Researchers in Belgium have discovered a new population of macrophages, important innate immune cells that populate the lungs after injury caused by respiratory viruses. These macrophages are instrumental in repairing the pulmonary alveoli. This groundbreaking discovery promises to revolutionise our understanding of the post-infectious immune response and opens the door to new regenerative therapies.
Respiratory viruses, typically causing mild illness, can have more serious consequences, as shown during the COVID pandemic, including severe cases requiring hospitalisation and the chronic sequelae of “long Covid.” These conditions often result in the destruction of large areas of the lungs, particularly the alveoli responsible for gas exchanges. Ineffective repair of these structures can lead to ARDS or a permanent reduction in the lungs’ ability to oxygenate blood, causing chronic fatigue and exercise intolerance.
While the role of macrophages during the acute phase of respiratory viral infections is well known, their function in the post-inflammatory period has been largely unexplored. This study by the GIGA Institute at the University of Liège reveals that atypical macrophages, characterised by specific markers and transiently recruited during the early recovery phase, play a beneficial role in regenerating pulmonary alveoli.
Led by Dr Coraline Radermecker and Prof. Thomas Marichal from the Immunophysiology Laboratory, the study was conducted by Dr Cecilia Ruscitti and benefited from the ULiège’s advanced technological platforms, including flow cytometry, fluorescence microscopy, and single-cell RNA sequencing. “Our findings provide a novel and crucial mechanism for alveolar repair by these atypical macrophages,” explains Coraline Radermecker. “We have detailed their characteristics, origin, location in the damaged lung, the signals they require to function, and their role in tissue regeneration, specifically acting on type 2 alveolar epithelial cells, the progenitors of alveolar cells.” The scientific community had overlooked these macrophages because they express a marker previously thought to be specific for another immune cell population, the neutrophils, and because they appear only briefly during the repair phase before disappearing.
“Our study highlights the reparative role of these macrophages, countering the prevailing idea that macrophages following respiratory viral infections are pathogenic,” adds Thomas Marichal. “By targeting the amplification of these macrophages or stimulating their repair functions, we could develop therapies to improve alveolar regeneration and reduce complications from serious respiratory infections and ARDS.”
To illustrate, consider the lungs as a garden damaged by a storm (viral infection). These newly discovered macrophages act like specialised gardeners who clear debris and plant new seeds, enabling the garden to regrow and regain its vitality.
In a new clinical trial, a drug commonly used to treat cystic fibrosis, dornase alfa, improved outcomes for patients with severe COVID pneumonia. The results, published in the journal eLife, also suggest that the drug could be used to treat other respiratory infections.
The study, found that the drug reduced hyper-inflammation in COVID pneumonia patients, which occurs when the body’s immune system reacts too strongly and can lead to tissue damage and death.
The next step will be to conduct larger clinical trials, with the ultimate goal of approving dornase alfa for wider use. As well as COVID, dornase alfa has the potential to treat other respiratory infections such as those caused by influenza or bacterial pneumonia, and even other lung diseases such as pulmonary fibrosis.
Since the beginning of the COVID pandemic, the proportion of SARS-CoV-2 infections that result in death has fallen, partly due to increased immunity from prior infection or vaccination, as well as improved treatments such as the steroid dexamethasone, which helps to tackle the hyper-inflammation that was a key factor in many COVID deaths. But this treatment isn’t suitable for some patients and is not always successful in severe cases.
In this study, researchers from UCL, UCLH and the Francis Crick Institute set out to assess whether dornase alfa could be used to improve outcomes for patients admitted to hospital with severe COVID pneumonia who required oxygen.
Out of a total of 39 participants, 30 were randomised to receive twice-daily treatment with nebulised dornase alfa in addition to best available care (BAC) which included dexamethasone, with nine patients randomised to BAC only.
Patients treated with dornase alfa had a 33% reduction in systemic inflammation on top of the reduction provided by dexamethasone, as measured by C-reactive protein (CRP) levels in the blood over seven days or until they were discharged from hospital.
Dr Venizelos Papayannopoulos, senior author of the study from the Francis Crick Institute, said: “Dexamethasone has been highly successful in treating patients with severe COVID-19 pneumonia and is now standard care in the UK. But it isn’t suitable for some patients, such as those with diabetes, those that do not require oxygen, and in very severe cases it may not be enough. Dornase alfa can be used to treat a wider variety of patients and gets right to the heart of the inflammatory response. Based on these results, we think it will be a valuable tool for tackling severe COVID-19 illness.”
Patients treated with dornase alfa were also more likely to need less oxygen and be discharged sooner compared to patients who received BAC. These additional benefits could help to free up beds and resources in the UK’s busy hospitals.
The next step will be to conduct larger clinical trials to ensure dornase alfa is safe and effective for treating severe COVID pneumonia. There is also potential for the drug to be trialled for other respiratory infections and conditions, such as acute exacerbations of pulmonary fibrosis, where inflammation of already scarred lung tissue affects how well oxygen can be absorbed.
Most tuberculosis (TB) tests still require a trip to the clinic. Now, new technology has made it possible to test people at home. This could be a big deal for South Africa, where much TB goes undiagnosed. We unpack the findings and implications of a recent study into such TB home testing.
One of the biggest challenges in combatting TB in South Africa is that many people who fall ill with the disease are diagnosed late, or not diagnosed at all.
The World Health Organization (WHO) estimates that 280 000 people fell ill with TB in the country in 2022. Of these, roughly 66 000 were not diagnosed, and accordingly also not treated. Apart from the damage to the health of the people who are not diagnosed and treated, this also has implications for the further spread of TB since untreated TB is often infectious TB – people become non-infectious within a few weeks of starting TB treatment.
Typically, people who fall ill with TB only get diagnosed once they turn up at clinics with TB symptoms – this is called passive case-finding. In recent years, there has been a growing recognition that passive case-finding alone is not good enough if we want to diagnose more people more quickly. As a result, many people in South Africa considered to be at high risk of TB are now offered TB tests whether or not they have symptoms – an approach called targeted universal testing. Screening for TB using new mobile X-ray technology has also been piloted in the country.
Now, in the latest such active case-finding innovation, researchers have been offering people TB tests in the comfort of their own homes.
Dr Andrew Medina-Marino, a senior investigator at the Desmond Tutu Health Foundation (DTHF), tells Spotlight no one in the world was testing for TB at home until they recently started doing so at the DTHF’s new research site in the Eastern Cape.
The testing is done using a molecular testing device, roughly the size of a two litre Coke bottle, called the GeneXpert Edge. The GeneXpert Edge is a portable version of the GeneXpert machines that have been used in labs across the country to diagnose TB for over a decade.
The GeneXpert Edge is a standardised testing device that detects TB DNA in sputum. (Photo: Nasief Manie/Spotlight)
One challenge with the device was that it needed to be plugged into a power outlet in a wall and not all homes in the area have power. “So what we did is, we hooked up a car-like battery to the device and we were able to take it into people’s homes,” says Medina-Marino.
‘Acceptable and feasible’
A study lead by Medina-Marino, and recently published in Open Forum Infectious Diseases, set out to determine the acceptability and feasibility of in-home testing of household contacts of people with TB.
The study was conducted among 84 households in Duncan Village, a township in the Buffalo City Metropolitan Municipality in the Eastern Cape. The Metro had an estimated TB incidence of 876 cases per 100 000 population in 2019, according to the National Institute for Communicable Diseases. This number is much higher than the latest WHO estimate of 468 per 100 000 for South Africa as a whole.
From July 2018 to May 2019, people diagnosed with pulmonary TB were recruited from six government health clinics in the area. They were asked for permission to visit their homes to screen their household contacts for TB. Household contacts were verbally assessed for signs or symptoms of TB, including night sweats, weight loss, persistent cough and a fever.
Households where people had any signs or symptoms of TB were randomised to either be referred to a local clinic for TB testing or tested immediately in their home. Of the eighty-four randomised households, 51 household contacts were offered in-home testing. Everyone accepted the offer for in-home testing.
For the test with the GeneXpert Edge, Medina-Marino says household contacts had to produce a sputum sample. About 47% (24/51) were able to produce sputum. This was then mixed with a reagent containing the required components for a polymerase chain reaction test. This solution was then loaded into a disposable cartridge/test module and inserted into the Edge device. Results were available in about 90 minutes. Anyone who received a positive test result in their home were immediately referred to a clinic for TB treatment.
Regarding the 47 household contacts referred for testing at the clinic, only 15% (7 people) presented for clinic-based TB evaluation, 6 were tested, and 4 out of 6 returned for their results.
Ultimately, the study found that in-home testing of household contacts for TB was acceptable and feasible.
“It’s feasible. If you compare the rate of uptake of treatment versus the rate of uptake for testing, it looks like it’s performing much better when you do home based testing versus referral for testing at the clinic,” says Medina-Marino.
Risk of stigma?
Similar to when HIV home-based testing studies were carried out, Medina-Marino says prior to their study, community members expressed concerns about stigmatising houses that were visited. “[A] lot of people were saying: ‘If you go to people’s houses, you’re going to stigmatise the household.’”
But what they actually found was that people didn’t feel stigmatised. Household contacts of people with TB felt that coming to the house to test people brought a sense of security in the home. He adds that it was easy for people to believe the results because everything was done in front of them.
In instances where people didn’t have TB, Medina-Marino says household contacts were comforted that they didn’t have to be scared of the person tested. In instances where people did have TB, he says the attitude of household contacts was supportive to start treatment.
How the test compares to other tests
Apart from testing for TB, the GeneXpert Edge can also detect whether someone’s TB is resistant to rifampicin. This is one of the medicines in the standard four-drug combination used to treat TB.
Unlike the latest lab-base GeneXpert tests, the GeneXpert Edge does not detect resistance to any TB medicines other than rifampacin. “It is hard to fit the probes needed to detect other forms of resistance into the cartridge,” says study co-author Professor Grant Theron, head of the Clinical Mycobacteriology and Epidemiology Research group at Stellenbosch University’s Molecular Biology and Human Genetics Unit.
Theron notes that the sensitivity and specificity of GeneXpert Edge is similar to that of lab-based GeneXpert machines if the tests are done on specimens from the same type of patient and the same test cartridge. (High sensitivity means the likelihood of false negatives is low wile high specificity means the likelihood of false positives is low.)
Performance may however differ because of differences between people who test at home and people who test at the clinic. Theron explains that in their study they tested people who did not yet feel sick enough to go to get tested at the clinic. People who are sicker, and who are accordingly more likely to go to the clinic, are likely to have more pathogen in their sputum samples and be easier to diagnose.
‘A breakthrough for TB’
Home-based tests is a significant breakthrough in TB because of its crucial role in detecting cases early and enabling timely tracing and testing of household contacts, says Dr Ntokozo Mzimela, a lecturer in integrated pathology in the Faculty of Health Sciences at Nelson Mandela University.
She tells Spotlight it also offers several advantages over clinic-based tests. “They are highly accessible, facilitate mass testing, reduce the risk of disease transmission, and address patient reluctance by allowing testing in the comfort and privacy of one’s home.”
Mzimela adds the GeneXpert Edge and portable X-ray screening serve complementary roles in TB diagnosis. “While the X-ray reveals lung abnormalities, the Edge confirms the presence of TB bacteria. Both tools are essential and should be used in conjunction to provide comprehensive diagnostic insights and ensure accurate and timely treatment for patients,” she says.
Professor Keertan Dheda agrees that home-based testing could link up neatly with portable X-ray, but adds it is still too early to determine where home-based TB testing will fit into the country’s TB testing programme. Dheda heads up the Division of Pulmonology at Groote Schuur Hospital and the University of Cape Town.
“We don’t yet know whether testing everyone is the right approach or whether reflex testing based on chest x-ray abnormalities is the right approach,” Dheda says. “Now that feasibility has been established, it means that more studies can be undertaken, and operational research can be commenced.”
Further studies are already underway, Medina-Marino tells Spotlight.
He says the study in Duncan Village found that about 60% of household contacts who had TB symptoms could not cough up a sputum sample. His team therefore decided to combine in-home testing with an oral swab.
“So in the study that we’re doing now in households, we found an additional 12 people who cannot produce sputum but on their swab test, they showed a positive swab result. Tongue swabs increase yield of case finding among those unable to produce sputum,” he says.
Scanning electron microscope image of bacteria responsible for Haemophilus influenzae type B infections. Photographer Alain Grillet. Copyright Sanofi Pasteur
Researchers from The University of Queensland have identified how a common bacterium is able to manipulate the human immune system during respiratory infections and cause persistent illness.
“These bacteria are especially damaging to vulnerable groups, such as those with cystic fibrosis, asthma, the elderly, and Indigenous communities,” Professor Kappler said.
“In some conditions, such as asthma and chronic obstructive pulmonary disease, they can drastically worsen symptoms.
“Our research shows the bacterium persists by essentially turning off the body’s immune responses, inducing a state of tolerance in human respiratory tissues.”
Professor Kappler said the bacterium had a unique ability to ‘talk’ to and deactivate the immune system, convincing it there was no threat.
The researchers prepared human nasal tissue in the lab, growing it to resemble the surfaces of the human respiratory tract, then monitored gene expression changes over a 14-day ‘infection’.
They found limited production of inflammation molecules over time, which normally would be produced within hours of bacteria infecting human cells.
“We then applied both live and dead Haemophilus influenzae, showing the dead bacteria caused a fast production of the inflammation makers, while live bacteria prevented this,” Professor Kappler said.
“This proved that the bacteria can actively reduce the human immune response.”
Co-author and paediatric respiratory physician Emeritus Professor Peter Sly from UQ’s Faculty of Medicine, said the results show how Haemophilus influenzae can cause chronic infections, essentially living in the cells that form the surface of the respiratory tract.
“This is a rare behaviour that many other bacteria don’t possess,” Emeritus Professor Sly said.
“If local immunity drops, for example during a viral infection, the bacteria may be able to ‘take over’ and cause a more severe infection.”
The findings will lead to future work towards new treatments to prevent these infections by helping the immune system to recognise and kill these bacteria.
“We’ll look at ways of developing treatments that enhance the immune system’s ability to detect and eliminate the pathogen before it can cause further damage,” Professor Kappler said.
Besides preventing illness and death, tuberculosis prevention therapy is estimated to be highly cost effective. Yet, uptake of the medication is not what it could be in South Africa. Tiyese Jeranji asks how much has changed since the Department of Health last year decided to make TB prevention therapy much more widely available.
Many people who have the TB bug in their lungs are not ill with TB disease. Having the bug in your body, does mean however that you are at risk of falling ill, should the TB bacteria get the overhand in its battle with your immune system.
Fortunately, we have medications that can kill TB bacteria before one falls ill. A recent World Health Organization (WHO) investment case, suggests such TB prevention therapy, commonly called TPT, reduces the risk of falling ill with TB in those exposed to the bug by 60% to 90% compared to people who do not get the treatment.
In South Africa, TPT has been available in the public sector for years, but until the publication of new government guidelines last year, only kids aged five or younger and people living with HIV could get the medication. Under the new guidelines, everyone who has had close contact with someone with TB should be offered a TB test and if they test negative be offered TPT – if they test positive they should be offered TB treatment. These changes dramatically expanded the number of people in South Africa who are eligible for TPT.
The antibiotics used for TPT has also changed in recent years. For many years, the only option was a medication called isoniazid taken for six or more months. We now also have two three-month options – isoniazid and rifapentine given once weekly and rifampicin and isoniazid given daily. These shorter duration treatment courses should help more people complete the treatment.
Down and up?
Dr Norbert Ndjeka, Chief Director of TB Control and Management at the National Department of Health, tells Spotlight that in recent years, South Africa has seen a steady decline in the number of people initiated on TPT.
The decline has been substantial. In people living with HIV, initiation on TPT dropped from 454 000 in 2018 to around 241 000 in 2023. In children aged five and younger who have had contact with someone with TB, it fell from 25 357 in 2018 to 15 775 in 2023.
TPT enrolments per province for 2023
Province
People living with HIV
Contacts < 5 Years
Contacts > 5 Years
Eastern Cape
34 623
2 551
4 771
Free State
14 535
562
1 027
Gauteng
67 333
1 368
4 241
KwaZulu-Natal
62 362
3 168
8 519
Limpopo
15 871
391
452
Mpumalanga
25 618
669
2 006
Northern Cape
3 178
855
1 595
North West
9 433
596
1 425
Western Cape
8 532
5 615
1 278
South Africa
241 485
15 775
25 314
*Typically, provinces with higher numbers of people diagnosed with TB or those with high numbers of people living with HIV will report higher TPT initiations.
There are two significant reasons for this decline, according to Ndjeka. Firstly, declining TB incidence, and secondly, declining HIV incidence.
“With fewer people diagnosed with TB disease, fewer contacts will need TPT, and with fewer people being diagnosed with HIV, fewer people will initiate TPT regardless of TB exposure,” he says.
WHO figures have shown a significant downward trend in the estimated TB cases per year in South Africa and according to Thembisa, the leading mathematical model of HIV in South Africa, the number of people newly starting HIV treatment has dropped from a peak of over 700 000 in 2011, to well under 300 000 in 2023.
But the recent downward trend in people taking TPT may be coming to an end. “We believe that the implementation of the new guidelines within the current strategic framework will lead to increases in TPT enrolment,” says Ndjeka.
In line with the new guidelines, there are also changes to what TPT data is being collected. “For example, we never used to report on TPT provision to contacts 5 years and older, but now we do and in 2023 at least 25 314 TB contacts 5 years and older were initiated on TPT,” he says.
20% increase expected in 2024
Based on the data reported for January and February of this year, Ndjeka expects that overall TPT initiations will increase by at least 20% in 2024 compared to 2023. Moreover, as documented in the National Strategic Plan for HIV, TB and STIs 2023-2028, there is a plan to have a steady annual increase in TPT enrolments leading up to 2028.
Ndjeka says based on the NSP TPT targets, South Africa is exceeding TPT targets for people living with HIV, but reaching less than 25% of targets for TB contacts. He points out that performance varies by province, but that all provinces have a long way to go in terms of reaching TB contacts.
‘Cost saving over time’
“The aim of offering TPT is to reduce the TB incidence,” Ndjeka says. “So, if everyone eligible is offered TPT there will obviously be increased costs initially but cost saving over time. This looks at cost of treating people with TB, lives saved/ deaths prevented as well as costs to patients.”
For South Africa, he says, it is estimated that we can reduce the number of people with TB by 138 000 by 2050 at an estimated cost of R23 226.90 per TB episode prevented.
Ndjeka says it costs the health department an estimated at R1 498.51 to treat one person with drug-susceptible TB for 6 months and R16 612.82 to treat one person with the standard drug-resistant TB treatment for 6 months. “These costs are for medications alone, which can also go beyond R70 000 depending on the patient and the type of resistant TB. Moreover, when factoring in clinical consultations, hospitalisations, and costs to patients the costs go up considerably,” he says.
The cost of providing TPT also depends on the regimen. One person on TPT can cost as little as R608.77 for a course of three months of isoniazid and rifapentine given once weekly, and up to R1 358.02 for 12 months of isoniazid. “TPT also has much lower associated costs for example there is no hospitalisation, fewer clinic visits and consultations,” Ndjeka says.
“By preventing TB, the cost of TB treatment is avoided along with the costs of treating some of the acute and chronic conditions that someone with TB may experience even after being cured of TB. These include chronic obstructive pulmonary disease, bronchiectasis and pneumonia,” says Alison Best, communication manager at Cape Town-based NGO TB HIV Care.
“For children under five in particular, who are at increased risk of disseminated TB like TB meningitis, the cost of not preventing TB could be death or severe lifelong disability,” she says, adding that preventing TB in a single individual also prevents the costs associated with any onwards transmission of TB from that individual to others.
Questions over implementation
Expanded TPT eligibility has been widely welcomed, but questions have been raised over how well the new guidelines are being implemented.
Best says government austerity measures have made implementing new initiatives in the healthcare setting challenging.
“There is not much political will to implement the guidelines (to expand eligibility for TPT) at provincial and district levels and this has translated into the slow release of circulars, delays in training health workers, poor knowledge of the policy and its low prioritisation,” she says.
Ingrid Schoeman, Director of Advocacy and Strategy at TB Proof (a local advocacy group), says often when a national policy is released, there are delays at provincial-level in releasing circulars to enable health worker training.
“This results in these services not being available at district-level. In the Western Cape, civil society organisations, the [provincial] Department of Health, City of Cape Town and implementing partners are now all working together to support health worker training, and implementing community-led awareness campaigns so that all close TB contacts know they are eligible for TPT,” she says.
Best adds that tracking the data to show how many people are starting and completing TPT tends to be difficult. She notes there are many gaps in capturing the information. This includes, at times, the limited recording of information in patient folders by clinicians and suboptimal inputting of data by data capturers.
Ndjeka says the national department of health has been conducting training on the new guidelines with provincial and district TB and HIV programme managers, district support partners and other trainers.
“They are then responsible for training health care workers. The antiretroviral therapy guideline training also includes TPT. Webinars on the knowledge hub (an online training platform) have also conducted,” he says.
However, Ndjeka conceded that there is a lack of awareness about the value of TPT. “Additionally,” he says, “there is reluctance from clinicians to provide TPT. This result in poor demand for TPT. Treatment adherence is another problem especially for people on the long regimen (12 months)”.
Plans to address these challenges, among other things, include marketing TPT as treatment for TB infection rather than prevention, targeted communication strategies, community mobilisation, and ongoing training and mentoring of healthcare workers, says Ndjeka.
For children seeking care at a California urban paediatric health centre, extreme heat events were associated with increased asthma hospital visits, according to research published at the ATS 2024 International Conference.
“We found that both daily high heat events and extreme temperatures that lasted several days increased the risk of asthma hospital visits,” said corresponding author Morgan Ye, MPH, research data analyst, Division of Pulmonary and Critical Care Medicine, University of California, San Francisco School of Medicine. “Understanding the impacts of climate-sensitive events such as extreme heat on a vulnerable population is the key to reducing the burden of disease due to climate change.”
Ms Ye and colleagues looked at 2017-2020 electronic health records from the UCSF Benioff Children’s Hospital Oakland, which included data on asthma hospital visits by patients of the hospital, some of whom are from Benioff Oakland’s Federally Qualified Health Center, and demographics including patients’ zip codes. They used data from the PRISM Climate Group of Oregon State University to determine the timing of daily maximum (daytime heat waves) and minimum (nighttime heat waves) for each zip code. The researchers restricted their analyses to the region’s warm season (June to September). To evaluate the potential range of effects of different heat wave measurements, they used 18 different heat wave definitions, including the 99th, 97.5th and 95th percentile of the total distribution of the study period for one, two or three days.
They designed the study in a way that allowed them to determine the association between each heat wave definition and a hospital visit. They repeated the analysis for Bay Area and Central California zip codes.
The team discovered that daytime heat waves were significantly associated with 19% higher odds of children’s asthma hospital visits, and longer duration of heat waves doubled the odds of hospital visits. They did not observe any associations for night-time heat waves.
According to Ye, “We continue to see global temperatures rise due to human-generated climate change, and we can expect a rise in health-related issues as we observe longer, more frequent and severe heat waves. Our research suggests that higher temperatures and increased duration of these high heat days are associated with increased risk of hospital visits due to asthma. Children and families with lower adaptation capacity will experience most of the burden. Therefore, it is important to obtain a better understanding of these heat-associated health risks and susceptible populations for future surveillance and targeted interventions.”
The authors note that past research has suggested positive associations between extreme heat and asthma, but findings regarding hospitalisations and emergency room visits have been conflicting. Additionally, many other studies have focused on respiratory hospitalizations and not hospitalizations for asthma, specifically, and have not included or had a focus on children. This study is also unique because it investigated the effect of daily high temperatures but also the effects of persistent extreme temperatures.
The San Francisco Bay Area and California overall are unique areas of interest because the state is considered a coastal region with less prevalence of cooling units, such as air conditioners. While temperatures may not reach the extremes experienced in other parts of the country, this study demonstrates that even milder extreme heat temperatures may significantly impact health. These effects are more pronounced in climate-susceptible populations, including children and those who are medically vulnerable, such as those served by the urban paediatric health centre in this study. The authors hope these study results will lead to more equitable health outcomes and reduce racial/ethnic disparities observed in climate-sensitive events.
“These results can be used to inform targeted actions and resources for vulnerable children and alleviate health-related stress during heat waves,” they conclude.
Creative artwork featuring colourised 3D prints of influenza virus (surface glycoprotein hemagglutinin is blue and neuraminidase is orange; the viral membrane is a darker orange). Note: Not to scale. Credit: NIAID
By Elri Voigt for Spotlight
COVID-19-related factors resulted in several years of lower-than-normal rates of the flu, but experts say that is now something of the past. As this year’s flu season gets under way, Elri Voigt asks several local experts what their expectations are, which flu vaccines are available this year, and whether we should be concerned about new strains of bird flu.
While most people who get the flu experience only mild to moderate symptoms, some can get severe symptoms and even die, especially the very young and the old. As Spotlight previously reported, the influenza virus causes around 11 000 deaths per year in South Africa, with around 40 000 people hospitalised.
Dr Sibongile Walaza, a medical epidemiologist and the Head of Epidemiology at the Centre for Respiratory Disease and Meningitis at the National Institute for Communicable Diseases (NICD), says that it is difficult to predict what a flu season will look like beforehand.
Nicole Jennings, spokesperson for the South African Pharmaceutical company Pharma Dynamics, agrees. “Influenza is a global disease and the spread of the virus in other parts of the world can influence the trajectory of flu seasons in different regions. For now, it’s too early to make any predictions,” she says.
It is difficult to predict the trajectory of flu seasons ahead of time, Jennings says, because of a “complex interplay” of factors, including the fact that influenza viruses are constantly mutating. This makes it difficult to accurately predict which strains of the influenza virus will dominate and how they will behave.
“The level of immunity in the population can also vary from year to year due to factors, such as vaccination rates, previous exposure to similar strains and so forth,” she adds. “However, surveillance efforts, modelling and ongoing research conducted by the NICD can help the public to prepare for the cold and flu season as best possible.”
NICD guidelines published in April 2023 already stated that since the COVID-19 pandemic, there have been some changes in the timing of flu transmission.
The transmission reduction strategies – like masking and social distancing – during the pandemic had an impact on the rates of flu transmission and the duration of the flu season between 2020 to 2022, according to Dr Jocelyn Moyes, a medical epidemiologist at the Centre for Respiratory Disease and Meningitis at the NICD.
Back to normal?
Although the numbers were still much lower, it appears that the winter flu season’s peak had started to return to levels seen pre-COVID-19 in 2022 and 2023, Walaza confirms.
“In 2023, the flu season was a little bit longer than we’d seen before [COVID-19], but it started on time. So, in terms of the timing, it was similar to what we would see before COVID-19,” she says.
When exactly the winter flu season starts each year varies, Walaza says, but on average it can start anytime from the third week of April and can circulate until August. It has been known to go on longer though.
At the time of the interview, the NICD had only detected sporadic cases of flu but had not yet seen the sustained uptick in transmission which usually signals the start of the flu season. The latest surveillance data published by the NICD indicate that 108 cases of influenza had been detected so far this year. The real number of flu cases will be much higher since most cases of flu are not diagnosed.
This year’s vaccines
Walaza explains that the flu vaccine is updated each year based on the World Health Organization’s (WHO) recommendations. This is to ensure it provides protection against evolving influenza viruses seen in global surveillance programmes.
Photo by National Cancer Institute
Flu shots used in South Africa are inactivated influenza vaccines. This means they do not contain live virus and cannot cause flu.
In the public healthcare sector, the government this year procured the trivalent vaccine which protects against three strains of the influenza virus – two influenza A strains (H1N1pdm 2009 and H3N2) and one influenza B strain (known as the B/Victoria), Walaza says. These jabs should be in public health clinics by the first week of May.
In the private healthcare sector, she says a trivalent and a quadrivalent vaccine are available. The quadrivalent shot includes protection against a second influenza B strain (B/Yamagata), but that strain has not been seen circulating in a few years. These flu shots are already available in the private healthcare sector.
The level of protection provided by the flu shot varies and generally it ranges in effectiveness against infection from about 30% to 60%, according to Walaza, but importantly it protects against severe illness.
How effective this year’s flu shot will be depends on which influenza strain or strains circulate in the country. “The hope is that if an individual gets infected by any of those strains [in the vaccine], then that individual is protected or has some level of protection [against these strains] and will have some protection against severe illness” she says.
However, she adds, it’s difficult to predict how effective this year’s flu shot will be against preventing someone from getting the flu or experiencing symptoms of the flu. This is because there is always the chance that the strains which do circulate this season are different from the ones in the vaccine or have mutated so the shot becomes less effective.
Should we worry about bird flu?
At the start of April, the WHO reported that one case of avian influenza A (H5N1), one of the avian/bird flu viruses, had been detected in a person in the United States after they had come into contact with a cow who was presumed to be infected. This was the second human case of influenza A (H5N1) detected in that country, and the first case of a person being infected with this strain after coming into contact with a non-avian species.
So far, the risk to the general public is low, according to the WHO.
“Since the virus [avian influenza A (H5N1)] has not acquired mutations that facilitate transmission among humans and based on available information the WHO assesses the public health risk to the general population posed by this virus to be low and for occupationally exposed persons, the risk of infection is considered low-to-moderate,” the WHO statement said.
There are many subtypes of influenza A viruses, Moyes tells Spotlight, and avian influenzas are similar to human influenza A viruses. And so, she explains, there is always a possibility that these viruses mutate, enabling them to infect humans, or more importantly develop the ability to transmit effectively from one person to another. This could potentially cause a pandemic.
She tells Spotlight that over the last decade sporadic cases of human avian influenza have been described related to global outbreaks in birds. These cases have all been in people who have had very close contact – usually during the culling process – with sick birds. She advises that people involved in the management of avian influenza outbreaks take precautions, such as using appropriate personal protective equipment to prevent infection.
When asked whether people in South Africa need to be concerned about a potential bird flu outbreak, Walaza says so far, no cases of bird flu infection in humans – even during the recent widespread outbreaks in birds – have been identified in the country. But it is something that the NICD is aware of and surveillance for human cases during outbreaks of bird flu in the country is being conducted.
“What’s important though to note is that even when cases have been detected [in other countries] the risk of person-to-person transmission is extremely low,” she adds.
Launch of Cough Watch SA
Walaza tells Spotlight that most of the data gathered by the NICD on influenza is from surveillance in healthcare facilities, which means that not all cases of influenza are necessarily identified.
To gather additional data, the NICD is in the process of rolling out an additional digital surveillance system to detect influenza cases, called Cough Watch SA. This online web application allows the public to report influenza symptoms.
People who sign up are asked to provide basic demographic data like age and postal code. Participants will then be sent a weekly prompt asking if they’ve had any flu symptoms. If they have had symptoms, according to Walaza, then they will be asked to provide more information. This data will then be linked to the NICD database where it will be compared to other surveillance data to see if the platform could serve as an early warning system for a flu outbreak.
Cough Watch SA will be launched in the week of 7 May, says Moyes, who urged the public to help keep an eye on flu by signing up.
The most common type of lung fibrosis is idiopathic – of unknown cause. Researchers are urgently trying to find ways to prevent or slow idiopathic pulmonary fibrosis (IPF) and related lung conditions, which can cause worsening shortness of breath, dry cough, and extreme fatigue. Average survival following diagnosis of IPF is just three to five years, and the disease has no cure.
A recent U-M study from a team led by Sean Fortier, MD and Marc Peters-Golden, MD at University of Michigan Medical School uncovers a pathway used during normal wound healing that has the potential to reverse IPF. They published their research in the Journal of Clinical Investigation.
Using a mouse model, they simulated IPF by administering bleomycin, a chemotherapy agent that causes cell injury and confirmed that the resulting lung scarring resolved itself over the span of about six weeks.
Because of this, “studying fibrosis is kind of tough,” said Fortier. “If we’re going to give experimental drugs to try and resolve fibrosis, we have to do it before it resolves on its own.
Otherwise, we will not be able to tell if the resolution was the action of the drug or natural repair mechanisms of the body.”
However, he said, “there’s actually a lot to learn about how the mouse gets better on its own. If we can learn the molecular mechanisms by which this occurs, we may uncover new targets for IPF.”
The process by which lung injury either leads to healing or fibrosis relies in part on what happens to fibroblasts – cells which forms connective tissue.
During injury or illness, fibroblasts are activated, becoming myofibroblasts that form scar tissue by secreting collagen. When the job is done, these fibroblasts must be deactivated, or de-differentiated, to go back to their quiet state or undergo programmed cell death and be cleared.
“This is the major distinction between normal wound healing and fibrosis – the persistence of activated myofibroblasts,” explained Fortier. That deactivation is controlled by molecular brakes. The study examined one of these brakes, called MKP1 – which the team found was expressed at lower levels in fibroblasts from patients with IPF.
By genetically eliminating MKP1 in fibroblasts of mice after establishing lung injury, the team saw that fibrosis continued uncontrolled.
“Instead of at day 63, seeing that nice resolution, you still see fibrosis,” said Fortier.
“We argued by contradiction: when you knock out this brake, fibrosis that would otherwise naturally disappear, persists and therefore MKP1 is necessary for spontaneous resolution of fibrosis.”
They performed several additional studies using CRISPR techniques to demonstrate how MKP1 applies the brakes, mainly by deactivating the enzyme p38α, which is implicated in a cell’s reaction to stress.
Furthermore, they demonstrated that neither of the two current FDA approved drugs for lung fibrosis, pirfenidone and nintedanib, are able to turn off myofibroblasts.
“That’s totally in keeping with the fact that they do slow the progression, but they don’t halt or reverse disease,” said Fortier.
Fortier hopes the discovery that this pathway reverses fibrosis leads to exploration of additional brakes on fibrosis.
“So much work on fibrosis has focused on how we can prevent it, but when a patient presents to my clinic with a dry cough, shortness of breath, and low oxygen as a result of underlying IPF, the scarring is already present. Of course, we’d love a way to prevent the scarring from getting worse, but the Holy Grail is to reverse it.”
Use of antibiotics provided no measurable impact on the severity or duration of coughs, even if a bacterial infection was present, finds a large prospective study of people seeking care for lower-respiratory tract infections. The study by researchers at Georgetown University Medical Center and colleagues appeared in the Journal of General Internal Medicine.
“Upper-respiratory tract infections usually include the common cold, sore throat, sinus infections and ear infections and have well established ways to determine if antibiotics should be given,” says the study’s lead author, Dan Merenstein, MD, professor of family medicine. “Lower-respiratory tract infections tend to have the potential to be more dangerous, since about 3% to 5% of these patients have pneumonia. But not everyone has easy access at an initial visit to an X-ray, which may be the reason clinicians still give antibiotics without any other evidence of a bacterial infection. Plus, patients have come to expect antibiotics for a cough, even if it doesn’t help. Basic symptom-relieving medications plus time brings a resolution to most people’s infections.”
The antibiotics prescribed in this study for lower-tract infections were all appropriate, commonly used antibiotics to treat bacterial infections. But the researchers’ analysis showed that of the 29% of people given an antibiotic during their initial medical visit, there was no effect on the duration or overall severity of cough compared to those who didn’t receive an antibiotic.
“Physicians know, but probably overestimate, the percentage of lower-tract infections that are bacterial; they also likely overestimate their ability to distinguish viral from bacterial infections,” says Mark H. Ebell, MD, MS, a study author and professor in the College of Public Health at the University of Georgia. “In our analysis, 29% of people were prescribed an antibiotic, while only 7% were given an antiviral. But most patients do not need antivirals, as there exist only two respiratory viruses where we have medications to treat them: influenza and SARS-CoV-2. There are none for all of the other viruses.”
To determine if there was an actual bacterial or viral infection present, beyond the self-reported symptoms of a cough, the investigators confirmed the presence of pathogens with advanced lab tests to look for microbiologic results classified as only bacteria, only viruses, both virus and bacteria, or no organism detected. Very importantly, for those with a confirmed bacterial infection, the length of time until illness resolution was the same for those receiving an antibiotic versus those not receiving one –about 17 days.
Overuse of antibiotics can result in dizziness, nausea, diarrhoea and rash, along with about a 4% chance of serious adverse effects including anaphylaxis, which is a severe, life-threatening allergic reaction; Stevens-Johnson syndrome, a rare, serious disorder of the skin and mucous membranes; and Clostridioides difficile-associated diarrhoea. The World Health Organization considers antibiotic resistance to be a major an emerging threat.
“We know that cough can be an indicator of a serious problem. It is the most common illness-related reason for an ambulatory care visit, accounting for nearly 3 million outpatient visits and more than 4 million emergency department visits annually,” says Merenstein. “Serious cough symptoms and how to treat them properly needs to be studied more, perhaps in a randomized clinical trial, as this study was observational and there haven’t been any randomized trials looking at this issue since about 2012.”
A cystic fibrosis drug targeting the basic defect that causes the condition has been shown to be safe and effective in newborns aged four weeks and above, new research involving RCSI University of Medicine and Health Sciences and Children’s Health Ireland has found.
The finding is described as a “huge moment” for cystic fibrosis by one of the lead researchers. The study included the first baby in the world with cystic fibrosis to be diagnosed from birth and enrolled directly onto a trial of this sort.
The drug, ivacaftor (Kalydeko), is the first drug designed to treat the basic defect in cystic fibrosis. It was originally approved for adults, then sequentially over several years for older and younger children. Currently, it is approved for babies aged four months and older, however, this new research suggests that it is safe and effective for babies as young as four weeks of age.
Cystic fibrosis experts predict that the earlier treatments can begin, the more likely that progression of the condition can be slowed down or halted in children, and this is the focus of several international research studies led by RCSI and Children’s Health Ireland. The findings of this study could pave the way for eligible newborns to start treatment on the medicine at the time of diagnosis (typically at newborn screening) rather than having to wait until they are four months old.
“This is a huge moment in cystic fibrosis,” said Paul McNally, Associate Professor of Paediatrics at RCSI and Consultant in Respiratory Medicine at CHI. McNally is one of the authors of the new study which was published in the Journal of Cystic Fibrosis.
“Over the years ivacaftor, or Kalydeko, has been put through clinical trials in younger and younger children. Now, through this study, it has been shown to be safe and effective all the way down to four weeks of age,” he said.
“This is an important development because almost all children are diagnosed through newborn screening at around this time. The availability of a treatment that targets the underlying cause of the disease in newborns and can be started immediately at diagnosis will provide a huge sense of reassurance and hope for families.”
Cystic fibrosis is an inherited disease that mainly affects the lungs and digestive system. Ireland has the highest incidence of the condition in the world: approximately 1400 children and adults in Ireland live with the condition and more than 30 new cases of cystic fibrosis are diagnosed here each year, typically around four weeks of age through the newborn screening programme.
In recent years, new medicines have emerged that target the basic defect that causes cystic fibrosis. Ivacaftor (Kalydeko) is one such treatment. It targets a genetic change seen in around 4% of people with cystic fibrosis worldwide, and around 10% in Ireland.
Siblings Kara (aged 5) and Isaac Moss (aged 2) both participated in the study through Children’s Health Ireland. Kara was part of an earlier phase of the study that paved the approval of the drug in older infants and led to the latest trial that Isaac took part in.
Isaac was the first baby with cystic fibrosis in the world to be diagnosed from birth and enrolled directly onto a trial of these ground-breaking treatments.
“Both Kara and Isaac are doing really well and remarkably are not experiencing any of the typical symptoms of cystic fibrosis at the moment,” said their mother Debbie.
“Research studies like this one are so important to ensuring that children get access to the right treatments as early as possible. With the right medications, they can enjoy a healthy childhood and look forward to a brighter future”
Ivacaftor is manufactured by pharmaceutical company Vertex Pharmaceuticals, who are currently applying to the European Medicines Agency for an extension to the marketing authorization for Ivacaftor down to one month of age.
The study involved researchers from RCSI, Children’s Health Ireland, the U.S. and the UK.
