Tag Archives: #pandemic

Face Masks Helped to Reduce Viral Transmission During the First Wave of the COVID-19 Pandemic in Italy (Medicine)

Face mask distribution and their mandatory use corresponds with an accelerated reduction in viral transmission – up to 30,000 less cases

Face masks likely played a role in reducing the spread of SARS-CoV-2 in Italy during the first half of 2020, according to a new study by mathematical modellers, who show that the use of face coverings could have reduced the number of official COVID-19 cases in Italy by up to 30,000 during Spring 2020.

Analysing official Italian data, the findings, published in the peer-reviewed journal Infectious Diseases, suggest that the protective masks also have important implications for public health decisions around their use.

“We found an excellent correspondence between nationwide lockdown and the peak of the epidemic in late March 2020, suggesting that this measure is the main factor in stopping the spread of the virus,” said lead author of the study associate professor Morten Gram Pedersen at the Department of Information Engineering of the University of Padova.

“Surprisingly, we identified further drops in viral transmission in mid-April 2020 within certain regions, which corresponded well with the provision of free face masks and/or their mandatory use. We did not see this reduction in places that did not introduce any additional local interventions at that time.”

In early March 2020, Italy was the first Western country to implement drastic measures to contain the spread of SARS-CoV-2, the virus that causes COVID-19. These restrictions, culminating in a full national lockdown between 11th March and 4th May 2020, proved effective at controlling the first wave of the epidemic. The number of new daily cases peaking at around 6,000 in late March to fewer than 300 by early June.

The researchers used mathematical modelling to compare official data from eight demographically similar Italian regions that had introduced specific local control measures at different times – or did not impose any additional restrictions beyond the national rules. Each region was effectively isolated from the rest of the country during the nationwide lockdown, making regional comparisons even more relevant.

“We found a change point reflecting a peak in the number of new cases for all eight regions that correspond well with the lockdown imposed between the 8th to 11th March 2020 depending on the region,” said Pedersen. “Five of the eight regions showed further change points during April 2020 that corresponded well with the introduction of additional general containment measures, mandatory face mask use and/or distribution of free face masks.”

The team explored alternative explanations for the accelerated decline in new cases in late April 2020 in these regions, including the activity of people using public data from Google and weather conditions. But they found that none of the investigated alternatives could account for the acceleration of the end of the first wave of the COVID-19 epidemic. “However, we cannot exclude that other, unobserved events caused the accelerated decline, as this was an observational study,” commented Pedersen.

“Several recent studies have advocated for the use of face masks, and our work is in line with other recent regional studies in Germany and the USA that correlate widespread face mask use with a reduction in the spread of COVID-19,” said Pedersen. “The reopening of society in May did not lead to any change in the decay rate. Therefore, our findings lend further support to the importance of face mask use in addition to lockdowns and other public health measures for the control of COVID-19.”

Co-author Matteo Meneghini, associate professor at the Department of Information Engineering at Padova, added: “The benefit of face mask wearing appears to be largely a cohort effect operating at the public-health, rather than the individual, level.

“We stress, however, that – whenever the situation is critical – face masks are insufficient, and should be used in addition to other containment measures such as partial or total lockdowns, to provide further contribution to public health protection.”


Reference: Morten Gram Pedersen & Matteo Meneghini (2021) Data-driven estimation of change points reveals correlation between face mask use and accelerated curtailing of the first wave of the COVID-19 epidemic in Italy, Infectious Diseases, DOI: 10.1080/23744235.2021.1877810


Provided by Taylor and Francis

Studies Use Mathematics to Analyze the Semantics of Dream Reports During the Pandemic (Neuroscience)

The COVID-19 pandemic has affected people’s behavior everywhere. Fear, apprehensiveness, sadness, anxiety, and other troublesome feelings have become part of the daily lives of many families since the first cases of the disease were officially recorded early last year.

These turbulent feelings are often expressed in dreams reflecting a heavier burden of mental suffering, fear of contamination, stress caused by social distancing, and lack of physical contact with others. In addition, dream narratives in the period include a larger proportion of terms relating to cleanliness and contamination, as well as anger and sadness.

All this is reported in a study published in PLOS ONE at the end of November. The principal investigator was Natália Bezerra Mota, a neuroscientist and postdoctoral fellow at the Brain Institute of the Federal University of Rio Grande do Norte (UFRN), in Brazil.

The study was part of Mota’s postdoctoral research and was supervised by Sidarta Ribeiro at UFRN and Mauro Copelli at the Federal University of Pernambuco (UFPE), both of whom are affiliated with the Neuromathematics Research, Innovation and Dissemination Center (NeuroMat).

Neuromat is hosted by the University of São Paulo (USP) and is one of many Research, Innovation and Dissemination Centers (RIDCs) supported by FAPESP.

The results are consistent with the hypothesis that dreams reflect the challenges of waking-life experience during the pandemic, and that the prevalence of negative emotions such as anger and sadness during the period reflects a higher emotional load to be processed, the authors write.

According to Mota, the findings are corroborated by those of other studies published later by researchers in the United States, Germany, and Finland.

The Brazilian study was initially reported in May in a preprint posted to medRxiv, and not yet peer-reviewed at that time (read more at: agencia.fapesp.br/33664). “It’s the first study on the subject to look empirically at these signs of mental suffering and their association with the peculiarities of dreams during the pandemic,” Mota told Agência FAPESP.

For Ribeiro, the authors of the study managed to document the continuity between what happens in the dream world and people’s mental lives, especially psychological distress. “This is interesting from the standpoint of dream theory,” he said. “Another point worth highlighting is that they did so quantitatively, using mathematics to extract semantics.”

The group deployed natural language processing tools to analyze 239 dream reports by 67 subjects produced in March and April 2020, shortly after the World Health Organization (WHO) declared a pandemic.

According to Mota, researchers at USP, UFRN, and the Federal Universities of Minas Gerais (UFMG), Rio Grande do Sul (UFRGS) and Rio de Janeiro (UFRJ) are conducting a multicentric study involving the analysis of data collected during a longer period (from the start of the pandemic through July) to see how dreams are affected by the deaths of family members, loved ones, friends and co-workers. “The plan is to publish the findings as soon as they’re ready so that mental health strategies can be based on this knowledge,” she said.

Methodology

For some time the researchers have been developing and using computer software that analyzes language to diagnose mental illnesses, such as schizophrenia, and adapting similar tools to perform cognitive assessments.

Dream accounts recorded by the volunteers using a smartphone app were transcribed and analyzed using three software tools. The first focused on discourse structure, word count, and connectedness.

The other two focused on content. One ranged words in certain emotional categories against a list associated with positive and negative emotions. The other used a neural network to detect semantic similarity to specified keywords, such as contamination, cleanliness, sickness, health, death and life.

In their PLOS ONE publication, the researchers say “the significant similarity to ‘cleanness’ in dream reports points towards new social strategies (e.g. use of masks, avoidance of physical contact) and new hygiene practices (e.g. use of hand sanitizer and other cleaning products) that have become central to new social rules and behavior. Taken together, these findings seem to show that dream contents reflect the different sources of fear and frustration arising out of the current scenario”.

Mota noted that more suffering was expressed in the dream reports submitted by female volunteers, although this was detected indirectly. “There are studies on gender difference in the literature. Women report more negative dreams and nightmares. I think this has to do with women’s history and daily lives, with working a double or triple shift, and the heavier mental burden entailed by concerning themselves with a job plus the home and children. The pandemic has made this worse,” she said.

The article “Dreaming during the Covid-19 pandemic: Computational assessment of dream reports reveals mental suffering related to fear of contagion” can be read at: journals.plos.org/plosone/article?id=10.1371/journal.pone.0242903#abstract0.

Featured image: Researchers at a center for neuromathematics say dreams reflect the fear and anxiety fueled by the disease (photo: Engin Akyurt/Pixabay)


Provided by FAPESP

Teenagers Catch Moods and Negative Moods Are More Contagious (Psychology)

Mental health and emotional wellbeing among young people could be better understood by findings in a recently published paper from the Universities of Birmingham and Oxford, which reveal that teenagers catch moods from friends and bad moods are more contagious than good ones.

The authors, Dr Stephanie Burnett Heyes, of the University of Birmingham’s  School of Psychology and Dr Per Block, of Oxford’s Leverhulme Centre for Demographic Science,  hope the ground-breaking study could lead to improved understanding of emotional wellbeing. 

Dr Block says, “Our study shows conclusively that individuals are affected by how others around them are feeling. Mood is contagious, and though both positive and negative moods are ‘caught’, bad moods are more potent. 

“We hope it is a step towards understanding why people fall into prolonged low states, the social factors that determine emotional wellbeing in adolescents, and, in the long run, how it may be possible to provide emotional support leading to improved mental health.”

Dr Burnett Heyes adds, “This study raises so many outstanding questions, especially in COVID-19 times, such as what do we lose when interaction is not face-to-face, and what is preserved? And finally, if everyone is struggling, is it too emotionally risky to connect with others and potentially ‘catch’ their low mood?”

The wide-ranging findings show mood goes both ways. While a teen ‘catches’ a low mood from a friend, the friend feels uplifted in the process. There was no evidence adolescents either avoid or seek contact with peers in a negative or positive frame of mind – suggesting mood does not determine popularity in the short term and socialising with someone in a low mood is a risk most are prepared to take. 

The study found teenagers’ moods become more similar to people they spend time with, that a bad mood is more infectious than a good, and these individuals did not select others with whom to socialise simply to match the way they felt themselves. 

Two groups of adolescents, 79 in total, aged 15 to 19-years-old participated in the study. Each group was on a short residential classical music performance tour.

Each young musician recorded daily moods and social interactions.  The situation allowed the study to overcome the challenges of environment, dispersed social networks and timeframes, which limited previous studies.

Dr Block adds, “What makes our study special is that, by having people in a group with few external influences, experiencing the same environment and spending their time together, we could see who interacted with whom and how that made others feel.

“We saw, first, the interaction, and then how mood became more similar. As mood changes frequently and is influenced by various environmental factors that differ between individuals, many studies find collecting comprehensive data difficult. But because our participants were living together, we overcame that challenge too.”

The results were identical from both groups and partly contradict previous understanding. Earlier research suggested good mood is more contagious than bad, and that bad mood is associated with social withdrawal. This study showed no evidence that teens feeling low withdrew.   

The research was conducted before social interaction was severely restricted by the coronavirus pandemic.


Reference: Block, P., & Burnett Heyes, S. (2020). Sharing the load: Contagion and tolerance of mood in social networks. Emotion. Advance online publication. https://doi.org/10.1037/emo0000952


Provided by University of Birmingham


About the Leverhulme Centre for Demographic Science

Societies and economies face unprecedented global demographic challenges, including radical shifts in age structures, global aging, rapid population growth in some areas but decline in others, substantial sudden flows of migrants and refugees, diverse families and fertility patterns and population-related environmental threats. The Leverhulme Centre for Demographic Science (LCDS) was set up in 2019 to build an internationally recognized centre of demographic science that will disrupt, realign and raise the value of demography in science and society.

About the University of Oxford 

Oxford has been placed number 1 in the Times Higher Education World University Rankings for the fifth year running, and at the heart of this success is our ground-breaking research and innovation. Oxford is world-famous for research excellence and home to some of the most talented people from across the globe. Our work helps the lives of millions, solving real-world problems through a huge network of partnerships and collaborations. The breadth and interdisciplinary nature of our research sparks imaginative and inventive insights and solutions.

About the University of Birmingham

The University of Birmingham is ranked amongst the world’s top 100 institutions. Its work brings people from across the world to Birmingham, including researchers, teachers and more than 6,500 international students from over 150 countries.

Pediatric Eye Injuries From Hand Sanitizers During COVID-19 Pandemic (Medicine)

KEY POINTS

Question: Is there an increase in severe ocular lesions associated with alcohol-based hand sanitizer exposures in children since March 2020?

Findings: In this national retrospective review from the French Poison Control Centers, a 7-fold increase of alcohol-based hand sanitizer-related ocular exposures in children was found in comparison with 2019, and a pediatric ophthalmology center reported 13% of patients requiring surgery for severe lesions.

Meaning: These findings support that, despite the importance of alcohol-based hand sanitizers for controlling the spread of coronavirus disease 2019, these agents should be used with caution and likely kept away from young children.Abstract

Importance:  The coronavirus disease 2019 (COVID-19) pandemic has made alcohol-based hand sanitizers (ABHS) widely available in public places. This may warrant determining whether cases of unintentional ocular exposure are increasing, especially in children.

Objective: To describe the epidemiologic trend of pediatric eye exposures to ABHS and to report the severity of the ocular lesions.

Design, Setting, and Participants: Retrospective case series conducted from April 1, 2020, to August 24, 2020. Cases were retrieved from the national database of the French Poison Control Centers (PCC) and from a pediatric ophthalmology referral hospital in Paris, France. Cases of ocular exposure to chemical agents in children younger than 18 years during the study period were reviewed. Cases of ABHS exposure were included.

Exposures: The following data were collected: age, sex, circumstances of exposure, symptoms, size of the epithelial defect at first examination, time between the incident and re-epithelialization, and medical and/or surgical management.

Main Outcomes and Measures:  Comparison of the number of eye exposures to ABHS in children between April to August 2020 and April to August 2019.

Results: Between April 1 and August 24, 2020, there were 7 times more pediatric cases of ABHS eye exposures reported in the PCC database compared with the same period in 2019 (9.9% of pediatric eye exposures in 2020 vs 1.3% in 2019; difference, 8.6%; 95% CI, 7.4-9.9; P < .001). The number of cases occurring in public places increased in 2020 (from 16.4% in May to 52.4% in August). Similarly, admissions to the eye hospital for ABHS exposure increased at the same period (16 children in 2020 including 10 boys; mean [SD] age, 3.5 [1.4] years vs 1 boy aged 16 months in 2019). Eight of them presented with a corneal and/or conjunctival ulcer, involving more than 50% of the corneal surface for 6 of them. Two cases required amniotic membrane transplant.

Conclusions and Relevance: These data support the likelihood of an increasing number of unintentional ocular exposures to ABHS in the pediatric population. To maintain good public compliance with hand disinfection, these findings support that health authorities should ensure the safe use of these devices and warn the parents and caregivers about their potential danger for children.

Reference: Gilles C. Martin, Gael Le Roux, Damien Guindolet, et al., “Pediatric Eye Injuries by Hydroalcoholic Gel in the Context of the Coronavirus Disease 2019 Pandemic”, JAMA Ophthalmol. Published online January 21, 2021. doi:10.1001/jamaophthalmol.2020.6346 https://jamanetwork.com/journals/jamaophthalmology/fullarticle/2775155?guestAccessKey=697c67bd-5876-4fa1-a9e4-08bdcab9996c&utm_source=For_The_Media&utm_medium=referral&utm_campaign=ftm_links&utm_content=tfl&utm_term=012121

Preventing Spread of COVID-19 Earlier Saves Lives (Medicine)

Rates of mortality from COVID-19 are lower in areas where public health measures aimed at preventing the spread of the disease were implemented earlier in the outbreak, according to a study from University of Hawaiʻi at Mānoa public health researchers. The findings are published in PLOS ONE.

© University of Hawai‘i at Manoa

For the study, researchers including Yan Yan Wu, an associate professor of biostatistics with the UH Mānoa Office of Public Health Studies, investigated data from 50 countries in Europe on COVID-19 mortality. The researchers compared the date when each country reported reaching its first 100 confirmed cases with its overall COVID-19 mortality rate.

The date of reaching 100 cases was used because it is a good indicator of the virus reaching community circulation. 

“We found that countries that reached 100 cases sooner also had higher mortality rates,” said Wu. “The European countries that experienced the earliest community circulation of COVID-19 suffered the worst consequences in terms of mortality.”

In Europe, most countries put containment measures such as closures of schools and nonessential businesses and bans on nonessential travel by mid-March 2020. Some cities were placed under lockdowns.

Timing matters

The World Health Organization first reported human-to-human transmission of the virus on January 22, 2020. For their analysis, the researchers calculated how many days it took (after January 22) for each country in Europe to reach 100 cases. They compared the countries that reached 100 cases in less than 50 days with those that took longer than 50 days.

Beyond mortality rates, the total incidence of the disease was higher and the overall life expectancy was lower in the countries that reached 100 cases in less than 50 days. Putting measures into place even a few weeks earlier could have dramatically reduced the amount of virus circulating in the community.

“We found clear evidence that timing matters,” Wu said. “Our data showed that efforts to delay the early spread of the virus may have saved an average 30 deaths daily per 1 million inhabitants.”

The findings may inform the response to the pandemic moving forward. Wu added, “The sooner measures to lower the spread of the virus are put in place, the lower the death rate.”

Wu’s coauthors include Catherine Pirkle and Tetine Sentell of the Office of Public Health Studies, and Alban and Genc Burazeri of the University of Medicine, Tirana, Albania.

Reference: Ylli A, Wu YY, Burazeri G, Pirkle C, Sentell T (2020) The lower COVID-19 related mortality and incidence rates in Eastern European countries are associated with delayed start of community circulation. PLoS ONE 15(12): e0243411. doi:10.1371/journal.pone.0243411 https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243411

Provided by University of Hawai‘i at Manoa

Rapid Blood Test Identifies COVID-19 Patients at High Risk of Severe Disease (Medicine)

Measuring mitochondrial DNA could predict who will need ICU care, intubation.

One of the most vexing aspects of the COVID-19 pandemic is doctors’ inability to predict which newly hospitalized patients will go on to develop severe disease, including complications that require the insertion of a breathing tube, kidney dialysis or other intensive care. Knowledge of a patient’s age and underlying medical conditions can help predict such outcomes, but there are still surprises when younger, seemingly healthier patients suffer severe complications that can lead to death.

A new study from Washington University School of Medicine in St. Louis suggests that measuring mitochondrial DNA in the blood of patients with COVID-19 can help predict which patients are at highest risk of severe disease, requiring more intensive care. Mitochondrial DNA levels are a measure of tissue damage. Pictured are damaged mitochondria (dark grey areas) released from human lungs. The small dark dots surrounding the mitochondria are magnetic beads that carry antibodies used to isolate and study unhealthy mitochondria that have been released from dying tissues. © Wandy Beatty

Now, scientists at Washington University School of Medicine in St. Louis have shown that a relatively simple and rapid blood test can predict — within a day of a hospital admission — which patients with COVID-19 are at highest risk of severe complications or death.

The study, published Jan. 14 in JCI Insight, involved nearly 100 patients newly admitted to the hospital with COVID-19.

The blood test measures levels of mitochondrial DNA, a unique type of DNA molecule that normally resides inside the energy factories of cells. Mitochondrial DNA spilling out of cells and into the bloodstream is a sign that a particular type of violent cell death is taking place in the body.

“Doctors need better tools to evaluate the status of COVID-19 patients as early as possible because many of the treatments — such as monoclonal antibodies — are in short supply, and we know that some patients will get better without intensive treatments,” said co-senior author Andrew E. Gelman, PhD, the Jacqueline G. and William E. Maritz Endowed Chair in Immunology and Oncology in the Department of Surgery.

“There’s so much we still don’t understand about this disease,” he added. “In particular, we need to understand why some patients, irrespective of their ages or underlying health in some cases, go into this hyperinflammatory death spiral. Our study suggests that tissue damage may be one cause of this spiral, since the mitochondrial DNA that is released is itself an inflammatory molecule.”

The researchers said the test could serve as a way to predict disease severity as well as a tool to better design clinical trials, identifying patients who might, for example, benefit from specific investigational treatments. They also said they would like to evaluate whether the test could serve as a way to monitor the effectiveness of new therapies. Presumably, effective treatments would lower mitochondrial DNA levels.

“We will need larger trials to verify what we found in this study, but if we could determine in the first 24 hours of admission whether a patient is likely to need dialysis or intubation or medication to keep their blood pressure from dropping too low, that would change how we triage the patient, and it might change how we manage them much earlier in the disease course,” said co-senior author Hrishikesh S. Kulkarni, MD, an assistant professor of medicine.

The researchers, including co-first authors Davide Scozzi, MD, PhD, a staff scientist, and Marlene Cano, PhD, a postdoctoral research scholar, evaluated 97 patients with COVID-19 at Barnes-Jewish Hospital, measuring their mitochondrial DNA levels on the first day of their hospital stays. They found that mitochondrial DNA levels were much higher in patients who eventually were admitted to the ICU, intubated or died. The researchers found this association held independently of a patient’s age, sex and underlying health conditions.

On average, mitochondrial DNA levels were about tenfold higher in patients with COVID-19 who developed severe lung dysfunction or eventually died. Those with elevated levels were almost six times more likely to be intubated, three times more likely to be admitted to the ICU and almost twice as likely to die compared with those with lower levels.

Further, the test predicted outcomes as well as or better than existing markers of inflammation currently measured in patients hospitalized with COVID-19. Most other markers of inflammation measured in patients with COVID-19, including those still under investigation, are general markers of systemic inflammation, rather than inflammation specific to cell death, according to the researchers.

“Viruses can cause a type of tissue damage called necrosis that is a violent, inflammatory response to the infection,” Gelman said. “The cell breaks open, releasing the contents, including mitochondrial DNA, which itself drives inflammation. In COVID-19 patients, there has been anecdotal evidence of this type of cell and tissue damage in the lung, heart and kidney. We think it’s possible that measures of mitochondrial DNA in the blood may be an early sign of this type of cell death in vital organs.”

The researchers also emphasized that the test is quick and straightforward to perform in most hospital settings because it uses the same machinery that processes the standard PCR test for COVID-19. The method they developed allows mitochondrial DNA levels to be quantified directly in the blood. Without requiring intermediate steps to extract the DNA from the blood, the technique returned results in less than an hour.

Before they can apply for approval from the Food and Drug Administration (FDA), the scientists will need to verify that the test is accurate in a larger multi-center trial. They have plans to expand the research to more sites.

The study utilized samples obtained from the School of Medicine’s COVID-19 biorepository, which was developed by co-authors Jane O’Halloran, MD, PhD, an assistant professor of medicine; Charles Goss, PhD, an instructor in biostatistics; and Phillip Mudd, MD, PhD, an assistant professor of emergency medicine.

This work was supported by the Barnes Jewish Hospital Foundation; the Children’s Discovery Institute; the National Institutes of Health (NIH), grant numbers, R01HL094601, P01AI116501 and K08HL148510; and the Washington University Institute of Clinical and Translational Sciences (ICTS) COVID-19 Research Program, which is funded by the National Center for Advancing Translational Sciences (NCATS) of the NIH, grant number UL1TR002345.

Reference: Scozzi D, Cano M, et al. Circulating mitochondrial DNA is an early indicator of severe illness and mortality from COVID-19. JCI Insight. Jan. 14, 2021. https://doi.org/10.1172/jci.insight.143299 https://insight.jci.org/articles/view/143299?utm_content=buffer269a7&utm_medium=social&utm_source=twitter.com&utm_campaign=buffer

Provided by Washington University School of Medicine

Wits Scientists Artificially Infect Mosquitoes with Human Malaria to Advance Treatment (Medicine)

Wits scientists and local and global partners have artificially infected mosquitoes with human malaria and identified a new chemical compound to treat malaria.

Scientists at the Wits Research Institute for Malaria (WRIM) in partnership with the University of Pretoria and colleagues in the US, Spain and Switzerland have identified novel antiplasmodial lead compounds for mass drug administration and vector control to eliminate malaria.

WRIM dissections of mosquito gut under microscope © WRIM

A vector refers to an organism that carries and transmits an infectious disease, as mosquitoes do malaria.

Lead compounds are chemical compounds that show promise as treatment for a disease and may lead to the development of a new drug.

Antiplasmodial lead compounds are those that counter parasites of the genus Plasmodium, which is the parasite that infects mosquitoes and causes malaria in people.

The study findings were published  in Nature Communications on 11 January 2021, at a time when malaria incidence generally peaks after the holiday season.

Mozzie infection experiment centre

Professor Lizette Koekemoer, co-director of the WRIM and the National Research Foundation SARChI Chair in Medical Entomology and Control, and an honorary member of the Centre for Emerging Zoonotic and Parasitic Diseases, National Institute for Communicable Diseases, co-authored the paper.

Koekemoer and her team at WRIM established a unique mosquito malaria infection centre in the Faculty of Health Sciences at Wits University, where the mosquito transmission blocking experiments took place.

“The WRIM infection centre is the only facility in South Africa and in the southern African region that can artificially infect mosquitoes with the human malaria parasite,” says Koekemoer. “The infection centre provided the high level of expertise required to infect mosquitoes with the human malaria parasite, Plasmodium falciparum, and allowed for this unique study to be done.”

Mid-gut of a mosquito that fed on infected blood with a transmission blocking compound showing no oocysts ©WRIM

Curating chemicals to combat transmission

Drugs are used to control human malaria but resistance to these drugs develops rapidly. Furthermore, the drugs mainly target just one stage of the parasite’s life cycle and are not good candidates for blocking transmission.

To expand drug suitability for malaria elimination strategies, drugs need to be able to act as a chemotype [a chemically distinct entity in a plant or microorganism] that blocks both human-to-mosquito transmission and mosquito-to-human transmission.

Koekemoer, with WRIM colleagues and co-authors, Erica Erlank, Luisa Nardini, Nelius Venter, Sonja Lauterbach, Belinda Bezuidenhout, and Theresa Coetzer conducted specialised experiments to measure the reduction of infection in the mosquitoes as well as the “killing effect” [endectocide effect] in the vectors.

Erica Erlank in the Wits Research Institute for Malaria evaluates number of oocysts per gut © WRIM

The scientists screened 400 chemical compounds available in the “Pandemic Response Box”, which is supplied by Medicines for Malaria Venture (MMV), to identify the compounds that are most effective across the life stages of the parasite that generally take place in the human host. 

The Pandemic Response Box contains 400 diverse drug-like molecules active against bacteria, viruses or fungi. It is available free of charge provided that researchers share data resulting from research on the molecules in the box with the public within 2 years of its generation.

The compounds that showed a good effect on late-stage gametocytes (those circulating in the blood and being transferred to a mosquito when it feeds on an infected human) were evaluated for their transmission-blocking potential.

Mosquitoes were fed infected blood that was treated either with or without the compound. After eight to 10 days, the mosquito guts [stomach] were removed and the number of parasites (called oocysts) counted and compared against those mosquitoes that received only an infected blood meal without treatment.

Nelius Venter in the Wits Research Institute for Malaria prepares mosquitoes for infection feeding © WRIM

Seeking the spark

Mass drug administration (MDA) is the administration of antimalarial drugs to target the parasite reservoir in humans, without necessarily testing whether those people are carrying the parasite that causes malaria.

The World Health Organization (WHO) recommends MDA for the elimination of the Plasmodium falciparum malaria parasite. However, the effort and cost required to implement MDA on a large scale is prohibitive.

Identifying the potential compounds for MDA is amongst the greatest hurdles to overcome and is therefore an intense research pipeline of development.

By leveraging the scarce skills and expertise available in different research institutes such as the WRIM, this study published in Nature Communication established the first such pipeline screening in South Africa.

This opens the door for screening additional chemistry effectively and rapidly to contribute towards the elimination of malaria.

Towards zero transmission targets

Although there were still an estimated 229 million malaria cases in 2019 and 409 000 deaths during this period (compared to some 88 million Covid-19 cases reported), the successes of reducing malaria cases over the past two decades has inspired many countries to commit to eliminating transmission altogether. 

To date, the WHO has certified 38 countries and territories malaria-free. In southern Africa, eight countries – including South Africa – have made the elimination of malaria a policy goal. 

However, progress towards eliminating transmission has numerous challenges and new drugs and insecticides are urgently needed to combat the development of drug resistance in the parasite and the vector. 

The WRIM and studies like these are pioneering novel approaches. However, it is still a long road between the laboratory and field operations. But the first steps have been taken.

Reference: Reader, J., van der Watt, M.E., Taylor, D. et al. Multistage and transmission-blocking targeted antimalarials discovered from the open-source MMV Pandemic Response Box. Nat Commun 12, 269 (2021). https://doi.org/10.1038/s41467-020-20629-8

Provided by University of Witwatersrand, Johannesburg

Acting Quickly After Heart Attack Symptoms Start Can Be a Heart Saver (Medicine)

Research Highlights:

  • The degree of heart muscle damage from a heart attack is associated with how long it takes from when heart attack symptoms start to when patients receive an artery-clearing procedure called percutaneous coronary intervention, or PCI.
  • The longer the time period before PCI, called symptom-to-balloon time, the more significant and damaging the heart attack.
  • The researchers said these findings emphasize the importance of public education strategies stressing the need for people to recognize the signs of a heart attack and seek emergency medical care as soon as they feel symptoms.

The longer the time between when heart attack symptoms start and a patient has an artery-clearing percutaneous coronary intervention (PCI), the more damage to the heart muscle, according to new research published today in Circulation: Cardiovascular Interventions, an American Heart Association journal.

AHA Heart attack warning-signs infographic 2021 Common heart attack warning signs: Pain or discomfort in chest Lightheadedness, nausea, or vomiting Jaw, neck or back pain Discomfort or pain in arm or shoulder Shortness of breath. copyright American Heart Association 2021

heart attack happens about every 40 seconds in the U.S., and the most common heart attack is caused by a complete blockage in a coronary artery, called ST-elevation myocardial infarction (STEMI). STEMI patients are most often treated with PCI, also known as angioplasty with stent, in which a catheter with a deflated balloon is inserted into the narrowed heart artery. Subsequently, the balloon is inflated, which clears the obstruction and restores blood flow. A stent is then inserted to keep the artery open.

“We know the time to opening the blocked coronary artery with PCI in heart attack patients is an important indicator for how a patient does after their heart attack. There are two measures for this time. One is symptom-to-balloon time, which is before the patient arrives to the hospital after symptoms start, to when that patient has a PCI; second is door-to-balloon time, the time from hospital arrival to PCI,” said study author Gregg W. Stone, M.D., director of academic affairs at Mount Sinai Heart Health System in New York City. “We focused on heart attack size, or damage, with both time measures and found symptom-to-balloon time was by far the more important.”

Stone and colleagues analyzed the data from 10 randomized controlled trials that followed more than 3,100 STEMI patients enrolled after PCI between 2002-2011. Patients’ hearts were assessed within between 3-12 days after PCI to measure the size of the heart attack, and some studies also included measures of ejection fraction (a measure of the percentage of blood the heart is able to pump with each contraction) and TIMI flow (a measure of blood flow in the coronary artery). All patients had clinical follow-up data for at least six months, with a median follow-up of 341 days after PCI.

The study found:

  • Symptom-to-balloon time was more strongly associated with heart attack size and patients’ clinical health after heart attack than door-to-balloon time.
  • The median symptom-to-balloon time was 185 minutes. The median door-to-balloon time was 46 minutes.
  • Symptom-to-balloon time represented approximately 80% of the total time from symptom onset to treatment of the artery.
  • The size of the heart attack increased with longer symptom-to-balloon times, whereas longer door-to-balloon times were not notably related to heart attack size.
  • Older age, female sex, arterial hypertension, diabetes and left circumflex artery as the culprit vessel were associated with longer symptom-to-balloon time.
  • For every 60-minute delay in symptom-to-balloon time, the one-year rate of death or hospitalization for heart failure was increased by 11%. In contrast, there was no relationship between delays in door-to-balloon time and these clinical results.

“Health care teams have worked to reduce door-to-balloon times and are achieving excellent results with a median time of 46 minutes. While we shouldn’t become complacent and relax our current standards of rapidly performing PCI as soon as possible after the patient reaches the hospital, this study suggests that major efforts to further shorten door-to-balloon times by 10 or 20 minutes might not translate to better PCI outcomes,” Stone said. “Our analysis indicates the more important and meaningful focus should be to shorten the delays from symptom onset to arrival at hospitals that can perform PCI. We must emphasize efforts to increase public awareness of heart attack symptoms and shorten the time it takes for patients to access emergency care.”

These findings are extremely important and particularly relevant right now, said American Heart Association president Mitchell S.V. Elkind, M.D., M.S., FAHA, FAAN, professor of neurology and epidemiology at Vagelos College of Physicians and Surgeons and attending neurologist at New York-Presbyterian/Columbia University Irving Medical Center.

“During the peaks of the COVID-19 pandemic, hospitals are reporting fewer people coming into the emergency room for heart attack and stroke symptoms – indicating people aren’t calling 911, or they are delaying or avoiding critical care,” Elkind said. “This concerns us because we know it’s very unlikely that there are fewer heart attacks or strokes occurring. These new findings emphasize just how crucial it is to call 911 at the first sign of a heart attack or stroke – because getting quick treatment can be the difference between life and death. As we have been urging even during the COVID-19 pandemic, don’t die of doubt. Call 911 as soon as possible.”

Among the limitations of this analysis, detailed information about the intensity of chest pain or other heart attack signs and symptoms, or about the time from symptom onset to PCI was not available from the clinical trials’ data..

Co-authors are Björn Redfors, M.D., Ph.D.; Reza Mohebi, M.D.; Gennaro Giustino, M.D.; Shmuel Chen, M.D., Ph.D.; Harry P. Selker, M.D., M.S.P.H.; Holger Thiele, M.D.; Manesh R. Patel, M.D.; James E. Udelson, M.D.; E. Magnus Ohman, M.D.; Ingo Eitel, M.D.; Christopher B. Granger, M.D.; Akiko Maehara, M.D.; Ziad A. Ali, M.D., D.Phil.; Ori Ben-Yehuda, M.D. Author disclosures are in the manuscript. The researchers reported no funding sources for this study.

Reference: Björn Redfors, Reza Mohebi, Gennaro Giustino, Shmuel Chen, Harry P. Selker, Holger Thiele, Manesh R. Patel, James E. Udelson, E. Magnus Ohman, Ingo Eitel, Christopher B. Granger, Akiko Maehara, Ziad A. Ali, Ori Ben-Yehuda, and Gregg W. Stone, “Time Delay, Infarct Size and Microvascular Obstruction After Primary PCI for ST-Segment Elevation Myocardial Infarction”, Circulation: Cardiovascular Interventions, 2021. https://doi.org/10.1161/CIRCINTERVENTIONS.120.009879 https://www.ahajournals.org/doi/10.1161/CIRCINTERVENTIONS.120.009879

Provided by Heart

Are Two Phases of Quarantine Better Than One? (Medicine)

New research into this question shows that the second wave of an epidemic is very different if a population has a homogenous distribution of contacts, compared to the scenario of subpopulations with diverse number of contacts.

The research, by American authors from Oakland University, Novi High School, and California Polytechnic State University, used a simulation approach to model the progress of an epidemic in a network where the connectivity of each individual changed over time, modelling the effects of political decisions made concerning various degrees of quarantine. It was published on December 23 in Europhysics Letters.

The authors stated: “Recently, several authors incorporated quarantine into COVID-19 modeling. However, these models were not network-based. In addition, they did not address the question of the optimal strategy for easing the quarantine in order to minimize the net number of infected individuals – one of the central questions in the present paper.” The benefits of a network-based model are that it more accurately accounts for a peaked distribution of individual disease durations, which is a problem for continuum models; also, it does not require the assumption of an equal number of contacts for each individual, so it more accurately models the underlying microscopic structure of the social network.

According to the authors, if a population has a homogeneous distribution of the number of contacts, “the total number of infected people at the end of the epidemic is the same as if no lockdown had been decreed (saturation of the health system aside),” whereas in the case of diverse frequency of contacts, the overall number of infected individuals can be significantly smaller. The reason for this effect is simple. After the individuals with a large number of contacts (high-degree nodes) have acquired immunity, they prevent the propagation of the epidemic through them, thus, slowing-down the spread of the epidemic through the network. Therefore, the optimal timing to allow the low-degree nodes to increase connections (by lifting the lockdown) would be after the high-degree nodes have become immune; this will minimize the net number of infected individuals over the course of the epidemic.

The results suggest an optimal degree-based procedure for lifting the quarantine: “high degrees go first. In practice, when the state lifts the strict quarantine (or moves from one phase of quarantine to the next phase), there is always a choice. One can open smaller stores (where cashiers are high-degree nodes) or/and one can allow gatherings (which typically consist of low-degree nodes). The model suggests that the stores need to be opened first: this way we can save many individuals (mostly low-degree nodes) from being infected”.

The authors continue: “This has two important consequences: first, it stresses the relevance of adopting lockdown measures to stop the first outbreak of an epidemic, and second, it shows that second and further waves may be milder than expected.”

The results are counterintuitive, as the controversy in the media about the relevance of adopting lockdown measures reveals. This paper points to the importance of a feature that is usually overlooked in the analysis of how epidemics spread: how the heterogeneity of people’s behaviours affects their ability to protect themselves from contagion.

Reference: Varun Nimmagadda, Oleg Kogan and Evgeniy Khain, “Path-dependent course of epidemic: Are two phases of quarantine better than one?”, EPL (Europhysics Letters), Volume 132, Number 2, 2020. https://iopscience.iop.org/article/10.1209/0295-5075/132/28003

Provided by IOP Publishing