by Charlotte Kilpatrick | Oct 21, 2024 | Global Health |
In October 2024 WHO certified Egypt as malaria-free after a “nearly 100-year effort” by the government and people to end the disease. WHO described this as a “significant public health milestone” for the country’s more than 100 million inhabitants. Egypt is the third country to receive this certification in the WHO Eastern Mediterranean Region, following the United Arab Emirates and Morocco.
Across the globe, 44 countries and 1 territory have achieved this status by proving beyond reasonable doubt that the chain of indigenous malaria transmission by Anopheles mosquitoes has been interrupted nationwide for at least the previous three consecutive years. A country must also demonstrate its capacity to prevent the re-establishment of transmission.
Malaria becomes history
WHO states that malaria has been traced back as far as 4000 BCE in Egypt; there is genetic evidence of the disease in Tutankhamun and other ancient Egyptian mummies. More recently, efforts to reduce human-mosquito contact began in the 1920s with the prohibition of rice cultivation and agricultural crops near homes. With much of the population living along the banks of the Nile River and malaria prevalence “as high as 40%”, malaria was designated as a notifiable disease in 1930.
By 1942, malaria cases in Egypt exceeded 3 million due to population displacement caused by the Second World War, the disruption of medical supplies and services, and the invasion of Anopheles arabiensis, which is a “highly efficient mosquito vector”. Egypt responded to the outbreak by establishing 16 treatment divisions and recruiting more than 4000 health workers. The Aswan Dam, completed in 1969, brought an additional risk of malaria as standing water provides a mosquito breeding ground. Thus, Egypt worked with Sudan to launch a “rigorous” vector control and public health surveillance project.
By 2001, malaria was “firmly under control”, encouraging the Ministry of Health and Population to work on preventing the re-establishment of local malaria transmission. Egypt “rapidly” contained a small outbreak in the Aswan Governorate in 2014. The recent certification recognises continued efforts and initiatives including the free provision of malaria diagnosis and treatment to the population, regardless of legal status, and health professionals’ training to detect and screen for malaria. The country also has “strong” cross-border partnerships with neighbours like Sudan, which have been “instrumental”.
The beginning of a new phase
Dr Tedros Adhanom Ghebreyesus, WHO Director-General, congratulated Egypt on its achievement.
“Malaria is as old as Egyptian civilisation itself, but the disease that plagued pharaohs now belongs to its history and not its future. This certification of Egypt as malaria-free is truly historic, and a testament to the commitment of the people and government of Egypt to rid themselves of this ancient scourge.”
Dr Tedros hopes that this will be an “inspiration to other countries in the region”, showing “what’s possible with the right resources and the right tools”. Deputy Prime Minister of Egypt H.E. Dr Khaled Abdel Ghaffar commented that the certification is “not the end of the journey but the beginning of a new phase”.
“We must now work tirelessly and vigilantly to sustain our achievement through maintaining the highest standard for surveillance, diagnosis and treatment, integrated vector management, and sustaining our effective and rapid response to imported cases. Our continued multisectoral efforts will be critical to preserving Egypt’s malaria-free status.”
Dr Abdel Ghaffar reaffirmed that the country will “continue with determination and strong will”. WHO Regional Director for the Eastern Mediterranean Dr Hanan Balkhy emphasised that the success is “not just a victory for public health but a sign of hope for the entire world”, including other endemic countries in the region.
“This achievement is the result of sustained, robust surveillance investments in a strong, integrated health system, where community engagement and partnerships have enabled progress. Furthermore, collaboration and support to endemic countries, such as Sudan, remain a priority.”
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by Charlotte Kilpatrick | Oct 21, 2024 | Therapeutic |
Research in Nature in October 2024 leverages evidence that bacteria “naturally home in on tumours and modulate antitumour immunity” to explore potential vaccine applications. The authors engineered a probiotic Escherichia coli Nissle 1917as an antitumour vaccination platform, revealing a promising immune response. In mouse models of advanced colorectal cancer and melanoma, the vaccine triggered the immune system to suppress the growth of primary and metastatic cancers. The team hopes that this research can advance personalised cancer vaccine approaches.
Bacteria as ideal vectors
The authors identified bacteria as “ideal vectors to augment and direct” antitumour immune responses thanks to their support of the activation of both innate and adaptive immunity. Furthermore, bacteria can be synthetically engineered with ease for “safe delivery” of immunomodulatory compounds. Although various tumour neoantigen vaccines have demonstrated “promising” clinical trial results, benefit is “limited to only a subset of patients”. Thus, programming bacteria with genetic directives to release high levels of specific tumour neoantigens offers a system for the precise instruction of neoantigen targeting in situ.
The study
The researchers developed an engineered bacterial system in probiotic Escherichia coli Nissle 1917 (EcN) to “enhance expression, delivery, and immune-targeting of arrays of tumour exonic mutation-derived epitopes”. These epitopes are “highly expressed” by tumour cells and predicted to bind major histocompatibility complex (MHC) class I and class II. The system engages several “key design elements” to enhance therapeutic use:
- Optimisation of synthetic neoantigen construct form with
- Removal of cryptic plasmids and deletion of Lon and OmpT proteases to increase neoantigen accumulation
- Increased susceptibility to phagocytosis for enhanced uptake by antigen-presenting cells (APCs) and presentation of MHC class II-restricted antigens
- Expression of listeriolysin O (LLO) to induce cytosolic entry for presentation of recombinant encoded neoantigens by MHC class I molecules and T helper 1 cell (T H1)-type immunity
- Improved safety for systemic administration due to reduced survival in the blood and biofilm formation
Through exome and transcriptome sequencing of subcutaneous CT26 tumours the researchers developed a repertoire of neoantigens, which were predicted from highly expressed tumour-specific mutations. They then endeavoured to create a microbial system that could “accommodate the production and delivery of diverse sets of neoantigens” to lymphoid tissue and the tumour microenvironment (TME).
“Synthetic neoantigen construct optimisation and genetic engineering achieved a microbial platform (EcNcΔlon/ΔompT/LLO+) capable of robust production across diverse sets of tumour neoantigens, which was attenuated in immune-resistance mechanisms, effectively taken up by and proficient in activating APCs, and able to drive potent activation of T cells specific for encoded recombinant antigens to support enhanced cellular immunity.”
Vaccine applications
The study revealed that antigen sets encompassing predicted MHC-II and MHC-II binding neoantigens mediated antitumour efficacy. Enhanced frequencies of neoantigen-specific CD4+ and CD8+ T cells were seen. Across distinct tumour models and genetic backgrounds, the antitumour effect of vaccination was “accompanied by broad modulation of the immune compartment within the TME”.
“The coordinated regulation of APCs, reduction of immunosuppressive myeloid, regulatory T and B cell populations, and activation of NK cells and CD4+ and CD8+ T cells together indicate the advantage of precisely engineered microbial platforms as next-generation antitumour vaccines that align several arms of immunity.”
Furthermore, the “unique ability” of microbial vaccines to “directly remodel” the TME could “promote synergy” across various forms of immunotherapy. Microbial neoantigen vectors locally increase neoantigens density, recruit and activate dendritic cells and CD4+ and CD8+ T cells, and reduce immunosuppressive populations and ligands within the TME. Therefore, in combination with adoptive T cell therapy (ACT), they could “oppose these resistance mechanisms and provide synergistic benefit”.
“Through extra programming of the microbial vectors and rational incorporation of other immunotherapeutics, this system may achieve reliable eradication of established solid tumours and metastases through precision cancer immunotherapy using living antitumour vaccines.”
Getting closer
Jongwon Im, PhD student at Columbia University, helped lead bacterial engineering aspects of the study, and commented on the “net effect”.
“The bacterial vaccine is able to control or eliminate the growth of advanced primary or metastatic tumours and extend survival in mouse models.”
These vaccines are personal, programmed to “direct the immune system” to target “distinct genetic mutations”, said Dr Nicholas Arpaia, associate professor of microbiology and immunology at Columbia University’s Vagelos College of Physicians and Surgeons.
“As we continue to integrate additional safety optimisations through further genetic programming, we are getting closer to the point of testing this therapy in patients.”
Dr Tal Danino, associate professor of biomedical engineering at Columbia’s School of Engineering, reflected that the time to treatment will “first depend on how long it takes to sequence the tumour” for each patient.
“Then we just need to make the bacterial strains, which can be quite fast. Bacteria can be simpler to manufacture than some other vaccine platforms.”
Another benefit of bacteria is the enabled delivery of a “higher concentration of drugs that can be tolerated when these compounds are delivered systemically throughout the entire body”, suggested Dr Arpaia.
“Here, we can confine delivery directly to the tumour and locally modulate how we’re stimulating the immune system.”
For the latest insights into cancer vaccine research make sure you join us at the Congress in Barcelona next week, and don’t forget to subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Oct 3, 2024 | Global Health |
WHO announced in October 2024 that it is launching the Global Strategic Preparedness, Readiness, and Response Plan (SPRP) to tackle dengue and other Aedes-borne arboviruses. The Plan is intended to reduce the burden of disease, suffering, and deaths from dengue and other Aedes-borne arboviral diseases, like Zika and chikungunya, by “fostering a global coordinated response”. It presents priority actions to control transmission and offers recommendations to affected countries across various sectors. With five “key components”, the Plan is to be implemented over one year until September 2025, demanding US$ 55 million.
“The SPRP is a call to action for all stakeholders – from government agencies and health-care providers to communities and individuals – to join forces in the fight against dengue and other Aedes-borne arboviruses, through innovation, new technologies, and improved vector control strategies.”
Turning the tide
In the foreword by WHO Director-General Dr Tedros Adhanom Ghebreyesus we learn that dengue has “afflicted humanity for centuries, and possibly longer”; the first report of a clinically compatible case is recorded in a Chinese medical encyclopaedia in 992. From a much more contemporary perspective, dengue has spread “rapidly” in the past 20 years, enabled by “increased global travel and the effects of climate change”. Between 2000 and 2019, WHO documented a “tenfold surge” in reported cases, to 5.2 million. Since then, the surge has continued; over 12.3 million cases were reported by the end of August 2024.
The global prevalence and effects of arboviruses like dengue are a “significant threat to public health”, particularly in tropical areas where they are endemic. Addressing this threat demands a “concerted, strategic, and informed response”, which the Director-General hopes to achieve with the SPRP, a “comprehensive plan” to outline ways of controlling Aedes-borne arbovirus transmission in affected countries.
“Our multifaceted approach emphasises integrated surveillance, laboratory diagnosis, vector control, community engagement, clinical management, and research and development.”
This approach should reduce the burden of disease, save lives, and minimise the socioeconomic consequences of these diseases. Furthermore, the Plan includes measures for “safe programming” to ensure interventions are “secure and do not exacerbate the risk” for those who are already vulnerable to disease or those involved in responding to the crisis. Dr Tedros states that prevention and control is a “shared responsibility”.
“Together, we can turn the tide against this disease, protect vulnerable populations, and pave the way for a healthier future.”
Understanding the threat
Dengue is a challenge across all of WHO’s regions, endemic in more than 100 countries. Various factors, such as unplanned urbanisation and the effects of climate change, fuel the spread of dengue and other Aedes-borne arboviruses, such as Zika and chikungunya, putting more than four billion people at risk. The growing threat must be addressed with a “robust and dynamic strategy” that accounts for the current global epidemiological landscape. This is complicated by the “still developing” global surveillance system.
Transmission drivers like the effects of climate change and population growth can explain the increase of these infections in some areas, but they also point to the need for a multisectoral approach to prevent and respond to outbreaks.
The Plan
The Plan is intended to “reduce the burden of disease and deaths from dengue and other Aedes-borne arbovirus diseases in all affected WHO regions”. The strategic objective is “to accelerate progress in preventing and controlling dengue and other Aedes-borne arboviral disease outbreaks worldwide”, with the following specific objectives:
- Strengthen global multisectoral coordination and collaboration among stakeholders and partners in preparedness, response, and resilience to dengue and other Aedes-borne arbovirus diseases
- Enhance the capacity of Member States in early detection, reporting, confirmation, and response to outbreaks of dengue and other Aedes-borne arboviruses
- Strengthen the capacity of Member States to implement effective vaccination and integrated vector management strategies for mitigating the transmission of dengue and other Aedes-borne arboviruses
The SPRP combines strategic interventions tailored to local contexts and leverages inter-stakeholder synergies to “confront the challenges” posed by these diseases and move closer to controlling them. The following “interconnected pillars” are included in the multidisciplinary approach:
- Leadership, coordination, planning, monitoring, and prevention of sexual misconduct
- Risk communication and community engagement (RCCE) and infodemic management
- Surveillance, case investigation, and contact tracing
- Travel, trade, and points of entry surveillance and control
- Laboratory and diagnostics
- Integrated vector management and WASH & IPC
- Clinical management and therapeutics
- Operational support and logistics
- Essential health services and systems
- Vaccination
- Research, innovation, and evidence
The 5Cs
The SPRP aligns with WHO’s 2023 Framework for Health Emergency Prevention, Preparedness, Response, and Resilience (HEPR) with a focus on five “core health emergency components”:
- Collaborative surveillance
- Strong national integrated disease, threat, and vulnerability surveillance,
- Effective diagnostics and laboratory capacity for pathogen and genomic surveillance
- Collaborative approaches for event detection, risk assessment, and response monitoring
- Community protection
- Community engagement, risk communication, and infodemic management
- Population and environmental public health interventions
- Multisectoral action for social and economic protection
- Access to countermeasures
- Fast tracked research and development
- Scalable manufacturing platforms
- Coordinated supply chains and emergency
- Emergency coordination
- Strengthened workforce capacity for health emergencies
- Strengthening health emergency preparedness, readiness, and resilience
- Health emergency alert and response coordination
- Safe and scalable care
- Scalable clinical care during emergencies
- Protection of health workers and patients
- Maintenance of essential health services
How do you think the SPRP can be effectively translated into specific contexts and implemented sustainably?
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by Charlotte Kilpatrick | Jul 17, 2024 | Infection |
In July 2024 Indian news outlets reported cases and deaths of suspected Chandipura virus (CHPV) in Gujarat. 8 children are said to have died already, with more “battling for their lives”. Samples have been sent to the National Institute of Virology (NIV) in Pune for confirmation, and Gujarat’s Health Minister Rushikesh Patel stated that the deaths can be attributed to the virus “after the reports come in”. There are no approved vaccines or treatments.
CHPV
Chandipura virus (CHPV) is an arbovirus of the Vesiculovirus genus in the Rhabdoviridae family. Among identified Vesiculoviruses, CHPV is “considered to be the most significant pathogen of public health importance” with a high case fatality ratio. It was first isolated in 1965 but has been considered an “orphan or concomitant virus” due to low pathogenicity to cause human or domestic animal infections.
CHPV causes two types of encephalitis: infection-related and auto-immune induced. It is “most commonly” associated with encephalitic sickness in children, clinically defined by a short high-grade fever, altered sensorium, vomiting, generalised convulsions, and decerebrate posture. This can lead to a grade IV coma and death within 48 hours of hospitalisation.
The situation in Gujarat
Telegraph India reports that cases have been identified in the Sabarkantha, Aravalli, Mahisagar, Kheda, Mehsana, and Rajkot districts. Since 10th July, 14 people have become ill, of whom 8 have died. The National Institute of Virology has received samples to confirm infection.
Experts comment
Weighing in on the apparent evolution of the disease manifestation and vector, Dr Sandipkumar Trivedi is quoted identifying a “new presentation” of two brain haemorrhages among the six deaths. Furthermore, sandflies have been found at “higher heights” than the usual 3 feet from the ground and “new outbreak centres” are emerging.
Dr Sayan Chakraborty of Manipal Hospital, Calcutta, is concerned that “this is a very rare form of virus” that “needs more research”. Dr Chakraborty wonders if it “thrives more in dry climate” and reflected that without specific treatment options the only solution is symptom management.
“Only symptomatic treatment is possible in the absence of any anti-viral and take proper care of the patient in an intensive care unit.”
Dr Abhishek Tiwari from ILS Hospitals, Calcutta, urged parents to be careful of insect bites and “keep our homes and surroundings clean”.
“Prevention is the only way out.”
If a child develops a sudden fever or falls unconscious “he or she should be immediately hospitalised”.
For more on emerging and re-emerging infectious diseases and vaccine development to address them, do join us in Barcelona for the Congress this October or subscribe to our weekly newsletters here.
by Charlotte Kilpatrick | Jul 16, 2024 | Global Health |
A paper in Nature Communications in July 2024 presents the concept of a “zoonotic web”, describing the “complex relationships” between zoonotic agents, hosts, vectors, food, and environmental sources. Created from a dataset of naturally occurring zoonotic interactions in Austria by a team from Complexity Science Hub (CSH), the web offers insights into zoonotic sources and spillovers. The authors present a “flexible network-based approach” to bring understanding of zoonotic transmission chains and facilitate the development of “locally relevant” One Health strategies against zoonoses.
Understanding interfaces
Zoonoses are caused by pathogens that are “naturally transmissible” between humans and animals; zoonotic agent transmission is enabled at “interfaces” where humans and animals, or animal products, interact. The researchers acknowledge that “approximately 99% of endemic zoonotic infections in humans” originate from domesticated animals in anthropogenic environments. Over 60% of human emerging infectious diseases (EIDs) are zoonotic, with more than 70% of these zoonotic emergences caused by pathogens with wildlife origin.
“However, the full host breadth of endemic and emerging zoonotic agents, as well as their animal and environmental reservoirs are rarely identified nor mapped.”
As interactions in “most” zoonotic disease systems occur among multiple animal host species and environmental sources and involve multiple infectious agents, the authors state that exploring disease dynamics “necessitates considering the complex ecology of the interactions”. However, a “lack of datasets” makes it hard to follow a transdisciplinary perspective. Additionally, network approaches tend to focus on the host-pathogen relationships over other sources of zoonotic infection, such as contaminated environment or food.
“A comprehensive understanding of circulating zoonotic agents, their hosts, vectors, food and environmental sources, and the key interfaces where spillover events may occur is essential for developing effective integrated One Health monitoring, prevention, and control of zoonoses.”
Zoonotic and emerging diseases have consequences on “multiple aspects” of society, but it is possible to predict the establishment of reservoirs, understand the facilitators of spillovers, and prevent such spillovers at the source through enhanced monitoring efforts and data collection. The authors describe a “pressing need” to develop analytical tools to “optimise surveillance strategies” that are “tailored” to regional or national contexts and conduct national studies.
“Bridging this gap is crucial for developing effective, locally relevant strategies to monitor and mitigate potential changes in spillover risk that could impact human and animal health.”
The study
The study is based in Austria, which has a “growing population” of nine million people. It is home to around 45,870 fauna species, of which 626 are vertebrates, including 110 mammalian and 418 avian species. 35% of 3.9 million Austrian households have pets and the country has ~53,300 cattle, 1 million pigs, and 5 million poultry. 133,000 hunting permits are issued each year. These figures demonstrate the significance of the “human-animal interfaces at the national scale”.
Although the country follows various European and national regulations on epidemiological surveillance and responses, the authors suggest that official figures “tend to overlook” non-regulated zoonotic agents circulating in the territory that present a public health risk. They conducted a literature search over 47 years of publications to generate a real-world network that describes the “web” of zoonotic interactions in Austria and to characterise the “various interfaces” through while spillover might occur.
The idea of a “zoonotic web” is presented as a “representation of zoonotic actors at human-animal-environment interfaces” to be used for One Health approaches. The researchers used it as a bipartite network and turned it into a one-mode projection representing the network of zoonotic agent sharing among zoonotic sources, weighting relationships (edges) between the sources (nodes) by the number of agents they shared.
Findings
The authors find that “most” zoonotic agents are “capable of infecting both human and diverse animal species across various taxa, while evolving within multi-source, multi-agent ecological communities”. This is “consistent” with “established principles in the parasite community ecology”. They suggest that the analysis of the zoonotic web provides “greater value” for studying potential zoonotic transmission chains than the host-pathogen network approach.
In their investigations of the centrality of zoonotic sources, they identified that certain sources “play a disproportionate role in the sharing of zoonotic agents”. They highlight the “crucial role” of arthropod vectors and foodstuffs in the risk of zoonotic disease emergence and transmission through the web, which offers potential targets for One Health surveillance programmes.
A key outcome is that ten genera of zoonotic agents constituted 41% of the published research on zoonotic diseases in Austria; seven of these involve agents subject to compulsory surveillance and reporting in humans and/or animals. This “underscores an imbalance” in research interest, which the authors attribute to funding opportunities and global- or national-level prioritisation.
“Bias may lead to a skewed assessment of the overall zoonotic risk, especially concerning potentially ‘neglected’ zoonoses such as certain helminth infections.”
Between 1975 and 2022, eight zoonotic agents emerged in Austria. Although there is “often an emphasis” on viral emergence, this research offers a “different perspective”: six out of eight emerging pathogens in Austria were bacteria and helminths.
“This highlights the importance of broadening our focus beyond viral threats and acknowledging the substantial role that bacterial and helminthic pathogens play in the landscape of emerging diseases.”
Another observation is that four emerging zoonoses are transmitted by arthropod vectors; as climate change and globalisation evolve, the authors identify a “growing likelihood” of new arthropod species populations becoming established in Austria. This increases the risk of future EID events.
The researchers express surprise at finding that no COVID-19-related publications concerning human cases describe it as a zoonotic disease, despite SARS-CoV-2 being notifiable for both humans and animals. Additionally, the publication that investigated SARS-CoV-2 in Austrian animals did not mention zoonotic potential.
The importance of studying the source-source network of zoonotic agent sharing to reveal indirect interactions is highlighted by the researchers. They present the example of an agent that is found in two sources, where its prevalence in one could affect the other, but acknowledge that indirect interactions could “lack epidemiological significance”. They show that the zoonotic agent sharing network in Austria is “organised” into six communities.
- Primarily comprising central hosts having higher values of centrality in the unipartite zoonotic agent sharing network and generally living in proximity to humans or having frequent interactions with humans. This community includes livestock, companion animals, synanthropic species, game species, and captive primates.
- Encompassing diverse reptiles and amphibians, including non-traditional pet (NTP) species and wild boar.
- Consisting of various avian taxa, including birds of prey, ducks, waterfowl, gamebirds, chickens, and pigeons – the hosts were broadly designated, lacking specific scientific nomenclature.
- Including various food products and environmental matrices related to food production as well as public lavatory and Meleagris gallopavo (turkey).
- Featuring mostly clustered West Nile virus (WNV) hosts and Usutu virus (USUV) hosts, including various bird species, the vector Culex, and horses.
- Representing USUV hosts and exclusively including bird species.
The highest risk of zoonotic spillover is identified from sources within the first community, where the most zoonotic agents are shared. Another observation is that a “limited number of highly connected zoonotic agents” in the bipartite zoonotic web, including USUV, S. enterica, WNV, and Influenza A, could “at least partly” drive zoonotic agent sharing community assemblage.
From the grouping of most food products into one community, the authors infer that anthropogenic activities, especially those that relate to food processing and transformation, might further influence the pattern of assembly within zoonotic source communities. This indicates that a combination of local epidemiological, ecological, human-related, and behavioural factors informs zoonotic agent sharing community patterns.
The researchers highlight the presence of central zoonotic sources in the network, with a higher number of interactions with zoonotic agents. These act as “hubs” or “bridge different zoonotic source communities” to act as “connectors”. For example, some livestock species, companion animals, wildlife, and vectors act as “bridge hosts” through which zoonotic agents can potentially spillover from maintenance populations or communities to target “protected” populations.
Implications
The authors offer a cross-disciplinary method for “unveiling the intricate web of zoonotic interactions involving multiple sources and infectious agents within an ecological system”. This approach also enables the identification of “influential” agents and sources that might have “epidemiological significance”. It could be applied in various settings to expose knowledge gaps and areas where understanding “may not always reflect on-the-ground realities”.
“This work emphasises the need for further modelling and empirical studies to explore how maintenance is influenced by multiple source-agent interactions. Establishing efficient and context-adapted One Health network-based surveillance and control strategies requires supplementing the network analysis with multi-source data, ensuring a holistic, multidimensional understanding of the zoonotic web to unravel the complex dynamics of zoonotic transmission chains.”
Commenting on the paper, CSH’s Dr Amélie Desvars-Larrive suggests that it started with the intention of characterising and visualising the zoonotic interfaces in Austria. From this came the first comprehensive overview of zoonotic pathogen transmission, a “complex system”. This could be useful for zoonosis surveillance programmes.
“With our interactive map, we aim to educate and spark curiosity. While we all encounter various pathogens, only a few lead to illness, so there’s no need for excessive concern.”
However, Dr Desvars-Larrive emphasises the importance of promoting awareness and demanding better data availability.
“We’re only seeing the tip of the iceberg in our data – only those zoonoses that have been diagnoses. For instance, leptospirosis, still relatively rare in Austria, can mimic flu-like symptoms. If not clearly diagnosed as leptospirosis, it won’t show up in the data.”
Therefore, this network is a good starting point to “facilitate the development of One Health strategies against zoonoses”.
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by Charlotte Kilpatrick | Jun 14, 2024 | Technology |
In June 2024 CyanVac announced that it has received a funding award under Project NextGen to support a Phase IIb study of CVXGA, the company’s PIV5-based vaccine candidate for protection against COVID-19. This is one of the first awards made through the Rapid Response Partnership Vehicle. The Phase IIb study of the intranasal vaccine will be conducted within BARDA’s clinical studies network.
The technology
CyanVac’s proprietary vaccines are based on parainfluenza virus 5 (PIV5). The company reports successful induction of three forms of immunity in preclinical studies:
- Cellular immunity – the vaccines “regularly” generate “robust” cytotoxic T-cell responses.
- Humoral immunity – the vaccines produce a “strong” antibody response with a single dose.
- Mucosal immunity – intranasal vaccines are introduced through the nasal mucosa, generating mucosal immunity.
“PIV5 is a respiratory virus, so our vaccines are “born intranasal”. Delivered as a spray in the nose, without injections, our vaccines will facilitate broad delivery not only to paediatric and other needle-hesitant populations, but also in parts of the world where healthcare professionals are scarce.”
The award
Through the award, CyanVac will sponsor a 10,000 participant, randomised, double-blinded study to compare the efficacy, safety, and immunogenicity of the vaccine candidate to a US FDA-approved mRNA-based COVID-19 vaccine. The study will evaluate the vaccine among participants at higher risk of severe disease and will evaluate CVXGA’s efficacy in preventing both severe COVID-19 infections and asymptomatic infections. It is expected to start in the autumn of 2024.
Dr Biao He, founder and CEO of CyanVac, looks forward to “building on our very promising Phase I and preliminary Phase IIa clinical trial results” through the award.
“PIV5 is a novel intranasal vaccine vector that has been shown to replicate safely in humans in clinical trials and stimulates all three pillars of immunity – cellular, mucosal, and humoral – with minimal uncomfortable side effects.”
Dr He hopes to “demonstrate the capabilities” of the platform and “benefit the development of PIV5-based vaccines for other emerging infectious diseases”.
“We are excited to work with BARDA on this large-scale trial and are grateful for their support.”
Dr Henry Radziewicz, Chief Medical Officer at CyanVac, identifies a “need for vaccines that can also block transmission of a pathogen to other people”.
“Our intranasal vaccine is delivered to mucosal surfaces, a key focus area for Project NextGen by BARDA because such vaccines have the potential to reduce the spread of disease.”
For more on innovative technologies to support infectious disease control, why not join us at the Congress in Barcelona this October or subscribe to our weekly newsletters here?
by Charlotte Kilpatrick | Jun 3, 2024 | Infection |
In May 2024 the WHO shared a disease outbreak news update on the global dengue situation, stating that by 30th April 2024 over 7.6 million dengue cases have been reported to WHO in 2024. This total includes 3.4 million confirmed cases, over 16,000 severe cases, and over 3,000 deaths. The “substantial increase” in cases has been “particularly pronounced” in the Region of the Americas, where the number of cases exceeded 7 million by the end of April 2024. This surpasses the annual high of 4.6 million cases in 2023. 90 countries have known active dengue transmission this year.
However, many endemic countries do not have strong detection and reporting mechanisms, which means that the true global burden of dengue is underestimated. WHO states that “real-time robust dengue surveillance” is needed to control transmission “more effectively”. This would address concerns about undetected cases, co-circulation and misdiagnosis as other arboviruses, and unrecorded travel movements.
“The overall capacity for countries to respond to multiple, concurrent outbreaks continues to be strained due to the global lack of resources, including shortages of good quality dengue diagnostic kits for early disease detection, lack of trained clinical and vector control staff, and community awareness.”
WHO maintains that the overall risk at the global level is “high”, with dengue remaining a global threat to public health.
Co-circulation concerns
There is “considerable overlap” in the geographic distribution of dengue, chikungunya, and Zika viruses; these are all transmitted by Aedes mosquitoes and share some clinical features. This can result in misdiagnoses and misreporting in the absence of differential laboratory testing. Surveillance systems that specifically target transmission of chikungunya or Zika are “weak or non-existent” in many countries.
“As dengue, chikungunya, and Zika viruses share the same Aedes mosquito vectors and co-circulate in the same geographic areas, they also share many prevention strategies, such as differential diagnosis, mosquito control, and public awareness campaigns.”
However, WHO notes “important differences” between these diseases that affect risk populations, patient management, and use of health care resources. Therefore, expanding surveillance for all three viruses will help public health authorities determine the true burden of each more accurately and respond appropriately.
Risk assessment and advice
In November 2023 WHO assessed the global risk of dengue as high. In December, the internal emergency response was assigned as G3 at the global level.
“Given the current scale of the dengue outbreaks, the potential risk of further international spread and the complexity of factors impacting transmission, the overall risk at the global level is still assessed as high and thus dengue remains a global threat to public health.”
Vector control interventions are “key” to dengue prevention and control, and WHO states that vector control activities should target “all areas” with risk of human-vector contact, including residences, workplaces, schools, and hospitals. WHO promotes Integrated Vector Management (IVM) to control Aedes species. Personal protective measures during outdoor activities are also encouraged. While there is no specific treatment for dengue infection, WHO highlights that early detection and access to appropriate healthcare for case management reduces mortality.
Vaccination should be considered within an integrated strategy to control the disease; WHO recommends the use of TAK-003 in children aged 6-16 years in settings with high dengue transmission intensity.
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by Charlotte Kilpatrick | Apr 25, 2024 | Infection |
For World Malaria Day 2024, WHO shared a message from the Director of the WHO Global Malaria Programme and emphasised the need to return to malaria progress in line with this year’s theme:
“Accelerating the fight against malaria for a more equitable world.”
WHO suggests that, in recent years, progress in reducing malaria has “ground to a standstill”, affecting health and costing lives. Furthermore, it “perpetuates a vicious cycle of inequity”. In this article we cover the message from WHO Global Malaria Programme Director, explore the key concerns shared for this year’s World Malaria Day, and share UKHSA’s update on malaria cases observed in the UK.
World Malaria Day: in pursuit of an equitable world
The theme, “accelerating the fight against malaria for a more equitable world”, highlights the fact that malaria “disproportionately” affects people who live in the “most vulnerable situations”. WHO states that the African Region “shoulders the heaviest burden” of the disease; in 2022 it accounted for 94% of malaria cases and 95% of malaria deaths. WHO reflects that the “current trajectory” indicates that we will miss critical 2025 milestones for reductions in cases and deaths.
The most likely to be affected are those who live in “situations of poverty and with less access to education”. This year, WHO is joining the RBM Partnership to End Malaria and other partners to highlight barriers to health equity, gender equality, and human rights in malaria responses worldwide, with “concrete measures to overcome them”.
Dr Ngamije’s message
Dr Daniel Ngamije, Director of the WHO Global Malaria Programme, shared a message in April 2024, highlighting the collaboration with the RBM Partnership and others. The statement begins by “acknowledging the tremendous contributions of national malaria programmes and their partners”.
“Our collective work will contribute to a more equitable future.”
However, malaria is still a “serious global health challenge” that takes the “heaviest toll on the most vulnerable”. Dr Ngamije is concerned that “too many people” are missing the services and information needed to prevent, detect, and treat malaria. This is particularly true for those “experiencing disadvantage, discrimination, and exclusion”.
“We need to strengthen and step up our support for these populations – not only is it our moral duty, it is the best way to get back on track to achieve our global malaria targets.”
Since 2017, WHO has been reporting “stalling of progress”, notably in countries that carry a high burden of disease. In 2022, malaria killed around 608,000 people and caused 249 million new cases.
“Without a change in the current trajectory, many people, especially those living in situations of greatest poverty and vulnerability, will continue to die from malaria – a disease that is preventable and treatable.”
High burden countries
Dr Ngamije identifies “health inequities” as “hampering efforts” to reduce malaria in the countries hardest hit by disease. With the “High burden to high impact” (HBHI) approach from 2018, countries have been identifying those who suffer most and responding with a “concerted effort” to provide customised packages of interventions and services.
Low burden countries
“Health inequities are also undermining efforts to complete the last mile in the pathway to eliminate malaria.”
In “many” lower burden countries, cases of malaria are “concentrated among vulnerable, hard-to-reach populations”. These populations include mobile and migrant workers, refugees, and indigenous communities.
“Reaching, engaging, and empowering these populations with targeted, gender-responsive, and culturally sensitive interventions and services is an important strategy for achieving our collective vision of a malaria-free world.”
Yaoundé Declaration
In March 2024, Ministers of Health from HBHI countries demonstrated “further political commitment” as they signed the Yaoundé Declaration in Cameroon. This declaration signified Ministers’ commitment to providing “stronger leadership and increased domestic funding for malaria control programmes”, ensuring investment in data technology, applying the latest technical guidance, and enhancing control efforts at all levels.
The declaration demands that countries “sustainably and equitably” address the challenge of malaria, with Ministers recognising the importance of “tackling the root causes of stagnating progress in malaria control”. Further commitments relate to ensuring all populations at risk of malaria “consistently receive the appropriate tools”.
What are WHO and partners doing?
The global malaria response can be strengthened by increased investment into the research and development of new tools to benefit anyone who is at risk, especially the “poorest and most marginalised populations”. WHO hopes that recommended tools will be scaled up in an “equitable and sustainable way”. For example, recent recommendations, such as dual active ingredient nets and malaria vaccines, could increase health equity for populations at risk of malaria.
WHO also suggests that the fight against malaria can be accelerated through a commitment to UHC (universal health coverage).
“Everyone should have access to the health services they need – when and where they need them, and without facing financial hardship.”
WHO recommends reorienting health systems towards primary care, which is understood to be the “most inclusive, equitable, and cost-effective way to achieve UHC”. A recent operational strategy from the Global Malaria Programme has the “potential to shape the malaria ecosystem and achieve impact at country level”. The strategy emphasises that efforts to fight malaria should be “rooted in the principles of health equity, gender equality, and human rights”.
UKHSA data
In advance of World Malaria Day, UKHSA shared data that reveal an increase in malaria cases across England, Wales, and Northern Ireland. Reported cases exceeded 2,000 for the first time since 2001, with cases confirmed in individuals who had “recently been abroad”. The number of cases is described as a sign of the importance of “taking precautions” while travelling abroad.
In 2023 there were 2,004 cases of malaria confirmed after international travel, which compares with 1,369 in 2022. UKHSA links this rise to a “resurgence of malaria in many countries” and an increase in overseas travel as pandemic restrictions were lifted.
ABCD and commentary
UKHSA shares the ABCD of malaria prevention: “Awareness of risk, Bite prevention, Chemoprophylaxis, and Diagnose promptly and treat without delay”. This method can ensure that travellers are protected as they follow travel advice for their destination. There are currently no licensed malaria vaccines for travellers.
Professor Peter Chiodini is Director of the UKHSA Malaria Reference Laboratory (MRL) and remarked that “all malaria cases are preventable”, with “simple steps” reducing infection risks.
“While malaria can affect anyone, the majority of Plasmodium falciparum malaria cases in the UK occur in those of African background. Even if you have visited or lived in a country before, you will not have the same protection against infections as local people and are still at risk.”
Professor Chiodini is working “in partnership with communities at greater risk” to improve access to and use of “effective” malaria prevention measures. Dr Dipti Patel, Director of the National Travel Health Network and Centre, encouraged travellers to “prioritise” their health and “plan ahead”.
“Check the relevant country information pages on our website, TravelHealthPro, and ideally speak to your GP or travel health clinic 4 to 6 weeks ahead of travelling to ensure you have had all the necessary vaccinations and advice you need to ensure your trip is a happy and healthy one.”
At The World Vaccine Congress malaria continues to be a topic of priority and we look forward to continuing these conversations with the community. Do make sure you have subscribed to our weekly newsletters here for more information and insights.
