administrative regions of Amhara, Oromia, and Southern Nations, indicating inequality within large regions. Inequality in perinatal mortality was associated with rural residence, younger age of women, and high birth rate, whereas pregnancy-related mortality was associated with low autonomy, younger age, and anemia. We found that anemia (P-value = .01) has a geographically varying relationship with perinatal mortality, while education (P-value = .03) and wealth (P-value = 0.01) are associated with pregnancy-related mortality. While there has been a reduction during the study period, geographical disparities in perinatal and pregnancy-related mortality still persist. Therefore, targeting intervention programs in areas where spatial inequalities still persist is essential for effectively utilizing scarce resources
Common myths and misconceptions surrounding hormonal contraception.
Get PDFNumerous community and professional myths and misconceptions around hormonal contraception exist, many promulgated through social media. As a result of these and other factors, people are moving away from hormonal methods and potentially exposing themselves to increased risk of unintended pregnancy. A number of key myths and misconceptions have been identified in a range of papers and here we summarise the evidence around the basis for these misunderstandings. The themes we explore are the physical side effects, the mental health effects, the impact on sexuality, the concerns about infertility, the concept of "unnaturalness", concerns about menstruation, concerns about safety and destigmatisation of side effects. For many of these themes, there is some evidence justifying the concern, but overall for most people, we argue that the benefits of hormonal contraception outweigh the disadvantages
Natural immunity and protection against variants in South African children through five COVID-19 waves: A prospective study.
Get PDFOBJECTIVES: Children have been largely spared from serious disease through the COVID-19 pandemic despite a high exposure to SARS-CoV-2. Antibody responses to exposure and their role in protecting children from subsequent variant infection remain poorly understood.
METHODS: This is a prospective cohort study of children in a South African community through ancestral/Beta/Delta/Omicron BA.1/BA.2 and BA.4/BA.5 SARS-CoV-2 waves (March 2020-October 2022). Health seeking behavior/illness was recorded and postwave serum samples measured for immunoglobulin (Ig) G to spike (S) (CoV2-S-IgG) by electrochemiluminescent immunosorbent assay. To estimate the protective CoV2-S-IgG threshold levels, logistic functions were fit to describe the correlation of CoV2-S-IgG measured before a wave and the probability for seroconversion/boosting thereafter.
RESULTS: Despite little disease, 125 per 366 (34.2%) children (median age 6.7 years [interquartile range 5.99-7.4 years]) were seropositive after wave I, rising to 53.6%, 76.0%, and 96.2% and 99.2% after waves II (Beta), III (Delta), and IV and V (Omicron variants), respectively. CoV2-S-IgG induced by natural exposure protected against subsequent SARS-CoV-2 infection, with the greatest protection for Beta and least for Omicron. The levels of IgG specific for ancestral S antigen that provided a 50% protective threshold for the subsequent wave were lowest for the Beta and highest for the Omicron BA.1/BA.2 wave. In the multivariate analysis, maternal seropositivity (adjusted odds ratio = 2.57 [95% confidence interval: 1.72-3.82]) was strongly associated with child seropositivity.
CONCLUSION: Children responded robustly to successive waves of SARS-CoV-2, mounting IgG responses to S antigen that were protective against subsequent waves. In the absence of vaccination, almost all children were seropositive after wave V but none were hospitalized, suggesting that natural immunity alone may be sufficient to protect children in a pandemic setting
Linear Growth During Treatment With a Simplified, Combined Protocol: Secondary Analyses of Severely Wasted Children 6-59 Months in the ComPAS Cluster Randomized Controlled Trial.
Get PDFA simplified, combined protocol treats children with moderate acute malnutrition (MAM), defined by mid-upper arm circumference (MUAC) of < 125 and ≥ 115 mm and no oedema, with 1 daily sachet of ready-to-use therapeutic food (RUTF) and those with severe acute malnutrition (SAM), defined by MUAC < 115 mm and/or oedema, with two daily sachets of RUTF. This protocol was previously shown to result in non-inferior recovery compared to standard treatment that used higher, weight-based RUTF dosing among children with SAM and ready-to-use supplementary food (RUSF) for MAM in a cluster-based randomised controlled trial in Kenya and South Sudan. We conducted a secondary analysis of this trial to compare linear growth among children admitted with MUAC < 115 mm. Linear and ponderal growth were calculated from admission to discharge and visualised using aggregate growth curves. HAZ change adjusted for admission characteristics was negative across the course of treatment but similar across arms [-0.21 ± 0.18 SE in the standard arm, -0.24 ± 0.18 SE in simplified; difference (95% confidence interval) 0.03 (-0.12, 0.18)]. The unadjusted mean ± SE linear growth velocity from admission to discharge was 1.8 ± 0.7 mm/week in the standard arm compared to 1.7 ± 0.7 mm/week in the simplified arm [difference = 0.09 (-0.36, 0.53)] and similar in adjusted analysis. MUAC and weight gain velocities were not significantly different by treatment arm. Reducing the RUTF dose prescribed to children during SAM treatment does not appear to affect linear growth or other growth velocities during treatment