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17 July 2022
Welcome to the Medical Week in Review for the week ending 17 July 2022.
This week we focus on stories linked to genomics, be it identifying genes, editing genes, or managing inherited genetic conditions. It's a fascinating new world and we hope you enjoy the stories we've chosen to cover.
Quick Access Links
Matters COVID
Infectious Disease Update
Special Report on the State of Global Childhood Vaccination
Ageing and Age care
Focus on Paediatrics
Ophthalmology
Ethics, Legalities and Medical Practice
Tech Talks
The Healthcare Market in Numbers
Emerging and Novel Therapeutics
Medical Trivia
Matters COVID
This week, our rolling 7- day average was 355 cases, almost half that of last week’s 735 cases, and well below our benchmark. At the WHO briefing this week, South Africa was lauded for its declining caseload - hopefully, the figures are a true reflection of the situation and not just the result of declining testing rates.
Regarding our neighbours, for the seven-day rolling average Namibia recorded another dramatic drop with only 7 cases being recorded; Botswana’s caseload continues to decline, reporting 98 cases, a hundred fewer cases than last week. Kenya and Zimbabwe continued to record a decline in cases with 126 and 21 cases respectively, while Nigeria, with 70 cases, is the only country to record an increase in cases, however slight (20 additional cases from last week).
In COVID News: This week saw two blue chip companies reversing their COVID vaccine mandate policy.
Standard Bank and Old Mutual, who had introduced the mandate only a few months ago, have now decided to reverse the decision. The problem for both companies moving forward is that they have already terminated of several employees based on the mandate: Standard Bank terminated the employment of 40 employees, while Old Mutual terminated the employment of 89 of its staff. Now the thorny issue appears to be whether to reverse those terminations or not. While the reasons for reversing the mandate, in the case of Standard Bank at least, have been given as the current state of the pandemic no longer warrants such a policy, the real reason is in all likelihood the threat of legal action against both companies. There is a precedent for such legal action, with the CCMA awarding in favour of Kgomotso Tshatshu, an employee who worked at Baroque Medical, and whose employment was terminated when she refused to receive the vaccination. Whatever your feelings are concerning vaccine mandates, it will be difficult to see how companies such as Discovery, Sanlam and Metropolitan Life can continue to enforce their policy in light of this decision. You can read the full story in our source article from the Daily Maverick.2
COVID Research: A study published in JAMA this week looked at the differing long-term immune response to SARS-COV-2 between children and adults who have been mildly infected with the virus.
The study, which looked at 252 family clusters, found that while the “..anti–SARS-CoV-2 spike receptor-binding domain IgG,” 3 persisted for 12 months post-infection in all age groups, younger individuals, in particular children younger than three years, were found to have developed higher levels of antibodies, than the adults in the study. According to the researchers, the finding offers valuable insights into how future vaccination and prevention strategies could be tailored to different age groups.
Vaccine Update: Finally in our vaccines update, researchers may have found a more efficient and effective way of delivering the COVID-19 vaccine.
Published in Science last week, the researchers looked at ways of delivering the vaccine using inhaled mosaic nanoparticles. Using murine models, they demonstrated that the inhaled mosaic nanoparticles, not only protected the mice from the eight viruses included in the vaccine but more importantly from the "...SARS-CoV virus which resulted in the SARS outbreaks in 2002 and 2004.”5 One of the reasons given for its effectiveness is the delivery of the inhaled vaccine directly to the pulmonary system as compared to conventional IM delivery. A second important factor - particularly for developing countries where optimal storage of these vaccines is an issue - is that the inhaled format is stable at room temperature, and therefore requires no specific storage facilities. Let’s hope that this format will also reduce the resistance to the injectable format vaccine in the long term.
Links
1. COVID-19 Data Repository by the Center for Systems Science and Engineering ( CSSE) at Johns Hopkins University
2. SA companies begin scrapping their Covid vaccine mandates (Daily Maverick)
3. Long-term Immune Response to SARS-CoV-2 Infection Among Children and Adults After Mild Infection (JAMA)
4. Mosaic RBD nanoparticles protect against challenges by diverse sarbecoviruses in animal models (Science)
5. Scientists explore 'mosaic' nanoparticles, inhaled COVID-19 vaccine options (Fiercepharma.com)
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Infectious Disease Update
Breaking News: Shortly before publishing this newsletter, the WHO announced that the two cases of suspected Marburg in Ghana, have now been confirmed.
To date, only the original two deaths have been recorded, and the WHO together with authorities on the ground are monitoring over 90 contacts which include health workers and community members.(@WHO Press Briefing, 17.7.22)6
Global Outbreaks: Monkeypox Update
In a quick update on the Monkeypox outbreak, this week Anthony Fauci indicated that the US needs to take the outbreak more seriously and he believes the window for controlling the spread is swiftly closing if it hasn’t already closed. As of the 16th of July, there have been 12,556 confirmed cases in 68 countries. While most of the cases detected seem to be in communities where men have sex with men, Former US Food and Drug Administration (FDA) Commissioner Scott Gottlieb, believes the spread is much broader - we have probably only been looking at a very narrow testing policy. So far in South Africa, we still have only two confirmed cases.7, 8
Report Back: Wild Polio Outbreak
As always, we promise to keep you posted on stories we originally reported on, and this time it’s the turn of the wild polio cases identified in Malawi and Mozambique early this year. You may recall that the WHO and affected countries in the region embarked on a vaccination drive, aimed at children under 5 years old, to try and halt the spread of the virus. Mozambique has commenced its third round of vaccinations, with Malawi, Zambia and Tanzania soon implementing their third rounds. To date over 36 million vaccine doses have been administered in these four countries.
Zimbabwe will join the vaccine campaign in these third and fourth rounds. As this newsletter is being written, only the two original cases – one in Malawi and one in Mozambique have been recorded, and Africa has not lost its status as a polio-free continent.9
Infectious Diseases Update: This week the WHO raised its concerns regarding the increasing incidence of zoonotic infectious, at the weekly Africa Region briefing. According to Dr Matshidiso Moeti, the regional director for Africa at the WHO, zoonotic diseases make up one in every 3 incidences of infectious diseases on the continent, and we have seen a 63% increase in these diseases in recent years. Much of this spread is the result of rapid urbanisation which brings people into contact with a host of conditions and practices – such as the increasing reliance on bushmeat – thought to be driving these outbreaks. The WHO is working closely with the organisations such as the Organisation for Animal Health, to develop policies and practices aimed at improving surveillance, reporting and management across the continent. You can watch the full briefing below.
Links
6. Ghana declares first-ever outbreak of Marburg virus disease (WHO)
8. Monkeypox case identified in South Africa (NCID)
9. Southern Africa in fresh vaccination drive to halt wild polio (WHO)
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Special Report: Declining rate of childhood vaccinations pose a grave danger
In our special update this week, the alarm is being sounded over the significant global decline in childhood vaccination rates in the last three years, largely resulting from the pandemic.
The WHO this week released a statement in which it indicated that vaccination rates have dropped to a 30-year low, with many of the pre-pandemic gains now negated. It’s no surprise that developing countries are most affected by the decline.
The administration of the three doses of the DTP3 vaccine (diphtheria, tetanus and pertussis) is the global marker for immunization coverage, and the WHO reports that 18 million children globally did not receive a single dose of the vaccine during the pandemic. Most of these children live in developing countries, with India, Nigeria, Indonesia, Ethiopia and the Philippines recording the lowest vaccination numbers. Worryingly it was Mozambique, together with Myanmar where the greatest drop in vaccination rates was seen for the period 2019-2022.
Other vaccination rates that have dropped include the HPV vaccine, which dropped to only 15% of it's coverage globally. Equally concerning, are the low rates of measles vaccination, with first dose coverage dropping by 81% in 2021, leaving 24.7 million children unvaccinated; a further 14.7million did not receive their second dose required to complete the vaccination schedule. A further 6,7 million more children than in 2019 did not receive their third dose of polio vaccine which, given the current outbreak of Wild Polio virus in Africa, should be of great concern to everyone.
Reasons for the decline in vaccinations include increased misinformation; COVID-related issues such as supply chain disruptions, resource diversions and containment measures; limited access and availability, together with an increasing number of children who live in places where supply is challenging such as in conflict areas. There are some exceptions to the global decline, most notably Uganda, which continued to run its immunisation program hand-in-hand with its COVID efforts and achieved high levels of vaccination, and Pakistan, where strong governmental support has seen vaccination rates return to pre-pandemic levels, proving it is possible to stem the tide.
The world cannot afford to let diseases such as polio and measles take hold again and a monumental effort will now be required to reverse these trends. To this end, the WHO and UNICEF are working with organisations such as Gavi, the vaccine alliance and others, to deliver on the global immunisation Agenda 2023 (IA2030)
Specifically, the IA2030 partners are calling on governments and relevant actors to:
· Implement evidence-based, people-centred, and tailored strategies to build trust in vaccines and immunization, counter misinformation and increase vaccine uptake, particularly among vulnerable communities;
· Ensure current pandemic preparedness and response and the global health architecture strengthening efforts lead to investment in primary health care (PHC) services, with explicit support to strengthen and sustain essential immunization;
· Ensure political commitment from national governments and increase domestic resource allocation to strengthen and sustain immunization within PHC;
· Prioritize health information and disease surveillance systems strengthening to provide the data and monitoring needed for programmes to have maximum impact; and
· Leverage and increase investment in research to develop and improve new and existing vaccines and immunization services that can achieve community needs and deliver on IA2030 goals.
You can access more information from the resources listed below. 11. UNICEF Immunisation Data (July 2022)
12 . WHO Immunisation Data (July 2022)
13. Immunization Agenda 2030 ( Document Download)
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Age and Age Care
In keeping with our theme this month of promoting early diagnosis, we’re focusing on a new trial published in JAMA Cardiology which reviewed the association of pathogenic DNA variants linked to the development of cardiomyopathy and the consequent outcomes of cardiovascular disease.
According to our research, by 2031,7 million people are expected to live with cardiomyopathy.15 While most of those patients will be in the US, here at home with our high rates of obesity, diabetes and chronic alcohol abuse, indications are that our public healthcare burden from cardiovascular disease will be significant. While that’s good news for the Pharma companies such as Pfizer, Bristol Myers and Alnylam, who all scored FDA approval for their blockbuster cardiomyopathy drugs last year,16 it’s less good news for the rest of us.
The genetic variant for inherited cardiomyopathy is well documented, and if caught early treatment for these patients is clinically actionable, significantly reducing the mortality and morbidity rate in these cases. However, as with most inherited conditions, these patients frequently only present once the condition is established negating the early-diagnosis effect. Several clinicians have, on this basis, stated that genomic screening for the pathological variant should where possible become standard practice.
The study we looked at had enrolled 59 409 individuals from 2 large prospective cohort studies. The participants were aged between 40 and 60 years of age, 52% (31,374) were female, and, in both studies, were predominantly white, although other ethnicities were representative.
The researchers found that 0.7% of the total cohort had an actionable or likely pathogenic variant, that was associated with either cardiomyopathy (0.61% [59]) or hypertrophic cardiomyopathy (73% [364]).
The risk of death increased 1.5-1.7-fold in these patients. Furthermore, despite clinical care given, there was a 1.7-1.2-fold increased risk of heart failure and a 2.0-2.9-fold increase in atiral fibrillation in these patients.
The authors state that the success in identifying these patients through standard practice diagnostics, such as ECG, would be variable. Therefore adopting a 'genome-first approach' may significantly improve early diagnosis, and adoption of appropriate risk management strategies, thereby reducing mortality and morbidity associated with these conditions.
Links
14. Association of Pathogenic DNA Variants Predisposing to Cardiomyopathy With Cardiovascular Disease Outcomes and All-Cause Mortality (JAMA Cardiology)
15. Global epidemiology and future trends of heart failure (AMJ)
16. Pfizer, Alnylam and BMS: US poised for huge CV disease jump (Fiercepharma.com)
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Focus on Paediatrics
First up this week is an update on the global outbreak of severe hepatitis of unknown aetiology in children.
You may recall the first reported cases of the condition occurred in April this year. According to the latest WHO disease update, on the 8th of July 22, 1011 cases have been recorded across 35 countries, resulting in a total of 22 deaths. The largest burden of cases is in Europe, 27% of which have occurred in the UK and the Republic of Ireland, followed by the Americas, Western Pacific, South East Asia and finally the Eastern Mediterranean region. No cases have yet been recorded in Africa. While adenovirus and the SARS-COV-2 virus are still on the suspect list of causative agents, neither have been conclusively proven to have resulted in the outbreak.17 We’ll keep you posted as soon as we have another update.
In our clinical trial this week, a study published in the NEJM has looked at the neuroprotective effects of administering erythropoietin to infants with hypoxic-ischemic encephalopathy.18
Specifically, the researchers, Wu, Y.W. et al. wished to determine whether the administration of erythropoietin to these infants, lowered their risk of mortality, and, as a secondary outcome, lowered the risk of neurodevelopmental impairment. Neurodevelopmental impairment was determined as either cerebral palsy; a score of at least 1 on the Gross Motor Function Classification System (0 being none, 5 being the worst) or a score of 90 on the Bayley Scales of Infant and Toddler Development. (3rd edition)
500 infants were enrolled in the study: 257 received erythropoietin and 243 received placebo. The results were not encouraging. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group. Furthermore, the risk of serious adverse events per child was higher in the erythropoietin group than in the placebo. You can access a short summary of the trial on the link below.
.
Links
17. Severe acute hepatitis of unknown aetiology in children - Multi-country Report (WHO)
18. Trial of Erythropoietin for Hypoxic–Ischemic Encephalopathy in Newborns (NEJM)
Ophthalmology
This week, we take another look at an exciting study, first published in 2020, which reviewed the potential of engineering mesenchymal stem cells (MSC) to provide an effective topical treatment for ocular surface inflammatory disorders (OSIDs).
OSIDs are a group of ocular conditions resulting from various diseases in which inflammation plays a role. They include dry eye disease, meibomian gland dysfunction, allergic eye disease, and traumatic injury, including chemical burns. Patients who suffer from OSIDs often experience a reduction in their quality of life, due to the levels of pain and eye irritation they experience. In addition, these patients are at a higher risk for major complications including: “...infectious keratitis, corneal vascularization, opacity, visual impairment, corneal melt, and perforation.”19
Until now, only three treatments have been available OSIDs sufferers - topical lubricants, cortisone and cyclosporin - all of which either did not treat corneal irritation, or had serious side effects when used in the long term.
Regenerative medicine cell therapies, “..particularly mesenchymal stem cells (MSCs), have shown great promise for immunosuppression and disease amelioration across multiple tissues, including the cornea.”19 Several challenges remain before the treatment becomes standard practice, not least is the source of the MSCs. The study looked at several sources, including those derived from bone marrow, adipose tissue and corneal-derived sources, dental pulp and MSCs obtained from the umbilical cord, to determine the pros and cons of each. Corneal MSCs and MSCs from the umbilical cord appear to offer the best results. In particular umbilical cord MSCs showed “...higher levels of proliferation, more potent levels of immunomodulation, and lower levels of senescence.”19 Bone marrow MSC was found to be effective, but the downside was the process of obtaining the cells; MSCs from adipose tissue however, have been the source of several complications when used in patients with retinal disease and appear to be a non-starter.
While much more research needs to be done to link the inflammatory nature of OSCDs, the immunomodulatory impact of the MSCs and the development of an effective corneal scaffolding, ultimately combining these immunomodulatory cells with functional scaffolds, could offer OSID suffers their best hope yet of efficacious, topical cell treatment.
Links
19. Potential of mesenchymal stem cells as topical immunomodulatory cell therapies for ocular surface inflammatory disorders
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Ethics, Legalities and Medical Practice
In the interview, he prefaces the discussion by noting that ethical concerns regarding gene editing have been in play since the days of Dolly the Sheep. The difference now is what he terms the “democratisation” of gene editing offered by the CRISPR-Cas9 technology, a process which has made gene editing relatively cheap, and considerably easier to access. As a result, regulating the use of gene editing technologies is now incrementally more difficult, as can be evidenced by the increase in so-called ‘rogue’ clinics, that are offering purportedly regenerative stem-cell interventions, which are untested and unregulated.
Other concerns that have arisen on the back of the CRISPR technologies include how to ensure equitable distribution of the technology while simultaneously managing the intellectual property arising from its use.
According to Kato, if ungoverned the CRISPR technology could be the source of significant societal harm, stating that:
It is a fascinating interview on an important topic, and well worth a read.
Links
20. Kazuto Kato: the ethics of editing humanity (Downloadable Document) (WHO)
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Tech Talks The Laboratory test that can detect Neurodegenerative Disease
In an exciting development, this week USA clinical giant LabCorp announced that it would be rolling out a new blood test capable of detecting a number of neurodegenerative diseases, including Parkinson’s, dementia and ALS, in addition to being able to determine the neurological fall out from brain injuries such as concussion.
The test, conducted on a simple blood draw, determines the amount of a protein known as neurofilament light or Nfl. The protein is found in cerebral neurons and is released in higher amounts when there is neuronal stress, such as occurs in brain injury or in neurodegeneration.
The test can be used as a marker to determine deterioration in a condition, or to determine whether a treatment is working or not, making it a powerful tool in the arsenal of early detection and timeous management of degenerative diseases such as Parkinson’s Additionally our source article indicates the test could be used to determine whether an athlete is ready to return to sport after a concussion.
All of which makes this innovation our Tech Talk Star of the Month.
Links
21. Labcorp launches blood test for a wide range of neurodegenerative diseases and brain injuries (FierceBiotech.com)
Healthcare Market in Numbers
The Global Genome Editing Market is set to expand by double-digit markets within the next 5 years.
Our source for all things market-related, ihealthcareanalyst,com, published the report on the 29th of June this year in which it predicts that the market for gene editing will reach $5.7billion by 2027. This represents a compound annual growth rate of 10.2%, driven, the analysts say, by the rapid growth in “...synthetic biology, human gene therapy, disease modelling, drug discovery, and neuroscience.” 22
This revolution in genome editing was triggered by the advent of CRISPR, a technology that has accelerated the pace of breakthroughs and advances in several key disease areas including oncology and hereditary conditions such as sickle-cell anaemia. So significant has the revolution been that in 2017, CRISPR technologies accounted for 40% of the global market advances. It’s fair to say, based on CRISPR's capabilities, we’ve barely scratched the surface of where this technology can take us. Links
22. Global Genome Editing Market $5.7 Billion by 2027 (healthcareanalyst.com)
Emerging and Novel Therapeutics
This week for our emerging and novel therapeutics, we looked new treatment for plaque psoriasis, which was approved for use by the FDA in May of this year (2022).
According to the PI, Vtama, whose active ingredient is tapinarof, is a steroid-free, topical treatment option for mild to severe plaque psoriasis in adults. It falls under the Aryl hydrocarbon receptor (AhR) agonist therapy class. The developer of the drug is Dermavant Sciences, a company that specialises in developing novel therapies for dermatological applications.
According to our source, clinicaltrialsdata.com, the FDA assessed the drug based on two identical multi-centre, randomised, double-blind, vehicle-controlled, Phase 111 clinical trials - PSOARING-1 and PSOARING-2.
The results from the trial were significant. Together the two trials enrolled 1,025 participants, who were randomised in a 2:1 ratio of 1% Vtama cream or vehicle cream, once a day for 12 weeks.
In the Psoaring-1 trial, 36% of patients on the treatment achieved clear or almost clear skin when treated with the cream, compared with just 6% of patients treated with vehicle cream. In the PSOARING-2 study, 40% of the patients who were treated with Vtama achieved clear or almost clear skin versus 6% in vehicle cream.
These results bode well for the estimated 125 million people who suffer from psoriasis globally.
When it will arrive on our shores is unknown.
Links
23. Vtama (tapinarof) for the Treatment of Plaque Psoriasis (Clinicaltrialsarena.com)
24. Dermavant Corporate Website
25. Novel Drug Approvals for 2022 (FDA)
Medical Trivia
Zoonotic diseases are nothing new to the world and date back as long as there are written records of disease.
But did you know that 6 out of 10 infectious diseases in humans occur due to this method of spread? According to the WHO there has been an increase of over 63% in the occurrence of diseases caused by zoonotic pathogens, posing a significant health threat, not only to Africa but to the world. Ebola and other viral haemorrhagic fevers make up nearly 70% of the outbreaks, with conditions such as “...dengue fever, anthrax, plague, monkeypox and a range of other diseases making up the remaining 30%."26
So if you didn't know, now you do
Link
26. How many infectious diseases are zoonotic (CDC)
27. In Africa, 63% jump in diseases spread from animals to people seen in last decade (WHO)
And that is all for the Week in Review
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All that's left is to say, wherever you are, stay safe, stay sane, and join us next week where we review the week in medicine.
Episode 11 9th of July
This marks 2 weeks post masks -off and our COVID numbers are holding steady, even as the B1.5 variant dominates global cases, with a warning from authorities that the new variant may prove more virulent than previous versions.
Ghana reports its first case of Marburg virus, and in the same week the DRC declares its Ebola outbreak over. We review a study which asked are children in Africa, who have Sickle Cell Disease, are inherently protected against severe malarial disease?
In matters ageing, studies have shown that the use of viscosupplementation may not be all is ‘cracked’ up to be and new research has linked low muscle tone to executive cognitive decline.
We look at the latest FDA-approved novel drug and unpack the numbers involved in the global radiography market. Dr McQuoid-Mason gives his legal opinion on the Dr Tim de Maayer story, and finally, we ask – how long do you think antimicrobial resistance.
It's a packed weekly round-up – we hope you enjoy the read.
Access the Review
This has been a production on the Medical Education Network – delivering quality medical education and information to Southern Africa since 2008. All thoughts and comments on this podcast remain that of its creators. Every effort has been made to fact check the information contained here. Any errors or misstatements that may occur are unintentional.
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