Updates and trend on monkeypox or mpox. recently renamed, is referred to Manual Control of Communicable Diseases published by American Public Health Association and WHO position paper on smallpox, mpox. Global figures for all countries are accessed from global dashboard. The occurrence in South East Asia region is accessed from weekly epidemiological bulletin of the region. Prequalification of the mpox vaccine was made recently by WHO. Monkeypox or Mpox was declared by WHO as Public Health Emergency of International Concern (PHEIC) by Director General of WHO on 14 August 2024 and member countries are still reporting cases and genomic analysis was made and reported. In our region India, Indonesia, Thailand, Nepal and Sri lanka are reporting cases and deaths.
Clinical features
Monkeypox is a sporadic zoonotic infection, first identified in 1970 from remote rural villages from Central and West African rainforest countries as smallpox disappear. Clinically, the disease closely resembles ordinary or modified smallpox. Clinically, lymphadenopathy is the most prominent feature in many cases and early stages of the disease. Pleomorphism and cropping similar to that seen in chickenpox are seen in 20 per cent of patients. Case fatality rate among children not vaccinated against smallpox ranges from 1% to 14%.
Causative agent
Monkeypox virus is a species of genus Orthopoxvirus with biological properties and a genome distinct from variola virus. At least two genetically distinct clades of exist with different human clinical and epidemiologic manifestations. To date, West African clade monkeypox without human-to-human transmission and without human mortality whereas Congo Basin clade is associated with human-to-human transmission and case fatality historically reported at an average of 10 % in unvaccinated cases.
Diagnosis
Identification of characteristic lesion; ascertainment of a history of direct or indirect contact with animals of West and Central African origin. Through electron microscopy demonstration of poxvirus in the lesion; by growth virus primate cell culture or positive molecular (e.g. PCR) or serological tests.
Occurrence
Between 1970 and 1994, more than 400 cases of monkeypox were reported Democratic Republic of Congo accounted for 95 % of the cases during five-year surveillance period (1981-1986). A 2000 introduction of monkeypox in USA, related to importation and sale of exotic animals from West Africa resulted in infection of North American prairie dog owners and animal handlers. In 1990s prolonged outbreak of human monkeypox was recognized in DRC and so also outbreaks of monkeypox in Congo. In 2003, a prolonged and efficient chain of human to human transmission was described in DRC. Sporadic cases have been identified elsewhere. The disease affected all age groups; children younger than 16 years historically have constituted the greatest proportion of cases.
Reservoir
The natural history of disease in unclear; human, primates and squirrels appear to be involved in enzootic cycle. Ecological studies in 1990 point the squirrel Funicisurus and Heliosciurus abundant among oil palms surrounding the villages at the studies sites as a significant local reservoir host. Monkeypox virus have been also demonstrated in terrestrial giant pouched Gambian rat and dormice. Maintenance of animal reservoir and animal contact appear to be required to sustain the disease among human.Transmission; In 1980s 75 % of reported cases are attributable to contact with affected animals in one recent DRC outbreaks in 1996-1997. It appears that a larger number of cases are attributed to person-to- person contact. Unaccustomed conditions of crowding at the start of the event due to civil disruption may have contributed to unusual pattern. The longest chain of person-to- person transmission was 7 reported serial cases but serial transmission does not extend beyond secondary cases. Epidemiological data suggest as secondary rate of 8 %. Most cases occur either singly or clusters in remote village in tropical rain forest where population have multiple contacts of several types of wild animals.
Risk groups
Hunters in tropical rainforest in West and Central Africa and their families, laboratory workers and others exposed directly or indirectly to rodent population from West to Central Africa.
Prevention
Smallpox vaccination is believed to be protective. However, protection provided by childhood smallpox vaccination is waning in the general population at risk since the cessation of smallpox vaccination in 1980s. Human infection may be controllable to some extent by education to limit contact with cases and potentially infected animals. However, in areas where the disease is endemic in zoonotic reservoir and population relies on hunting as the food source, sporadic infection continues to occur.
The 2003 outbreak in USA clearly demonstrates the potential for monkeypox to be a public health threat outside the enzootic area and there is also evidence that infection has also emerged in nature outside of historic known enzootic area. Full evaluation of monkeypox ecology, epidemiology, virology associated with human monkeypox outbreaks in endemic areas will enable the understanding of prevention and control measures. Management of patients- Patients should be managed symptomatically and if hospitalized placed under strict infection control measures with sterilization of any implements used in patient management and safe disposal of bandages by sterilization by boiling, autoclaving and incineration. Physical contact with others should be avoided until the lesions have completely resolved.
Management of contacts and the environment No special management is required for persons who have had contacts with a case of monkeypox except for self-monitoring and if symptoms and signs occur, should be examined by a medical worker.
Special consideration; smallpox vaccination is used as outbreak response intervention in USA outbreak in 2003. A WHO Technical Advisory Committee on monkeypox recommended continued studies of human monkeypox intensified prospective surveillance and ecological studies in order to determine risk/benefit of potential use of vaccine to prevent monkeypox in human in relevant areas.
Source; American Public Health Association. Monkeypox. In: Control of Communicable Diseases Manual. 20th ed. Washington, DC: American Public Health Association; 2015.
What Is Monkeypox?
Monkeypox is an infectious disease caused by the monkeypox virus which results in a rash and flu-like symptoms. Monkeypox is currently spreading globally and within the United States primarily from close contact with an infected person, but historically has also been transmitted to people from contact with an infected animal. Monkeypox is part of the same family of viruses as variola virus, the virus that causes smallpox. It causes similar but milder symptoms than smallpox and is rarely fatal.
Monkeypox spreads when a person comes in contact with an animal or a person who has the virus. Transmission occurs through: Direct contact with an infected person’s bodily fluids, sores, scabs or respiratory droplets. This can also occur through cuddling, kissing or sex. Contact with recently contaminated materials exposed to skin lesions, including clothing or bedding. Scratches or bites from an infected animal, preparing or eating meat or other products from an infected animal, or direct contact with an infected animal’s blood, bodily fluid or sores.
Monkeypox Symptoms
After exposure to the monkeypox virus, the average incubation period is 1 to 2 weeks before symptoms appear. Early signs of monkeypox include the following flu-like symptoms: chills, exhaustion, fever, headache, muscle aches and backache and swollen lymph nodes. These flu-like symptoms are then typically followed by the development of a rash. The rash can look like pimples or blisters and can be painful. Lesions can appear on the face, in the mouth, and on the hands, feet, chest, genitals, or anus. Some people get the rash first, followed by other, flu-like symptoms, while some experience only a rash. The rash goes through different stages, including pimple-like bumps and blisters that crust and fall off before healing completely. The illness caused by monkeypox typically lasts 2 to 4 weeks.
When to seek medical care for monkeypox symptoms
Call your health care provider if you have:
Fever, aches or swollen lymph nodes A new rash or sores
Close contact with a person infected with monkeypox
Seek emergency medical care if you have: A stiff neck, chest pain, confusion, difficulty speaking, loss of consciousness, loss of mobility, seizures trouble breathing
Prevention of Monkeypox Infection
Anyone can get monkeypox, but it can be prevented by limiting close contact with people with confirmed or suspected monkeypox and by vaccination.
Take the following precautions to help prevent monkeypox infection: Avoid close contact with people who have been diagnosed with monkeypox or who have signs and symptoms of monkeypox, including fever and rash; this includes not sharing bedding, towels, and utensils used by the infected individual, which may be contaminated with the virus from skin lesions. Clean and disinfect high-touch surfaces.
If it is necessary to be in close contact with someone with monkeypox, wear a mask that covers your mouth and nose and wash your hands frequently with soap and warm water. Monkeypox can spread between the time symptoms first appear until the time the rash has fully healed. If you suspect you have monkeypox or have been diagnosed with monkeypox, there are steps you should take to help prevent spreading the disease to others, including all guidance from your local department of health:
If you have an active rash or other symptoms, stay in a separate room or area away from people or pets you live with, when possible. Isolate at home until all of your skin lesions have scabbed and other symptoms have resolved.
Wear a mask that covers your nose and mouth if you must be around others.
Vaccination to prevent monkeypox
Vaccination can help prevent monkeypox infection for people who have been in close contact with someone with confirmed or suspected monkeypox, or who are at high risk for exposure to monkeypox.
Monkeypox Diagnosis
To diagnose monkeypox, your healthcare provider will take a swab from a skin lesion and send it to a lab for polymerase chain reaction (PCR) testing which can detect the virus.
Monkeypox Treatment and Symptoms Management
Monkeypox symptoms typically last from 2 to 4 weeks and most people with monkeypox get better on their own without treatment. However, there are things you can do to feel better, including: Drinking plenty of fluids, resting, Taking a warm oatmeal bath. Soaking an oatmeal bath can provide relief for dry, itchy rashes. Using over-the-counter pain relievers and fever reducers
Currently, there are no treatments specifically for monkeypox infection. However, given the similarity between monkeypox and smallpox viruses, therapies such as antiviral drugs and immune globulin developed to protect against smallpox may be used to treat monkeypox virus infections, especially for people with severe symptoms. If you are infected with monkeypox, talk to your healthcare provider for more information on your eligibility for certain treatments, including the antiviral drug, tecovirimat.
How Does Monkeypox Spread?
Monkeypox spreads when a person comes in contact with an animal or a person who has the virus.
Transmission occurs through: Direct contact with an infected person’s bodily fluids, sores, scabs or respiratory droplets. This can also occur through cuddling, kissing or sex. Contact with recently contaminated materials exposed to skin lesions, including clothing or bedding. Scratches or bites from an infected animal, preparing or eating meat or other products from an infected animal, or direct contact with an infected animal’s blood, bodily fluid or sores.
Monkeypox Symptoms
After exposure to the monkeypox virus, the average incubation period is 1 to 2 weeks before symptoms appear. Early signs of monkeypox include the following flu-like symptoms: Chills, Exhaustion, Fever, Headache, Muscle aches and backache, Swollen lymph nodes. These flu-like symptoms are then typically followed by the development of a rash. The rash can look like pimples or blisters and can be painful. Lesions can appear on the face, in the mouth, and on the hands, feet, chest, genitals, or anus. Some people get the rash first, followed by other, flu-like symptoms, while some experience only a rash.
The rash goes through different stages, including pimple-like bumps and blisters that crust and fall off before healing completely. The illness caused by monkeypox typically lasts 2 to 4 weeks.
Prevention of Monkeypox Infection
Anyone can get monkeypox, but it can be prevented by limiting close contact with people with confirmed or suspected monkeypox and by vaccination.
Take the following precautions to help prevent monkeypox infection:
Avoid close contact with people who have been diagnosed with monkeypox or who have signs and symptoms of monkeypox, including fever and rash; this includes not sharing bedding, towels, and utensils used by the infected individual, which may be contaminated with the virus from skin lesions.
Clean and disinfect high-touch surfaces. If it is necessary to be in close contact with someone with monkeypox, wear a mask that covers your mouth and nose and wash your hands frequently with soap and warm water.
Monkeypox can spread between the time symptoms first appear until the time the rash has fully healed. If you suspect you have monkeypox or have been diagnosed with monkeypox, there are steps you should take to help prevent spreading the disease to others, including all guidance from your local department of health:
If you have an active rash or other symptoms, stay in a separate room or area away from people or pets you live with, when possible. Isolate at home until all of your skin lesions have scabbed and other symptoms have resolved.
Vaccination to prevent monkeypox
Vaccination can help prevent monkeypox infection for people who have been in close contact with someone with confirmed or suspected monkeypox, or who are at high risk for exposure to monkeypox.
If you are infected with monkeypox, talk to your healthcare provider for more information on your eligibility for certain treatments, including the antiviral drug, tecovirimat.
Weekly Epidemiological Record 9934
Smallpox and mpox (orthopoxviruses) vaccine position paper
Background
Epidemiology
Smallpox
Smallpox is an infectious disease caused by the variola virus of the Orthopoxvirus genus. Variola virus is transmitted from person to person via inhalation of contaminated droplets and particles during close contact with symptomatic persons, skin contact, or through contaminated clothing or bedding. Notably, variola virus does not infect animals and lacks an animal reservoir. Smallpox was fatal in up to 30% of cases (Variola major) and caused millions of deaths each year before it was eradicated.
Smallpox is estimated to have killed up to 300 million people in the 20th century, and many survivors were left with disfiguring scars or were blind.1, 2 In 1967, WHO launched an intensified programme to eradicate smallpox. Global widespread immunization and surveillance was conducted for several years. The last known naturally transmitted case occurred in Somalia in 1977, and in 1980 WHO declared smallpox eradicated.
Mpox
Mpox has an incubation period that ranges from 2 to 21 days, although some people can acquire infection without developing symptoms. The initial phase of clinical illness typically lasts 1–5 days and is marked by symptoms such as fever, headache, back pain, muscle aches, lack of energy and lymphadenopathy, which is a characteristic sign of the disease. Subsequently, a second phase ensues, typically within 1–3 days after the fever subsides, characterized by the onset of a rash. Typically, the rash presents in sequential stages: macules, papules, vesicles and pustules followed by umbilication before eventually forming crusts and desquamating over a period of 2–3 weeks. However, mpox can also present with less severe illness, fewer or less widely disseminated lesions, the appearance of lesions before symptoms, or appearance of lesions in different stages of development. Such atypical features have been observed in the global mpox outbreak which began in 2022, with some cases showing a rash appearing either before or concurrently with other symptoms. Moreover, during the global Clade IIb outbreak, the initial lesions more often localized on the genitals and mucous membranes, such as the mouth. In addition, new clinical complications, such as severe proctitis related to sexual transmission have been observed. Persons with mpox may be infectious from the onset of any symptom until all scabs have fallen off. There is limited information which suggests that pre-symptomatic transmission may also occur, particularly in the context of contact with mucosal lesions.
Mpox Clade IIb is usually self-limiting and most people recover within a few weeks. However,mpox due to Clade I MPXV may more often lead to more severe disease and death. Regardless of the mpox clade, the risk of severe disease and complications – such as secondary infection, sepsis, pneumonia and encephalitis – may also be increased in immunocompromised persons (e.g. persons with untreated or uncontrolled advanced HIV infection), young children and pregnant women. Reported deaths during the global Clade IIb mpox outbreak have been documented in persons with advanced HIV or other severe immunocompromised conditions, including in the 2024 mpox outbreak in South Africa.
Diagnosis
Mpox
Detection of viral DNA by PCR is the preferred laboratory test for mpox. The best diagnostic specimens are taken directly from lesion material (skin, fluid or crusts) collected by vigorous swabbing. In the absence of lesions, testing can be done with oropharyngeal or, depending on clinical presentation and exposure, rectal swabs. However, while a positive result of an oropharyngeal or rectal sample is indicative of mpox, a negative result does not rule out MPXV infection. Testing of blood is not recommended. Antibody detection methods may be used for retrospective case classification but not for diagnosis. During the global outbreak, mpox became a notifiable disease in many countries – a designation now recommended by WHO for all countries.
Treatment
Mpox
Patients with severe mpox should be actively screened for HIV because of the strong association with severe mpox. Establishing antiretroviral therapy in persons diagnosed with HIV requires attention to pharmacological interactions but should be started as soon as clinically reasonable to ensure longer-term immune reconstitution and to maximize the linkage to care. Antivirals, such as tecovirimat and brincidofovir, originally developed to treat smallpox, have been used to treat severe mpox as emergency measures. Randomized controlled trials of tecovirimat are underway to determine its effectiveness for treatment of mpox.
Symptomatic measures are primarily supportive care and analgesics to relieve pain and fever and to prevent complications and co-infection with other pathogens.
Mpox
The role of MPXV neutralizing antibodies for protection against disease and transmissibility is currently unclear and no specific correlate of protection against MPXV infection has been identified. However, one study found a significant correlation between the effectiveness of the third-generation mpox vaccine, Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN), and vaccinia-binding antibody titres, suggesting that antibody levels may be a correlate of protection.
During the global mpox outbreak, cases were observed in persons with a recently documented infection. A global case series documented 8 persons who experienced reinfection with mpox, of which 3 were HIV positive. Those who had acquired immunity after their initial infection had a shorter disease course with less mucosal involvement during reinfection compared to their initial infection regardless of HIV status. While acquired immunity does not seem to offer complete protection against Clade IIb mpox reinfection, this small series suggests that both the duration and severity of disease may be reduced by prior infection.
Acquired immunity may differ according to the exposure route and the clade, although there is no good data on such differences.
Vaccines
Currently available smallpox and mpox vaccines are all based on live vaccinia virus, an orthopoxvirus. Smallpox vaccines that were produced and successfully used during the smallpox eradication programme of the 1950s to the 1970s are called first-generation vaccines.
The first-generation vaccines widely employed strains as the New York City Board of Health (NYCBH) and Lister strains among others – which were cultivated on the skins of animals.
Second-generation smallpox vaccines (such as ACAM2000) use the same vaccinia virus vaccine strains as those employed for manufacture of first-generation vaccines. However, the second-generation vaccines are produced in tissue culture cells from isolated virus plaques, are free of adventitious agents and can be further attenuated. First- and second-generation vaccines are replication-competent.
The term “third-generation” refers to more attenuated vaccinia vaccine strains developed by further passage in cell culture or animals to enhance safety. These vaccines were developed towards or after the end of the smallpox eradication phase. They include the vaccinia strain LC16m8 (a minimally replicating vaccine developed in Japan from the Lister strain with a mutation in the B5R gene) and the vaccinia strain known as MVA-BN (a non-replicating vaccine with some 30kb deleted from the viral genome).
Also developed is a fourth-generation vaccine known as VacΔ6 or OrthopoxVac. This relies on modification of the vaccinia virus genome through targeted deletion of genetic material responsible for encoding virulence proteins. In addition, other vaccines are under development – e.g. lipid encapsulated mRNA-based vaccines against diseases caused by orthopoxviruses such as mpox and smallpox.
Licensed vaccine products
MVA-BN was approved in 2013 for the prevention of smallpox in Canada and the European Union (EU) in persons 18 years of age and older. In 2019, MVA-BN was approved for the prevention of smallpox and mpox in adults in the United States. In the same year, Canada extended the indication of MVA-BN to mpox. On 22 July 2022, the EU approved the indication of MVA-BN for the prevention of mpox in adults. MVA-BN is not licensed for persons under 18 years of age. However, in 2022, the United States granted emergency use authorization for the use of MVA-BN in persons under 18 years of age.
In Japan, LC16m8 was licensed in 1975 for smallpox without age restriction and the indication was extended for the prevention of mpox in August 2022. ACAM2000 is approved by the FDA for immunization against smallpox and is made available for use against mpox under an Expanded Access Investigational New Drug protocol.
Administration, manufacturer’s stipulated schedule and storage
MVA-BN
According to the manufacturer, MVA-BN is administered as a 2-dose subcutaneous injection – 0.5 mL dose containing 1×108 PFU (plaque forming units) – given4 weeks apart. During the global mpox outbreak, MVA-BN was also administered intradermally (0.1mL dose) in a few jurisdictions as a dose-sparing option. MVA-BN should be stored frozen at -15 to -25°C or -45 to -55°C or -75 to -85°C. The shelf- life depends on the storage temperature. After thawing, the vaccine should be used immediately or, if previously stored at -15°C to -25°C, the vaccine can be stored at 2°C to 8°C in the dark for up to 4 weeks prior to use. Once the vaccine has been thawed it cannot be refrozen.
LC16m8
LC16m8 should be administered as a single dose using the scarification method with a bifurcated needle. LC16m8 is a freeze-dried vaccine, packaged in multidose vials and should be stored at a temperature between -35°C and -20°C for long-term storage. It can be stored at 5°C for 2 years and 37°C for up to 4 weeks. The vaccine should be stored away from sunlight as the vaccine is weakened by sunlight and is rapidly inactivated.
Before vaccination, the vaccine should be dissolved in 0.5mL diluent. After mixing the vaccine with the diluent, each vial contains more than 250 doses of 0.0017–0.0029 mL of the vaccine solution extracted by the bifurcated needle.26 After reconstitution, LC16m8 may be stored in a refrigerator (2–6°C) for 1 month or at room temperature conditions (23–27°C) for 24 hours.
ACAM2000
ACAM2000 should be administered as a single dose using the scarification method with a bifurcated needle.
ACAM2000 should be stored in a freezer with an average temperature of -5°C to -25°C. ACAM2000 is reconstituted by the addition of 0.3 mL of diluent to the vial containing lyophilized vaccine. The vaccine vial should be removed from cold storage and brought to room temperature before reconstitution. After reconstitution, ACAM2000 vaccine may be administered within 6–8 hours if kept at room temperature. Unused, reconstituted ACAM2000 vaccine may be stored in a refrigerator (2–8°C) for up to 30 days, after which it should be discarded as biohazardous material. After reconstitution of the lyophilized preparation, each vial contains approximately 100 doses of 0.0025 mL of live vaccinia virus containing 2.5–12.5×105 PFU per dose.
Immunogenicity, efficacy, effectiveness and impact of smallpox/mpox vaccines
Smallpox
The impact of smallpox vaccines was demonstrated by early non-randomized clinical and epidemiological studies and the successful use of successive vaccine formulations over almost 2 centuries culminating in the global eradication of smallpox. Historically, information on post-exposure vaccine effectiveness derives from data on secondary attack rates among vaccinated and unvaccinated family contacts of smallpox cases.2 One study from rural districts in Pakistan comprised 464 contacts, 54 of whom were vaccinated after smallpox exposure while 412 contacts either did not receive vaccination after exposure or were vaccinated more than 1 week after exposure.28 The study showed that 1.9% (n=1/52) of the contacts vaccinated within 7 days of exposure developed smallpox compared with 22% (n=90/512) of the contacts not vaccinated after exposure.
Additionally, historical data from the United Kingdom found that vaccination with first-generation smallpox vaccines within 3–4 days after smallpox exposure protects against disease and/or death.29
While MVA-BN, LC16m8 and ACAM2000 were developed for use against smallpox, these vaccines are further discussed in the mpox section below.
Mpox
MVA-BN
While MVA-BN efficacy studies in animals were aimed at understanding its protective efficacy against smallpox, licensing studies were conducted using challenge with MPXV. In one study, 3 groups of macaques were vaccinated with 1 dose of ACAM2000, 1 dose of MVA-BN or 2 doses of MVA-BN. After aerosol challenge with a lethal dose of MPXV at 28 days following the last vaccine dose, vaccine efficacy against death compared to an unvaccinated control group was 100% for the ACAM2000 and 2-dose MVA-BN groups, and 67% for the 1-dose MVA-BN group.
During the global mpox outbreak, several observational studies were published on the real-world vaccine effectiveness of MVA-BN. No randomized controlled trials assessing vaccine efficacy were conducted during this period. A systematic review31 estimated vaccine effectiveness (VE) for a single subcutaneously-administered dose of MVA-BN at 76% (95%CI 64–88%) across 12 studies.
Similarly, the VE of 2 doses was estimated at 82% (95%CI 72–92%) on the basis of findings from6 studies. In contrast, lower VE estimates were reported when MVA-BN was used as post-exposure vaccination in the context of sexual transmission.
Post-exposure VE was estimated at 20% (95% CI -24% to 65%), as reported by 7 studies. Additionally, one study reported a VE of 80% for fractional dosing of one-fifth of a standard dose with intradermal administration. All these recent VE estimates pertain to the global outbreak linked to the Clade IIb MPXV genetic lineage. As such, the published studies on VE concerned the use of MVA-BN among gay, bisexual or other men who have sex with men, aged between 18 and 49 years from North America and Europe with a relatively short follow-up after vaccination. It is anticipated that MVA-BN and other vaccinia-based vaccines will also demonstrate effectiveness against Clade I MPXV due to the cross-protection afforded between orthopoxviruses.
This is supported by available evidence from VE data for first-generation vaccinia-based vaccine collected in the DRC during enhanced surveillance for smallpox and mpox in the 1980s.
MVA-BN, as a non-replicating vaccine administered subcutaneously, does not induce a “take”. Consequently, the absence of a “take” prevents assessment of effectiveness using this method in MVA-BN vaccinees.
However, across 8 different studies involving a cumulative total of 1222 participants, the proportion of MVA-BN vaccinees that reached seroconversion consistently exceeded 98%.
LC16m8
There are no studies that report directly on the vaccine effectiveness of LC16m8 for smallpox because the vaccine was developed after the last cases occurred in Japan. Studies for mpox vaccine effectiveness are still underway. The clinical effectiveness of LC16m8 against smallpox and mpox is inferred from indirect evidence.
Protective efficacy was evaluated in various studies using animal models. Data from these studies have shown that mice, rabbits and monkeys were protected against lethal challenges with MPXV when immunized with LC16m8.
In addition, 4 studies report on LC16m8 take rates and the proportion of adult vaccinees reaching seroconversion.
The proportion of vaccinees with a take following vaccination with a bifurcated needle ranged from 90% to 100% between 6 and 14 days following the immunization of 3614 individuals. The proportion of LC16m8 vaccinees that reached seroconversion ranged from 60% in previously vaccinated participants to 100% in vaccinia-naïve participants at 30 days from vaccination in 381 vaccinees.
ACAM2000
There are no published clinical studies that evaluate the clinical effectiveness of vaccination with ACAM2000 against mpox. Efficacy data from animal challenge studies with a lethal dose of MPXV found that vaccine efficacy against death compared to an unvaccinated control group was 100% for the ACAM2000 group.
Clinical studies conducted in healthy vaccinia-naïve adults aged 18–29 years confirmed that vaccination with ACAM2000 results in high take rates of nearly 100%.
The proportion of ACAM2000 vaccinees that reached seroconversion ranged from 76% in previously vaccinated participants to 97% in vaccinia-naïve participants across 4 studies involving a total of 317 vaccinees.52–55
Duration of protection
Smallpox
Historically, after successful vaccination with first-generation vaccines, the duration of protection against smallpox was thought to last for a minimum of 3 years, with a likelihood of some level of protection persisting for 10 years or even longer. Evidence supporting the enduring immunological memory generated by traditional smallpox vaccination is provided by a study analysing antibody response and geometric mean titres (GMTs) in previously-vaccinated individuals. The study found that, after receiving 1 or 2 doses of MVA-BN, healthy individuals who had not been exposed to vaccinia virus showed average neutralizing antibody levels of 6 and 45, respectively. In contrast, those who had previous exposure to vaccinia virus exhibited an average neutralizing antibody response of 175 2 weeks after receiving a single dose of MVA-BN as a booster immunization. The GMTs in both vaccinia-naïve groups were lower 2 years after the initial vaccination with MVA-BN compared to the baseline GMTs of subjects with previous exposure to vaccinia virus and who had received their last smallpox vaccination over 10 years before. Moreover, neutralizing antibody titres observed 2 years after booster vaccination in persons with prior exposure to vaccinia virus were higher than those observed in vaccinia-naïve persons who had received either 1 or 2 doses of MVA-BN.
Mpox
A definitive correlate of protection against MPXV infection has not yet been established. Thus, the significance of orthopoxvirus and MPXV neutralizing antibodies in providing protection against disease and transmission remains uncertain. However, one study found a significant correlation between MVA-BN effectiveness and vaccinia-binding antibody titres, suggesting that antibody levels may be a correlate of protection.23 Using these orthopoxvirus antibody responses, a study investigated the duration of serological responses to 2 doses of MVA-BN vaccine in a cohort of 999 health-care workers from the DRC in a region that is endemic for mpox.
The findings reveal that MVA-BN elicits a strong orthopoxvirus-specific antibody response in participants that peaks around 2 weeks after the second dose is administered, and that total orthopoxvirus-specific IgG titres and neutralizing antibody titres decline from their peak and return close to baseline levels by the 2-year mark. Breakthrough infections have been documented after vaccination. A global case study from 9 countries described 29 individuals who experienced mpox infections subsequent to completing 2 appropriately spaced injections of MVA-BN vaccine. Infections post-vaccination were, however, characterized by few lesions, little mucosal disease and minimal analgesia requirements.
The duration of immunity of ACAM2000 and LC16m8 against mpox has not been studied. Vaccine safety Local and systemic side-effects of vaccination using current licensed vaccines are generally mild. However, during the eradication phase of smallpox, rare but serious complications were documented following vaccination with first-generation, replicating vaccines. These complications included generalized vaccinia, eczema vaccinatum, progressive vaccinia (vaccinia necrosum), post-vaccinial encephalitis (PvE) and death. A review examining serious adverse events during the eradication campaign revealed that, following primary vaccination with the NYCBH strain vaccines, the risk of PvE and death from PvE was highest among infants under 1 year of age, with an estimated 6.8 cases of PvE and 3 deaths per million vaccinations, respectively. The risk was considerably lower for primary vaccinees aged 1 year and older, ranging between 1.8 and 3.3 cases of PvE per million vaccinations, with fatalities ranging from 0 to 1.2 per million vaccinations. Another serious adverse event following smallpox vaccination to consider is myopericarditis. During the smallpox eradication campaign, myopericarditis was rarely diagnosed and therefore not reported. However, with the re-introduction of Dryvax, a first-generation replicating smallpox vaccine used in 2002 to vaccinate military personnel, health-care workers and first responders, instances of myopericarditis emerged among the vaccinees.
Consequently, with the introduction of second and third generation smallpox vaccines, designed to be safer by using contemporary vaccine manufacturing techniques,special attention was given to monitoring myopericarditis as an adverse event.
MVA-BN
Eight studies reported on adverse events following vaccination with MVA-BN, indicating both local and systemic adverse events occurring frequently among vaccinees. However, serious adverse events were not reported following MVA-BN immunization across 22 studies involving a total of 17 420 participants. An observational study identified 4 cases of myocarditis among 839 178 MVA-BN vaccine doses administered to individuals registered in national vaccine safety surveillance programmes.59 This corresponds to an incidence rate of 4.77 (95% CI, 1.3–12.2) cases per million doses, within a 30-day window following each dose.
LC16m8
Three studies reported on the safety of LC16m8 in adult vaccinees. Common local adverse events such as erythema, induration and lymphadenopathy were frequently reported. Two studies involving a total of 3346 participants reported on cardiac events and found no myopericarditis among LC16m8 vaccine recipients. Additionally, 1 case of autoinoculation was reported.
ACAM2000
Information regarding the safety of ACAM2000 has been chiefly derived from clinical trial experience and observational studies that included military personnel and health workers. Local and systemic adverse events were frequently reported in 6 studies involving 862 369 vaccinees. In addition, 187 cases of myocarditis were reported among 900 253 vaccinees across 5 studies, yielding an overall incidence of 20.1 cases of myopericarditis per 100 000 ACAM2000 vaccinees (95% CI: 17–23). Compared to an expected background myopericarditis rate of 2.2 cases per 100 000 among non-vaccinated military personnel, the incidence rate of 20.1 cases per 100 000 among ACAM2000 vaccinees is considerable higher than the expected background rate. Additionally, in studies involving over 840 000 persons vaccinated with ACAM2000, 6 cases of generalized vaccinia, 5 cases of autoinoculation and 2 deaths that were reported were considered to be related to vaccination.
Interchangeability
While MVA-BN was originally developed to be administered in a heterologous schedule with a second-generation vaccine in order to improve vaccine safety, the interchangeability of different smallpox/mpox vaccines has not been studied.
Alternative schedules and routes of administration
According to the manufacturer, MVA-BN is administered as a 2-dose subcutaneous injection (0.5mL dose) given 4 weeks apart. However, during the global mpox outbreak MVA-BN was also administered intradermally (0.1mL dose) as a dose-sparing option. The intradermal use of MVA-BN was supported by a clinical study published in 2015. This study compared intradermal and subcutaneous administration of MVA-BN and concluded that the intradermal group was non-inferior to the subcutaneous group.63 Additionally, a study published in 2023 estimated the vaccine effectiveness of 2 doses of MVA-BN administered intradermally to be 80.3% (95% CI 22.9–95).46 A systematic review estimated the vaccine effectiveness for a single subcutaneously administered dose of MVA-BN at 76% (95%CI 64–88%). Another study, based on immunogenicity data, found that delaying the second dose of MVA-BN vaccination provides durable protection and may be an option during an outbreak with limited vaccine availability.
However, the longevity of MVA-BN protection is not yet fully characterized and may vary depending on the number of doses or route of administration.
Special populations
MVA-BN in infants, children and adolescents
MVA-BN is not licensed for use in children under the age of 18 years. However, a few studies have included children and adolescents. One observational study examined 72 individuals aged under 18 years (ranging from 4 months to 17 years) who received at least 1 dose of MVA-BN. Mild adverse events occurred in 10 vaccinees after the first dose (out of 57) and in 5 vaccinees after the second dose (out of 24). No serious adverse events were reported. Another study evaluated the safety of a single dose of MVA-BN administered to children undergoing post-exposure vaccination. In 2022, a total of 87 children were administered a single dose of MVA-BN, and subsequent questionnaires were completed by 45 participants. The median age of participants was 5 years (IQR 5-9). No serious adverse events or cases of mpox were reported following vaccination. Among the surveyed group, 18 children (40%) experienced local reactions such as pain and swelling at the injection site, while 24% reported systemic symptoms, either independently or in conjunction with local reactions. Seven of the surveyed children provided blood samples, and it was found that a single dose of MVA-BN induced antibody and cellular immune responses up to 15 weeks after vaccination in these children. Furthermore, a passive surveillance study reported that 1003 persons under the age of 18 years received MVA-BN with no serious adverse events observed.
While MVA-BN has not been specifically studied in clinical trials in children, the same non-replicating MVA viral vector is used as a platform for other vaccines that include MVA-filo (Mvabea™) against Ebola virus disease (EVD). The EVD vaccine is approved by the EU for adults and children aged 1 year and older. Data from 5 published studies on MVA-BN as a viral vector platform for the prevention of EVD, with a total population of 52 229 children, support the favourable safety profile of the product.
LC16m8 in infants, children and adolescents
Vaccine effectiveness of LC16m8 has not been studied in children. However, a large study was conducted between 1974 and 1975 to assess the safety and take rates of LC16m8 in a cohort of 50 000 children. The study was conducted in 2 stages. The first study consisted of 10 578 children predominantly aged 2–5 years (some infants were included) in whom measurements of adverse events and take rates were monitored for a month following immunization. The second study comprised 30 466 children, predominantly 1–4 years of age, who were monitored daily for a month following immunization. Reported adverse events were mild and vaccine-related serious adverse events were rarely reported – this included eczema vaccinatum (up to 0.01%) among 10 578 vaccinees from the first study and autoinoculation (0.1%) among 40 004 vaccinees from both studies. Post-vaccinial encephalitis and skin disorders were not detected among the vaccinees from both studies (n=50 000).
The proportion of children reaching the formation of a “take” following immunization at 1 month was 97% (range: 95–98%) in both studies.
ACAM2000 in infants, children and adolescents
Vaccine effectiveness of ACAM2000 has not been studied in children. However, before the eradication of smallpox disease, first-generation, live vaccinia virus smallpox vaccine was administered routinely in all paediatric age groups, including neonates and infants, and was effective in preventing smallpox. During that time, live vaccinia virus was occasionally associated with serious complications in children, with the highest risk being in infants younger than 12 months of age. ACAM2000 is contraindicated for use in infants.
MVA-BN in pregnant persons
Available human data on MVA-BN administered to pregnant persons are insufficient to determine vaccine-associated risks in pregnancy. However, MVA-BN is a non-replicating vaccine and 4 development and reproductive toxicology animal studies in rats and rabbits have shown no evidence of harm to the fetus. In addition, limited available data on inadvertent exposure to MVA-filo (Mvabea™), a vaccine against EVD that uses the same non-replicating MVA viral vector, during pregnancy did not raise any safety concerns. MVA-BN safety and efficacy has not been evaluated in breastfeeding women. Data are not available to assess the impact of MVA-BN on milk production or the safety of MVA-BN in breastfed infants.
LC16m8 in pregnant persons
No data are available for assessing the risk of LC16m8
– a minimally replicating vaccine – during pregnancy. No development and reproductive toxicology studies have been performed. LC16m8 is contraindicated for use in pregnant persons.
ACAM2000 in pregnant persons
ACAM2000 has not been studied in pregnancy. Congenital infection, principally occurring during the first trimester, has been observed after vaccination with first-generation live vaccinia smallpox vaccines, although the risk may be low. Generalized vaccinia of the fetus, early delivery of a stillborn infant, or a risk of perinatal death have been reported with first-generation smallpox vaccines. Pregnant persons who are close contacts of vaccinees may be at risk because live vaccinia virus can shed and can be transmitted to close contacts. ACAM2000 has not been studied in lactating women. It is not known whether vaccinia virus or antibodies are secreted in human milk. ACAM2000 is contraindicated for use in pregnant persons.
Prequalification approval
The World Health Organization (WHO) has announced the MVA-BN vaccine as the first vaccine against mpox to be added to its prequalification list. The prequalification approval is expected to facilitate timely and increased access to this vital product in communities with urgent need, to reduce transmission and help contain the outbreak. WHO’s assessment for prequalification is based on information submitted by the manufacturer, Bavarian Nordic A/S, and review by the European Medicines Agency, the regulatory agency of record for this vaccine. “This first prequalification of a vaccine against mpox is an important step in our fight against the disease, both in the context of the current outbreaks in Africa, and in future,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “We now need urgent scale up in procurement, donations and rollout to ensure equitable access to vaccines where they are needed most, alongside other public health tools, to prevent infections, stop transmission and save lives.” The MVA-BN vaccine can be administered in people over 18-years of age as a 2-dose injection given 4 weeks apart. After prior cold storage, the vaccine can be kept at 2–8°C for up to 8 weeks.
Epidemiological Bulletin WHO SEAR
Monkeypox situation in WHO SEAR
Situation overview in WHO South-East Asia Region as of 22 December 2024
In the WHO South-East Asia Region, as of 22 December 2024, a total of 992 laboratory-confirmed Monkeypox cases, including 11 deaths, have been reported since 14 July 2022.In 2024, a total of 199 Monkeypox cases have been reported in the Region – 178 from Thailand, 15 from Indonesia, five from India and one from Nepal. One death was reported from Thailand. In epidemiological weeks 50 and 51 (9 to 22 December), one new Monkeypox case was reported from Nepal.
So far, two Monkeypox cases with Clade Ib infection have been detected in the Region, one case in Thailand and another case in India. Both cases had recent international travel history and were symptomatic during the air travel. Both countries implemented robust public health measures, including contact tracing, and no subsequent transmission has been detected. Both cases were notified to WHO through the respective National International Health Regulations (IHR) Focal Point.
2022-24 Mpox (Monkeypox) Outbreak:
Global Trends
World Health Organization
Produced on 08 January 2025
Overview
This report provides an overview of the mpox epidemiological situation in Africa, on a weekly basis (as of 05 January 2025), as well as the global epidemiological situation on a monthly basis (as of November 2024). Data in this report are based on global surveillance data collected from 01 January 2022, initiated due to the unprecedented human-to-human spread of monkeypox virus (MPXV) globally occurring in the same year. On 14 August 2024, under the International Health Regulations (2005), the WHO Director General declared that the increase in mpox cases in the Democratic Republic of the Congo and its expansion to neighboring countries constitutes a Public Health Emergency of International Concern (PHEIC). This spread presents a public health risk to other Member States and requires a coordinated international response. Based on currently available information, the spread of mpox cases in the Democratic Republic of the Congo is attributed to two main outbreaks – spread of MPXV clade Ia in Equateur and other previously affected provinces of the country, and the spread of clade Ib MPXV in the provinces of North and South Kivu, as well as several clade Ib cases detected in Kinshasa. Current sequencing in the country is limited and clade distribution might be broader than what is currently known. WHO conducted the latest global mpox rapid risk assessment in November 2024. Based on the available information, the risk is assessed as follows:
Clade Ib MPXV: Predominantly affecting non-endemic areas for mpox in the Democratic Republic of the Congo and neighboring countries — High
Clade Ia MPXV: Primarily affecting endemic areas for mpox within the Democratic Republic of the Congo — High
Clade II MPXV: Observed in Nigeria and other endemic countries in West and Central Africa— Moderate
Clade IIb MPXV: Associated with the global mpox epidemic — Moderate
Please note that regardless of geographic area, epidemiological context, biological sex, gender identity or sexual behaviour, individual-level risk is largely dependent on individual factors such as exposure risk and immune status.
Case reporting mainly focuses on laboratory confirmed case and death as defined by WHO’s working case definition published in the Surveillance, case investigation and contact tracing for monkeypox interim guidance.
In Africa, laboratory confirmed and suspected cases are both shown where possible.
Note that countries may use their own case definitions separate from those outlined in the above document. On of 28 November 2022, WHO recommended using the name mpox as a new name for monkeypox. The virus causing mpox is named monkeypox virus (MPXV).
Situation in Africa
Since 1 January 2022, cases of mpox have been reported to WHO from 24 Member States across Africa. As of 05 January 2025, a total of 17 104 laboratory confirmed cases, including 89 deaths, have been reported to WHO. From 2024, as of 05 January 2025, 20 countries have reported 14 700 confirmed cases, including 66 deaths. The three countries with the majority of the cases from 2024 are Democratic Republic of the Congo, (n = 9 513), Burundi, (n = 3 035), and Uganda, (n = 1 552). A significant number of suspected mpox cases, that are clinically compatible with mpox remain untested due to limited diagnostic capacity in some African countries and thus never get confirmed. For this reason, we include suspected cases in this section of the report. As of 20 November 2024, the all cases indicator no longer includes test-negative cases at a national level. This indicator should be interpreted with caution, as suspected mpox cases are recorded according to varying national case definitions. Moreover, not all countries have robust surveillance systems for mpox, meaning reported case counts are likely underestimate the extent of community transmission.
Outbreak status and MPXV clade distribution
The distribution of clades reported in Africa, and the outbreak status of the continent is shown in the maps below. Countries with active mpox transmission are classified as those that have reported cases to WHO within the past 42 days. If a country does not share information on mpox cases or provide regular zero-case reporting to WHO or any other open-access resources, its outbreak status may not accurately reflect its current situation on the map.
Case definition
Suspected Case:
Any person presenting with sudden onset of fever >38.3°C (101°F), intense headaches, adenopathy, back pain, myalgia, and intense weakness, followed 1-3 days later by a vesiculopustular skin rash that develops progressively, often starting on the face (more dense) and then spreading to other parts of the body, including the soles of the feet and palms of the hands.
Confirmed Case:
Any case that has been clinically and epidemiologically diagnosed with mpox and laboratory confirmed.
Author Information
Ye Hla
Director (Retired),
(Department of Medical Research, Central Myanmar)
