A global overview of antibiotic resistance determinants

To understand the main determinants behind worldwide antibiotic resistance dynamics, scientists from the Institut Pasteur, Inserm, Université de Versailles Saint-Quentin-en-Yvelines and Université Paris-Saclay developed a statistical model based on a large-scale spatial-temporal analysis. Using the ATLAS antimicrobial resistance surveillance database, the model revealed significant differences in trends and associated factors depending on bacterial species and resistance to certain antibiotics. For example, countries with high quality health systems were associated with low levels of antibiotic resistance among all the gram-negative bacteria1 investigated, while high temperatures were associated with high levels of antibiotic resistance in Enterobacteriaceae. Surprisingly, national antibiotic consumption levels were not correlated with resistance for the majority of the bacteria tested. The results suggest that antibiotic resistance control measures need to be adapted to the local context and to targeted bacteria-antibiotic combinations. The results of the study were published in the journal The Lancet Planetary Health on July 10, 2023.
Antibiotic resistance (ABR) is currently one of the most urgent threats to global health. It is a natural phenomenon, but improper use of antibiotics is contributing to it by selecting resistance and complicating bacterial infection-control strategies. Worldwide surveillance of antibiotic resistance, especially under the aegis of WHO has been set up, and several databases have been created to record ABR worldwide, with the long-term aim of improving understanding of the causes to help tackle the phenomenon. Antibiotic resistance varies considerably depending on the bacterial species, but a recent study2 estimated that in 2019, 1.27 million deaths worldwide were attributable globally to ABR and ABR was associated with 4.95 million deaths.
To identify the main factors associated with worldwide antibiotic resistance dynamics, a multidisciplinary research team at the Institut Pasteur developed a statistical model and analyzed antibiotic resistance data from the ATLAS database, which contains data collected since 2004 in more than 60 countries on every continent. The scientists analyzed the data by testing a large number of determinants to reveal the main factors of antibiotic resistance and understand how they relate to the dynamics observed worldwide. “Research teams study how antibiotic resistance emerges in a bacterium in a Petri dish or in an individual, but we are currently lacking a population-level, global overview that can be used to investigate links between resistance and specific factors like national health system quality for different species of pathogenic bacteria. To understand the dynamics of antibiotic resistance, it needs to be studied at every level. That is what this study sets out to do,” explains Eve Rahbé, a PhD research student in the Institut Pasteur’s Epidemiology and Modeling of Bacterial Escape to Antimicrobials Unit and first author of the study.
The first stage of the study was to select relevant factors that could influence antibiotic resistance dynamics. “Although some biological factors are known, it was also important for us to investigate hypotheses associated with socioeconomic and climate factors,” continues the scientist. A total of eleven independent factors were selected, including health system quality (based on the GHS index3), antibiotic consumption and national wealth (GDP per capita), as well as data on travel and climate variables. Statistical models were then developed to study potential associations between the ATLAS data and the selected factors.
The analysis of global data for the period 2006-2019 initially revealed an increase in resistance to carbapenems for several species, although global trends were stable for other resistances. The study also demonstrated that the dynamics and factors associated with antibiotic resistance depend on bacteria-antibiotic combinations. Surprisingly, however, national antibiotic consumption was not significantly associated with resistance for the majority of bacteria tested (except for quinolone consumption for fluoroquinolone-resistant Escherichia coli and Pseudomonas aeruginosa and carbapenem consumption for carbapenem-resistant Acinetobacter baumannii).
Conversely, high health system quality was associated with low levels of antibiotic resistance in all the gram-negative bacteria1 tested. High temperatures were associated with high levels of antibiotic resistance, but only for Enterobacteriaceae (Escherichia coli and Klebsiella pneumoniae).
“This study reveals the wide range of factors leading to antibiotic resistance among different pathogenic bacteria at global level, and the need to adapt resistance control approaches to the local context (country, transmission context) and the specific bacteria-antibiotic combination,” concludes Philippe Glaser, Head of the Institut Pasteur’s Ecology and Evolution of Antibiotic Resistance Unit and co-last author of the study.
“Our statistical model can be applied to other databases, such as the WHO database. Improving understanding of resistance determinants, which differ from one country to the next and probably even vary among regions in the same country, is crucial and will be useful in adapting public health measures,” concludes Lulla Opatowski, a Professor at Université de Versailles Saint-Quentin-en-Yvelines, scientist in the Epidemiology and Modeling of Bacterial Escape to Antimicrobials Unit and co-last author of the study.
This research was funded by the research organizations cited above, the LabEx IBEID and an independent research Pfizer Global Medical Grant.

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Droplet levitation is a new way to explore airborne viruses and microorganisms

Self-sustained levitation of millimeter-sized droplets was recently discovered by researchers at Tyumen State University, in Russia, during an experiment to select combinations of immiscible liquids, which don’t form homogeneous mixtures.
Researchers Natalia Ivanova and Denis Klyuev noticed something amazing happen: Droplets of butyl alcohol, after being detached from the syringe needle, levitated above the surface of the layer of another liquid without collapsing onto it for a long period of time.
In Applied Physics Letters, from AIP Publishing, they report achieving self-sustaining and long-term levitation of millimeter-sized droplets of several different liquids — without any external forces.
What was it like to see the droplets levitate? “It was amazing,” said Ivanova. “The phenomenon of noncoalescence of droplets with an underlying liquid is well known. But under natural conditions, a droplet levitates above a liquid pool only an instant — milliseconds, at most. We witnessed a droplet continue to levitate for tens of minutes.”
To get the droplets to levitate, they use solutocapillary convection within a pool of silicone liquid. Solutocapilllary convection occurs when a surface tension gradient is formed by nonuniform distribution of vapor molecules from the droplet at the pool surface.
“Sometimes interesting and miraculous phenomena lie right in front of us and we don’t notice them,” said Ivanova. “By focusing on a certain task, we begin to think ‘tunnel-like’ to some extent and stop noticing alternative approaches to problem solving.”
Typically, to keep the droplets levitating for a long time — from seconds to a long-term period — it’s necessary to continuously generate excess pressure inside an ultrathin gap between a droplet and the surface of underlying liquid. This can be achieved via different methods, such as using vibrations so a droplet acts as if it’s jumping or by creating air flows within the gap under the droplet.

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Lewy body disease can be detected before symptoms

Lewy body disease is the second most common neurodegenerative disease after Alzheimer’s disease. A research group from Lund University has now shown that the disease can be detected before symptoms appear, using a spinal fluid test. The studies are published in Nature Medicine, where the researchers also demonstrate that reduced sense of smell is strongly linked to Lewy body disease even before other clear symptoms have developed. The findings are also reported simultaneously at the Alzheimer’s Association International Conference.
Lewy body disease is an umbrella term for Parkinson’s disease and Lewy body dementia. When movement difficulties are more dominant, the disease is called Parkinson’s disease, and when cognitive impairments are dominant, the term Lewy body dementia is used.
“Lewy body disease is caused by the misfolding of the alpha-synuclein protein in the brain. When this happens, the protein clumps together and forms what are called Lewy bodies, which damage the nerve cells,” says Oskar Hansson, Professor of Neurology at Lund University andsenior consultant at Skåne University Hospital.
Until very recently, it was not possible to determine with certainty, whether a person with movement difficulties or cognitive impairments had Lewy bodies in the brain until after their death. But now, with a spinal fluid test, it is possible to see if the person has the misfolded protein. Oskar Hansson’s research group has just completed a large study involving over 1,100 individuals, none of whom initially showed any cognitive impairments or motor difficulties. However, it turned out that nearly ten percent had Lewy bodies in their brains according to the spinal fluid test. Therefore, it is possible to detect Lewy body disease even before the first symptoms appear.
“Despite the participants not having any cognitive or neurological problems at the beginning of the study, we observed that those with Lewy bodies in the brain subsequently experienced a decline in their cognitive functions over time. They were also the ones who developed Parkinson’s disease or Lewy body dementia in the coming years,” says Oskar Hansson.
An interesting finding was also that Lewy bodies are strongly associated with a reduced sense of smell even before other symptoms have developed. The sense of smell also deteriorates as the disease progresses. The correlation is so clear that it could be justified to screen individuals over 60 years of age with a smell test and then proceed with testing spinal fluid if one wants to detect Lewy body disease early, according to Oskar Hansson.
“Several drugs targeted at Lewy bodies are currently being developed, with the hope of slowing down the disease. Most likely, this type of medication has the best chance of being effective if administered early in the course of the disease. If symptom-free individuals with reduced sense of smell were identified, and the test for Lewy bodies was positive, they could participate in drug trials aimed at developing new medications that can halt the disease early,” says Oskar Hansson.

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It's sewage, not fertilizer fueling nitrogen surge in Florida's Indian River Lagoon

From recurring harmful algal blooms — including brown tides — to catastrophic seagrass losses, fish kills and unusual marine mammal deaths — including the threatened Florida manatee — the Indian River Lagoon is environmentally distressed. For decades, water managers, policy makers and environmental activists have implicated fertilizer use as the primary contributing source responsible for about 71 percent of these impairments in the lagoon.
Consequently, fertilizer restrictions have been implemented in counties and municipalities along the 156-mile-long Indian River Lagoon on Florida’s Atlantic coast to reduce nutrient inputs from urban and agricultural land uses to achieve total maximum daily loads for the lagoon. Excess nutrient inputs, particularly nitrogen, often result in increased harmful algal blooms, seagrass die-offs and fish kills. The hope was that water quality would improve by reducing the nitrogen load.
While these restrictions were well-intended, a new study by Florida Atlantic University’s Harbor Branch Oceanographic Institute reveals fertilizer use is not the root cause of these environmental problems in the Indian River Lagoon. It’s sewage.
Findings of the study, published in the journal Marine Pollution Bulletin, show recent estimates for residential fertilizer contributions to the Indian River Lagoon are much lower than the originally defined contribution of 71 percent. In fact, current nitrogen loading estimates represent a 21 percent contribution from residential fertilizers compared to 79 percent from septic systems. These loading estimates are similar to those reported in other septic system-impacted urbanized estuaries.
Following five years of mandatory wet season fertilizer blackouts along the lagoon, researchers discovered water quality and harmful algal blooms have worsened in the northern Indian River Lagoon and Banana River, leading to unprecedented seagrass die-offs and starvation of manatees.
To assess the effectiveness of these fertilizer bans, researchers collected seawater and macroalgal samples at 20 sites “pre” and about five-years “post” bans. They tested by comparing dissolved seawater nutrient concentrations and tissue nutrient and isotope data of brown tides and macroalgae. Gathering evidence from stable nitrogen isotope values enabled researchers to discriminate between sewage, rainfall and fertilizer, providing a unique “fingerprint” of the samples they collected.
“Our comparative pre- versus post-ban nutrient data indicate that the wet season fertilizer blackouts were not as effective as hoped,” said Brian Lapointe, Ph.D., senior author and a research professor at FAU Harbor Branch. “Our findings also suggest that the increasing concentrations of dissolved inorganic nitrogen and phosphorus observed in some segments of the lagoon following five years of fertilizer bans would support the worsening trend of algal blooms.”
Researchers analyzed a total of 450 macroalgae samples, including 211 that were collected pre-ban and 239 collected post-ban. During the wet season, 217 macroalgae samples were collected, while 233 were collected during the dry season. They examined if there was an associated decrease in dissolved ambient nutrients or a change in the tissue nutrient and/or stable isotope values of phytoplankton or macroalgae that would suggest a shift in the available nutrients and stoichiometry fueling eutrophication in the lagoon.

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Cell protein discovery points to healthier aging

Researchers at The University of Queensland have found an anti-ageing function in a protein deep within human cells.
Associate Professor Steven Zuryn and Dr Michael Dai at the Queensland Brain Institute have discovered that a protein called ATSF-1 controls a fine balance between the creation of new mitochondria and the repair of damaged mitochondria.
Mitochondria, with their own DNA, produce energy within cells to power biological functions but the toxic by-products of this process contribute to the rate at which the cell ages.
“In conditions of stress, when mitochondrial DNA has been damaged, the ATSF-1 protein prioritises repair which promotes cellular health and longevity,” Dr Zuryn said.
As an analogy, Dr Zuryn likened the relationship to a race car needing a pitstop.
“ATSF-1 makes the call that a pitstop is needed for the cell when mitochondria need repairs,” he said.
“We studied ATFS-1 in C. elegans, or round worms and saw that enhancing its function promoted cellular health, meaning the worms became more agile for longer.

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An early breakfast may reduce the risk of developing type 2 diabetes

Eating breakfast after 9 a.m. increases the risk of developing type 2 diabetes by 59% compared to people who eat breakfast before 8 a.m. This is the main conclusion of a study in which ISGlobal, an institution supported by “la Caixa” Foundation, took part and which followed more than 100,000 participants in a French cohort. The results show that we can reduce the risk of diabetes not only by changing what we eat, but also when we eat it.
Type 2 diabetes is associated with modifiable risk factors, such as an unhealthy diet, physical inactivity and smoking. But another factor may be important: the time at which we eat. “We know that meal timing plays a key role in regulating circadian rhythms and glucose and lipid control, but few studies have investigated the relationship between meal timing or fasting and type 2 diabetes,” says Anna Palomar-Cros, ISGlobal researcher and first author of the study.
In this study, a team from ISGlobal joined at team from INSERM in France to investigate the association between meal frequency and timing and the incidence of type 2 diabetes among 103,312 adults (79% women) from the French NutriNet-Santé cohort. Participants filled in online dietary records of what they ate and drank over a 24-hour period on 3 non-consecutive days, as well as the timing of their meals. The research team averaged the dietary records for the first two years of follow-up and assessed the participants’ health over the following years (an average of seven years).
Early breakfast, early dinner
There were 963 new cases of type 2 diabetes during the study. The risk of developing the disease was significantly higher in the group of people who regularly ate breakfast after 9 a.m., compared to those who ate breakfast before 8 am. “Biologically, this makes sense, as skipping breakfast is known to affect glucose and lipid control, as well as insulin levels,” explains Palomar-Cros. “This is consistent with two meta-analyses that conclude that skipping breakfast increases the risk of type 2 diabetes,” she adds.
The research team also found that a late dinner (after 10 pm) seemed to increase the risk, while eating more frequently (about five times a day) was associated with a lower disease incidence. In contrast, prolonged fasting is only beneficial if it is done by having an early breakfast (before 8am) and an early dinner.
“Our results suggest that a first meal before 8 am and a last meal before 7 pm may help reduce the incidence of type 2 diabetes,” concludes Manolis Kogevinas, ISGlobal researcher and co-author of the study. In fact, the same ISGlobal team had already provided evidence on the association between an early dinner and a lower risk of breast or prostate cancer.
Taken together, these results consolidate the use of chrononutrition (i.e. the association between diet, circadian rhythms and health) to prevent type 2 diabetes and other chronic diseases.

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New cholera substrains in Bangladesh uncovered by genomic surveillance confirm the importance of vaccination

Researchers have uncovered two new cholera substrains in a displaced refugee population in southern Bangladesh, where a pre-emptive mass vaccination campaign of over one million refugees was successful in preventing an epidemic. They also showed that the cholera bacterium initiating this campaign was the high risk pandemic strain that has caused outbreaks of cholera globally.
In a new study, published in Nature Communications, a team led by the Wellcome Sanger Institute and the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b), used whole genome sequencing to analyse and track cholera strains in the Rohingya Refugee population in Southern Bangladesh.
By analysing 223 cholera samples, collected between 2017 and 2019, researchers identified that the main strain circulating was 7PET (1) — one that has already caused millions of deaths worldwide in a pandemic that has been ongoing since the 1960s.
The work also uncovered two new cholera sublineages of this virulent strain, 7PET, one with a global presence and another found in Asia and the Middle East. These two cholera sublineages also affect people differently, with differences in the number of purging events (2) or types of stool, for example. Researchers showed variations in the bacterium’s genetic code, which could explain why each strain presents a different disease pattern. This also proved that a mass vaccination campaign at the refugee site was vital and justified.
Being able to assign the risk of causing a major disease outbreak for each unique lineage ensures public health officials can prepare for epidemics, especially for vulnerable populations such as those in refugee camps.
It is estimated that there are 1.3 to 4 million cases of cholera annually, and 21,000 to 14,000 deaths worldwide due to this disease. If left untreated, it is quickly lethal (3). Access to safe water and sanitation is critical to prevent and control the transmission of cholera, meaning that less affluent communities are more exposed to this disease. In Bangladesh, cholera is endemic, with an estimated 66 million people at risk. Differentiating lineages of the bacterium, Vibrio cholerae, which causes cholera can be difficult or impossible to do accurately without genomic data.
Dr Alyce Taylor-Brown, postdoctoral fellow at the Wellcome Sanger Institute and first author of the study, said: “It’s important that we demonstrate how genomics can be used to track the strains of cholera that are circulating in different parts of the world. This is the first time that we have this type of evidence and it is vital in helping public health authorities make the right decisions to ensure health in vulnerable populations.

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PFAS reduce the activity of immune cells, study suggests

Because they are persistent, per- and polyfluoroalkyl substances (PFAS) are also known as “chemicals for eternity.” They can lead to liver damage, thyroid disorders, obesity, hormonal disorders, and cancer. A team of researchers from the Helmholtz Centre for Environmental Research (UFZ) has now shown that PFAS can also reduce the activity of human immune cells and thus impair health. The study was recently published in Chemosphere. The method developed at the UFZ could be used to reveal the immunomodulatory effects of other chemicals.
Whether in cosmetics, coated pans, or outdoor clothing — PFAS are used in many everyday products. This is because PFAS are water- and fat-repellent, heat resistant, and extremely durable. PFAS have been produced since the 1950s and there are now around 10,000 different compounds. “PFAS are poorly to hardly biodegradable — and that is a real problem,” says UFZ environmental immunologist Dr Gunda Herberth. “They therefore accumulate in the environment — in soils and bodies of water. They can even be found in Antarctica. They can enter the human body via food, drinking water, or the air. Studies have shown that PFAS can be detected in the blood of almost everyone in the world. What this means for our long-term health is not yet known..”
However, exposure to PFAS is known to cause liver damage, hormonal disorders and lower birth weights. Many epidemiological studies have shown an association between increased PFAS exposure and reduced immune responses after childhood vaccinations. Could PFAS be affecting our immune systems? And if so, how exactly? What happens in the immune cells? These were the questions that Gunda Herberth and further scientists set out to answer in their study.
Targeted look inside immune cells
To find out exactly what happens at the cellular level after PFAS exposure, the researchers used a special immunological measurement method they developed. “Using multiparameter spectral flow cytometry, we can detect up to 30 markers in a blood sample using different fluorescent dyes and thus identify many different immune cell types and their activation,” explains UFZ environmental immunologist Dr Arkadiusz Pierzchalski, who developed the method together with Gunda Herberth. The team used immune cells from the blood of healthy donors. First, the isolated immune cells were exposed to different PFAS mixtures for 20 hours in the laboratory. “We selected six PFAS that are particularly common in the environment and prepared three mixtures. One mixture with three short-chain PFAS, one with three long-chain PFAS and one with all six PFAS,” explains Ambra Maddalon, a toxicologist at the University of Milan and first author of the study with Arkadiusz Pierzchalski. “The immune cells were then stimulated using standard activation methods. The researchers then determined how active they were at the cellular level by using multi-parameter spectral flow cytometry.
PFAS significantly reduce the activity of T cells
The result: immune cells previously exposed to PFAS showed significantly lower activity than untreated cells. This was particularly true of T-cells. ” For example, the T-cells produced less of the messenger substances they normally use to communicate with each other and to recruit other immune cells or to trigger inflammation” says Gunda Herberth. “The strongest effects occurred when all six PFAS were mixed. Here, the effects of the different PFAS are clearly compounded. PFAS reduced the activity of two out of five types of immune cells in particular: MAIT cells (mucosa-associated invariant T cells) and T-helper cells. MAIT cells are found in the mucous membranes and form the first effective defence response. “If the activity of MAIT cells is restricted, it is much easier for pathogens to invade the body,” says Gunda Herberth. “T-helper cells are involved in the production of antibodies. If they are inhibited by PFAS, it is likely that fewer antibodies are produced — which could explain the reduced immune response to vaccination.

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Each mom passes unique set of breast milk antibodies to baby

Breast milk from each individual contains a unique assemblage of antibodies that are surprisingly stable throughout lactation and across pregnancies, according to a new Journal of Experimental Medicinestudy from the University of Pittsburgh School of Medicine.
As a baby’s early immunity is directed by antibodies from breast milk, the new research provides insight into why protection against different infections varies among infants and why some develop a life-threatening gut disease called necrotizing enterocolitis (NEC).
“While each milk donor in our study had very different antibody profiles from one another, we found that antibodies from the same donor were quite similar over time — even across the span of months,” said senior author Timothy Hand, Ph.D., associate professor of pediatrics and immunology at Pitt’s School of Medicine and UPMC Children’s Hospital of Pittsburgh. “This means that if a baby’s parent happens to lack particular antibodies — such as those that fend off NEC, they’re never going to receive that immunity. This could help explain why some babies get NEC and others don’t.”
According to Hand, NEC is a devastating inflammatory gut disease that mainly affects preterm infants. NEC, which has been linked with a family of bacteria called Enterobacteriaceae, is about 2 to 4 times more frequent in formula-fed babies than those fed breast milk.
Before their immune system matures, babies are protected from harmful bacteria by antibodies transferred via the mother’s placenta and through breast milk. These antibodies bind to bacteria in the intestine, preventing them from invading the host.
In an earlier study, Hand and his team found that Enterobacteriaceae in fecal samples of healthy babies were mostly bound by maternal antibodies. In contrast, infants who went on to develop NEC had more bacteria that escaped being bound. Hand suspected that variation in babies’ immunity to NEC was because different mothers passed along different antibodies, and the new study lends support to this idea.
Hand and his team analyzed donor breast milk from the Human Milk Science Institute and Biobank in Pittsburgh and Mommy’s Milk Human Milk Research Biorepository in San Diego. Using an array of different bacteria, they measured which strains each donor’s antibodies bound to.

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UK codeine cough syrup sales could be restricted

Published18 July 2023Shareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesCough syrup or codeine linctus could no longer be available over the counter because of concerns it is addictive and can lead to serious health problems.Rising numbers of reports of drug abuse and dependence to codeine medicines are being made to the UK medicines safety regulator.It now wants views on reclassifying it as a prescription-only medicine because of fears of misuse.Pharmacists also say they are worried about the overdose risk.Codeine linctus is an oral solution or syrup containing the ingredient codeine phosphate, which is sold as a cough remedy in pharmacies. But some people are also using it for its opioid effects – to feed an addiction to pain-relieving medication – and the Medicines and Healthcare products Regulatory Agency (MHRA) says the rules around how people get hold of it should be tightened.”Codeine linctus is an effective medicine, but as it is an opioid, its misuse and abuse can have major health consequences,” said Dr Alison Cave, chief safety officer of the MHRA.The problem has been getting noticeably worse in the last five years, with increasing numbers of reports of misuse and criminal activity linked to codeine, often promoted through social media. The MHRA says it has received 116 reports of recreational drug abuse, dependence and/or withdrawal to codeine medicines, including codeine linctus, since 2018. There were 277 serious and fatal adverse reactions to medicines containing codeine in 2021 and 243 in 2022, and there have already been 95 this year.As a result, the regulator has launched a consultation to gather views from health professionals and members of the public on making the medicine available only when prescribed by a GP.Pharmacists welcomed the move, saying there was “insufficient robust evidence” for the benefits of codeine linctus for treating coughs safely.”We also have significant concerns about its misuse and addictive potential, as well as the risk of overdose,” said Prof Claire Anderson, president of the Royal Pharmaceutical Society.She said there were many non-codeine based products which people could use for a dry cough, which would probably go away on its own anyway.Up to 60% of people worldwide may be prone to opioid dependence, studies suggest.Cough syrups have also been in the news for a different reason in India, where some cough syrups made there were linked to deaths in The Gambia and Uzbekistan. The Indian government has made it compulsory for cough syrup makers to get samples tested before exporting their products.What happens to codeine in the body?Codeine is a painkiller that is part of a group of medicines called opiatesIt works in the central nervous system and the brain to block pain signals to the rest of the bodyIt also reduces the anxiety and stress caused by painIt can be used when other painkillers have not workedIt is possible to become addicted to codeine, so if you need to take it for more than a few weeks, your doctor will tell you how and when to stop taking itChildren under 12 should not be given codeine unless advised otherwiseThe consultation on codeine linctus runs until 15 August 2023.Related Internet LinksCodeine- medicine to treat pain and diarrhoea. – NHSWho can and cannot take codeine – NHSThe BBC is not responsible for the content of external sites.

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