In March 2023 the CDC commented on data published in the Annals of Internal Medicine that revealed an “alarming” spread of the emerging fungus Candida auris in healthcare facilities in 2020-2021.It also identified a “concerning” increase in 2021 of the number of cases that were resistant to the antifungal medicine echinocandins. In its statement, the CDC deemed the fungus an “urgent” antimicrobial resistant threat, particularly with its growing resistance to antifungal drugs and its potential to cause “severe infections with high death rates”.
What is Candida auris?
Candida auris (C. auris) is a type of yeast that has been causing “severe illness” in hospitalised patients in several countries. For some patients, it enters the bloodstream and causes serious invasive infections throughout the body. The CDC identifies three main causes of concern associated with the fungus:
It is often “multidrug-resistant”.
It is difficult to identify with “standard laboratory methods” and can be misidentified.
Although first identified in Japan in 2009, C. auris was first reported in 2016 in the US. Since then, a total of 3,270 clinical cases (where infection is present) and 7,413 screening cases (where the fungus is present but not causing infection) have been reported to the end of 2021. The most dramatic increase in cases occurred during 2020-2021. Dr Meghan Lyman, lead author of the paper that presents these results, called for continued efforts to identify and contain infections.
“The rapid rise and geographic spread of cases is concerning and emphasises the need for continued surveillance, expanded lab capacity, quicker diagnostic tests, and adherence to proven infection prevention and control.”
Healthcare settings
The CDC reports that patients in healthcare facilities who have been there a long time, have lines of tubes entering their body, or have previously received antibiotics or antifungal medications appear to be at “highest risk of infection”. The increase in cases is linked to both “poor general infection prevention and control (IPC) practices” but also “enhanced efforts to detect cases”.
“The timing of this increase and findings from public health investigations suggest C. auris spread may have worsened due to strain on healthcare and public health systems during the COVID-19 pandemic.”
Professor William Schaffner of the Vanderbilt University Medical Centre told Washington Post that once the fungi get into a hospital, they are “very difficult to control”.
“They can persist, smouldering, causing infections for a considerable period of time despite the best efforts of the infection control team and everyone else in the hospital.”
AMR and C. auris
A particularly concerning feature of these infections is the growing resistance to specific medications. The CDC offers reassurances that “most” of these infections are treatable with echinocandins. However, some infections have been resistant to “all three main classes of antifungal medications”. When this occurs, multiple classes of antifungals at “high doses” are required.
Vaccine possibilities
With increased media attention caused by the CDC’s warning, eyes are on vaccine developers to see if there are preventative measures that could be taken. On 23rd March 2023, The Lundquist Institute (TLI) announced that it has a vaccine candidate in development. This vaccine has reported been shown to “effectively treat mice” with the fungal infection, with the next step being human clinical trials.
“The vaccine used to immunise mice is composed of dual Candida cell surface antigens, which upon vaccination produce neutralising and immune enhancer antibodies. The vaccine also induces a robust T-cell immunity against the fungus, allowing mice to survive the infection.”
Furthermore, TLI suggests that in combination with antifungal drugs, the vaccine results in an “augmented survival”. Dr Ashraf Ibrahim, Investigator at TLI hopes the vaccine can be produced in “good quantities” for the next stage of clinical trials.
“We now have the capability to protect patients who infected by this deadly pathogen.”
We look forward to discussing the possibilities of AMR prevention at the World Vaccine Congress in Washington next week. Join us by getting your tickets here!
Just under a month after the confirmation of an outbreak of Marburg virus disease (MVD) in Equatorial Guinea in February 2023, the WHO has issued an update confirming further cases. The statement from WHO suggests that 8 additional laboratory-confirmed cases have been reported, bringing the total to 9 confirmed cases and 20 probably cases since the declaration last month.
“There are seven deaths among the laboratory confirmed, and all probable cases are dead.”
Of particular concern to health experts is the observation that the areas reporting cases are about 150 kilometres apart, which WHO identifies as a suggestion of “wider transmission of the virus”. WHO assess the risk posed by the outbreak as “very high at the national level”, “moderate” on a regional level, and “low” at the global level.
Equatorial Guinea “recommitted” to containment
WHO’s Dr Abdi Mahamud commented on the situation, recognising that this is Equatorial Guinea’s first outbreak of MVD. It is therefore experiencing a steep learning curve but must not be tempted to think it “could go away”. Dr Mahamud stated that the country is “recommitted” to containing the outbreak.
Cross-border and case increase concern
As WHO notes, the three affected provinces have international borders with Cameroon and Gabon. These borders are “very porous”, and although no cases have been reported in these neighbouring countries, the “risk of international spread cannot be ruled out”.
Furthermore, concern has been raised over the communication between the health authorities and WHO. Helen Branswell writes for STAT that WHO “typically issues more frequent updates” but relies on information from the affected countries.
“The length of time between this update and the one that preceded it is notable.”
Branswell’s description of the outbreak as “significantly larger than has previously been acknowledged” conveys a sense of the anxiety around accurate and timely communication. She contrasts this to quick disclosures from Tanzanian officials as the country also grapples with an outbreak.
We will hear more about vaccine development for Marburg and other filoviruses at the World Vaccine Congress in Washington, where there will also be opportunities to explore the importance of surveillance and transparency in disease outbreaks.
On Friday 24th March 2023 the WHO and other organisations and individuals observe ‘World Tuberculosis Day’ with the theme “Yes! We can end TB!”. This uplifting and emphatic statement is intended to “inspire hope” and encourage action among leaders.
In particular, 2023 is a “critical” year, with opportunities for “visibility and political commitment” offered at the 2023 UN High-Level Meeting on TB. WHO’s “spotlight” for this year will be “urging countries to ramp up progress” as we get closer to this meeting. World TB Day is observed annually on 24th March as this marks the day in 1882 when the TB-causing bacterium was discovered.
What is TB and why are we still fighting?
TB is described by WHO as “one of the world’s deadliest infectious killers”, claiming the lives of “close to 4,400 people” every day. Caused by Mycobacterium tuberculosis, it most commonly affects the lungs and is spread from person to person through the air. Although TB is found across the globe, the largest number of new cases in 2021 occurred in the WHO South-East Asian Region, with 46% of new cases.
As TB is “preventable and curable”, efforts to this end have saved up to 74 million lives since 2000. However, we continue to experience devastating infections and deaths. Most recently, the COVID-19 pandemic has caused major disruptions to global efforts against other diseases, and this has combined with “conflicts” and “socioeconomic inequities” to undo years of progress. Indeed, WHO recently highlighted that “for the first time in over a decade, estimated TB incidence and deaths have increased”.
When we spoke to Dr Mark Feinberg about why this has happened, he offered an interesting insight into how we as humans respond to threats. He suggests that “if you have a problem and it’s there for a long time, and it’s hard to deal with, you tend to try and ignore it and put it in the back of your mind”. Dr Feinberg argues that for TB, as with other infectious diseases, media attention may have slipped but progress continues to be made by researchers.
Missing key goals
In an article in The Lancetin March 2023, authors Dr Tereza Kasaeva, Hannah Monica Dias, and Dr Madhukar Pai wrote about the importance of meeting the “ambitious targets” from previous UN meetings that have been missed.
For example, treatment goals were identified in 2018 for countries to treat an “additional 40 million” people with TB and provide preventative treatment to “at least 30 million people at risk” by 2022. However, between 2018 and 2021, 26.3 million were treated. This is “still far short of the 40 million. Furthermore, the number of people provided with preventative treatment was “12.5 million”, again “still far from the target”. Why is this?
Disruptions and devastation
The authors identify the “health-care disruptions due to the COVID-19 pandemic” as a key factor. In addition, conflicts and “widening socioeconomic and health inequities” have been “devastating” for TB care.
“As sobering as this news is, it is important to find hope and keep the fight going.”
Turning the TB tide
The paper does identify “reasons for optimism”. Through a combination of “high-level leadership, increased investments, faster uptake of new WHO recommendations and adoption of innovations, accelerated action, and multisectoral collaboration” the authors identify potential to “turn the tide” on TB.
“2023 will be a crucial year.”
As we continue to engage with lessons learnt through the COVID-19 pandemic, we can exploit the “remarkable investments” made across the countermeasure spectrum.
“It is time to develop and scale new vaccines for tuberculosis, and the case for investment is strong.”
The authors state that COVID-19 vaccine development platforms could be “leveraged and deployed” for TB vaccines to “enormous” effect.
Priorities for partners
The paper also offers ten priorities that require a “unified response across sectors and partners” to “fast-track the fight” against TB.
Enhancing high-level leadership and advocacy to prioritise ending tuberculosis driving down deaths and ending suffering.
Strengthening multisectoral engagement and accountability to address the upstream and wider health and social determinants of tuberculosis.
Urgently increasing funding for essential tuberculosis services, including the health workforce.
Substantially increasing investments in tuberculosis research to drive technological breakthroughs, such as vaccines and the rapid uptake of innovations.
Advancing universal health coverage and integration of efforts to end tuberculosis into primary health care to ensure all people with tuberculosis have access to affordable quality care while strengthening health systems and engaging all providers.
Addressing the drug-resistant tuberculosis crisis, with a focus on roll-out of WHO-recommended universal drug susceptibility testing and shorter, all-oral, injectable-free treatment to close persistent gaps in care.
Markedly scaling up provision of preventative treatment for tuberculosis, especially for household contacts.
Ensuring meaningful engagement of civil society, communities, and people affected by tuberculosis.
Promoting human rights and combating stigma and discrimination.
Aligning with the ongoing efforts on pandemic preparedness to proactively tackle future disruptions to tuberculosis services through key partnerships and collaborations for better efficiency and synergy, particularly at the country level.
“Although the COVID-19 pandemic has been a massive setback for progress in ending tuberculosis, it has shown us that nothing is impossible if we set our minds to it and make the necessary investments.”
“We must be bold enough to imagine a world where people with tuberculosis receive humane and quality care wherever they are and have access to the best tools we have and where tuberculosis finally gets the budget and political attention we need to end this great plague.”
We will hear more from experts like Dr Mark Feinberg on diseases that have been “neglected” during the COVID-19 pandemic at the World Vaccine Congress in Washington, so join us by getting your tickets here.
Africa CDC has confirmed that the Ministry of Health of the Republic of Tanzania declared an outbreak of Marburg virus disease (MVD) on 21st March 2023. The outbreak has been reported in Bukoba district, Kagera region, in north-western Tanzania. So far, a total of 8 confirmed cases and 5 deaths have been announced.
MVD
Marburg is a highly infectious and highly fatal zoonotic haemorrhagic disease. Africa CDC describes that human-to-human transmission occurs through “direct contact with body fluids” from infected persons or contact with materials that have been contaminated with infectious fluids. As noted by the CDC, there is no licensed vaccine or approved treatment, but “supportive management improves survival”.
The situation in Tanzania
The cases in Tanzania presented with “fever, vomiting, and bleeding from different body orifices” according to Africa CDC. Samples collected were tested positive for MVD by PCR at the National Public Health Laboratory.
This is the first confirmed incidence of MVD in Tanzania, and the high population mobility within the region poses a risk of cross-border transmission to neighbouring countries: Uganda, Rwanda, and Burundi.
The Ministry of Health has reportedly deployed rapid response teams to support further investigations. 161 contacts have already been identified and are being monitored, with active case search, case management, and risk communication “ongoing” in affected areas. Africa CDC is also sending experts to support the local response. The importance of understanding the “cross-border context” of the outbreak has been emphasised. Tanzania is the second African Union Member State to report an active outbreak at the moment, after Equatorial Guinea declared an outbreak in February.
Dr Ahmed Ogwell Ouma, Acting Director of Africa CDC, highlighted the organisation’s commitment to supporting “Tanzania and her neighbours” to “arrest this outbreak as soon as possible”. He urged members of the public to “continue sharing information in a timely manner” to promote an “effective response”.
“These emerging and re-emerging infectious diseases are a sign that the health security of the continent needs to be strengthened to cope with the disease threats.”
We will hear more about current efforts to develop effective Marburg vaccines at the World Vaccine Congress in Washington next month. Join us by getting your tickets here.
In March 2023 new metagenomics data and SARS-CoV-2 sequences appeared on GISAID (the Global Initiative for Sharing Avian Influenza Data) and were available to researchers across the world for a short period of time. Although access was restricted to allow further updates, WHO was notified of this data and later learnt that they are the basis for an update to a paper that is being re-submitted to Nature by China CDC.
A statement from WHO in March indicated that discussions between WHO, SAGO, and China CDC, with participation from “some of those who had accessed the data”, enabled the organisations to “gauge the significance of this data and the analyses of this data”.
New data, new ideas
WHO suggests that the presentations from China CDC and “invited international researchers” identified newly available data from the Huanan Seafood Wholesale Market. This included metagenomic data of environmental samples from stalls and wastewater collection sites from as early as January 2020.
Not only were SARS-CoV-2 sequences available, but “mitochondrial DNA of several animal species” and human DNA. Among the animal species, DNA from “wild raccoon dogs, Malaysian porcupine, and bamboo rats” were included in “SARS-CoV-2 positive environmental samples”. WHO believes that these findings demonstrate the presence of animals at the market “shortly before the market had been cleared” on the 1st of January 2020 during public health measures.
“These results provide potential leads to identifying intermediate hosts of SARS-CoV-2 and potential sources of human infections in the market.”
WHO refers to a pre-print by Liu et al, 2022, which indicates that raccoon dogs were not among the animals tested in early 2020. However, the presence of “high levels of raccoon dog mitochondrial DNA” in this data does indicate that raccoon dogs and other animals may have been present at the market before it was cleaned.
SAGO encourages sharing
SAGO states that it will continue to evaluate “any and all” scientific data that are shared by researchers from “anywhere in the world”.
“SAGO encourages any and all data related to the studying of the origins of SARS-CoV-2 be made available immediately for robust and comprehensive review.”
Although previously accused of neglecting the investigations into the origins of the COVID-19 pandemic, SAGO continues to “strongly” recommend that researchers in China investigate the “upstream sources of the animals and animal products present” at the Huanan market before its closure in January 2020. As Dr Mike Ryan emphasised in a WHO briefing in February 2023, WHO relies on Member States’ independent research to be shared with the global scientific community.
For more on SARS-CoV-2 data and vaccine development, join us at the World Vaccine Congress in Washington next month.
The Global Polio Eradication Initiative (GPEI) and WHO Africa confirmed in March 2023 that cases of circulating vaccine-derived poliovirus type 2 (cVDPV2) had been detected in Burundi and the Democratic Republic of the Congo (DRC). These cases have been linked to the novel oral polio vaccine type 2 (nOPV2). The viruses were identified in stool samples from 7 children with acute flaccid paralysis (AFP) and from 5 environmental samples.
Acute flaccid paralysis is defined by WHO as the “acute onset of weakness or paralysis with reduced muscle tone in children”. WHO emphasises that “early detection” is critical to containing polio outbreaks, which are one cause of the condition.
CVDPVs
GPEI describes cVDPVs as variant polioviruses that can emerge when the “weakened live virus” of an oral polio vaccine, shed by vaccinated children, circulates in “under-immunised populations for long enough to genetically revert to a version that causes paralysis”.
The crucial detail that GPEI emphasises is that a child “cannot get cVDPV infection from receiving a polio vaccine”. In fact, they emerge when “not enough children are vaccinated” and the strain circulates in areas with “poor sanitary conditions”. Over time, with this circulation, genetic changes can result in “reversion to a form that can cause paralysis”.
The current situation
Health authorities in Burundi declared an outbreak after confirming 8 polioviruses. This is the first detection of its kind in “more than three decades”, suggests WHO. The cases were confirmed in a 4-year-old child who “had not received any polio vaccination” and in contacts of the child. Further samples from environmental surveillance of wastewater confirmed the presence of circulating poliovirus type 2.
Dr Matshidiso Moeti, WHO Regional Director for Africa, commented on the “effectiveness of the country’s disease surveillance”.
“Polio is highly infectious and timely action is critical in protecting children through effective vaccination.”
Dr Moeti emphasised that WHO will support national efforts to “ramp up polio vaccination”. This will ensure that “no child is missed” and will therefore face “no risk of polio’s debilitating impact”. The government of Burundi declared the detection of the virus to be a national public health emergency.
Health authorities, in collaboration with WHO and GPEI partners, are embarking on “further epidemiological investigations”. GPEI states that it will support local authorities in both Burundi and the DRC as well as neighbouring countries to “conduct a thorough risk assessment’ and “plan vaccination responses”.
In DRC, the eastern regions are classified as one of GPEI’s seven most “consequential geographies for poliovirus outbreak risk”. This is due to “complex humanitarian challenges” creating “longstanding barriers” to effective polio vaccination.
Vaccination continues
GPEI estimates that almost 600 million doses of nOPV2 have been administered across 28 countries. The organisation states that “focused safety, effectiveness, and genetic stability monitoring” will continue as the vaccine continues to be used.
“Ultimately no vaccine sitting in a vial can protect a child.”
GPEI calls for “rapidly” implemented and “high-quality” immunisation campaigns to promote effective and efficient vaccination to stop the spread of the virus. For more on the importance of childhood immunisation join us at the World Vaccine Congress in Washington next month. In particular, a session on the “policy and politics” of childhood vaccination may be of interest.
In March 2023 WHO Africa reported that the Ugandan Ministry of Health is planning to vaccinate over 1.9 million children against yellow fever in collaboration with UNICEF, WHO, and Gavi. Uganda was one of 14 African countries that reported confirmed cases of yellow fever in 2022
Yellow fever is transmitted by the Aedes Aegypti or Haemagogus mosquito species. Infections can cause serious illness and, for between 30% and 60% of patients with severe cases, death. Although there are “no specific therapeutics” there is a vaccine. It is “safe, highly effective, and only a single dose is needed for lifelong protection”.
Uganda is a “high-risk country” for transmission due to less than 10% of the population being immunised against yellow fever. It confirms “sporadic outbreaks” every 3 to 5 years. Most recently, cases have been reported in urban areas, which is where around 24% of Ugandans live.
Strategy and collaboration
WHO reports that, with the support of the Eliminate Yellow fever Epidemics (EYE) Strategy and key partners, a “multi-country outbreak response” was organised in countries that face “more serious yellow fever transmission”.
In October 2022, during Integrated Child Health Days (ICHD), Uganda moved forward with plans to introduce the yellow fever vaccine into routine immunisation. This was despite the declaration of an Ebola outbreak just a month before. Children aged 9 months will be vaccinated with yellow fever and measles-rubella vaccines.
Commitment to control
Dr Jane Ruth Aceng Ocero is Uganda’s Minister of Health and is “committed to controlling yellow fever transmission”.
“We want to ensure that our people are protected against this high-threat disease, and vaccines remain the main tool we have.”
Dr Yonas Tegegn Woldemariam, Who Representative in Uganda, applauded this “important step towards immunisation against yellow fever”.
“Vaccination is the single most important measure for preventing yellow fever, and the prevention of outbreaks can only be achieved if the majority of the population is immunised.”
Thabani Maphosa serves as Gavi’s Managing Director, Country Programmes Delivery, and believes the introduction of this vaccine is “so important” after a rise in recent outbreaks. He hopes that the commitment of the government will “save many lives”. Dr M. Munir A. Safieldin, UNICEF Representative to Uganda, stated that “there is no cure for yellow fever” but it “can be prevented”. The addition of a vaccine to the routine immunisation schedule is “critical” to saving children’s lives and “eliminating epidemics”.
We will hear more on routine immunisations at the World Vaccine Congress in Washington next month. Join us by purchasing your tickets here.
In March 2023 researchers at Tel Aviv University and the Israel Institute for Biological Research announced that they have developed an mRNA-based vaccine that is “100% effective against a type of bacteria that is lethal to humans”. With results published in Science Advances, the authors claim that although “a multitude” of mRNA vaccines are being designed and deployed against viral diseases or cancer, “bacterial pathogens remain largely untapped”. Thus, they investigated the potential that mRNA lipid nanoparticles (LNPs) present.
mRNA-LNP meets plague
The authors note that mRNA-LNPs are “clinically relevant, rapidly manufactured, and inherently modular”. These qualities were demonstrated during the COVID-19 pandemic, which emphasised the importance of the platform in “emergency preparedness”.
The Gram-negative bacterium Yersinia pestis is well-known as the culprit of the infectious disease that has “claimed the lives of millions of people throughout human history”. Indeed, the authors recognise that “because of its lethality and infectivity”, it is “classified as a potential bioterror agent”. Despite this, antimicrobials have led to a decrease in morbidity and mortality, yet there is a pressing need to develop vaccines in the face of antimicrobial resistance.
The paper suggests that “several” candidates confer protection in animal models and clinical studies, but none has been approved for use in “Western countries”. Thus, the research goal was to design several mRNA vaccine versions based on the F1 capsule protective antigen, evaluate the antigen-specific humoral and cellular responses in mice, and assess the protection effectiveness against a “fully virulent Y. pestis strain using challenge trials”.
Attaining the unattainable
Dr Edo Kon, first author, refers to the “great advantage” of mRNA vaccines, besides their “effectiveness”: “the ability to develop them very quickly”.
“However, until now scientists believed that mRNA vaccines against bacteria were biologically unattainable.”
The study demonstrates the opposite, Dr Kon says, with the results indicating that it is entirely possible to develop vaccines that are “100% effective against deadly bacteria”.
“Our study demonstrates a rapid, fully protective mRNA-LNP vaccine against the lethal Y. pestis bacteria”.
The authors hope that the platform can be “harnessed” for the development of effective vaccines against other bacterial pathogens.
“These findings are of substantial relevance and immense importance, considering the global emerging crisis of antibiotic resistance and the lack of effective conventional therapies and vaccine candidates.”
Professor Dan Peer of the Laboratory of Precision Nano-Medicine hopes that the study will “provide a pathway” for any bacterial pandemic threats that we might face in the future.
Myriad mRNA benefits
Compared to “traditional recombinant protein vaccines”, the mRNA-LNP vaccine platform has “several advantages”, according to the scientists. For example, mRNA vaccines are “highly versatile” and can be “rapidly manufactured and easily adjusted” to respond to variants of concern in pandemics.
Another advantage is the induction of “both humoral and cellular immune responses”, which expands the “potential antipathogenic effect against pathogens” through “both intra- and extracellular life cycles”.
Storage sensitivities
As we have explored in previous posts, a “major limitation” for vaccines developed with mRNA-LNP is the “inherent instability of mRNA molecules”. Consequently, there is a requirement for “cold” or “ultracold” shipping and storage.
For more about technological partnerships to combat these challenges, head to our technology section to read our posts.
We will hear more about preparations for a bacterial pandemic and developments in mRNA technology at the World Vaccine Congress in Washington next month. To join us, get your tickets here.
After the news of the death of a child from avian influenza A (H5N1) in Cambodia in February 2023, the WHO has published an update on the situation with recommendations and risk assessments. This statement also confirmed that a second case, a family contact of the first, has been reported. Investigations are underway to determine the exposure of the cases to the virus.
What does WHO know?
WHO reports that the first case was reported on 23rd February 2023 by the Cambodia International Health Regulations (IHR) National Focal Point (NFP), with a second case reported on 24th February 2023. These cases are the first to be reported from Cambodia since 2014.
The first case was an 11-year-old girl from Prey Veng province, who was receiving treatment for symptoms at a local hospital from 16th February. She was then admitted to the National Paediatric Hospital on 21st February with severe pneumonia. A sample collected that day tested positive for H5N1 at the National Institute of Public Health and confirmed positive by Institute Pasteur Cambodia, the National Influenza Centre. The child died on 22nd February 2023.
From this index case, 12 close contacts were identified, and samples collected and tested. Investigations confirmed the second case on 23rd February as the father of the child. He is asymptomatic and in isolation at the referral hospital. The other samples were negative.
Cambodia’s public health response
WHO states that a “joint animal-human health investigation” is underway in the province, with the intention of identifying the source and means of transmission. Furthermore, a “high-level government response” is being implemented to limit further spread.
WHO assesses the risk
WHO considers that, as the virus “continues to be detected in poultry populations”, additional human cases “can be expected”. Although the virus “does not infect humans easily” and human-to-human transmission “appears to be unusual”, there is a risk due to exposure to infected poultry or contaminated environments.
Public health measures at human and animal level have been implemented, and further “characterisation” of the virus is expected. However, “available epidemiological and virological evidence suggest that current A(H5) viruses” do not have the “ability of sustained transmission among humans”. Thus, the “likelihood of sustained human-to-human spread is low”.
“Based on available information so far, WHO assesses the risk to the general population posed by this virus to be low.”
Vaccines
Although vaccines against H5N1 have been developed for human use, they are “note widely available”. WHO, through the Global Influenza Surveillance and Response System (GISRS), will continue to monitor the virus’ evolution and recommends continued vaccine development for “pandemic preparedness purposes”.
Further advice
Acknowledging the widespread reports of circulation in birds, “sporadic” cases in humans, and the “constantly evolving nature” of this virus, WHO emphasises the importance of global surveillance. When avian influenza viruses are detected in a specific location, people who are engaged in “high-risk tasks”, such as those that involve interaction with sick or dead birds, should be “provided with and trained in the proper use of appropriate personal protective equipment”.
When a case is suspected or confirmed in humans, a history of exposure to animals and travel should be conducted alongside contact tracing. Although there is no widely available vaccine to protect humans against avian influenza, WHO recommends that all people who interact with birds should have a seasonal influenza vaccination to “reduce the potential risk of reassortment”.
Travellers to locations with known outbreaks of animal influenza should avoid areas such as live animal markets, places where animals are slaughtered, or farms. The usual sensible precautions are encouraged, including regular hand washing and good safety and hygiene practices. However, WHO is not advising the application of travel or trade restrictions at the moment.
For more on avian influenza vaccines and the challenges they present, join us at the World Vaccine Congress in Washington this April.
Just months after the conclusion of an outbreak of Marburg virus in the Ashanti region of Ghana, the Ghana Health Service has issued a statement to confirm two cases of Lassa fever in the capital, Accra. The first confirmed case has sadly died, but the second, a contact of the fatal case, is reportedly “stable”. Contacts have been identified and precautionary measures are being taken.
Information provided by the Health Service
On 26th February 2023, the Ghana Health Service published a release to announce that it had been notified of two confirmed Lassa fever cases from the Noguchi Memorial Institute for Medical Research on 24th February 2023. The first case was a 40-year-old who had been unwell for “about two weeks” before death at the Korle-Bu Teaching Hospital. The contact of this case is “currently on admission but is very stable”. 56 contacts are being “followed up”.
The statement indicates that Lassa fever is endemic in the country, which recorded its first case in 2011. The following public health measures are being implemented:
Public Health Emergency Management committees at all levels (National, Regional, and District) have been activated
Detailed investigation including environmental assessment has started
Essential medications and logistics including PPE are being mobilised
Contact tracing and management are ongoing
Quarantine of contacts has been instituted and daily follow up by health staff is ongoing
Strict Infection Prevention and Control (IPC) with barrier nursing has been instituted
Sensitisation of health staff on Lassa fever has started
Community sensitisation and education on Lassa fever are ongoing
Lassa fever and a vaccine
The statement suggests that the incubation period can be up to 21 days with transmission through direct contact with bodily fluids of a person who is infected. Furthermore, it identifies the lack of licensed vaccine, emphasising the importance of prevention and control measures.
“The Ministry of Health and Ghana Health Service, in collaboration with our partners, wishes to assure the general public that all efforts are being made to contain this outbreak and prevent further spread of the virus.”
Recent collaborations into Lassa fever vaccine research might have an application in this outbreak, such as the IAVI-CEPI or the DARPA-The Vaccine Group partnerships. We will hear more about Lassa fever and related viruses at the World Vaccine Congress in Washington this April. Join us by getting your tickets here.
Following the announcement of an outbreak of Marburg virus in Equatorial Guinea in February 2023, WHO has issued a situation update from the limited information available. This includes advice to the country itself and other countries about the risk posed by travel to and from the region.
What WHO knows so far
The situation summary states that on 7th February 2023, the Ministry of Health and Social Welfare of Equatorial Guinea reported the deaths of a “number of individuals” with suspected haemorrhagic fever. 5 days later, a sample was confirmed positive for Marburg virus by a real-time polymerase chain reaction (RT-PCR) at the Institut Pasteur in Senegal. Current investigations continue to identify additional cases.
“WHO is supporting the response by strengthening contact tracing, case management, infection prevention and control, laboratory, risk communication, and community engagement.”
As this is Equatorial Guinea’s first reported Marburg outbreak, WHO describes the “country’s capacity to manage the outbreak” as “insufficient”.
Risk level
WHO describes the outbreak risk as “high at the national level”, but “moderate” on a regional level and “low” at a global level. These risk assessments were made using “available information”, such as the possibility of “transmission chains that have not been tracked” and unidentified contacts of the 9 deceased cases.
WHO also notes that “with the exception of one case”, who died in a health facility, the remaining 8 died “in the community” with “unknown” burial conditions. Furthermore, “cross-border population movements are frequent”, and the borders between districts and other countries are “very porous”. Thus, there is a risk of cross-border spread.
Public health response
WHO identifies the following measures comprising a public health response on the ground:
In-depth epidemiological investigations are underway to determine the source of the outbreak.
National teams have been deployed to the affected districts for active case finding, contact tracing, isolating and providing medical care to cases.
WHO has deployed experts in epidemiology, case management, infection prevention, laboratory and risk communication to support national response efforts and ensure community engagement.
WHO is also facilitating the shipment of tents, materials for sample collection and analysis, and a viral haemorrhagic fever kit including personal protective equipment for 500 health workers.
WHO is supporting the transportation of samples to laboratories in Senegal and Gabon as plans are underway to set up laboratory facilities in-country.
Advice from WHO
The current advice from WHO to other countries is that travel or trade restrictions are unnecessary “based on available information for the current outbreak”. However, it provides further guidance for the communities that are currently affected, or at risk of becoming affected. Interventions include “case management, surveillance including contact tracing, a good laboratory service, infection prevention and control including safe and dignified burials, and social mobilisation”.
“Community engagement is key to successfully controlling MVD outbreaks.”
As part of this engagement, WHO recommends “raising awareness of risk factors” and protective measures.
Research continues into safe and effective vaccine candidates, and we hope to hear more on this front at the World Vaccine Congress in Washington.
With growing concern at the increasing cases of avian influenza in mammals across the world, the spread has taken a tragic turn with the death of an 11-year-old girl in Prey Veng province, Cambodia. After her death, samples were sent to the National Institute of Public Health for confirmation of the cause. It is not known how she became infected.
Details of the case
BNO News reports that the girl lived in Roleang village, Prey Veng province. She was taken ill just under a week before her death, displaying symptoms such as a cough and fever. The Infectious Diseases Department of Cambodia’s Ministry of Health stated that she received treatment at “local level” before becoming tired.
After being sent to the National Children’s Hospital in Phnom Penh, she sadly died on 22nd February and was buried in her village. Following her death, a sample was sent to be tested and was confirmed positive for H5N1.
Although it is unclear how or when she became infected, it is reported that an unusually high number of wild animals had been found dead in the area. An emergency response team has been dispatched.
The human threat
With increasing infections in mammals across the world, such as minks and foxes, questions have been raised about the possibility of transmission to and/or between humans. Dr Tedros Adhanom Ghebreyesus, WHO Director-General, said in a statement earlier in February that the spread must be “monitored closely”.
Although WHO “assesses the risk to humans as low”, he advised preparing for “any change in the status quo”. More recently, Dr Jeremy Farrar, newly appointed Chief Scientist at WHO, warned of a need to develop safe and effective vaccines in response to this “concerning issue”.
Despite repeated assurance for global health experts that the human risk is low, the death of a child is likely to increase fear. Once again, we are reminded of the importance of protecting communities with greater exposure to potentially infected animals, and those for whom their daily lives involve interaction with livestock.
We will hear more about the threat of and response to avian influenza at the World Vaccine Congress in Washington this April.
After an update from WHO in November 2022 that almost 40 million children are “dangerously susceptible” to measles, the Measles and Rubella Initiative (M&RI) released a statement on the future of the fight. Founded in 2001 as the Measles Initiative, it was expanded to include rubella elimination in 2012.
The founding partners are the American Red Cross, US CDC, the United Nations Foundation, UNICEF, and WHO. It also involves the Bill and Melinda Gates Foundation and Gavi. The Initiative is part of the Immunisation Agenda 2030 (IA2030).
Huge strides
The founding partners suggest that since the foundation and expansion of the initiative, “huge strides have been made”. An estimated 5 million lives have been saved through the delivery of vaccines to children across the world, and more than $1.2 billion has been invested in “control activities” in partnership with Gavi and the Gates Foundation.
The statement indicates that from 2000 to 2021, the annual number of estimated measles deaths decreased 83%, from 761,000 to 128,000. The goal is to save “another 50 million lives” by the end of 2030, with measles immunisation contributing heavily to this.
Strategic Framework
The founding partners have adopted a Measles and Rubella Strategic Framework 2030, “fully aligned with IA2030”, to “maximise the lifesaving impact of vaccines”. This Framework envisions “a world free from measles and rubella” with the ambition of achieving and sustaining regional elimination goals.
After a consultation process to “fully integrate the strategy, coordination, and action” with the IA2030 strategy and partnership process, the “newly revitalised” partnership will be called the IA2030 Measles and Rubella Partnership (M&RP). The membership includes the original founders, Gavi, and the Gates Foundation.
This is described as “opportune” in the context of the “worst continued backsliding in global immunisation coverage in 30 years”. This is largely attributed to the COVID-19 pandemic and “related disruptions”.
“We need to work more closely than ever before to address the nearly 40 per cent increase in the number of unvaccinated children.”
For more discussion on partnering to overcome routine immunisation challenges, come to the World Vaccine Congress in Washington this April.
In February 2023 BactiVac, the Bacterial Vaccines Network, announced that it had secured £1 million in funding from Wellcome to “accelerate the development of bacterial vaccines” and “combat the threat” of AMR.
BactiVac
BactiVac comprises 1,400 members across 78 countries, bringing academia, undustry, policymakers, and funders together with the goal of advancing the development of vaccines against “bacterial pathogens of global importance”. It is hosted at the University of Birmingham in the UK and was established in 2017 by Professors Calman MacLennan and Adam Cunningham.
“From the start, BactiVac has been a leading advocate for bacterial vaccinology, enabled collaborations in vaccine development through research project funding, delivered key training for members, supported training exchanges, and hosted Annual Network Meetings.”
BactiVac has a specific focus on LMICs, aiming to “address bottlenecks” and “capacity building among early career researchers in these countries”.
Bacterial infections
BactiVac states that “over 7 million people” die from bacterial infections each year. Director of Infectious Diseases at Wellcome, Professor Gordon Dougan, described the “scale of the challenge” that “deadly bacterial infections” and AMR present as “clearer than ever before”.
“We are proud to continue supporting [BactiVac] as they embark on scaling up their impact.”
Funding for 4 years
The funding from Wellcome is expected to “enhance the impact” of the Network over 4 years. BactiVac Co-Director Professor Calman MacLennon is “delighted” at the news, hoping to “build on what has been achieved over the first five years”.
“We will…continue to promote the development of bacterial vaccines and champion their importance in overcoming the silent pandemic of antimicrobial resistance.”
Professor Adam Cunningham, another Co-Director, is “grateful” for the “generous support” and shared vision.
“In this exciting new phase, BactiVac will continue to support its membership to develop new vaccines, particularly those that are relevant to LMICs.”
For more on BactiVac’s vision, read our interview with Dr Micoli here. We look forward to hearing further details on vaccine advances from BactiVac at the World Vaccine Congress in Washington this April. Join us there by purchasing your tickets today.
During a meeting of the International Health Regulations (IHR) Emergency Committee in February 2023 on the mpox outbreak, the current infection rates and containment measures were considered alongside plans for the future. Although the Committee commended global efforts, it elected to continue to classify mpox as a PHEIC while “beginning to consider plans to integrate mpox prevention, preparedness, and response” into national surveillance and control programmes.
Dr Tedros Adhanom Ghebreyesus
Dr Tedros Adhanom Ghebreyesus, Director General of WHO, described the decline in cases as “very pleasing”. Since the PHEIC was declared, “affected countries” have demonstrated “hard work” in what he believes to be a “sustained decline”.
“More than 85,000 cases of mpox have now been reported to WHO, with 92 deaths.”
Despite the progress, “more than 30 countries” reported last month. The majority of cases are from the Regions of the Americas. In his remarks, Dr Adhanom Ghebreyesus also noted that it is “difficult to chart the true trajectory of the epidemic in the African Region due to the limited data available”.
“Data sharing remains critical for all countries.”
He suggested that, regardless of the decision made by the Committee, “bringing the outbreak to an end still requires intense effort”. Furthermore, we “must remember” that mpox has been “endemic in many low-income countries in Africa for many years”. Thus, as we force it out of countries that have “not seen major outbreaks before”, the outbreak “must spur sustained investment in addressing this disease everywhere”.
The Committee convenes
During the meeting the Committee acknowledged progress but identified “several concerns”. These include:
Ongoing transmission in some regions
Insufficient evidence regarding vaccine effectiveness on the individual and population levels and duration of immunity, either disease or vaccination-induced
A potential shift in some countries towards the most marginalised populations who have the least access the prevention measures and treatments
The possibility that behaviour change is not sustained in the long run
Reduced surveillance and lack of reporting of cases to WHO, particularly in countries where the disease is endemic
Despite these concerns, the Committee noted that the global risk is “moderate” and that “the predominant mode of transmission remains through direct and sexual contact”. Thanks to “community engagement activities” transmission has declined in many areas. However, there are concerns about the “possible resurgence of cases in some regions”, due to “seasonal differences” and “the resumption of events and other mass gatherings” as well as inequities in vaccine distribution and testing.
“The Committee advised maintaining PHEIC”.
For more discussion on the containment and prevention of mpox at the World Vaccine Congress in Washington, get your tickets now.
After an article in Nature in February 2023 in which it was suggested that WHO had “quietly” abandoned plans to continue the investigation into the origins of COVID-19, senior members of the organisation responded on Twitter and in a press conference. Dr Maria van Kerkhove, who was quoted in the article as expressing frustration at the political situation, stated emphatically that WHO had not “abandoned” the investigation, saying they “have not, and will not”.
Twitter response
Initially Dr van Kerkhove and colleagues took to Twitter to “make one thing clear”. Dr van Kerkhove described the headlines, prompted by the Nature article, as “inaccurate”. She emphasised that the allegation that WHO had neglected or moved on from the investigation was “not true”.
“We have never, nor will we ever abandon this. We have said this loudly, clearly, repeatedly. We will continue to say this.”
In an earlier tweet, Dr van Kerkhove suggested that “we need more cooperation and collaboration with China”. Later, during the press conference, she echoed these calls for “cooperation”, saying that studies “need to be conducted in China” as recommended by WHO and SAGO.
“We need cooperation from our colleagues there to advance our understanding.”
Press conference
In a press conference on the same day, questions were raised about the article, giving senior representatives an opportunity to respond. Although Dr van Kerkhove is quoted, she indicated that the quotations were misleading in the context of a lengthy discussion with the reporter. She commented that it was an “error in reporting”.
During the press conference, reference was made to SAGO, the Scientific Advisory Group for the Origins of Novel Pathogens. Established in 2021, SAGO published a preliminary report in June 2022, calling for continued collaboration and investigation from Member States. The responsibility of Member States was highlighted by Dr Mike Ryan, who criticised the “constant narrative” that expected WHO to take the lead beyond its jurisdiction.
Dr Ryan suggested that SAGO “laid out very specifically” what was needed for the future of the investigation. Dr van Kerkhove stated that although initially a kind of “phase 2” was intended, this evolved into SAGO, which became WHO’s “best effort” to move forward.
SAGO
The report from SAGO in June 2022 emphasised that “its work has only just begun” and it is “firmly focused on science and public health”. Therefore, its recommendations involve “important elements that will need to be considered as part of a global framework”.
“There are, however, further studies needed to follow up on several gaps in our knowledge.”
The full SAGO report outlines “primary recommendations” in 3 areas:
The development of a global framework that will outline necessary studies to conduct once an emerging pathogen appears or re-appears.
Preliminary recommendations for additional studies urgently needed to understand the origins of SARS-CoV-2.
Areas to be explored concerning the emergence of SARS-CoV-2 variants of concern, such as Omicron.
Science and morality
Dr Tedros Adhanom Ghebreyesus emphasised the importance of investigations from two perspectives: “science” and “moral”.
“When I say science, we need to know how this started in order to prevent the next one. Second, when I say moral…it’s morally very important to know how we lost our loved ones…we need to continue to push until we get the answer.”
What further work would you like to see from the global community, and what responsibility does WHO have to drive this?
We look forward to hearing more from WHO at the World Vaccine Congress in Washington this April.
In February 2023 an article in Nature announced that the WHO has “quietly shelved the second phase” of the “much-anticipated scientific investigation” into the origins of the COVID-19 pandemic. Referring to political challenges, the team of experts will not conduct Phase 2 of the investigation into where, when, and how the virus originated. This is likely to enable further fuel for theories that COVID-19 was the result of laboratory leaks.
Note: the article by Nature has been refuted by Dr van Kerkhove and colleagues at WHO.
Hands are tied
Nature reports that, without access to China, WHO is unable to investigate the origins of COVID-19 further. Dr Angela Rasmussen of the University of Saskatchewan told Nature that “their hands are really tied”.
This is potentially due to political tensions exacerbated by claims that the virus was a lab leak from the Wuhan Institute of Virology. Encouraged by politicians in the US in particular, the theory lends itself to accusatory and demonising narratives. However, the report from Phase 1 of WHO’s investigation suggested in 2021 that the possibility of a lab leak was “extremely unlikely”.
Dr Maria van Kerkhove, WHO epidemiologist, told Nature that there “is no Phase 2” as “plans have changed”. Although she did not specifically point fingers, she did indicate that “politics” had “hampered progress”.
A delicate situation poorly handled
Dr Gerald Keusch, associate director at the National Emerging Infectious Diseases Laboratory Institute in Massachusetts blames the investigation’s demise on poor handling from the global community, China, and WHO. He suggests that WHO should have been “relentless” in forging more positive relations with China, and more transparent about the state of play.
Dr van Kerkhove is allegedly frustrated that efforts to establish collaboration with colleagues in China have not been fruitful.
“We really, really want to be able to work with our colleagues there”.
Other studies
Nature reports that beyond the confines of the “formal WHO-led process”, some studies have gone ahead. For example, an analysis of donor blood at the Wuhan Blood Centre before December 2019 was conducted by researchers in Beijing and Wuhan. Looking for signs that SARS-CoV-2 had infected patients early in the pandemic, the team did not find any blocking antibodies in more than 88,000 samples.
This study suggests that the virus had “probably” not emerged as early as September and was “not widespread in Wuhan in late 2019”. Another Chinese study has not yet been peer reviewed, by reports traces of SARS-CoV-2 at the Huanan seafood market, Wuhan. Samples from sewage and surfaces led the researchers to conclude that the virus was most likely shed by humans. However, others are eager to examine the data to potentially identify animal species.
For more on pandemic threats and understanding emerging diseases join us at the World Vaccine Congress in Washington this April.
In February 2023, WHO Africa confirmed that Equatorial Guinea had announced an outbreak of Marburg virus disease following the deaths of at least nine people. Preliminary tests after these deaths in the western Kie Ntem Province were positive for the viral haemorrhagic fever.
Deaths and suspected cases
The health authorities in Equatorial Guinea sent samples to the Institut Pasteur reference laboratory in Senegal, with support from WHO, to “determine the cause of the disease” after an alert by a district health official on 7th February. 8 samples were tested at the lab, with one being confirmed positive for the virus.
“So far nine deaths and 16 suspected cases with symptoms including fever, fatigue, blood-stained vomit, and diarrhoea have been reported.”
Investigations and containment efforts
WHO emphasises that further investigations are ongoing, with advance teams deployed in the affect districts to “trace contacts” and “isolate and provide medical care” to symptomatic patients.
“Efforts are also underway to rapidly mount emergency response, with WHO deploying health emergency experts in epidemiology, case management, infection prevention, laboratory, and risk communication to support the national response efforts and secure community collaboration in the outbreak control.”
WHO will also facilitate the shipment of laboratory glove tents for testing as well as a viral haemorrhagic fever kit with protective equipment for 500 health workers.
Marburg
Dr Mtashidiso Moeti, Regional Director for Africa, emphasised that “Marburg is highly infectious”.
“Thanks to the rapid and decisive action by the Equatorial Guinean authorities in confirming the disease, emergency response can get to full steam quickly so that we can save lives and halt the virus as soon as possible.”
An outbreak of Marburg in Ghana was successfully contained in 2022, but it is a highly virulent disease with a fatality ratio of up to 88%. Although there are no approved vaccines, NIH reported “encouraging” results with a candidate earlier this year. We will continue to report on the situation as it unfolds.
For more on viruses such as Marburg at the World Vaccine Congress in Washington this year, get your tickets today.
With reports of avian flu sweeping through minks in Spain, foxes in the UK, and now other mammals across the world, concern is growing about the threat both to human and animal health from H5N1. Although the position from WHO is that the risk to humans is “low”, experts are unsure about the implications that the increasing infections in mammals will have.
Human risk
The messaging at the moment is clear: the risk to humans is low. However, as Gavi notes, the “more often bird flu infects mammals, the more chance it has to evolve” to infect mammalian hosts better. This ability to mutate was of concern when experts noticed genetic mutations in samples from the infected minks in Spain that have also been seen in other infected mammals.
“This could be the lightning fuse that gives it the ability to spread between people.”
On the other hand, Gavi reminds us to consider the many changes that would need to happen before we see “real transmission capability”.
Past pandemics
Another point that Gavi raises is the possibility that the pandemic influenza in 1918 could have been a bird flu, mutated to affect the upper airways for greater transmissibility. However, things were different then, with no vaccines or antivirals. Are we in a better position to face an influenza pandemic?
Vaccines
The call to vaccinate birds in the UK resounded against the official position that ineffective vaccination could in fact undermine containment efforts. For people, we have a couple of options that “do not produce really good, strong immune responses”, WHO’s Professor Ian Barr told Gavi. Furthermore, potential to scale up is limited by the development process.
WHO’s message in February 2023 was of caution, but emphasised the organisation’s intent to “engage with manufacturers to make sure that if needed, supplies of vaccines and antivirals would be available for global use”.
Agricultural concerns
From a different perspective, experts are also worried about the consequences of these outbreaks on the agricultural industry. Professor Tim Uyeki of the CDC told Stat News that it presents a “major problem”. Professor Marion Koopmans of Erasmus Medical Centre warns that we are “playing with fire”. Each new outbreak increases the chances of mutation, and adds fuel to the fire of fear.
The question remains, will we handle this emerging threat with the surveillance and sensitivity that WHO is encouraging, or will we allow things to escalate further? For more on how we plan to address this growing threat, come to the World Vaccine Congress in Washington.
In findings published in Jama Pediatrics in February 2023 a CDC study revealed that the maternal Tdap (tetanus toxoid, reduced diptheria toxoid, and acellular pertussis) vaccine decreases incidence of pertussis in infants younger than 2 months. Infants younger than a year old have the “highest burden of pertussis morbidity and mortality”. Thus, the US introduced the Tdap vaccination during pregnancy in 2011, to protect infants before vaccinations begin.
The study
The ecologic study examined more than 57,000 cases reported in children under one year old between 2000 and 2019. Statistical analysis was performed between 2020 and 2022. The study was divided into two periods: the pre-maternal Tdap vaccination period (2000-2010) and the post-maternal vaccination period (2012-2019).
A total of 57,460 cases were reported in infants younger than 1 year across both periods, with 19,322 of these occurring in infants under 2 months old. The authors note that in the pre-maternal Tdap vaccination period, incidence did not change among infants under 2 months, but decreased in the post-maternal Tdap vaccination period for infants under 2 months.
There were about 165 cases per 100,000 infants under 2 months each year before maternal vaccination was introduced. During the vaccination period, average cases dropped to 122 per 100,000. Further into the post-maternal vaccination period, from 2017-2019, this fell to 81 per 100,000. However, the authors note that there was not a similar decrease in cases among children between 6 and 11 months old, who were not dependent on maternal vaccination.
Safe and effective
Dr Linda Eckert, American College of Obstetricians and Gynaecologists’ liaison to the CDC encourages “everyone who is pregnant” to “feel confident in knowing that the Tdap vaccine is safe and effective”.
“Knowing that Tdap vaccination during pregnancy protects nine in ten babies from being hospitalised with whooping cough, I strongly recommend this vaccine to all my pregnant patients for the peace of mind and for their family’s health and well-being.”
Dr José Romero, Director of the CDC’s National Centre for Immunisation and Respiratory Diseases, said that this vaccine “offers infants the best protection before they are old enough to receive their whooping cough vaccines”.
“This protection is critical because those first few months are when infants are most likely to have serious complications, be hospitalised, or die if they get whooping cough.”
A plateau in vaccination
Although the CDC recommends that pregnant patients take the vaccine, only around 55% did in 2019. This “plateau” is attributed to poor health communication by Dr Suellen Hopfer of the University of California-Irvine.
“The most credible and obvious and straightforward channels are the paediatricians and physicians, but I think we just need to do a better job at disseminating and prioritising this information through pharmacies, through social media”.
Another issue might be access, suggests Dr Elizabeth Cilenti of Georgetown University. Speaking to Healthline, she indicated that “not all obstetricians’ offices administer the vaccine”, which could “make things more difficult”.
