Liverpool School of Tropical Medicine

A new study that has the potential to change the landscape of hepatitis B transmission in Africa. Researchers conducted an analysis revealing key interventions that could effectively eliminate vertical transmission of chronic hepatitis B, one of the leading causes of liver cancer and cirrhosis in the region. Researchers at the University of Liverpool have conducted a large-scale analysis that sheds light on the critical steps needed to combat the vertical transmission of chronic hepatitis B virus (HBV) in Africa. Almost two thirds of all new hepatitis B infections globally occur in Africa. The newly published paper in The Lancet Global Health shows the importance of giving the hepatitis B birth dose vaccine (HepB-BD) within 24 hours of birth, and the potential impact of providing antiviral therapy (antiviral prophylaxis) to mothers during pregnancy. The study estimates for the first time that hepatitis B vertical transmission (passed from mother to baby) could be eliminated in Africa, with increased coverage of these two key interventions. Chronic hepatitis B is the leading cause of liver cancer and liver cirrhosis in Africa and deaths are rising. Most cases of liver cancer are diagnosed late and are associated with a very poor prognosis in the region. Vertical transmission is one of the commonest routes of infection and is associated with an increased lifetime risk of severe liver disease. Dr Alexander Stockdale, Senior Clinical Lecturer at the University's Department of Clinical Infection, Microbiology and Immunology, based at the Malawi-Liverpool-Wellcome Trust Clinical Research Programme, together with Dr Nicholas Riches at Liverpool School of Tropical Medicine, led the comprehensive analysis of more than 113 individual studies which reported on the prevalence of hepatitis B in more than 190,000 women and investigated rates of vertical transmission. The World Health Organization (WHO) African region faces a significant burden, accounting for 63% of the global total of new infections. This amounted to 771,000 new infections and 272,000 deaths in 2022. Among children under 5 years, the prevalence of HBV stands at 2.5% in the WHO African region -- the highest globally. Dr Alexander Stockdale said: "This study makes the case for investment in birth dose vaccination and maternal antiviral prophylaxis, in view of the exciting potential for elimination of vertical transmission in the WHO African region in our lifetime. Vertical transmission is a key route of new hepatitis B infections. Due to limited implementation of interventions, elimination targets are not currently being met. We project that expanding HepB-BD vaccination coverage to 90% could reduce transmission events by 44%, and adding maternal antiviral prophylaxis for 90% of eligible women could further reduce transmission by 86% and achieve the WHO targets for elimination." Dr Stockdale and colleagues have also recently been awarded £3million funding from the National Institute of Health and Care Research to conduct implementation research in Malawi and The Gambia. The NIHR Global Health Research Grant will allow researchers in Malawi, led by Dr Stockdale and in The Gambia, led by Professor Maud Lemoine and Dr Gibril Ndow, to evaluate the effectiveness, safety, feasibility and cost-effectiveness of giving antiviral treatment (tenofovir) to all pregnant women living with chronic hepatitis B to prevent transmission. This study will provide vital evidence on the potential impact of this strategy to guide public health policy in Africa, which has been recognised as a key knowledge gap by the WHO in the 2024 hepatitis B guidelines.

Scientists have discovered a new snakebite treatment to prevent the devastating tissue damage caused by African spitting cobra venom. Spitting cobra venom is incredibly potent and causes dermonecrosis, which presents as rapid destruction of skin, muscle and bone around the site of the snakebite, and can lead to permanent injuries and disfigurements, including limb loss and amputations in extreme cases. Using the repurposed small molecule drug varespladib to block one of the two major dermonecrosis-causing toxins in spitting cobra venom prevents skin and muscle damage. Each year, it is estimated that snakebite causes long term detrimental effects in around 400,000 people across the world, with a substantial proportion of those in Africa the result of spitting cobra bites. Scientists have discovered a groundbreaking new snakebite treatment to prevent the devastating tissue damage caused by African spitting cobra venom. Spitting cobra venom is incredibly potent and causes dermonecrosis, which presents as rapid destruction of skin, muscle and bone around the site of the snakebite, and can lead to permanent injuries and disfigurements, including limb loss and amputations in extreme cases. Professor Nicholas Casewell and Liverpool School of Tropical Medicine colleagues including Dr Steven Hall -- who is now at Lancaster University- discovered that using the repurposed small molecule drug varespladib to block one of the two major dermonecrosis-causing toxins in spitting cobra venom prevents skin and muscle damage. Each year, it is estimated that snakebite causes long term detrimental effects in around 400,000 people across the world, with a substantial proportion of those in Africa the result of spitting cobra bites. Currently, there is no effective treatment for tackling severe local envenoming caused by spitting cobra venom. Existing antivenoms only work on bites by other snake species and are often ineffective for treating local envenoming because antivenom antibodies are too large to effectively penetrate into the region around the bite site. Professor Nicholas Casewell of LSTM said: "Our findings hold much promise to improve the treatment of tropical snakebite. Current treatments for spitting cobra bites are widely regarded as being ineffective, meaning that rates of disability and amputation have remained high across much of Africa. Our data shows that blocking just one of the main toxin families in spitting cobra venom will likely prevent the debilitating tissue damage seen in thousands of snakebite patients each year." Professor Casewell's team, led by PhD student Keirah Bartlett and Dr Steven Hall, then of LSTM and now at Lancaster University, and also involving researchers from Canada, Denmark, Costa Rica and the USA, first analysed spitting cobra venom to identify the toxins responsible for causing venom-induced dermonecrosis. The results showed that cytotoxic three-finger toxins (CTx) are largely responsible but that phospholipases A2 (PLA2) toxins play a critical role in the process. Local injection of the PLA2-inhibiting drug varespladib reduced the extent of dermonecrosis, even when delivered up to an hour after the venom, and the protection conferred by the drug also extended to venom-induced muscle toxicity. According to the authors, the findings suggest that varespladib could become an invaluable treatment against the tissue-damaging effects of black-necked and red spitting cobra venoms, which cause extensive morbidity in snakebite victims across the African continent. Lead author Keirah Bartlett said: "These findings are extremely promising, not only does this offer up a new mode of treatment where previously nothing effective existed, but because varespladib has already gone through testing in human clinical trials, including for snakebite, it could be available for use in real world patients very soon." Dr Hall added: "Snakebite is a devastating neglected tropical disease, with tissue destruction caused by necrotic snake venoms permanently injuring hundreds of thousands of victims every year. Our work shows that the repurposed drug, Varespladib, is incredibly effective at inhibiting such necrosis caused by African spitting cobras; an exciting finding as their venoms are particularly fast-acting and destructive. We hope this work helps pave the way to future snakebite therapies that can save the lives and limbs of victims worldwide." Professor Casewell's team are already looking for viable treatments that effectively block the venom CTx. Having treatments available against both toxins has the potential to enhance the potency of varespladib, and could significantly reduce the long-term morbidity associated with spitting cobra bites in Africa and beyond.

New research has been published that identifies positive steps towards a better understanding of antimicrobial resistance (AMR), specifically in hospital-acquired pneumonia (HAP). New research has been published that identifies positive steps towards a better understanding of antimicrobial resistance (AMR), specifically in hospital-acquired pneumonia (HAP). Antimicrobial, or antibiotic resistance, is a growing global issue, yet little is known about how to dose antibiotics to minimise bacteria developing resistance in patients. However, the University of Liverpool is playing a key role in contributing to international efforts to better understand AMR. In a paper published today (Thursday 18 January), Dr Christopher Darlow, from the Antimicrobial Pharmacology & Therapeutics (APT) group at the University of Liverpool details a new experimental animal model of HAP. The model tests both the effect of meropenem -- a commonly used antibiotic for HAP -- and crucially determines how resistance to meropenem emerges. Infections of the lungs are quite common in hospitals, with HAP accounting for approximately 10% of deaths in hospital. Because of the types of bacteria causing HAP and the large numbers of bacteria in the lungs during HAP, development of resistance to administered antibiotics to treat it is common. This is partly because doses of antibiotics are determined by drug developers to treat HAP effectively, but without consideration to the dose needed to prevent resistance emerging. The team at the APT group, including Dr Darlow, have developed a new experimental model of HAP and used it to test the effects of meropenem. This model has allowed the team to detect both the amount of bacteria in the lungs as the antibiotic is given (i.e. is the antibiotic working to treat the infection) and also to detect the emergence of resistance, including by measuring the mutations in the genes of the bacteria that drive this. In this work, the team demonstrated that too low doses of meropenem do treat HAP, but also cause a greater emergence of resistance. Conversely, resistance can be reduced by increasing the meropenem dose or by giving a second type of antibiotic (amikacin) at the same time. Both strategies may be used in clinical settings to reduce antimicrobial resistance. The team also mapped how the bacteria mutates and adapts to develop this resistance, giving insight into the underlying mechanisms. Dr Christopher Darlow said: "Through this work we have highlighted the problem of resistance development in HAP when treated by meropenem and demonstrated potential strategies to prevent this i.e. increasing the meropenem or using a second antibiotic in combination. Beyond the implications for HAP, this is also a new experimental platform to allow antibiotics (both new and old) to be assessed for their ability to cause development of resistance and identify strategies to mitigate against this. We hope to use this platform for other antibiotics in the future to improve the use of antibiotics and prevent antibiotic resistance development." This pioneering research is being delivered through the Infection Innovation Consortium: iiCON, a global collaborative infectious disease R&D programme led by Liverpool School of Tropical Medicine, of which the University of Liverpool is a core partner.