Day: February 24, 2022

SA COVID Study: ‘No Longer at Code Red’, Prof Madhi Says

Image from Pixabay

Commenting on a recently published South African study showing a high COVID antibody sero-prevalence and decoupling of hospitalisation and death rates, first author Professor Shabir Madhi said that “we [are] no longer at “code red’.”

The study, published in the New England Journal of Medicine, was conducted in Gauteng from October 22 to December 9, 2021, showed a high sero-positivity rate even as the Omicron wave started. Under-12s (56%) had the lowest rate of sero-positivity, while it was 80% in over-50s and 85% in inner city residents. Unsurprising, vaccinated individuals had much higher rates (93%) than unvaccinated ones (68%). Epidemiologic data showed that the incidence of COVID infection increased and subsequently declined more rapidly during the fourth wave than it had during the three previous waves.

The researchers imputed 10.4 million infections, compared to the <1 million COVID cases recorded before Omicron. The researchers also evaluated COVID epidemiologic trends in the province, including cases, hospitalisations, recorded deaths, and excess deaths from the start of the pandemic through January 12, 2022.

At time of Omicron wave onset, 59159 Covid attributable deaths using excess mortality data (rate 396/100,000) in Gauteng. Infection fatality risk for Gauteng 0.57% pre-omicron (substantially higher than 0.019% imputed for seasonal flu pre-Covid calculated using similar methods).

In Gauteng at the start of the Omicron wave. vaccine coverage 36% for at least 1 dose in Gauteng, but 61% in over-50s (responsible for >80% deaths pre-Omicron). The sero-survey showed that, 70% of vaccinated were also infected pre-omicron, indiciating a substantial prevalence of hybrid immunity

Prof Madhi further noted analysis of the incidence trends shows a “massive decoupling” of COVID cases to hospitalisation and death rates over the course of Omicron dominance, which was seen in all age groups.
Omicron was responsible for only 3% of COVID deaths compared to 50% for those in Delta-dominant waves. In the 50-59 age group, Omicron was responsible for only 2% of deaths compared to 53% of Delta-dominant deaths.

They also found that children under 12 were not seriously affected during the Omicron wave, with the Omicron wave making up 26% of hospitalisations and 17% of deaths versus 39% and 47%, respectively with the Delta wave.

The researchers concluded that the SA experience indicates that we are now moving into the convalescent phase of the COVID pandemic. Prof Madhi noted in his tweets that this is likely to be similar in other countries that have had a low or modest vaccine uptake, but which have also seen high rates of natural infection – which, in low- and middle-income countries, has likely been accompanied by significant under-reporting of COVID fatalities. 

Given low rates of vaccine rollout and donations, Africa should focus on vaccinating its vulnerable elderly population, Prof Madhi recommended.

He tweeted that SA had expressed optimism that the pandemic had reached a turning point “which many in high income countries dismissed as ’empirical’ and not applicable to their settings despite high vaccine coverage,” subsequently materialised around the world wherever COVID was “not [a] zero-sum game.”

Hypersensitivity Link Between MRI and X-Ray Contrast Agents

Photo by Mart Production on Pexels

People with a history of hypersensitivity to iodine-based contrast agents for X-ray based scans, are also susceptible to similar reactions from commonly used MRI contrast agents, according to a large, eight-year cohort study. The study, published in the journal Radiology, also found that premedication or switching to a different MRI contrast agent may reduce risk in patients who have had previous contrast agent reactions.

For a long time, gadolinium-based contrast agents (GBCA) have been used to enhance visualisation of organs, tissues and blood vessels on MRI and provide a more accurate depiction of disease. Though GBCA are relatively safe, recent studies have reported several adverse reactions related to their use, including allergic-like hypersensitivity reactions, such as rash and flushing.

These reactions are increasing in incidence with the widespread use of GBCA, prompting an urgent need for research into risk factors, according to the study’s senior author Hye-Ryun Kang, MD, PhD.

Analysing more than 330 000 cases of GBCA exposure in 154 539 patients over an eight-year period, the researchers found 1304 cases of allergic-like hypersensitivity reactions, for a rate of 0.4%. In patients who had a previous GBCE reaction, the average recurrence rate was 15%.

Acute allergic-like hypersensitivity reactions, or those that occur within one hour of contrast administration, accounted for 1178 cases, while a far smaller number of 126 cases were delayed allergic-like hypersensitivity reactions, or those that occur beyond the first hour and mostly within one week after exposure.

The risk of allergic-like hypersensitivity reactions to GBCAs was higher in those with a history of similar reactions to iodinated contrast media. Normally, having a history of iodinated contrast media hypersensitivity was not thought to be a risk factor for hypersensitivity to GBCAs and vice versa, because of their structural and compositional differences.

“The results of our study challenge this idea,” Dr Kang said.

An underlying predisposition to drug allergies in susceptible patients could be the cause, Dr Kang said, as opposed to any cross-reactivity associated with structural similarities between iodinated contrast media and GBCA. In fact, the risk of hypersensitivity reactions to iodinated contrast media was also higher in those who previously experienced a similar reaction to GBCA.

“Thus, physicians should be aware that patients with a history of hypersensitivity to one of iodinated contrast media or GBCA are at greater risk of developing hypersensitivity reactions to the other,” she said.

Analysis of the data showed that premedication, typically with steroids and antihistamines, and changing the GBCA showed preventive effects in patients with a history of acute allergic-like hypersensitivity reactions. Patients who received premedication and before MRI or were switched to a different GBCA showed the lowest rate of recurrence. Only premedication significantly reduced the incidence of reactions in patients with a history of delayed reactions.

“As the most important preventive measure is avoidance of the culprit agent, a precise record of previously used GBCA should be kept for all patients,” Dr. Kang said. “Physicians should discuss appropriate premedication strategies with their patients prior to MRI procedures.”

Dr Kang nevertheless stressed that contrast-enhanced MRI examinations are invaluable in the diagnosis and follow-up of various diseases, and the overall risk remains low.

“As most of these reactions are mild, we believe the benefits of MRI outweigh the potential risks associated with GBCA use,” she said.

Dr Kang recommended that in all patients receiving an MRI with GBCA exposure, a detailed history of previous hypersensitivity allergic reactions be conducted, and when necessary, appropriate prevention measures should be implemented, such as using premedication and switching to different GBCA types.

Future work would be to perform studies with larger populations to identify possible risk factors and effective preventive strategies for delayed hypersensitivity reactions to GBCA.

Source: Radiological Society of North America

Severe COVID Raises Risk of Pregnancy Complications

Source: Pixabay

A University of Oxford study of over 4000 pregnant women indicates that severe COVID in pregnancy increases the risk of pre-labour caesarean birth, a very or extreme preterm birth, stillborn birth, and the need for admission to a neonatal unit.  

The study, published in Acta Obstetricia et Gynecologica Scandinavica, included 4436 pregnant women hospitalised in the UK with symptomatic COVID from March 1, 2020 to October 31, 2021, of whom 13.9% of had severe COVID. As well as having increased risks of adverse pregnancy-related outcomes, women with severe infection were more likely to be aged 30 years or over, be overweight or obese, be of mixed ethnicity, or have gestational diabetes compared with those with mild or moderate infection.  

“This new analysis shows that certain pregnant women admitted to a hospital with COVID face an elevated risk of severe disease. However, it shows once again the strongly protective effect of vaccination against severe disease and adverse outcomes for both mother and baby,” said senior author Marian Knight, FMedSci, of the University of Oxford. “This study emphasises the importance of ensuring that interventions to promote vaccine uptake are particularly focused towards those at highest risk.”

Source: Wiley

CVD Risk Warning for Paracetamol That Contains Sodium

Graphical abstract from European Heart Journal editorial: sodium hidden in medication warrants warning labels by drug companies

Clinicians have recommended avoiding effervescent, soluble paracetamol that contains sodium, following findings from a large study that shows a link with a significantly increased risk of cardiovascular disease (CVD) and mortality in people who have hypertension and even in people with normal blood pressure.

The study of nearly 300 000 patients registered with UK GPs was published in the European Heart Journal.

Sodium is often used to help drugs such as paracetamol dissolve and disintegrate in water. However, effervescent and soluble formulations of 0.5g tablets of paracetamol can contain 0.44 and 0.39g of sodium respectively. If a person took the maximum daily dose of two 0.5g tablets every six hours, they would consume 3.5 and 3.1g of sodium respectively – a dose that exceeds the WHO-recommended total daily intake of 2g a day. In 2018, 170 people per 10 000 of the population in the UK were using sodium-containing medications, with a higher proportion among women. There are alternative formulations that contain little or no sodium.

Excessive salt in the diet remains a major public health problem and is associated with an increased risk of cardiovascular disease (CVD) and death among patients with hypertension. However, there is inconsistent evidence showing an increased risk in normotensive individuals.

Professor Chao Zeng led a team which analysed data from a medical database of UK GPs’ records. They looked at 4532 hypertensive patients who had been prescribed sodium-containing paracetamol and compared them with 146 866 hypertensive patients who had been prescribed sodium-free paracetamol. They also compared 5351 normotensive patients who were prescribed sodium-containing paracetamol with 141 948 normotensive patients prescribed sodium-free paracetamol. The patients were aged 60-90 years and followed up for one year.

The researchers found the risk of heart attack, stroke or heart failure after one year for patients with high blood pressure taking sodium-containing paracetamol was 5.6% (122 cases of CVD), while it was 4.6% (3051 CVD cases) among those taking sodium-free paracetamol. Mortality risk was also higher; the one-year risk was 7.6% (404 deaths) and 6.1% (5510 deaths), respectively.

A similar increased risk was seen among normotensive patients. Among those taking sodium-containing paracetamol, the one-year CVD risk was 4.4% (105 cases of CVD) and 3.7% (2079 cases of CVD) among those taking sodium-free containing paracetamol. The risk of dying was 7.3% (517 deaths) and 5.9% (5190 deaths), respectively.

Prof Zeng said: “We also found that the risk of cardiovascular disease and death increased as the duration of sodium-containing paracetamol intake increased. The risk of cardiovascular disease increased by a quarter for patients with high blood pressure who had one prescription of sodium-containing paracetamol, and it increased by nearly a half for patients who had five or more prescriptions of sodium-containing paracetamol. We saw similar increases in people without high blood pressure. The risk of death also increased with increasing doses of sodium-containing paracetamol in both patients with and without high blood pressure.”

Prof. Zeng said that clinicians and patients should be aware of the risks associated with sodium-containing paracetamol and avoid unnecessary consumption, especially when the medication is taken for a long period of time.

“Given that the pain relief effect of non-sodium-containing paracetamol is similar to that of sodium-containing paracetamol, clinicians may prescribe non-sodium-containing paracetamol to their patients to minimise the risk of cardiovascular disease and death. People should pay attention not only to salt intake in their food but also not overlook hidden salt intake from the medication in their cabinet,” he said.

“Although the US Food and Drug Administration requires that all over-the-counter medications should label the sodium content, no warning has been issued about the potentially detrimental effect of sodium-containing paracetamol on the risks of hypertension, cardiovascular disease and death. Our results suggest re-visiting the safety profile of effervescent and soluble paracetamol.”

Being an observational study it can only show only that there is an association between salt in paracetamol and CVD and deaths, rather than that salt causes these events. Other limitations include a lack of data on dietary intake of salt and excretion of salt from urinary samples. The use of over-the-counter paracetamol was not also recorded, however by restricting the study to those over 60 who qualify for free prescriptions in the UK, the risk of this is minimised.

Source: EurekAlert!

Indoor Air Pollution Linked to Pneumonia in Children

Streptococcus pneumoniae. Credit: CDC

A new study published in The Lancet Global Health, highlights the impact indoor air pollution can have on the development of child pneumonia, showing that increases in airborne particulate matter results in greater carriage of Streptococcus pneumoniae.

Streptococcus pneumoniae is a major human pathogen causing more than two million deaths per year; more than HIV/AIDS, measles and malaria combined, but it is also part of the normal microbial community of the nasopharynx. It is the leading cause of death due to infectious disease in children under five years of age; in sub-Saharan Africa, the burden of pneumococcal carriage and pneumonia is especially high.

Household air pollution from solid fuels increases the risk of childhood pneumonia. Nasopharyngeal carriage of S. pneumoniae is a necessary step in the development of pneumococcal pneumonia. More than 2.6 billion people are exposed to household air pollution worldwide. Inefficient indoor biomass burning is estimated to cause 3.8 million premature deaths annually and approximately 45% of all pneumonia deaths in children aged younger than five years. However, a causal pathway between household air pollution and pneumonia had not yet been identified.

In order to understand the connection between exposure to household air pollution and the risk of childhood pneumonia researchers from the UK, Malawi and the United States conducted the MSCAPE (Malawi Streptococcus pneumoniae Carriage and Air Pollution Exposure) study embedded in the ongoing CAPS (Child And Pneumonia Study) trial. The MSCAPE study assessed the impact of PM2.5, the single most important health-damaging pollutant in household air pollution, on the prevalence of pneumococcal carriage in a large sample of 485 Malawian children.

Through exposure-response analysis, a statistically significant 10% increase in risk of S. pneumoniae carriage in children was observed for a unit increase (deciles) of exposure to PM2.5 (ranging from 3.9 μg/m³ to 617.0 μg/m³).

Dr. Mukesh Dherani, the study principal investigator, indicated: “This study provides us with greater insight into the impact household air pollution can have on the development of child pneumonia. These findings provide important new evidence of intermediary steps in the causal pathway of household air pollution exposure to pneumonia and provide a platform for future mechanistic studies.”

Study author Professor Dan Pope said: “Moving forward further studies, particularly new randomized controlled trials comparing clean fuels (e.g. liquefied petroleum gas) with biomass fuels, with detailed measurements of PM2.5 exposure, and studies of mechanisms underlying increased pneumococcal carriage, are required to strengthen causal evidence for this component of the pathway from household air pollution exposure to ALRI in children.”

Professor Nigel Bruce, co-principal investigator, stated: “This study provides further important evidence that emphasises the need to accelerate to cleaner fuels, such as LPG, which are now being promoted by many governments across the continent in order to meet SDG7 by 2030.”

Source: University of Liverpool

Investigating Vaping’s Impact on Gum Disease

Photo by Chiara summer on Unsplash

A series of new studies investigates how e-cigarettes alter oral health and may be contributing to gum disease. The latest, published in mBio, finds that e-cigarette users have a distinctive oral microbiome that is less healthy than nonsmokers but potentially healthier than cigarette smokers, and measures worsening gum disease over time.

“To our knowledge, this is the first longitudinal study of oral health and e-cigarette use. We are now beginning to understand how e-cigarettes and the chemicals they contain are changing the oral microbiome and disrupting the balance of bacteria,” said co-lead researcher Prof Deepak Saxena.

While cigarette smoking is known to increase gum disease risk, much less is known about the impact of e-cigarette use on oral health, especially in the long term.

The researchers studied the oral health of 84 adults from three groups: cigarette smokers, e-cigarette users, and people who have never smoked. Gum disease was assessed through two dental exams six months apart, during which plaque samples were taken to analyse the bacteria present.

Gum health changes
All participants had some gum disease at the start of the study, with cigarette smokers having the most severe disease, followed by e-cigarette users. After six months, the researchers observed that gum disease had worsened in some participants in each group, including several e-cigarette users.

Clinical attachment loss is a key indicator of gum disease, measured by gum ligament and tissue separating from a tooth’s surface, leading the gum to recede and form pockets. These pockets are bacterial breeding grounds and can lead to worsening gum disease. In a study of the same participants published in Frontiers in Oral Health, the research team found that clinical attachment loss was significantly worse only in the e-cigarette smokers after six months.

A unique microbiome
Analysis of the bacteria in plaque samples showed that e-cigarette users had a different oral microbiome than smokers and nonsmokers, in line with their earlier results.

While all groups shared roughly a fifth of the types of bacteria, the bacterial makeup for e-cigarette users had strikingly more in common with cigarette smokers than nonsmokers. Several types of bacteria, including Selenomonas, Leptotrichia, and Saccharibacteria, were abundant in both smokers and vapers compared to nonsmokers. Several other bacteria – including Fusobacterium and Bacteroidales, linked to gum disease – were particularly dominant in the mouths of e-cigarette users.

When plaque samples were gathered and analysed in the six-month follow-up, the researchers found greater diversity in bacteria for all groups studied, yet each group maintained its own distinct microbiome.

“Vaping appears to be driving unique patterns in bacteria and influencing the growth of some bacteria in a manner akin to cigarette smoking, but with its own profile and risks to oral health,” said Fangxi Xu, study co-first author.

An altered immune response
The researchers found that the distinct microbiome in e-cigarette users was correlated with clinical measures of gum disease and changes to the host immune environment. In particular, vaping was associated with different levels of cytokines. Certain cytokines are linked to an imbalance in oral bacteria and can worsen gum disease by making people prone to inflammation and infection.

TNFα, a cytokine that causes inflammation, was significantly elevated among e-cigarette users. In contrast, cytokines IL-4 and IL-1β were lower among e-cigarette users; because IL-4 tends to be reduced in people with gum disease and increases after treatment, it suggests that certain bacteria in the mouths of e-cigarette users are worsening inflammation.

The researchers concluded that the distinct oral microbiome of e-cigarette users elicits altered immune responses, which along with clinical markers for gum disease illustrate how vaping presents its own challenge to oral health.

“E-cigarette use is a relatively new human habit,” said Scott Thomas, study co-first author. “Unlike smoking, which has been studied extensively for decades, we know little about the health consequences of e-cigarette use and are just starting to understand how the unique microbiome promoted by vaping impacts oral health and disease.”

Source: New York University

Blood Test for Alzheimer’s Proves Highly Accurate

Plaques and neurons. Source: NIAH

A study in the journal Neurology has shown that a less expensive blood test to detect Alzheimer’s is highly accurate at early detection, providing further evidence that the test should be considered for routine screening and diagnosis. 

“Our study shows that the blood test provides a robust measure for detecting amyloid plaques associated with Alzheimer’s disease, even among patients not yet experiencing cognitive declines,” said senior author Professor Randall J. Bateman, MD.

“A blood test for Alzheimer’s provides a huge boost for Alzheimer’s research and diagnosis, drastically cutting the time and cost of identifying patients for clinical trials and spurring the development of new treatment options,” Prof Bateman said. “As new drugs become available, a blood test could determine who might benefit from treatment, including those at very early stages of the disease.”

Developed by Prof Bateman and colleagues, the blood test assesses whether amyloid plaques have begun accumulating in the brain based on the ratio of the levels of the amyloid beta proteins Aβ42 and Aβ40 in the blood.

The gold standard PET scan evaluation requires a radioactive brain scan, at an average cost of $5000–$8000 (R75 000–R120 000) per scan. Another common test, which analyses levels of amyloid-beta and tau protein in cerebrospinal fluid, costs about $1000 (R15 000) but requires a spinal tap process.

This study estimates that prescreening with a $500 (R7500) blood test could halve both the cost and the time it takes to enrol patients in clinical trials that use PET scans. Using only blood testing for screening could be done in under six months, a tenth or less of the cost. The test is currently only available in the US and Europe.

The current study shows that the blood test remains highly accurate, even when performed in different labs following different protocols, and in different cohorts across three continents.

Scientists didn’t know if small differences in sampling methods (such as anticoagulant use) could have a big impact on test accuracy because results are based on subtle shifts in amyloid beta protein levels in the blood. Subtle interfernece in these amyloid protein ratios could have triggered a false negative or positive result.

To confirm the test’s accuracy, researchers tested blood samples from current Alzheimer’s studies in the United States, Australia and Sweden, each of which uses different protocols for the processing of blood samples and related brain imaging.

Findings from this study confirmed that the Aβ42/Aβ40 blood test using a high-precision immunoprecipitation mass spectrometry technique developed at Washington University provides highly accurate and consistent results for both cognitively impaired and unimpaired individuals across all three studies.

When blood amyloid levels were combined with another major Alzheimer’s risk factor – the presence of the genetic variant APOE4 – the blood test accuracy was 88% compared to brain imaging and 93% when compared to spinal tap.

“These results suggest the test can be useful in identifying nonimpaired patients who may be at risk for future dementia, offering them the opportunity to get enrolled in clinical trials when early intervention has the potential to do the most good,” Prof Bateman said. “A negative test result also could help doctors rule out Alzheimer’s in patients whose impairments may be related to some other health issue, disease or medication.”

Source: Washington University School of Medicine