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A new lineage of the mpox virus linked to efficient human-to-human transmission has been identified in the Democratic Republic of the Congo (DRC) — and the researchers behind the finding are calling for swift action to 'avert another global mpox outbreak.' A team of Canadian and international scientists working on the ground in DRC began tracking a large mpox outbreak in the country's Kamituga mining region last year. From October 2023 onward, cases spread rapidly with more than 240 suspected infections identified within five months. Out of roughly 100 confirmed cases, a third were among sex workers, the team wrote in their latest paper. Mpox — previously known as monkeypox — burst onto the global landscape in 2022, spreading to dozens of countries through sexual networks that largely impacted men who have sex with men. Infections can lead to painful lesions and, in more severe cases, sepsis, lung nodules and even death. Genomic analysis of the recent Kamituga outbreak uncovered what lead researcher Dr. Placide Mbala-Kingebeni calls an "alarming" finding: a new, distinct clade Ib lineage of the mpox virus featuring mutations that are a hallmark of efficient transmission between humans. Mbala-Kingebeni's findings were published online this week as a pre-print, meaning the research has not yet been peer-reviewed. The researchers say the ongoing situation in Kamituga echoes the 2017 to 2018 outbreak of clade IIb mpox in Nigeria, which is now widely considered a harbinger to the unprecedented global spread of the disease a few years later. Mbala-Kingbeni told CBC News the worldwide spread of mpox in 2022 involved a form of the virus that's thought to cause less severe disease, though some scientists warn underreporting of cases makes it tricky to know the precise differences between each clade. (Clades are subtypes of a virus that arise from a common ancestor. In the case of mpox, the two main clades identified so far are clade I and clade II.) "There is a high risk that this more virulent clade, that's more adapted to human-to-human transmission ... can be transmitted silently from one person to another and be sustained at a global level," added Mbala-Kingbeni, an associate professor at the University of Kinshasa and head of epidemiology and global health at the DRC National Institute of Biomedical Research's Clinical Research Center. Urgent measures are needed — including expanded surveillance, contact tracing and targeted vaccination efforts — to contain this "pandemic-potential" outbreak, the researchers wrote. Ongoing DRC outbreaks 'alarming' The team's concern stems, in part, from Kamituga's demographics. The densely-populated region lacks healthcare infrastructure to handle a large-scale outbreak, and the researchers believe the reported cases are likely an underestimate. It's also a travel hub, with large amounts of movement between the region and neighbouring countries in Africa, such as Rwanda and Burundi, including sex workers who "frequently return to their countries of origin." "The highly mobile nature of this mining population poses a substantial risk of outbreak escalation beyond the current area and across borders," reads the paper. Toronto-based infectious diseases specialist Dr. Isaac Bogoch, who was not involved in the research, praised the team for showing a "subtle but real" genetic difference in the mpox virus samples from Kamituga. The research further raises alarms about the record-breaking levels of mpox circulating in DRC, he added, and the country's lack of vaccines or therapeutics to contain the spread of the virus. But he cautioned against over-interpreting the results, saying the findings don't prove this new lineage is even more transmissible than before or capable of evading existing treatments and vaccines. Further research is needed, Bogoch stressed, to better understand a virus that's causing massive outbreaks in Africa and is still quietly circulating locally in Canada as well — with more than 20 cases reported in Toronto alone so far this year. The study also doesn't change the existing possibility that a different lineage of mpox could eventually jump internationally, Bogoch added. "Without this mutation we would have this exact same conversation," he said. "The alarming part to me is we know there's an ongoing outbreak in [DRC], and we still don't have a coordinated global response." Preprint of the study available in medRxiv (April 15, 2024); https://doi.org/10.1101/2024.04.12.24305195
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In its latest monthly update, the World Health Organization (WHO) reported 906 new mpox cases from 26 countries in November, reflecting an increase of 26% compared to October. With nearly 300 cases, the United States reported the steepest rise in the Americas, followed by Portugal reporting 128 new cases, which makes Europe the region with the second highest number of cases. Singapore's cases increased, and though China's cases declined, the country continues to contribute to high case counts in the Western Pacific region. Africa reported a small decline, but the WHO said irregular reporting and high numbers of suspected cases in the Democratic Republic of Congo (DRC) outbreak make it difficult to interpret the trend there. "The constantly changing geographical distribution of the cases does not allow for an accurate prediction of the regional trends, but the continued high number of cases globally highlights the fact that this outbreak is not over, and the virus continues to find pockets of susceptible individuals," the WHO said. The group did not note any major changes in the epidemiology of the disease. Latest W.H.O. report on Mpox (Dec. 23, 2023): https://www.who.int/publications/m/item/multi-country-outbreak-of-mpox--external-situation-report-31---22-december-2023
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Skin organoids offer a powerful platform for drug discovery in the ongoing fight against the virus formerly known as monkeypox. A new model system for studying mpox virus infections in the laboratory is providing valuable insights into the virus's mechanisms of attack on skin cells, offering a potential catalyst in the quest to discover innovative drugs to combat this emerging pathogen. An international research team that included KAUST scientists has demonstrated that lab-grown human skin — stem cell-derived 3D structures called organoids — can effectively facilitate the active replication of mpox virus, the virus formerly known as monkeypox virus, that spread rapidly during a major outbreak in 2022. "Researchers can now use this model to study how the mpox virus causes disease and to test new therapeutics," says Intikhab Alam, a bioinformatician who contributed to the study along with his colleague Roberto Incitti, both from KAUST. People infected with the mpox virus typically develop rashes and skin lesions, often leading to scarring and disfigurement — and the lab-grown skin organoids now help show why. KAUST's Alam and Incitti collaborated with Qiuwei Abdullah Pan and his team from the Erasmus MC-University Medical Center in Rotterdam to report that the virus takes up residence inside keratinocytes, the predominant cell type in the skin's outer layer. There, the virus undergoes its four steps of assembly, a process that the researchers could observe under high-power microscopes. Gene expression analyses conducted by the researchers revealed that numerous viral genes become activated in the days following infection. This activation, in turn, appears to induce changes in host cells, leading to alterations in the activity of multiple human genes associated with immunity and cell death. These genetic alterations likely compromise the skin's protective barrier, resulting in the characteristic lesions observed in infected people. The observed effects could be reversed through use of an antiviral drug called tecovirimat. In the infected organoids, this drug proved highly effective in halting virus replication and thwarting the subversion of host cells. The findings validate the mpox-inhibiting potential of tecovirimat, a drug approved to treat infections with the related smallpox virus. They also underscore the potential of the organoid system as a versatile platform with which to screen for novel substances with similar properties. Notably, the impact of mpox extends beyond skin-related issues. In severe cases, the virus can wreak havoc on internal organs. The same KAUST-affiliated research team previously developed a kidney organoid system designed to study mpox infections in renal tissues. Other groups have investigated mpox dynamics within colon and brain organoids. Collectively, the efforts in organoid models — which the KAUST researchers and their collaborators are now extending to other viral infection systems as well — should "help to combat the current mpox outbreak and enhance pandemic preparedness for the future," Incitti says. Studies published in Nature Microbiology (Oct. 13, 2023): https://doi.org/10.1038/s41564-023-01489-6
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Back in January, Moderna set a planned mpox vaccine on the back burner as the immediate outbreak waned, but now the shot has slid into the priority lane, with entry to the clinic likely a “month or | Back in January, Moderna set a planned mpox vaccine on the back burner as the immediate outbreak waned, but now the shot has slid into the priority lane, with entry to the clinic likely a “month or so” away, according to a top vaccine developer and strategist at the company. Moderna is set to launch a phase 1/2 trial of the shot this summer, Hamilton Bennett, senior director of vaccine access and partnerships at Moderna, said in an interview at the the BIO International Convention. The company had previously teased launching human trials sometime this year. Bennett said the goal is to build a preclinical data package that shows efficacy across orthopoxviruses, which include mpox and smallpox, and then generate "robust" phase 1/2 data to inform dose selection and eventually licensure. She added that the company has met with the U.S. mpox response team a couple of times to say, “this is where we are, these are the barriers that we're seeing.” “They've been incredibly helpful in helping us get access to samples and people and information,” she said. Moderna CEO Stéphane Bancel told Fierce Biotech in January that developing a mpox vaccine was not a high priority as development pressed ahead on more than a dozen unique assets beyond the COVID vaccine that helped make the company a household name. Bennett clarified that he was speaking relative to Moderna’s urgency to develop a COVID-19 vaccine during the pandemic. “I think when Stéphane says it's not a priority, it is not a COVID-like priority,” she said. The upcoming trials are just the latest example of the swiftness of Moderna's mRNA platform. The company announced in May 2022 that preclinical work would begin on an mpox vaccine. But no update had been made on the progress prior to Bancel's comments at the beginning of the year. For Bennett, the development of the shot means more than just the potential for a new product; it’s an opportunity to flex her muscles leading the company’s public health portfolio, a position she’s pivoted to since helping lead development and dissemination of the COVID shot. That new role broadly puts her in charge of coordinating with developing nations to help scale up vaccine-related economic infrastructure and ensuring that Moderna is accountable and its products are available to those nations. Bennett said that mpox is a “perfect example” of some of the barriers the company will face as it develops these products, in part because, as of now, funding for an mpox vaccine is really for a smallpox vaccine. At a grander level, mpox represents a virus that only gained national attention when people outside of Africa began to be infected. Bennett doesn’t want Moderna to be caught on its back foot when addressing diseases of significance, even if they aren’t affecting high-income countries. “Our portfolio in global health is designed to allow those associations to happen because they're not something where we can pick up the phone when the clock starts,” she said. “We need to build those relationships now.”
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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.
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Background People living with HIV have accounted for 38–50% of those affected in the 2022 multicountry mpox outbreak. Most reported cases were in people who had high CD4 cell counts and similar outcomes to those without HIV. Emerging data suggest worse clinical outcomes and higher mortality in people with more advanced HIV. We describe the clinical characteristics and outcomes of mpox in a cohort of people with HIV and low CD4 cell counts (CD4 <350 cells per mm3). Methods A network of clinicians from 19 countries provided data of confirmed mpox cases between May 11, 2022, and Jan 18, 2023, in people with HIV infection. Contributing centres completed deidentified structured case report sheets to include variables of interest relevant to people living with HIV and to capture more severe outcomes. We restricted this series to include only adults older than 18 years living with HIV and with a CD4 cell count of less than 350 cells per mm3 or, in settings where a CD4 count was not always routinely available, an HIV infection clinically classified as US Centers for Disease Control and Prevention stage C. We describe their clinical presentation, complications, and causes of death. Analyses were descriptive. Findings We included data of 382 cases: 367 cisgender men, four cisgender women, and ten transgender women. The median age of individuals included was 35 (IQR 30–43) years. At mpox diagnosis, 349 (91%) individuals were known to be living with HIV; 228 (65%) of 349 adherent to antiretroviral therapy (ART); 32 (8%) of 382 had a concurrent opportunistic illness. The median CD4 cell count was 211 (IQR 117–291) cells per mm3, with 85 (22%) individuals with CD4 cell counts of less than 100 cells per mm3 and 94 (25%) with 100–200 cells per mm3. Overall, 193 (51%) of 382 had undetectable viral load. Severe complications were more common in people with a CD4 cell count of less than 100 cells per mm3 than in those with more than 300 cells per mm3, including necrotising skin lesions (54% vs 7%), lung involvement (29% vs 0%) occasionally with nodules, and secondary infections and sepsis (44% vs 9%). Overall, 107 (28%) of 382 were hospitalised, of whom 27 (25%) died. All deaths occurred in people with CD4 counts of less than 200 cells per mm3. Among people with CD4 counts of less than 200 cells per mm3, more deaths occurred in those with high HIV viral load. An immune reconstitution inflammatory syndrome to mpox was suspected in 21 (25%) of 85 people initiated or re-initiated on ART, of whom 12 (57%) of 21 died. 62 (16%) of 382 received tecovirimat and seven (2%) received cidofovir or brincidofovir. Three individuals had laboratory confirmation of tecovirimat resistance. Interpretation A severe necrotising form of mpox in the context of advanced immunosuppression appears to behave like an AIDS-defining condition, with a high prevalence of fulminant dermatological and systemic manifestations and death. Published in The Lancet (feb. 21, 2023):
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CNN — The US public health emergency declaration for mpox, formerly known as monkeypox, ends Tuesday. The outbreak, which once seemed to be spiraling out of control, has quietly wound down. The virus isn’t completely gone, but for more than a month, the average number of daily new cases reported to the US Centers for Disease Control and Prevention has hovered in the single digits, plummeting from an August peak of about 450 cases a day. Still, the US led the world in cases during the 2022-23 outbreak. More than 30,000 people in the US have been diagnosed with mpox, including 23 who died. Cases are also down across Europe, the Western Pacific and Asia but still rising in some South American countries, according to the latest data from the World Health Organization. It wasn’t always a given that we’d get here. When mpox went global in 2022, doctors had too few doses of a new and unproven vaccine, an untested treatment, a dearth of diagnostic testing and a difficult line to walk in their messaging, which needed to be geared to an at-risk population that has been stigmatized and ignored in public health crises before. Experts say the outbreak has taught the world a lot about this infection, which had only occasionally been seen outside Africa. But even with so much learned, there are lingering mysteries too – like where this virus comes from and why it suddenly began to spread from the Central and West African countries where it’s usually found to more than 100 other nations. How long has it been spreading? Before May 2022, when clusters of people with unusual rashes began appearing in clinics in the UK and Europe, the country reporting the most cases of mpox was the Democratic Republic of Congo, or DRC. There, cases have been steadily building since the 1970s, according to a study in the CDC’s Morbidity and Mortality Weekly Report. In the DRC, people in rural villages depend on wild animals for meat. Many mpox infections there are thought to be the result of contact with an animal to which the virus has adapted; this animal host is not known but is assumed to be a rodent. For years, experts who studied African outbreaks observed a phenomenon known as stuttering chains of transmission: “infections that managed to transmit themselves or be transmitted from person to person to a limited degree, a certain number of links in that chain of transmission, and then suddenly just aren’t able to sustain themselves in humans,” said Stephen Morse, an epidemiologist at Columbia University’s Mailman School of Public Health. Informally, scientists kept track, and Morse says that for years, the record for links in a mpox chain was about four. “Traditionally, it always burned itself out,” he said. Then the chains started getting longer. In 2017, Nigeria – which hadn’t had a confirmed case of mpox in more than four decades – suddenly saw a resurgence of the virus, with more than 200 cases reported that year. “People have speculated maybe it was a change in the virus that allowed it to be made better-adapted to humans,” Morse said. From 2018 through 2021, eight cases of mpox were reported outside Africa. All were in men ages 30 to 50, and all had traveled from Nigeria. Three reported that the rashes had started in their groin area. One went on to infect a health care provider. Another infected two family members. This Nigerian outbreak helped experts realize that mpox could efficiently spread between people. It also hinted that the infection could be sexually transmitted, but investigators couldn’t confirm this route of spread, possibly because of the stigma involved in sharing information about sexual contact. In early May 2022, health officials in the UK began reporting confirmed cases of mpox. One of the people had recently traveled to Nigeria, but others had not, indicating that it was spreading in the community. Later, other countries would report cases that had started even earlier, in April. Investigators concluded that mpox had been silently spreading before they caught up to it. Declaring an emergency In early summer, as US case numbers began to grow, the public health response bore some uncomfortable similarities to the early days of Covid-19. People with suspicious rashes complained that it was too hard to get tested because a limited supply was being rationed. Because the virus had so rarely appeared outside certain countries in Africa, most doctors weren’t sure how to recognize mpox or how to test for it and didn’t understand all its routes of spread. A new vaccine was available, and the government had placed orders for it, but most of those doses weren’t in the United States. Beyond that, its efficacy against mpox had been studied only in animals, so no one knew whether it would actually work in humans. There was an experimental treatment, Tpoxx, but it too was unproven, and doctors could get it only after filling out reams of paperwork required by the government for compassionate use. Some just gave up. “Tpoxx was hard to get,” said Dr. Jeffrey Klausner, a clinical professor of public health at the University of Southern California’s Keck School of Medicine. “I was scrambling to find places that could prescribe it because my own institution just became a bureaucratic nightmare. So I basically would be referring people for treatment outside my own institution to be able to get monkeypox treatment,” he said. Finally, in August, the federal government declared a public health emergency. This allowed federal agencies to access pots of money set aside for emergencies. It also allows the government to shift funds from one purpose to another to help cover costs of the response – and it helped raise awareness among doctors that mpox was something to watch for. The government also set up a task force led by Robert Fenton, a logistics expert from the Federal Emergency Management Agency, and Dr. Demetre Daskalakis, director of the CDC’s Division of HIV and AIDS Research. Daskalakis is openly gay and sex-positive, right down to his Instagram account, which mixes suit-and-tie shots from White House briefings with photos revealing his many tattoos. “Dr. Daskalakis … really walks on water in most of the gay community, and then [Fenton is] a logistics expert, and I think that combination of leadership was the right answer,” Klausner said...
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Highlights - Phylodynamic models reveal swift early mpox spread between five global regions
- Extensive, underdetected dissemination promoted rapid local transmission
- Later mpox introductions played a negligible role in prolonging regional epidemics
- N. America epidemic declined before 10% of high-risk group had vaccine-induced immunity
Summary The World Health Organization declared mpox a public health emergency of international concern in July 2022. To investigate global mpox transmission and population-level changes associated with controlling spread, we built phylogeographic and phylodynamic models to analyze MPXV genomes from five global regions together with air traffic and epidemiological data. Our models reveal community transmission prior to detection, changes in case reporting throughout the epidemic, and a large degree of transmission heterogeneity. We find that viral introductions played a limited role in prolonging spread after initial dissemination, suggesting that travel bans would have had only a minor impact. We find that mpox transmission in North America began declining before more than 10% of high-risk individuals in the USA had vaccine-induced immunity. Our findings highlight the importance of broader routine specimen screening surveillance for emerging infectious diseases and of joint integration of genomic and epidemiological information for early outbreak control. Published in Cell (Feb. 29, 2024):
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Experts warn the strain of the disease behind the new outbreak has the potential to spread worldwide. Nearly 600 have died of suspected mpox in the Democratic Republic of Congo this year, with a further 11,988 infected, in what has become the nation’s largest-ever outbreak. The death toll surpasses the 112 global fatalities recorded during last summer’s outbreak, when the disease spread among multiple Western nations for the first time, including the UK. Experts warn the outbreak is being driven by a strain of the virus that previously spread exclusively through animal to human contact, but is now rapidly spreading between humans. “The risk of mpox further spreading to neighbouring countries and worldwide appears to be significant,” the WHO said. DRC’s struggles with mpox, a viral infection spread primarily through close human contact previously known as monkeypox, has been attributed to the nation’s poor health infrastructure. Mpox, formerly known as monkeypox, has now been discovered in 85 per cent of provinces in the DRC, including Kinshasa, Lualaba and South Kivu, where there were no prior documented cases. The death rate stands at 4.6 per cent. The outbreak has been attributed to a Belgian resident visiting Kenge in Kwango province in March, who tested positive for the virus. Epidemiological investigations identified five sexual contacts that subsequently contracted the infection - a strain of mpox that is distinct from the one which circulated globally last year. According to the WHO, “this event is unusual and highlights the risk that MPXV clade I could also be widely spread among sexual networks, as seen for clade II during the 2022-23 global outbreak.” Common symptoms include a skin rash or lesions, accompanied by fever, headache, muscle aches, back pain, low energy, and swollen lymph nodes that typically last 2-4 weeks. Complications from severe cases include bacterial infection from skin lesions, pneumonia, and adverse lung and heart effects. These cases may require hospitalisation and antiviral medication, which proves challenging in some regions of the DRC. National response capacities in the country face immense challenges, including limited epidemiological information on exposure and infection risk factors, a lack of public awareness amongst vulnerable groups, and competing priorities. Mpox is zoonotic, meaning it derives in animals and spreads to humans. Evidence of the virus has previously been found in squirrels, Gambian pouched rats, dormice and various species of monkeys. The global outbreak of the virus last summer caused a spate of cases in previously unaffected regions, including the UK, US, Australia, Europe, and Canada. It circulated primarily amongst men who have sex with men, and sex workers.
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BioNTech is taking its mRNA mpox vaccine into the clinic, thanks in part to $90 million from a leading pandemic prevention organization. | BioNTech has partnered up with pandemic prevention organization CEPI to the tune of $90 million to help advance a couple of phase 1 stage mpox vaccines. The funding is part of CEPI's latest 100 Days Mission to help stymie future outbreaks. BioNTech began work on its vaccine, BNT166, as mpox (formerly known as monkeypox) began to spread globally in the summer of 2022. A phase 1/2 trial just got off the ground in August and will test two similar candidates (BNT166a and BNT166c) in patients with or without prior history of mpox infection. “Our work on mpox could broaden the portfolio of vaccines available against this potentially deadly disease, while building our understanding of how mRNA technology performs against orthopoxviruses, a family of viruses that have long afflicted humankind and remain an ongoing threat today,” CEPI CEO Richard Hatchett, M.D., said in the release....
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In the recent Morbidity and Mortality Weekly Report (MMWR) published by the Centers for Disease Control and Prevention (CDC), researchers reported on JYNNEOS vaccine effectiveness (VE) against Mpox infections among New York (NY) residents in 2022. Bavarian Nordic’s JYNNEOS (Modified Vaccinia Ankara) vaccine was used in the state- and nation-wide vaccination campaigns during the 2022 Mpox outbreak, which primarily affected gays, bisexuals, and males who had sex with males (MSM). As a result, health authorities prioritized postexposure prophylaxis (PEP) and vaccinating high-risk individuals (mainly MSM). However, data on JYNNEOS VE from controlled trials are limited. About the report In the present report, researchers presented JYNNEOS VE in preventing Mpox infections among NY residents during 2022. The team compared JYNNEOS vaccination results among adult males with laboratory-verified Mpox (case-patients) diagnosed between 24 July and 31 October 2022, in New York, to those among control individuals diagnosed with primary syphilis or rectal gonorrhea and prior history of sexual intercourse with males without Mpox infection. Surveillance data were systematically obtained for the analysis. The team matched cases and controls to the vaccination system records of the state. Logistic regression modeling was performed to calculate the odds ratios (OR), which were used along with the number of JYNNEOS vaccination doses received to estimate VE. The data were adjusted for age, ethnicity, race, a residential region within New York but outside of New York City, and the Mpox diagnosis week. The status of JYNNEOS vaccination was classified into the following groups: an unvaccinated group (zero JYNNEOS vaccine doses received); vaccinated for Mpox or sexually transmitted infections (STIs) with specimens obtained within two weeks of initial vaccine administration; vaccinated with STI specimens obtained after two or more weeks of the initial vaccination; and vaccinated with STI specimens obtained following the subsequent vaccination. Reports were assessed by population health staff members and entered into the Communicable Disease Electronic Surveillance System (CDESS). One-dose, two-dose, and combined estimates of JYNNEOS vaccine effectiveness were obtained. Results Between 2 June and 31 December 2022, the NYSDOH recorded 375 Mpox cases, and the NYSIIS recorded 27,385.0 vaccine doses administered, of which 61% (n=16,769) and 39% (n=10,616) were the first and second doses, respectively. The case counts were highest in the middle of August, five weeks following the JYNNEOS immunization campaign launch. Between 24 July and 31 October, 252 cases and 255 controls (80 and 175 with primary-type syphilis and rectal gonorrhea, respectively) satisfied the eligibility criteria and had similar ages. Hispanics were more common among cases than controls (44% versus 19%, respectively), and more cases (69%) than controls (36%) resided in urban areas outside New York City. The majority (91%) of participants (n=220) were unvaccinated, and 9.0% of cases (n=22) were JYNNEOS vaccinees, among whom 10 individuals (4.0%), 10 individuals (4.0%), and two individuals (1.0%) had received one dose <2.0 weeks prior, one dose ≥2.0 weeks prior, and two doses, respectively. Among controls, 51 (20%) were JYNNEOS vaccinees, including 42 individuals (17%) who were diagnosed with an STI ≥2.0 weeks after receiving the initial dose (9.0%, 23 individuals) or both doses (7.5%, 19 individuals). The adjusted one-dose, two-dose, and combined JYNNEOS VE estimates were 68%, 89%, and 76%, respectively. JYNEEOS VE observed in less than two weeks of receiving the initial dose was non-significant, probably due to the inclusion of PEP recipients and individuals with Mpox exposure after vaccination but before developing protective immunity. Multiple sensitivity analyses were performed to assess the robustness of the study findings. The initial analyses, excluding males aged ≥50.0 years who may have been administered smallpox vaccines before the termination of regular non-military US vaccinations in 1972, yielded similar results. The second analysis comprised 71.0 control individuals diagnosed with secondary syphilis and yielded a single-dose or double-dose VE of 65.0%. Among controls, 84% (n=213) underwent testing due to the presence of symptoms (41%, 88 individuals), partner referrals (9.0%, 19 individuals), screening purposes (48%, 103 individuals), or other reasons (1.40%, three individuals). The third sensitivity analysis, including only control individuals undergoing testing due to referrals or symptoms, yielded a one-dose or two-dose VE estimate of 64.0%. The fourth sensitivity analysis included the findings of only individuals with known ethnicity and race estimates, yielded single-dose or double-dose VE estimates of 81.0%. The lower estimated VE obtained by analyzing secondary syphilis patients may reflect control individuals with different clinical presentations or more remote risk behaviors. Lower VE obtained by limiting the control group to individuals undergoing testing due to symptoms or referrals may reflect the intended elimination of low-risk individuals seeking care or the inadvertent elimination of high-risk individuals accessing Mpox screening frequently. Based on the findings, the adjusted combined one-dose (administered ≥2.0 weeks prior) or two-dose JYNNEOS vaccine effectiveness was 76%. The findings underpin the advocacy of two-dose JYNNEOS vaccination regimens to prevent Mpox, following CDC and NY State Department of Health (NYSDOH) recommendations. The vaccine may be incorporated into broader sexual health programs. Cited study published (May 19, 2023) in MMWR: http://dx.doi.org/10.15585/mmwr.mm7220a4
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Juan Lama
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As of Tuesday, Japan had reported 80 cases of mpox, formerly known as monkeypox, with the country seeing a gradual increase in new cases this year. Health ministry statistics show that the number of mpox patients in Japan has crept up this month, in contrast with many other countries where the number of cases has recently declined. As of Tuesday, Japan had reported 80 cases of mpox, an infectious viral disease that is primarily transmitted through men having sex with men. But anyone who has close contact with an infected person is also at risk. All of the patients are men in their 20s to 60s, but the age range with the highest number of infections were those in their 30s and 40s. Since July, when the nation reported its first case of mpox, formerly known as monkeypox, it saw only eight cases through the end of the year. But the country has seen a gradual increase in new cases this year, from seven in January to 12 in February and 53 this month. The infected patients were diagnosed with mpox after a doctor saw them with tell-tale symptoms such as rash, fever and swollen lymph nodes. Domestic reports this year are from men with no recent history of traveling abroad. They are all in a stable condition, according to the health ministry. The World Health Organization declared mpox a public health emergency of international concern two days before Japan reported its first case. Amid the current outbreak in nonendemic countries, which was first reported in May 2022, almost 90,000 cases have been logged in more than 110 countries, resulting in 97 deaths, according to the WHO. In typical mpox cases, fever, headache and swollen lymph nodes appear first, followed several days later by skin rashes. Rashes tend to appear on the face and then spread to the rest of the body, changing to blisters and scabs over time. Most people recover naturally within two to four weeks. However, some patients amid the current outbreak have also developed skin rashes without early symptoms such as fever and the swelling of lymph nodes, and rashes have frequently been reported in genital areas and inside the mouth, the ministry said. Under the Infectious Diseases Control Law, doctors are required to report suspected mpox cases to their local public health center. Smallpox vaccines are effective against mpox, and Japan has approved one for use in preventing infections with the mpox virus and the development of severe symptoms. Also, avoiding contact with the infected and reducing the number of sexual partners is key to prevent the disease’s spread, experts say. The outbreak in Japan comes amid a recent spike in cases of syphilis, an infectious disease that spreads through sexual contact. In 2022, Japan reported nearly 13,000 cases of syphilis, a record number since the law went into effect in 1999. Syphilis also causes rashes, but symptoms progress in several stages over years and can cause serious damage to the nervous, visual and auditory systems if left untreated. In the primary stage, syphilis, caused by bacteria called treponema, shows up as minor tumors in areas such as the genitals and lips. It can be cured with antibacterial drugs. Condoms reduce the risks of giving or getting syphilis by preventing contact with a sore, but sores can also occur in areas not covered by a condom. The only way to completely avoid syphilis is to not have vaginal, anal or oral sex, or to be in a long-term mutually monogamous relationship with a partner who does not have syphilis, according to the U.S. Centers for Disease Control and Prevention.
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Scooped by
Juan Lama
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Analysis of hundreds of mpox patients suggests it is “a different disease” in those with compromised immune systems. In June 2022, a young man in his 30s severely sick with mpox, the viral disease formerly known as monkeypox, was admitted to the Salvador Zubirán National Institute of Health Sciences and Nutrition hospital in Mexico City. Tests showed the patient was also HIV-positive, which he had not known, and that his blood had few CD4 cells, critical immune cells that HIV attacks. The man’s immune system was so weak it could not keep mpox in check and painful lesions kept spreading across his body, eating away at, or necrotizing, the flesh, according to HIV researcher Brenda Crabtree Ramirez, who was on his care team. Then the virus spread to his lungs, too. “He just kept getting worse and worse and worse,” she says. With no treatments available, his doctors got the hospital’s ethics board to approve a desperate plan: They would transfer blood plasma from a colleague who had been vaccinated in the United States against mpox to the patient, in the hope that the antibodies from the donation might help fight his infection with the poxvirus. The experimental therapy failed—the man died 2 weeks later, one of the first deaths from the disease in Mexico. Although mpox cases have plummeted globally since then, the outbreak still simmers in Latin America and other locations. The World Health Organization (WHO) last week reaffirmed that the disease remains a global emergency. And a grim report today in The Lancet and being presented at a conference in Seattle, which analyzes the death last summer in Mexico and the cases of 381 other mpox patients who also had advanced HIV infections, makes clear the disease poses an enormous risk to those living with uncontrolled HIV. Of the 179 patients with less than 200 CD4 cells per microliter—more than 500 is considered normal—27 died. Mpox isn’t just more severe in these immunocompromised patients, says Oriol Mitjà, an infectious disease researcher at the Germans Trias i Pujol University Hospital in Barcelona and one of the study authors. “It’s like a different disease.” In the cases where people had few CD4 cells, mpox’s normally small skin lesions grew into large necrotizing patches and their infection sometimes spread to the lungs or caused severe secondary infections with bacteria. Mitjà, Crabtree Ramirez, and their colleagues argue this disseminated form of mpox should be added to the list of AIDS-defining conditions, opportunistic secondary infections that are a typical sign of advanced HIV infection. That might alert physicians to test mpox patients for HIV to be able to prioritize them for any possible treatments. Health authorities should also prioritize people living with HIV for mpox vaccination, Mitjà says. But the Lancet report also contained a warning for physicians: Starting coinfected patients on antiretrovirals for their HIV infection could worsen their mpox. The data presented in the Lancet report are compelling and WHO plans to assemble a group to consider the research team’s recommendation to make mpox an AIDS-defining condition, says Meg Doherty, who heads the program for HIV and other sexually transmitted infections at the agency. In some ways the world may have been lucky with the strain of mpox virus that has been spreading globally. The two types previously known from cases in Africa were thought to kill 10% and 1% of patients, respectively. The current outbreak strain has infected more than 85,000 people globally, predominantly affecting gay men and their sexual networks, and caused fewer than 100 deaths, or a mortality rate of about 0.1%. A paper published last week in the Proceedings of the National Academy of Sciences found that in a particular strain of laboratory mice, this virus, known as clade IIb, is far less deadly than its relatives. “We were unable to cause the mice to be sick even at 100 times the lethal dose [for the current strain],” says Bernard Moss, a poxvirus researcher at the U.S. National Institute of Allergy and Infectious Diseases and one of that study’s authors. But the Lancet paper, which covers more than one-quarter of all known mpox deaths for the clade IIb strain, shows the virus can still cause devastating disease in a particularly vulnerable group of people. Men who have sex with men are much more likely to acquire an HIV infection, but are also less likely in most parts of the world to have access to HIV testing and treatment, notes Gregg Gonsalves, a Yale School of Public Health epidemiologist and former HIV activist. “This creates a dangerous situation, in which our failures to address the AIDS epidemic among this population now may create new risks” for this group, he says. The Lancet report also revealed an important dilemma for physicians caring for these coinfected people. When those with untreated HIV were given antiretrovirals, one-quarter of them seemed to develop a condition in which the recovering immune system responds to the opportunistic infection—mpox in this case—with an overzealous inflammatory response. More than half the patients suspected to have this overreaction, known as immune reconstitution inflammatory syndrome, died. “We are grappling with these scenarios and clinicians do not know what the best approach is at this time,” says Boghuma Titanji, a virologist at Emory University who was not involved with the study. For now, there are far fewer severely sick patients to care for globally than in the summer and Europe is working on a plan to eliminate the virus entirely. Still, cases continue to be reported from dozens of countries, especially in Latin America. The disease might not cause another large outbreak, Mitjà says. “But I think that it will continue to circulate as an STI [sexually transmitted infection] … with the potential to cause death in a few people.” When WHO extended the Public Health Emergency of International Concern (PHEIC) for mpox for another 3 months on 15 February, it noted the risk of a resurgence in some regions and “a potential shift in some countries towards the most marginalized populations who have the least access to prevention measures and treatments.” The extension is an opportunity for the world to address the inequities in how it has responded to mpox, Titanji says. The PHEIC keeps the disease “on the radar globally and hopefully this will also translate into better access to vaccines and therapeutics as well as diagnostics for low- and middle-income countries in Africa and South America,” she says. So far, the countries in Central and West Africa that have borne the burden of mpox longer than anywhere else have gained little from the global attention on the disease, says Dimie Ogoina, an infectious disease specialist at Niger Delta University in Nigeria and a co-author on the Lancet paper. “The ‘package for Africa’ is largely still in the realm of promises.” Continued attention on the disease is important for Mexico, too, Crabtree Ramirez says. She worries conditions there could let the disease linger. On the one hand, there is little incentive for those with milder infections to be diagnosed because neither treatment nor a preventive vaccine is available in the country. The main consequence of a diagnosis is mandatory isolation, Crabtree Ramirez says. “And for many people in Mexico, if they don’t work, they don’t eat,” she adds. On the other hand, there are many people at a high risk for deadly disease—almost half the people diagnosed with HIV in Mexico are at an advanced stage of the infection with a CD4 count of 200 or less—which makes it clear that vaccines and drugs are needed, Crabtree Ramirez says. “For me, it’s unacceptable that people do not have access to what is needed to survive.” Research cited published in The Lancet (Feb. 21, 2023): https://doi.org/10.1016/S0140-6736(23)00273-8
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