Epidemiological Updates of MPOX: An Emerging Disease

Abstract

MPOX is a zoonotic disease caused by orthopoxvirus. The disease is endemic in African countries, but major outbreak was reported in the early 2022 outside the endemic countries and subsequently spreading in the whole world following which it was declared as a Public Health Emergency of International Concern on July 23, 2022. MPOX is a self-limiting disease with symptoms generally lasting from 2 to 4 weeks. Vesiculopustular skin rashes begin 1 to 3 days after prodromal symptoms and can last up to 4 weeks. Transmission can occur from animal to human as well as from human to human via body fluids, close contact with respiratory secretions, skin lesions, contaminated material etc. As there is no specific treatment for MPOX, isolation of the confirmed cases is the key modality to control the spread of the disease.

1. Introduction

MPOX previously known as “Monkeypox” is a viral zoonotic disease transmitted to humans from vertebrate animals, predominantly found in tropical rainforest areas of west and central Africa. Monkeypox virus belongs to the orthopoxvirus genus of the family poxviridae [1]. Following smallpox eradication and successive termination of smallpox vaccination, MPOX has emerged as the most important orthopoxvirus for public health. The clinical sign and symptom range from less severe, that is, fever, headache, muscle aches, back pain, low energy and swollen lymph node followed by rash to more serious illnesses such as encephalitis, pneumonia, sepsis [2].

2. Problem statement

MPOX was first discovered in colonies of monkeys kept for research in Denmark in 1958, hence the name “monkeypox.” First ever human monkeypox was identified in a 9-month-old boy in 1970 in the Democratic Republic of the Congo region. Since then, the majority of the outbreaks in the period 1970–99 have been reported from the rural and rainforest regions of 11 African countries: Benin, Cameroon, the Central African Republic, the Democratic Republic of the Congo, Gabon, Cote d’Ivoire, Liberia, Nigeria, the Republic of the Congo, Sierra Leone, and South Sudan [2]. In 2003, the United State of America was the first country in which MPOX outbreak was reported outside of Africa with 47 confirmed cases [3]. The index case was a 3 years old girl who had contact with an infected pet prairie dog housed with Gambian pouched rats imported from Ghana. Since then, occasional cases have been reported in other non-endemic countries including UK, Singapore, Israel, etc. from 2010 to 2019 (Figure 1) [4].

Figure 1.

Timeline of MPOX outbreak.

3. Epidemiological determinants

Agent: MPOX is an enveloped double-stranded DNA virus belonging to genus Orthopoxvirus of Poxviridae family. There are two discrete genetic clades, namely, central African (Congo Basin) and the western African Clade. Western African clade has further subtypes: clade IIa and clade IIb. Congo basin, also known as clade I, is prevalent in DRC, Gabon, Central African Republic, and western Africa. Clade II is found in Nigeria, Liberia, Sierra Leone and Cote d’lvoire. Clade IIa is prevalent in West Africa and has low mortality; Clade IIb is responsible for the current 2022 global outbreak (Table 1) [5]. The geographical distribution overlaps in Cameroon.

	Clade I	Clade II
Severity	More severe	Less severe
Case fatality	Up to11%	6%
Transmission	More human-to-human transmission	Less human-to-human transmission

Table 1.

Clades of MPOX.

Source: WHO.

Host: The natural host of MPOX is not known. Many species of small rodents as well as non-human primates are known to be vulnerable to monkeypox virus. These include squirrels, Gambian pouched rats, dormice, etc. [6, 7].

Incubation period: The incubation period (interval from infection to onset of symptoms) of MPOX is generally from 6 to 13 days (range: 5–21 days). A person is not normally contagious during this period [8].

4. Clinical features

MPOX is a self-limiting disease with symptoms generally lasting from 2 to 4 weeks. Infection in humans can be divided into two phases: invasion phase and rash phase.

Invasion/febrile phase: It is marked by prodromal symptoms such as fever, severe headache, lymphadenopathy, back pain, muscle ache, and profound weakness lasting up to 5 days. Lymphadenopathy is a peculiar feature of MPOX differentiating it from other diseases such as chickenpox, measles, smallpox.

Eruption/rash phase: Skin rashes begin within 1–3 days of appearance of prodromal symptoms. Distribution of rash is more on the face (in 95% of cases) and extremities (in 75% of cases). Oral mucus membrane (70%), genitalia (30%), conjunctiva (20%), and cornea can also be affected. The rash goes through several stages, beginning as macules and advancing to papule, vesicle, pustule, and scab formation. Mostly 10–150 lesions are observed, which can last up to 4 weeks. Classical lesion is vesiculopustular. In contrast to smallpox lesions, rashes of MPOX are similar in size and are unimorphic (present at the same stage).

In this outbreak, predominant symptoms at the time of diagnosis are skin rash frequently with anogenital or oropharyngeal lesions along with fever, chills, and lymphadenopathy. This is a stark difference from earlier outbreaks in which prodromal symptoms precede the rash onset (Figures 2–4) [9].

Figure 2.

Stages of MPOX rash.

Figure 3.

MPOX Rash. *Source: CDC.

Figure 4.

Commonly reported symptoms of MPOX disease in 2022 outbreak. Source: WHO *38626 cases with at least one reported symptom from a country where at least two unique symptoms reported were used as denominator.

MPOX is generally a self-limiting disease, but secondary complications may occur in some cases such as gastroenteritis, sepsis, pneumonia, encephalitis, myocarditis, epiglottis, bacterial skin infection, conjunctivitis, and corneal scarring [10].

4.1 Period of communicability

A person suffering from the disease is infectious from the time of onset of symptoms until the rash has completely healed and fresh layer of skin has formed. But in the current outbreak, recent scientific evidence has discovered that some people can spread the infection even 1 to 4 days before the onset of symptoms [11].

4.2 Mode of transmission

Transmission can occur from animal to human (zoonosis) and human to human.

4.3 Animal to human transmission

MPOX virus is transmitted via close contact with an infected animal or contact with the infectious material. The virus enters the body via broken skin or mucus membrane [12, 13].

Direct contact with

1. Body fluids

2. Lesions of an infected animal

3. Bite or scratch

Indirect contact with

1. Contaminated material

2. Eating inadequately cooked meat of an infected animal [13].

Human-to-human transmission: Human-to-human transmission can occur through various routes like:

• Close contact with respiratory secretions, skin lesions of an infected individual, or recently contaminated object [14, 15].

• Transplacental transmission leading to congenital MPOX in the fetus or through close contact during and after birth [15].

• Transmission can also occur through contaminated clothing that have infectious skin particles (fomites transmission) [13].

• The longest documented human-to-human chain of transmission has increased in a recent outbreak from 6 to 9 reflecting declining immunity in communities (Figure 5) [13].

Figure 5.

Common identified modes of transmission in MPOX. Source: WHO.

4.4 Factors responsible for animal-to-human transmission

Many factors contribute to the emergence and re-emergence of various zoonotic diseases including MPOX. The spread can be attributed to: (i) deforestation and climate change (owing to disruption in environmental condition and habitat), (ii) urbanization and population growth resulting in more people coming in contact with wild and domestic animal as well as expanding into new geographical area, (iii) industrialization, (iv) air travel, and (v) cessation of smallpox vaccination. These provide more opportunities for diseases to pass between animals and people (Figure 6).

Figure 6.

Five stages through which the animal pathogen evolves to cause human diseases (disease spillover) [16].

4.5 At-risk population

People who are at a risk of getting MPOX include: international travelers recently in endemic countries, individuals who had engaged in anonymous sex, healthcare providers and household members exposed to confirmed cases, eating partially cooked meat and other animal products of infected animals, people living in or near forested areas, through placenta from mother to fetus (congenital MPX), or close contacts during and after birth; 99% of the cases are seen among gay, bisexual, MSM, and transgender.

Human-to-animal transmission: In endemic countries, only wild animals (rodents and primates) have been found to transmit the MPOX virus. Even though, transmission of MPOX virus in prairie dogs has been reported in USA and in captive primates in Europe that were in contact with imported infected animals, infection among pet animals such as dogs and cats has never been reported. But in the current outbreak, a case was reported in which mucocutaneous lesions including abdomen pustules and a thin anal ulceration were observed in a male Italian greyhound aged 4 years with no previous medical disorder 12 days after the symptom onset in their owner. The dog was positive for MPOX virus, indicating human-to-animal transmission [17].

4.6 Diagnosis of MPOX

As per WHO guidelines, any individual that meets the suspected case definition for monkeypox should be offered testing. Use personal protective equipment and safety measures for handling the clinical specimens.

Serological testing should only be done if modalities for viral testing like PCR are unavailable, as it has limited use because of cross-reactivity. Serological testing is useful for epidemiological purposes (for monitoring epidemics in non-endemic areas). Patients will have elevated anti-orthopoxvirus IgM and IgG antibodies (Figure 7) [18].

Figure 7.

Flow diagram of MPOX diagnosis (Source: ICMR).

4.7 Recommended specimen types

Recommended specimen types are skin lesion material including swabs of lesion surface and/or exudate and roofs from more than one lesion or lesion crust.

Sample storage: Should be refrigerated at 2–8°C or frozen at –20°C within 1 h of sample collection. For longer term (more than 60 days), specimen is stored at –70°C.

Sample transportation: All the specimen are transported in appropriate triple package along with labeling and documentation.

5. Management of MPOX

As of now, there is no specific treatment for MPOX. The foremost step in the management is isolation of the confirmed case in a separate room with adequate ventilation until all the lesions have resolved and scabs have completely fallen off. Active skin lesions should be covered to minimize the risk to others. The mainstay of the treatment is supportive management only, which is described as follows (Table 2).

Treatment of prodromal symptoms by	Antipyretics, antihistaminic, antiemetics, topical calamine lotion, etc.
Adequate diet and hydration to alleviate dehydration. Encourage ORS/oral fluids/intravenous fluid as per the requirement
Specific treatment	Skin rash	Clean with antiseptic; mupirocin acid; Keep the lesion covered; Avoid touching or scratching the lesion; Antibiotics in the case of secondary infection
	Genital ulcer	Sitz bath
	Oral ulcer	Warm saline gargle/topical anti-inflammatory gel

Table 2.

Treatment of MPOX.

(Source: ICMR).

Monitor the patient for the appearance of danger signs such as blurring of vision, shortness of breath, chest pain, altered consciousness, decreased urine output [19].

Drugs under trial: Several drugs are being assessed in trials, namely,

1. STOMP trial and PALM trial: Tecovirimat

2. Brincidofovir

6. Contact tracing

6.1 Definition of contact

A contact is defined as a person who, in the period beginning with the onset of the source case’s first symptoms, and ending when all scabs have fallen off, has had one or more of the following exposures with a probable or confirmed case of monkey pox:

• face-to-face exposure (including healthcare workers without appropriate PPE)

• direct physical contact, including sexual contact

• contact with contaminated materials such as clothing or bedding

Contact identification: Identify the contacts across households, workplace, school, healthcare places, transportation, social gathering, sexual contacts or any other record interactions.

Contact monitoring: Contacts should be monitored for a period of at least 21 days for the onset of signs and symptoms. Children should be excluded from daycare/school or other group settings. For exposed healthcare worker, active surveillance of signs and symptoms for 21 days is recommended.

6.2 2022 MPOX outbreak

6.2.1 Global synopsis

• From the beginning of 2022, the cluster of cases began occurring in many countries where MPOX was not endemic. The early cluster of cases was found in the United Kingdom, where the primary case was identified on May 6, 2022 in an individual with travel links to Nigeria, and since then, 110 member states covering all 6 WHO regions have reported the disease. At the time of writing this chapter, a total of 86,309 cases have been confirmed including 92 deaths, with the majority of cases being reported from region of Americas (80%) followed by Europe (17%).

• WHO evaluated the global risk of MPOX as moderate. Region-wise highest risk was assessed in the United States of America followed by moderate risk in Africa, Eastern Mediterranean, Europe and South-East Asia, and low risk in Western Pacific region (Table 3).

	Total confirmed cases	Total detailed confirmed cases*
Region of the Americas	58,241	55,638
European Region	25,830	25,732
African Region	1,341	401
Western Pacific Region	244	138
Eastern Mediterranean Region	82	57
South-East Asia Region	40	40

Table 3.

WHO region-wise case distribution.

^*

Note that in rare cases total detailed cases may exceed total confirmed cases due to ongoing data cleaning issues.

6.2.2 India

As of February 7, 2023, India has reported 22 confirmed cases and 1 death. The first case from India was reported on July 14, 2022 from Kerala in a 35-year-old man who had a travel history to UAE. India confirmed its first death by MPOX in Kerala in a 22-year-old man who had travelled from UAE. At the time of hospitalization, he had fever and swollen lymph node.

6.3 Salient features of 2022 outbreak:

• 2022 year was the first time that the cluster of cases on such a large scale was reported from endemic as well as non-endemic countries and also for the first time, in the present series of outbreaks, chains of transmission were reported in Europe without known epidemiological links to West or Central Africa. In this outbreak, Clade II (Western African clade) is responsible for the unprecedented rise of cases with a high frequency of human-to-human transmission observed in this event, with the most common route identified on the basis of history from the reported cases as close skin-to-skin contact.

  Public Health Emergency of International Concern

• Meeting the criteria of International Health Regulations, MPOX was declared a Public Health Emergency of International Concern by WHO on July 23, 2022.

• Following the issues related to racism and stigmatizing language online, WHO after consultation with global experts changed the name of “monkeypox” to “MPOX.”

7. Case definitions (WHO)

Suspected case

A person, any age presenting since January 1, 2022 with an unexplained acute rash or ≥1 acute skin lesions

AND

≥1 of following signs/symptoms

1. Headache

2. Acute onset of fever (>38.5°C)

3. Myalgia

4. Backpain

5. Lymphadenopathy

6. Asthenia

AND

After ruling out other cause of acute rash or skin lesions, for example, Varicella zoster, herpes Zoster, measles, Herpes simplex, bacterial skin infections, syphilis, chancroid, LGV, etc.

Probable case

A person meeting the case definition for a suspected case

AND

One or more of the following:

1. has an epidemiological link to a probable or confirmed case of monkeypox in the 21 days before symptom onset.

2. multiple or anonymous sexual partners in the 21 days before symptom onset.

3. detectable levels of OPXV IgM antibody b (4–56 days after rash onset), or a fourfold rise in IgG antibody titer based on acute (up to day 5–7) and convalescent (day 21 onwards) samples; in the absence of a recent small pox/mpox vaccination or other known exposure to OPXV.

4. has a positive test result for orthopoxviral infection (e.g., OPXV-specific PCR without MPXV-specific PCR or sequencing).

Confirmed case

Laboratory confirmed monkeypox virus by detection of unique sequences of viral DNA by real-time polymerase chain reaction (PCR) and/or sequencing.

Discarded case

A suspected or probable case for which laboratory testing of lesion fluid, skin specimens or crusts by PCR, and/or sequencing is negative for MPXV.

8. Prevention

Implementing effective community strategies with conveying adequate and correct education and information along with carrying forward the learnings from the COVID19 pandemic is of utmost important.

Personal protection measures

• Avoid intimate/skin-to-skin contact with people who have rash resembling MPOX.

• Avoid contact with objects and materials that a person with MPOX has used.

• Adequate hand hygiene. Wash hand with soap and water or use an alcohol-based sanitizer.

Safer sex and social gatherings: Although MPOX is not a sexually transmitted disease, it can be transmitted via close, sustained physical contact.

• If you feel sick or have signs and symptoms of MPOX disease, avoid attending social gatherings.

• Make a habit of exchanging contact information with any new partner.

• Do not share personal belongings such as towels, razor, fetish gear and toothbrushes.

• In the case of confirmed or suspected MPOX, avoid sex of any kind and kissing or touching each other’s body.

Prevention in congregate settings (Figure 8)

Figure 8.

Preventive strategies of MPOX (Source: WHO).

VACCINE

Two Orthopoxvirus vaccines are available from the CDC drug service for persons at risk for occupational exposure

1. MVA vaccine (JYNNEOS): It is a live attenuated, non-replicating vaccine available for smallpox and MPOX disease in adults 18 years of age and above. Given as a two-dose schedule 4 weeks apart.

2. ACAM2000: It is a live, competent smallpox vaccine that can be used in selected patients. It can be used for prevention of MPOX under an expanded access investigational new drug (IND) application through CDC. It is associated with more severe adverse event (myocarditis, pericarditis, psoriasis, eczema, etc.) [20].

Pre-exposure prophylaxis

It is recommended for individuals at high risk due to occupational exposure, for example personnel working with Orthopoxvirus by using the MVA vaccine [21].

Post-exposure prophylaxis

Post-exposure risk is classified in three categories as follows:

High-risk exposure: A patient is considered as having high-risk exposure if he/she had

1. Contact with skin, mucous membrane, skin lesions, or body fluids of confirmed MPOX case.

2. Being within 6 feet of a patient undergoing aerosol generating procedures like bronchoscopy, laryngoscopy, etc., without wearing personal protective equipment.

Intermediate risk exposure: Individual coming in contact with a confirmed case for 3 hours or more. Individual should wear at a least surgical mask.

Low-risk exposure: When a person comes in contact with an infected patient

1. While taking all necessary precautions

2. Without wearing eye protection

3. Is within 6 feet for less than 3 hours

Post-exposure prophylaxis is indicated for the high-risk group and should be given within 4 days of exposure (and up to 14 days in the absence of symptoms) [19].

Indian context of MPOX surveillance

WHO has made MPOX a notifiable disease and an event of PHEIC. India so far has reported 22 confirmed cases and 1 death with MPOX. Even 1 case of MPOX is to be considered as an outbreak. A detailed investigation by the Rapid Response Teams needs to be initiated through IDSP. Report any suspected case immediately to the DSU/State Surveillance Units (SSUs) and CSU (Central Surveillance Unit), which shall report the same to Dte. GHS MoHFW [19].

The salient features include the following:

1. Targeted surveillance for probable case or clusters.

2. Initiate contact tracing and testing of the symptomatic after the detection of the probable/confirmed case.

Core Surveillance Strategy

1. Hospital-based surveillance: health facility-based surveillance and testing in dermatology clinics, STD clinics, medicine, pediatrics OPDs, etc.

2. Targeted surveillance: this can be achieved by:

   1. Measles surveillance by immunization division

   2. Targeted intervention sites identified by NACO for MSM and FSW population

9. Discussion

MPOX disease, now a Public Health Emergency of International Concern (PHEIC), was initially limited to African countries, but an outbreak in the United States of America marked the spread of virus in non-endemic areas. During the 2022 outbreak, the primary case was identified in the United Kingdom on May 6, 2022, in an individual with travel links to Nigeria. Striking differences have been noticed regarding the characteristics of this outbreak as compared to the previous one. As reported in a systematic review conducted by Kumar et al. [22], among 5110 cases of MPOX disease, the median age of MPOX virus infection has increased and is now more common among adults; also, greater male preponderance has been observed. Interestingly, increased human-to-human transmission was detected with a majority of cases having no epidemiological link. One of the main reasons for greater susceptibility of adults toward the disease can be attributed to the stoppage of routine smallpox virus vaccination in 1980, which had offered cross-immunity against MPOX. Another reason reported for the increased susceptibility of adults during this outbreak is disease clustering in MSM [22].

9.1 One World-One Health approach: future perspective

It is a well-known fact that no single sector can alone prevent the emergence or resurgence of diseases. It is the need of the hour to devise adoptive, forward-looking and multidisciplinary solutions. It is important to recognize the link between human, animal, and wild life health as well as increase investment in human and animal health infrastructure by enhancing global human and animal health surveillance and information sharing. At last, it is of utmost important to educate and raise awareness among people and influencing the policy makers to recognize the need to adopt one health approach for a healthier planet [23].

9.2 Executive summary

MPOX has emerged as the most important othropoxvirus for public health. The year 2022 was the first time that clusters of cases on such a large scale were reported from endemic as well as non-endemic countries. Even one case of MPOX is to be considered as an outbreak. MPOX was declared a Public Health Emergency of International Concern by WHO on July 23, 2022. Early identification, isolation, and contact tracing should be at par as the disease manifestation is easy to identify. There is a need to continue epidemiological investigations and surveillance of the cases to combat the risk of mutations within the viral genome, which can make the control of future outbreaks challenging, especially now when the transmission modes have changed. Implementing effective community strategies with conveying adequate and correct education and information is important for prevention. Mass immunization can be suggested in the areas where MPOX has become endemic. For combating mis-infodemic, myths and generating awareness regarding high-risk behavior, time to time relevant media campaign needs to be started.

Conflict of interest

None.