Monkeypox: Symptoms, Types, Causes and Treatment

Monkeypox, once a rare viral disease restricted to certain parts of Africa, has emerged as a global public health concern. Its sudden spread in recent years has raised urgent questions about how to recognize symptoms, understand its types and causes, and manage or prevent infection. In this article, we break down the latest scientific findings on monkeypox, based on comprehensive research and global case data. Whether you’re a healthcare professional, someone concerned about recent outbreaks, or simply curious, here’s an in-depth, evidence-based overview to guide your understanding.

Symptoms of Monkeypox

Recognizing monkeypox early is crucial for timely intervention and to prevent further spread. The disease’s symptoms vary in severity and sequence, often resembling other viral illnesses, which can complicate diagnosis. However, certain features are distinctive and understanding them helps differentiate monkeypox from similar conditions.

Symptom	Frequency/Pattern	Notable Features	Sources
Rash	~93-95% of cases	Often starts as vesicular/umbilicated lesions, commonly genital/anogenital; can be few or widespread	1 2 3 5
Fever	~52-72%	May precede rash; sometimes absent in atypical cases	1 2 3 5 9
Lymphadenopathy	~56-62%	Swollen lymph nodes are more common vs. smallpox	1 3 5 9
Myalgia/Asthenia	~31-67%	Muscle aches, fatigue, and general malaise	1 2 3 5 9
Headache	~27%	Often accompanies early systemic illness	1 5 9
Mucosal Lesions	~41%	Oral, pharyngeal, and sometimes genital mucosa	1 5
Rectal Pain, Penile Edema	~16-36%	Newly recognized features in recent outbreaks	5
Sore Throat	~17%	May be due to tonsillar involvement	5

Table 1: Key Symptoms

Progression and Variability of Symptoms

Monkeypox typically starts with a prodrome – fever, chills, headache, muscle aches, and fatigue. Lymphadenopathy (swollen lymph nodes) is a distinguishing feature, often presenting before the rash. The rash usually appears 1-4 days after fever onset, starting as flat spots that become raised, then form vesicles and pustules, and finally crust over. In the 2022 global outbreak, many patients reported that skin lesions—especially in the genital and perianal regions—were sometimes the first or only symptom, rather than fever or systemic illness. This is a notable shift from classical presentations observed in endemic regions 1 2 5.

Systemic vs. Localized Manifestations

• Systemic symptoms (fever, malaise, headache, myalgia, lymphadenopathy) may precede or follow the rash.
• Localized symptoms are often characterized by:
  • Genital, perianal, and/or oral lesions.
  • Rectal pain and penile swelling (penile edema), especially in men who have sex with men (MSM) 5.
• Some patients may present only with mucocutaneous lesions and have minimal or no systemic symptoms 5.

Severity and Outcomes

Most monkeypox cases are mild and self-limited, resolving in 2-4 weeks. Hospitalization is generally uncommon (10-35% in different reports) and is often due to severe pain, bacterial superinfection, or complications involving the eyes or mouth. Fatal outcomes are rare in recent non-endemic outbreaks (<5%), but rates may be higher in children, pregnant women, or immunocompromised individuals 1 3 5.

Types of Monkeypox

Monkeypox is not a single, uniform disease; rather, it exists in two genetically distinct clades, each with different epidemiological and clinical characteristics. Understanding these types is essential for public health management and vaccine strategy.

Type (Clade)	Geographic Origin	Severity/Mortality Rate	Sources
West African	West Africa	Lower (~1% mortality); milder disease	2 4 7 10
Congo Basin	Central Africa	Higher (up to 10% mortality); more severe	4 7 10

Table 2: Monkeypox Virus Types

West African Clade

• Epidemiology: Historically found in Western African countries, but responsible for the majority of recent global outbreaks.
• Clinical features: Generally milder, with a lower case fatality rate (~1%) 2 10.
• Transmission: Human-to-human spread, including sexual transmission, has been prominent in the 2022 outbreak 2 4 10.
• Recent relevance: All genetic sequencing from the 2022 outbreaks in Europe, the US, and other regions traces back to the West African clade 2.

Congo Basin Clade

• Epidemiology: Found mainly in Central Africa, especially the Democratic Republic of the Congo.
• Clinical features: Associated with more severe disease and higher mortality (up to 10%) 4 7 10.
• Transmission: Animal-to-human is common, but human-to-human can also occur.
• Prevalence: Not detected in recent outbreaks outside Africa.

Importance of Clade Identification

Identifying the clade involved in an outbreak helps:

• Predict clinical severity and risk.
• Guide public health responses.
• Inform vaccine and treatment strategies 4 10.

Causes of Monkeypox

Monkeypox is a zoonotic disease, meaning it originates in animals and can spill over to humans. However, recent outbreaks have highlighted new causes and transmission dynamics.

Cause/Source	Description	Transmission Route(s)	Sources
Animal Reservoirs	Mainly African rodents; non-human primates	Bite, scratch, direct/indirect contact	4 7 8 9 10
Human-to-Human	Infected individuals	Skin-to-skin, respiratory droplets, sexual contact, fomites	1 4 6 7 8 9 10 12
Environmental	Contaminated materials (fomites)	Bedding, towels, clothing	9 12

Table 3: Causes and Transmission Routes

Animal Reservoirs and Zoonotic Transmission

• Reservoirs: Rodents (like Gambian pouched rats, dormice, squirrels) are the suspected primary reservoirs. Non-human primates can also be infected but are not considered the main source 4 7 8.
• Spillover: Humans become infected through bites, scratches, or handling of infected animals, or via contact with animal fluids or lesions 4 7 10.
• Geography: Most zoonotic cases have occurred in Central and West Africa, often in forested/rural areas 7.

Human-to-Human Transmission

• Routes:
  • Direct contact: With lesions, bodily fluids, or scabs of an infected person.
  • Respiratory droplets: Prolonged face-to-face contact can transmit the virus, though less efficiently than smallpox 4 7 8 10.
  • Sexual contact: The 2022 outbreak has seen a high prevalence among MSM, with sexual transmission playing a key role 1 2 10.
  • Fomites: Contact with contaminated objects (clothing, bedding, towels) can also spread the virus 9 12.
• Incubation period: Typically 7-14 days, but can range from 3-20 days 1 9.

Environmental and Emerging Factors

• Fomites: The virus can survive on surfaces, increasing risk in shared living spaces or hospitals 9 12.
• Mutation and Adaptation: While monkeypox is a DNA virus (less prone to rapid mutation than RNA viruses), ongoing surveillance for changes in transmission or virulence is essential 8 10.

Treatment of Monkeypox

While most monkeypox cases are mild and resolve with supportive care, severe cases and those at high risk may require specific treatments. The recent outbreaks have accelerated research into antivirals and vaccines, though options are still limited.

Treatment Option	Usage/Indication	Notes/Effectiveness	Sources
Supportive Care	All cases	Pain relief, hydration, wound care; usually sufficient	1 2 5 12
Antivirals	Severe/at-risk cases	Tecovirimat (most used), cidofovir, brincidofovir	1 12 13 14
Vaccines	Pre/post-exposure prophylaxis	JYNNEOS, ACAM2000 (smallpox vaccines, not MPX-specific)	4 7 10 12
Immune globulin (VIGIV)	Complicated/severe cases	Reserved for those with severe disease/immunosuppression	12

Table 4: Treatment and Prevention Options

Supportive Care

• Mainstay for most patients: Includes pain management, fluids, nutrition, and treatment of secondary bacterial infections.
• Hospitalization: Required primarily for severe pain (especially rectal or genital), dehydration, or complications 1 5 12.

Antiviral Therapy

• Tecovirimat: The most commonly used antiviral during recent outbreaks. It blocks viral spread and has shown a favorable safety and efficacy profile in compassionate use and case series 13 14. Used primarily for:
  • Severe disease
  • Immunocompromised patients
  • Children, pregnant/breastfeeding women
  • Complicated lesions near eyes, mouth, genitals 12 13 14
• Cidofovir & Brincidofovir: Used less frequently due to limited data and potential side effects (e.g., liver toxicity with brincidofovir) 14.
• Topical trifluridine: Used for ocular involvement as an adjunct with antivirals 14.

Vaccination

• JYNNEOS (Imvamune/Imvanex): A non-replicating smallpox vaccine, approved for prevention of monkeypox in some countries 4 7 10 12.
• ACAM2000: Live, replicating smallpox vaccine; more side effects than JYNNEOS and not suitable for immunocompromised individuals 12.
• Usage: Given as pre-exposure prophylaxis for high-risk groups (e.g., healthcare workers, laboratory staff) and post-exposure prophylaxis for contacts 12.

Other Measures

• Isolation: Infected individuals should be isolated to prevent transmission 6 12.
• Public Health Response: Contact tracing, vaccination of close contacts, and clear public messaging are essential to control outbreaks 1 4 8 12.

Conclusion

Monkeypox is a complex, evolving disease whose public health significance has grown dramatically. Here’s what you need to remember:

• Recognize the symptoms: Rash (especially in genital/perianal areas), fever, swollen lymph nodes, and systemic symptoms are most common.
• Know the types: Two main clades (West African and Congo Basin) differ in severity and global impact.
• Understand the causes: Animal reservoirs and new human-to-human transmission patterns (including sexual contact) are central.
• Treatment is supportive: Most recover with basic care, but antivirals and vaccines are available for severe or high-risk cases.

Key points:

• Monkeypox is now a global, not just African, concern 1 2 4.
• Recent outbreaks show new clinical and transmission patterns, especially among MSM 1 2 5 10.
• Early diagnosis, isolation, and vaccination are vital to control outbreaks 4 8 12.
• Most cases are mild, but vigilance is needed for vulnerable groups and severe presentations 1 3 5 12 14.

Stay informed, recognize the signs, and rely on evidence-based interventions to manage and prevent monkeypox.