A Timeline of the Spread of Monkeypox

This blog post is a timeline of the spread of the monkeypox virus. Everything in here comes from a credible source – or is reporting on information from a credible source. This blog post will be updated if and when new information is found.

May 18, 2022: World Health Organization (WHO) posted information titled: “Monkeypox – United Kingdom of Great Britain and Northern Ireland”. From the information:

Situation at a glance

On 13 May 2022, WHO was notified of two laboratory confirmed cases and one probably cause of monkeypox, from the same household, in the United Kingdom. On 15 May, four additional laboratory confirmed cases have been reported amongst Sexual Health Services attendees presenting with a vesicular rash illness in men who have sex with men (MSM).

As response measures, an incident team has been established to coordinate contact tracing efforts.

In contrast to sporadic cases with travel links to endemic countries (see Disease outbreak news on Monkeypox in the United Kingdom published 16 May 2022), no source of infection has been confirmed yet. Based on currently available information, infection seems to have been locally acquired in the United Kingdom. The extent of local transmission is unclear at this stage and there is the possibility of identification of further cases.

Description of the cases

On 13 May 2022, the United Kingdom notified WHO of two laboratory confirmed cases and one probably cause of monkeypox to WHO. All three cases belonged to the same family.

The probable cause is epidemiologically linked to the two confirmed cases and has fully recovered. The first case identified (index case) developed a rash on 5 May and was admitted to hospital in London, the United Kingdom, on 6 May. On 9 May, the case was transferred to a specialist infectious disease centre for ongoing care. Monkeypox was confirmed on 12 May. Another confirmed case developed a vesicular rash on 30 April, confirmed to have monkeypox on 13 May, and is in stable condition.

The West African clade of monkeypox was identified in the two confirmed cases using reverse transcriptase polymerase chain reaction (RT PCR) on vesicle swabs on 12 May and 13 May.

On 15 May, WHO was notified of four additional laboratory confirmed cases, all easily identified among MSM attending Sexual Health Services and presenting with a vesicular rash. All four were confirmed to have the West African clade of the monkeypox virus.

Epidemiology of the disease

Monkeypox is a sylvatic zoonosis with incidental human infections that usually occur in forested parts of Central and West Africa. It is caused by the monkeypox virus which belongs to the orthopoxvirus family. Monkeypox can be transmitted by droplet exposure via contaminated materials. The incubation period of monkeypox is usually from 6 to 13 days but can range from 5 to 21 days. The disease is often self-limiting with symptoms usually resolving spontaneously within 14 to 21 days. Symptoms can be mild or severe, and lesions can be very itchy or painful. The animal reservoir remains unknown, although is likely to be among rodents. Contact with live and dead animals through hunting and consumption of wild game or bush meat are known risk factors.

There are two clades of monkeypox virus: the West African clade and Congo Basin (Central African) clade. Although the West African clade of monkeypox virus infection sometimes leads to severe illness in some individuals, disease is usually self-limiting. The case fatality ratio for the West African clade has been documented around 1%, whereas for the Congo Basin clade, it may be as high as 10%. Children are also at higher risk, and monkeypox during pregnancy may lead to complications, congenital monkeypox or stillbirth.

Milder cases of monkeypox may go undetected and represent a risk of person-to-person transmission. There is likely to be a little immunity to the infection in those traveling or otherwise exposed, as endemic disease is normally geographically limited to parts of West and Central Africa. Historically, vaccination against smallpox was shown to be protective against monkeypox. While one vaccine (MVA-BN) and one specific treatment (tecovirimat) were approved for monkeypox in 2019 and 2022 respectively, these countermeasures are not yet widely available, and populations worldwide under the age of 40 or 50 years no longer benefit from the protection afforded by smallpox vaccination programmes.

Public health response

Health authorities in the United Kingdom have established incident management team to coordinate the extensive contact tracing which is currently underway in health care settings and the community for those who have contact with the confirmed cases. Contracts are being assessed based on their level of exposure and followed up through active or passive surveillance for 21 days from the date of last exposure to a case. Vaccination is being offered to higher risk contacts.

A detailed backwards contact tracing investigation is also being carried out to determine the likely route of acquisition and establish whether there are any further chains of transmission within the United Kingdom for all cases. Sexual contacts and venues visited are actively being investigated for the four recent cases.

WHO risk assessment

No source of infection has yet been confirmed for either the family or MSM clusters. Based on currently available information, infection seems to have been locally acquired in the United Kingdom. The extent of local transmission is unclear at this stage and there is the possibility of identification of further cases. However, once monkeypox was suspected, authorities in the United Kingdom promptly initiated appropriate public health measures, including isolation of the cases and extensive forward and backward contact tracing to enable source identification.

In the United Kingdom, there have been eight previous cases of monkeypox reported: all importations were related to a travel history to or from Nigeria. In 2021, there were also two separate human monkeypox cases imported from Nigeria reported by the United States of America. During an outbreak of monkeypox in humans in 2003 in the United States of America, exposure was traced to contact with pet prairie dogs that had been co-housed with monkeypoxvirus-infected small mammals imported from Ghana.

WHO advice

Intensive public health measures should continue in the United Kingdom. In addition to the ongoing forward and backward contact tracing and source tracing, case searching, and local rash-illness surveillance should be strengthened by MSM and wider community, as well as in primary and secondary health care settings. Any patient with suspected monkeypox should be investigated and isolated with supportive care during the presumed and known infectious periods, that is, during the prodromal and rash stages of the illness, respectively. Timely contact tracing, including sexual health and dermatology clinics, are essential for preventing further secondary cases and effective management of the current outbreak. Additionally, deployment of pharmaceutical countermeasures under investigational protocols can be considered.

Health workers and other care givers caring for patients with suspected or confirmed monkeypox should implement standard, contact and droplet infections control precautions. Samples taken from people with suspected monkeypox or animals with suspected monkeypox virus infection should be safely handled by trained staff working in suitably equipped laboratories.

Any illness during travel or upon return from an endemic area should be reported to a health professional, including information about all recent travel and immunization history. Residents and travellers to endemic countries should avoid contact with sick animals (dead or alive) the could harbour monkeypox virus (rodents, marsupials, primates) and should refrain from eating or handling wild game (bush meat). The importance of hand hygiene by using soap and water or alcohol-based sanitizer should be emphasized.

International travel or trade: WHO does not recommend any restriction for travel to and trade fwith the United Kingdom based on available information at this time.

WHO continue to closely monitor as the situation is evolving rapidly.

---

May 19, 2022: World Health Organization (WHO) posted Key Facts About Monkeypox. From the information:

Key Facts

• Vaccines used during the smallpox eradication programme also provided protection against monkeypox. Newer vaccines have been developed of which one has been approved for prevention monkeypox.
• Monkeypox is caused by monkeypox virus, a member of the Orthopoxvirus genus in the family Poxviridae.
• Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Severe cases can occur. In recent times, the case fatality ratio has been around 3-6%.
• Monkeypox is transmitted to humans through close contact with an infected person or animal, or with material contaminated with the virus.
• Monkeypox virus is transmitted from one person to another by close contact with lesions, body fluids, respiratory droplets and contaminated materials such as bedding.
• Monkypox is a viral zoonotic disease that occurs primarily in tropical rainforest areas of central and west Africa and is occasionally exported to other regions.
• An antiviral agent developed for the treatment of smallpox has also been licensed for the treatment of monkeypox.
• The clinical presentation of monkeypox resembles that of smallpox, a related orthopoxvirus infection which was declared eradicated worldwide in 1980. Monkeypox is less contagious than smallpox and causes less severe illness.
• Monkeypox typically presents clinically with fever, rash and swollen lymph nodes and may lead to a range of medical complications.

Introduction

Monkeypox is a viral zoonosis (a virus transmitted to humans from animals) with symptoms similar to those seen in the past in smallpox patients, although it is clinically less severe. With the eradication of smallpox in 1980 and subsequent cessation of smallpox vaccination, monkeypox has emerged as the most important orthopoxvirus for public health. Monkeypox primarily occurs in central and west Africa, often in proximity to tropical rainforests, and has been increasingly appearing in urban areas. Animal hosts include a range of rodents and non-human primates.

The pathogen:

Monkeypox virus is an enveloped double-stranded DNA virus that belongs to the Orthopoxvirus genus of the Poxviridae family. This includes rope squirrels, tree squirrels, Gambian pouched rats, dormice, non-human primates and other species. Uncertainty remains on the natural history of monkeypox virus and further studies are needed to identify the exact reservoir(s) and how the virus circulation is maintained in nature.

Outbreaks:

Human monkeypox was first identified in humans in 1970 in the Democratic Republic of the Congo in a 9-month old boy in a region where smallpox had been eliminated in 1968. Since then, most cases have been reported from rural, rainforest regions of the Congo Basin, particularly in the Democratic Republic of the Congo and human cases have increasingly reported from across central and west Africa.

Since 1970, human cases of monkeypox have been reported in 11 African countries: Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Côte d’Ivoire, Liberia, Nigeria, the Republic of the Congo, Sierra Leone and South Sudan. The true burden of monkeypox is not known. For example, in 1996-97, an outbreak was reported in the Democratic Republic of the Congo with a lower case fatality ratio and a higher attack rate than usual. A concurrent outbreak of chickenpox (caused by the varicella virus, which is not an orthopoxvirus) and monkeypox was found, which could explain real or apparent changes in transmission dynamics in this case. Since 2017, Nigeria has experienced a large outbreak, with over 500 suspected cases and over 200 confirmed cases and a case fatality ratio of approximately 3%. Cases continue to be reported until today.

Monkeypox is a disease of global public health importance was it not only affects countries in west and central Africa, but the rest of the world. In 2003, the first monkeypox outbreak outside of Africa was in the United States of America and was linked to content with infected pet prairie dogs. These pets had been housed with Gambian pouched rats and dormice that had been imported into the country form Ghana. This outbreak led to over 70 cases of monkeypox in the U.S. Monkeypox has also been reported in travelers from Nigeria to Israel in September 2018, and to the United Kingdom in September 2018, December 2019, May 2021, and May 2022, to Singapore in May 2019, and to the United States of America in July and November 2021. In May 2022, multiple cases of monkeypox were identified in several non-endemic countries. Studies are currently underway to further understand the epidemiology, sources of infection, and transmission patterns.

Transmission

Animal-to-human (zoonotic) transmission can occur from direct contact with the blood, bodily fluids, or cutaneous or mucosal lesions of infected animals. In Africa, evidence of monkeypox virus infection has been found in many animals including rope squirrels, tree squirrels, Gambian pouched rats, dormice, different species of monkeys and others. The natural reservoir of monkeypox has not yet been identified, through rodents are the most likely. Eating inadequately cooked meat and other animal products of infected animals is a possible risk factor. People living in or near forested areas may have indirect or low-level exposure to infected animals.

Human-to-human transmission can result from close contact with respiratory secretions, skin lesions of an infected person or recently contaminated objects. Transmission via droplet respiratory particles usually requires prolonged face-to-face contact, which puts health workers, household members and other close contacts of active cases at greater risk. However, the longest documented chain of transmission in a community has risen in recent years from 6 to 9 successive person-to-person infections. This may reflect declining immunity in all communities due to cessation of smallpox vaccination. Transmission can also occur via the placenta from the mother to fetus (which can lead to congenital monkeypox) or during close contact during and after birth. While close physical contact is a well-known risk factor for transmission, it is unclear at this time if monkeypox can be transmitted specifically through sexual transmission routes. Studies are needed to better understand this risk.

Signs and symptoms

The incubation period (interval from infection to onset of symptoms) of monkeypox is usually from 6 to 13 days but can range from 5 to 21 days.

The infection can be divided into two periods:

• the invasive period (lasts between 0-5 days) characterized by fever, intense headache, lymphadenopathy (swelling of the lymph nodes), back pain, myalgia (muscle aches) and intense asthenia (lack of energy). Lymphadenopathy is a distinctive feature of monkeypox compared to other diseases that may initially appear similar (chickenpox, measles, smallpox)

• the skin eruption usually begins within 1-3 days of appearance of fever. The rash tends to be more concentrated on the face and extremities rather than on the trunk. It affects the face (in 95% of cases), and palms of the hands and soles of the feet (in 75% of cases). Also affected are oral mucous membranes (in 70% of cases), genitalia (30%), and conjunctivae (20%), as well as the cornea. The rash evolves sequentially from macules (lesions with a flat base) to papules (slightly raised firm lesions), vesicles (lesions filled with clear fluid) pustules (lesions filled with yellowish fluid), and crusts which dry up and fall off. The number of lesions varies from a few to several thousand. In severe cases, lesions can coalesce until large sections of skin slough off.

Monkeypox is usually a self-limited disease with the symptoms lasting from 2 to 4 weeks. Severe cases occur more commonly among children and are related to the extent of virus exposure, patient health status and nature of complications. Underlying immune deficiencies may lead to worse outcomes. Although vaccination against smallpox was protective in the past, today persons younger than 40 to 50 years of age (depending on the country) may be more susceptible to monkeypox due to cessation of smallpox vaccination campaigns globally after eradication of the disease. Complications of monkeypox can include secondary infections, bronchopneumonia, sepias, encephalitis, and infection of the cornea with ensuing loss of vision. The extent to which asymptomatic infection may occur is unknown.

The case fatality ratio of monkeypox has historically ranged from 0 to 11 % in the general population and has been higher among young children. In recent times, the case fatality ratio has been around 3-6%.

Diagnosis

The clinical differential diagnosis that must be considered includes other rash illnesses, including chickenpox, measles, bacterial skin infections, scabies, syphilis, and medication-associated allergies. Lymphadenopathy during the prodromal state of illness can be a clinical feature to distinguish monkeypox from chicken or smallpox.

If monkeypox is suspected, health workers should collect an appropriate sample and have it transported safely to a laboratory with appropriate capability. Confirmation of monkeypox depends on the type and quality of the specimen and the type of laboratory test. Thus, specimens should be packaged and shipped in accordance with national and international requirements. Polymerase chain reaction (PCR) is the preferred laboratory test given its accuracy and sensitivity. For this, optimal diagnostic samples for monkeypox are from skin lesions – the roof or fluid from vesicles and pustules, and dry crusts. Where feasible, biopsy is an option. Lesion samples must be stored in a dry, sterile tube (no viral transport media) and kept cold. PCR blood tests are usually inconclusive because of the short duration of viremia relative to the timing of the specimen collection after symptoms begin and should not be routinely collected from patients.

As orthopoxivruses are serologically cross-reactive, antigen and antibody detection methods do not provide monkeypox-specific confirmation. Serology and antigen detection methods are therefore not recommended for diagnosis or case investigation where resources are limited. Additionally, recent or remote vaccination with a vaccine-based vaccine (e.g. anyone vaccinated before smallpox eradication, or more recently vaccinated due to higher risk such as orthopoxvirus laboratory personnel) might lead to false positive results.

In order to interpret test results, it is critical that patient information be provided with the specimens including: a) date of onset fever, b) date of onset rash, c) date of specimen collection, d) current status of the individual (stage of rash), and e) age.

Therapeutics

Clinical care for monkeypox should be fully optimized to alleviate symptoms, manage complications and prevent long-term sequelae. Patients should be offered fluids and food to maintain adequate nutritional status. Secondary bacterial infections should be treated as indicated. An antiviral agent known as tecovirimat that was developed of smallpox was licensed by the European Medicines Agency (EMA) for monkeypox in 2022 based on data in animal and human studies. It is not widely available.

If used for patient care, tecovirimat should ideally be monitored in a clinical research context with prospective data collection.

Vaccination

Vaccination against smallpox was demonstrated through several observational studies to be about 85% effective in preventing monkeypox. Thus, prior smallpox vaccination may result in milder illness. Evidence of prior vaccination against smallpox can usually be found as a scar on the upper arm. At the present time, the original (first-generation) smallpox vaccines are no longer available to the general public. Some laboratory personnel or health workers may have received a more recent smallpox vaccine to protect them in the event of exposure to orthopoxviruses in the workplace. A still newer vaccine based on a modified attenuated vaccinia virus (Ankara strain) was approved for the prevention of monkeypox in 2019. This is a two-dose vaccine for which availability remains limited. Smallpox and monkeypox vaccines are developed in formulations based on the vaccinia virus due to cross-protection afforded for the immune response to orthopoxviruses.

Prevention

Raising awareness of risk factors and educating people about the measures they can take to reduce exposure to the virus is the main prevention strategy for monkeypox. Scientific studies are now underway to assess the feasibility and appropriateness of vaccination for the prevention and control of monkeypox. Some countries have, or are developing, policies to offer vaccine to persons who may be at risk such as laboratory personnel, rapid response teams and health workers.

Reducing the risk of human-to-human transmission

Surveillance and rapid identification of new cases is critical for outbreak containment. During human monkeypox outbreaks, close contact with infected persons is the most significant risk factor for monkeypox virus infection. Health workers and household members are at a greater risk of infection. Health workers caring for patients with suspected or confirmed monkeypox virus infection, or handling of specimens from them, should implement standard infection control precautions. If possible, persons previously vaccinated against smallpox should be selected to care for the patient.

Samples taken from people and animals with suspected monkeypox virus infection should be handled by trained staff working in suitably equipped laboratories. Patient specimens must be safely prepared for transport with triple packaging in accordance with WHO guidance for transport of infectious substances.

The identification in May 2022 of clusters of monkeypox cases in several non-endemic countries with no direct travel links to an endemic area is atypical. Further investigations are underway to determine the likely source of infection and limit further onward spread. As the source of this outbreak is being investigated, it is important to look at all possible modes of transmission in order to safeguard public health. Further information on this outbreak can be found here.

Reducing the risk of zoonotic transmission

Over time, most human infections have resulted from a primary, animal-to-human transmission. Unprotected contact with wild animals, especially those that are sick or dead, including their meat, blood, and other parts must be avoided. Additionally, all foods containing animal meat or parts must be thoroughly cooked before eating.

Preventing monkeypox through restrictions on animal trade

Some countries have put in place regulations restricting importation of rodents and non-human primates. Captive animals that are potentially infected with monkeypox should be isolated from other animals and placed into immediate quarantine. Any animals that might have come into contact with an infected animal should be quarantined, handled with standard precautions and observed for monkeypox symptoms for 30 days.

How monkeypox relates to smallpox

The clinical presentation of monkeypox resembles that of smallpox, a related orthopoxvirus infection which has been eradicated. Smallpox was more easily transmitted and more often fatal as about 30% of patients died. The last case of naturally acquired smallpox occurred in 1977, and in 1980 smallpox was declared to have been eradicated worldwide after a global campaign of vaccination and containment. It has been 40 or more years since all countries ceased routine smallpox vaccination with vaccinia-based vaccines. As vaccination also protected against monkeypox in the west and central Africa unvaccinated populations are now also more susceptible to monkeypox virus infection.

Whereas smallpox no longer occurs naturally, the global health sector remains vigilant in the event it could reappear through natural mechanisms, laboratory accident or deliberate release. To ensure global preparedness in the event of reemergence of smallpox, newer vaccines, diagnostics and antiviral agents are being deployed. These may also now prove useful for prevention and control of monkeypox.

WHO response

WHO supports Member States with surveillance, preparedness and outbreak response activities for monkeypox in affected countries. More information can be found here.

---

July 23, 2022: World Health Organization (WHO) posted the WHO Director-General’s statement titled: “WHO Director-General’s statement at the press conference following IHR Emergency Committee regarding the multi-country outbreak of monkeypox – 23 July 2022”. From the statement:

Good morning, good afternoon, and good evening.

A month ago, I convened the Emergency Committee under the International Health Regulations to assess whether the multi-country monkeypox outbreak represented a public health emergency of international concern.

At that meeting, while differing views were expressed, the committee resolved by consensus that the outbreak did not represent a public health emergency of international concern.

At the time, 3040 cases of monkeypox had been reported to WHO, from 47 countries.

Since then, the outbreak has continued to grow, and there are now more than 16 thousand reported cases from 75 countries and territories, and five deaths.

In light of the evolving outbreak, I reconvened the committee on Thursday of this week to review the latest data and advise me accordingly.

I thank the committee for its careful consideration of the evidence, and issues.

On this occasion, the committee was unable to reach a consensus on whether the outbreak represents a public health emergency of international concern.

The reasons the committee members gave for and against are laid out in the report we are publishing today.

Under the International Health Regulations, I am required to consider five elements in deciding whether an outbreak constitutes a public health emergency of international concern.

First, the information provided by countries – which in this case shows that this virus has spread rapidly to many countries that have not seen it before;

Second, the three criteria for declaring a public health emergency of international concern, which have been met;

Third, the advice of the Emergency Committee, which has not reached consensus;

Fourth, scientific principles, evidence and other relevant information – which are currently insufficient and leave us with many unknowns;

And fifth, the risk to human health, international spread, and the potential for interference with international traffic.

WHO’s assessment is that the rise of monkeypox is moderate globally and in all regions, except in the European region where we assess the risk as high.

There is also a clear risk of further international spread, although the risk of interference with international traffic remains low for the moment.

So in short, we have an outbreak that has spread around the world rapidly, through new modes of transmission, about which we understand too little, and which meets the criteria in the International Health Regulations.

For all of these reasons, I have decided that the global monkeypox outbreak represents a public health emergency of international concern.

Accordingly, I have made a set of recommendations for four groups of countries:

First, those that have not yet reported a case of monkeypox, or have not reported a case for more than 21 days;

Second, those with recently imported cases of monkeypox and that are experiencing human-to-human transmission.

This includes recommendations to implement a coordinated response to stop transmission and protect vulnerable groups;

To engage and protect affected communities;

To intensify surveillance and public health measures;

To strengthen clinical management and infection prevention and control in hospitals and clinics;

To accelerate research into the use of vaccines, therapeutics and other tools

And recommendations on international travel.

The third group of countries is those with transmission of monkeypox between animals and humans;

And the fourth is countries with manufacturing capacity for diagnostics, vaccines and therapeutics.

My full recommendations are laid out in my statement.

I thank the Emergency Committee for its deliberations and advice. I know this has not been an easy or straightforward process, and that there are divergent views among the members.

The International Health Regulations remains a vital tool for responding to the international spread of disease.

But this process demonstrates once again that this vital tool needs to be sharpened to make it more effective.

So I’m pleased that alongside the process of negotiating a new international accord on pandemic preparedness and response, WHO’s Member States are also considering targeted amendments to the International Health Regulations, including ways to improve the process for declaring a public health emergency of international concern.

Although I am declaring a public health emergency of international concern, for the moment, this is an outbreak that is concentrated among men who have sex with men, especially those with multiple partners.

That means that this is an outbreak that can be stopped with the right strategies in the right group.

It is therefore essential that all countries work closely with communities of men who have sex with men, to design and deliver effective information and services, and to adopt measures that protect the health, human rights, and dignity of affected communities.

Stigma and discrimination can be as dangerous as any virus.

In addition to our recommendations to countries, I am also calling on civil society organizations, including those with experience in working with people living with HIV, to work with us on fighting stigma and discrimination.

But with the tools we have right now, we can stop transmission and bring this outbreak under control.

I thank you.

---

August 12, 2022: World Health Organization posted news titled: “Monkeypox: experts give virus variants new names”. From the news:

A group of global experts convened by WHO has agreed on new names for monkeypox virus variants, as part of an ongoing efforts to align the names of the monkeypox disease, virus and variants – or clades – with current best practices. The experts agreed to name the clades using Roman numerals.

The monkeypox virus was named upon first discovery in 1958, before current best practices in naming diseases and viruses were adopted. Major variants were identified by geographic regions where they were known to circulate.

Current best practice is that newly-identified viruses, related disease, and virus variants should be given names with the aim to avoid causing offense to any cultural, social, national, regional, professional, or ethnic groups, and minimize any negative impact on trade, travel, tourism or animal welfare.

Disease: Assigning new names to existing diseases is the responsibility of WHO under the International Classification of Diseases and the WHO Family of International Health Related Classifications (WHO-FIC). WhO is holding an open consultation for a new disease name for monkeypox. Anyone wishing to propose new names can do so here. (see ICD-11, Add proposals).

Virus: The naming of virus species is the responsibility of the International Committee on the Taxonomy of Viruses (ICTV), which has a process underway for the name of the monkeypox virus.

Variants/clades: The naming of variants for existing pathogens is normally the result of debate among scientists. In order to expedite agreement in the context of the current outbreak, WHO convened an ad hoc meeting on 8 August to enable virologists and public health experts to reach consensus on new terminology.

Experts in pox virology, evolutionary biology and representatives of research instututes from across the globe reviewed by the phylogeny and nomenclature of known and new monkeypox virus variants or clades. They discussed the characteristics and evolution of monkeypox virus variants, their apparent phylogenetic and clinical differences, and potential consequences for public health and future virological and evolutionary research.

The group reached a consensus on new nomenclature for the virus clades that is in line with best practices. They agreed on how the virus clades should be recorded and classified on genome sequence repository sites.

Consensus was reached to refer to the former Congo Basin (Central African) clade as Clade one (I) and the former West African clade as Clade two (II). Additionally, it was agreed that the Clade II consists of two subclades.

The proper naming structure will be represented by a Roman numeral for the clade and a lower-case alphanumeric character for the subclades. Thus, the new naming convention compromises Clade I, Clade IIa, and Clade IIb, with the latter referring primarily to the group of variants circulating in the 2022 global outbreak. The naming of lineages will be proposed by scientists as the outbreak evolves. Experts will be reconvened as needed.

The new names for the clades should go into effect immediately while work continues on the disease and virus names.

August 24, 2022: World Health Organization (WHO) posted “Vaccines and immunization for monkeypox: Interim guidance, 24 August 2022”. From the information:

Overview

The goal of the global outbreak response for monkeypox is to stop human-to-human transmission of monkeypox, with a priority focus on communities at high risk of exposure which may differ according to context, and to effectively use strong public health measures to prevent onward spread of the disease. Judicious use of vaccines can support this response. This interim guidance, developed with the advice and support of the Strategic Advisory Group of Experts (SAGE) Working Group on smallpox and monkeypox. Key points follow.

• Mass vaccination is not required nor recommended for monkeypox at this time.

• For contacts of cases, post-exposure preventative vaccination (PEPV) is recommended with an appropriate second- or third-generation vaccine, ideally within four days of first exposure to prevent onset of disease.

• Primary preventative vaccination (PPV) is recommended for persons at high risk of exposure, including but not limited to gay or bisexual men who have sex with men or other persons with multiple sex partners, health workers at risk, laboratory personnel working with orthopoxviruses, clinical laboratory staff performing diagnostic testing for monkeypox, and others who may be at risk, as per national policy.

• Vaccination programmes must be backed by through surveillance and contact-tracing, and accompanies by a strong information campaign, robust pharmacovigilance, ideally in the context of collaborative vaccine effectiveness studies with standardized protocols and data collection tools.

• Decisions on use of smallpox or monkeypox vaccines should be based on a full assessment of risks and benefits on a case-by-case basis.

Many interim recommendations provided here concern off-label use of vaccines. The guidance will be updated as more information becomes available.

August 26, 2024: World Health Organization posted information about Mpox

Key facts

Mpox, previously known as monkeypox, is a viral illness caused by the monkeypox virus, a species of the genus Orthopoxvirus. There are two distinct clades of the virus: clade I (with subclades Ia and Ib) and clade II (with subclades II and IIb). In 2022 – 2023 a global outbreak of mpox was caused by the clade IIb strain.

Mpox continues to be a threat today, and an upsurge of cases in the Democratic Republic of Congo and other countries caused by clades Ia and Ib has raised concern.

There are vaccines for mpox. Vaccination should be considered along with other public health interventions.

Common symptoms of mpox are a skin rash or mucosal lesions which can last 2-4 weeks accompanied by fever, headache, muscle aches, back pain, low energy and swollen lymph nodes.

Mpox can be transmitted through close contact with someone who has mpox, with contaminated materials, or with infected animals. During pregnancy, the virus may be passed to the fetus, or to the newborn during or after birth.

Mpox is related with supportive care for symptoms such as pain and fever, with close attention to nutrition, hydration, skin care, prevention of secondary infections and treatment of co-infections, including HIV where present.

Overview

Mpox is an infectious disease that can cause painful rash, enlarged lymph nodes, fever, headache, muscle ache, back pain and low energy. Most people fully recover, but some get very sick.

Mpox is caused by the monkeypox virus (MPXV). It is an enveloped double-standard DNA virus of the Orthopoxvirus genus in the Poxviridae family, which includes various, cowpox vaccinia and other viruses. There are two distinct clades of the virus: clade I (with subclades Ia and Ib) and clade II (with subclades II and IIb).

A global outbreak of Clade IIb began in 2022 and continues to this day, including in some African countries. There are also growing outbreaks of clades Ia and Ib affecting the Democratic Republic of the Congo and other countries in Africa. As of August 2024, clade Ib has also been detected beyond Africa.

The natural reservoir of the virus is unknown, but various small mammals such as squirrels and monkeys are susceptible.

Transmission

Mpox spreads from person to person daily through close contact with someone who has mpox, including members of a household. Close contact includes skin-to-skin (such as touching or sex) and mouth-to-mouth or mouth-to-skin contact (such as kissing), and it can also include being face-to-face with someone who has mpox (such as talking or breathing close to one another, which can generate infectious respiratory particles.)

People with multiple sexual patterns are at higher risk of acquiring mpox.

People can also contract mpox from contaminated objects such as clothing or linen, through needle injuries in health care, or in community settings such as tattoo parlours.

During pregnancy or with, the virus may be passed to the baby. Contracting mpox during pregnancy can be dangerous for the fetus or newborn infant and can lead to loss of pregnancy, stillbirth, death of the newborn, or complications for the parent.

Animal-to-human transmission of mpox occurs from infected animals to humans from bites or scratches, or during activities such as hunting, skinning, trapping, cooking, playing with carcasses or eating animals. The animal reservoir of the monkeys virus remains unknown and further studies are underway.

More research is needed on how mpox spreads during outbreaks in different settings and under different conditions.

Signs and symptoms

Mpox causes signs and symptoms which usually begin within a week but can start 1-21 days after exposure. Symptoms typically last 2-4 weeks but may last longer in someone with a weakened immune system.

Common symptoms of mpox are:

• rash
• fever
• sore throat
• headache
• muscle aches
• back pain
• low energy
• swollen lymph nodes.

For some people, the first symptom of mpox is a rash, while others might have fever, muscle aches or sore throat first.

The mpox rash often begins on the face and spread over the body, extending to the palms of the hands and soles of the feet. It can also start on other parts of the body where contact was made, such as the genitals. It starts as a flat store, which develops into a blister filled with liquid that may be itchy or painful. As the rash heals the lesions dry up, crust over, and fall off.

Some people may have one or a few skin lesions and others have hundreds or more. These can appear anywhere on the body including:

• palms of hands and soles of feet
• face, mouth and throat
• groin and genital areas
• anus

Some people also have painful swelling of their rectum (proctitis) or pain and difficulty when peeing (dysuria) or when swallowing.

People with mpox can pass the disease on to others until all sores have healed and a new layer of skin has formed. Some people can be infected without developing any symptoms. Although getting mpox from someone who is asymptomatic (not showing symptoms) has been reported, information is still limited on how common it is.

Children, pregnant people and people with weak immune systems, including people living with HIV that is not well controlled, are at higher risk for serious illness and death due to complications from mpox.

Some people with mpox become very sick. For example, the skin can become infected with bacteria, leading to accesses or serious skin damage. Other complications include pneumonia; corneal infection with loss of vision; pain or difficulty swallowing; vomiting and diarrhoea causing dehydration or malnutrition; and infections of the blood (sepsis), brain (encephalitis) heart (myocarditis) rectum (proctitis), genital organs (balantis) or uninary passages (urethritis). Mpox can be fatal in some cases.

Diagnosis

Identifying mpox can be difficult because of other infections and conditions can look similar. It is important to distinguish mpox from chickenpox, measles, bacteria skin infections, scabies, herpes, syphilis and other sexually transmitted diseases. Alternatively, a child with suspected mpox may also have chickenpox. For these reasons, testing is key for people to get care as early as possible and prevent severe illness and further spread.

The preferred laboratory test for mpox is detection of viral DNA by polymerase chain reaction (PCR). The best diagnostic specimens are taken directly from the rash – skin, fluid, or crusts — collected by vigorous swabbing. In the absence of skin lesions, testing can be done using swabs of the throat or anus. Testing blood is not recommended. Antibody detection methods may not be useful as they do not distinguish between different orthopoxviruses.

HIV testing should be offered to adults with mpox, and children as appropriate. Diagnostic tests for other conditions should be considered where feasible, for example, varicella zoster virus (VZV), syphilis and herpes.

Treatment and vaccination

The goal of treating mpox is to take care of the rash, manage pain and prevent complications. Early and supportive care is important to help manage symptoms and avoid further problems.

Getting an mpox vaccine can help prevent infection (pre-exposure prophylaxis). It is recommended for people at high-risk of getting mpox, especially during an outbreak.

Groups that may be at high risk of mpox include:

• health and care workers at risk of exposure,
• people in the same household or close community as someone who has mpox, including children
• people who have multiple sex partners, including men who have sex with men; and
• sex workers of any gender and their clients.

The vaccine can also be administered after a person has been in contact with someone who has mpox (post-exposure prophylaxis). In these cases, the vaccine should be given less than 4 days after contact with someone who has mpox. The vaccine can be given for up to 14 days if the person has not developed symptoms.

Some antivirals have received emergency use authorization in some countries and are being evaluated in clinical trials. To date, there is no proven effective antiviral treatment for mpox. It is a priority to continue evaluation of therapeutics in robust clinical trials and to focus on optimizing supportive care for patients.

Individuals with HIV and mpox should continue taking heir antiretroviral therapy (ART) ART should be initiated within 7 days of diagnosis of HIV.

Self-care and prevention

Most people with mpox will recover within 2-4 weeks. Things to do to help the symptoms and prevent transmitting mpox to others:

Do

• contact your health care provider for advice;
• stay at home and in your own, well-ventilated room if possible;
• wash hands often with soap and water or hand sanitizer, especially before or after touching sores
• wear a mask and cover lesions when around other people until your rash heals
• keep skin dry and uncovered (unless in a room with someone else);
• use saltwater rinses for sores in the mouth
• take warm baths with baking soda or Epsom salts for body sores; and
• take over-the-counter medications for pain like paracetamol (acetaminophen) or ibuprofen.

Do not

• pop blisters or scratch sores, which can slow healing, spread the rash to other parts of the body, and cause sores to become infected; or
• shave areas with sores until scabs have healed and you have new skin underneath (this can spread the rash to other parts of the body).

To prevent spread of mpox to others, people with mpox should isolate at home, following guidance from their health care provider, or in hospital if needed, for the duration of the infectious period (from onset of symptoms until lesions have healed and scabs fall off). Covering lesions and wearing a well-fitting mask when in the presence of others may help prevent spread. Using condoms during sex will help reduce the risk of getting mpox but it will not prevent spread from skin-to-skin or mouth-to-skin contact. If having sex, use condoms as a precaution for 12 weeks (about 3 months) after you have recovered.

Taking a break from sexual activity with new partners during periods of increased transmission can reduce the risk of getting mpox. Those who have had contact with someone with mpox should monitor for signs and symptoms for 21 days (3 weeks) and take precautions such as avoiding sexual activity during this period.

Health workers should follow infection prevention control measures to protect themselves while caring for patients with mpox by wearing appropriate personal protective equipment (PPE) (i.e gloves. gown, eye protection and respirator) and adhering to protocol for safely swabbing lesions for diagnostic testing and handling sharp objects such as needles.

Stigma and discrimination

Stigma and discrimination for any disease are never acceptable. Stigma linked to mpox can undermine public health efforts or prolong a disease outbreak, as people may be more reluctant to come forward and seek care and treatment. For mpox, stigma, discrimination and racism have been particularly directed against communities initially most affected by the disease, namely men who have sex with men, trans people and gender diverse communities…

October 30 2024: World Health Organization WHO lists additional mpox diagnostic tests for emergency use

As part of ongoing efforts to enhance quality-assured testing options, the World Health Organization (WHO) has listed two additional mpox in vitro diagnostics under its Emergency Use Listing (EUL) procedure. WHO’s EUL is based on the review of quality, safety and performance date in compliance with international standards while addressing the specific needs of low- and middle-income countries (LMICs).

Polymerase Chain Reaction (PCR) testing, which detects viral DNA, is considered the gold standard for diagnosing mpox infection.

WHO listed the Xpert Mpox, a real-time PCR test manufactured by Cepheid under its EUL procedure, on 25 October. This test is designed for use on compatible GeneXpert systems. The Xpert Mpox test is easy to operate and delivers results in under 40 minutes. Once the cartridge is placed in the system, the process is fully automated, with real-time PCR detecting viral DNA of monkeypox virus clade II. The GeneXpert system is a near-point-of-care testing option, which can support decentralized testing.

Another PCR-based option, the cobas MPXV assay, developed by Roche Molecular System’s Inc., was listed on 14 October 2024. It is intended for use on the cobas 6800/8800 Systems. This tool is intended for use on the cobas clades and delivering results in under 2 hours. It can process multiple samples simultaneously and is suitable for clinical laboratories that handle large volumes of tests.

“Ensuring global access to mpox diagnostic tests that meet WHO standards for quality, safety and performance is essential for efficient and effective testing in settings affected by mpox outbreaks,” said Dr Rogerio Gaspar, WHO Director for Regulation and Prequalification. “Rapid access to those listed products is critical not only for prompt diagnosis and timely treatment, but also for effectively containing the spread of the virus.”

WHO previously listed Alinity m MPXV assay, manufactured by Abbott Molecular Inc. under EUL on 3 October.

In 2024, 19 countries in Africa have reported over 40 000 suspected mpox cases with most remaining unconfirmed due to limited testing capacity, especially in LMICs. In the Democratic Republic of the Congo — the hardest-hit country — testing has significantly increased in 2024, following the efforts to decentralize testing with support from WHO and partners. However, the proportion of tested cases remains low, accounting for 40-50% of the suspected cases.

WHO is working with manufacturers of the EUL-listed products and national regulatory authorities in affected countries to facilitate domestic registration or emergency listing. Fast-tracking approvals and applying reliance principles will enhance access to quality-assured mpox tests.

Overall, WHO has received over 60 expressions of interest for the EUL review of mpox diagnostic tests. Seven of these progressed to EUL applications, with 2 products currently under review and 2 more expected soon.