A new Cochrane review finds that chlorhexidine likely cuts umbilical cord infection rates by about 29% in low- and middle- income countries, and may reduce newborn deaths.
Umbilical cord care is a key part of newborn hygiene that helps prevent infection and promotes healthy healing. According to the World Health Organization (WHO), approximately 2.3 million newborn babies died in 2023, with the highest burden in low- and middle-income countries (LMICs).
Cord care practice varies widely around the world, shaped by local culture, healthcare infrastructure and available resources.
In settings with adequate obstetric care and low neonatal mortality, current WHO guidelines recommend dry cord care, involving keeping the stump clean and dry without antiseptics. In settings with higher neonatal mortality, the guidelines recommend daily application of 4% chlorhexidine for a week.
Antiseptic cord care offers protection
The researchers systematically reviewed 18 randomised controlled trials involving 143 150 newborns to evaluate whether applying antiseptics to the umbilical cord stump reduces infection, death, or delays cord separation compared to no treatment. The review covered antiseptics including 4.0% chlorhexidine (CHX), 70% alcohol, silver sulfadiazine, and povidone iodine.
The findings show that applying chlorhexidine to newborns’ umbilical cords likely reduces the number of infections from around 87 to 62 per 1000 newborns and the numbers of deaths may fall from around 18 to 15 per 1000 newborns in LMICs. Chlorhexidine likely also delays the time it takes for the cord stump to fall off by one to two days.
Only one study from a high-income country evaluated chlorhexidine. Evidence for preventing the bacterial infection omphalitis and its effect on cord separation was very uncertain, meaning conclusions cannot be drawn for these settings at this time.
“In many parts of the world, newborns are still born into environments where hygiene conditions are poor. Simple and accessible cord-care interventions can significantly reduce infections in these settings, which is critical given the large share of neonatal deaths linked to infection.”
– Dr Aamer Imdad, University of Iowa
Evidence for alcohol use in LMICs was very uncertain for both infection prevention and cord separation time. In high-income countries, moderate-certainty evidence suggests alcohol delays cord separation by approximately 1.6 days, but no studies reported on mortality or omphalitis in these settings.
Umbilical cord care should be contextualised to local settings
Dry cord care remains the recommended approach in countries with adequate obstetric care and low neonatal mortality. The authors explain that in many places, clean and dry cord care may be sufficient, while in others antiseptic approaches can reduce infection risk. The key is choosing interventions that match the realities families and health systems face.
“Our findings broadly support current World Health Organization guidance, but they also underline an important point: these interventions are not necessarily universal solutions. The benefits depend strongly on the context in which babies are born. What works best depends on local circumstances.”
– Professor Zulfiqar Ahmed Bhutta, Centre for Global Child Health in Canada and Aga Khan University in Pakistan
Many studies did not share individual patient data, which the authors say would have helped answer some remaining questions more clearly. Greater and timely data sharing could greatly strengthen transparency and in-depth scientific analysis for policy.
Finnish registry study finds that infections like cystitis and bacterial disease are linked to higher dementia risk independently of other coexisting conditions
Source: CC0
Severe infections increase the risk of dementia independently of other coexisting illnesses, according to a new study published March 24th in the open-access journal PLOS Medicine by Pyry Sipilä of the University of Helsinki, Finland, and colleagues.
Severe infections have been linked to an increased risk of dementia. However, it has been unclear whether this association is explained by other coexisting, non-infectious diseases that predispose people to both infections and dementia.
In the new study, researchers used nationwide Finnish health registry data covering more than 62 000 individuals aged 65 or older who were diagnosed with late-onset dementia between 2017 and 2020, along with more than 312 000 matched dementia-free controls. Taking a broad approach, they examined all hospital-treated diseases recorded during the previous twenty years, identifying 29 diseases that were robustly associated with increased dementia risk. Nearly half (47%) of dementia cases had at least one of the 29 identified diseases before their diagnosis.
Of those diseases, two were infections: cystitis (a urinary tract infection) and bacterial infection of an unspecified site. Among the non-infectious diseases, the strongest associations with dementia were seen for mental disorders due to brain damage or physical disease, Parkinson’s disease, and alcohol-related mental and behavioural disorders.
When the researchers then adjusted for all 27 non-infectious dementia-related diseases identified, the association between both infections and dementia remained largely intact. Less than one-seventh of the excess dementia risk among individuals with hospital-treated cystitis or bacterial infections was attributable to pre-existing conditions. The link between infections and dementia was even stronger for early-onset dementia (diagnosed before age 65), where five types of infection – including pneumonia and dental caries – were associated with elevated risk.
The study was limited by the lack of baseline cognitive assessments and clinical examination data before dementia diagnoses, as well as a lack of data on infection treatments.
“Overall, our findings support the possibility that severe infections increase dementia risk; however, intervention studies are required to establish whether preventing or effectively treating infections yields benefits for dementia prevention,” the authors say.
The authors add, “We found 27 diverse severe, hospital-treated diseases that were robustly associated with an increased risk of dementia. Two of these diseases were infections, namely urinary tract infections and unspecified bacterial infections.”
“In our study, dementia-related infections occurred on average 5 to 6 years before dementia diagnosis. Given that the development of dementia often takes years or even decades, these findings suggest that severe infections might accelerate underlying cognitive decline. However, as these findings were observational, we cannot exclude the possibility that some unmeasured confounding factors might also have affected our findings. Thus, we cannot prove cause and effect.”
“Ideally, intervention trials should examine whether better infection prevention helps reduce dementia occurrence or delay the onset of this disease.”
Doctors in the UK have identified promising evidence for the effectiveness of an early and rapid diagnostic test for sepsis.
Sepsis is a serious complication arising from infection, which can swiftly progress to life-threatening organ failure and is responsible for around 48 000 deaths annually in England. Recent findings, published today in The Lancet Respiratory Medicine, demonstrate that an accessible clinical decision-making tool significantly reduced mortality, with the greatest benefit seen among patients from the most deprived communities. However, the study also showed no difference in the speed of intravenous antibiotic initiation, despite initial expectations.
Diagnosing sepsis in emergency departments remains difficult, as many non-infectious illnesses can mimic its symptoms and there is currently no definitive diagnostic test. This uncertainty contributes to both over- and underdiagnosis. In both situations, delayed treatment can cost lives, while rapid antibiotics are required for those with confirmed sepsis some patients may be treated for sepsis unnecessarily, contributing to the urgent global issue of antimicrobial resistance (AMR). At the same time, misdiagnosis can lead to a failure to correctly identify and treat the actual underlying condition.
A procalcitonin‑guided algorithm is a clinical decision‑making tool that uses levels of the biomarker procalcitonin (PCT) to help guide antibiotic therapy in patients with suspected bacterial infections. However, it is not currently recommended for use in emergency settings because previous research has been inconsistent.
To address this gap, the research team conducted a large, controlled trial which randomised 7667 patients who presented to emergency departments with suspected sepsis. The study tested whether adding the rapid procalcitonin-guided algorithm testing to current clinical practice could help clinicians recognise sepsis more accurately, reduce unnecessary antibiotic prescribing, and maintain at least the same level of patient safety, measured by overall mortality.
The study shows:
There was a 17% relative reduction in mortality from 16.6% to 13.6% which means for every 1000 patient treated as suspected sepsis, 31 lives are potentially saved.
Patients from the most deprived areas experienced the greatest mortality benefit. Existing research explores inequality in sepsis outcomes, and this latest research may help to overcome identified systemic biases.
Importantly, the trial found that regardless of whether patients were treated with the procalcitonin‑guided algorithm or received standard care, there was no difference in how quickly intravenous antibiotics were started. Although the research team had anticipated that the algorithm might improve early antibiotic initiation, the trial showed it did not – a key finding, given this was one of the co‑primary outcomes.
Co-chief investigator, Dr Stacy Todd, Consultant in Infectious Diseases and General Medicine, NHS University Hospitals of Liverpool Group, said: “The evidence supports the value of early and rapid diagnostics and indicates a need for further biomarker and algorithm development. Uptake of procalcitonin-guided care into health systems will now depend on greater understanding of the mechanism of effect, further health economic evaluations, and robust implementation frameworks.”
The study reveals that the combination of antibiotics reduces mortality in patients with high-risk Staphylococcus aureus bacteriaemia by half, if applied in a personalised way
A study led by researchers from the Infectious Diseases Service of the Bellvitge University Hospital (HUB), the Bellvitge Biomedical Research Institute (IDIBELL) and the University of Barcelona (UB) shows for the first time that the combination of antibiotics can significantly improve the prognosis of patients with high-risk Staphylococcus aureus bacteriaemia, if it is applied selectively and in a personalised way.
The article has been published in the prestigious scientific journal The Lancet Regional Health – Europe and is the result of the collaboration of a dozen Spanish hospitals.
A reanalysis that redefines the strategy against bacteriaemia
Bacteraemia for S. aureus is a frequent and serious infection, with mortality reaching 30%. Its management requires prolonged intravenous antibiotherapy, the removal of possible infected devices and a thorough evaluation to rule out complications such as endocarditis or metastatic focus. In recent years, several clinical trials evaluating the combination of antibiotics had failed to demonstrate clear benefits in the global set of patients, a fact that the authors of the present study attributed to the lack of stratification according to risk.
For this reason, the study has carried out a reanalysis of the individualised data of two previously performed randomised clinical trials, differentiating patients according to their risk profile. This stratification was done through the FEN-AUREUS classification – a recently developed clinical tool that allows estimating the risk of mortality with information available during the first 24 hours of evolution – and the complication criteria of the Infectious Diseases Society of America (IDSA).
A personalised medicine according to individual risk
The re-evaluated trials include, on the one hand, a study with 155 patients from 18 Spanish hospitals that compared the use of daptomycin with the combination of daptomycin and phosphomycin; and, on the other, a study with 215 patients from 19 hospitals that compared cloxacillin in monotherapy with the combination of cloxacillin and phosphomycin. In both cases, the initial conclusions had shown no significant benefits of combined therapy in the overall set of patients, beyond a reduction in the duration of bacteraemia in patients treated with phosphomycin.
After the new risk group analysis, the work shows that low-risk and uncomplicated patients do not obtain significant benefits from combined therapy. On the other hand, high-risk patients showed remarkable therapeutic success at eight weeks (69.2% vs. 25.8%) and lower mortality at 60 days (23.1% vs. 45.2%).
According to first author Dr Francesc Escrihuela-Vidal, “the integration of risk and complications criteria can help identify patients who can really benefit from combined therapy.”.
In the same vein, co-author Dr Jordi Carratalà points out that “the results represent a real paradigm shift in the approach to this infection: we move from a uniform strategy for all patients to a precision medicine based on individual risk”. In addition, it highlights that this approach allows to avoid unnecessary intensive treatments in low-risk patients and will contribute to improving the design of future clinical trials.
Just over one in 10 deaths from a wide range of infectious diseases are associated with obesity worldwide, finds a major new study led by a UCL researcher.
People with obesity face a 70% higher risk of hospitalisation or death from an infection than those of a healthy weight, suggest the findings published in The Lancet.
Obesity is linked to an increase in the risk posed by many different infectious diseases, from flu and COVID to stomach bugs and urinary tract infections, and the researchers found that the higher the BMI, the greater the risk.
The study’s lead author, Professor Mika Kivimaki (UCL Faculty of Brain Sciences), said: “Obesity is well known as a risk factor for metabolic syndrome, diabetes, cardiovascular disease, and many other chronic conditions. Here we have found robust evidence that obesity is also linked to worse outcomes from infectious diseases, as becoming very ill from an infection is markedly more common among people with obesity.”
The researchers studied data from over 540 000 people who participate in large cohort studies in the UK (the UK Biobank dataset) and Finland, to look at the relationship between obesity and severe infectious disease. Participants had their body mass index (BMI) assessed when they entered the studies and were then followed up for an average of 13-14 years.
The researchers found that people with obesity (defined as a BMI of 30 or higher) had a 70% higher risk of hospitalisation or death from any infectious disease in the study period compared to people with a BMI between 18.5 to 24.9 (classified as a healthy weight).
The risk increased steadily as body weight increased. People with a BMI of 40 or higher had three times the severe infection risk compared to people with a healthy weight.
The link between obesity and severe infections was consistent regardless of the measure of obesity used (BMI, waist circumference, or waist-to-height ratio, where data was available) and for a wide range of infection types.
The study included data on 925 bacterial, viral, parasitic, and fungal infectious diseases, and the authors also honed in on 10 common infectious diseases in more detail. For most of these diseases, including flu, Covid-19, pneumonia, gastroenteritis, urinary tract infections, and lower respiratory tract infections, they found that people with obesity were more likely to be hospitalised or die than people with a healthy BMI. However, obesity did not appear to increase the risk of severe HIV or tuberculosis.
The analysis found that the link to severe infections was not explained by obesity-related chronic conditions, as the association was consistent in people with obesity who did not have metabolic syndrome, diabetes, or heart disease, while the association was also not explained by lifestyle factors such as physical activity.
While the study did not investigate the causes of the association, the researchers say that previous studies have suggested that obesity contributes to a general impairment of immune function, including immune dysregulation, chronic systemic inflammation, and metabolic disturbances.
Professor Kivimaki said: “Our findings suggest that obesity weakens the body’s defences against infections, resulting in more serious diseases. People may not get infected more easily, but recovery from infection is clearly harder.”
The researchers found evidence that losing weight can reduce the risk of severe infections as people with obesity who lost weight had a roughly 20% lower risk of severe infections than those who remained obese.
First author Dr Solja Nyberg (University of Helsinki) commented: “As obesity rates are expected to rise globally, so will the number of deaths and hospitalisations from infectious diseases linked to obesity.
“To reduce the risk of severe infections, as well as other health issues linked with obesity, there is an urgent need for policies that help people stay healthy and support weight loss, such as access to affordable healthy food and opportunities for physical activity. Furthermore, if someone has obesity, it is especially important to keep their recommended vaccinations up to date.”
The authors used infectious disease mortality data from the Global Burden of Diseases (GBD) Study to model the impact of obesity on infectious disease deaths for different countries, regions and globally.
The analysis suggested 0.6 million out of 5.4 million (10.8% or one in 10) infectious diseases deaths globally were linked with obesity in 2023.
The researchers estimated that in the UK, one in six (17%) infection-related deaths can be attributable to obesity, and 26% in the US.
Co-author Dr Sara Ahmadi-Abhari (Imperial College London), who conducted the Global Burden of Diseases (GBD) analyses, said: “Estimates of the global impact give a sense of how large the problem may be, but they should be interpreted with caution. Data on infection-related deaths and obesity in the GBD are not always accurate, particularly in low-resource countries.”
A new study suggests adding microscopic particles to vinegar can make them more effective against dangerous bacterial infections, with hopes the combination could help combat antibiotic resistance.
The research, led by researchers at QIMR Berghofer, Flinders University and the University of Bergen in Norway, has resulted in the ability to boost the natural bacterial killing qualities of vinegar by adding antimicrobial nanoparticles made from carbon and cobalt.
Wounds that do not heal are often caused by bacterial infections and are particularly dangerous for the elderly and people with diabetes, cancer and other conditions.
Acetic acid (more commonly known as vinegar) has been used for centuries as a disinfectant, but it is only effective against a small number of bacteria, and it does not kill the most dangerous types.
The findings have been published in the international journal ACS Nano.
Flinders University and QIMR Berghofer molecular biologists Dr Adam Truskewycz and Professor Nils Halberg found these particles could kill several dangerous bacterial species, and their activity was enhanced when added to a weak vinegar solution.
As part of the study, Dr Truskewycz and Professor Halberg added cobalt-containing carbon quantum dot nanoparticles to weak acetic acid (vinegar) to create a potent antimicrobial treatment.
They used this mixture against several pathogenic species, including the drug-resistant Staphylococcus aureus, Escherichia coli (E. coli) and Enterococcus faecalis.
Dr Truskewycz says the acidic environment from the vinegar made bacterial cells swell and take up the nanoparticle treatment.
“Once exposed, the nanoparticles appear to attack dangerous bacteria from both inside the bacterial cell and also on its surface, causing them to burst. Importantly, this approach is non-toxic to human cells and was shown to remove bacterial infections from mice wounds without affecting healing,” he says.
The anti-bacterial boost in vinegar found in the study could potentially be an important contribution towards the ongoing battle against the rising antimicrobial resistance levels worldwide, with an estimated 4.5 million deaths associated with a direct infectious disease.
Professor Halberg adds this study shows how nanoparticles could be used to increase the effectiveness of traditional bacterial treatments.
“Combination treatments such as the ones highlighted in this study may help to curb antimicrobial resistance. Given this issue can kill up to 5 million people each year, it’s vital we look to find new ways of killing pathogens like viruses, bacteria and fungi or parasites,” he says.
The article, ‘Cobalt-Doped Carbon Quantum Dots Work Synergistically with Weak Acetic Acid to Eliminate Antimicrobial-Resistant Bacterial Infections’ (2025) by Adam Truskewycz, Benedict Choi, Line Pedersen, Jianhua Han, Melanie MacGregor and Nils Halberg has been published in ACS Nano.
Study finds washing machine biofilms may harbour potential pathogens and antibiotic resistance genes, which could have an impact on domestic laundering of healthcare workers uniforms
Pre- and post-domestic laundering of bacteria contaminated textiles.
Credit: Dr Caroline Cayrou, CC-BY 4.0
Healthcare workers who wash their uniforms at home may be unknowingly contributing to the spread of antibiotic-resistant infections in hospitals, according to a new study led by Katie Laird of De Montfort University, published April 30, 2025 in the open-access journal PLOS One.
Hospital-acquired infections are a major public health concern, in part because they frequently involve antibiotic-resistant bacteria. Many nurses and healthcare workers clean their uniforms at home in standard washing machines, but some studies have found that bacteria can be transmitted through clothing, raising the question of whether these machines can sufficiently prevent the spread of dangerous microbes.
In the new study, researchers evaluated whether six models of home washing machine successfully decontaminated healthcare worker uniforms, by washing contaminated fabric swatches in hot water, using a rapid or normal cycle. Half of the machines did not disinfect the clothing during a rapid cycle, while one third failed to clean sufficiently during the standard cycle.
The team also sampled biofilms from inside 12 washing machines. DNA sequencing revealed the presence of potentially pathogenic bacteria and antibiotic resistance genes. Investigations also showed that bacteria can develop resistance to domestic detergent, which also increased their resistance to certain antibiotics.
Together, the findings suggest that many home washing machines may be insufficient for decontaminating healthcare worker uniforms, and may be contributing to the spread of hospital-acquired infections and antibiotic resistance. The researchers propose that the laundering guidelines given to healthcare workers should be revised to ensure that home washing machines are cleaning effectively. Alternatively, healthcare facilities could use on-site industrial machines to launder uniforms to improve patient safety and control the spread of antibiotic-resistant pathogens.
The authors add: “Our research shows that domestic washing machines often fail to disinfect textiles, allowing antibiotic-resistant bacteria to survive. If we’re serious about transmission of infectious disease via textiles and tackling antimicrobial resistance, we must rethink how we launder what our healthcare workers wear.”
Researchers at the University of Oklahoma have made a breakthrough discovery that could potentially revolutionise treatments for antibiotic-resistant infections, cancer and other challenging gram-negative pathogens without relying on precious metals.
Currently, precious metals like platinum and rhodium are used to create synthetic carbohydrates, which are vital components of many approved antibiotics used to combat gram-negative pathogens, including Pseudomonas aeruginosa, a notorious hospital-acquired infection responsible for the deaths of immunocompromised patients. However, these elements require harsh reaction conditions, are expensive to use and are harmful to the environment when mined. In an innovative study published in the journal Nature Communications, an OU team led by Professor Indrajeet Sharma has replaced these precious metals with either blue light or iron, achieving similar results with significantly lower toxicity, reduced costs, and greater appeal for researchers and drug manufacturers.
By using abundant, inexpensive, iron or metal-free, non-toxic blue light, the team can more easily and rapidly synthesize these important carbohydrates. Since most antibiotics rely on a carbohydrate molecule to penetrate the thin, external layer of the gram-negative bacteria, this discovery could transform the way doctors treat multi-drug-resistant pathogens.
“Drug-resistant infections are a major problem and are expected to rise unless something is done,” Sharma said. “By using our methods to make late-stage drug modifications, synthetic carbohydrate-based antibiotics could help treat these infections. Furthermore, since carbohydrates can also increase a drug’s solubility, they can be easily deployed as a pro-drug that a patient can simply take it with water.”
A pro-drug is a medication that it less active when administered and metabolized into its active form. To help drug molecules last longer in the body and work more effectively, Sharma’s team is exploring ways to attach specially designed sugars or unnatural sugar to them. They are using a unique blue light-based method, developed by Surya Pratap Singh, a lead researcher and doctoral student in Dr. Sharma’s lab, that does not require metals.
“If a drug molecule is broken down too quickly, it loses its potency. By replacing an oxygen atom in the carbohydrate molecule with a sulfur one, enzymes in the human body won’t recognise the molecule as a carbohydrate and won’t break it down as quickly,” Sharma said. “These modified compounds, commonly called thiosugars, could be used to more effectively treat infections and diseases like cancer.”
Study suggests onsite monitoring at buildings or complexes could aid efforts against disease spread
Photo by Jan Antonin Kolar on Unsplash
In a new study, wastewater surveillance for multiple pathogens at five different sites—including an office and a museum—identified local trends that were not captured in larger surveillance programs, and some sites used the data to inform efforts to prevent disease spread. Jay Bullen of Untap Health in London, U.K., and colleagues present these findings in the open-access journal PLOS Global Public Health.
People with viral infections produce waste containing viral RNA that ends up in wastewater in sewage systems. Measuring viral RNA levels in wastewater at treatment plants can be a cost-effective way to monitor community health. For instance, this method has been useful for monitoring COVID-19 infection trends and tracking polio eradication efforts.
Prior research suggests that wastewater surveillance programs that track multiple diseases at once could be beneficial at the municipal level. However, few studies have assessed their potential value at smaller, site-specific scales.
To fill that gap, Bullen and colleagues monitored daily wastewater concentrations of multiple viruses at five different sites in the U.K.; an office, a charity center for elderly citizens, a museum, a university co-working space, and a care home. The community size of the sites ranged from 50 to 2,000 people, and the researchers measured wastewater levels of the viruses SARS-CoV-2, influenza A and B, RSV A and B, and norovirus GI and GII.
Analysis of trends captured in the wastewater measurements revealed links with site-specific reported events, including staff illness, cleaning practices, and holidays. At the care home, where the community had less contact with the larger regional community, wastewater data captured local events that were not seen in public health data. In larger, more open communities, such as the university space, wastewater data aligned more closely with public health data.
Some sites began using the wastewater data to help inform decisions about disease prevention efforts, such as enhanced cleaning routines and notices in bathrooms about washing hands with soap.
These findings suggest that near-source wastewater monitoring could benefit local communities and perhaps provide earlier warnings of wider trends. Further research is needed to refine understanding of these potential benefits.
The authors add: “Building-level wastewater surveillance enables detection of norovirus, influenza, RSV and COVID-19 in a local population not captured by national surveillance. We see a future with near-source wastewater surveillance scaled across different communities to provide tailored local infection prevention and control measures, reducing outbreaks.”
For centuries, it was believed that tuberculosis spread primarily when a vulnerable person spends hours in a poorly ventilated space with someone infectious. But new findings suggest that much TB transmission also occurs through casual contact.
Conventional thinking held that enclosed spaces such as households, prisons, and shelters, where people spent long periods of time together, were where most TB transmission took place. But new data suggest that casual contact at social settings like shopping malls, restaurants, bars, and places of worship also account for much TB transmission.
A recent study found that close contact explained only 9% of TB transmission links, while casual contact accounted for 49%. The study, called CONTEXT (Casual Contact and Migration in XDR TB), was conducted in KwaZulu-Natal.
The study’s lead author, Professor Neel Gandhi of Emory University in Atlanta, recently presented the findings at the Conference on Retroviruses and Opportunistic Infections (CROI) in San Francisco. The work has not yet been published in a peer-reviewed medical journal.
The new findings come in the context of other research (much of which was conducted in Cape Town) that suggest TB could be transmitted through breathing, and growing evidence that people with asymptomatic TB can transmit the infection.
Where transmission occurs
Gandhi tells Spotlight that TB transmission has traditionally been linked to prolonged, close contact, with previous studies showing that 9 to 30% of cases could be attributed to this type of contact. A compelling alternative argument, he says, is that the remaining 70% of transmission occurs due to casual contact in community settings – which is what their research sought to explore.
He elaborates: “For much of history, we have thought that most TB transmission occurs through close and prolonged contact, meaning that a susceptible person is spending a lot of time in a poorly ventilated area with somebody who is infectious. And so most often we think of households as places where transmission occurs; or congregate settings, places like prisons or homeless shelters.”
On defining casual contact, he says: “In our research, we wanted to understand less intense forms of contact where transmission can occur. So, we understood where people lived, but we also asked them where they spent time in a typical week. The phrase we used was: ‘where do you spend two hours or more, most weeks?’ To try to identify the places people spend substantial amounts of time; and seeing whether they crossed paths with somebody else to whom their molecular fingerprints (of their TB bacteria infection) match.”
Genotyping, and geomapping
In their study, Gandhi and his colleagues made use of both genotyping and geospatial mapping to figure out where TB transmission likely occurred.
Genotyping, explains Gandhi, is a technology developed about 30 years ago that allows us to examine the genetic code of TB bacteria, and to compare similarity between patients’ bacteria.
“TB is a bacteria that keeps its genetic code similar across many generations of replication. In layman’s terms, we call this molecular fingerprinting. If I were to transmit TB to somebody else; my TB bacteria and that person’s TB bacteria’s genetic codes would look very similar – almost identical – so we could use this fingerprinting technique by sequencing the genomes of the two TB bacteria to try to fully get a sense of what the likelihood of transmission was.”
Commenting on their geospatial methodology, he says: “When our participants told us where they live or where they spend time in the community, or where they get outpatient healthcare; our team went to those sites and captured a GPS coordinates.
“Just like we use GPS for mapping when we’re trying to get around town, we would get specific coordinates… If two people went to the same shop, they might have used different names for that shop, or let’s say they went to a shopping mall, they may have used different names for those places; but we used GPS coordinates allowing us to determine whether they were at the same place or close to one another. And we used the concept of proximity to try to understand the likelihood that they may have crossed paths.”
In the study they used the metric of “community proximity” defined as a radius of 500 metres, or less.
Gandhi illustrates the nuance of geomapping, using his university campus: “So the example I like to give is; I work in a building called the School of Public Health. Across the courtyard is the School of Nursing. If you just asked me, where do you work? I would tell you, I work in this building. If you ask the next person where they work, they may say, I work in the School of Nursing. That wouldn’t match up in terms of place name. But if we used a radius of 100 metres or 500 metres, we can determine that we work very close to one another. And there’s a cafe in yet another building that we may have eaten lunch in at the same time. TB being an airborne disease, I don’t have to sit next to that person or even to know that person; if I’m infectious, I could have transmitted to them if they were sitting and eating in the same room.”
Essentially, the researchers used genotyping, particularly molecular fingerprinting to help understand the likelihood of transmission between people who have drug resistant TB. And once individuals with similar molecular fingerprints were found, they used geomapping to see whether these patients could be connected through close contact – and if not close contact, then through casual contact.
He adds: “The most common place people told us were friends and family members’ homes. Then the next most common was places of shopping so shopping malls.”
At CROI, Gandhi responded to a question from a conference delegate around risk, saying that there appears to be a greater risk of TB transmission in social settings than previously understood.
Symptoms and disease
To Spotlight, he says more work is needed to understand why casual contact transmission is happening. “And it connects to another topic in the TB community that is gaining a lot of attention currently, which is trying to understand what the association is between symptoms and having TB disease,” says Gandhi.
He notes that the challenge for researchers moving forward is understanding the link between infectiousness and symptoms – specifically, understanding when a person becomes infectious, even if they show no symptoms.
Most TB public health interventions are still based on the assumption that people with TB will present at health facilities with classic TB symptoms such as persistent cough, night sweats, fever, weight loss, and chest pain. South Africa has however in recent years been offering TB tests to asymptomatic people thought to be at high risk of TB, as part of its targeted universal testing strategy.
“So you may have heard of this concept of what some people have called subclinical TB or asymptomatic TB. And that is to say, if you were to test a group of people who didn’t come to a health clinic, but let’s say you were on a street corner and you tested everybody who went by for TB, we’re coming to appreciate that as many as 50% of people may not either have any symptoms or may not have symptoms that are worrisome enough for them to seek healthcare, but are actually testing positive for TB disease,” Gandhi adds.
Gandhi says this reminds him of the early days of COVID-19, when scientists weren’t sure if people only became infectious after showing symptoms.
“Eventually we learned that people were infectious probably for a few days before they developed symptoms. And in the TB world, this may be an area we need to investigate. If there’s the possibility that somebody is infectious when they have absolutely no symptoms, they would go about their regular activities; going to work, going to school, going shopping, going to religious ceremonies, going to restaurants, and they may unknowingly be infectious with TB. So this is the challenge.”
The bigger picture
Commenting on the findings, Robert Wilkinson, Honorary Professor in the Department of Medicine at the University of Cape Town and director of the Centre for Infectious Diseases Research in Africa, says: “It is interesting, and the proportion of transmission estimated to occur outside the household is a low estimate, but not incompatible with other estimates.”
He notes that the phenomenon of transmission occurring after brief casual contact is not novel though, and has been investigated in previous studies.
Asked how the findings presented by Gandhi might affect the outlook on TB interventions, Wilkinson says: “Whilst close household exposure to infectious tuberculosis should prompt clinical evaluation especially if there are symptoms, finding a close contact by conventional contact tracing approaches is far from invariable. Therefore, in high incidence environments like South Africa more attention needs to be placed on mass radiographic (X-ray) and, or microbiological screening of asymptomatic persons.”
In a recent public lecture called ‘Hunting Bosons, Finding the Bummock’, Emeritus Professor in Medicine at the University of Cape Town, Robin Wood, former CEO of the Desmond Tutu Health Foundation, states: “I think we are changing the paradigm of tuberculosis.” He notes that research now targets “hidden reservoirs of TB transmission beyond visible, symptomatic cases… [as] TB silently spreads within communities through carriers who exhibit no symptoms yet contribute to transmission.” Asked about Gandhi’s findings, Wood told Spotlight he would reserve comment until the data is submitted for further peer review and publication.
Study details
The 305 respondents in the CONTEXT study were patients with extensively drug-resistant TB or pre-extensively drug-resistant TB. They were diagnosed between 2019 and 2022 in the eThekwini, Ilembe, Umgungundlovu, and Ugu regions. The average age was 36 years, with 137 (45%) women and 216 (73%) people living with HIV.
The study was conducted in collaboration with the Durban-based Centre for the AIDS Programme of Research in South Africa (CAPRISA).
“CAPRISA played a leadership role in conceptualising the science, development of the protocol and data collection instruments, oversight of all aspects of field work, including screening and enrolling patients, obtaining informed consent from patients or their proxy’s, field and laboratory data collection, data verification and data clean-up activities for all data used in this study,” says CAPRISA’s deputy director, Professor Kogieleum Naidoo.
CONTEXT was funded through the United States National Institutes of Health (NIH), the world’s largest health research funder which has in recent weeks terminated several grants in South Africa and elsewhere. “The funding period has ended,” says Gandhi. “Now we’re analysing all of the data, so it won’t be impacted by any changes happening at NIH.”
