Virus World

The global failure to reduce fossil fuels is leaving small island states trapped in a never-ending cycle of fightback against disease and extreme weather. In the summer of 2023, the world recorded the highest temperature in 100,000 years. All continents were affected and even the gentle breeze often felt in the tropics did little to cool the sweltering heat experienced by small island developing states (Sids). Our latest Lancet Countdown report, tracking the connections between health and the climate crisis, showed that Sids experienced 103 health-threatening heat days each year between 2018 and 2022 – equating to almost a third of the year being above the threshold whereby heat-related deaths are likely to increase. Aside from the direct dangers of exposure to health-threatening heat such as heat stress, heatstroke, and, in severe circumstances, death, increased heat improves the climate suitability for the spread of infectious diseases such as dengue fever, malaria and vibrio by expanding their climatic boundaries, our most recent data shows. Our mathematical models of dengue fever show an increase in the frequency of outbreaks with an increase in heat, and the evidence suggests that the climate crisis has exacerbated the frequency of these outbreaks.

Dengue fever is a climate-sensitive disease that is spread through the saliva of an infected female Aedes mosquito when it bites an uninfected person. Dengue fever presents with high fever, severe headache, flu-like symptoms, intense joint and muscle pain, and other flu-like symptoms. It is usually a mild disease that can be adequately treated with rest, hydration and acetaminophen/paracetamol. However, it can also be severe, requiring hospitalisation and, in rare cases, causing death. Its most severe form is dengue haemorrhagic fever. The virus has four strains: Denv-1, Denv-2, Denv-3, and Denv-4. These strains are distinct, and immunity to one does not provide protection from the others. Denv-2 is the most severe strain. Exposure to one strain after being infected with another increases the severity of the disease, and repeated infection increases the risk of acquiring dengue haemorrhagic fever. Before 2007, the frequency of dengue outbreaks in Jamaica was once every 10 years; after 2007, the frequency increased to one every three to four years. The last epidemic was in 2019. While other risk factors such as behaviour and environment are implicated in the spread of dengue, the climate crisis is believed to be a significant contributor to the frequency of outbreaks, with the increase in temperature being the primary reason. The Jamaican summer of 2023 provided the perfect conditions for an increase in mosquito proliferation. First, there was a drought, which led to an increase in the storage of water, often in containers ideal for mosquito breeding. The drought was followed by a record-breaking hot and dry summer that ended with rain. Added to the mix is hyperendemnicity, with all four dengue strains circulating.

In September 2023, Jamaica’s ministry of health and wellness declared a dengue fever outbreak. The number of cases reported by health officials as of 6 November was 3,147 (suspected, presumed and tested), with nine deaths, adding pressure on the island’s already burdened health system. The dominant strain in circulation was Denv-2, and the hospitalisation rate was 72 people a week. Children aged between five and 14 were the most affected, with 360 cases per 100,000 people. Children were disproportionately affected because the last dengue outbreak with Denv-2 as the dominant strain occurred in 2010; these children were born after 2010 and did not acquire immunity to Denv-2. The outbreak is ongoing. Small island states often feel as if we are in a constant state of recovery from the impacts of the climate crisis. Recovery from extreme weather events, such as tropical cyclones; recovery from disease outbreaks exacerbated by climate change; recovery from sea level rise causing coastal erosion and salinisation of our water and land. We have repeatedly lost land, lives and livelihoods because of the climate crisis, a phenomenon to which we collectively contribute less than 1%. We should not lose sight of the progress made: the lethality of extreme weather events in Sids has fallen, and we have recorded progressively fewer deaths. This is a result of meteorological early warning systems, better disaster preparedness and management, as well as prompt appropriate health responses.  But we risk exceeding the power of these adaptation efforts, as the world moves in the wrong direction: expanding oil and gas activities, forgoing climate financing commitments, and leaving countries such as Sids behind in the uptake of clean, renewable energy. In October, when I visited my 14-year-old niece, who was in hospital with dengue, I reflected on the children of small island developing states whose lives will continue to be affected by the climate crisis. Urgent action must be taken at the global level to reduce fossil fuel production and consumption to protect the health of all people, especially those living in Sids, who bear the brunt of the climate crisis.

Dr Georgiana Gordon-Strachan is the executive director of the Lancet Countdown Regional Centre for Small Island Developing States, and director of the Tropical Metabolism Research Unit at the Caribbean Institute for Health Research, University of the West Indies in Jamaica

Jab does not offer complete protection against illness but usually prevents infection. French health authorities have launched an investigation after 59 per cent of people in a new mpox cluster said they were fully vaccinated. Vaccination does not offer complete protection against the virus – though only one in four French cases are usually in immunised people. Mpox, formerly known as monkeypox, can cause and unusual spots, ulcers or blisters anywhere on the body; fever; headaches; muscle aches; chills; fatigue and swollen glands. Though most people have a mild illness, with recovery within three weeks, some cases can cause severe illness and occasionally result in death. Mpox is not normally a sexually-transmitted infection, but it can be passed on by direct contact during sex. The cluster in France’s Centre-Val de Loire comes despite the region having a high vaccination rate, with experts warning of a potential mutation in the virus.

The mpox vaccine is not tailored to the disease and was originally created to protect against smallpox. Last year, the UK Health Security Agency (UKHSA) recommended offering Imvanex to those at increased risk of exposure to the virus. Dr Michael Marks, Associate Professor at the London School of Hygiene and Tropical Medicine, told the Telegraph that health authorities may need to investigate whether a mutation has affected the vaccine’s efficacy. He also noted that many mpox cases have been reported in people with HIV. “HIV may modify how effective the vaccine is. We don’t know the HIV status of this cluster at the moment.”

France’s public health body, Sante Publique France, have said they are investigating the cluster and are waiting for “robust data” on the efficacy of the vaccine. Mpox can also be spread through touching clothing, bedding or towels used by someone with the mpox rash, and through the coughs and sneezes of somebody with the infection. An outbreak of the disease in London and other British cities made headlines last year – though infections have slowed following a targeted vaccination programme. The outbreaks raised alarm because the viral disease, which spreads through close contact and was first found in monkeys, mostly occurs in west and central Africa and only occasionally spreads elsewhere. Over 25,800 cases have been reported in Europe since spring 2022, mostly among men who have sex with men.

LIMA, Peru – Peru on Thursday declared a “health emergency” in 13 departments in the country’s north, center and southeast due to an outbreak of dengue. The emergency would remain in place for 90 days, according to an official notice, after the health ministry recorded more than 11,500 cases and 16 deaths due to the disease so far in 2023. This represented a “considerable increase” of 72 percent from the same period in 2022. Last year, the country had more than 72,800 dengue cases and 84 deaths. Dengue fever is a mosquito-borne tropical disease that can provoke a high fever, headache, vomiting, muscle and joint pain, and sometimes death. Earlier this month, neighbor Bolivia also declared a health alert with a cumulative number of more than 6,800 cases and 26 deaths.

BF.7 is a new version of the coronavirus SARS-CoV-2 that's driving a surge of infection in China. Since the COVID variant omicron emerged in late 2021, it has rapidly evolved into multiple subvariants. One subvariant, BF.7, has recently been identified as the main variant spreading in Beijing, and is contributing to a wider surge of COVID infections in China. But what is this new variant, and should we be worried? Although reports from China about this variant's characteristics are concerning, it doesn't appear to be growing too much elsewhere in the world. Here's what we know. BF.7, short for BA.5.2.1.7, is a sub-lineage of the omicron variant BA.5. Reports from China indicate BF.7 has the strongest infection ability out of the omicron subvariants in the country, being quicker to transmit than other variants, having a shorter incubation period, and with greater capacity to infect people who have had a previous COVID infection, or been vaccinated, or both. To put this into context, BF.7 is believed to have an R0, or basic reproduction number, of 10 to 18.6. This means an infected person will transmit the virus to an average of 10 to 18.6 other people. Research has shown omicron has an average R0 of 5.08. The high transmission rate of BF.7, taken with the risk of hidden spread due to the many asymptomatic carriers, is understood to be causing significant difficulty in controlling the epidemic in China.

The symptoms of an infection with BF.7 are similar to those associated with other omicron subvariants, primarily upper respiratory symptoms. Patients may have a fever, cough, sore throat, runny nose and fatigue, among other symptoms. A minority of people can also experience gastrointestinal symptoms like vomiting and diarrhoea. BF.7 may well cause more serious illness in people with weaker immune systems. As omicron has evolved, we've seen the emergence of new subvariants better able to escape immunity from vaccination or prior infection. BF.7 is no different. BF.7 carries a specific mutation, R346T, in the spike protein of SARS-CoV-2 (a protein on the surface of the virus that allows it to attach to and infect our cells). This mutation, which we also see in BF.7's "parent" variant BA.5, has been linked with enhancing the capacity of the virus to escape neutralising antibodies generated by vaccines or previous infection. A recent study examined the neutralisation of BF.7 in sera (a component of blood that should contain antibodies) from triple-vaccinated healthcare workers, as well as patients infected during the omicron BA.1 and BA.5 waves of the pandemic. BF.7 was resistant to neutralisation, driven partly by the R346T mutation.

BF.7 has been detected in several other countries around the world including India, the U.S., the U.K. and several European countries such as Belgium, Germany, France and Denmark. Despite BF.7's immune-evasive characteristics, and worrying signs about its growth in China, the variant seems to be remaining fairly steady elsewhere. For example, in the U.S. it was estimated to account for 5.7% of infections up to December 10, down from 6.6% the week prior. While the U.K. Health Security Agency identified BF.7 as one of the most concerning variants in terms of both growth and neutralisation data in a technical briefing published in October (it accounted for over 7% of cases at that time), the most recent briefing says BF.7 has been de-escalated due to reduced incidence and low growth rates in the U.K. We don't know exactly why the situation looks different in China. BF.7's high R0 might be due in part to a low level of immunity in the Chinese population from previous infection, and possibly vaccination too.

We should, of course, be cautious about the data from China as it's based on reports, not peer-reviewed evidence yet. Since the emergence of SARS-CoV-2 three years ago, the virus has continued to evolve, acquiring genetic mutations more rapidly than expected. The emergence of BF.7 and other new variants is concerning. But vaccination is still the best weapon we have to fight COVID. And the recent approval by the U.K. drugs regulator of bivalent boosters, which target omicron alongside the original strain of SARS-CoV-2, is very promising.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

‘We expect cases to rise further in the coming days and weeks,’ the UKHSA says. Monkeypox is mutating up to 12 times faster than expected, a study says, amid warnings the UK could see as many as 60,000 new cases a day by the end of the year. As of Sunday 26 June, there were 1,076 cases across the UK, up by 166 on the previously Friday with health experts stating the outbreak is likely to spread further over the coming weeks.  While a surge to tens of thousands of daily cases in six months might seem extreme, scientists have found the virus appears to be mutating at an unusual rate. In a study published in journal Nature Medicine, Portuguese researchers found samples of the virus had 50 mutations in its DNA compared to 2018. That’s between six and 12 times the number scientists would normally expect over the same time period.  Professor Adam Kleczkowski, a mathematician at the University of Strathclyde, warned Britain's infections could keep rising until the end of year — when a peak of just under 60,000 people could be catching the virus every day. “Unless a combination of contact tracing and ring vaccination stops the spread, the monkeypox will continue spreading,” Professor Kleczkowski said. Professor Kleczkowski estimated that each infected person would go on to infect two more people - known as the R number. He added that 53 per cent of a population would need to be infected for enough people to have immunity to stop the virus spreading — known as herd immunity. Based on these parameters, he modelled how the outbreak would unfold if all males aged 50 and under are susceptible to the virus. This equates to 40 per cent of the UK's population — around 26.8million people — and is classified as a “large population at risk”. 

He said the parameters are based on the over-50s likely having some immunity from smallpox vaccinations, which the UK stopped rolling out in 1971, and the spread so far mainly occurring among men.  Professor Kleczkowski also highlighted another scenario that would see cases drop dramatically this summer as “at risk” groups become immune to the virus. So the R number can be close to or even lower than one, and the transmission would stop.  The UKHSA announced last week a vaccine shown to be effective against monkeypox is to be offered more widely in the UK in an attempt to curb the spread of the viral infection. Dr Mary Ramsay, head of immunisation at UKHSA, said: “We are continuing to see a notable proportion of cases in gay, bisexual and other men who have sex with men. By expanding the vaccine offer to those at higher risk, we hope to break chains of transmission and help contain the outbreak.”  Dr Sophia Makki, incident director at the UKHSA, added: “The monkeypox outbreak in the UK continues to grow, with over a thousand cases now confirmed nationwide. “We expect cases to continue to rise further in the coming days and weeks. If you are attending large events over the summer or having sex with new partners, be alert to any monkeypox symptoms so you can get tested rapidly and help avoid passing the infection on.

The virus did not spread well between people in the past but may have found a new niche in tightly connected sexual networks.  Ever since monkeypox started sickening thousands of people worldwide this spring, two big questions have loomed: Why is a virus that has never managed to spread beyond a few cases outside Africa suddenly causing such a big, global outbreak? And why are the overwhelming majority of those affected men who have sex with men (MSM)? A long history of work on sexually transmitted infections and early studies of the current outbreak suggest the answers may be linked: The virus may have made its way into highly interconnected sexual networks within the MSM community, where it can spread in ways that it cannot in the general population. An epidemiological modeling study posted as a preprint last week by researchers at the London School of Hygiene & Tropical Medicine (LSHTM) supports that idea. It suggests the outbreak will keep growing rapidly if the spread isn’t curtailed. It also has implications for how to protect those most at risk and limit spread, while suggesting the risk for the wider population remains low. But there are still many uncertainties, and communication is fraught because of the risk of stigmatizing MSM—and because communicating frankly about sexual behavior is hard. “I think we have to talk more about sex,” says Yale School of Public Health epidemiologist and former HIV activist Gregg Gonsalves. “Everybody has been very clear about stigma, and saying it over and over again. The point is that you still have to address the risk of infection in our community.” Since early May, more than 2000 monkeypox cases have been reported in more than 30 countries where the virus is not normally seen. (Outbreaks are more common in at least a dozen countries in West and Central Africa, where the virus has animal reservoirs. More than 60 cases and one death have been confirmed there this year.)

The vast majority of cases in the current outbreak have been in MSM. Researchers at the UK Health Security Agency (UKHSA), for example, asked patients to fill out questionnaires. Of 152 who did, 151 said they were MSM, the team wrote in a technical briefing published on 10 June; the remaining patient refused to answer. Other countries have seen similar patterns.

That could be a skewed picture, of course. “MSM have a better relationship with medical practitioners than heterosexual men,” says Lilith Whittles, an infectious disease modeler at Imperial College London, which could mean they are more likely to report monkeypox symptoms and get tested for the virus. “I don't know that we're necessarily looking enough in heterosexual social networks to make the conclusion that this is not a broader problem,” says Boghuma Titanji, a virologist at Emory University who works at a sexual health clinic. But most researchers say such “ascertainment bias” is unlikely to explain the striking pattern. Although some monkeypox patients have mild infections that may be missed or misdiagnosed, others have very characteristic rashes and agonizing pains that require hospitalization for pain treatment. If many people outside the MSM community had monkeypox, more would have shown up in the statistics by now. Ashleigh Tuite, an infectious disease epidemiologist at University of Toronto, says she “understands the hesitation” to focus on MSM, given the risk of stigma that could worsen discrimination and cause those who are affected to delay seeking care. “But based on the data that we have, and based on the contact tracing that's been done, it’s very clear that this is an MSM-focused outbreak at this point,” she says. “Anyone can get monkeypox, but we’re seeing disease activity primarily among” MSM, confirms Demetre Daskalakis, an HIV prevention specialist at the U.S. Centers for Disease Control and Prevention. Sexual encounters clearly play a role in transmission. Of the 152 people in the UKHSA data set, 82 were invited for additional interviews focusing on their sexual health. Among the 45 who participated, 44% reported more than 10 sexual partners in the previous 3 months, and 44% reported group sex during the incubation period. Exactly how the virus is passed on is less clear. Researchers have found viral DNA, and even infectious virus, in the semen of some patients, but they aren’t sure that is important for transmission; skin-to-skin contact may be enough. (Other sexually transmitted infections, including herpes and scabies, also primarily spread this way.)

To those who study how pathogens spread through social and sexual networks, the pattern is not a big surprise. In the 1970s and ’80s, researchers trying to understand the spread of sexually transmitted diseases such as gonorrhea were stumped, says LSHTM epidemiologist Adam Kucharski: Survey data showed that people’s average numbers of sexual partners were too low to sustain transmission. But averages obscured that although many people have few sexual partners, some have large numbers. This helps drive transmission because, if infected, they are also more likely to infect others. Sexual networks among MSM are not different in nature from those of other groups, Whittles stresses, but a core group of people are much more densely connected than people outside the MSM community. They change partners more frequently and are more likely to have several partners at the same time. “These things occur in all sexual networks, it is just a question of the degree,” Whittles says. And in a densely connected network, the virus is less likely to hit a dead end. “It's entirely possible for this epidemic to rage among a subset of people just because that subset is connected in a network differently than everyone else,” says Keletso Makofane, a social network epidemiologist at the FXB Center for Health and Human Rights at Harvard University. Together with colleagues, Makofane hopes to launch a study in New York City in August to better understand the spread of the disease. “The idea is to get a sense of how many people report symptoms that are consistent with monkeypox and how they are connected,” he says. The LSHTM study, posted on medRxiv on 13 June, used U.K. data about sexual partnership patterns to model the spread of monkeypox among MSM and outside that group. Because it is not yet clear how contagious the virus is, the researchers modeled scenarios based on different risk levels. Without effective intervention measures or behavioral changes, a large and sustained outbreak with more than 10,000 cases among MSM globally is “highly likely,” they write. “In contrast, sustained transmission in the non-MSM population is unlikely in all scenarios considered.” Because the model is based on U.K. data, the findings may not apply elsewhere, first author Akira Endo says.

And other factors may have made the outbreak worse. Monkeypox may have mutated in ways that allow it to transmit more easily, and the share of the population who have had the smallpox vaccine—which also offers some protection against monkeypox—is declining because smallpox vaccination was abandoned worldwide starting in the 1970s. But the modeling shows “we do not necessarily need [those factors] to explain the observed patterns,” Endo says. Such conclusions put epidemiologists in a delicate position, and some declined to talk to Science for fear of stigmatizing MSM. Endo says he understands that and agrees the findings could easily be misunderstood. “Meanwhile I also understand that there’s a risk in the other direction—that the information doesn’t reach those who need it most before it’s too late,” he says. Whittles agrees, calling the findings “practical information, in terms of where it’s spreading. It is a morally neutral thing,” she says. “Knowledge of what’s happening is power, even though that knowledge is imperfect and will change,” Daskalakis adds. The virus could still find other networks with similar characteristics. Daskalakis recalls a U.S. outbreak of methicillin-resistant Staphylococcus aureus in the 2000s that started in the MSM community but later spread in gyms, among athletes, and in prisons. Monkeypox could also start spreading among sex workers and their clients, Tuite says. How fast the virus will spread in the months ahead depends on control efforts. National health authorities in Europe, Canada, and the United States have issued guidance about how to reduce the risk of infection, and dating apps have alerted users to the risk of monkeypox and to its symptoms, which may change contact patterns. Increasing awareness among health care workers may have an impact as well, Whittles says: Faster diagnoses mean patients will isolate sooner in their infection, reducing onward transmission. “So there's a couple of different ways that behavior can change, even if it's not people having less sex,” she says. And the model did not account for infected individuals developing immunity. That means “we may see a slowdown of the outbreak earlier than we might imagine,” Endo says. Many countries are also gearing up to start immunization campaigns. Vaccinating those with many sexual partners may be the most efficient approach; in the Canadian province of Quebec, the vaccine is already being offered to MSM who had two or more sexual partners in the previous 14 days. It’s important to alert that community and do it the right way, Gonsalves says. “We should say: It’s not about who you are. It’s about what you’re doing. And we’re not going to stigmatize it. But just know that you’re at greater risk if you fit this profile.”

• The CDC on Monday ramped up its monkeypox alert to level 2 and encouraged people to “practice enhanced precautions” to stem the recent outbreak.
• The new guidance includes wearing face masks while traveling, as well as avoiding close contact with sick animals and people, especially those with skin lesions.
• As of Monday, 1,019 confirmed and suspected cases of monkeypox have so far been reported in 29 countries, according to the public health body.

U.S. detects two monkeypox strains

The first draft genome sequence of monkeypox virus, taken from a swab of a confirmed case of the current outbreak, was sequenced and released online.   On May 19, a research group led by João Paulo Gomes, PhD, a researcher from the department of infectious diseases, National Institute of Health Doutor Ricardo Jorge (INSA), in Lisbon, Portugal, posted the sequence online on virological.org. There are currently almost 200 (confirmed and suspected) cases of monkeypox associated with the recent outbreak across the world.  The authors write that, “The determination of the genome sequence of the virus causing these infections will certainly contribute to better understand the epidemiology, sources of infection, and transmission patterns.” The work was celebrated by the scientific community almost immediately after being posted, including Trevor Bedford, PhD, a professor of biostatistics, bioinformatics, and epidemiology program in the vaccine and infectious disease division at the Fred Hutch. The first draft sequence of SARS-CoV-2 was made available in a similar fashion. On January 10, 2020, Eddie Holmes, PhD, a virologist and evolutionary biologist at the University of Sydney, tweeted that the first draft sequence of “the coronavirus associated with the Wuhan outbreak” had been posted. Like the monkeypox sequence, it took only weeks to produce the data and post it online. The SARS-CoV-2 sequence was made possible through the work of Yong-Zhen Zhang, PhD, a virologist at Shanghai’s Fudan University.

Monkeypox virus is an enveloped double‐stranded DNA virus with a genome size of around 190 kb. It belongs to the Orthopoxvirus genus of the Poxviridae family. The paper posted on www.virological.org is the first draft genome sequence of the monkeypox virus associated with the major outbreak affecting multiple countries worldwide. The virus, taken from a swab collected on May 4 from skin lesions from a patient, was sequenced using the Oxford Nanopore MinION. The team then quickly performed phylogenetic analysis of the virus. In doing so, they found that the 2022 virus belongs to the West African clade. Indeed, the West African clade has now been confirmed in at least six of the cases in the recent outbreak. There are two clades of monkeypox virus: the West African clade and the Congo Basin (Central African) clade. The West African clade of monkeypox virus infection—which has a lower case fatality ratio (roughly 1%) than the Congo Basin clade (up to 10%)—can lead to severe illness in some individuals.

However, the disease typically resolves.  The phylogenetic analysis also suggests that the virus circulating in the outbreak is most closely related to viruses associated with the exportation of monkeypox virus from Nigeria to several countries—the United Kingdom, Israel, and Singapore—in 2018 and 2019. The findings sparked the interest of Tulio de Oliveira, PhD, professor at Stellenbosch University, Western Cape, South Africa and director of the Centre for Epidemic Response & Innovation (CERI), and the KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP). The authors noted that these data are preliminary, and “will be soon updated upon the release of new genome data.” They also said that these future additions will be important to elucidate the origin and international spread of the currently circulating virus.

Sequence of monkeypox isolate available at Virological:

https://virological.org/t/first-draft-genome-sequence-of-monkeypox-virus-associated-with-the-suspected-multi-country-outbreak-may-2022-confirmed-case-in-portugal/799 

This briefing is produced to share data useful to other public health investigators and academic partners undertaking related work. Although a detailed clinical case review is also taking place, that data is not shared here as, given the small number of cases, there are some risks to confidentiality.

Cases

As of 3 May 2022, there have been 163 cases of acute non-A-E hepatitis with serum transaminases greater than 500 IU/l identified in children aged under 16 years old in the UK since 1 January 2022. This is the result of an active case finding investigation commencing in April which identified retrospective as well as prospective cases. Eleven cases have received a liver transplant. No cases resident in the UK have died. New cases continue to be identified. Whilst there is some apparent reduction in confirmed cases in the past 2 weeks overall in the UK, there are continued new case reports in Scotland, the number of cases pending classification in England is substantial and the likely reporting lags mean that we cannot yet say there is a decrease in new cases. Cases pending classification are usually those in which laboratory testing to rule out known causes of hepatitis has not been completed.

Working hypotheses

The working hypotheses have been refined. The leading hypotheses remain those which involve adenovirus. However, we continue to investigate the potential role of SARS-CoV-2 and to work on ruling out any toxicological component.

Associated pathogens

Adenovirus remains the most frequently detected potential pathogen. Amongst 163 UK cases, 126 have been tested for adenovirus of which 91 had adenovirus detected (72%). Amongst cases the adenovirus has primarily been detected in blood. On review of some of the adenovirus negative cases it was notable that some had only been tested on respiratory or faecal samples, and some had been tested on serum or plasma rather than whole blood (whole blood being the optimal sample). It is therefore not possible to definitively rule out adenovirus in these cases. SARS-CoV-2 has been detected in 24 cases of 132 with available results (18%). SARS-CoV-2 serological testing is in process. A range of other possible pathogens have been detected in a low proportion of cases and are of uncertain significance, although the inclusive nature of the UKHSA case definition intentionally will pick up some cases of non-A-E hepatitis with recognised causes.

Adenovirus characterisation

Typing by partial hexon gene sequencing consistently shows that the adenovirus present in blood is type 41F (18 of 18 cases with an available result). Whole genome sequencing (WGS) has been attempted on multiple samples from cases but the low viral load in blood samples, and limited clinical material from historic cases, mean that it has not been possible to get a good quality full adenovirus genome from a case as yet.

Metagenomics

Metagenomics undertaken on blood and liver tissue has detected primarily adeno-associated virus 2 (AAV-2) in high quantities. Whilst contamination was originally suspected, AAV-2 is now detected in multiple samples from different hospital sources and tested in more than one sequencing laboratory. This finding is of uncertain significance and may represent a normal reactivation of AAV-2 during an acute viral infection (for example, adenovirus) or during liver injury of another cause. It is not unusual to detect bystander, reactivating or other incidental species during metagenomic sequencing. However, given the presence of AAV-2 in a number of cases, the significance will be further explored through testing of additional sets of controls.

Toxicology

Toxicological investigations continue with no positive findings to date. Detection of paracetamol is likely to be related to appropriate therapeutic use (also noted in the trawling questionnaires) which would not be a concern, however verification work is being undertaken to confirm this.

Host investigations

Host (for example, immunological) investigations require full research consent and are undertaken under the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC) Clinical Characterisation Protocol. Thirty-seven cases have been recruited to the ISARIC clinical characterisation protocol to date and retrospective and prospective recruitment continues...

Update 2 (May 6, 2022):

https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1073704/acute-hepatitis-technical-briefing-2.pdf 

A second Ebola patient has died in northwestern Democratic Republic of Congo, the World Health Organization (WHO) said on Tuesday, days into a fresh outbreak of the deadly disease. Genetic testing showed an infection confirmed last week in the city of Mbandaka was a new "spillover event", a transmission from an infected animal, and not linked to any previous outbreaks, said the country's National Institute of Biomedical Research.  The second fatality was a 25-year-old woman who was the sister-in-law of the first case, the WHO said on Twitter. She began experiencing symptoms 12 days earlier, it said. The first patient began showing symptoms on April 5, but did not seek treatment for more than a week. He died in an Ebola treatment centre on April 21. The lag time has health workers rushing to identify contacts who may have been infected, the WHO said.

At least 145 people came into contact with the confirmed cases and their health is being closely monitored, the WHO said, noting later that one of the first cases was a health worker.  Mbandaka, a trading hub on the banks of the Congo River, is a city of over one million where people live in close proximity with road, water and air links to the capital Kinshasa. WHO emergencies director for Africa, Ibrahima Soce Fall, said there was a risk the disease could spread to neighbouring Central African Republic and Congo Brazzaville.  "This is concerning but taking into account the capacity build up and experience in Congo we believe it can be contained," Fall said at a press conference in Geneva. Congo has seen 13 previous outbreaks of Ebola, including one in 2018-2020 in the east that killed nearly 2,300 people, the second highest toll recorded in the history of the hemorrhagic fever. The most recent outbreak ended in December in the east after six deaths. Mbandaka, the capital of Equateur province, has also contended with two previous outbreaks - in 2018 and in 2020. The country's equatorial forests are a natural reservoir for the Ebola virus, which was discovered near the Ebola River in northern Congo in 1976.

More than 20 states have reported avian influenza in commercial and backyard farms.  A growing epidemic of bird flu across the East Coast and Midwest has led to more than 20 million birds dying or being destroyed since February, fueling a surge in egg and poultry prices. After circulating for months in Asia and Europe, highly pathogenic avian influenza (HPAI) has been detected in commercial and backyard farms in more than 20 states, according to the US Department of Agriculture. Individual farmers have been forced to cull hundreds of thousands -- sometimes millions -- of birds to check the spread of the disease.  Shell egg prices have jumped to $2.88 a dozen (up more than 50%) since Feb. 8, when the first case was identified in a commercial turkey flock in Indiana. No humans have tested positive in the US yet, but the economic toll could be major: The first US epidemic in 2015 cost the poultry industry more than $1.5 billion and caused egg prices to nearly double. Here's what you need to know about bird flu, including what the outbreak means for consumers, how the industry is combating it and if it poses a threat to humans.

What is bird flu?

Bird flu is caused by avian influenza Type A viruses, which spread naturally among waterfowl and can infect wild birds, domestic poultry and other animals, though rarely humans. There are more than a dozen strains of bird flu, which are classified as either "low pathogenic" or "highly pathogenic," depending on their ability to spread disease and kill poultry.   The strain bombarding the US right now, Eurasian H5N1, is considered highly pathogenic.

How is bird flu transmitted?

The main source of infection is migratory waterfowl, such as ducks and geese. "They get infected but don't get sick," Denise Derrer, public information director for the Indiana State Board of Animal Health, told CNET. "Then they shed the virus in their droppings or wherever the land." That means the spread could peak in a few weeks, when spring migration reaches its high point, and not abate until June, when the birds settle into their summer breeding grounds. How the virus gets from barn to barn is still not entirely clear, which makes it hard to get a grip on the situation, according to Dr. Yuko Sato, a professor at Iowa State's school of veterinary medicine. "There's no concluded study on how it's coming in," Sato told NPR. "We can identify some weak links -- for example, people tracking it in." 

Where have bird flu outbreaks been detected?

The current strain of H5N1 was first reported in Asia and Europe. In the UK, eggs can no longer be labeled free-range because hens have been cooped up for months to avoid infection. Since the USDA confirmed the first US case in a wild duck in South Carolina in mid-January, infections have been reported in commercial farms and backyard flocks in Connecticut, Delaware, Illinois, Indiana, Iowa, Kansas, Kentucky, Maine, Maryland, Massachusetts, Michigan, Minnesota, Missouri, Nebraska, North Carolina, North Dakota, New Hampshire, New York, Ohio, South Dakota, Wisconsin and Wyoming.  As a result, more than 20 million egg-laying hens, poultry chickens and turkeys have been or will soon be "depopulated," or killed, with more infections detected nearly every day. On March 31 alone, infections were detected in five states.

Among the worst outbreaks:

India is taking urgent steps to halt the transmission of a rare but deadly virus that spreads from bats to humans. In the southern Indian state of Kerala, the bat-borne Nipah virus has infected six people — two of whom have died — since it emerged in late August. More than 700 people, including health-care workers, have been tested for infection over the past week. State authorities have closed some schools, offices and public-transport networks. The Nipah outbreak is the fourth to hit Kerala in five years — the most recent one was in 2021. Although such outbreaks usually affect a relatively small geographical area, they can be deadly, and some scientists worry that increased spread among people could lead to the virus becoming more contagious. Nipah virus has a fatality rate between 40% and 75% depending on the strain, says Rajib Ausraful Islam, a veterinary physician who specializes in bat-borne pathogens at the International Centre for Diarrhoeal Disease Research, Bangladesh, in Dhaka. “Each outbreak is a concern,” he says. “Every outbreak is giving the pathogen an opportunity to modify itself.” The virus can cause fever, vomiting, respiratory issues and inflammation in the brain. It is carried mainly by fruit bats, but can also infect domestic animals such as pigs, along with humans. It spreads through contact with bodily fluids from infected animals or people. There are no approved vaccines or treatments, but researchers are investigating candidates....

Africa is grappling with not one, but two outbreaks of Marburg fever, a disease that causes symptoms and a death rate comparable to Ebola, its viral cousin.  Health officials in Tanzania announced Tuesday that they had confirmed the country’s first-ever Marburg outbreak, involving at least eight people so far, five of whom have died. One of the people who died is a health care worker. Across the continent, Equatorial Guinea has been combating its first-ever Marburg outbreak for several weeks now, though in an unusual turn of events for a viral hemorrhagic fever outbreak, scant information has been shared with the international community. The last update from the World Health Organization on that outbreak was issued nearly a month ago, on Feb. 25. Tanzanian Health Minister Ummy Mwalimu announced that the country’s national public health laboratory had confirmed that Marburg was the cause of an outbreak that was first reported last week. Five members of a single family are among the cases. At least 161 people who have been in contact with the cases have been identified and are being monitored. “We are working with the government to rapidly scale up control measures to halt the spread of the virus and end the outbreak as soon as possible,” Matshidiso Moeti, the WHO’s regional director for Africa, said in a statement.

Moeti noted that while Tanzania has not previously battled Marburg, it has coped with a number of health emergencies in recent years, including Covid-19, cholera, and dengue fever. “The lessons learnt, and progress made during other recent outbreaks should stand the country in good stead as it confronts this latest challenge,” she said.But Gary Kobinger, a veteran of numerous Ebola and Marburg responses, questioned that line of thinking, and urged the two countries to both be transparent and to accept outside help. “Managing a filovirus outbreak is completely different than a typical emergence of let’s say cholera or measles or even Rift Valley fever,” said Kobinger, who is director of the Galveston National Laboratory at the University of Texas Medical Branch. Marburg and Ebola viruses are both filoviruses. Kobinger said that even countries that have experience with these viruses struggle sometimes to contain outbreaks. “You need to act very fast. The first two weeks, three weeks are extremely important. And this is where you’re going to define the evolution of the outbreak,” he told STAT. “If you lose control of a SARS-CoV-2 outbreak, which happens, that’s one thing. If you lose control of an Ebola outbreak or a Marburg outbreak, you have a different problem on your hands.” Viral hemorrhagic fever outbreaks pose significant and unique challenges, because of their death rates, which are generally in the high double digits. These diseases spark panic in the communities in which they spread at the very time when community cooperation is essential to stop transmission.

“People are scared. One case in one village will shut down the place. And people will not want to go there and people that come out of there will be treated as if they are infected, potentially,” Kobinger said. “So it’s very difficult in terms of trade, in terms of social movement, in terms of social acceptance. It’s much more traumatic than Covid or something else.”bHistorically Marburg outbreaks have been smaller than Ebola outbreaks; there have been none that involved thousands of cases, like the Ebola outbreaks in West Africa (2014-2016) or in the Democratic Republic of the Congo (2018-2020). But in 2004-2005, 252 people were infected in an outbreak in Angola, with 227 or 90% of them dying. There are no licensed vaccines to protect against Marburg and no approved drugs. A WHO-led meeting in mid-February convened to explore whether there were supplies of experimental vaccines or drugs that could be tested in the Equatorial Guinea outbreak found there are few doses available to test. The outbreak in Equatorial Guinea dates back to at least early January; by late February, nine cases — one confirmed, four probable and four suspected — had been identified. It is not unusual to see probable and suspected cases in a viral hemorrhagic fever outbreak, especially in the early days. People die and are buried without a diagnosis. Even after authorities realize what they are dealing with and testing protocols are established, some families hide their dead so as to be able to perform burial rituals which, while important culturally, serve to spread the virus further. It is believed additional cases have been identified in Equatorial Guinea, but the country’s leadership has been unwilling to disclose the information.

Equatorial Guinea has just confirmed its first outbreak of deadly Marburg virus, a hemorrhagic fever related to Ebola. Equatorial Guinea has just confirmed its first outbreak of Marburg virus, one of the families of hemorrhagic fevers related to Ebola. As with last year’s outbreak in Ghana, patient specimens had to be sent to the Institut Pasteur in Senegal for confirmation, as it requires specialized testing. One of eight samples has been confirmed thus far. There have been 16 suspected cases and 9 deaths so far. Symptoms of Marburg are nonspecific and include (the often abrupt onset of) fever, headache, nausea, vomiting and diarrhea, so it might be confused with many other infections. When there is blood in the emesis or stool, the diagnosis of a hemorrhagic fever becomes much clearer. The incubation period is from 2-21 days. Like Ebola, Marburg can be quite deadly, with an 88% fatality rate.

Unlike Ebola, we have no vaccines to protect people yet, or other specific treatments. Monoclonal antibodies have been used to successfully treat some people ill with Ebola, with a moderate reduction in death, from 49.4% to 35.1% for Ebanga (Ansuvimab-zykl) treatment. The vaccine for Ebola offered a 97.5% protection rate in the 2018-20 outbreak in the Democratic Republic of Congo, which was due to the Ebola Zaire strain. The most recent outbreak of Ebola in Africa occurred in Uganda in September 2022. It was due to a different strain, Ebola Sudan, for which we have no vaccines or specific treatment. For Marburg, Ebola Sudan, and other hemorrhagic fevers, treatment is supportive by providing fluids and electrolytes to avoid shock. The primary focus now will be controlling the spread of the infection, which occurs through these infected secretions or contaminated surfaces, and by quarantine. Patients who are symptomatic need to be carefully isolated. The WHO and local officials will provide education on infection control and supplies of gowns and gloves (PPE). Contact with bodies is common in many cultures and has previously been a source of transmission.

Marburg has now been seen in Ghana, Angola, Uganda, the Democratic Republic of the Congo, Kenya, and South Africa. The first outbreak was seen in 1967 in Germany and Serbia. It came from the importation of green monkeys from Angola. A quarter of the 31 people infected died. Subsequently, there were larger outbreaks in the DRC in 1998-2000, with 152 people and 83% mortality. The largest outbreak was in 2005 in Angola. There were 252 cases and a 90% death rate. This was thought to be caused by reusing contaminated transfusion equipment between patients. Egyptian Rousette bats, which live in caves and mines, are reservoirs for the Marburg virus. There have been infections among Uganda miners in 2007 from the Python Cave in Uganda. Subsequently, two tourists became infected from the same site, where they had gone caving. Bat guano or infected aerosols were the likely sources of transmission. One of the problems with Marburg, as with other animal-related infections (zoonosis), is that there is limited surveillance and diagnostic tests; until there is an outbreak, early cases are likely to be missed. Many of these events—called spillover events—occur because we encroach on wildlife. As we do this more—be it in mining, deforestation for cattle, or other disruptions of the environment, we can expect to see more such outbreaks.

What is already known about this topic?

Severe   acute   respiratory   syndrome   coronavirus   2(SARS-CoV-2)  Omicron  subvariant  has  a  stronger transmission  capacity  and  faster  transmission  speed than the previous strain.

What is added by this report?

The first coronavirus  disease  2019  (COVID-19)  case infected  with  the  SARS-CoV-2  Omicron  subvariant BA.2.76 who caused local transmission was reported in Chongqing  Municipality  on  August  16,  2022.  For 35minutes, the Patient Zero jogged along a lake at a local park without wearing a mask. Among the 2,836 people potentially exposed  at  the  time,  39  tested  positive. Overall, 38 out of 39 cases did not wear a mask on the morning of August 16. All 39 cases lacked any previous exposure to the variant before testing positive on their nucleic acid test.

What are the implications for public health practice?

It is essential to  maintain  personal  wellbeing  by ensuring one maintains personal protection and follows regulated  guidelines  such  as  maintaining  safe  distances from others both indoors and outdoors.

The first coronavirus disease 2019 (COVID-19) case infected with the  severe  acute  respiratory  syndrome coronavirus   2   (SARS-CoV-2)   Omicron   subvariant BA.2.76  causing  local  transmission  was  reported  in Chongqing Municipality on August 16, 2022. For 35 minutes, Patient Zero jogged along  a  lake  in  a  park without wearing mask. Of the 2,836 people potentially exposed in the park,  39  tested  SARS-CoV-2  positive. Gene   analysis   from   the   39   cases   showed   highly homologous   when   compared   to   Patient   Zero. Epidemiological  investigations  supported  Patient  Zero transmitted  to  the  following  33  visitors  and  2  park cleaners and the 2 cleaners transmitted to 4 colleagues. This outbreak indicated  that  the  Omicron  subvariant BA.2.76 could be easily transmitted to others outdoors if  they  are  not  equipped  with  effective  protection equipment.  The public  should  be  encouraged  to  use good  protection  measures  and  retaining  safe  distances amongst others both indoors and outdoors....

Preprint available in China CDC Weekly (Nov. 18, 2022)

https://doi.org/10.46234/ccdcw2022.209 

BARCELONA, Spain (AP) — Spain reported Saturday a second death in as many days from monkeypox. These are believed to be the first confirmed fatalities from the disease in Europe since its recent spread beyond Africa. The ministry based in Madrid said both fatalities were young men. It reported its first death on Friday, the same day that Brazil also reported its first death from monkeypox.  The global monkeypox outbreak has seen more than 22,000 cases in nearly 80 countries since May. There have been 75 suspected deaths in Africa, mostly in Nigeria and Congo, where a more lethal form of monkeypox is spreading than in the West.  In the U.S. and Europe, the vast majority of monkeypox infections have happened in men who have sex with men, though health officials have stressed that anyone can catch the virus. The deaths outside Africa come one week after the World Health Organization declared the monkeypox outbreak a global health emergency. “The notification of deaths due to monkeypox does not change our assessment of the outbreak in Europe. We know that although the disease is self-limiting in most cases, monkeypox can cause severe complications,” said Catherine Smallwood, Senior Emergency Officer at WHO Europe. “With the continued spread of monkeypox in Europe, we will expect to see more deaths. Our goal needs to be on interrupting transmission quickly in Europe and stopping this outbreak,” she said.

On Friday, Spain’s health ministry reported 4,298 people were infected with the virus, making it the leading European country for monkeypox cases. Of that total, some 3,500 cases were of men who had had sex with other men. Only 64 were women. The ministry said 120 have needed hospital attention. Smallwood said around 8% of the monkeypox cases in Europe have required hospitalization. Monkeypox has been endemic to parts of Africa for decades. Its leap to Europe and North America was linked by experts to two raves in Belgium and Spain. Spanish health authorities are administering 5,300 vaccines that Spain received from the joint EU vaccine purchase scheme. Health workers say that’s far fewer than the number needed to cover the at-risk groups. But the rush to buy limited vaccines by richer Western countries is putting Africa in danger of being left out. Monkeypox spreads mainly through skin-to-skin contact, but it can also be transmitted through bed sheets used by someone with monkeypox. Symptoms include fever, body aches, chills, fatigue and hives. The illness has been relatively mild in many men. But people can be contagious for weeks, and the lesions can be extremely painful.

All but 3 of 52  patients had lesions and rashes on their genitals or anal regions.  A new study published in The Lancet Infectious Diseases found that the clinical profile in recent monkeypox cases is different than in past events, with fatigue and fever less common and genital skin lesions more likely. This is the first study to look at these differences among cases in the current outbreak, and points to the important role sexual transmission among mostly men who have sex with men (MSM) has played in spreading monkeypox in non-endemic countries, many of which had never seen a monkeypox case before. 

Most had 5 or more new partners

In the study of UK cases, all 54 of the participants identified as MSM, and their median age was 41. The patients presented to UK sexual health clinics during a 2-week period in May, at the beginning of the global outbreak. None of the men had traveled to sub-Saharan Africa, but many reported recent European travel. Of the 54 men, 52 said they were not aware of being in recent contact with anyone with monkeypox.  Forty-seven of 52 men who answered questions on recent sexual history said they had at least one new sexual partner in the 3 weeks prior to symptoms, and 29 of 52 (55.8%) had more than 5 new partners in the 12 weeks prior to diagnosis. Almost all (49/52) patients presented with lesions and rashes on their genitals or anal regions. Only five patients required hospitalization, and no one died. One-quarter of the patients also were diagnosed with another sexually transmitted infection at the same time as monkeypox. "The commonly observed symptom of skin lesions in the anal and penile areas, and the fact that a quarter of the patients tested positive for gonorrhoea or chlamydia at the same time as the monkeypox infection, suggests that transmission of the monkeypox virus in this cohort is occurring from close skin-to-skin, for example in the context of sexual activity," said Ruth Byrne, MD, from the Chelsea & Westminster Hospital NHS Foundation Trust, in a press release on the study. Study authors also suggested that the primary symptom of genital rashes should be added to case definitions of monkeypox to more accurately identify symptomatic individuals. There are now more than 5,700 cases of monkeypox in non-endemic countries, mostly in Europe and North America.

Iowa, Wisconsin, Connecticut report first cases

US cases of monkeypox are continuing to grow, with Iowa, Wisconsin, and Connecticut reporting their first cases of the virus. According to the Centers for Disease Control and Prevention, the country has 460 cases in 32 states. In Iowa, health officials said the patient likely acquired the virus when traveling internationally. In Connecticut, health officials confirmed the patient was a man in his 40s from New Haven. California has the most the most cases in the country, with 95, followed by 90 cases in New York. Illinois has 53 cases.

Research cited published in The Lancet Infectious Diseases (July 1, 2022): 

https://doi.org/10.1016/S1473-3099(22)00411-X

Even as cases rise, genetic analysis suggests that the virus has been silently circulating in people since 2018.  When the first monkeypox cases were identified in early May, European health officials were stumped. The virus was not known to spread easily among people, let alone infect dozens — and soon hundreds — of young men. The origins of the outbreak are now becoming clearer. Genetic analysis suggests that although the monkeypox virus is rapidly spreading in the open, it has been silently circulating in people for years. Health officials have already identified two versions of monkeypox among American patients, suggesting at least two separate chains of transmission. Researchers in several countries have found cases with no known source of infection, indicating undetected community spread. And one research team argued last month that monkeypox had already crossed a threshold into sustainable person-to-person transmission. The genetic information available so far indicated that, at some point in the last few years, the virus became better at spreading between people, said Trevor Bedford, an evolutionary biologist at the Fred Hutchinson Cancer Research Center in Seattle. “Genomic patterns would suggest this occurred around 2018,” Dr. Bedford said. If the virus has adapted to include people as hosts, monkeypox outbreaks could become more frequent and more difficult to contain. That carries the risk that monkeypox could spill over from infected people into animals — most likely rodents — in countries outside Africa, which has struggled with that problem for decades. The virus may persist in infected animals, sporadically triggering new infections in people.

The report distinguished two patterns of liver involvement after COVID-19: acute liver failure that required transplantation and acute hepatitis with injury to the bile system.  On June 7, 2022, the World Health Organization (WHO) and the World Hepatitis Alliance, at their World Hepatitis Summit 2022, released a joint news statement in which they also briefly addressed the current cases of unexplained acute hepatitis (liver inflammation) among young children. There have been some 700 such cases in the last five months, spanning 34 countries, coinciding with the Omicron phase of the pandemic. The United Kingdom and the United States lead in the number of cases, each with more than 200.  The clinical signs of the disease come on suddenly, with a high proportion of children developing liver failure and around six percent needing a liver transplant. Nine have died. The most common symptoms are vomiting and jaundice, the yellowing of the skin and the sclera of the eyes.  Many in the scientific community speculated that the disease fell into the spectrum of the multisystem inflammatory syndrome-children (MIS-C) arising from a previous COVID infection, which can afflict a minority of children and adolescents after the acute phase of COVID has passed and their infections have already cleared, meaning that once acute hepatitis manifests, their COVID tests are negative. Many have also not had antibody tests conducted to confirm previous COVID infections.  Speaking with New Scientist, Dr. Deepti Gurdasani of Queen Mary University of London said, “I think we have seen hepatitis as part of MIS-C before, but not in the numbers that are being seen now.” She explained that the rise could be because Omicron has infected millions of children in a few short months. Many public health officials, including the US Centers for Disease Control and Prevention (CDC) and the WHO, have placed undue emphasis on adenovirus infections, which commonly cause colds and flu-like symptoms in the population. However, they almost never cause liver failure among previously healthy children, or even the immuncocompromised, for that matter. 

Despite experience with adenoviruses and ample expertise on viral infections and liver injury that have been amply documented in the literature, this didn’t stop the CDC from writing on May 6, 2022, “This cluster [in Kentucky], along with recently identified possible cases in Europe, suggest that adenovirus should be considered in the differential diagnosis of acute hepatitis of unknown etiology among children.”  But in their report they clearly stated that on liver biopsies no [adenovirus] viral infections were ever observed. Even with the use of the electron microscope, no viral particles were evident. In the very rare instances where adenoviruses have caused liver failure among immunocompromised children, in 100 percent of cases the adenovirus was detected in liver cells. On May 22 the WHO provided a more nuanced perspective, writing, “While adenovirus is a plausible hypothesis as part of the pathogenesis mechanism [the manner of development of disease], further investigations are ongoing for the causative agent; adenovirus infection (which generally causes mild self-limiting gastrointestinal or respiratory infections in young children) does not fully explain the more severe clinical picture observed with these cases.” Dr. Farid Jalali, a gastroenterologist, has emphatically denounced the claim that these recent unexplained pediatric acute liver failures are associated with the detection of adenovirus in the patients, especially in the context of the COVID-19 pandemic and recent massive waves of Omicron infections.

Adenoviruses are common and can colonize the areas of the respiratory and intestinal tracts. Finding them doesn’t necessarily indicate they were the cause of the disease. He emphasized that public health institutions are doing a disservice to the children and families of the afflicted by suggesting such an association and are only minimizing the dangers posed by the current policies that allow SARS-CoV-2 to persist in human communities.  The debate in the scientific community has been ongoing. However, a recent study from Tel Aviv University has provided new evidence that COVID is indeed responsible for these acute liver failure cases. Lead author Dr. Shiri Cooper and colleagues submitted a report last Friday to the Journal of Pediatric Gastroenterology and Nutrition on five pediatric cases that had recovered from asymptomatic or mild COVID and later suffered acute liver injury. They distinguished two patterns of liver involvement after COVID-19: acute liver failure that required transplantation and acute hepatitis with injury to the bile system. Interestingly, the two patients with liver failure were aged only three and five months, and those older, aged eight to 13, developed a disease pattern similar to their adult counterparts.  In adults, post-COVID liver injury has been described in the medical literature but usually as a late complication of severe COVID and hospitalization that leads to progressive liver failure.  Cooper and colleagues in the current study from Tel Aviv University wrote, “The clinical manifestation of the pediatric patients suggests that the pathogenesis is not related to the severity of acute [COVID] disease” as it is in adults. The disease among children frequently presents several months after the diagnosis of COVID-19. In their study, the mean time from COVID to liver failure was 75 days, which explains why so many of these cases were missed as Long-COVID complications, because children are routinely missed in diagnosing the milder form of acute disease. 

Many of the findings in the children with liver failure have also been seen in adults, such as the swelling and enlargement of the liver. The walls of the gallbladders were thickened, and the bile ducts were dilated. Biopsies of the liver showed extensive inflammation. In other words, the disease process that has been attributed to adults after their COVID infection has distinct parallels with these children and their acute liver inflammation. Because of the claimed association with adenovirus, the authors of the Israeli study also attempted to investigate this hypothesis.  First, they commented on published results by the European CDC on 14 cases. None showed adenovirus in any residual liver cells, called hepatocytes: “One case underwent adenovirus PCR of liver tissue which was negative.” In another case series of six patients, none of the liver biopsies showed the presence of any adenovirus particles. But as already noted, in rare cases of adenovirus-induced liver failure, liver biopsies in all the cases showed viral particles were present.  In the five patients in Israel, “The adenovirus stain was negative in all, and the histologic features [under the microscope] were not suggestive of adenovirus hepatitis. Three patients had adenovirus PCR performed from whole blood, and in one, it was positive. However, as the liver histology was not suggestive of adenovirus infection, we did not consider it as the culprit for the hepatitis.” As to the mechanism of injury, the authors suggested that damage to the immune system from COVID is likely the cause, and considerable effort is needed to understand these complex processes. It is all the more necessary that public health authorities stop being obstructionists, heed the weight of the evidence that has already been presented, and acknowledge the dangers posed by COVID and the reckless “herd immunity” policy that exposes children to unnecessary harm.  Dr. Lisa Iannattone stated bluntly on Twitter, “Anyone putting forth the hypothesis that there are two novel pediatric liver failure outbreaks caused by two different viruses happening at the same time is not someone to be taken seriously. I don’t care what ‘very serious institution’ they work for. This is absurd. It’s COVID.”

Research Cited available in the Journal of Pediatric Gastroenterology and Nutrition (June 10, 2022):

https://journals.lww.com/jpgn/abstract/9900/long_covid_19_liver_manifestation_in_children.84.aspx 

A rare smallpox relative has jumped from Africa to four other continents with a disproportionate number of cases in men who have sex with men.  With the COVID-19 pandemic still raging, a second public health threat has the world on high alert: a global outbreak of monkeypox. As of 26 May, two dozen countries in the Americas, Europe, North Africa, the Middle East, and Australia had reported more than 350 suspected and confirmed cases of the disease, a much milder cousin of smallpox, the deadly scourge that the World Health Organization (WHO) deemed eradicated in 1980. A disproportionate number of cases are in men who have sex with men (MSM), an unusual twist given that researchers have never convincingly shown sexual transmission occurs in monkeypox. Monkeypox is endemic in West and Central Africa, and the virus occasionally causes outbreaks elsewhere in the world, but most are quickly contained or peter out by themselves. This outbreak looks very different, says Anne Rimoin, an epidemiologist at the University of California, Los Angeles, who has long studied monkeypox in the Democratic Republic of the Congo (DRC). “We get concerned when we see a virus doing things that we don’t normally see it doing,” Rimoin says. “We now have to really reevaluate what we know about monkeypox—which has all been gleaned, essentially, from low-resource settings in Africa—in very, very different kinds of populations.” “We should definitely be concerned about this new situation,” agrees epidemiologist Rosamund Lewis, head of poxvirus diseases at WHO. Still, Lewis stresses that monkeypox, which causes skin lesions resembling those of smallpox, is not easily transmitted, and its spread can typically be limited by isolating cases. “It’s not a concern for most people,” she says. What’s more, several drugs and vaccines developed for smallpox can also treat and prevent monkeypox.

A WHO technical advisory group that specializes in infectious hazards, chaired by epidemiologist and monkeypox veteran David Heymann of the London School of Hygiene & Tropical Medicine, met last week to develop recommendations covering everything from the need for more aggressive surveillance to the use of vaccines. In a 23 May rapid risk assessment, the European Centre for Disease Prevention and Control warned there’s a “potential risk” for human-to-animal transmission, which could enable the virus to become established in European wildlife, as it is in Africa.

U.K. officials on 7 May were the first to report a monkeypox case, a patient who had arrived from Nigeria 3 days earlier. But that person apparently did not transmit the virus to anyone else and is not the source of the wider outbreak; public health officials in Montreal say a man there had symptoms as early as 29 April. At the time, he wasn’t tested for monkeypox. Most doctors would not think to do so because the disease is vanishingly rare outside of Africa and its lesions can resemble those of chickenpox and syphilis. Portuguese doctors collected a sample on 4 May from a baffling case but didn’t test it for monkeypox either—until they learned of the unusual clusters of cases in the United Kingdom. “No one could imagine a case of monkeypox,” says João Paulo Gomes at Portugal’s National Institute of Health. Given the torrent of cases reported over the past 2 weeks, it’s possible the virus has been spreading under the radar for months, Heymann says. He expects “many more cases” to come to light in the days and weeks ahead. Rimoin says a much larger outbreak could be underway in Nigeria and nearby countries, from which the disease might have been exported repeatedly to the rest of the world. “We’re not looking for these kinds of things, and if you don’t look for them, you don’t find them,” she says.

"Monkeypox is a misnomer; the virus was discovered in 1958 in research monkeys, but its natural hosts are likely rodents and other small mammals. The virus first surfaced in humans in 1970 in what is now the DRC, causing fever, headaches, and lymph node swelling followed by an eruption of pus-filled blisters. Outbreaks occur occasionally in sub-Saharan Africa after someone comes in contact with an infected wild animal, and infected travelers sometimes carry the disease to other countries. The biggest known outbreak in the United States occurred in 2003, when 47 people were infected by pet prairie dogs that had picked up the virus from rodents imported from Ghana. Most people recover within a few weeks. The Congo Basin strain kills up to 10% of those infected, but the current outbreak appears to only involve the West African strain, which in past outbreaks had a fatality rate of about 1%. Outbreaks “generally fizzle out on their own,” Lewis notes, because many infected people simply never infect anyone else. says “Only a small subset of the population are currently affected and while I would not be surprised if there are more cases, we don’t expect it to be taking off the way COVID-19, for example, took off,” says Agam Rao, a scientist in the poxvirus and rabies branch of the Centers for Disease Control and Prevention (CDC), which confirmed the first U.S. case. Monkeypox usually spreads through close contact and respiratory droplets, but in 2017 Nigerian researchers suggested sexual transmission might have occurred in several patients with genital ulcers. Those are being seen now as well, says Fernando Simón, who directs the Spanish Ministry of Health’s coordination center for health alerts and emergencies. Among the first confirmed reported cases, “most have lesions exclusively perigenital, perianal, and around the mouth,” Simón says. Some of the first cases detected in Spain are MSM or transgender people who had attended a sauna in Madrid or a gay pride festival in the Canary Islands. In Belgium, several cases were linked to a gay festival in Antwerp. No studies have ever found that semen can transmit the virus. “So far, the most acceptable hypothesis is that it is transmitted after contact with lesions,” Simón says. MSM and transgender communities have a high prevalence of HIV, but there’s no evidence that compromised immune systems have played any role in this outbreak. Health officials in many affected countries have, for privacy reasons, offered few details about the infected people, but Simón notes that two of the early cases detected in Spain were people living with HIV infections that were well controlled with medication.

Public health officials face a tricky balance as they seek to clearly communicate the risks to the MSM community while avoiding stigmatization. “Stigma and blame undermine trust and capacity to respond effectively during outbreaks like this one,” Matthew Kavanagh, deputy executive director of the Joint United Nations Programme on HIV/AIDS, said in a statement this week. Researchers have begun to sequence viral samples, which can help trace how the virus has spread and reveal mutations that might make it more pathogenic or more transmissible. It’s a laborious job: With more than 200,000 base pairs, the monkeypox genome is about seven times the size of SARS-CoV-2’s and more than 20 times larger than HIV’s. The first full genome, posted on 19 May by a Portuguese team led Gomes, showed that the strain most closely resembles viruses carried by travelers from Nigeria to Singapore, Israel, and the United Kingdom in 2018 and 2019. Sequences posted by the CDC and scientists in Belgium and Germany support that conclusion. “We’re not seeing any evidence that this virus has changed to become more efficiently transmitted person to person,” Jennifer McQuiston, the head of CDC’s pox virus and rabies branch, said at a 23 May press conference. Because it’s a DNA virus, monkeypox has far better genetic repair mechanisms than RNA viruses such as HIV and SARS-CoV-2, which means it changes more slowly. Still, studies by Gustavo Palacios, a virologist at the Icahn School of Medicine at Mount Sinai and co-workers suggest mutations are frequent enough for investigators to create virus family trees that can help clarify how cases connect to each other. Monkeypox's cousin, smallpox, was a major scourge for centuries that killed up to 30% of those infected. A massive global campaign in the 1960s and ’70s brought transmission to a halt; today, the virus is the only human pathogen to have been eradicated, although samples still exist at laboratories in Russia and the United States. As cases plummeted in the early ’70s, countries began to stop using the smallpox vaccine because its risks outweighed potential benefits. The vaccine contained a virus called vaccinia, which has a confusing history but appears to be a natural pox virus that was cultured in labs. Vaccinia replicates inside the recipient and sometimes caused severe side effects, killing one in 1 million vaccinated people. WHO’s vaccination campaign ended in 1977, the last year a natural case of smallpox occurred. Smallpox infections and the smallpox vaccine both protect against monkeypox, so an increasing number of people have become vulnerable to monkeypox over the past 50 years. Some researchers have worried that monkeypox might evolve to fill the “ecological niche” left behind by smallpox. Indeed, reported cases have steadily increased Africa over the years—and the new outbreak is the first one to take place on several continents simultaneously.

The strategy to contain monkeypox outbreaks has always relied on educating people and finding cases early to reduce the chance they transmit the virus. But vaccines, which prevent disease even if used up to 4 days after a person is exposed to the virus, could also be used. Two vaccines are licensed by the U.S. Food and Drug Administration (FDA). One, manufactured by Emergent BioSolutions, is similar to the smallpox vaccine used during the eradication campaign and can still cause severe disease and even death in people who have compromised immune systems. It only requires a single dose. The other, from Bavarian Nordic, uses a nonreplicating form of vaccinia, specifically designed to cause fewer side effects. It requires two doses given 4 weeks apart. Animal studies suggest the first dose works more quickly than the vaccine from Emergent BioSolutions, whereas the second dose increases the durability of protection. FDA has explicitly approved the Bavarian Nordic vaccine for both smallpox and monkeypox.   The United Kingdom is already offering vaccines to health care workers and other contacts of known cases—a strategy called ring vaccination, which was key to the success of the smallpox eradication campaign. The United States has begun to offer vaccination to some contacts but is undecided about health care workers caring for monkeypox patients. Rimoin says ring vaccination doesn’t seem warranted yet but that might change “if in the next couple of days … we see that there are hundreds and hundreds of cases.”

Both vaccines are in short supply, however. In a bizarre coincidence, Bavarian Nordic held a meeting with Heymann and nine other public health leaders from around the world last week, planned 6 months ago, to discuss the need for more countries to stockpile its vaccine, given the increase in monkeypox cases over the past few years. “We were really thinking that experts in this field and authorities need to start to reflect on it,” says Bernard Hoet, the company’s vice president of medical strategy. “A company like ours cannot stockpile for all the countries forever. Today we have some doses available and we are going to distribute them, but how do you want us to decide if they go here or there?” Drugs exist as well. One, tecovirimat, in 2018 became the first ever approved by FDA to treat smallpox after it proved safe in human trials and effective in animals given closely related viruses. FDA approved a second drug for smallpox, brincidofovir, in 2021. Although neither has been approved for monkeypox, both showed promising results against the virus in animal studies.

But a report published on 24 May in The Lancet Infectious Diseases reported no evidence that brincidofovir had “any convincing clinical benefit” in three patients treated in the United Kingdom over the past 3 years and said the drug had serious toxicities. Tecovirimat, in contrast, did not cause side effects and appeared to lead to a decrease in viral levels and a speedier recovery. How far and fast the virus spreads in the coming days will determine how aggressively clinicians put these tools to the test. “These are very early days,” Rimoin says.

Health ministry says cases yet to be confirmed and come after the viral infection detected in UK and Portugal.  Health authorities in Spain have issued an alert over a possible outbreak of monkeypox after eight men showed symptoms compatible with the viral infection, which has already been detected in the UK and Portugal. In a statement, the health ministry cautioned that the eight suspected cases – all in the Madrid region – had yet to be confirmed, but said a nationwide alert had been issued “to guarantee a swift, coordinated and timely response”. A spokesperson for Madrid’s regional health department said the suspected cases were being analysed by the National Microbiology Centre to obtain a definitive diagnosis.  “Generally speaking, monkeypox is spread by respiratory transmission, but the characteristics of the eight suspected cases point towards fluid contact,” the spokesperson said. “The eight suspected cases in Madrid are among men who have sex with men. They are doing well but this illness can require hospital treatment.” Fernando Simón, an epidemiologist who heads Spain’s health emergencies centre, said while it was unlikely that monkeypox would spread significantly, “that can’t be ruled out”.

Portuguese authorities have confirmed five cases and are investigating another 15 suspected cases. In a statement on Wednesday, Portugal’s health ministry said the cases it had detected – all in the Lisbon and Tagus Valley region – had all involved men whose symptoms included ulcerative lesions. “The UK has reported similar cases of ulcerative lesions, with confirmed monkeypox virus infection,” it said. “We are monitoring the situation at national level and in conjunction with European institutions.” The first of the seven cases logged in the UK involved a person who had recently been to Nigeria, where they are believed to have contracted the infection. According to the UK Health Security Agency, all four of the most recent cases are men who identify as gay or bisexual or other men who have sex with men. The health body is asking these groups “to be alert” to possible symptoms, which include rashes or lesions on any part of their body, especially their genitalia, and to contact a sexual health service if they have concerns.  Early symptoms of monkeypox include fever, headache, muscle aches, swollen lymph nodes and chills. A rash that can look like chickenpox or syphilis can also develop and spread from the face to other parts of the body, including the genitals. Most people recover within a few weeks. A handful of cases of monkeypox, which has two forms and is typically found in central and western Africa, have been diagnosed in the UK in the past. It is thought the seven UK cases involve the west African strain, which is milder than the more severe central African, or Congo, strain.

Health officials in the UK have released new details in their ongoing investigation of an unusual series of hepatitis cases in children. The new report helps explain why they have zeroed in on a possible link to the adenovirus family, the UK Health Security Agency announced Monday.  Since the beginning of the year, at least 111 children have been identified in the UK with acute liver inflammation that does not appear to be caused by the group of hepatitis viruses that would've been a more likely culprit. Many more cases have been announced in the US and other countries around the world. Roughly three-quarters of the 53 children who were tested for adenovirus in the UK came back positive. The virus that causes Covid-19, on the other hand, was found in only a sixth of children who were tested — in line with the levels of community transmission in the UK. 

With six confirmed and two suspected cases, health officials are ramping up a vaccination push amid fears of a wider outbreak.  A polio outbreak centered in Jerusalem has prompted Israel’s return to the World Health Organization’s list of polio “outbreak countries.” Israel now appears along with 28 other countries on the WHO’s Global Polio Eradication Initiative’s list of countries with polio outbreaks, after being declared polio-free in 1988. Nations including Egypt, Iran, Ethiopia and Ukraine are also on the list of outbreak countries — places where the virus was halted but has resurfaced — while Afghanistan and Pakistan are considered endemic countries. Last month, the first case of polio in more than 30 years was confirmed in Jerusalem, spurring deep concerns and a renewed vaccination drive.  According to the latest Health Ministry figures, released last week, there have been six confirmed polio cases, all among unvaccinated patients. In addition, there is a high likelihood of another case in an unvaccinated child, and an eighth potential case that is being investigated. Traces of the disease have also been found in the sewage system in Jerusalem, Beit Shemesh, Tiberias and Modiin Illit.

Over the past month, more than 18,000 children in the Jerusalem area have received a polio vaccine dose as part of the ministry’s push to reach those who were unvaccinated or partially vaccinated. Like much of the world, Israel administers polio vaccines — spread out in multiple doses — to children as part of its standard vaccine regimen. Polio spreads mostly from person to person or through contaminated water. It attacks the nervous system and can sometimes paralyze people within hours. The disease mostly affects children under 5 and has been largely wiped out in wealthy countries. Dr. Sharon Alroy-Preis, the Health Ministry’s public health director, explained last week that during the years 2005-2013, polio vaccinations were scaled back as the disease was vanquished in the country and many babies did not get all the necessary doses. “We are definitely seeing an outbreak of polio in Israel,” Alroy-Preis said. “It reaches unvaccinated pockets and is spreading.” One Jerusalem child who was recently diagnosed with polio has weakness and paralysis on one side, she reported. “That is just the tip of the iceberg, under which there are many other infected children,” she assessed. Disease experts have warned of the real prospect of a resurgence of polio cases — in manageable numbers but enough to leave some children with long-term damage. Traces of the virus have occasionally been found in sewage samples in Israel, but have not resulted in any clinical cases for several decades.